Datasets:

pbaoo2705

/

qa_processed_eval

like 0

Is callus formation related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing?

Study characterizes ovariectomized (OVX)-induced osteoporotic fracture healing with focus on estrogen receptors (ERs) Callus formation plays a critical role in fracture healing, and ERs are well-known mechanosensors in osteogenic pathways . It was hypothesized that callus formation was related to and partially determined by the difference in expression patterns of ERs in both normal and OVX-induced fractures . Study found that OVx-induced fracture was delayed at 2-4 weeks with impaired endpoint mechanical properties .

We conclude that the delayed healing rate and impaired callus quality in OVX-induced osteoporotic fracture is related to the delayed expression of ERs. A high ER-α:ER-β ratio favors callus formation.

yes

### Human: Study characterizes ovariectomized (OVX)-induced osteoporotic fracture healing with focus on estrogen receptors (ERs) Callus formation plays a critical role in fracture healing, and ERs are well-known mechanosensors in osteogenic pathways . It was hypothesized that callus formation was related to and partially determined by the difference in expression patterns of ERs in both normal and OVX-induced fractures . Study found that OVx-induced fracture was delayed at 2-4 weeks with impaired endpoint mechanical properties . Is callus formation related to the expression ratios of estrogen receptors-alpha and -beta in ovariectomy-induced osteoporotic fracture healing?### Assistant: We conclude that the delayed healing rate and impaired callus quality in OVX-induced osteoporotic fracture is related to the delayed expression of ERs. A high ER-α:ER-β ratio favors callus formation.

A high ER-α:ER-β ratio favors callus formation in osteoporotic fracture . A high callus ratio favors

Is expression of EphB6 in ovarian serous carcinoma associated with grade , TNM stage and survival?

Eph receptors are the largest known family of receptor tyrosines characterised in humans . These receptors are involved in the development and progression of various diseases including cancer . EphB6 contains kinase domains that are altered in several conserved amino acids and is catalytically inactive . The expression of Ephb6 protein was significantly associated with grade (p < 0.001) and TNM stage (p = 0.017) The survival analysis showed that patients with negative or weak expression of the protein had a poorer outcome than those with positive expression .

Our results show that EphB6 is a new biomarker for distinguishing high- and low-grade OSC, and may be a potential prognostic marker in OSCs.

yes

### Human: Eph receptors are the largest known family of receptor tyrosines characterised in humans . These receptors are involved in the development and progression of various diseases including cancer . EphB6 contains kinase domains that are altered in several conserved amino acids and is catalytically inactive . The expression of Ephb6 protein was significantly associated with grade (p < 0.001) and TNM stage (p = 0.017) The survival analysis showed that patients with negative or weak expression of the protein had a poorer outcome than those with positive expression . Is expression of EphB6 in ovarian serous carcinoma associated with grade , TNM stage and survival?### Assistant: Our results show that EphB6 is a new biomarker for distinguishing high- and low-grade OSC, and may be a potential prognostic marker in OSCs.

EphB6 is a new biomarker for distinguishing high- and low-grade OSCs . It may be a potential prog

Is prenatal tobacco smoke exposure associated with childhood DNA CpG methylation?

Using Illumina HumanMethylation27 microarrays, we estimated the degree of methylation at 27,578 distinct DNA sequences located primarily in gene promoters . Exposure was associated with a 2% increase in mean CpG methylation in FRMD4A and Cllorf52 compared to no exposure . Exposure increased the methylation of these genes in two genes . Four additional genes, XPNPEP1, PPEF2, SMPD3 and CRYGN, were nominally associated in one replication group .

These data suggest that prenatal exposure to tobacco smoke is associated with reproducible epigenetic changes that persist well into childhood. However, the biological significance of these altered loci remains unknown.

yes

### Human: Using Illumina HumanMethylation27 microarrays, we estimated the degree of methylation at 27,578 distinct DNA sequences located primarily in gene promoters . Exposure was associated with a 2% increase in mean CpG methylation in FRMD4A and Cllorf52 compared to no exposure . Exposure increased the methylation of these genes in two genes . Four additional genes, XPNPEP1, PPEF2, SMPD3 and CRYGN, were nominally associated in one replication group . Is prenatal tobacco smoke exposure associated with childhood DNA CpG methylation?### Assistant: These data suggest that prenatal exposure to tobacco smoke is associated with reproducible epigenetic changes that persist well into childhood. However, the biological significance of these altered loci remains unknown.

Pregnant exposure to tobacco smoke is associated with reproducible epigenetic changes that persist well into childhood . However, the biological significance of

Does microhardness and surface roughness of glass ionomer cement after APF and TiF4 applications?

Fuji IX Extra, Fuji II LC and Ketac N100 were prepared and stored in 2 ml of artificial saliva at 37 degrees C for 8 weeks . Specimens of each material were divided randomly into three subgroups as 1 and 4 minutes application of 1.23% APF gel and 1 minute application of TiF4 solution . Surface roughness was not affected at any time interval for three restorative materials . Surface morphology was not altered at any interval for Fuji IILC or Fuji IX .

Within the limitations of this vitro study it was revealed that, potential adverse effects of APF and TiF4 applications might be material dependant. Hence, restorative materials should be selected in accordance with kind, frequency and application time of fluoridation to avoid deteriorations of the restorations.

yes

### Human: Fuji IX Extra, Fuji II LC and Ketac N100 were prepared and stored in 2 ml of artificial saliva at 37 degrees C for 8 weeks . Specimens of each material were divided randomly into three subgroups as 1 and 4 minutes application of 1.23% APF gel and 1 minute application of TiF4 solution . Surface roughness was not affected at any time interval for three restorative materials . Surface morphology was not altered at any interval for Fuji IILC or Fuji IX . Does microhardness and surface roughness of glass ionomer cement after APF and TiF4 applications?### Assistant: Within the limitations of this vitro study it was revealed that, potential adverse effects of APF and TiF4 applications might be material dependant. Hence, restorative materials should be selected in accordance with kind, frequency and application time of fluoridation to avoid deteriorations of the restorations.

Potential adverse effects of APF and TiF4 applications might be material dependant . Restorative materials should be selected in accordance with kind

Is semiannual surveillance superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival?

The current guidelines recommend surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC) This study aimed at comparing cancer stage, treatment applicability, and survival between patients on semiannual or annual surveillance . The median observed survival was 45 months (95% CI 40.0-50.0) in Group 1 and 30 months in Group 2 (p=0.028) The median corrected survival of Group 1 was 40.3 months . Age, platelet count, alpha-fetoprotein, Child-Pugh class, cancer stage and cancer stage were independent prognostic factors .

Semiannual surveillance increases the detection rate of very early hepatocellular carcinomas and reduces the number of advanced tumors as compared to the annual program. This translates into a greater applicability of effective treatments and into a better prognosis.

yes

### Human: The current guidelines recommend surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC) This study aimed at comparing cancer stage, treatment applicability, and survival between patients on semiannual or annual surveillance . The median observed survival was 45 months (95% CI 40.0-50.0) in Group 1 and 30 months in Group 2 (p=0.028) The median corrected survival of Group 1 was 40.3 months . Age, platelet count, alpha-fetoprotein, Child-Pugh class, cancer stage and cancer stage were independent prognostic factors . Is semiannual surveillance superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival?### Assistant: Semiannual surveillance increases the detection rate of very early hepatocellular carcinomas and reduces the number of advanced tumors as compared to the annual program. This translates into a greater applicability of effective treatments and into a better prognosis.

Semiannual surveillance increases the detection rate of very early hepatocellular carcinomas and reduces the number of advanced tumors as compared to

Does cheese intake in large amounts lower LDL-cholesterol concentrations compared with butter intake of equal fat content?

Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with butter intake . This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat . After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-ch cholesterol concentrations and higher glucose concentrations than did the butter intervention . Fecal fat excretion did not differ between the cheese and butter periods . Cheese intake was found to be less dense than butter intake and less dense .

Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.

yes

### Human: Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with butter intake . This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat . After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-ch cholesterol concentrations and higher glucose concentrations than did the butter intervention . Fecal fat excretion did not differ between the cheese and butter periods . Cheese intake was found to be less dense than butter intake and less dense . Does cheese intake in large amounts lower LDL-cholesterol concentrations compared with butter intake of equal fat content?### Assistant: Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.

Cheese lowers LDL cholesterol when compared with butter intake of equal fat content . Cheese does not increase LDL cholesterol compared with a habitual diet .

Does in vitro antimicrobial effects of two antihalitosis mouth rinse on oral pathogens and human tongue microbiota?

The aim of the study was to compare the antimicrobial activity of a mouth rinse containing chlorhexidine and cetylpyridinium chloride (MR1) with a stannous fluoride-based mouth rinse (MR2) in vitro . MR1 showed a significantly higher in vitro antimacterial activity against the whole tongue microbiota and Fusobacterium nucleatum than MR2 in both groups of subjects . In the SIK test, MR1 was found to have a significantly greater killing capacity .

This in vitro observation supports the use of chlorhexidine and cetylpyridinium chloride in the treatment of oral halitosis.

yes

### Human: The aim of the study was to compare the antimicrobial activity of a mouth rinse containing chlorhexidine and cetylpyridinium chloride (MR1) with a stannous fluoride-based mouth rinse (MR2) in vitro . MR1 showed a significantly higher in vitro antimacterial activity against the whole tongue microbiota and Fusobacterium nucleatum than MR2 in both groups of subjects . In the SIK test, MR1 was found to have a significantly greater killing capacity . Does in vitro antimicrobial effects of two antihalitosis mouth rinse on oral pathogens and human tongue microbiota?### Assistant: This in vitro observation supports the use of chlorhexidine and cetylpyridinium chloride in the treatment of oral halitosis.

In vitro observation supports the use of chlorhexidine and cetylpyridinium chloride in the treatment of oral halit

Does tGF-beta inhibit CYP17 transcription in H295R cells acting via activin receptor-like kinase 5?

H295R cells were culture and incubated with TGF-beta, transcription inhibitor (DRB), activin receptor-like kinase 5 ALK5 (TbetaRII) inhibitor (SB431542) and mitogen activated kinases inhibitors (PD98059 and SB203580) We investigated the mechanism how CYP17 is inhibited by the growth factor beta in adrenocortical cells . Mitogen activated Kinases MEK1 and p38 MAPK are not involved in the inhibitory effect .

We concluded that the TGF-beta-dependent decrease of 17alpha-hydroxylase/17,20 lyase activity in the H295R cells is caused by inhibition of CYP17 transcription and is mediated by the ALK5 receptor.

yes

### Human: H295R cells were culture and incubated with TGF-beta, transcription inhibitor (DRB), activin receptor-like kinase 5 ALK5 (TbetaRII) inhibitor (SB431542) and mitogen activated kinases inhibitors (PD98059 and SB203580) We investigated the mechanism how CYP17 is inhibited by the growth factor beta in adrenocortical cells . Mitogen activated Kinases MEK1 and p38 MAPK are not involved in the inhibitory effect . Does tGF-beta inhibit CYP17 transcription in H295R cells acting via activin receptor-like kinase 5?### Assistant: We concluded that the TGF-beta-dependent decrease of 17alpha-hydroxylase/17,20 lyase activity in the H295R cells is caused by inhibition of CYP17 transcription and is mediated by the ALK5 receptor.

TGF-beta-dependent decrease of 17alpha-hydroxylase/17,20 lyase activity in H295R cells

Is akt required for Stat5 activation and mammary differentiation?

The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism . It is one of the most commonly activated pathways in human cancer . A role for Akt in epithelial differentiation, however, has not been established . In mice lacking Akt1, but not Akt2, Akt mice exhibit normal mammary epithelial cell development and Stat5 activation . We considered the possibility that Akt may play an essential role in mammary development that is not evident in Akt-deficient mice due to compensation by other isoforms .

Our findings demonstrate an unexpected requirement for Akt in Prlr-Jak-Stat5 signaling and establish Akt as an essential central regulator of mammary epithelial differentiation and lactation.

yes

### Human: The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism . It is one of the most commonly activated pathways in human cancer . A role for Akt in epithelial differentiation, however, has not been established . In mice lacking Akt1, but not Akt2, Akt mice exhibit normal mammary epithelial cell development and Stat5 activation . We considered the possibility that Akt may play an essential role in mammary development that is not evident in Akt-deficient mice due to compensation by other isoforms . Is akt required for Stat5 activation and mammary differentiation?### Assistant: Our findings demonstrate an unexpected requirement for Akt in Prlr-Jak-Stat5 signaling and establish Akt as an essential central regulator of mammary epithelial differentiation and lactation.

Akt is an essential central regulator of mammary epithelial differentiation and lactation . The findings demonstrate an unexpected requirement for Akt in

Does ethanol selectively attenuate NMDAR-mediated synaptic transmission in the prefrontal cortex?

Understanding how ethanol affects the physiology of PFC neurons may help explain this loss of control and lead to better treatments for alcohol addiction, authors say . Brain imaging studies have revealed abnormal function in the prefrontal cortex (PFC) of alcoholics that may contribute to the impulsive behavior and lack of control over drinking that characterizes this disorder . In a study, whole-cell patch clamp recordings were used to directly examine the effects of ethanol on the glutamatergic and GABAergic components that underlie persistent activity .

Together, these results suggest that NMDAR-mediated processes in the mPFC may be particularly susceptible to disruption following the acute ingestion of ethanol.

yes

### Human: Understanding how ethanol affects the physiology of PFC neurons may help explain this loss of control and lead to better treatments for alcohol addiction, authors say . Brain imaging studies have revealed abnormal function in the prefrontal cortex (PFC) of alcoholics that may contribute to the impulsive behavior and lack of control over drinking that characterizes this disorder . In a study, whole-cell patch clamp recordings were used to directly examine the effects of ethanol on the glutamatergic and GABAergic components that underlie persistent activity . Does ethanol selectively attenuate NMDAR-mediated synaptic transmission in the prefrontal cortex?### Assistant: Together, these results suggest that NMDAR-mediated processes in the mPFC may be particularly susceptible to disruption following the acute ingestion of ethanol.

NMDAR-mediated processes in the mPFC may be particularly susceptible to disruption following the acute ingestion of ethanol .

Does high-intensity Interval training enhance mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia?

Exercise training improves endothelium-dependent vasodilation, whereas hypoxic stress causes vascular endothelial dysfunction . Monocyte-derived endothelial progenitor cells (Mon-EPCs) contribute to vascular repair process by differentiating into endothelial cells . The study investigates how high-intensity interval (HIT) and moderate-intensity continuous (MCT) exercise training affect circulating Mon-Epc levels and EPC functionality under hypoxic condition . After the intervention, the HIT group exhibited larger improvements in VO .

HIT is superior to MCT for improving hemodynamic adaptation and Mon-EPC production. Moreover, HIT effectively enhances EPC functionality and suppresses endothelial injury undergoing hypoxia.

yes

### Human: Exercise training improves endothelium-dependent vasodilation, whereas hypoxic stress causes vascular endothelial dysfunction . Monocyte-derived endothelial progenitor cells (Mon-EPCs) contribute to vascular repair process by differentiating into endothelial cells . The study investigates how high-intensity interval (HIT) and moderate-intensity continuous (MCT) exercise training affect circulating Mon-Epc levels and EPC functionality under hypoxic condition . After the intervention, the HIT group exhibited larger improvements in VO . Does high-intensity Interval training enhance mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia?### Assistant: HIT is superior to MCT for improving hemodynamic adaptation and Mon-EPC production. Moreover, HIT effectively enhances EPC functionality and suppresses endothelial injury undergoing hypoxia.

HIT is superior to MCT for improving hemodynamic adaptation and Mon-EPC production . HIT effectively enhances EPC functionality and suppresses

Does defective Intestinal Mucin-Type O-Glycosylation cause Spontaneous Colitis-Associated Cancer in Mice?

Core 1- and core 3-derived mucin-type O-linked oligosaccharides (O-glycans) are major components of the colonic mucus layer . Defective forms of colonic O-glyCans frequently are observed in patients with ulcerative colitis and colorectal cancer, but it is not clear if they contribute to their pathogenesis . We used mice that lack core 1- or core 3 O- glycans to study mice lacking core 1 O- Glycans .

Impaired expression of O-glycans causes colonic mucus barrier breach and subsequent microbiota-mediated activation of caspase 1-dependent inflammasomes in colonic epithelial cells of mice. These processes could contribute to colitis-associated colon cancer in humans.

yes

### Human: Core 1- and core 3-derived mucin-type O-linked oligosaccharides (O-glycans) are major components of the colonic mucus layer . Defective forms of colonic O-glyCans frequently are observed in patients with ulcerative colitis and colorectal cancer, but it is not clear if they contribute to their pathogenesis . We used mice that lack core 1- or core 3 O- glycans to study mice lacking core 1 O- Glycans . Does defective Intestinal Mucin-Type O-Glycosylation cause Spontaneous Colitis-Associated Cancer in Mice?### Assistant: Impaired expression of O-glycans causes colonic mucus barrier breach and subsequent microbiota-mediated activation of caspase 1-dependent inflammasomes in colonic epithelial cells of mice. These processes could contribute to colitis-associated colon cancer in humans.

Impaired expression of O-glycans causes colonic mucus barrier breach and subsequent microbiota-mediated activation of caspase 1

Do human gingival and pulpal blood flow during healing after Le Fort I osteotomy?

The occurrence of a hypervascular period during healing after orthognathic surgery has not been investigated rigorously . This study used laser Doppler flowmetry to investigate the effects of Le Fort I osteotomy on maxillary pulpal and gingival blood flow . Blood flow measurements were made before surgery and at intervals between 7 and 10 days, 14 and 17 days, and 21 and 24 days after surgery . Analysis of the postsurgical change from baseline blood flow values indicated a significant increase in pulpal blood flow in the maxillary surgery patients relative to the patients treated with mandibular surgery .

This study provides evidence that pulpal blood flow is increased between the first and third week after Le Fort I osteotomy, but it did not find a significant change in gingival blood flow.

yes

### Human: The occurrence of a hypervascular period during healing after orthognathic surgery has not been investigated rigorously . This study used laser Doppler flowmetry to investigate the effects of Le Fort I osteotomy on maxillary pulpal and gingival blood flow . Blood flow measurements were made before surgery and at intervals between 7 and 10 days, 14 and 17 days, and 21 and 24 days after surgery . Analysis of the postsurgical change from baseline blood flow values indicated a significant increase in pulpal blood flow in the maxillary surgery patients relative to the patients treated with mandibular surgery . Do human gingival and pulpal blood flow during healing after Le Fort I osteotomy?### Assistant: This study provides evidence that pulpal blood flow is increased between the first and third week after Le Fort I osteotomy, but it did not find a significant change in gingival blood flow.

This study provides evidence that pulpal blood flow is increased between the first and third week after Le Fort I osteotomy . It did not

Are low serum levels of soluble CD44 variant 6 significantly associated with poor prognosis in patients with pancreatic carcinoma?

The soluble forms of CD44 standard (CD44s) and CD44v6 are present in the serum of normal individuals . The aim of the current study was to evaluate the concentrations and the prognostic potential of soluble CD44s in patients with pancreatic carcinoma . The median survival in the group with CD44 v6 serum concentrations below 100 ng/mL was significantly decreased compared with that in the . group with serum concentrations higher than 100ng/mL (6.7 vs. 15.1 months, P < 0.00005)

These results suggest that serum CD44v6 is significantly reduced in pancreatic carcinoma patients and could serve as a good prognostic marker for patients with this disease.

yes

### Human: The soluble forms of CD44 standard (CD44s) and CD44v6 are present in the serum of normal individuals . The aim of the current study was to evaluate the concentrations and the prognostic potential of soluble CD44s in patients with pancreatic carcinoma . The median survival in the group with CD44 v6 serum concentrations below 100 ng/mL was significantly decreased compared with that in the . group with serum concentrations higher than 100ng/mL (6.7 vs. 15.1 months, P < 0.00005) Are low serum levels of soluble CD44 variant 6 significantly associated with poor prognosis in patients with pancreatic carcinoma?### Assistant: These results suggest that serum CD44v6 is significantly reduced in pancreatic carcinoma patients and could serve as a good prognostic marker for patients with this disease.

serum CD44v6 is significantly reduced in pancreatic carcinoma patients and could serve as a good prognostic marker for patients with this

Does an assessment of fall in elderly men and women?

Study examined the abilities of elderly fallers and nonfallers to perform various functional activities . The data indicated that fallers exhibited significantly reduced static balance, walking and stair descent performance . The fallers showed that they exhibited significantly lower selective attention abilities and increased choice resisted reaction times, both measures of the central processing control system component . The nonfaller exhibited reduced proprioceptive function, suggesting that this is not a major contributor to the performance of balance and mobility skills . The study examined the balance control components of sensory input: vision, vestibular function, and proprioception .

The data suggest that actual performance of mobility skills is an efficient means of identifying potential fallers. The decrements in functional activity performance appear to be related to central information processing control components, specifically selective attention and choice reaction time. The significant correlations between the sensory input, central processing control, and effector components with the functional activities suggest that the marginal declines in the sensory and effector components may have an additive effect, which may adversely affect the ability of fallers to perform the functional activities. The data suggest that selective attention and choice reaction time are the two most significant balance control components predictive of falls.

yes

### Human: Study examined the abilities of elderly fallers and nonfallers to perform various functional activities . The data indicated that fallers exhibited significantly reduced static balance, walking and stair descent performance . The fallers showed that they exhibited significantly lower selective attention abilities and increased choice resisted reaction times, both measures of the central processing control system component . The nonfaller exhibited reduced proprioceptive function, suggesting that this is not a major contributor to the performance of balance and mobility skills . The study examined the balance control components of sensory input: vision, vestibular function, and proprioception . Does an assessment of fall in elderly men and women?### Assistant: The data suggest that actual performance of mobility skills is an efficient means of identifying potential fallers. The decrements in functional activity performance appear to be related to central information processing control components, specifically selective attention and choice reaction time. The significant correlations between the sensory input, central processing control, and effector components with the functional activities suggest that the marginal declines in the sensory and effector components may have an additive effect, which may adversely affect the ability of fallers to perform the functional activities. The data suggest that selective attention and choice reaction time are the two most significant balance control components predictive of falls.

The data suggest that actual performance of mobility skills is an efficient means of identifying potential fallers . The decrements in functional activity performance appear

Does release of endogenous opioids from duodenal enteroendocrine cells require Trpm5?

Little is known about less typical endocrine cells in the intestinal mucosa that do not contain secretory granules, such as brush or caveolated cells . We studied a subset of these cells in duodenum that produce several peptides, including endogenous opioids, and that also express the Trpm5 cation channel . We describe a type of enteroendocrine cell in mouse duoden that is defined by the presence of Trp5 and that does not contain typical secretory granules .

Solitary chemosensory cells that coexpress beta-endorphin, Met-enkephalin, uroguanylin, and Trpm5 exist in mouse duodenum. These cells are likely to secrete the bioactive peptides into the intestinal lumen in response to dietary factors; release of the opioid peptides requires the Trpm5 ion channel.

yes

### Human: Little is known about less typical endocrine cells in the intestinal mucosa that do not contain secretory granules, such as brush or caveolated cells . We studied a subset of these cells in duodenum that produce several peptides, including endogenous opioids, and that also express the Trpm5 cation channel . We describe a type of enteroendocrine cell in mouse duoden that is defined by the presence of Trp5 and that does not contain typical secretory granules . Does release of endogenous opioids from duodenal enteroendocrine cells require Trpm5?### Assistant: Solitary chemosensory cells that coexpress beta-endorphin, Met-enkephalin, uroguanylin, and Trpm5 exist in mouse duodenum. These cells are likely to secrete the bioactive peptides into the intestinal lumen in response to dietary factors; release of the opioid peptides requires the Trpm5 ion channel.

Chemosensory cells that coexpress beta-endorphin, Met-enkephalin, uroguanylin,

Is skin perfusion pressure of the foot a good substitute for toe pressure in the assessment of limb ischemia?

Toe pressure is often used in the evaluation of severity of arterial disease and in the assessment for critical limb ischemia . Skin lesions on the toes or previous digital amputations may preclude the measurement of toe pressures . Measurements of skin perfusion pressure (SPP) are not subject to such limitations and were shown to be useful in assessing the severity of peripheral arterial diseases . Toe pressures measured with photoplethysmography were correlated with foot SPP measured with laser Doppler scanning .

We concluded that SPP measured in the foot correlates well with toe pressure and can be substituted for toe pressure measurement in patients in whom toe pressures cannot be measured.

yes

### Human: Toe pressure is often used in the evaluation of severity of arterial disease and in the assessment for critical limb ischemia . Skin lesions on the toes or previous digital amputations may preclude the measurement of toe pressures . Measurements of skin perfusion pressure (SPP) are not subject to such limitations and were shown to be useful in assessing the severity of peripheral arterial diseases . Toe pressures measured with photoplethysmography were correlated with foot SPP measured with laser Doppler scanning . Is skin perfusion pressure of the foot a good substitute for toe pressure in the assessment of limb ischemia?### Assistant: We concluded that SPP measured in the foot correlates well with toe pressure and can be substituted for toe pressure measurement in patients in whom toe pressures cannot be measured.

SPP measured in the foot correlates well with toe pressure . SPP can be substituted for toe pressure measurement in patients in whom toe pressures

Does overexpression of factor VII ameliorate bleeding diathesis of factor VIII-deficient mice with inhibitors?

Factor VIII (FVIII) treatment for hemophilia A has difficulties in correcting bleeding diathesis in the presence of inhibitors . Overexpression of FVIIa ameliorated the bleeding phenotype of FVIII-deficient mice with inhibitors and significantly increased the survival rate after tail clipping . Thromboelastography analysis showed significant improvements in clotting time, clot formation time, and mean clot firmness in AAV8 vector-injected FVII mice with . inhibitors .

These data suggest that FVII overexpression is an alternative strategy for the treatment of hemophilia A with inhibitors.

yes

### Human: Factor VIII (FVIII) treatment for hemophilia A has difficulties in correcting bleeding diathesis in the presence of inhibitors . Overexpression of FVIIa ameliorated the bleeding phenotype of FVIII-deficient mice with inhibitors and significantly increased the survival rate after tail clipping . Thromboelastography analysis showed significant improvements in clotting time, clot formation time, and mean clot firmness in AAV8 vector-injected FVII mice with . inhibitors . Does overexpression of factor VII ameliorate bleeding diathesis of factor VIII-deficient mice with inhibitors?### Assistant: These data suggest that FVII overexpression is an alternative strategy for the treatment of hemophilia A with inhibitors.

These data suggest that FVII overexpression is an alternative strategy for the treatment of hemophilia A with inhibitors .

Do beta2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells?

Airway epithelial cells are critical in host defense against bacteria including Mycoplasma pneumoniae in chronic obstructive pulmonary disease (COPD) and asthma . Whether beta2-agonists directly affect host defense functions is unclear . COPD cells did not respond to drug treatment with a significant decrease in Mp or an increase in SPLUNC1 or an increased in SPLunC1 . IL-13 attenuated drug effects on Mp, and markedly decreased SPLUN C1 and beta2 C1 receptors .

These results for the first time show that beta2-agonists enhance host defense functions of primary bronchial epithelial cells from normal and asthma subjects, which is attenuated by IL-13.

yes

### Human: Airway epithelial cells are critical in host defense against bacteria including Mycoplasma pneumoniae in chronic obstructive pulmonary disease (COPD) and asthma . Whether beta2-agonists directly affect host defense functions is unclear . COPD cells did not respond to drug treatment with a significant decrease in Mp or an increase in SPLUNC1 or an increased in SPLunC1 . IL-13 attenuated drug effects on Mp, and markedly decreased SPLUN C1 and beta2 C1 receptors . Do beta2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells?### Assistant: These results for the first time show that beta2-agonists enhance host defense functions of primary bronchial epithelial cells from normal and asthma subjects, which is attenuated by IL-13.

Beta2-agonists enhance host defense functions of primary bronchial epithelial cells from normal and asthma subjects, which was attenuated by

Is sHOX2 DNA methylation a tumour marker in pleural effusions?

Epi proLung® BL Reflex Assay (Epigenomics AG, Berlin, Germany) has been reported as being highly sensitive and specific for lung cancer using bronchial aspirates . We hypothesize the assay to be of use in the detection of MPE . With a re-defined cut-off criterion, the test achieved a sensitivity of 39.5% with a specificity of 96.2% . The test detects metastases of lung cancer, as well as metastases .

This assay is able to detect MPE while not limited to the detection of lung cancer.

yes

### Human: Epi proLung® BL Reflex Assay (Epigenomics AG, Berlin, Germany) has been reported as being highly sensitive and specific for lung cancer using bronchial aspirates . We hypothesize the assay to be of use in the detection of MPE . With a re-defined cut-off criterion, the test achieved a sensitivity of 39.5% with a specificity of 96.2% . The test detects metastases of lung cancer, as well as metastases . Is sHOX2 DNA methylation a tumour marker in pleural effusions?### Assistant: This assay is able to detect MPE while not limited to the detection of lung cancer.

This assay is able to detect MPE while not limited to the detection of lung cancer . It is also capable of detecting MPE in

Does hyperinsulinemia in polycystic ovary syndrome correlate with increased cardiovascular risk independent of obesity?

Women with PCOS carried more cardiovascular risk than their normoinsulinemic counterparts, who in turn had more risk than the control women . The study found that PCOS itself and body mass index both contribute to insulin resistance . The authors conclude that the risk of cardiovascular disease is dependent on insulin resistance, independent of obesity, in determining cardiovascular risk among women with the polycystic ovarian syndrome (PCOS) Study: Hyperinsulinemia, composite cardiovascular risk scores, and prevalence of individual risk factors among lean and obese women .

Our data support the hypothesis that insulin resistance in PCOS is a determinant of overall cardiovascular risk independent of obesity. The mechanism of this relationship remains uncertain and is the subject of ongoing research.

yes

### Human: Women with PCOS carried more cardiovascular risk than their normoinsulinemic counterparts, who in turn had more risk than the control women . The study found that PCOS itself and body mass index both contribute to insulin resistance . The authors conclude that the risk of cardiovascular disease is dependent on insulin resistance, independent of obesity, in determining cardiovascular risk among women with the polycystic ovarian syndrome (PCOS) Study: Hyperinsulinemia, composite cardiovascular risk scores, and prevalence of individual risk factors among lean and obese women . Does hyperinsulinemia in polycystic ovary syndrome correlate with increased cardiovascular risk independent of obesity?### Assistant: Our data support the hypothesis that insulin resistance in PCOS is a determinant of overall cardiovascular risk independent of obesity. The mechanism of this relationship remains uncertain and is the subject of ongoing research.

Insulin resistance in PCOS is a determinant of overall cardiovascular risk independent of obesity . The mechanism of this relationship remains uncertain and is

Does intra-articular injection of Torin 1 reduce degeneration of articular cartilage in a rabbit osteoarthritis model?

Torin 1 is a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin . Intra-articular injection of Torin reduced degeneration of articular cartilage after induction of OA . Torin-1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection . Autophagosomes andBeclin--1 and LC3 expression were increased in the chondrocytes from Torin .

Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA.Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218-224. DOI: 10.1302/2046-3758.56.BJR-2015-0001.

yes

### Human: Torin 1 is a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin . Intra-articular injection of Torin reduced degeneration of articular cartilage after induction of OA . Torin-1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection . Autophagosomes andBeclin--1 and LC3 expression were increased in the chondrocytes from Torin . Does intra-articular injection of Torin 1 reduce degeneration of articular cartilage in a rabbit osteoarthritis model?### Assistant: Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA.Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218-224. DOI: 10.1302/2046-3758.56.BJR-2015-0001.

Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at

Does tobacco smoking in adolescence predict maladaptive coping styles in adulthood?

The data came from a longitudinal study of New Zealand adolescents followed into adulthood at age 32 years . We examined the predictive association between daily smoking of cigarettes and symptoms of tobacco dependence from 18 to 26 years of age . We included pathways from childhood family disadvantage in addition to both adolescent stress-worry and adult coping in the model . We found that cigarette smoking had a small but direct inverse effect on later adaptive coping (-.14) and a direct effect on maladaptive coping (.23) independent of the relationships between adolescent coping and stress worry and later adult coping .

The findings are consistent with the hypothesis that tobacco smoking may inhibit the development of self-efficacy or one's ability to act with appropriate coping behaviors in any given situation.

yes

### Human: The data came from a longitudinal study of New Zealand adolescents followed into adulthood at age 32 years . We examined the predictive association between daily smoking of cigarettes and symptoms of tobacco dependence from 18 to 26 years of age . We included pathways from childhood family disadvantage in addition to both adolescent stress-worry and adult coping in the model . We found that cigarette smoking had a small but direct inverse effect on later adaptive coping (-.14) and a direct effect on maladaptive coping (.23) independent of the relationships between adolescent coping and stress worry and later adult coping . Does tobacco smoking in adolescence predict maladaptive coping styles in adulthood?### Assistant: The findings are consistent with the hypothesis that tobacco smoking may inhibit the development of self-efficacy or one's ability to act with appropriate coping behaviors in any given situation.

The findings are consistent with the hypothesis that tobacco smoking may inhibit the development of self-efficacy .

Do statins differ in their ability to block NF-kappaB activation in human blood monocytes?

Six statins were tested for their ability to influence induction of NF-kappaB in human monocytes during inflammation . Cer (45 +/- 9% inhibition, p < 0.05) was 9-fold more effective in reducing NF-KappaB activation than Flu (5 +/- 10% inhibition) The inhibitory effect was due to reduced phosphorylation and degradation of the inhibitor protein IkappaB-alpha . The differences in the potency of statins (Cer > Atv > Sim > Sim> Pra > Lov > Flu) were also reflected at the transcriptional level and the protein level of NF

The finding that statins differ in their potency in interfering with the activation of NF-kappaB signaling in human monocytes further supports the hypothesis that some statins inhibit the inflammatory response more than others.

yes

### Human: Six statins were tested for their ability to influence induction of NF-kappaB in human monocytes during inflammation . Cer (45 +/- 9% inhibition, p < 0.05) was 9-fold more effective in reducing NF-KappaB activation than Flu (5 +/- 10% inhibition) The inhibitory effect was due to reduced phosphorylation and degradation of the inhibitor protein IkappaB-alpha . The differences in the potency of statins (Cer > Atv > Sim > Sim> Pra > Lov > Flu) were also reflected at the transcriptional level and the protein level of NF Do statins differ in their ability to block NF-kappaB activation in human blood monocytes?### Assistant: The finding that statins differ in their potency in interfering with the activation of NF-kappaB signaling in human monocytes further supports the hypothesis that some statins inhibit the inflammatory response more than others.

The finding that statins differ in their potency in interfering with the activation of NF-kappaB signaling in human monocytes supports the

Does follow-up analysis of genome-wide association data identify novel loci for type 1 diabetes?

Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes . Genotyping these in an independent set of nuclear families with 974 affected offspring revealed 75 markers that also had P < 0.05 in a third cohort . Six single nucleotide polymorphisms in five novel locoides also had . P < .05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 type 1 . diabetes probands from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complicated (DCCT/EDIC)

Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with type 1 diabetes. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity.

yes

### Human: Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes . Genotyping these in an independent set of nuclear families with 974 affected offspring revealed 75 markers that also had P < 0.05 in a third cohort . Six single nucleotide polymorphisms in five novel locoides also had . P < .05 in the Wellcome Trust Case-Control Consortium dataset and were further tested in 1,303 type 1 . diabetes probands from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complicated (DCCT/EDIC) Does follow-up analysis of genome-wide association data identify novel loci for type 1 diabetes?### Assistant: Evaluation of a large number of statistical GWA candidates in several independent cohorts has revealed additional loci that are associated with type 1 diabetes. The two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity.

Two genes at these respective loci, UBASH3A and BACH2, are both biologically relevant to autoimmunity

Does whole-body muscle magnetic resonance imaging in SEPN1-related myopathy show a homogeneous and recognizable pattern?

The aim of this study was to delineate the spectrum of muscle involvement in patients with a myopathy due to mutations in SEPN1 (SEPN1-RM) Severe wasting of sternocleidomastoid muscle and atrophy of semimembranosus were detected . Selective paraspinal, gluteus maximus, and thigh muscle involvement was also observed . The lower leg was less constantly affected . The study was conducted by using whole-body magnetic resonance imaging (WBMRI)

WBMRI scoring of altered signal and atrophy in muscle can be represented by heatmaps and is associated with a homogeneous, recognizable pattern in SEPN1-RM, distinct from other genetic muscle diseases.

yes

### Human: The aim of this study was to delineate the spectrum of muscle involvement in patients with a myopathy due to mutations in SEPN1 (SEPN1-RM) Severe wasting of sternocleidomastoid muscle and atrophy of semimembranosus were detected . Selective paraspinal, gluteus maximus, and thigh muscle involvement was also observed . The lower leg was less constantly affected . The study was conducted by using whole-body magnetic resonance imaging (WBMRI) Does whole-body muscle magnetic resonance imaging in SEPN1-related myopathy show a homogeneous and recognizable pattern?### Assistant: WBMRI scoring of altered signal and atrophy in muscle can be represented by heatmaps and is associated with a homogeneous, recognizable pattern in SEPN1-RM, distinct from other genetic muscle diseases.

WBMRI scoring of altered signal and atrophy in muscle can be represented by heatmaps . Heatmaps are associated with a homogeneous

Does zinc supplementation attenuate alcohol-induced cerebellar Purkinje cell loss during the brain growth spurt period?

Alcohol-induced zinc deficiency is one of the mechanisms proposed as a cause of developmental brain damage associated with fetal alcohol syndrome . It is known that alcohol exposure during the brain growth spurt period leads to cerebellar Purkinje cell loss . Study examined whether zinc supplementation was capable of preventing alcohol-induced Purkinj cell loss in the cerebella vermis in a neonatal rat model system . The zinc supplementation had no effect in attenuating alcohol- induced Purkinjit cell loss, the study found .

These findings indicate that alcohol exposure during the third trimester equivalent did not result in zinc deficiency in this neonatal rat model system, nor did zinc supplementation rescue the alcohol-induced Purkinje cell loss in the cerebellar vermis. These findings showed clearly that the serum zinc concentration was not correlated with Purkinje cell loss, suggesting that alcohol-induced loss of cerebellar Purkinje cells in this neonatal rat model system is independent of the availability of serum zinc.

no

### Human: Alcohol-induced zinc deficiency is one of the mechanisms proposed as a cause of developmental brain damage associated with fetal alcohol syndrome . It is known that alcohol exposure during the brain growth spurt period leads to cerebellar Purkinje cell loss . Study examined whether zinc supplementation was capable of preventing alcohol-induced Purkinj cell loss in the cerebella vermis in a neonatal rat model system . The zinc supplementation had no effect in attenuating alcohol- induced Purkinjit cell loss, the study found . Does zinc supplementation attenuate alcohol-induced cerebellar Purkinje cell loss during the brain growth spurt period?### Assistant: These findings indicate that alcohol exposure during the third trimester equivalent did not result in zinc deficiency in this neonatal rat model system, nor did zinc supplementation rescue the alcohol-induced Purkinje cell loss in the cerebellar vermis. These findings showed clearly that the serum zinc concentration was not correlated with Purkinje cell loss, suggesting that alcohol-induced loss of cerebellar Purkinje cells in this neonatal rat model system is independent of the availability of serum zinc.

Alcohol exposure during the third trimester equivalent did not result in zinc deficiency in this neonatal rat model system, nor did zinc supplementation rescue

Does skin intrinsic fluorescence correlate with autonomic and distal symmetrical polyneuropathy in individuals with type 1 diabetes?

The prevalence of autonomic neuropathy and confirmed distal symmetrical polyneuropathy (CDSP) was 61 and 66% . Autonomic neuropathy was defined as an electrocardiographic abnormal heart rate response to deep breathing (expiration-to-inspiration ratio <1.1) CDSP was defined using the Diabetes Control and Complications Trial clinical exam protocol . SIF and updated mean HbA(1c accounted for 80 and 57% of the area under the curve (AUC)

SIF, a marker of dermal advanced glycation end products, appears to be more strongly associated with the presence of both CDSP and autonomic neuropathy than mean HbA(1c).

yes

### Human: The prevalence of autonomic neuropathy and confirmed distal symmetrical polyneuropathy (CDSP) was 61 and 66% . Autonomic neuropathy was defined as an electrocardiographic abnormal heart rate response to deep breathing (expiration-to-inspiration ratio <1.1) CDSP was defined using the Diabetes Control and Complications Trial clinical exam protocol . SIF and updated mean HbA(1c accounted for 80 and 57% of the area under the curve (AUC) Does skin intrinsic fluorescence correlate with autonomic and distal symmetrical polyneuropathy in individuals with type 1 diabetes?### Assistant: SIF, a marker of dermal advanced glycation end products, appears to be more strongly associated with the presence of both CDSP and autonomic neuropathy than mean HbA(1c).

SIF, a marker of dermal advanced glycation end products, appears to be more strongly associated with the presence of both CDSP

Does bag-valve-mask ventilation with airway adjuncts improve neurological outcomes of in-hospital cardiac arrest?

The study was undertaken to determine the characteristics and outcome of in-hospital cardiac arrests and the effectiveness of BVM ventilation with airway adjuncts . The initial rhythm of cardiac arrests was pulseless electrical activity in 63.8% (67/105) and respiratory failure (44.8%) was the most common cause . The neurological outcome was good (cerebral performance category-1) in 66.7% of those who suffered cardiac arrests . Bag-valve-mask ventilation improved the neurological outcome (OR 3.52, 95%CI 1.52)

Bag-valve-mask ventilation with airway adjuncts improved neurological outcomes.

yes

### Human: The study was undertaken to determine the characteristics and outcome of in-hospital cardiac arrests and the effectiveness of BVM ventilation with airway adjuncts . The initial rhythm of cardiac arrests was pulseless electrical activity in 63.8% (67/105) and respiratory failure (44.8%) was the most common cause . The neurological outcome was good (cerebral performance category-1) in 66.7% of those who suffered cardiac arrests . Bag-valve-mask ventilation improved the neurological outcome (OR 3.52, 95%CI 1.52) Does bag-valve-mask ventilation with airway adjuncts improve neurological outcomes of in-hospital cardiac arrest?### Assistant: Bag-valve-mask ventilation with airway adjuncts improved neurological outcomes.

Bag-valve-mask ventilation with airway adjuncts improved neurological outcomes .

Do lactobacillus reuteri 6475 Increases Bone Density in Intact Females Only under an Inflammatory Setting?

A mild inflammatory state was induced in female mice by dorsal surgical incision (DSI) Animals were orally supplemented with L. reuteri or vehicle control for a period of 8 weeks . Lactobacillus Reuteri 6475 enhanced bone health and prevented bone loss in estrogen-deficient female mice . Unexpectedly we identified that L.Reuteri treatment increased bone density in females but only in those that underwent DSI . In the bone marrow, dorsal surgery induced CD4+ T cell numbers, a response that was unaffected by L.reuteri .

Our data reveals a previously unappreciated effect of a mild surgical procedure causing a long-lasting effect on inflammatory gene expression in the gut and the bone. Additionally, we demonstrate that in intact female mice, the beneficial effect of L. reuteri on bone requires an elevated inflammatory status.

yes

### Human: A mild inflammatory state was induced in female mice by dorsal surgical incision (DSI) Animals were orally supplemented with L. reuteri or vehicle control for a period of 8 weeks . Lactobacillus Reuteri 6475 enhanced bone health and prevented bone loss in estrogen-deficient female mice . Unexpectedly we identified that L.Reuteri treatment increased bone density in females but only in those that underwent DSI . In the bone marrow, dorsal surgery induced CD4+ T cell numbers, a response that was unaffected by L.reuteri . Do lactobacillus reuteri 6475 Increases Bone Density in Intact Females Only under an Inflammatory Setting?### Assistant: Our data reveals a previously unappreciated effect of a mild surgical procedure causing a long-lasting effect on inflammatory gene expression in the gut and the bone. Additionally, we demonstrate that in intact female mice, the beneficial effect of L. reuteri on bone requires an elevated inflammatory status.

The beneficial effect of L. reuteri on bone requires an elevated inflammatory status .

Is fibrosis caused by loss of PTEN expression in mouse fibroblasts crucially dependent on CCN2?

PTEN gene is reduced in dermal fibroblasts isolated from patients with diffuse cutaneous systemic sclerosis, a fibrotic autoimmune disease . Deplication of the PTEN genes in mice has been shown to result in skin fibrosis and in vivo overexpression of connective tissue growth factor (CTGF; CCN2), a proadhesive matricellular protein . This study was undertaken to investigate the role of CCN 2 in fibrosis caused by reduced PTEN expression .

These data are consistent with the notion that CCN2 is required for particular aspects of the fibroproliferative response; therapeutic strategies blocking CCN2 may be of clinical benefit in combating fibrotic disease.

yes

### Human: PTEN gene is reduced in dermal fibroblasts isolated from patients with diffuse cutaneous systemic sclerosis, a fibrotic autoimmune disease . Deplication of the PTEN genes in mice has been shown to result in skin fibrosis and in vivo overexpression of connective tissue growth factor (CTGF; CCN2), a proadhesive matricellular protein . This study was undertaken to investigate the role of CCN 2 in fibrosis caused by reduced PTEN expression . Is fibrosis caused by loss of PTEN expression in mouse fibroblasts crucially dependent on CCN2?### Assistant: These data are consistent with the notion that CCN2 is required for particular aspects of the fibroproliferative response; therapeutic strategies blocking CCN2 may be of clinical benefit in combating fibrotic disease.

These data are consistent with the notion that CCN2 is required for particular aspects of the fibroproliferative response . Ther

Is early pancreas graft failure associated with inferior late clinical outcomes after simultaneous kidney-pancreas transplantation?

Early pancreas graft failure is common after simultaneous kidney and SPK transplantation . We studied the impact of early pancrease graft failure on long-term kidney and patient survival . Early panceas graft failures were associated with lower subsequent kidney graft and survival . The study included all primary SPK transplants performed in the U.S. between January 1, 2000 and December 31, 2007 . The causes of death were similar between the two cohorts . The risk of kidney graft failure more than doubled the risk for death among SPK recipients with early graft failure .

Early pancreas graft failure in SPK transplant recipients is associated with an increased risk for subsequent kidney failure and death. Optimization of therapeutic interventions after early pancreas graft failure is needed.

yes

### Human: Early pancreas graft failure is common after simultaneous kidney and SPK transplantation . We studied the impact of early pancrease graft failure on long-term kidney and patient survival . Early panceas graft failures were associated with lower subsequent kidney graft and survival . The study included all primary SPK transplants performed in the U.S. between January 1, 2000 and December 31, 2007 . The causes of death were similar between the two cohorts . The risk of kidney graft failure more than doubled the risk for death among SPK recipients with early graft failure . Is early pancreas graft failure associated with inferior late clinical outcomes after simultaneous kidney-pancreas transplantation?### Assistant: Early pancreas graft failure in SPK transplant recipients is associated with an increased risk for subsequent kidney failure and death. Optimization of therapeutic interventions after early pancreas graft failure is needed.

Early pancreas graft failure in SPK transplant recipients is associated with an increased risk for subsequent kidney failure and death . Optimization of

Does four weeks of IV iron supplementation reduce perceived fatigue and mood disturbance in distance runners?

Fourteen distance runners with serum ferritin 30-100 µg · L(-1 were randomly assigned to receive three blinded injections of intravenous ferric-carboxymaltose (2 ml, 100 mg, IRON) or normal saline (PLACEBO) over four weeks . Hemoglobin mass (Hbmass) was assessed via carbon monoxide rebreathing at weeks 0 and 6 . Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score (TFS) and Total Mood Disturbance (TMD)

During 6 weeks of training, intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency, without concurrent improvements in oxygen transport capacity or performance.

yes

### Human: Fourteen distance runners with serum ferritin 30-100 µg · L(-1 were randomly assigned to receive three blinded injections of intravenous ferric-carboxymaltose (2 ml, 100 mg, IRON) or normal saline (PLACEBO) over four weeks . Hemoglobin mass (Hbmass) was assessed via carbon monoxide rebreathing at weeks 0 and 6 . Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score (TFS) and Total Mood Disturbance (TMD) Does four weeks of IV iron supplementation reduce perceived fatigue and mood disturbance in distance runners?### Assistant: During 6 weeks of training, intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency, without concurrent improvements in oxygen transport capacity or performance.

intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency . Without concurrent improvements in oxygen transport capacity or performance

Is polymorphism of SLC25A32 , the folate transporter gene , associated with plasma folate levels and bone fractures in Japanese postmenopausal women?

The SLC25A32 gene, the mitochondrial inner membrane folate transporter, also could be implicated in the regulation of folate metabolism and fracture . A total of 851 Japanese postmenopausal women participated in the association study . The AA genotype of a single nucleotide polymorphism at the 3'UTR region in the SLC 25A32 genes was associated with lower plasma folate concentration compared with the other genotypes in 851 women . The study was followed up for 5.5 ± 0.1 years (mean ± SE)

These results show that the SLC25A32 gene polymorphism could be a risk factor for lower folate concentration and future fracture.

yes

### Human: The SLC25A32 gene, the mitochondrial inner membrane folate transporter, also could be implicated in the regulation of folate metabolism and fracture . A total of 851 Japanese postmenopausal women participated in the association study . The AA genotype of a single nucleotide polymorphism at the 3'UTR region in the SLC 25A32 genes was associated with lower plasma folate concentration compared with the other genotypes in 851 women . The study was followed up for 5.5 ± 0.1 years (mean ± SE) Is polymorphism of SLC25A32 , the folate transporter gene , associated with plasma folate levels and bone fractures in Japanese postmenopausal women?### Assistant: These results show that the SLC25A32 gene polymorphism could be a risk factor for lower folate concentration and future fracture.

These results show that the SLC25A32 gene polymorphism could be a risk factor for lower folate concentration and future fracture .

Is loxin polymorphism associated with increased resistin levels and with oxidative status?

LOX-1 polymorphism may impact on inflammation and cardiovascular risk by modulating systemic resistin expression .276 men were randomly selected from a population-based cohort . Metabolic and inflammatory markers were evaluated at baseline and after 6-years follow-up, OLR1 (loxin) IVS4-14 A>G polymorphism was assessed . Mean plasma resistin and nitrotyrosine values were significantly higher, and TAS was significantly lowered in homozygous for the G allele .

Enhanced oxidized-LDL uptake by LOX-1 G-allele carriers is associated with increased pro-oxidant status and resistin levels, suggesting a major uptake of ox-LDL by macrophages, smooth muscle cells, and monocytes.

yes

### Human: LOX-1 polymorphism may impact on inflammation and cardiovascular risk by modulating systemic resistin expression .276 men were randomly selected from a population-based cohort . Metabolic and inflammatory markers were evaluated at baseline and after 6-years follow-up, OLR1 (loxin) IVS4-14 A>G polymorphism was assessed . Mean plasma resistin and nitrotyrosine values were significantly higher, and TAS was significantly lowered in homozygous for the G allele . Is loxin polymorphism associated with increased resistin levels and with oxidative status?### Assistant: Enhanced oxidized-LDL uptake by LOX-1 G-allele carriers is associated with increased pro-oxidant status and resistin levels, suggesting a major uptake of ox-LDL by macrophages, smooth muscle cells, and monocytes.

LOX-1 G-allele carriers are associated with increased pro-oxidant status and resistin levels . The uptake of

Are gastric atrophy and xanthelasma markers for predicting the development of early gastric cancer?

The significance of gastric xanthelasma in relation to gastric cancer still remains unclear . We investigated whether gastric . xantheasma would be a useful marker for predicting the development of early gastric. cancer . A total of 1823 patients who underwent a medical health checkup were enrolled were enrolled . The presence of gastrixanthelasm was significantly associated with age . age .65 years, male gender, open-type atrophy, and the presence of diabetes mellitus (DM)

Gastric xanthelasma is a useful marker for predicting the development of gastric cancer.

yes

### Human: The significance of gastric xanthelasma in relation to gastric cancer still remains unclear . We investigated whether gastric . xantheasma would be a useful marker for predicting the development of early gastric. cancer . A total of 1823 patients who underwent a medical health checkup were enrolled were enrolled . The presence of gastrixanthelasm was significantly associated with age . age .65 years, male gender, open-type atrophy, and the presence of diabetes mellitus (DM) Are gastric atrophy and xanthelasma markers for predicting the development of early gastric cancer?### Assistant: Gastric xanthelasma is a useful marker for predicting the development of gastric cancer.

Gastric xanthelasma is a useful marker for predicting the development of gastric cancer .

Does fucoidan induce cancer cell apoptosis by modulating the endoplasmic reticulum stress cascades?

Fucoidan, a fucose-rich polysaccharide isolated from marine brown alga, is a promising natural product with significant anti-cancer activity . Little is known about the role of endoplasmic reticulum (ER) stress in fucoidan-induced cell apoptosis . Fucodan treatment inhibits cell growth and induces apoptosis in cancer cells . It also promotes ER Ca2+-dependent calmodulin-dependent kinase II phosphorylation, Bcl-associated X protein (Bax) and caspase 12 expression in MDA-MB-231 cells, but not in HCT116 cells .

Fucoidan exerts its anti-tumor function by modulating ER stress cascades. Contribution of ER stress to the fucoidan-induced cell apoptosis augments our understanding of the molecular mechanisms underlying its anti-tumour activity and provides evidence for the therapeutic application of fucoidan in cancer.

yes

### Human: Fucoidan, a fucose-rich polysaccharide isolated from marine brown alga, is a promising natural product with significant anti-cancer activity . Little is known about the role of endoplasmic reticulum (ER) stress in fucoidan-induced cell apoptosis . Fucodan treatment inhibits cell growth and induces apoptosis in cancer cells . It also promotes ER Ca2+-dependent calmodulin-dependent kinase II phosphorylation, Bcl-associated X protein (Bax) and caspase 12 expression in MDA-MB-231 cells, but not in HCT116 cells . Does fucoidan induce cancer cell apoptosis by modulating the endoplasmic reticulum stress cascades?### Assistant: Fucoidan exerts its anti-tumor function by modulating ER stress cascades. Contribution of ER stress to the fucoidan-induced cell apoptosis augments our understanding of the molecular mechanisms underlying its anti-tumour activity and provides evidence for the therapeutic application of fucoidan in cancer.

Fucoidan exerts its anti-tumor function by modulating ER stress cascades . Contribution of ER stress to the

Are steroidogenic factor 1 overexpression and gene amplification more frequent in adrenocortical tumors from children than from adults?

SF-1 protein expression was assessed in a cohort of 103 adrenocortical tumors from 36 children and 67 adults . SF--1 is a key determinant of endocrine development and function of adrenal cortex . SF1 overexpression and gene amplification were previously demonstrated in a small group of pediatric adrenocortsical tumors . The frequency of SF-One overexpressment and gene amplibation was similar in carcinomas and adenomas of carcinomas . All tumors with SF1 gene amplification showed a strong SF1 staining, whereas most of the tumors (61%) without SF-

We demonstrated a higher frequency of SF-1 overexpression and gene amplification in pediatric than in adult adrenocortical tumors, suggesting an important role of SF-1 in pediatric adrenocortical tumorigenesis.

yes

### Human: SF-1 protein expression was assessed in a cohort of 103 adrenocortical tumors from 36 children and 67 adults . SF--1 is a key determinant of endocrine development and function of adrenal cortex . SF1 overexpression and gene amplification were previously demonstrated in a small group of pediatric adrenocortsical tumors . The frequency of SF-One overexpressment and gene amplibation was similar in carcinomas and adenomas of carcinomas . All tumors with SF1 gene amplification showed a strong SF1 staining, whereas most of the tumors (61%) without SF- Are steroidogenic factor 1 overexpression and gene amplification more frequent in adrenocortical tumors from children than from adults?### Assistant: We demonstrated a higher frequency of SF-1 overexpression and gene amplification in pediatric than in adult adrenocortical tumors, suggesting an important role of SF-1 in pediatric adrenocortical tumorigenesis.

SF-1 overexpression and gene amplification in pediatric than in adult adrenocortical tumors . This suggests an important role of SF

Is the transcription factor Nfix essential for normal brain development?

The Nuclear Factor I (NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems . Nfix-deficient mice show callosal agenesis and forebrain defects resembling those seen in Nfia and Nfib KO mice . The Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix . In particular, there appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix mice .

These data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects.

yes

### Human: The Nuclear Factor I (NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems . Nfix-deficient mice show callosal agenesis and forebrain defects resembling those seen in Nfia and Nfib KO mice . The Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix . In particular, there appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix mice . Is the transcription factor Nfix essential for normal brain development?### Assistant: These data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects.

The delays seen in eye and ear opening and brain morphology defects appear independent of nutritional deprivation . Rescue of perinatal lethality with soft

Do postoperative comparison of four perioperative analgesia protocols in dogs undergoing stifle joint surgery?

Dogs undergoing tibial plateau leveling osteotomy were randomly assigned to receive a constant rate infusion of morphine, lidocaine, and ketamine . Dogs with a postoperative pain score > 5 of 24 were given morphine as rescue analgesia . No differences in pain score, sedation score, rescue analgesa requirement, or time to first rescue analgesic after surgery were detected among groups . Dogs were given a lumbosacral epidural with morphine and ropivacaine; or only IM premedication with morphine .

Pain scores were similar among groups, and all 4 groups had similar rescue analgesia requirements and similar times to first administration of rescue analgesia. All 4 analgesic protocols provided acceptable analgesia for 24 hours after stifle joint surgery.

yes

### Human: Dogs undergoing tibial plateau leveling osteotomy were randomly assigned to receive a constant rate infusion of morphine, lidocaine, and ketamine . Dogs with a postoperative pain score > 5 of 24 were given morphine as rescue analgesia . No differences in pain score, sedation score, rescue analgesa requirement, or time to first rescue analgesic after surgery were detected among groups . Dogs were given a lumbosacral epidural with morphine and ropivacaine; or only IM premedication with morphine . Do postoperative comparison of four perioperative analgesia protocols in dogs undergoing stifle joint surgery?### Assistant: Pain scores were similar among groups, and all 4 groups had similar rescue analgesia requirements and similar times to first administration of rescue analgesia. All 4 analgesic protocols provided acceptable analgesia for 24 hours after stifle joint surgery.

Pain scores were similar among groups, and all 4 groups had similar rescue analgesia requirements . All 4 protocols provided acceptable analgesia for 24

Do substantial skin disorders in psychiatric illness coincide with diabetes and addiction?

Dermatitis was associated with affective disorder (OR=2.5; 95% CI: 1.12-5.43) but not with psychosis . Dermatitic patients with skin infections were likely to have diabetes [odds ratio (OR): 3.6; 95%, CI: 0.23-0.90]. Dermatism was associated . with affectives disorder (or = 2.5) but with psychosis (OR = 0.5), only a poor correlation existed between the length of hospital stay and skin problems .

Dermatological problems are common in hospitalized psychiatric patients. Patients with diabetes mellitus are at high risk for skin infections. There are significant relationships between the psychiatric and the dermatological diagnoses. The length of the admission to a psychiatric hospital does not seem to play a major role in skin diseases.

yes

### Human: Dermatitis was associated with affective disorder (OR=2.5; 95% CI: 1.12-5.43) but not with psychosis . Dermatitic patients with skin infections were likely to have diabetes [odds ratio (OR): 3.6; 95%, CI: 0.23-0.90]. Dermatism was associated . with affectives disorder (or = 2.5) but with psychosis (OR = 0.5), only a poor correlation existed between the length of hospital stay and skin problems . Do substantial skin disorders in psychiatric illness coincide with diabetes and addiction?### Assistant: Dermatological problems are common in hospitalized psychiatric patients. Patients with diabetes mellitus are at high risk for skin infections. There are significant relationships between the psychiatric and the dermatological diagnoses. The length of the admission to a psychiatric hospital does not seem to play a major role in skin diseases.

Dermatological problems are common in hospitalized psychiatric patients . Patients with diabetes mellitus are at high risk for skin infections . The length of

Does strength training normalize resting blood pressure in 65- to 73-year-old men and women with high normal blood pressure?

Twenty-one sedentary, healthy older men and women served as subjects for the study . Six months of progressive whole body ST performed 3 days per week using Keiser K-300 air-powered resistance machines . Resting BP was reduced significantly in men (134 +/- 3 vs 127 +/- 2 mm Hg, P < .01) but not in women . Diastolic BP was also reduced following training in both men (81 +/- 3) and women (78 +/- 2 vs 74 +/- 2mm Hg)

Six months of heavy resistance ST may reduce resting BP in older persons. According to the latest guidelines from the Joint National Committee for the Detection, Evaluation, and Treatment of Hypertension, the changes in resting BP noted in the present study represent a shift from the high normal to the normal category.

yes

### Human: Twenty-one sedentary, healthy older men and women served as subjects for the study . Six months of progressive whole body ST performed 3 days per week using Keiser K-300 air-powered resistance machines . Resting BP was reduced significantly in men (134 +/- 3 vs 127 +/- 2 mm Hg, P < .01) but not in women . Diastolic BP was also reduced following training in both men (81 +/- 3) and women (78 +/- 2 vs 74 +/- 2mm Hg) Does strength training normalize resting blood pressure in 65- to 73-year-old men and women with high normal blood pressure?### Assistant: Six months of heavy resistance ST may reduce resting BP in older persons. According to the latest guidelines from the Joint National Committee for the Detection, Evaluation, and Treatment of Hypertension, the changes in resting BP noted in the present study represent a shift from the high normal to the normal category.

Six months of heavy resistance ST may reduce resting BP in older persons .

Does local delivery of antithrombin inhibit platelet deposition after balloon injury in a porcine coronary model?

A therapeutic approach may be effectively to inhibit thrombin activity at the site of the vessel wall injury . The number of platelets per cm2 was significantly lower in the antithrombin group than in the control group . No macroscopic thrombus was detected in the anti-antithrombi group, while three out of eight pigs in a control group had visible thrombotic formation (NS) There was an increase in the plasma concentration of antitrombin after local delivery .

Antithrombin can be administered and deposited locally in the coronary vessel wall thereby reducing platelet deposition after balloon injury.

yes

### Human: A therapeutic approach may be effectively to inhibit thrombin activity at the site of the vessel wall injury . The number of platelets per cm2 was significantly lower in the antithrombin group than in the control group . No macroscopic thrombus was detected in the anti-antithrombi group, while three out of eight pigs in a control group had visible thrombotic formation (NS) There was an increase in the plasma concentration of antitrombin after local delivery . Does local delivery of antithrombin inhibit platelet deposition after balloon injury in a porcine coronary model?### Assistant: Antithrombin can be administered and deposited locally in the coronary vessel wall thereby reducing platelet deposition after balloon injury.

Antithrombin can be administered and deposited locally in the coronary vessel wall . It reduces platelet deposition after balloon injury . Antith

Do autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy?

The ability of mesenchymal stem cells to heal the chronically injured heart remains controversial . Here we tested the hypothesis that autologous MSCs can be safely injected into a chronic myocardial infarct scar, reduce its size, and improve ventricular function . Ectopic tissue formation was not observed with the MSC . The authors conclude that high-dose MSC therapy reduced infarCT size from 18.2 +/- 0.9 to 14.4 +/- 1.0% of LV mass .

Together these data demonstrate that autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling. These findings demonstrate the safety and efficacy of autologous MSC therapy and support clinical trials of MSC therapy in patients with chronic ischaemic cardiomyopathy.

yes

### Human: The ability of mesenchymal stem cells to heal the chronically injured heart remains controversial . Here we tested the hypothesis that autologous MSCs can be safely injected into a chronic myocardial infarct scar, reduce its size, and improve ventricular function . Ectopic tissue formation was not observed with the MSC . The authors conclude that high-dose MSC therapy reduced infarCT size from 18.2 +/- 0.9 to 14.4 +/- 1.0% of LV mass . Do autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy?### Assistant: Together these data demonstrate that autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling. These findings demonstrate the safety and efficacy of autologous MSC therapy and support clinical trials of MSC therapy in patients with chronic ischaemic cardiomyopathy.

Autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling . These

Is risk for bipolar disorder associated with face-processing deficits across emotions?

Youth with euthymic bipolar disorder (BD) have a deficit in face-emotion labeling that is present across multiple emotions . It is unclear whether this deficit in at-risk youths is present in all emotions or if the impairment presents initially as an emotion-specific dysfunction that then generalizes to other emotions as the symptoms of BD become manifest . The patients with BD and the at risk youths did not differ from each other. Group-by-emotions interactions were not significant, indicating that the group effects did not vary based on the facial emotion .

The youths at risk for BD demonstrate nonspecific deficits in face-emotion recognition, similar to patients with the illness. Further research is needed to determine whether such deficits meet all the criteria for an endophenotype.

yes

### Human: Youth with euthymic bipolar disorder (BD) have a deficit in face-emotion labeling that is present across multiple emotions . It is unclear whether this deficit in at-risk youths is present in all emotions or if the impairment presents initially as an emotion-specific dysfunction that then generalizes to other emotions as the symptoms of BD become manifest . The patients with BD and the at risk youths did not differ from each other. Group-by-emotions interactions were not significant, indicating that the group effects did not vary based on the facial emotion . Is risk for bipolar disorder associated with face-processing deficits across emotions?### Assistant: The youths at risk for BD demonstrate nonspecific deficits in face-emotion recognition, similar to patients with the illness. Further research is needed to determine whether such deficits meet all the criteria for an endophenotype.

The youths at risk for BD demonstrate nonspecific deficits in face-emotion recognition, similar to patients with the illness . Further research

Are energy requirements greater in elderly patients suffering from pressure ulcers?

To estimate energy requirements in diseased elderly patients with pressure ulcers (PUs) To estimate how much energy requirements can be compared to those of adults undergoing light physical activity . Measured RMR did not differ between the two groups (P=.48), and was not related to grade or size of the PUs . Energy intake was lower than energy requirements by 176 to 479 kcal/d . Energy requirements therefore ranged between 1,536+/-340 kcal/D and 1,828+/-405 kcal/day .

Diseased elderly patients with PUs do not have greater energy expenditure, with their requirements suggested to range between 25 and 30 kcal/kg body weight per day. Malnutrition within this population is most likely the result of low energy intake.

no

### Human: To estimate energy requirements in diseased elderly patients with pressure ulcers (PUs) To estimate how much energy requirements can be compared to those of adults undergoing light physical activity . Measured RMR did not differ between the two groups (P=.48), and was not related to grade or size of the PUs . Energy intake was lower than energy requirements by 176 to 479 kcal/d . Energy requirements therefore ranged between 1,536+/-340 kcal/D and 1,828+/-405 kcal/day . Are energy requirements greater in elderly patients suffering from pressure ulcers?### Assistant: Diseased elderly patients with PUs do not have greater energy expenditure, with their requirements suggested to range between 25 and 30 kcal/kg body weight per day. Malnutrition within this population is most likely the result of low energy intake.

Malnutrition within this population is most likely to be the result of low energy intake .

Does de novo sequencing of circulating miRNAs identify novel markers predicting clinical outcome of locally advanced breast cancer?

MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients . Discovery profiling of circulating small RNAs has not been reported in breast cancer . Study was carried out to identify blood-based small RNA markers of BC clinical outcome . Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified . Two circulating miRNA markers exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease . In the validation cohort, higher levels of circulating MiR-122 specifically predicted metastatic recurrence in stage II-III BC patients .

Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

yes

### Human: MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients . Discovery profiling of circulating small RNAs has not been reported in breast cancer . Study was carried out to identify blood-based small RNA markers of BC clinical outcome . Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified . Two circulating miRNA markers exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease . In the validation cohort, higher levels of circulating MiR-122 specifically predicted metastatic recurrence in stage II-III BC patients . Does de novo sequencing of circulating miRNAs identify novel markers predicting clinical outcome of locally advanced breast cancer?### Assistant: Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients . These results may allow optimized chemotherapy treatments and preventive

Is tDAG51 an ERK signaling target that opposes ERK-mediated HME16C mammary epithelial cell transformation?

Signaling downstream of Ras is mediated by three major pathways, Raf/ERK, phosphatidylinositol 3 kinase (PI3K), and Ral guanine nucleotide exchange factor (RalGEF) Ras signal transduction pathways play an important role in breast cancer progression . We examined whether a highly transcriptionally regulated ERK pathway target, PHLDA1 (TDAG51), suggested to be a tumor suppressor, might modulate the transformation process .

Our results suggest that multiple Ras signal transduction pathways contribute to mammary epithelial cell transformation, but that the ERK signaling pathway may be a crucial component downstream of EGFR activation during tumorigenesis. Furthermore, persistent activation of ERK signaling up-regulates TDAG51. This event serves as a negative regulator of both Erk activation as well as matrix-detached cellular proliferation and suggests that TDAG51 opposes ERK-mediated transformation in breast epithelial cells.

yes

### Human: Signaling downstream of Ras is mediated by three major pathways, Raf/ERK, phosphatidylinositol 3 kinase (PI3K), and Ral guanine nucleotide exchange factor (RalGEF) Ras signal transduction pathways play an important role in breast cancer progression . We examined whether a highly transcriptionally regulated ERK pathway target, PHLDA1 (TDAG51), suggested to be a tumor suppressor, might modulate the transformation process . Is tDAG51 an ERK signaling target that opposes ERK-mediated HME16C mammary epithelial cell transformation?### Assistant: Our results suggest that multiple Ras signal transduction pathways contribute to mammary epithelial cell transformation, but that the ERK signaling pathway may be a crucial component downstream of EGFR activation during tumorigenesis. Furthermore, persistent activation of ERK signaling up-regulates TDAG51. This event serves as a negative regulator of both Erk activation as well as matrix-detached cellular proliferation and suggests that TDAG51 opposes ERK-mediated transformation in breast epithelial cells.

ERK signaling may be a crucial component downstream of EGFR activation during tumorigenesis . Persistent activation of ERK up-reg

Do male and female runners demonstrate different sagittal plane mechanics as a function of static hamstring flexibility?

Forty subjects (30.0±6.4 years) participated and were placed in one of 4 groups: flexible males (n=10), inflexible males, flexible females (n =10), flexible females, flexible males, and inflexable females (N=10) All subjects were free of injury at the time of data collection . Three-dimensional kinematics and kinetics were collected while subjects ran over ground across 2 force platforms . Sagittal plane joint angles and moments were calculated at the knee and hip and compared with a 2-way (sex X flexibility) ANOVA (α=0.05)

Hamstring flexibility results in different mechanical profiles in males and females. Flexibility in the hamstrings may result in decreased moments via active or passive tension. These differences may have implications for performance and injury in flexible female runners.

yes

### Human: Forty subjects (30.0±6.4 years) participated and were placed in one of 4 groups: flexible males (n=10), inflexible males, flexible females (n =10), flexible females, flexible males, and inflexable females (N=10) All subjects were free of injury at the time of data collection . Three-dimensional kinematics and kinetics were collected while subjects ran over ground across 2 force platforms . Sagittal plane joint angles and moments were calculated at the knee and hip and compared with a 2-way (sex X flexibility) ANOVA (α=0.05) Do male and female runners demonstrate different sagittal plane mechanics as a function of static hamstring flexibility?### Assistant: Hamstring flexibility results in different mechanical profiles in males and females. Flexibility in the hamstrings may result in decreased moments via active or passive tension. These differences may have implications for performance and injury in flexible female runners.

Flexibility in the hamstrings may result in decreased moments via active or passive tension . These differences may have implications for performance and injury in

Are high levels of platelet/lymphocyte ratio associated with metastatic gastric cancer?

PLR values of advanced gastric cancer (not including metastatic cases) were significantly higher compared to early gastric cancers (231.6±107.45 and 160.3±71.5, respectively; p<0.001) PLR was an independent predictive factor for tumor burden in both stage and metastasis groups . PLR showed mild correlation with stage and stage and tumor burden groups . The study was published in the journal Nature Biologia, published online on June 14, 2015 .

Pretreatment PLR values were correlated with tumor burden, and most higher values were detected in metastatic disease. Our findings may be useful, especially in the decision-making for laparoscopic staging in patients who have no radiological evidence of metastatic disease.

yes

### Human: PLR values of advanced gastric cancer (not including metastatic cases) were significantly higher compared to early gastric cancers (231.6±107.45 and 160.3±71.5, respectively; p<0.001) PLR was an independent predictive factor for tumor burden in both stage and metastasis groups . PLR showed mild correlation with stage and stage and tumor burden groups . The study was published in the journal Nature Biologia, published online on June 14, 2015 . Are high levels of platelet/lymphocyte ratio associated with metastatic gastric cancer?### Assistant: Pretreatment PLR values were correlated with tumor burden, and most higher values were detected in metastatic disease. Our findings may be useful, especially in the decision-making for laparoscopic staging in patients who have no radiological evidence of metastatic disease.

Pretreatment PLR values were correlated with tumor burden . Most higher values were detected in metastatic disease . Findings may be useful

Is expression of CD40 a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP ( rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisone )?

The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab-CHOP . The study found CD40 expressions were not statistically different between the germinal center B-Cell-like (GCB) type and the non-GCB type . A low expression of CD 40 compared to high expression is related to poor OS and PFS .

Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP.

yes

### Human: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab-CHOP . The study found CD40 expressions were not statistically different between the germinal center B-Cell-like (GCB) type and the non-GCB type . A low expression of CD 40 compared to high expression is related to poor OS and PFS . Is expression of CD40 a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP ( rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisone )?### Assistant: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP.

CD40 level at onset acts as independent prognostic predictor of DLBCL patients treated with R-CHOP .

Does botulinum toxin type A reduce histamine-induced itch and vasomotor responses in human skin?

Botox is believed to be effective against itch as it inhibits the release of acetylcholine as well as some other substances that may be involved in itch . BoNT/A reduced the histamine-induced itch intensity (F(1,39) = 30.2, P < 0.001) and itch area (F) = 8.8, P = 0.011) Compared with saline, the duration of itch was shorter for the BoNT-treated areas (F: 19.4) with a peak effect at day 7 .

BoNT/A reduced the itch intensity, blood flow and neurogenic inflammation in response to the histamine prick test in human skin. The findings could be applicable in the treatment of some pruritic conditions that can be difficult to treat with conventional treatments.

yes

### Human: Botox is believed to be effective against itch as it inhibits the release of acetylcholine as well as some other substances that may be involved in itch . BoNT/A reduced the histamine-induced itch intensity (F(1,39) = 30.2, P < 0.001) and itch area (F) = 8.8, P = 0.011) Compared with saline, the duration of itch was shorter for the BoNT-treated areas (F: 19.4) with a peak effect at day 7 . Does botulinum toxin type A reduce histamine-induced itch and vasomotor responses in human skin?### Assistant: BoNT/A reduced the itch intensity, blood flow and neurogenic inflammation in response to the histamine prick test in human skin. The findings could be applicable in the treatment of some pruritic conditions that can be difficult to treat with conventional treatments.

BoNT/A reduced itch intensity, blood flow and neurogenic inflammation in response to the histamine prick test in human skin . The

Is bronchodilatory effect of deep inspiration absent in subjects with mild COPD?

We measured deep inspiration-induced bronchodilation in 19 patients with COPD and 17 healthy subjects . Each subject underwent a series of single-dose methacholine provocations to induce at least a 15% reduction in inspiratory vital capacity (IVC) When this was achieved, subjects were asked to perform four consecutive deep inspirations . The percentage of reduction in IVC from baseline prior to the deep inspiration did not differ between the two groups (COPD, 20.1 +/- 1.6%; healthy, 22.7 +/- 2.4%; p = 0.38)

The bronchodilatory ability of deep inspiration is lost in mild COPD. We speculate that the absence of deep inspiration-induced bronchodilation contributes to the development and severity of chronic respiratory symptoms in patients with COPD.

yes

### Human: We measured deep inspiration-induced bronchodilation in 19 patients with COPD and 17 healthy subjects . Each subject underwent a series of single-dose methacholine provocations to induce at least a 15% reduction in inspiratory vital capacity (IVC) When this was achieved, subjects were asked to perform four consecutive deep inspirations . The percentage of reduction in IVC from baseline prior to the deep inspiration did not differ between the two groups (COPD, 20.1 +/- 1.6%; healthy, 22.7 +/- 2.4%; p = 0.38) Is bronchodilatory effect of deep inspiration absent in subjects with mild COPD?### Assistant: The bronchodilatory ability of deep inspiration is lost in mild COPD. We speculate that the absence of deep inspiration-induced bronchodilation contributes to the development and severity of chronic respiratory symptoms in patients with COPD.

The bronchodilatory ability of deep inspiration is lost in mild COPD patients . The absence of the ability contributes to the development

Does thrombin generation during reperfusion after coronary artery bypass surgery associate with postoperative myocardial damage?

Thrombin contributes to myocardial ischemia-reperfusion injury in animal studies, but the role of thrombin in mycardial damage after CABG is unknown . We measured thrombi generation and fibrin turnover during . reperfusion after CACG to evaluate their associations with postoperative hemodynamic changes and . myocard . damage . Patients with evidence of myocardrial damage had significantly higher F(1+2) during . reperfusions than others (P < 0.002)

Reperfusion caused a burst in thrombin generation and fibrin turnover despite generous heparinization. Thrombin generation during reperfusion after CABG associated with pulmonary vascular resistance and postoperative myocardial damage.

yes

### Human: Thrombin contributes to myocardial ischemia-reperfusion injury in animal studies, but the role of thrombin in mycardial damage after CABG is unknown . We measured thrombi generation and fibrin turnover during . reperfusion after CACG to evaluate their associations with postoperative hemodynamic changes and . myocard . damage . Patients with evidence of myocardrial damage had significantly higher F(1+2) during . reperfusions than others (P < 0.002) Does thrombin generation during reperfusion after coronary artery bypass surgery associate with postoperative myocardial damage?### Assistant: Reperfusion caused a burst in thrombin generation and fibrin turnover despite generous heparinization. Thrombin generation during reperfusion after CABG associated with pulmonary vascular resistance and postoperative myocardial damage.

Thrombin generation during reperfusion after CABG associated with pulmonary vascular resistance and postoperative myocardial damage . Throm

Is problem drinking associated with increased prevalence of sexual risk behaviors among men who have sex with men ( MSM ) in Lima , Peru?

Alcohol use is an important but understudied HIV risk factor among men who have sex with men (MSM) We studied the relationship between problem drinking and sexual risk among MSM in Lima, Peru . Problem drinkers were significantly more likely to report failing to always use condoms, use alcohol or drugs prior to their most recent sexual encounter, report a history of sexual coercion and to engage in transactional sex . They also reported significantly higher numbers of recent and lifetime sexual partners, including receiving compensation for sex in the last six months .

We found a high prevalence of problem drinking among MSM in Lima, Peru, which was associated with increased sexual risk in our study. Of note, individuals who were already HIV-infected were less likely to be problem drinkers. Further studies and targeted interventions to reduce problem drinking among MSM are warranted.

yes

### Human: Alcohol use is an important but understudied HIV risk factor among men who have sex with men (MSM) We studied the relationship between problem drinking and sexual risk among MSM in Lima, Peru . Problem drinkers were significantly more likely to report failing to always use condoms, use alcohol or drugs prior to their most recent sexual encounter, report a history of sexual coercion and to engage in transactional sex . They also reported significantly higher numbers of recent and lifetime sexual partners, including receiving compensation for sex in the last six months . Is problem drinking associated with increased prevalence of sexual risk behaviors among men who have sex with men ( MSM ) in Lima , Peru?### Assistant: We found a high prevalence of problem drinking among MSM in Lima, Peru, which was associated with increased sexual risk in our study. Of note, individuals who were already HIV-infected were less likely to be problem drinkers. Further studies and targeted interventions to reduce problem drinking among MSM are warranted.

A high prevalence of problem drinking among MSM in Lima, Peru, was associated with increased sexual risk . Individuals who were already HIV-infect

Is persistent poststroke hyperglycemia independently associated with infarct expansion and worse clinical outcome?

Hyperglycemia at the time of stroke is associated with increased mortality and morbidity . Animal studies suggest that infarct expansion may be responsible . We measured the blood glucose profile after acute stroke and correlated it with infarCT volume changes using T2- and diffusion-weighted MRI . Multiple regression analysis indicated that both mean CGMS glucose levels >or=7 mmol/L were independently associated with . increased final infarict volume change . Acute and final infartct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CG MS glucose or mean BGL glucose >or =7 mmol/.

Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infarct expansion and is associated with worse functional outcome. There is an urgent need to study normalization of blood glucose after stroke.

yes

### Human: Hyperglycemia at the time of stroke is associated with increased mortality and morbidity . Animal studies suggest that infarct expansion may be responsible . We measured the blood glucose profile after acute stroke and correlated it with infarCT volume changes using T2- and diffusion-weighted MRI . Multiple regression analysis indicated that both mean CGMS glucose levels >or=7 mmol/L were independently associated with . increased final infarict volume change . Acute and final infartct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CG MS glucose or mean BGL glucose >or =7 mmol/. Is persistent poststroke hyperglycemia independently associated with infarct expansion and worse clinical outcome?### Assistant: Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infarct expansion and is associated with worse functional outcome. There is an urgent need to study normalization of blood glucose after stroke.

Hyperglycemia on serial glucose monitoring is independent determinant of infarct expansion and associated with worse functional outcome . There is an

Are identification of large rearrangements of the PCDH15 gene by combined MLPA and a CGH : large duplications responsible for Usher syndrome?

PCDH15, encoding protocadherin 15, is mutated in Usher syndrome type 1F (USH1F) patients . Not only point mutations, but also large deletions have been detected within this gene . The purpose of the present work was to identify large genomic rearrangements of PC DH15 in a cohort of patients and to accurately identify the location of the junction breakpoints of the detected rearrangement . The exact breakpoints were identified . The study was published in the journal Nature Biologia .

This is the first time that large duplications have been associated with Usher syndrome. USH patients have not been extensively tested for large genomic rearrangements such as duplications and deletions. This type of mutation easily escapes detection by traditional PCR-based

yes

### Human: PCDH15, encoding protocadherin 15, is mutated in Usher syndrome type 1F (USH1F) patients . Not only point mutations, but also large deletions have been detected within this gene . The purpose of the present work was to identify large genomic rearrangements of PC DH15 in a cohort of patients and to accurately identify the location of the junction breakpoints of the detected rearrangement . The exact breakpoints were identified . The study was published in the journal Nature Biologia . Are identification of large rearrangements of the PCDH15 gene by combined MLPA and a CGH : large duplications responsible for Usher syndrome?### Assistant: This is the first time that large duplications have been associated with Usher syndrome. USH patients have not been extensively tested for large genomic rearrangements such as duplications and deletions. This type of mutation easily escapes detection by traditional PCR-based

This is the first time that large duplications have been associated with Usher syndrome . USH patients have not been extensively tested for large

Does three-dimensional invasion of human glioblastoma cells remain unchanged by X-ray and carbon ion irradiation in vitro?

Migration and invasion capability of glioblastoma cells on and in collagen type I were evaluated upon irradiation with X-rays or carbon ions . Clonogenic radiation survival, proliferation, DNA double-strand breaks, and expression of invasion-relevant proteins (eg, β1 integrin, FAK, MMP2, and MMP9) were explored . Intriguingly, irradiated cells migrated unhampered, despite DNA double strand breaks and reduced proliferation .

These findings indicate that X-rays and carbon ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of glioblastoma cells in a collagen type I environment. Addition of targeted agents against members of the MAPK and PI3K signaling axis to conventional chemoradiation therapy seems potentially useful to optimize glioblastoma therapy.

yes

### Human: Migration and invasion capability of glioblastoma cells on and in collagen type I were evaluated upon irradiation with X-rays or carbon ions . Clonogenic radiation survival, proliferation, DNA double-strand breaks, and expression of invasion-relevant proteins (eg, β1 integrin, FAK, MMP2, and MMP9) were explored . Intriguingly, irradiated cells migrated unhampered, despite DNA double strand breaks and reduced proliferation . Does three-dimensional invasion of human glioblastoma cells remain unchanged by X-ray and carbon ion irradiation in vitro?### Assistant: These findings indicate that X-rays and carbon ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of glioblastoma cells in a collagen type I environment. Addition of targeted agents against members of the MAPK and PI3K signaling axis to conventional chemoradiation therapy seems potentially useful to optimize glioblastoma therapy.

X-rays and carbon ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of gliob

Is mucinous differentiation in colonic adenocarcinoma associated with a reduction in tumour-infiltrating lymphocytes?

The density of tumour-infiltrating lymphocytes (TILs) in colorectal carcinomas showing mucinous differentiation was compared to that of 65 adenocarcinomas of no special type (NOS) showing no mucinous differentiate . Mucinous differentiation is associated with a significantly lower density of TILs . This reduction in density is present also in adjacent foci of adenokarcinoma NOS within mucinous tumours . This is also present also .

There is a reduction in the number of TILs in all areas of colorectal adenocarcinomas that show mucinous differentiation, which may help explain the increased biological aggressiveness associated with this pattern of differentiation.

yes

### Human: The density of tumour-infiltrating lymphocytes (TILs) in colorectal carcinomas showing mucinous differentiation was compared to that of 65 adenocarcinomas of no special type (NOS) showing no mucinous differentiate . Mucinous differentiation is associated with a significantly lower density of TILs . This reduction in density is present also in adjacent foci of adenokarcinoma NOS within mucinous tumours . This is also present also . Is mucinous differentiation in colonic adenocarcinoma associated with a reduction in tumour-infiltrating lymphocytes?### Assistant: There is a reduction in the number of TILs in all areas of colorectal adenocarcinomas that show mucinous differentiation, which may help explain the increased biological aggressiveness associated with this pattern of differentiation.

There is a reduction in the number of TILs in all areas of colorectal adenocarcinomas that show

Is anti-L1CAM radioimmunotherapy more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model?

Anti-L1CAM radioimmunotherapy (RIT) with (67)Cu- and (177)Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts . In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6% for the (161)Tb-DOTA-chCE7 than the (177,Lu) RIT .

Our study is the first to show that anti-L1CAM (161)Tb RIT is more effective compared to (177)Lu RIT in ovarian cancer xenografts. These results suggest that (161)Tb is a promising candidate for future clinical applications in combination with internalising antibodies.

yes

### Human: Anti-L1CAM radioimmunotherapy (RIT) with (67)Cu- and (177)Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts . In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6% for the (161)Tb-DOTA-chCE7 than the (177,Lu) RIT . Is anti-L1CAM radioimmunotherapy more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model?### Assistant: Our study is the first to show that anti-L1CAM (161)Tb RIT is more effective compared to (177)Lu RIT in ovarian cancer xenografts. These results suggest that (161)Tb is a promising candidate for future clinical applications in combination with internalising antibodies.

Anti-L1CAM (161)Tb RIT is more effective compared to (177)Lu RIT in ovarian cancer

Is just-in-time learning effective in helping first responders manage weapons of mass destruction events?

Low frequency of CBRNE incidents leads to significant skill decay among first responders . Mobile training modules were developed for mobile devices to provide just-in-time training to first responders en route to a CBNNE event . This study assessed the efficacy and usability of the mobile training . The intervention group outperformed the control group in the explosives and chemical nerve agent scenarios; the differences were statistically significant . The change in pretest to posttest cognitive scores was significantly higher in the intervention group than in the control .

Mobile just-in-time training improved first-responder knowledge of CBRNE events and is an effective tool in helping first responders manage simulated explosive and chemical agent scenarios.

yes

### Human: Low frequency of CBRNE incidents leads to significant skill decay among first responders . Mobile training modules were developed for mobile devices to provide just-in-time training to first responders en route to a CBNNE event . This study assessed the efficacy and usability of the mobile training . The intervention group outperformed the control group in the explosives and chemical nerve agent scenarios; the differences were statistically significant . The change in pretest to posttest cognitive scores was significantly higher in the intervention group than in the control . Is just-in-time learning effective in helping first responders manage weapons of mass destruction events?### Assistant: Mobile just-in-time training improved first-responder knowledge of CBRNE events and is an effective tool in helping first responders manage simulated explosive and chemical agent scenarios.

Mobile just-in-time training has improved first-responder knowledge of CBRNE events . Mobile training is an effective tool in

Are total cholesterol and lipoprotein composition associated with dry eye disease in Korean women?

Korean study enrolled 5,627 adults (aged >19 years) who were participating in the first year of the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2011 . Dyslipidemia was defined as any of the following: hypercholesterolemia (total cholesterol > 200 mg/dL) or high levels of low-density lipoprotein (40  mg/dL), or low levels of high-densityliprotein (100 g/dL/dL).

DED in a Korean population was found to be associated with high serum cholesterol levelsThe results of this study highlight the significance of eye examinations and independent lipid profile monitoring in patients with dyslipidemia because of its possible correlation with DED progression.

yes

### Human: Korean study enrolled 5,627 adults (aged >19 years) who were participating in the first year of the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2011 . Dyslipidemia was defined as any of the following: hypercholesterolemia (total cholesterol > 200 mg/dL) or high levels of low-density lipoprotein (40  mg/dL), or low levels of high-densityliprotein (100 g/dL/dL). Are total cholesterol and lipoprotein composition associated with dry eye disease in Korean women?### Assistant: DED in a Korean population was found to be associated with high serum cholesterol levelsThe results of this study highlight the significance of eye examinations and independent lipid profile monitoring in patients with dyslipidemia because of its possible correlation with DED progression.

DED in a Korean population was found to be associated with high serum cholesterol levels . The study highlights the significance of eye examinations and independent

Does recombinant TSH and Lithium overcome Amiodarone-Induced Low Radioiodine Uptake in a Thyrotoxic Female?

Recombinant human thyroid-stimulating hormone increases radioactive iodine uptake in selected populations . Lithium is used as an adjunct to radioactive iodine (RAI) therapy in Graves' disease with low RAIU . Both drugs used in combination, overcame low iodine-131 uptake in a Graves' patient . The patient became hypothyroid and is currently on levothyroxine replacement therapy. She became hyporyroid and became hypothroid and . is currently . on levoryroxine replacements therapy .

This case demonstrates the efficacy of combining rhTSH and lithium to overcome amiodarone-induced low iodine-131 uptake in Graves' disease.

yes

### Human: Recombinant human thyroid-stimulating hormone increases radioactive iodine uptake in selected populations . Lithium is used as an adjunct to radioactive iodine (RAI) therapy in Graves' disease with low RAIU . Both drugs used in combination, overcame low iodine-131 uptake in a Graves' patient . The patient became hypothyroid and is currently on levothyroxine replacement therapy. She became hyporyroid and became hypothroid and . is currently . on levoryroxine replacements therapy . Does recombinant TSH and Lithium overcome Amiodarone-Induced Low Radioiodine Uptake in a Thyrotoxic Female?### Assistant: This case demonstrates the efficacy of combining rhTSH and lithium to overcome amiodarone-induced low iodine-131 uptake in Graves' disease.

This case demonstrates the efficacy of combining rhTSH and lithium to overcome amiodarone-induced low iodine-131 uptake in Graves

Does adipocyte enhancer-binding protein 1 modulate adiposity and energy homeostasis?

AEBP1 is a transcriptional repressor that is down-regulated during adipogenesis . We generated AEBP 1-null mice and examined the physiological role of AEB1 as a key modulator of in vivo adiposity . AEBP-null animals are resistant to diet-induced obesity and resistant to obesity . AEB-null mouse mice have reduced adipose tissue mass and enhanced apoptosis with suppressed survival signal. AEBPone-null rodents are also resistant to the diet of diet-inducing obesity .

Our results suggest that AEBP1 negatively regulates adipose tissue PTEN levels, in conjunction with its role in proliferation and differentiation of pre-adipocytes, as a key functional role in modulation of in vivo adiposity.

yes

### Human: AEBP1 is a transcriptional repressor that is down-regulated during adipogenesis . We generated AEBP 1-null mice and examined the physiological role of AEB1 as a key modulator of in vivo adiposity . AEBP-null animals are resistant to diet-induced obesity and resistant to obesity . AEB-null mouse mice have reduced adipose tissue mass and enhanced apoptosis with suppressed survival signal. AEBPone-null rodents are also resistant to the diet of diet-inducing obesity . Does adipocyte enhancer-binding protein 1 modulate adiposity and energy homeostasis?### Assistant: Our results suggest that AEBP1 negatively regulates adipose tissue PTEN levels, in conjunction with its role in proliferation and differentiation of pre-adipocytes, as a key functional role in modulation of in vivo adiposity.

AEBP1 negatively regulates adipose tissue PTEN levels, in conjunction with its role in proliferation and differentiation of pre-adipocytes

Does transcriptome analysis identify TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis?

Alcoholic hepatitis (AH) is a severe clinical condition that needs novel therapies . The identification of targets for therapy is hampered by the lack of animal models of advanced AH . The authors performed a translational study through a transcriptome analysis in patients with AH to identify new molecular targets . The study showed 207 genes >5-fold differentially expressed in patients . It also revealed seven pathways differentially regulated including 'cytokine-cyrokine receptor interaction' Several tumour necrosis factor (TNF) superfamily receptors, but not ligands, were overexpressed in AH . It correlated with both 90-day mortality and severity of portal hypertension .

Translational research revealed that TNF superfamily receptors are overexpressed in AH. Fn14, the receptor for TNF-like weak inducer of apoptosis, is selectively upregulated in patients with AH. TNF superfamily receptors could represent a potential target for therapy.

yes

### Human: Alcoholic hepatitis (AH) is a severe clinical condition that needs novel therapies . The identification of targets for therapy is hampered by the lack of animal models of advanced AH . The authors performed a translational study through a transcriptome analysis in patients with AH to identify new molecular targets . The study showed 207 genes >5-fold differentially expressed in patients . It also revealed seven pathways differentially regulated including 'cytokine-cyrokine receptor interaction' Several tumour necrosis factor (TNF) superfamily receptors, but not ligands, were overexpressed in AH . It correlated with both 90-day mortality and severity of portal hypertension . Does transcriptome analysis identify TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis?### Assistant: Translational research revealed that TNF superfamily receptors are overexpressed in AH. Fn14, the receptor for TNF-like weak inducer of apoptosis, is selectively upregulated in patients with AH. TNF superfamily receptors could represent a potential target for therapy.

TNF superfamily receptors are overexpressed in AH . Fn14, the receptor for TNF-like weak inducer of apopt

Does iQGAP1-dependent signaling pathway regulate endothelial cell proliferation and angiogenesis?

VEGF signaling is an obligate requirement for normal development and pathological angiogenesis such as cancer and age-related macular degeneration . Autophosphorylation of tyrosine 1173 (Y1173) of VEGFR-2 is considered a focal point for its angiogenic signal relay, however, the mechanism of phosphorylation is not fully understood . In this study we demonstrate that c-Src kinase directly through its Src homology 2 (SH2) domain and indirectly via c-Cbl binds to phospho-Y1057 of the protein . In turn, IQGAP1 activates b-Raf and mediates proliferation of endothelial cells .

Angiogenesis contributes to the pathology of numerous human diseases ranging from cancer to age-related macular degeneration. Determining molecular mechanism of tyrosine phosphorylation of VEGFR-2 and identification of molecules that are relaying its angiogenic signaling may identify novel targets for therapeutic intervention against angiogenesis-associated diseases. Our study shows that recruitment and activation of c-Src by VEGFR-2 plays a pivotal role in relaying angiogenic signaling of VEGFR-2; it phosphorylates VEGFR-2 at Y1173, facilitates association and activation of IQGAP1 and other signaling proteins to VEGFR-2. IQGAP1-dependent signaling, in part, is critically required for endothelial cell proliferation, a key step in angiogenesis. Thus, Y1057 of VEGFR-2 serves to regulate VEGFR-2 function in a combinatorial manner by supporting both diversity of recruitment of angiogenic signaling proteins to VEGFR-2, and its ability to promote angiogenesis.

yes

### Human: VEGF signaling is an obligate requirement for normal development and pathological angiogenesis such as cancer and age-related macular degeneration . Autophosphorylation of tyrosine 1173 (Y1173) of VEGFR-2 is considered a focal point for its angiogenic signal relay, however, the mechanism of phosphorylation is not fully understood . In this study we demonstrate that c-Src kinase directly through its Src homology 2 (SH2) domain and indirectly via c-Cbl binds to phospho-Y1057 of the protein . In turn, IQGAP1 activates b-Raf and mediates proliferation of endothelial cells . Does iQGAP1-dependent signaling pathway regulate endothelial cell proliferation and angiogenesis?### Assistant: Angiogenesis contributes to the pathology of numerous human diseases ranging from cancer to age-related macular degeneration. Determining molecular mechanism of tyrosine phosphorylation of VEGFR-2 and identification of molecules that are relaying its angiogenic signaling may identify novel targets for therapeutic intervention against angiogenesis-associated diseases. Our study shows that recruitment and activation of c-Src by VEGFR-2 plays a pivotal role in relaying angiogenic signaling of VEGFR-2; it phosphorylates VEGFR-2 at Y1173, facilitates association and activation of IQGAP1 and other signaling proteins to VEGFR-2. IQGAP1-dependent signaling, in part, is critically required for endothelial cell proliferation, a key step in angiogenesis. Thus, Y1057 of VEGFR-2 serves to regulate VEGFR-2 function in a combinatorial manner by supporting both diversity of recruitment of angiogenic signaling proteins to VEGFR-2, and its ability to promote angiogenesis.

Angiogenesis contributes to the pathology of numerous human diseases ranging from cancer to age-related macular degeneration . Determining molecular

Does incidence and risk factors of poststroke fall after discharge from inpatient rehabilitation?

Patients who had a stroke and had severe deficits showed a lower probability of post stroke falls . Left-sided hemiplegia/hemiparesis was associated with an increased risk of falls . Falls frequently occurred in winter, and most falls occurred indoors (70%) of patients experienced repeated falls . About half of those who fell were injured, and 11% sustained fractures . Patients who have severe deficits show a lower likelihood of falls, and those with ambulatory capacity are at risk of falling .

This study reveals a high incidence of poststroke falls after discharge from inpatient rehabilitation. More caution should be taken for patients with ambulatory ability and left hemiplegia/hemiparesis because they are more vulnerable to falls after a stroke. An increased prevalence of fear of falling in people who fell suggests that an appropriate intervention to reduce fear of falling should be provided to patients who have had a stroke.

yes

### Human: Patients who had a stroke and had severe deficits showed a lower probability of post stroke falls . Left-sided hemiplegia/hemiparesis was associated with an increased risk of falls . Falls frequently occurred in winter, and most falls occurred indoors (70%) of patients experienced repeated falls . About half of those who fell were injured, and 11% sustained fractures . Patients who have severe deficits show a lower likelihood of falls, and those with ambulatory capacity are at risk of falling . Does incidence and risk factors of poststroke fall after discharge from inpatient rehabilitation?### Assistant: This study reveals a high incidence of poststroke falls after discharge from inpatient rehabilitation. More caution should be taken for patients with ambulatory ability and left hemiplegia/hemiparesis because they are more vulnerable to falls after a stroke. An increased prevalence of fear of falling in people who fell suggests that an appropriate intervention to reduce fear of falling should be provided to patients who have had a stroke.

More caution should be taken for patients with ambulatory ability and left hemiplegia/hemiparesis .

Does integrin beta1 mediate hepatocellular carcinoma cells chemotaxis to laminin?

Study was designed to study integrin beta1 mediating chemotaxis of hepatocellular carcinoma (HCC) cells to laminin(LN) Cells were exposed to a range of chemotactic pseudopod protrusion . The study was carried out using a dual-pipette set-up in which two pipettes filled with LN solution were positioned in close contact with the same cell . The lengths of pseudopods were measured and plotted against time to obtain a pseudoopod growth curve .

Integrin beta1 subunit was an important constituent receptor subunit for mediating chemotactic pseudopod protrusion of HCC cell to LN.

yes

### Human: Study was designed to study integrin beta1 mediating chemotaxis of hepatocellular carcinoma (HCC) cells to laminin(LN) Cells were exposed to a range of chemotactic pseudopod protrusion . The study was carried out using a dual-pipette set-up in which two pipettes filled with LN solution were positioned in close contact with the same cell . The lengths of pseudopods were measured and plotted against time to obtain a pseudoopod growth curve . Does integrin beta1 mediate hepatocellular carcinoma cells chemotaxis to laminin?### Assistant: Integrin beta1 subunit was an important constituent receptor subunit for mediating chemotactic pseudopod protrusion of HCC cell to LN.

Integrin beta1 subunit was an important constituent receptor subunit for mediating chemotactic pseudopod protrusion of HCC

Is short androgen receptor allele length a poor prognostic factor in epithelial ovarian carcinoma?

Androgen activity may be modulated by altered expression or activity of the androgen receptor (AR) or AR polymorphisms . Exon 1 of the AR gene contains a polymorphic (CAG)(n) sequence whose length is inversely correlated with transcriptional activity . Patients with an AR allele containing < or =19 CAG repeats had a shorter time to recurrence (5.5 versus 19.4 months, P < 0.0001) and overall survival (9 versus 32.6 months)

These data support epidemiological evidence linking heightened androgenicity to the pathogenesis and tumor biology of epithelial ovarian cancer.

yes

### Human: Androgen activity may be modulated by altered expression or activity of the androgen receptor (AR) or AR polymorphisms . Exon 1 of the AR gene contains a polymorphic (CAG)(n) sequence whose length is inversely correlated with transcriptional activity . Patients with an AR allele containing < or =19 CAG repeats had a shorter time to recurrence (5.5 versus 19.4 months, P < 0.0001) and overall survival (9 versus 32.6 months) Is short androgen receptor allele length a poor prognostic factor in epithelial ovarian carcinoma?### Assistant: These data support epidemiological evidence linking heightened androgenicity to the pathogenesis and tumor biology of epithelial ovarian cancer.

These data support epidemiological evidence linking heightened androgenicity to the pathogenesis and tumor biology of epithelial ovarian cancer .

Is compliance with gastric cancer guidelines associated with improved outcomes?

The California Cancer Registry was used to identify cases of gastric cancer from 2001 to 2006 . Compliance with NCCN Guidelines occurred in just 45.5% of patients overall . Compliant care was associated with a 55% decreased hazard of mortality . Compliances were associated with median survival of 20 versus 7 months for noncompliant care . Patients with TNM staging or summary stage (SS) were also analyzed separately . Patients older than 55 years were less likely to receive guideline-compliant treatment .

Compliance with NCCN Guidelines and stage-specific therapy at presentation for the treatment of patients with gastric cancer was poor, which was a significant finding given that compliant care was associated with a 55% reduction in the hazard of death. Additionally, patients with TNM-staged cancer were more likely to receive compliant care, perhaps a result of having received more intensive therapy. Combined with the improved survival among compliant TNM-staged patients, these differences have meaningful implications for health services research.

yes

### Human: The California Cancer Registry was used to identify cases of gastric cancer from 2001 to 2006 . Compliance with NCCN Guidelines occurred in just 45.5% of patients overall . Compliant care was associated with a 55% decreased hazard of mortality . Compliances were associated with median survival of 20 versus 7 months for noncompliant care . Patients with TNM staging or summary stage (SS) were also analyzed separately . Patients older than 55 years were less likely to receive guideline-compliant treatment . Is compliance with gastric cancer guidelines associated with improved outcomes?### Assistant: Compliance with NCCN Guidelines and stage-specific therapy at presentation for the treatment of patients with gastric cancer was poor, which was a significant finding given that compliant care was associated with a 55% reduction in the hazard of death. Additionally, patients with TNM-staged cancer were more likely to receive compliant care, perhaps a result of having received more intensive therapy. Combined with the improved survival among compliant TNM-staged patients, these differences have meaningful implications for health services research.

Compliance with NCCN Guidelines and stage-specific therapy at presentation for the treatment of patients with gastric cancer was poor . Compliance

Are glycA , a novel proinflammatory glycoprotein biomarker , and high-sensitivity C-reactive protein inversely associated with sodium intake after controlling for adiposity : the Prevention of Renal and Vascular End-Stage Disease study?

The extent to which dietary sodium intake may confer alterations in the inflammatory status is unclear . GlycA is a novel proton nuclear magnetic resonance spectroscopy-measured biomarker of systemic inflammation, which is associated with the development of cardiovascular disease and diabetes . We determined associations of the inflammatory markers GlyCA and high-sensitivity C-reactive protein (hsCRP) with 24-h sodium excretion . After additional adjustment for body mass index (BMI), both GlycAs and ln hsCRP were inversely associated with sodium intake .

The proinflammatory biomarkers GlycA and hsCRP are inversely related to higher 24-h sodium excretion when taking into account the variation in adiposity. These inverse relations remain present after taking into account other covariates.

yes

### Human: The extent to which dietary sodium intake may confer alterations in the inflammatory status is unclear . GlycA is a novel proton nuclear magnetic resonance spectroscopy-measured biomarker of systemic inflammation, which is associated with the development of cardiovascular disease and diabetes . We determined associations of the inflammatory markers GlyCA and high-sensitivity C-reactive protein (hsCRP) with 24-h sodium excretion . After additional adjustment for body mass index (BMI), both GlycAs and ln hsCRP were inversely associated with sodium intake . Are glycA , a novel proinflammatory glycoprotein biomarker , and high-sensitivity C-reactive protein inversely associated with sodium intake after controlling for adiposity : the Prevention of Renal and Vascular End-Stage Disease study?### Assistant: The proinflammatory biomarkers GlycA and hsCRP are inversely related to higher 24-h sodium excretion when taking into account the variation in adiposity. These inverse relations remain present after taking into account other covariates.

Proinflammatory biomarkers GlycA and hsCRP are inversely related to higher 24-h sodium excretion . These inverse

Is aA-Amyloid cleared by endogenous immunological mechanisms?

AA-amyloidosis was induced in mice with injections of amyloid enhancing factor (AEF) and silver nitrate . The inflammation was induced by inflammation induced with injections . Resolution of the amyloids was monitored over time . Virtually all amylid was cleared within 34 weeks and macrophages were shown to internalize amylyloid . Passive immunization with an amylod specific monoclonal antibody reduced amyloidal development in murine AA-Amyloidosi .

Immunoglobulins co-localize with amyloid deposits and can contribute to amyloid degradation by Fc-receptor mediated phagocytosis, and should be considered key players in the degradation process.

yes

### Human: AA-amyloidosis was induced in mice with injections of amyloid enhancing factor (AEF) and silver nitrate . The inflammation was induced by inflammation induced with injections . Resolution of the amyloids was monitored over time . Virtually all amylid was cleared within 34 weeks and macrophages were shown to internalize amylyloid . Passive immunization with an amylod specific monoclonal antibody reduced amyloidal development in murine AA-Amyloidosi . Is aA-Amyloid cleared by endogenous immunological mechanisms?### Assistant: Immunoglobulins co-localize with amyloid deposits and can contribute to amyloid degradation by Fc-receptor mediated phagocytosis, and should be considered key players in the degradation process.

Immunoglobulins co-localize with amyloid deposits and contribute to amyloids degradation by Fc-re

Does pyruvate restore contractile function and antioxidant defenses of hydrogen peroxide-challenged myocardium?

Pyruvate neutralizes peroxides by a direct decarboxylation reaction, and indirectly augments the glutathione (GSH) antioxidant system by generating NADPH reducing power via citrate formation . H(2)O(2), exposure depleted myocardial energy and antioxidant reserves and produced marked contractile impairment that persisted throughout the H2(2(O(1) washout period . Relative to untreated post-H2(1), pyruvates restored contractile performance, increased GSH/GSSG 52% and maintained phosphocreatine phosphorylation state .

Pyruvate promoted robust contractile recovery of H(2)O(2)-challenged myocardium by the combination of citrate-mediated antioxidant mechanisms and maintenance of myocardial energy reserves.

yes

### Human: Pyruvate neutralizes peroxides by a direct decarboxylation reaction, and indirectly augments the glutathione (GSH) antioxidant system by generating NADPH reducing power via citrate formation . H(2)O(2), exposure depleted myocardial energy and antioxidant reserves and produced marked contractile impairment that persisted throughout the H2(2(O(1) washout period . Relative to untreated post-H2(1), pyruvates restored contractile performance, increased GSH/GSSG 52% and maintained phosphocreatine phosphorylation state . Does pyruvate restore contractile function and antioxidant defenses of hydrogen peroxide-challenged myocardium?### Assistant: Pyruvate promoted robust contractile recovery of H(2)O(2)-challenged myocardium by the combination of citrate-mediated antioxidant mechanisms and maintenance of myocardial energy reserves.

Pyruvate promoted robust contractile recovery of H(2)O(2)-challenged myocardium by the combination of

Does resveratrol attenuate high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK?

Resveratrol, a naturally occurring polyphenol, has shown beneficial effects on some cardiovascular complications associated with diabetes . We aimed to examine the role of resvatrol on high glucose-induced ROS production and cardiac apoptosis . We found that it suppressed the increased activity of NADPH oxidase and Rac1, as well as the enhanced expression of p67(phox), p47(phx), and gp91(phX) in cardiomyocytes exposed to high glucose .

Our data demonstrated that resveratrol protected cardiomyocytes against high glucose-induced apoptosis through suppression NADPH oxidase-derived ROS generation and maintenance endogenous antioxidant defenses. And the protective effects of resveratrol are mostly mediated by AMPK related pathway.

yes

### Human: Resveratrol, a naturally occurring polyphenol, has shown beneficial effects on some cardiovascular complications associated with diabetes . We aimed to examine the role of resvatrol on high glucose-induced ROS production and cardiac apoptosis . We found that it suppressed the increased activity of NADPH oxidase and Rac1, as well as the enhanced expression of p67(phox), p47(phx), and gp91(phX) in cardiomyocytes exposed to high glucose . Does resveratrol attenuate high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK?### Assistant: Our data demonstrated that resveratrol protected cardiomyocytes against high glucose-induced apoptosis through suppression NADPH oxidase-derived ROS generation and maintenance endogenous antioxidant defenses. And the protective effects of resveratrol are mostly mediated by AMPK related pathway.

Resveratrol protected cardiomyocytes against high glucose-induced apoptosis through suppression NADPH oxidase-derived ROS generation and

Does chronic smoking prevent amelioration of endothelial function in the course of the menstrual cycle?

Flow-mediated dilation (FMD) and nitro-mediated (NMD) were assessed in healthy smoking and non-smoking women . FMD did not show differences between smoking and . non-smokers at menstruation and mid-follicular phase . At the mid-luteal phase, FMD was significantly reduced in smoking when compared with . non . smoking women . NMD was found to be similar to FMD at the different cycle phases, but did not differ between smoking .

In healthy women, smoking eliminates the physiological amelioration of endothelial function during the menstrual cycle. This study underlines the importance of an exact description of menstrual cycle phase and smoking status in studies investigating endothelial function in premenopausal women.

yes

### Human: Flow-mediated dilation (FMD) and nitro-mediated (NMD) were assessed in healthy smoking and non-smoking women . FMD did not show differences between smoking and . non-smokers at menstruation and mid-follicular phase . At the mid-luteal phase, FMD was significantly reduced in smoking when compared with . non . smoking women . NMD was found to be similar to FMD at the different cycle phases, but did not differ between smoking . Does chronic smoking prevent amelioration of endothelial function in the course of the menstrual cycle?### Assistant: In healthy women, smoking eliminates the physiological amelioration of endothelial function during the menstrual cycle. This study underlines the importance of an exact description of menstrual cycle phase and smoking status in studies investigating endothelial function in premenopausal women.

Smoking eliminates physiological amelioration of endothelial function during the menstrual cycle . This study underlines the importance of an exact description of

Does aquaporin-1 facilitate angiogenic invasion in the pathological neovasculature that accompanies cirrhosis?

Study of mechanisms governing liver endothelial cell invasion during cirrhosis is of great importance . Research suggests that AQP-1 is involved in amoeboid-type motility and membrane blebbing as features that may facilitate invasion through matrix-rich microenvironments . AQP levels modulated in LEC using retroviral overexpression or small interfering RNA (siRNA) knockdown and functional effects on invasion and osmotic water permeability were assayed . Results demonstrate AQP1 is up-regulated in the small, angiogenic, neovasculature within the fibrotic septa of cirrhotic liver .

AQP-1 enhances osmotic water permeability and FGF-induced dynamic membrane blebbing in LEC and thereby drives invasion and pathological angiogenesis during cirrhosis.

yes

### Human: Study of mechanisms governing liver endothelial cell invasion during cirrhosis is of great importance . Research suggests that AQP-1 is involved in amoeboid-type motility and membrane blebbing as features that may facilitate invasion through matrix-rich microenvironments . AQP levels modulated in LEC using retroviral overexpression or small interfering RNA (siRNA) knockdown and functional effects on invasion and osmotic water permeability were assayed . Results demonstrate AQP1 is up-regulated in the small, angiogenic, neovasculature within the fibrotic septa of cirrhotic liver . Does aquaporin-1 facilitate angiogenic invasion in the pathological neovasculature that accompanies cirrhosis?### Assistant: AQP-1 enhances osmotic water permeability and FGF-induced dynamic membrane blebbing in LEC and thereby drives invasion and pathological angiogenesis during cirrhosis.

AQP-1 enhances osmotic water permeability and FGF-induced dynamic membrane blebbing in LEC . It

Do indocyanine green kinetics characterize blood volume and flow distribution and their alteration by propranolol?

Propranolol reduced cardiac output from 10.6 to 4.1 L/min . Most of the decrease in cardiac output was at the expense of blood flow to the fast peripheral circuit, which represented nonsplanchnic circulation . The recirculatory pharmacokinetic model incorporates data from both the initial transient oscillations and the later post-mixing portions of the blood indocyanine green concentration versus time curves to characterize blood volume and cardiac output . The model was used to describe the effect of propranolanolol on blood flow distribution .

Our indocyanine green model is able to derive estimates of blood volume and cardiac output, as well as their systemic distribution during different physiologic conditions.

yes

### Human: Propranolol reduced cardiac output from 10.6 to 4.1 L/min . Most of the decrease in cardiac output was at the expense of blood flow to the fast peripheral circuit, which represented nonsplanchnic circulation . The recirculatory pharmacokinetic model incorporates data from both the initial transient oscillations and the later post-mixing portions of the blood indocyanine green concentration versus time curves to characterize blood volume and cardiac output . The model was used to describe the effect of propranolanolol on blood flow distribution . Do indocyanine green kinetics characterize blood volume and flow distribution and their alteration by propranolol?### Assistant: Our indocyanine green model is able to derive estimates of blood volume and cardiac output, as well as their systemic distribution during different physiologic conditions.

Our indocyanine green model is able to derive estimates of blood volume and cardiac output, as well as their systemic distribution during different

Is reduced ADAMTS13 activity associated with an ADAMTS13 SNP , fever and microparticles in a malaria-like model?

ADAMTS13 activity is reduced in malaria patients, but the reason why is it is unclear . The number of rs4962153 A alleles correlated with the reduced level of antigen and activity . MPs showed an inhibitory effect on ADAMts13 activity . The interaction between these two factors was also observed (p-value <0.001) Finally, ADAMT13 activity was decreased in a temperature and time-dependent manner. The interaction was also seen between the two factors .

These findings suggest that the A allele of rs4962153, MPs, and febrile temperature, contribute to reduce ADAMTS13 activity in plasma. These data are useful in malaria or other diseases with reduced ADAMTS13 activity.

yes

### Human: ADAMTS13 activity is reduced in malaria patients, but the reason why is it is unclear . The number of rs4962153 A alleles correlated with the reduced level of antigen and activity . MPs showed an inhibitory effect on ADAMts13 activity . The interaction between these two factors was also observed (p-value <0.001) Finally, ADAMT13 activity was decreased in a temperature and time-dependent manner. The interaction was also seen between the two factors . Is reduced ADAMTS13 activity associated with an ADAMTS13 SNP , fever and microparticles in a malaria-like model?### Assistant: These findings suggest that the A allele of rs4962153, MPs, and febrile temperature, contribute to reduce ADAMTS13 activity in plasma. These data are useful in malaria or other diseases with reduced ADAMTS13 activity.

A allele of rs4962153, MPs, and febrile temperature, contribute to reduce ADAMTS13 activity in plasma

Is nocturnal haemoglobin oxygen saturation variability associated with vitamin C deficiency in Tanzanian children with sickle cell anaemia?

To test the hypothesis that vitamin C deficiency (VCD; <11.4 μmol/L) is associated with nocturnal haemoglobin oxygen desaturation in children with sickle cell anaemia (SCA) and controls . 11 of 23 children with SCA had VCD; logged vitamin C concentrations showed a 66% decrease per 0.1 unit increase in delta12 s [95% CI -86%, -15%], p=0.023] and delta12s >0.4 was associated with VCD (odds ratio 8.75 [1.24-61.7], p =0.029)

Obstructive sleep apnoea (OSA), detected from nocturnal haemoglobin oxygen saturation variability, is common in Tanzanian children and associated with vitamin C Deficiency in SCA. The direction of causality could be determined by comparing OSA treatment with vitamin C supplementation.

yes

### Human: To test the hypothesis that vitamin C deficiency (VCD; <11.4 μmol/L) is associated with nocturnal haemoglobin oxygen desaturation in children with sickle cell anaemia (SCA) and controls . 11 of 23 children with SCA had VCD; logged vitamin C concentrations showed a 66% decrease per 0.1 unit increase in delta12 s [95% CI -86%, -15%], p=0.023] and delta12s >0.4 was associated with VCD (odds ratio 8.75 [1.24-61.7], p =0.029) Is nocturnal haemoglobin oxygen saturation variability associated with vitamin C deficiency in Tanzanian children with sickle cell anaemia?### Assistant: Obstructive sleep apnoea (OSA), detected from nocturnal haemoglobin oxygen saturation variability, is common in Tanzanian children and associated with vitamin C Deficiency in SCA. The direction of causality could be determined by comparing OSA treatment with vitamin C supplementation.

Obstructive sleep apnoea is common in Tanzanian children and associated with vitamin C Deficiency in SCA . The

Is uric acid an independent predictor of cardiovascular mortality in type 2 diabetes : a population-based study?

Study base was population-based cohort of 1540 diabetic subjects (median age 68.9 years) of the Casale Monferrato Study . Baseline levels of serum uric acid were negatively correlated with HbA1c, were higher in men and in the elderly and were independently associated with components of the metabolic syndrome . Out of 14,179 person-years, 1000 deaths (514 due to cardiovascular diseases) were observed . The latter appeared to be due to neoplastic diseases .

In diabetic people, uric acid is associated with components of the metabolic syndrome but it may not be accounted as an independent risk factor for cardiovascular mortality. The increased all-cause mortality risk with higher levels of uric acid might be due to increased neoplastic mortality and deserves future studies.

no

### Human: Study base was population-based cohort of 1540 diabetic subjects (median age 68.9 years) of the Casale Monferrato Study . Baseline levels of serum uric acid were negatively correlated with HbA1c, were higher in men and in the elderly and were independently associated with components of the metabolic syndrome . Out of 14,179 person-years, 1000 deaths (514 due to cardiovascular diseases) were observed . The latter appeared to be due to neoplastic diseases . Is uric acid an independent predictor of cardiovascular mortality in type 2 diabetes : a population-based study?### Assistant: In diabetic people, uric acid is associated with components of the metabolic syndrome but it may not be accounted as an independent risk factor for cardiovascular mortality. The increased all-cause mortality risk with higher levels of uric acid might be due to increased neoplastic mortality and deserves future studies.

In diabetic people, uric acid is associated with components of the metabolic syndrome but it may not be accounted as an independent risk factor for

Do peritoneal dialysate IgG/C3 levels predict susceptibility to peritonitis?

Thirty-four patients were studied . IgG and C3 levels were found to be useful in predicting likelihood of developing peritonitis . There were no significant differences between IgG levels in the two groups at any time point, and large interpatient and intrapatient variation in levels were seen . We examined opsonin levels in group as a whole, and then in two subgroups of patients: those who remained peritonitic-free throughout the study, and those who did not .

Dialysate levels of IgG and C3 from the overnight dwell are not helpful in predicting the risk of developing continuous ambulatory peritoneal dialysis peritonitis in individual patients. No correlation was found between opsonin levels and onset of clinical peritonitis.

no

### Human: Thirty-four patients were studied . IgG and C3 levels were found to be useful in predicting likelihood of developing peritonitis . There were no significant differences between IgG levels in the two groups at any time point, and large interpatient and intrapatient variation in levels were seen . We examined opsonin levels in group as a whole, and then in two subgroups of patients: those who remained peritonitic-free throughout the study, and those who did not . Do peritoneal dialysate IgG/C3 levels predict susceptibility to peritonitis?### Assistant: Dialysate levels of IgG and C3 from the overnight dwell are not helpful in predicting the risk of developing continuous ambulatory peritoneal dialysis peritonitis in individual patients. No correlation was found between opsonin levels and onset of clinical peritonitis.

No correlation was found between opsonin levels and onset of clinical peritonitis . IgG and C3 levels are not helpful in

Are serum brain-derived neurotrophic factor levels associated with dyssomnia in females , but not males , among Japanese workers?

Recent evidence suggests that BDNF is a sleep regulatory substance that contributes to sleep behavior . The prevalence of dyssomnia was 35.1% in males and 30.0% in females . In the females, the BDNF levels were found to be negatively associated with dysomnia after adjusting for age, body mass index, hypertension, dyslipidemia, hyperglycemia, depression, smoking, alcohol intake, and regular exercise . No such relationships were found in the males. No such associations were found .

The serum BDNF levels are associated with dyssomnia in Japanese female, but not male, workers.

yes

### Human: Recent evidence suggests that BDNF is a sleep regulatory substance that contributes to sleep behavior . The prevalence of dyssomnia was 35.1% in males and 30.0% in females . In the females, the BDNF levels were found to be negatively associated with dysomnia after adjusting for age, body mass index, hypertension, dyslipidemia, hyperglycemia, depression, smoking, alcohol intake, and regular exercise . No such relationships were found in the males. No such associations were found . Are serum brain-derived neurotrophic factor levels associated with dyssomnia in females , but not males , among Japanese workers?### Assistant: The serum BDNF levels are associated with dyssomnia in Japanese female, but not male, workers.

The serum BDNF levels are associated with dyssomnia in Japanese female, but not male, workers .

Is preference of lethal methods the only cause for higher suicide rates in males?

Data on completed and attempted suicides were collected (n=3235, Nuremberg and Wuerzburg, years 2000-2004). Men chose high-risk methods like hanging significantly more often than women . This was most apparent in "hanging" (men 83.5%, women 55.3%; φ=-0.28; p<0.001) and "poisoning by drugs" (Men 7.2%, women 3.4%; p=0.09)

The sample size (n=3235) was not enough for comparing method and gender specific case fatalities with a fine-meshed stratification regarding age.

no

### Human: Data on completed and attempted suicides were collected (n=3235, Nuremberg and Wuerzburg, years 2000-2004). Men chose high-risk methods like hanging significantly more often than women . This was most apparent in "hanging" (men 83.5%, women 55.3%; φ=-0.28; p<0.001) and "poisoning by drugs" (Men 7.2%, women 3.4%; p=0.09) Is preference of lethal methods the only cause for higher suicide rates in males?### Assistant: The sample size (n=3235) was not enough for comparing method and gender specific case fatalities with a fine-meshed stratification regarding age.

The sample size (n=3235) was not enough for comparing method and gender specific case fatalities with a fine-meshed strat

Does intramyocardial transplantation of cardiac mesenchymal stem cells reduce myocarditis in a model of chronic Chagas disease cardiomyopathy?

Stem cell therapy focused on improving cardiac function is a promising approach for treating heart disease . CMSCs demonstrated adipogenic, osteogenic, chondrogenic, cardiogenic differentiation potentials . Cells were isolated from green fluorescent protein (GFP) transgenic C57BL/6 mouse hearts . CMSC-treated mice had a significantly decreased number of inflammatory cells, but no reduction in fibrotic area, two months after treatment . Cells expressed endothelial cell and cardiomyocyte features upon defined stimulation conditions .

We conclude that the CMSCs exert a protective effect in chronic chagasic cardiomyopathy primarily through immunomodulation.

yes

### Human: Stem cell therapy focused on improving cardiac function is a promising approach for treating heart disease . CMSCs demonstrated adipogenic, osteogenic, chondrogenic, cardiogenic differentiation potentials . Cells were isolated from green fluorescent protein (GFP) transgenic C57BL/6 mouse hearts . CMSC-treated mice had a significantly decreased number of inflammatory cells, but no reduction in fibrotic area, two months after treatment . Cells expressed endothelial cell and cardiomyocyte features upon defined stimulation conditions . Does intramyocardial transplantation of cardiac mesenchymal stem cells reduce myocarditis in a model of chronic Chagas disease cardiomyopathy?### Assistant: We conclude that the CMSCs exert a protective effect in chronic chagasic cardiomyopathy primarily through immunomodulation.

CMSCs exert a protective effect in chronic chagasic cardiomyopathy through immunomodulation . We conclude that the CMS

Does nitric oxide inhibition attenuate systemic hypotension produced by protamine?

In vitro studies suggest this may be mediated by release of nitric oxide from the endothelium . We measured hemodynamic parameters in 12 heparinized dogs (150 U/kg) to study the systemic effects of protamine . After treatment with Ng-monomethyl-L-arginine and methylene blue, the second infusion of prolamine caused no significant change in blood pressure or cardiac output . The effect of the effect could be reversed by the addition of (6 mg/kg), L-argine but not D-argina .

Protamine-heparin complex does not cause direct myocardial depression but does lead to severe hypotension in vivo. The finding that hypotension can be blocked by inhibitors of the nitric oxide pathway confirms previous in vitro studies indicating that the effects of protamine are mediated, in part, by the vascular endothelium. Further, these studies suggest a novel approach to prevention of hemodynamic complications caused by heparin reversal after cardiopulmonary bypass.

yes

### Human: In vitro studies suggest this may be mediated by release of nitric oxide from the endothelium . We measured hemodynamic parameters in 12 heparinized dogs (150 U/kg) to study the systemic effects of protamine . After treatment with Ng-monomethyl-L-arginine and methylene blue, the second infusion of prolamine caused no significant change in blood pressure or cardiac output . The effect of the effect could be reversed by the addition of (6 mg/kg), L-argine but not D-argina . Does nitric oxide inhibition attenuate systemic hypotension produced by protamine?### Assistant: Protamine-heparin complex does not cause direct myocardial depression but does lead to severe hypotension in vivo. The finding that hypotension can be blocked by inhibitors of the nitric oxide pathway confirms previous in vitro studies indicating that the effects of protamine are mediated, in part, by the vascular endothelium. Further, these studies suggest a novel approach to prevention of hemodynamic complications caused by heparin reversal after cardiopulmonary bypass.

Protamine-heparin complex does not cause direct myocardial depression but does lead to severe hypotension in vivo . The finding

Does increased orexin expression promote sleep/wake disturbances in the SOD1-G93A mouse model of amyotrophic lateral sclerosis?

Orexin is a crucial neurotransmitter in promoting wakefulness in sleep/wake regulation, and may play an important role in sleep disturbances in ALS . For the first time in SOD1-G93A transgenic mice, we observed significantly increased wakefulness, reduced sleep time, and up-regulated orexins (prepro-orexin, orexin A and B) at both 90 and 120 days . Correlation analysis confirmed moderate to high correlations between sleep time (total sleep time) and increase in orexIN .

Sleep/wake disturbances occur before disease onset in this ALS mouse model. Increased orexins may promote wakefulness and result in these disturbances before and after disease onset, thus making them potential therapeutic targets for amelioration of sleep disturbances in ALS. Further studies are required to elucidate the underlying mechanisms in the future.

yes

### Human: Orexin is a crucial neurotransmitter in promoting wakefulness in sleep/wake regulation, and may play an important role in sleep disturbances in ALS . For the first time in SOD1-G93A transgenic mice, we observed significantly increased wakefulness, reduced sleep time, and up-regulated orexins (prepro-orexin, orexin A and B) at both 90 and 120 days . Correlation analysis confirmed moderate to high correlations between sleep time (total sleep time) and increase in orexIN . Does increased orexin expression promote sleep/wake disturbances in the SOD1-G93A mouse model of amyotrophic lateral sclerosis?### Assistant: Sleep/wake disturbances occur before disease onset in this ALS mouse model. Increased orexins may promote wakefulness and result in these disturbances before and after disease onset, thus making them potential therapeutic targets for amelioration of sleep disturbances in ALS. Further studies are required to elucidate the underlying mechanisms in the future.

Increased orexins may promote wakefulness and result in these disturbances before and after disease onset, thus making them potential therapeutic targets for am

Is qTc prolongation measured by standard 12-lead electrocardiography an independent risk factor for sudden death due to cardiac arrest?

Rotterdam QT Project followed up 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography for 2 years . Of these, 245 patients died suddenly . In patients without evidence of cardiac dysfunction, QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death . Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks . In contrast, in patients with evidence of heart dysfunction, the relative risk was 1.0 (0.5)

These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death.

yes

### Human: Rotterdam QT Project followed up 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography for 2 years . Of these, 245 patients died suddenly . In patients without evidence of cardiac dysfunction, QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death . Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks . In contrast, in patients with evidence of heart dysfunction, the relative risk was 1.0 (0.5) Is qTc prolongation measured by standard 12-lead electrocardiography an independent risk factor for sudden death due to cardiac arrest?### Assistant: These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death.

In patients without cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent

Is progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice variable and asymmetric?

DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions . We have used two labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the betaGeo reporter gene, respectively, to evaluate the time course of optic nerve degeneration in aging mice . Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe . Although nerve damage is bilateral, the progression of disease is asymmetric between the eyes of individual mice .

A comparison of the data collected from the two cohorts of mice used for this study suggests that the initial site of damage in this disease is to the axons in the optic nerve, followed by the subsequent death of the ganglion cell soma.

yes

### Human: DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions . We have used two labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the betaGeo reporter gene, respectively, to evaluate the time course of optic nerve degeneration in aging mice . Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe . Although nerve damage is bilateral, the progression of disease is asymmetric between the eyes of individual mice . Is progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice variable and asymmetric?### Assistant: A comparison of the data collected from the two cohorts of mice used for this study suggests that the initial site of damage in this disease is to the axons in the optic nerve, followed by the subsequent death of the ganglion cell soma.

Initial site of damage in this disease is to axons in the optic nerve, followed by the subsequent death of the ganglion cell

Do aggregate analysis of regulatory authority assessors ' comments to improve the quality of periodic safety update reports?

A novel instrument aiming at improving quality of PSURs based on standardized analysis of PSur assessment reports . The most frequent comments were requests for labeling changes (35 HA comments in 19 ARs) The aggregate analysis revealed commonly raised issues and prompted changes of the MAH's procedures related to the preparation of the PSUR reports . A total of 476 comments were identified through the analysis of 63 PSUR HA ARs received in 2013 and 2014; 47 (10%) were classified as "Requests for regulatory actions," 309 (65%) as " Requests for medical and scientific information"

The authors believe that this novel instrument based on the evaluation of PSUR HA ARs serves as a valuable mechanism to enhance the quality of PSURs and decisions about optimization of the use of the products and, therefore, contributes to improve further the MAH's pharmacovigilance system and patient safety.

yes

### Human: A novel instrument aiming at improving quality of PSURs based on standardized analysis of PSur assessment reports . The most frequent comments were requests for labeling changes (35 HA comments in 19 ARs) The aggregate analysis revealed commonly raised issues and prompted changes of the MAH's procedures related to the preparation of the PSUR reports . A total of 476 comments were identified through the analysis of 63 PSUR HA ARs received in 2013 and 2014; 47 (10%) were classified as "Requests for regulatory actions," 309 (65%) as " Requests for medical and scientific information" Do aggregate analysis of regulatory authority assessors ' comments to improve the quality of periodic safety update reports?### Assistant: The authors believe that this novel instrument based on the evaluation of PSUR HA ARs serves as a valuable mechanism to enhance the quality of PSURs and decisions about optimization of the use of the products and, therefore, contributes to improve further the MAH's pharmacovigilance system and patient safety.

The authors believe that this novel instrument based on the evaluation of PSUR HA ARs serves as a valuable mechanism to enhance the quality of

Are changes in gait performance over several years associated with recurrent falls status in community-dwelling older women at high risk of fracture?

135 female volunteers at high risk of fracture were assessed at four annual clinics over 3.7±0.5 years . Gait parameters (speed, cadence, step length, step width, swing time and double support phase) were assessed using the GAITRite Electronic Walkway System . No significant associations were observed for baseline gait parameters . At the second follow-up, an increase in swing time was associated with reduced likelihood of being a recurrent faller in the subsequent 1.3 years following this time point .

Changes in gait parameters over several years are significantly associated with the likelihood of being a recurrent faller among community-dwelling older women at high risk of fracture. Further research is required to develop gait monitoring guidelines and gait parameter decline cut points that may be utilised by clinicians to identify older adults at risk of incident falls and sarcopenia.

yes

### Human: 135 female volunteers at high risk of fracture were assessed at four annual clinics over 3.7±0.5 years . Gait parameters (speed, cadence, step length, step width, swing time and double support phase) were assessed using the GAITRite Electronic Walkway System . No significant associations were observed for baseline gait parameters . At the second follow-up, an increase in swing time was associated with reduced likelihood of being a recurrent faller in the subsequent 1.3 years following this time point . Are changes in gait performance over several years associated with recurrent falls status in community-dwelling older women at high risk of fracture?### Assistant: Changes in gait parameters over several years are significantly associated with the likelihood of being a recurrent faller among community-dwelling older women at high risk of fracture. Further research is required to develop gait monitoring guidelines and gait parameter decline cut points that may be utilised by clinicians to identify older adults at risk of incident falls and sarcopenia.

Changes in gait parameters over several years are significantly associated with the likelihood of being a recurrent faller among community-dwelling older

Are pLAUR polymorphisms associated with asthma , PLAUR levels , and lung function decline?

Several studies have suggested that chromosome 19q13.1-3 contains asthma susceptibility genes . Linkage and association analyses using 587 United Kingdom and Dutch asthma families (n = 2819 subjects) were used to investigate this region . PLAUR SNPs in the 5' region, intron 3, and 3' region are associated with asthma and BHR susceptibility and predict FEV1 and plasma PLAUR levels . The same SNPs were found to be determinants of FEV 1 decline in subjects with asthma .

This study represents the first report to identify PLAUR as a potential asthma susceptibility gene and determine PLAUR regions underlying this association, including a role in influencing plasma PLAUR levels. Finally, the association of PLAUR with lung function decline supports a role for PLAUR in airway remodeling in asthma.

yes

### Human: Several studies have suggested that chromosome 19q13.1-3 contains asthma susceptibility genes . Linkage and association analyses using 587 United Kingdom and Dutch asthma families (n = 2819 subjects) were used to investigate this region . PLAUR SNPs in the 5' region, intron 3, and 3' region are associated with asthma and BHR susceptibility and predict FEV1 and plasma PLAUR levels . The same SNPs were found to be determinants of FEV 1 decline in subjects with asthma . Are pLAUR polymorphisms associated with asthma , PLAUR levels , and lung function decline?### Assistant: This study represents the first report to identify PLAUR as a potential asthma susceptibility gene and determine PLAUR regions underlying this association, including a role in influencing plasma PLAUR levels. Finally, the association of PLAUR with lung function decline supports a role for PLAUR in airway remodeling in asthma.

PLAUR is the first report to identify PLAUR as a potential asthma susceptibility gene . PLAUR regions underlying this association, including a role

Is the Prevalence of Syphilis from the Early HIV Period Correlated With Peak HIV Prevalence at a Country Level?

Earlier studies have shown positive correlations between various sexually transmitted infections at different population levels . In this article, we test the hypothesis that there was a residual variation in the national prevalence rates of syphilis and that these rates could predict subsequent peak HIV prevalence rates . A moderately strong association is found for the 76 countries with data available (R = 0.53, P < 0.001) The association was weakened but remained significantly positive when we adjusted for the type of test results used . The association remained significantly .

Syphilis prevalence in the 1990s predicted approximately 53% of the variation in peak HIV prevalence. Populations with generalized HIV epidemics had a higher prevalence of syphilis in the pre-HIV period. This finding provides additional rationale to carefully monitor sexual behavior, sexual networks, and sexually transmitted infection incidence in these populations.

yes

### Human: Earlier studies have shown positive correlations between various sexually transmitted infections at different population levels . In this article, we test the hypothesis that there was a residual variation in the national prevalence rates of syphilis and that these rates could predict subsequent peak HIV prevalence rates . A moderately strong association is found for the 76 countries with data available (R = 0.53, P < 0.001) The association was weakened but remained significantly positive when we adjusted for the type of test results used . The association remained significantly . Is the Prevalence of Syphilis from the Early HIV Period Correlated With Peak HIV Prevalence at a Country Level?### Assistant: Syphilis prevalence in the 1990s predicted approximately 53% of the variation in peak HIV prevalence. Populations with generalized HIV epidemics had a higher prevalence of syphilis in the pre-HIV period. This finding provides additional rationale to carefully monitor sexual behavior, sexual networks, and sexually transmitted infection incidence in these populations.

Syphilis prevalence in the 1990s predicted 53% of the variation in peak HIV prevalence . Populations with generalized HIV epidemics had a

Does endobronchial perfluorocarbon reduce inflammatory activity before and after lung transplantation in an animal experimental model?

The aim of this study was to evaluate the use of liquid perfluorocarbon (PFC) as an adjuvant substance for lung preservation and assess its role in pulmonary protection after transplantation . After transplantation, the NF-κB, iNOS, nitrotyrosine expression as well as caspase 3 activity were significantly lower in the PFC groups after transplant . There was a significant increase in oxidative stress in the control group at 6 h of cold ischemic time compared with the P FC3 and PFC7 groups .

The use of endobronchial PFC as an adjuvant to the current preservation strategy improved graft viability.

yes

### Human: The aim of this study was to evaluate the use of liquid perfluorocarbon (PFC) as an adjuvant substance for lung preservation and assess its role in pulmonary protection after transplantation . After transplantation, the NF-κB, iNOS, nitrotyrosine expression as well as caspase 3 activity were significantly lower in the PFC groups after transplant . There was a significant increase in oxidative stress in the control group at 6 h of cold ischemic time compared with the P FC3 and PFC7 groups . Does endobronchial perfluorocarbon reduce inflammatory activity before and after lung transplantation in an animal experimental model?### Assistant: The use of endobronchial PFC as an adjuvant to the current preservation strategy improved graft viability.

The use of endobronchial PFC as an adjuvant to the current preservation strategy improved graft viability .

Do changes in circulating IGF1 receptor stimulating activity parallel changes in total IGF1 during GH treatment of GH-deficient adults?

106 patients (54 m; 52 f) diagnosed with GHD were included; 22 were GH-naïve, 84 were already on GH treatment and discontinued therapy 4 weeks before baseline values were established . IGF1RSA was determined by the IGF1 kinase receptor activating assay, total IGF1 by immunoassay (Immulite) GH doses were titrated to achieve total IGF 1 levels within the normal range . After 12 months, total . IGF 1 normalized in 81% of patients, IGF1 in 51% and IGF1 . remained below normal in more . than 40% of . patients in whom total IGF .1 had normalized .

During 12 months of GH treatment, changes in IGF1RSA did not parallel changes in total IGF1. Despite normalization of total IGF1, IGF1RSA remained subnormal in a considerable proportion of patients. At present our results have no short-term consequences for GH therapy of GHD patients. However, based on our findings we propose future studies to examine whether titrating GH dose against IGF1RSA results in a better clinical outcome than titrating against total IGF1.

no

### Human: 106 patients (54 m; 52 f) diagnosed with GHD were included; 22 were GH-naïve, 84 were already on GH treatment and discontinued therapy 4 weeks before baseline values were established . IGF1RSA was determined by the IGF1 kinase receptor activating assay, total IGF1 by immunoassay (Immulite) GH doses were titrated to achieve total IGF 1 levels within the normal range . After 12 months, total . IGF 1 normalized in 81% of patients, IGF1 in 51% and IGF1 . remained below normal in more . than 40% of . patients in whom total IGF .1 had normalized . Do changes in circulating IGF1 receptor stimulating activity parallel changes in total IGF1 during GH treatment of GH-deficient adults?### Assistant: During 12 months of GH treatment, changes in IGF1RSA did not parallel changes in total IGF1. Despite normalization of total IGF1, IGF1RSA remained subnormal in a considerable proportion of patients. At present our results have no short-term consequences for GH therapy of GHD patients. However, based on our findings we propose future studies to examine whether titrating GH dose against IGF1RSA results in a better clinical outcome than titrating against total IGF1.

IGF1RSA remained subnormal in a considerable proportion of patients . At present our results have no short-term consequences for GH therapy

Does n-butanol fraction of Entada phaseoloides ethanol extract inhibit hepatocellular carcinoma HepG2 cell proliferation by inducing apoptosis?

HepG2 cell line from extracts of traditional Chinese medicinal plants were screened for inhibitory effects on the proliferation of hepatocellular carcinoma (HCC) HepG 2 cell line . The n-butanol fraction of Entada phaseoloides ethanol extract exhibited the highest inhibition rate . Treatment of HepG1 cells with 500, 250, and 100 μg/ml n-Butanol extract resulted in 89.92±0.58% decrease in cell viability . In the presence of 100 mg/ml Entada Phaseoloides n- butanol extract for 24h, apoptotic nuclei and hyperchromatic, dense fluorescent massive granules were observed in the cytoplasm .

Entada phaseoloides n-butanol extract inhibits HepG2 cell proliferation by inducing cell apoptosis likely through mitochondrial apoptotic pathway. This extract is therefore a potential natural source towards the discovery for a new drug-candidate for the treatment of HCC.

yes

### Human: HepG2 cell line from extracts of traditional Chinese medicinal plants were screened for inhibitory effects on the proliferation of hepatocellular carcinoma (HCC) HepG 2 cell line . The n-butanol fraction of Entada phaseoloides ethanol extract exhibited the highest inhibition rate . Treatment of HepG1 cells with 500, 250, and 100 μg/ml n-Butanol extract resulted in 89.92±0.58% decrease in cell viability . In the presence of 100 mg/ml Entada Phaseoloides n- butanol extract for 24h, apoptotic nuclei and hyperchromatic, dense fluorescent massive granules were observed in the cytoplasm . Does n-butanol fraction of Entada phaseoloides ethanol extract inhibit hepatocellular carcinoma HepG2 cell proliferation by inducing apoptosis?### Assistant: Entada phaseoloides n-butanol extract inhibits HepG2 cell proliferation by inducing cell apoptosis likely through mitochondrial apoptotic pathway. This extract is therefore a potential natural source towards the discovery for a new drug-candidate for the treatment of HCC.

Entada phaseoloides n-butanol extract inhibits HepG2 cell proliferation by inducing cell apoptosis likely through mitochondrial apoptotic pathway

Does the calculation of baseline serum creatinine overestimate the diagnosis of acute kidney injury in patients undergoing cardiac surgery?

Creatinine is the most commonly used of the recommended parameters (creatinine, glomerular filtration rate and diuresis) If the baseline value is not known, it can be calculated based on the simplified MDRD equation . The incidence of postoperative acute kidney injury in 2103 cases between 2002 and 2007 was 29.1% according to estimated creatinine (14.3% with the measure). This represents an overestimation of 104%, with an intraclass correlation of 0.12.12 .

The calculation of baseline creatinine using the MDRD equation overestimates the incidence of acute kidney injury after cardiac surgery, and is an inadequate method for detection when the baseline value is unknown.

yes

### Human: Creatinine is the most commonly used of the recommended parameters (creatinine, glomerular filtration rate and diuresis) If the baseline value is not known, it can be calculated based on the simplified MDRD equation . The incidence of postoperative acute kidney injury in 2103 cases between 2002 and 2007 was 29.1% according to estimated creatinine (14.3% with the measure). This represents an overestimation of 104%, with an intraclass correlation of 0.12.12 . Does the calculation of baseline serum creatinine overestimate the diagnosis of acute kidney injury in patients undergoing cardiac surgery?### Assistant: The calculation of baseline creatinine using the MDRD equation overestimates the incidence of acute kidney injury after cardiac surgery, and is an inadequate method for detection when the baseline value is unknown.

The calculation of baseline creatinine using the MDRD equation overestimates the incidence of acute kidney injury after cardiac surgery . It is

Is antiproliferative effect of HSP90 inhibitor Y306zh against pancreatic cancer mediated by interruption of AKT and MAPK signaling pathways?

HSP90 is a potential strategy to treat pancreatic cancer (PC) Many client proteins of HSP80 are found to be over-expressed and/or genetically mutated in PC . Y306zh binds tightly to the NH2-terminus of the protein with an IC50 of 85 nM . This causes ATP incapable to attach to the same binding site, and disrupts HSP70-p23 association . The molecular mechanism of Y306z was studied in human PC cell lines and Miapaca2 xenograft model .

Y306zh, a novel HSP90 inhibitor, interrupts ATP binding to HSP90 and disrupts HSP90-p23 interaction, and eventually inhibits the growth of PC cells.

yes

### Human: HSP90 is a potential strategy to treat pancreatic cancer (PC) Many client proteins of HSP80 are found to be over-expressed and/or genetically mutated in PC . Y306zh binds tightly to the NH2-terminus of the protein with an IC50 of 85 nM . This causes ATP incapable to attach to the same binding site, and disrupts HSP70-p23 association . The molecular mechanism of Y306z was studied in human PC cell lines and Miapaca2 xenograft model . Is antiproliferative effect of HSP90 inhibitor Y306zh against pancreatic cancer mediated by interruption of AKT and MAPK signaling pathways?### Assistant: Y306zh, a novel HSP90 inhibitor, interrupts ATP binding to HSP90 and disrupts HSP90-p23 interaction, and eventually inhibits the growth of PC cells.

Y306zh, a novel HSP90 inhibitor, interrupts ATP binding to HSP 90 and disrupts HSP80-p23

Do [ A randomized study comparing the efficacy and bleeding pattern of Implanon and Norplant hormonal contraceptive implant ]?

100 healthy female volunteers received Implanon (75 cases) or Norplant (25 cases) for 4 years . They followed up with complain, bleeding patterns, hemoglobin, blood pressure, weight, weight . There were no pregnancies during the study . The average bleeding number of times was 2.25 of Implon and 2.99 of Norplant per reference period (P < 0.05) The mean insert time was 11 second of Implan on and 103 second of Norplans .

Both contraceptive systems demonstrated excellent contraceptive efficacy and were well tolerated. Because of its single-rod design, Implanon was significantly quicker to insert and remove than the multiple-capsule system.

yes

### Human: 100 healthy female volunteers received Implanon (75 cases) or Norplant (25 cases) for 4 years . They followed up with complain, bleeding patterns, hemoglobin, blood pressure, weight, weight . There were no pregnancies during the study . The average bleeding number of times was 2.25 of Implon and 2.99 of Norplant per reference period (P < 0.05) The mean insert time was 11 second of Implan on and 103 second of Norplans . Do [ A randomized study comparing the efficacy and bleeding pattern of Implanon and Norplant hormonal contraceptive implant ]?### Assistant: Both contraceptive systems demonstrated excellent contraceptive efficacy and were well tolerated. Because of its single-rod design, Implanon was significantly quicker to insert and remove than the multiple-capsule system.

Implanon was significantly quicker to insert and remove than the multiple-capsule system . Both contraceptive systems demonstrated excellent efficacy and were well

Does mild traumatic brain injury induce prolonged visual processing deficits in children?

A prospective design was used to assess 18 children with mTBI and 18 matched healthy controls . Sensitivity to simple and complex visual stimuli of children who have sustained a mild traumatic brain injury (mTBI) was assessed at 1, 4 and 12 weeks post-injury and at equivalent times for controls . Orientation and direction identification thresholds were measured for all participants for static and dynamic conditions, respectively . In addition, sensitivity to radial optic flow (inward vs outward), a complex motion stimulus, was assessed .

These findings suggest that injured children present selective processing deficits for higher-order information and that this deficit persists over relatively long periods. Such measures could be useful to assess children who have sustained mTBI and possibly contribute to identifying potential risks of returning these children to demanding physical activities.

yes

### Human: A prospective design was used to assess 18 children with mTBI and 18 matched healthy controls . Sensitivity to simple and complex visual stimuli of children who have sustained a mild traumatic brain injury (mTBI) was assessed at 1, 4 and 12 weeks post-injury and at equivalent times for controls . Orientation and direction identification thresholds were measured for all participants for static and dynamic conditions, respectively . In addition, sensitivity to radial optic flow (inward vs outward), a complex motion stimulus, was assessed . Does mild traumatic brain injury induce prolonged visual processing deficits in children?### Assistant: These findings suggest that injured children present selective processing deficits for higher-order information and that this deficit persists over relatively long periods. Such measures could be useful to assess children who have sustained mTBI and possibly contribute to identifying potential risks of returning these children to demanding physical activities.

These findings suggest that injured children present selective processing deficits for higher-order information and that this deficit persists over relatively long periods . Such measures

Does reduction in bone resorption by exogenous glucagon-like peptide-2 administration require an intact gastrointestinal tract?

Glucagon-like peptide-2 (GLP-2) is a peptide secreted from endocrine L cells in the intestinal mucosa in relation to food-intake . Consumption of a meal reduced s-CTX in all groups but significantly less so in the jejunostomy group . Patients with an ileostomy had a preserved endogenous postprandial GLP-1 secretion, which was absent in patients with a jejunstomy . Consumption was reduced in the group but in the patients with an intact gastrointestinal tract .

Reductions in bone resorption by exogenous GLP-2 require an intact gastrointestinal tract. The decreased meal-induced inhibition of bone resorption in the jejunostomy patients, who lack a GLP-2 response, supports the view that GLP-2 plays a role in postprandial reduction in bone resorption.

yes

### Human: Glucagon-like peptide-2 (GLP-2) is a peptide secreted from endocrine L cells in the intestinal mucosa in relation to food-intake . Consumption of a meal reduced s-CTX in all groups but significantly less so in the jejunostomy group . Patients with an ileostomy had a preserved endogenous postprandial GLP-1 secretion, which was absent in patients with a jejunstomy . Consumption was reduced in the group but in the patients with an intact gastrointestinal tract . Does reduction in bone resorption by exogenous glucagon-like peptide-2 administration require an intact gastrointestinal tract?### Assistant: Reductions in bone resorption by exogenous GLP-2 require an intact gastrointestinal tract. The decreased meal-induced inhibition of bone resorption in the jejunostomy patients, who lack a GLP-2 response, supports the view that GLP-2 plays a role in postprandial reduction in bone resorption.

GLP-2 plays a role in postprandial reduction in bone resorption in the jejunostomy patients, who