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Autophagy plays a critical role in cellular homeostasis by clearing damaged or unnecessary organelles or macronutrients dependent on the lysosomal degradation pathway (Xie et al., 2011). Dysfunction of autophagy is shown to be involved in diabetic cardiomyopathy (Lavandero et al., 2015). It has been revealed that H2S is a regulator in autophagy during the process of diabetic cardiomyopathy. In type 2 db/db mouse heart tissues, NaHS facilitates autophagosome content degradation and promotes ubiquitin aggregate clearance via autophagy, which might exert its cardiovascular effect in diabetic cardiomyopathy (Wu et al., 2017). It is likely that H2S increases autophagic flux to ameliorate diabetic cardiomyopathy.

0biomedical

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The study has several limitations. The cross-sectional study design is a major limitation of this study. Furthermore, to participate in the survey, the respondent must be 18 years old and literate. The convenience sampling technique was used under the non-probability sampling method according to the objective and nature of the study. The study results cannot be generalized to the whole population because it is hard to replicate the convenience sample results.

0biomedical

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Given the high metastasis relapse rate of breast cancer patients, eliciting an immune response against antigens found in cells with a high self-renewal capacity and metastatic potential is critical. Cripto is specifically expressed in cancer cells with stem cell properties, so the effect of an anti-Cripto immune response was tested in xenograft models . An anti-Cripto vaccine effectively reduced the primary and lung metastatic tumor burden in the orthotopic 4T1 mouse BrCa xenograft. In a more clinically relevant spontaneous BrCa model (BALBc NeuT), a Cripto vaccination resulted in a decreased number of lung metastasis foci, but had no effect on the primary tumor, which had low Cripto expression. A prophylactic effect of a Cripto vaccine was observed upon xenografting Cripto expressing tumor cancer stem cell (CSC) spheres .

0biomedical

0Study

The mean of BATMOMA’s performance evaluation for succinate production is in the range of 0.41–0.55, with a standard deviation of 0.10–0.16. The mean for lactate production performance is between 0.12 and 0.22, and the standard deviation is between 0.10 and 0.25, which is close to zero. This implies that the lower the dispersion of the growth rate, the closer the value is to zero; it also implies that the data appears to be very close to the mean. Since the variation between the outcomes for each independent run is negligible, these statistical results show that the hybrid algorithm is very stable.

0biomedical

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Our observations of the directed deposition at low fluence and jets during high-fluence, multi-spot ultrafast laser ablation of stainless steel in air constitute a potentially interesting new area of research, providing a basis for further investigations to build a thorough understanding of these complex phenomena. Our study and its findings are considered important for a deeper understanding of the interaction of multi-spot arrays in laser patterning and enhanced laser deposition of thin films . The phenomena of plasma collisions and shocks observed and explored here should also be relevant to astrophysics and physics research, such as in magnetic re-connection and phenomena such as bi-directional jet formation and particle acceleration observed at ultrahigh laser intensities (1014–1015 W cm−2) in two spot ablation with high transient B fields.

2other

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Feature pyramid networks (FPN) adopt pyramid hierarchy to collect feature information from low-level to high-level. In detail, a pair of multi-scale feature pyramids are identically constructed by upsampling and downsampling, so as to fuse features with low resolution, abundant semantic information and features with fine resolution, inferior semantic information through top-down pathway and lateral connections.

0biomedical

1Other

Given that most of the studies in this area are cross-sectional in nature, this study brings in a different perspective of diarrhea in under-5 children and health seeking behavior from a more robust study design (longitudinal);Hence a causal relationship was ascertained which is imperative in coming up with specific interventions aimed at reducing the incidence of childhood diarrhea cases in resource-limited settings;The study has shown that in this setting majority of mothers sought care from outside the home; of those who sought care outside the home, majority relied on community health workers, which shows that community health workers are still an important source of care in low resource settings.

0biomedical

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Several large national initiatives will address dementia prevention in line with the 2013 G8 Dementia Summit. These draw largely on healthy or presymptomatic disease populations and offer new opportunities for systematic, prospective evaluations of people at scale, and often long-term sample biobanking, genetics, and imaging, enabling some powerful study designs. These include the Rhineland study (Germany, DZNE, n = 40,000), the Canadian Longitudinal Study on Aging (50,000 individuals), the Canadian Alliance for Healthy Hearts and Minds and Prospective Urban Rural Epidemiological MIND (PURE-MIND, 11,200 persons), and the UK Biobank (500,000 people aged 40–70, 100,000 with detailed imaging). These long-term initiatives are complemented by several national and regional efforts to establish disease-based cohorts, for example, the Canadian Consortium on Neurodegeneration in Aging (1400 persons; AD, mixed dementia, MCI, and VCI), or to combine existing cohorts, for example, the DPUK , (29 UK community cohorts), Cohort Studies of Memory in an International Consortium (COSMIC) , Virtual International Stroke Trials Archive (VISTA) Cognition , and STROKOG . Other regions should be encouraged and are creating large repositories of data—Asia Pacific Region, Central and America , Russia, Africa , and Australasia .

0biomedical

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The matrilineal genealogical analysis showed that 82 haplotypes diverged into two main branches. One main branch contains the Heihe River G. chilianensis. Another branch contains Shule River G. chilianensis, G. przewalskii and G. eckloni which the Shule River G. chilianensis from a haplotype clade, bootstrap values were 84%, G. przewalskii and G. eckloni from another haplotype clade, bootstrap values were 73% (Figure 1).

0biomedical

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Proteins were reduced in 10 mM dithiothreitol (Thermo Fisher Scientific) at 55 °C and alkylated in 25 mM iodoacetamide (Thermo Fisher Scientific) for 30 min at room temperature in the dark. The protein was digested with trypsin (Sigma; 100 ng) overnight at 37 °C. Digestion was quenched by adding trifluoroacetic acid to a final concentration of 1%, and peptides were extracted from the gel and dried. Peptides were separated and analyzed on an EASY nLC 1200 System (Thermo Fisher Scientific) in line with the Orbitrap Fusion Lumos Tribrid Mass Spectrometer (Thermo Fisher Scientific) with instrument control software, version 4.2.28.14. Two micrograms of tryptic peptides were pressure loaded onto a C18 reversed-phase column (Acclaim PepMap RSLC, 75 μm × 50 cm [2 μm, 100 Å]; Thermo Fisher Scientific; catalog no.: 164536) and separated using a gradient of 5 to 40% B in 180 min (solvent A: 5% acetonitrile/0.2% formic acid; solvent B: 80% acetonitrile/0.2% formic acid) at a flow rate of 300 nl/min. Mass spectra were acquired in data-dependent mode with a high resolution (60,000) FTMS survey scan, mass range of m/z 375 to 1575, followed by tandem mass spectra (MS/MS) of the most intense precursors with a cycle time of 3 s. The automatic gain control target value was 4.0e5 for the survey MS scan. High-energy collision dissociation fragmentation was performed with a precursor isolation window of 1.6 m/z, a maximum injection time of 50 ms, and high-energy collision dissociation collision energy of 35%. Monoisotopic-precursor selection was set to “peptide.” Precursors within a mass tolerance of 10 ppm were dynamically excluded from resequencing for 15 s. Advanced peak determination was not enabled. Precursor ions with charge states that were undetermined, 1, or >5 were excluded.

0biomedical

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All patients followed for HD or ARM at the University Hospitals of Nantes, Angers and Paris-Necker (French center of expertise for anorectal and rare pelvic malformations) were contacted if they were aged 12 or older in April 2011. In accordance with the exclusion criteria used by Hanneman and colleagues , patients were excluded if they had a cloaca, were mentally retarded, or lacked a basic proficiency in French.

1clinical

0Study

Overall, our findings show that HTT is stabilised by interaction with HAP40 through an extensive hydrophobic interface with its distinct HEAT repeat subdomains, creating a highly stable complex. Expanded and unexpanded exon 1 remains highly dynamic in the context of this complex, sampling a vast range of conformational space and interacting with different regions of both HTT and HAP40. We present novel insight into the structural differences of WT and mutant HTT, which suggests that the conformational constraints of WT and mutant exon 1 are different and that models of HD pathogenesis relying on the hypothesis that polyglutamine expansion drives large-scale changes in HTT conformation may need to be re-examined.

0biomedical

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Triathlons involve sequential swimming, cycling and running. Only athletes with around a top 150 world ranking may compete in the World Triathlon Series (WTS), i.e., the highest level of competition below the Olympic Games. The annual WTS circuit involves up to nine races over the Olympic (OD) (1.5 km swim, 40 km bike, 10 km run) and Sprint (0.75 km swim, 20 km bike and 5 km run) distances, plus a (more highly scored) Grand Final over the OD. The final WTS season ranking equates to a world championship ranking. Climatic conditions permitting, at any given event, both sexes compete over the same race distances. Within-competition analyses have, however, demonstrated that gender differences exist in the relative importance of individual swimming, cycling and running performance to the overall race result in elite triathlon.

0biomedical

1Other

Several genome-wide association studies (GWASs) have been performed to identify variants associated with LDL-cholesterol levels [10–17]. However, most of these studies were conducted in European populations with a limited number in African Americans. A meta-analysis of >100,000 European individuals found 22 loci associated with LDL-cholesterol levels including LDLR, APOB, PCSK9 and LDLRAP1 . Studies in African Americans have replicated some of these associations, and in some cases, significantly narrowed down the size of the associated regions, due to generally lower linkage disequilibrium in African populations [19–25]. However, African specific variants that alter LDL-cholesterol levels have not been fully investigated.

0biomedical

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The RAPD analysis undertaken used the Ready-To-Go RAPD kit (GE Healthcare, Bucks, UK) with solely the RAPD Primers 2 (5′-d[GTTTCGCTCC]-3′), 5 (5′-d[AACGCGCAAC]-3′), and 6 (5′-d[CCCGTCAGCA]-3′) employed under the PCR conditions of an initial denaturation for 5 min at 95 °C, followed by 45 cycles at 95 °C for 1 min, 36 °C for 1 min, and 72 °C for 2 min. The final elongation step was increased to 10 min, after which the samples were cooled to 4 °C. The PCR products were analyzed on 2.5% agarose gels containing ethidium bromide, while gel images were captured using the GelDoc documentation system (Bio-Rad®) and the band profile was analyzed for the further generation of phylogenetic trees using the Quantity One 4.6.3 program (BIO-RAD®), scoring 1 for the presence of major bands and 0 for their absence.

0biomedical

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Proper diet and the use of topical agents such as nitric acid 60% to treat onychomycosis resulted in 40% microbiological cure in the population studied, which is within the range of efficacy of other treatments. It requires limited perseverance because all patients need to visit their health professional for treatment. Moreover, it is painless and involves no risk of pharmacological interaction.

0biomedical

1Other

Cell cultures were harvested at 70% confluence and cell pellets resuspended in radioimmunoprecipitation (RIPA) assay buffer (0.1% SDS, 1% NP40 and 0.5% Na-deoxycholate in PBS) complemented with protease inhibitors (Pepstatine 5 μg/μl, PMSF 0.3 mM, Aprotinine 1 μg/μl and Sodium orthovanadate 0.1 μM). Aliquots of total protein (100 μg) were loaded on 10% acrylamide gels. After gel electrophoresis, proteins were transferred to a PVDF membrane and probed as described with rabbit anti-Epha3 (1:200; clone L18, Santa Cruz), rabbit anti-EphrinA5 (1:500; Novus Biological), mouse anti-phospho-tyrosine (1:2000; clone PY20, BD Transduction Laboratories) or mouse anti-β-Tubulin (1:2500; clone TUB 2.1; Sigma).

0biomedical

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The study was part of a wider PhD in Public Health research project, to develop an application towards determining how national HRH policy interventions impact local HRH systems in peri-urban communities using Decision Space Mapping Analysis. The protocol received approval from the Academic Advisory Committee, the Research Ethics Committee of the University of Pretoria, South Africa (Reference number 413/2014), and the Medical Research Council of Zimbabwe (Approval Number MRCZ/A/1941). Written informed consent was obtained from all participants, who were approached and took part in the research.

0biomedical

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Bioinformatic analysis of the SVBP6 genome allowed us to detect the presence of all genetic elements of a typical Gac/Rsm global regulatory cascade : a gacS gene encoding the membrane associated histidine kinase sensor, which was one of the targets of Tn5 in our mutagenesis approach (Fig 5); the gacA gene encoding the GacS cognate transcriptional activator of expression of the dedicated regulatory sRNA genes; three homologue genes encoding members of the CsrA/RsmA family of RNA-binding and translational regulators; and one copy of each of the rsmZ and rsmY sRNA gene homologues whose transcripts are regulatory sponges that titrate CsrA/RsmA proteins and therefore activate translation of different mRNAs . The sequence similarity of the SVBP6 rsmY and rsmZ homologues were found to be 91% and 93% with those from P. protegens CHA0, respectively . Such degree of identity allowed us to confirm expression of the SVBP6 rsmY homologue in the wild type strain by Northern blot using the P. protegens CHA0 dsDNA probe. The SVBP6 RsmY was strongly expressed all along the growth curve, but its cellular abundance was markedly downregulated in the gacS::Tn5 mutant clone (Fig 5E). Further directed mutagenesis is required to verify expression and roles of all identified members of the Gac/Rsm cascade in the control of SVBP6 antagonistic traits.

0biomedical

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Notch signaling has been shown to regulate distinct events in the different developmental stages of a tissue (Hartman et al., 2010; Radtke et al., 2004; Shih et al., 2012). A recent study reported that Notch activity is enriched in cTECs and that repression of Notch by HDAC3 is important for expansion/maintenance of developing mTECs (Goldfarb et al., 2016). This study analyzed the same Notch overexpression line used herein, but at the later time-points of 10 days and 6 weeks postnatally (Goldfarb et al., 2016). The conclusions of this and our own studies are entirely compatible, with the data presented here establishing a requirement for Notch signaling at the earliest stages of TEC lineage divergence, and the data of Goldfarb indicating that downregulation of Notch signaling is required for later stages of mTEC differentiation (Goldfarb et al., 2016). It is also possible that Notch has secondary roles in TECs subsequent to its initial role in mTEC specification.

0biomedical

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Immunofluorescence staining was used to detect glomerular IgG and complement C3 deposition in glomerular sections from pristane-injected and non-injected WT and TG mice. In contrast to the other groups, TG pristane-treated mice showed IgG and C3 deposits within the glomeruli, suggesting that glomerulonephritis had already progressed. Additionally, the severity of IgG and C3 deposition in non-injected TG mice and pristane-injected WT mice was comparable (Fig. 4f). The TG pristane-treated mice presented more severe renal dysfunction and glomerulonephritis. Interestingly, untreated TG mice also presented these symptoms. These results suggest that the TG mice spontaneously developed renal disease over time.

0biomedical

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We used a linear mixed effects (LME) model of AGB observed at each census in each plot as a function of time, a categorical variable indicating whether plots were near an edge, and their interaction. The fixed effect time represents the estimate of AGB change for interior plots, and the time × edge interaction represents how edge effects influence the AGB change. This model formulation thus allows us to quantify the rate of AGB change in interior and edge plots, and test if these rates are different. Plot identity was included as a random effect, allowing us to include any idiosyncratic differences between plots, with a random intercept term capturing variation in AGB between plots and a random slope with the time fixed effect capturing variation in change in AGB among plots68. The equation of the model was thus AGBij = β0 + β1 timeij + β2 edgeij + β3 timeij: edgeij + u0i + u1i timeij + eij, where AGBij is the above-ground biomass in plot i and census j, β0 to β3 are fixed effect parameters, u0i and u1i are respectively the random intercept and slope for plot i, and eij is residual error. The LME model was fitted using the lme function in the nlme R package78.

0biomedical

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Breast malignancy is a rare disease in childhood; it can be a primary or a secondary neoplasm. The latter is the most common: in this case, the breast is involved as a metastatic site of different cancer originated elsewhere, such as rhabdomyosarcoma, neuroblastoma, lymphoma, or leukemia. Primary tumors, instead, arise from the breast, and in childhood, there are occasional reports about carcinoma , rhabdomyosarcoma , and lymphoma .

0biomedical

1Other

Genetic diversity and population dynamics of begomoviruses through time were estimated using the HTS data. In this analysis, the reads were mapped to three reference databases comprising all ToMoLCV, ToSRV, and begomovirus sequences available in GenBank using BWA MEM v.0.7.17 (Li, 2013) with a seed length (-k) of 55 nucleotides. We opted for using the number and frequency of unique k-mers extracted from the aligned reads to estimate the diversity in order to mitigate cross alignments between different species, which should be common considering the 91% nucleotide identity thresholds for species demarcation (Brown et al., 2015). Twenty-seven mers were extracted and counted from the reads that aligned to each database using SAMtools v1.9 (Li et al., 2009) and Jellyfish v.2.2.3 (Marçais and Kingsford, 2011). Shannon entropy (Shannon, 1948) was calculated for each data set based on the frequency of each unique 27-mer. The number of reads aligned to each database was used to calculate the relative abundance of ToSRV and ToMoLCV for each sample group. To investigate whether the diversity of ToSRV and ToMoLCV significantly changed over time, we aligned previously extracted reads mapped to the genomes of these viruses in order to annotate single nucleotide polymorphisms (SNP) with LoFreq (Wilm et al., 2012). Thereafter, the entropy of each SNP was calculated and the cumulative sum of the entropy was used to perform the Wilcoxon signed-rank tests between two time points.

0biomedical

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To assess which models performed best, we calculated the Mantel–Haenszel risk ratios to compare the risk of death at 6 months between patients with COPD and without COPD adjusting for predicted risk of death for the model in question. We also calculated C-statistics and Hosmer–Lemeshow goodness of fit tests. Strategies involving multiplication of risk for patients with COPD using the existing GRACE model were compared with the existing GRACE model. To make a fair comparison, models which involved adding other variables (smoking or COPD) were compared with our models which included all of the GRACE variables. To assess how well each model stratified risk, we also plotted the proportion of all deaths by deciles of predicted risk of death at 6 months for the normal GRACE model and for modifications. We calculated how many people would be reclassified in terms of risk level (low, moderate or high) for each modification, we also performed this analysis stratified by type of ACS. Finally, we also calculated the continuous net reclassification improvement (NRI) statistic18 for adding COPD to the GRACE score model.

0biomedical

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Confusion matrix: inter-rater variability. Confusion matrix for the inter-rater variability between two experienced human coders, for a video from FD. “Other Upper” and “Other Lower” represent all the upper face and lower face labels that were not part of the task of the automatic classifier. Download Figure 5-1, DOCX file.

0biomedical

1Other

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

2other

1Other

According to the United Nations' Convention on the Rights of the Child, adolescents should be able to enjoy the highest attainable standard of health (Article 24). 1 Their rights should be respected irrespective of their and their parents' or legal guardians' ‘race, colour, sex, language, religion, political or other opinion, national, ethnic or social origin, property, disability, birth or other status’ (Article 2). Furthermore, one of the four general principles of the UN Convention on the Rights of the Child (Article 12) states that children should have the right to express their views and their opinion should be given due weight. The Council of Europe points out that each country should ensure that adolescents are listened to and involved in any decisions affecting them. 2 In its Manual on the Revised European Charter on the Participation of Young People in Local and Regional Life, the Council of Europe describes different levels at which youth can be involved, ranging from ‘nonparticipation’ through to being informed, consulted, or involved in decision‐making processes and sharing decision‐making power. 3

2other

1Other

Depending on participant preference, baseline assessment will occur face-to-face at the hospital site with a research assistant, or remotely. For participants completing baseline assessment remotely, a research team member will be available to provide support via phone call or video-conferencing software. Participants will be required to complete an online (electronic) baseline questionnaire to record demographic and anthropometric data (age, height, weight), and the study outcomes (see Additional file 3). In addition, participants will be given a tri-axial accelerometer (Axivity) to wear for 7 consecutive days on their right thigh. During the 7-day period, participants will be asked to document any physical activities or exercises completed in a paper-based logbook (see Additional file 7). After 7 days, participants will return the accelerometer and logbook to the research team via a pre-paid reply envelope. At baseline assessment, all participants will also receive a paper-based weekly diary (see Additional file 8) to document any adverse events which may occur during the intervention period (6 months) - see below. For participants who complete the baseline assessment at the hospitals, the online baseline questionnaire will be completed on-site and the research team member will directly attach the accelerometer onto the participant’s thigh. For participants who complete the baseline assessment remotely, they will receive a link to the online baseline questionnaire via SMS or email, and any relevant study documents and equipment will be posted to them. The participant will receive a detailed sheet with labelled images and instructions on how to self-attach the accelerometer device (see Additional file 7). As required, a research team member will be available to provide support for any baseline assessment procedures, via phone call or video-conferencing software.

0biomedical

0Study

In the current study, we investigated the neural reward processes for personal and vicarious rewards by using a false-choice gambling task while participants underwent fMRI scanning. In this vicarious reward task participants were asked to choose between two unknown distributions of resources upon which they were presented with the outcomes of rewards for themselves and for another target, who could be their mother, father, or a stranger. In addition, we employed a behavioral prisoner’s dilemma game (outside the scanner) to allow for explicit cooperative prosocial behavior (Gutiérrez-Roig et al., 2014). This task was presented in two conditions, the classic prisoner’s dilemma condition and a second condition in which cooperative behavior was beneficial for both parties (social dilemma or snowdrift game; Doebeli and Hauert, 2005; Kummerli et al., 2007). As such, the current study allows for a novel approach investigating whether the neural correlates of vicarious reward processing are related to actual cooperative behavior towards family members and strangers. Here, we examined these processes in adolescents between ages 8–19 years to test whether vicarious rewards for parents and strangers changed across adolescence (Silverman et al., 2015). In this critical phase of social reorientation and the drive for autonomy and independence concepts of in-versus-out groups are solidified. We have therefore chosen the two target groups carefully to help improve our understanding of how adolescents perceive members of these groups at a fundamental affective level, namely vicarious reward processing. Considering the high significance of parents across adolescence, we chose to include both parents as in-group members. Strangers were chosen as an out-group member as they are most likely to be perceived in similar ways across different individuals.

0biomedical

0Study

The structure of ODH, the first characterized enzyme within the ODH subclade of AA3_2 enzymes, represents a major step toward understanding the enzymatic diversity within the GOX/GDH clade as it represents the first structure of such an enzyme derived from a Basidiomycete and the second structure of a dehydrogenase from the GOX/GDH clade. Structure–function analysis points out some novel, unexpected features of ODH substrate recognition, especially: (i) the lack of specific glucose-binding residues (as found instead in GDH class-I and GOX) and the presence of three key aromatic residues (Phe416, Phe421 and Trp430 in ODH) providing CH-π stabilization; (ii) the involvement of a highly flexible substrate-binding loop in the process of substrate recognition; (iii) the presence of external SBSs, which might play a role in sensing substrate availability and directing the enzymatic activity toward the polysaccharide matrix, thus contributing to the overall enzymatic efficiency. ODH characterization is a good example of extended versatility, even within a small group of phylogenetically related enzymes such as the GOX/GDH clade of AA3_2 enzymes. As seen from previous phylogenetic analysis, increased biodiversity supported by novel, uncharacterized and unexpected enzymatic functions is yet to be expected within the AA3_2 subfamily of GMC oxidoreductases, including about 10 phylogenetic (sub)clades of enzymes of unknown function.

0biomedical

0Study

We wanted to confirm the kinetics of daughter centriole growth using an assay that was independent of Sas-6-GFP fluorescence incorporation. Our 3D-SIM analysis of the centrioles in early D. melanogaster embryos revealed that mother centrioles are usually oriented end-on to the cortex, so they appear as hollow rings (Fig. 7 A, Fig. S5, and Video 5). Thus, mother centrioles do not freely rotate in the z-axis, but rather adopt a relatively fixed orientation in reference to the cortex. We reasoned, therefore, that we could use the centriole distal-end binding protein GFP-Cep97 (Fig. 7 B) to measure the distance between the center of the mother centriole and the distal end of the growing daughter using Airyscan superresolution microscopy (Fig. 7 C).

0biomedical

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With this study, it was seen that our gamma-irradiated inactivated vaccine candidates can effectively trigger the production of SARS-CoV-2 specific antibodies along with long-term T cell response. Hence, the findings of this study prompted us to plan a new in vivo experiment with the second version of SK-01 and OZG-3861 (1 × 1013 or 1 × 1014 viral copies per dose) in humanized ACE2 + mice14. In this report, we determined that GMCSF adjuvant positive vaccine administration should be removed in the newly designed version of the OZG-38.61 vaccine model due to the finding of inflammatory reaction in the skin, cerebellum, and kidney in toxicity analysis of vaccinated mice. Therefore, it was decided to increase the SARS-CoV-2 effective viral copy dose (1 × 1013 or 1 × 1014 viral copies per dose) in the last version of vaccine candidates. In the challenge study, we produced the third and final version of the OZG-38.61 without an adjuvant14. In this study, it was demonstrated that the OZG-38.61.3 vaccine candidates that we created with gamma-irradiated inactivated SARS-CoV-2 viruses produced neutralizing antibodies, especially effective in 1014 viral copy formulation, and this was effective in transgenic human ACE2 expressing mice. We showed that it can protect against infection14. This preclinical study has encouraged us to try phase 1 vaccine clinical trials to avoid the COVID-19 pandemic.

0biomedical

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A growing interest in Neuroscience-related knowledge in recent years has led to an exponential growth in the amount of related information (correct or not) made available online as well as the market for Neuroscience-related courses in Brazil. Despite this growing interest and course availability, Brazilians from all walks of life show poor knowledge in this field. We observed this even among people studying or working in the areas of biological or health sciences, and even among those reporting several years of graduate education or professional experience, suggesting much work needs to be done to improve the quality of (neuro)science-related course options. While overall, participants seemed to know more about themes that are often presented in the media, they all displayed high endorsement of common neuromyths (e.g., left- vs. right-hemisphere dominance, and using only 10% of the brain). We also observed differences among Brazilian regions, which reflect long-standing inequalities in terms of access to quality education and other resources. Thus, professionals seeking to improve the quality of scientific content and communication (in courses or otherwise) may begin by focusing on ways of combatting neuromyths and developing ways of reaching individuals in the health sector as well as those living in disadvantaged regions. To the best of our knowledge, this is the first study testing these questions in such a large sample of Brazilians from all regions and several walks of life. We hope future studies further explore these questions and others that were raised here and remain unanswered.

0biomedical

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We found seven regions of cortical thinning in BDPMDD compared to controls: (i) left insula; (ii) right middle temporal gyrus; (iii) right medial orbitofrontal gyrus; (iv) left pars triangularis; (v) left rostral middle frontal gyrus; (vi) right cuneus; and (vii) right superior frontal gyrus (all pCORR < 0.05). Compared to PMDD the BDPMDD group had increased cortical thickness in the (i) left superior temporal gyrus; (ii) right pars orbitalis; (iii) left lingual gyrus; and (iv) right superior parietal gyrus and decreased cortical thickness in the (i) right medial orbitofrontal gyrus and (ii) right inferior parietal gyrus (all pCORR < 0.05) (Table 5, Figure 2). There were no within-group differences in cortical thickness across the mid-follicular and late luteal menstrual phases.

0biomedical

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Cox regression was used to assess time to 90-day and 1-year mortality, in relation to sBTLA on day 1–2 and day 7, with complete follow up for all patients. sBTLA was evaluated on a continuous scale, and as a binary marker (high vs. low), where the threshold concentration was defined as the nearest even concentration above the highest concentration in the control group. Adjustments were made for age, sex, comorbidity on a categorical scale (0, 1–2, ≥3), and severity (day 1 Δ SOFA), on a continuous scale.

0biomedical

0Study

Firstly, we performed the cell mitochondrial stress test with seahorse analyzer. BMSCs or ST2 cells were induced with osteogenic or adipogenic media for 7 days and then used for Seahorse assays. Compared to undifferentiated cells, osteogenic committed hBMSCs exhibited a notable increase in the basal oxygen consumption rate (OCR) but little change in basal extracellular acidification rate (ECAR) (Fig. 1A, B). Mitochondrial stress tests showed that basal respiration, OCR related to ATP production, and spare capacity were all significantly increased in osteogenic BMSCs over undifferentiated cells or adipogenic BMSCs (Fig. 1C), suggesting that under conditions of increased energetic demand, osteogenic committed cells had a higher capacity to increase ATP synthesis through mitochondrial OXPHOS. On the other hand, the adipogenic committed BMSCs showed an increase in basal ECAR level without any significant changes in OCR measurement (Fig. 1A, B). The energy map based on the OCR and ECAR demonstrated that undifferentiated BMSCs showed lower energy levels while differentiated cells had a higher OCR or ECAR level, which may corroborate the functional demand. Besides, the osteogenic committed BMSCs tend to be more aerobic, and adipogenic committed BMSCs were more energetic (Fig. 1D). Consistently, the osteogenic ST2 cells showed an increase in OCR, whereas the adipogenic ST2 cells exhibited a comparable OCR level and elevated basal ECAR level compared with undifferentiated ST2 cells (Additional file 1: Fig. S2A). Furthermore, the seahorse glycolytic rate assay of the ST2 cell line showed that the glycolytic rate was dramatically reduced by 24% during osteogenesis (Fig. 1E), indicating that the glycolytic flux receded during osteogenesis.Fig. 1Distinct metabolic profiles in osteogenic and adipogenic committed BMSCs. A Seahorse mito-stress test for oxygen consumption rate (OCR) in BMSCs on Day 7. B Seahorse mito-stress test for extracellular acidification rate (ECAR) in BMSCs on Day 7. C Quantification of OCR parameters in BMSCs. D Energy map of BMSCs. Mean basal OCR in dependence of mean basal ECAR is shown. E Seahorse glycolytic test and quantification for ECAR in ST2 cells on Day 7. F Glucose consumption rate in BMSCs on Day 7. G Lactate production rate in BMSCs on Day 7. Ctrl: control; Osteo: osteogenesis; Adipo: adipogenesis; Oligo: oligomycin; FCCP: Trifluoromethoxy carbonylcyanide phenylhydrazone; Rot: rotenone; Ant: antimycin A. N = 3. Statistical significance was calculated with one-way ANOVA. *p < 0.05; **p < 0.01. Data are represented as mean ± SD

0biomedical

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We will develop a data extraction sheet to guide data extraction. The sheet will be pilot-tested by two reviewers (VNN and JF) on a random sample of 05 articles and revised as needed. Two reviewers will independently read each eligible full-text article and extract the relevant data. Both sets of data will be entered into Microsoft Excel (version 2016 for Windows, Microsoft Corp., Redmond, WA, USA). Any discrepancies in the extracted data will be resolved by consensus, in discussion with a third reviewer (DT or JF) if necessary.

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The experiment consists of four phases. In Phase 1, subjects perform 3 trials of 45 tasks. Phase 2 involves different forms of training. Subjects in the task repetition group repeat the same 45 tasks twice and with extra time. If subjects are in the synergy repetition group, eight postural synergies were derived from kinematic data in Phase 1. These subjects trained on performing the eight postural synergies. Subjects in the control group were required to rest for ~10 min. In Phase 3, all subjects were retested on the tasks performed in Phase 1. In Phase 4, 32 new tasks were introduced to test transference of the new skill.

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The WHO has established definitive criteria for diagnosing CJD, taking into account different diagnostic modalities and variances in clinical presentations . Considering these criteria, our patient had rapidly progressive dementia along with myoclonus, nystagmus, and increased rigidity of his right side. MRI showed increased signals in the caudate nucleus along with cortical ribboning, which makes CJD a probable diagnosis. EEG findings were nonspecific in our patient, and the CSF protein 14-3-3 testing was not available in our set-up. Post-mortem examination of the patient could not be done due to the family's refusal to give consent.

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3Clinical case

The fitting process is operated by using a well-developed program by our lab. By using different trail values of unknown parameters, the theoretical phase shifts are calculated over the specified modulation frequency range. The value that gives the least square deviation between the theoretical phase shifts and the experimental ones is taken as the real property of materials. Here, the thermal resistance induced by the SiO2 layer and the β-W/SiO2 interface (noted as \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{W/Si{O}_{2}/Si}$$\end{document}RW/SiO2/Si) and the cross-plane k of β-W films are both unknown. However, one single measurement of the sample cannot distinguish these two properties. What we can get from the fitting of one sample measurement is the total thermal resistance (R total) of the sample, which includes both the thermal resistance induced by the β-W film and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{W/Si{O}_{2}/Si}$$\end{document}RW/SiO2/Si. Then we measure samples of different thickness that are synthesized under the exactly same conditions to vary the effect of thermal resistance of the β-W film. By studying how R total varies with the W film thickness (L), k of β-W film and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${R}_{W/Si{O}_{2}/Si}$$\end{document}RW/SiO2/Si can be distinguished and determined.

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In the third method the stepwise regression was used. This method is useful in case of large amount of explanatory regressors (the questionnaire data subcategories in our case). Gradual draining of individual explanatory variables, for which H0:βi=0 cannot be dismissed, simplifies the regression model and identification of statistically significant explanatory regressors.

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In this paper we leverage the GEE platform to figure out the influence of different impact factors on forest NPP and how forests of different NPP-levels respond to climate change and short-term climate fluctuations (i.e., ENSO events), and to understand spatiotemporal dynamics of the global forest NPP and explore its relationships with forest traits, climate conditions, and ENSO. The article is organized as follows: datasets and preprocessing are introduced in the second section; methodology is depicted in the third section; results and analyses are presented in the fourth section; comparison and discussion are shown in the fifth section; and finally, we conclude the article in the last section.

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This index is an adaptation of Gaussen aridity index (Bagnouls & Gaussen, 1953) developed by Montero de Burgos and González‐Rebollar (1974) that measures monthly soil water availability for plant as an index of plant productivity. It uses meteorological information on monthly precipitation and average monthly temperature but also water runoff (we chose 10%, appropriate for soils on moderate slopes) and soil water retention capacity (100 mm, typical of most soils). It has been used previously in the study area (Martínez‐Jauregui et al., 2009; Peláez et al., 2018; Pelaez et al., 2017) to determine food availability for hinds during late gestation (March and April) and early lactation (May and June). Low mean values of RBI indicate low plant productivity as a result of drought (low precipitation and hot temperature) or winter vegetative rest (low temperatures). Spring plant productivity (from March to June) is very important in Mediterranean environments as a long productive spring shortens the deleterious effect of the summer drought, when females are lactating, allowing females to come into the rutting season with higher body reserves (Bugalho & Milne, 2003; San Miguel et al., 1999). Meteorological data were obtained from a weather station located at Los Cortijos, 2 km south of the estate and from Los Quintos de Mora weather station (Spanish National Meteorological Agency).

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Rare pathogenic CNVs have also been shown to increase liability to more common mental health disorders, such as MDD. Here, short deletions (<100 kb) and known neuropsychiatric CNVs are enriched in people with depression [14•,22], and significant association has been found for 3 specific CNVs (1q21.1 duplication, PWS/AS duplication, and 16p11.2 duplication) (Supplementary Table S1) [14•].

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In this study, we examined the association of maternal BV with a mothers' condition and infants' morbidities. Our analysis showed an increase in the frequency of maternal hospital admissions among women with BV compared to non-exposed subjects. In our literature review, we did not find any publication that directly reports on maternal perinatal adverse outcome associated with BV, and reports have universally focused on fetal/neonatal outcome. The closest article was a systematic review on the use of probiotics to improve maternal microbiota, which demonstrated a reduction in gestational diabetes and better blood sugar control. Prolonged hospital admission has a cost implication and increases the risk of nosocomial infections (29).

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This study shows that constitutively activating mutations of eLH/CGR (M398T, L457R, D564G, and D578Y) resulted in a significant increase in the basal cAMP production and a faster loss of the cell-surface receptor compared to wild-type eLH/CGR despite low cell-surface expression, which has been reported for mutations of these highly conserved amino acids in mammalian LHRs. The rate of loss of the M398T and L457R mutants from the cell surface was found to be very similar to that of wild-type eLH/CGR, whereas the half-life (t1/2) of the cell-surface receptor loss indicated a faster loss for the former than for wild-type eLH/CGR. The other two activating mutants (D564G and D578Y) exhibited a slightly faster rate of cell-surface receptor loss. However, the loss of the cell-surface receptor considerably decreased to 55–62% until termination after 15 min. Thus, we suggest that D564G and D578Y mutants exhibit a similar cAMP response as wild-type eLH/CGR for the constitutive loss of the cell-surface receptor. In contrast, the inactivating mutations (D405N, R464H, and Y546F) completely impaired the signal transduction of the agonist-mediated receptor response. The loss of the D405N and Y546F mutants from the cell-surface receptor was not complete; however, the loss of the R464H mutant was considerably slower than that of the agonist-occupied wild-type receptor. Thus, we suggest that the activation process might involve an agonist-induced conformational change in the eLH/CG receptor-eCG complex. These findings are extremely important for our understanding of eLH/CGR function and regulation with respect to mutations of highly conserved amino acids in mammalian glycoprotein hormone receptors. Future studies on the mutations of glycoprotein hormone receptors could provide highly useful information for identifying the cellular mechanism responsible for the structure–function relationship of eLH/CGR-eCG complexes in signal transduction.

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The above pending Be–Te and Zn–Te issues at the term of our experimental Zn1−xBexTe Raman study at small Be content, together with the missing insight at large Be content, are tackled below by extending to high pressure the ab initio calculations on the Zn1−xBexTe supercells at x \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sim $$\end{document}∼ (0,1). Generally, the AIMPRO (Raman signal, Fig. 3) and SIESTA (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Gamma $$\end{document}Γ-PhDOS, see Figs. S2, S9 of Supplementary Sects. I, II, related to Zn30Be2Se and Zn30Be2Te, respectively) trends are consistent, which gives confidence for the discussion.

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Statistical analyses indicated that the transverse and longitudinal diameters of the nuclei in Leydig cells of cryptorchid Bactrian camels were significantly increased compared to those in normal testicles (p< 0.05). The average areas of the Leydig cells were significantly larger in cryptorchid testes than in normal testes (p<0.01, Table 1).

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Since shh is expressed in the prospective floor plate from the beginning of the notochord formation as well as in the node, we asked whether its expression is initiated prior to node and prechordal mesoderm formation. Surprisingly, chick embryos are shh positive already between stages 2 and 3 (Fig. 2a). At this stage, the primitive streak appears as a density extending from the posterior pole to the center of the blastodisk and is in its posterior part wider and resembles an isosceles triangle . The expression of shh is strong and related to the zone in the front of the medial thickening and in its anterior area. The area anterior to the primitive streak density has been shown to correspond to the prospective neuroectoderm, especially to the future floor plate, whereas the anterior portion of the primitive streak gives rise to the prechordal mesoderm and notochord [42, 79]. Transverse technovit sections near the posterior border of staining reveal a medial thickening with a groove (Fig. 2c), which corresponds to the anterior part of the primitive streak. Sections at the anterior level (Fig. 2b) reveal expression of heterogeneous intensity, which is confined to epiblast cells displaying a columnar epithelial shape. Additionally, single scattered mesenchyme-like positive cells representing early mesoderm are found under the epiblast. These cells correspond to local EMT areas, which were shown to occur at low intensity at this stage within the entire epiblast .Fig. 2Early shh expression in the chick stage 2 +/3 − embryo. Arrow: position of the tip of the primitive streak

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Prior to the COVID-19 pandemic, telehealth was not widely used in pediatric rehabilitation settings despite numerous studies supporting its use as a feasible alternative to conventional in-person healthcare . A World Health Organization (WHO) report “Global diffusion of eHealth” from 2016 documented the use of telehealth services in different countries based on a survey sent to their member states. One hundred and twenty-two countries (out of 194) responded, with only 22% of the countries reporting the use of telehealth services. In a similar report, Camden and Silva surveyed 76 countries in 2019 and found that only 4% used telehealth prior to COVID-19. It appears that technical, logistical and training challenges deterred therapists from using tele-rehabilitation. However, in May 2020, just three months since the global awareness of COVID-19, the same polled countries reported an increase of 70% .

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2Review

To analyze the presence of genes putatively associated with phage resistance systems, a custom database based on genes from the ‘‘PADS Arsenal database’’1 was created (Zhang et al., 2020). The genes were grouped in five systems: ABI systems related (not belonging to toxin/antitoxin system), TA systems related, R–M system related, CRISPR-Cas-associated proteins, and newly (NEW) characterized systems-related genes. In this last category, we included those genes which hit against known phage-resistant genes but were associated with genes predicted to be associated with phage-resistant functions and whose function in A. baumannii is not clear yet, such as newly characterized systems (e.g., Zorya, Druantia, and Thoeris). In this category, it is also included those genes related to known and characterized systems but without a complete functional characterization in A. baumannii (e. g. BREX). A blast search of the complete genomes against this database and filtered out those hits with an e-value > 1E-04 was made. Statistical significance was determined by comparing the absolute number of each system in the nine genomes of Ab_GEIH-2000 collection against the absolute numbers of genes of Ab_GEIH-2010 collection with the Student’s t-test. The percentage of the genes involved in resistance was calculated by dividing the genes predicted to be associated with phage resistance by the total number of genes in the bacteria genome.

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All experiments were performed on PamStation12® where up to 12 assays can be performed simultaneously (PamGene International B.V., ‘s-Hertogenbosch, North Brabant, The Netherlands). To prevent unspecific antibody binding, the PamChips® were first blocked with 2% BSA, by pumping it up and down 30 times through the arrays. The chips were then washed three times with Protein Kinase Buffer and assay mix was applied. The assay mix was pumped up and down through the arrays for 60 min. Afterwards, the arrays were washed and FITC labelled secondary antibody mix was applied on the arrays. The images of the arrays were recorded at multiple exposure times .

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One puzzle about the commonly accepted mechanism of paclitaxel action is the issue with mitosis as the target . Unlike cells in tissue cultures, the neoplastic cells found in tumors in vivo are much less proliferative, with a doubling time significantly longer than cultured cells . At any given time, only a small fraction of cancer cells are undergoing mitosis . Thus, non-mitotic cells, in addition to cells undergoing mitosis, are likely targets of paclitaxel in cancer therapy . Particularly in clinical settings, the susceptibility of cancer cells to killing by paclitaxel does not correlate with the proliferative index of the cancer . This problem inspired the concept of “proliferative index paradox” , denoting that mitosis may not be a key target of paclitaxel or explain its efficacy as an anti-cancer agent .

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From January 2010 to April 2014, 190 patients with newly histopathologically confirmed GBM, based on the World Health Organization criteria, who had undergone surgical resection, were selected from the electronic medical database of our institution. The inclusion criteria were as follows: (a) gross total surgical resection; (b) CCRT with TMZ and adjuvant TMZ after complete resection; (c) immediate (up to 48 hours) post-operative contrast enhanced MR imaging demonstrating absence of any post contrast enhancement at the surgical cavity wall; (d) post-CCRT contrast enhanced MR imaging and DWI within three months after the completion of CCRT with TMZ; (e) newly developed non-measurable wall enhancement at the surgical cavity on post-CCRT MR imaging; and (f) serial follow-up MR imaging studies. In total, 46 GBM patients with newly appearing non-measurable surgical cavity wall enhancement were identified, and of those, 13 patients were excluded for the following reasons: (a) definite disease progression, after the completion of CCRT with newly developed or enlarged measurable enhancing lesion, which was defined as a bi-dimensionally measurable, contrast-enhancing lesion with two perpendicular diameters of at least 10 mm on post-CCRT MR imaging (n = 4); (b) seeding lesions developing after the completion of CCRT with TMZ (n = 9)

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TC71, A4573, and SK-ES-1 cells were plated in 96 well plates in RPMI-1640 media with 10% FBS at a density of 2x104 cells per well, and were treated with 1µM WNT974 or DMSO 1:1000 as a control. After 48 hours of incubation, cells were assessed for viability with the Cell Counting Kit-8 (Dojindo Molecular Technologies, Rockville, MD) per manufacturer’s instructions.

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FOREST is an academic-driven, multicenter, open-label, randomized clinical trial of fosfomycin vs ceftriaxone or meropenem (if the bacteria is ceftriaxone resistant) in the targeted treatment of bUTI caused by MDR E coli. Patients were recruited from June 2014 to December 2018 at 22 Spanish hospitals. The original protocol included only extended-spectrum β-lactamase (ESBL)–producing E coli, and the comparator was meropenem11; in January 2015, the protocol was modified owing to low recruitment to include any MDR E coli, and ceftriaxone was added as comparator for susceptible isolates.12 The study protocol is available in Supplement 1.

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We point out that the stimulation duration is another relevant parameter; that is particularly important when it comes to the long-lasting effects of the stimulation. While stimulation parameters such as the number of stimulation sites, the stimulation amplitude, and the stimulation frequency determine whether the stimulation leads to a reduction of the mean synaptic weight, the time it takes to achieve a sufficient weight reduction and drive the network into the attractor of a stable desynchronized state depends on the actual rate of synaptic weight reduction. In Figure 8, stimulation is capable of inducing long-lasting desynchronization effects for all considered numbers of stimulation sites. However, the required stimulation duration to drive the network into the attractor of a desynchronized state varies by more than one order of magnitude. Thus, for too short stimulation duration, stimulation might be considered ineffective for inducing long-lasting effects even though it would be well capable of inducing such effects for a longer stimulation duration. This is particularly important as, e.g., the current parameter adjustment procedures for standard DBS focus on acute effects (Volkmann et al., 2006), which may compromise the potential long-lasting effects.

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Most reported OCC systems rely on a line of sight (LOS) path from the transmitter to the receiver. However, there are scenarios where the transmitter is not within the receiver’s FOV, for example a bookshelf blocks the transmission link between the lamp and smartphone in indoor, or two vehicles approach a cross-road in outdoor. In such cases, the connection cannot be established directly. Instead, an NLOS OCC system explores either indoor surface reflections or outdoor atmospheric scattering. Figure 12 depicts two typical NLOS OCC scenarios, where figure 12a is for an indoor environment and figure 12b is for an outdoor environment. Figure 12.Typical NLOS OCC scenarios. (a) Indoor and (b) outdoor. (Online version in colour.)

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A gas chromatography-mass spectrometry (GC-MS) approach was employed to identify pre-defined metabolites associated with the central carbon metabolism (CCM). This includes the basic energy pathways of glycolysis, the tricarboxylic acid (TCA) cycle and amino acids (AA). The comparison of the benign HOS to the malignant MNNG/HOS and metastatic 143B cell line revealed an upregulated CCM (Figure 1A, Table S1 and Figure S1). The comparison of the malignant MNNG/HOS to the metastatic 143B cell line showed decreased pools of the metabolites from the CCM in the 143B cells. To analyze the general effect on energy metabolism, the data were treated as follows. First, the results for each metabolite across all cell types were univariate scaled . This had the advantage of giving all the metabolites a common non-parametric scale for comparison. Next, the metabolites were grouped according to their metabolic class (e.g., glycolysis, TCA cycle or amino acids), and the results for all the metabolites per class were considered together for analysis by plotting them on a common axis and assessing trends for increases or decreases per biological class. The combined analysis revealed a significant increase in metabolites from glycolysis, the TCA cycle and amino acids in MNNG/HOS cells compared to HOS cells (Figure 1B). The comparison of 143B to the HOS cells revealed a significant increase in the metabolites from the TCA cycle and the amino acids in the 143B cells. A significant decrease in metabolites from the TCA cycle and amino acids could be shown for the 143B cells in comparison to the MNNG/HOS cells.

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Firstly, the increase of CD4 cells count at 24 months from the baseline was considered, which implies missing or lost patients before the end of follow-up period were excluded in the analysis. In that case, the total number of patient in the analysis reduced to n=334, with nR=169 and nN=165. “Observed data” will refer to the case where data are analyzed by excluding participants with missing observation at 24 months.

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The first cases of COVID-19 in CGPP implementation areas were reported between January 30 and April 5, 2020, and stigma quickly followed. Stigma impacts health education, testing, contact tracing, and even treatment for infected individuals. In India, a fruit vendor, his wife, and two adult children were the first with COVID-19 in their village. They fully recovered and returned home from an isolation center only to be boycotted by neighbors and relatives, leaving the family ostracized, isolated, and cutoff from their only source of income. In South Sudan, unfamiliar contact tracers who enter a village are faced with suspicion, beaten, or chased off. Figure 1 highlights the different manifestations of stigma, the various populations affected, and its consequences in CGPP areas.

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Cells were fixed using formaldehyde solution for the preparation DNA-protein cross-link. Chromatin fragments were obtained by application of ultrasonic sound (10 seconds each time at an interval of 10 seconds, 12 times). The supernatant was collected through centrifugation at 12000g and 4°C for 10 minutes. Thereafter, the supernatant was incubated with antibody to IgG or antibody to SP1 at 4°C overnight. The DNA-protein complex was precipitated using protein agarose/sepharose, followed by centrifugation at 16099g for 5 minutes. The supernatant was discarded, and the non-specific complex was washed. De-cross-linking was conducted at 65°C overnight. DNA fragment was purified and extracted using phenol/chloroform. The binding of SP1 to the MG53 promoter was determined by RT-qPCR.

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Earlier, inhibin alpha-subunit (INHA) was found to have a tumor suppressive role in adrenocortical tumorigenesis. In INHA knockout mice, 99% developed steroid-secreting ACCs after gonadectomy . Hofland et al. (2014) investigated the methylation and expression of Inhibin α-subunit (encoded by INHA) in adrenal tumors. They found a significant difference in methylation of the INHA promotor between normal adrenals and ACCs. However, the promoter methylation in the ACC samples was not associated with tumor characteristics or ENSAT stage.

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Rates of CVA/TIA were reported in all trials. Only the study from Guha reported both CVA and TIA, while the rest of the studies described only the rates of CVA. The overall stroke rate was 2.4% (264 of 11,126) compared with 2.7% (1,141 of 41,661) in the control group. Patients in the cancer group had an odds ratio of 0.87 (95% confidence interval: 0.76–0.99; p < 0.04) for periprocedural stroke compared to the patients without cancer. There was no evidence of statistical heterogeneity among studies (I2 = 0%; heterogeneity p = 0.92). There was no evidence of publication bias on visual estimation of the funnel plot (Supplementary Figure 2).

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After the conversion from bcl to fastq format, the short reads were processed to clean up from sequencing adapters, and to filter or trim the reads for sequence quality (minimum Phred quality of 10 and minimum length of trimmed sequence of 30). Both these steps were performed with AdapterRemoval v.1.5.4 tool , after which the cleaned reads were mapped on human reference genome hg19 with Burrows–Wheeler Aligner (BWA v0.7.12) for WES data, in paired-end or single-end mode according to the type of sample, and with the TopHat/Bowtie v2.0.9 pipeline for RNA-seq data. Samtools v1.4 was adopted to remove the optical and PCR duplicates and to index the alignment files. Then, the RNA-seq data analysis was performed to examine for the presence of any chromosomal rearrangements leading to gene fusions. For this purpose, four different tools were adopted: TopHat-Fusion v.2.0.9 , Defuse v0.6.2 , ChimeraScan v0.4.5 , FusionMap v2015 . In order to increase the specificity, a predicted gene fusion was considered for further investigation if it was detected at least by two of four predictors. Gene expression profiling and differential expression of D842V mutant was evaluated comparing them with a set of seven GIST tumors with mutation on KIT exon 11 as previously described by Nannini et al. (2014) , and the pathway enrichment analysis was performed with WEB-based GEne SeT AnaLysis Toolkit (www.webgestalt.org) adopting the Reactome functional database (https://reactome.org/) as reference and the default settings of the tool. This analysis was run on the pre-ranked gene list of 1882 differentially expressed genes, selected by soft filtering cut-off (p < 0.05 and |log2Ratio| < 0.4).

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In regard to V. harveyi, the synthetic compounds, bithionate sodium, N,N-diethyl-M-toluamide, and 4-hexylresorcinol showed a significant bactericidal activity at increased concentrations of the strain (Table 2). The natural compounds, such as eucalyptol, garlicin 80%, monocrotaline, and pyrethrins 50%, showed a significant antimicrobial activity at 10 µM (p < 0.05) (Table 3).

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Mutations in ACTG2 are the least common, with just over 20 described. Almost all of these (96%) are missense (Figure 1 and Supplementary Table S1). The expression of this γ-actin isoform is restricted to smooth muscle cells in the gut, prostate, bladder and adrenal gland. Mutations in ACTG2 cause Megacystis microcolon-Intestinal hypoperistalsis syndrome , also known as chronic intestinal pseudo-obstruction, visceral myopathy (or degenerative leiomyopathy) . All of these are disorders of enteric smooth muscle function. They mainly affect the intestine leading to chronic intestinal obstruction, and can also affect the bladder. The smooth muscle cells in the smooth muscle layers that surround the gut epithelium are important for moving the contents of the gut along its length. The organisation of these smooth muscle cells is often disordered in this disease, likely leading to decreased smooth muscle contraction and the resultant intestinal obstruction .

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Full-thickness cornea (two corneas per sample) and bulbar and palpebral conjunctiva (conjunctiva from two eyes per sample) were collected from naïve and DED mice and stored in reagent (TRIzol; Invitrogen, Carlsbad, CA, USA) at −80°C. After homogenization, RNA was isolated and reverse transcribed using an RNA purification kit (RNeasy Micro Kit; Qiagen, Valencia, CA, USA) and a cDNA synthesis kit (Superscript III; Invitrogen), respectively. Polymerase chain reaction was performed using a master mix (Taqman Universal PCR Master Mix; Applied Biosystems, Foster City, CA, USA) and the following primers: GM-CSF (Mm00438331_g1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH, Mm99999915_g1; Applied Biosystems). Comparative threshold (CT) values for GM-CSF and GAPDH were measured using a real-time PCR system (LightCycler 480 II System; Roche, Indianapolis, IN, USA). Comparative threshold GM-CSF values were normalized to GAPDH CT values (endogenous control), and the level of GM-CSF mRNA expression in DED mice relative to naïve mice was then calculated. Samples were run in triplicate.

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A total of 2,284,061 quality-filtered reads were obtained from 23 water samples (Figure 1). They grouped into 1414 protistan and 37 metazoan OTUs delineated using a cut-off value of 99% of sequence identity. The metazoans belonged to known Baikal multicellular organisms (mainly copepoda). The protistan OTUs were analysed according to their relative abundance . In total, 24 OTUs were abundant (>1% of all reads), 1129 OTUs were rare (<0.01%), and 317 OTUs had intermediate abundances (0.01% < OUT < 1%). Among the rare OTUs, only 344 OTUs were represented by less than 10 reads, while others were represented by up to 230 reads. The rarefaction curves (Figure S1) indicated that we approached diversity saturation.

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To unravel these different theories of UBC development we tested if TERT promoter mutations occur early in proposed pre-stage tissues associated with the tumor and play a role during tumorigenesis. Therefore, we analyzed TERT mutations at different known promoter nucleotide positions using a large cohort of whole-organ mapping bladder tumors.

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The total number of consultations for men in the whole period was 7,134, almost 4 times that of women, which was 2,138. The baseline level of the number of consultations for men was 193.23 at the beginning of the whole period, while it was 44.92 for women. During the pre-intervention phase, while a non-significant increase of 2% in the trend of consultations was observed among men from one quarter to the next (RR = 1.02; 95% CI = 0.99, 1.04) there was a significant trend decrease of 2% in consultations for women during the same period (RR = 0.98; 95% CI = 0.95, 1.01). The level of the number of consultations decreased significantly by 40% for men and increased 187% for women per quarter just after the intervention. Finally, the trend of consultations experienced a non-significant increase of 1% per quarter in the post-intervention phase (RR = 1.01; 95% CI = 0.99, 1.03) for men and a statistically non-significant decrease of 1% per quarter in the attendance trend for women (RR = 0.99; 95% CI = 0.96, 1.04) (Table 5) (Figure 1) Figure 1.Number of consultations for men and women at CASSIN from January 2007 to June 2017Table 5.Segmented negative binomial regression results expressed as rate ratios (95% CI in brackets) of the number of consultations at a free clinic by sex (January 2007 to June 2017) Baseline levelPre-interventionInterventionPost-interventionMen193.23 (147.58, 253.01)0.99 (0.98, 1.02)0.65 (0.46, 0.91)1.01 (0.99, 1.02) 205.15 (130.37, 322.87)a1.02 (0.99, 1.04) a0.60 (0.42, 0.84) a1.01 (0.99, 1.03) aWomen44.92 (34.35, 58.74)0.98 (0.96, 1.00)2.64 (1.78, 3.91)1.00 (0.99, 1.02) 56.99 (30.18, 107.64)a0.98 (0.95, 1.01) a2.87 (1.80, 4.58) a0.99 (0.96, 1.04) aaAdjusted for unemployment, seasonality and percentage of documented migrant population

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DENV 1−4 exhibited a serotype-specific response to mAb ZKA185 (Figure 2B). ZKA185 did not significantly neutralize DENV1 or DENV2 (Figure 2B). DENV3 was significantly more inhibited than DENV4 with viral inhibition occurring a 5.0 ug/ml, and 0.5 ug/ml (Figure 2B) (p = 0.003). DENV4 was significantly enhanced in the presence of ZKA184 (p = 0.0058) with enhancement occurring in a dose-dependent manner at both 0.5 ug/ml and 0.05 ug/ml (r = 0.8707) (Figure 2B).

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Other risk factors that are potentially important in explaining waste-related diseases have been discovered to play a significant role. Among other aspects, irregular waste disposal is significantly determining the incidence of being sick [25, 26]. This finding is also significant in the debate over the relative strength of municipal service providers in planning and assessing measures to provide adequate and fully effective waste collection services. Waste-related illness does not appear to be primarily driven by burning, dumping waste into Nalas, or water supply lines passing through drainage. Furthermore, the education level of household head is irrelevant as a predictor of illness and is inversely related to the likelihood of illness [25, 47].

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The observation of Mg2+ binding to the low-affinity site of N-cTnC has led to the suggestion that differences in affinity may be due, at least in part, to Ca2+ buffering, and thus, the free concentration of the ion in these experiments. Given the kinetic rates associated with these interactions, it is difficult to have confidence in EGTA-determined rates of binding (93). Moreover, the temperature sensitivity of cTnC alone can alter experimental outcomes by orders of magnitude (53, 94). Change in sensitivity in the face of altered temperature has been suggested to result mostly from binding to the low-affinity sites and possibly through interactions with other members of the cTn complex (95, 96, 97).

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Another potential barrier to the efficacy of iron fortified CF in Côte d’Ivoire is the widespread persistent low-grade inflammation caused by Plasmodium spp. (the causative agent of malaria) parasitemia that is reported to decrease iron absorption through increase in hepcidin . Previous efficacy studies with iron fortified foods conducted in malaria-endemic settings revealed conflicting results. Iron status improved in young Kenyan children fed NaFeEDTA-fortified maize porridge and in Ivorian school-age children who received meals containing salt fortified with micronized ground FePP , which was in line with findings obtained from children in non-malaria endemic areas . In contrast, another trial conducted in Ivorian school-age children found that electrolytic iron fortified biscuits did not improve children’s iron status ; the authors suggested this was due to malaria-induced inflammation and use of an iron fortificant with low bioavailability (electrolytic iron) .

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This analysis is performed on the largest single homogeneous population sample, to date. We detected most known genetic associations with common variants (MAF > 5%) using the genotyped dataset alone. For many of these associations, a weaker signal was detected using the genotyped GWAS, which became stronger in imputed SNPs that are presumably more closely linked to the causal variant. We identify such associations in many of the traits reported in Table 1 and the majority are within a known association signal.

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IcIgA and icIgG tended to represent the predominant isotypes in intra- and subepithelial PCs. However, there were two individuals in whom intra-/subepithelial icIgD PCs were more frequent than icIgA and icIgG PCs. Subepithelial PCs tended to be larger than the plasma cells found in GCs and exhibited more regular round nuclei. In all individuals, the majority of the intra-/subepithelial icIg+ cells were large oval Ki-67− PCs. Only cells with less icIg and a relatively round shape occasionally exhibited Ki-67+ nuclei. However, one individual exhibited a higher number of large icIgD+Ki-67+ cells of typical PC morphology. Near the deep connective tissue septa between crypts, most PCs contained icIgG in all individuals. The second-most frequent isotype in this location was IgA.

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It needs to be stressed further that one of the important advantages of the gold nanodevices is their high stability with high resistance to thermal and chemical damage mechanisms. In our studies on the ultrafast optical modulation performance, we did not observe any obvious morphology changes due to strong optical irradiation and the transient spectroscopic response stays stably over the whole measurement procedures. In Figure S3 in the Supporting Information, we present experimental data to verify the stability of the AuNW grating under continuous illumination of femtosecond laser pulses for nearly 3 h (correspond to the continuous excitation by more than 107 laser pulses).

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Large clusters of wind turbines in Karnataka are located in Chitradurga and Gadag districts. We selected wind farms in these two districts for the current study (Fig. 1). Chitradurga district lies between 14.23° N and 76.39° E. We selected Vani Vilas Sagar (VV Sagar) (24.8 km2), Jogimatti hills (100.5 km2), and Challkere hills (2.0 km2) in the district, having established wind farms. We selected adjoining or the same hills without wind turbines as control sites having a similar habitat, like the wind turbine locations in VV Sagar and Jogimatti (Table 1). Gadag district is located in the north-western part of northern Karnataka, which lies between 15.42° N and 75.62° E. Malaprabha River in the north and Tungabhadra River in the south form the natural boundaries of the district. The district spans over a total geographical area of 4656.0 km2. We selected Kappatagudda (320.9 km2), Kelur (40.0 km2), and Papanasi (27.5 km2) wind farm sites in the Gadag district (Table 1) and one site in Kappatagudda without any wind turbines as a control site. Most of the wind turbines were of 0.8–1.25 MW capacity.Figure 1The select wind farms and control sites studied for animal fatality rate, and bird diversity and mammal distribution in Karnataka. The map is prepared on QGIS platform (QGIS Development Team 2009). Figure was prepared with the layers downloaded from the DIVA-GIS website (https://www.diva-gis.org/Data) which is a freely downloadable spatial data source. Hence, it does not require any certification to use its layers. Other layers are created by us which are overlayed on the base map downloaded from the DIVA-GIS website. These layers are processed using the QGIS platform. QGIS Development Team. (2009). QGIS Geographic Information System. Open-Source Geospatial Foundation. http://qgis.org.Table 1Location and physical characteristics of wind farm and control study sites in Chitradurga and Gadag districts in Karnataka, India.Sl no.ParametersChitradurga DistrictGadag DistrictWind farm sitesControl sitesWind farm sitesControl sitesVV Sagar WSJogimatti WSChallkere WSVV Sagar CSJogimatti CSKelur WSPapanasi WSKappatagudda WSKappatagudda CS1Geocoordinates13° 49′ 52.45″ N76°30′ 2.71″ E14° 11′ 35.09″ N76° 25′ 5.66″ E14° 14′ 29.50″ N76° 26′ 37.65″ E13° 52′ 0.33″ N76° 32′ 12.33″ E14° 10′ 51.39″ N76° 24′ 13.04″ E15° 10′ 15.51″ N75° 45′ 33.67″ E15° 21′ 25.96″ N75° 40′ 36.83″ E15° 14′ 10.30″ N75° 43′ 14.32″ E15° 11′ 44.79″ N75° 45′ 22.19″ E2Name and status of the patchMarikanive RFJogimatti RFPrivate landMarikanive RFJogimatti RFKappatagudda RFPrivate landKappatagudda RFKappatagudda RF3Vegetation coverDry grassland and scrub forest + mostly Dodonaea viscosa coverDry grassland + Acacia sp. vegetation coverDry scrublandDry grassland and scrub forest + mostly Dodonaea viscosa coverDry grassland + Acacia sp. vegetation coverThorny scrub and dry grasslandAgricultural landThorny scrub and dry grasslandThorny scrub and dry grassland4Altitude (m asl)700–948700–1010700–767700–740700–1067660–769660660–967665–9005No. of wind turbines1231818––19116203-6Vegetation typeSouthern Tropical dry deciduous forest and Southern tropical thorn forest6Average annual temperature22.1 °C26.9 °C7Average annual rainfall573 mm612.50 mm8Average annual humidity73.65%55.97%9Mean wind speed8.2 km/h11.4 km/hWS wind farm site, CS control site, RF reserved forest.

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During foraging, bees fly back and forth several times during the day between the hive and the food location, collecting nectar/pollen and bringing it to the hive for their colony. Foraging involves highly systematic and dynamic behavioral capacities that include long distance navigation using the sun as compass, evaluation of food quality, learning and memorizing flower cues, sense of colour, and social communication/interaction for coordination in collecting nectar, pollen, and water . For decades the outdoor experiments have been routinely performed by feeding bees on pollen or sucrose solution placed in a specific place in order to mimic the natural foraging environment in close proximity. Using this experimental setup, we attempted to identify foraging regulatory genes in the European honey bee species Apis mellifera while the bees were performing their daily routine foraging. For this, the immediate early genes (IEGs) were the ultimate targets to examine, as they are well known as neural markers.

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Findings of the current study further indicate that most of the patients suffering from the ischemic heart diseases aged above 55 years. These findings are in line with those provided in the study of Sun according to which the incidences of stroke are frequent after the age of 55 years. Yousuf and Young further supported the idea and stated the prevalence of ischemic stroke risk factors increases by the age of 65.

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CAR-T cells were generated from commercial normal donor peripheral blood mononuclear cells (PBMCs) from AllCells. The cells were further enriched from PBMC by CD3 magnetic beads (Miltenyi) and stimulated by anti-CD3/CD28 beads (Dynabeads, human T activator CD3/CD28; Life Technologies) at a 1:3 bead:T cell ratio and then cultured in H3 medium (Takara) with 4% human AB serum and 10 ng/mL recombinant human IL-7 and IL-15 (Miltenyi). Cells were exposed to lentivirus containing supernatant on days 2 and 3 with MOI = 5 on retronectin-coated non-tissue culture plates (Takara/Clontech). Beads were magnetically removed on day 4 or 5, and cells were further expanded for 3−5 days in H3 media containing 10 ng/mL recombinant human IL-7 and IL-15 until use in vitro or in vivo.

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Please include the following items when submitting your revised manuscript:A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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The tissue samples were fixed in 4% paraformaldehyde at 4 °C and sectioned into slices. After deparaffinizing and rehydration, the sections were put into a pressure cooker for 5 min to restore the antigen in the nucleus using the citrate method. To reduce the background, H2O2 was used to suppress the endogenous peroxidase activity. The samples were blocked in normal goat serum with 5% BSA in TBS for 1 h at room temperature. The sections were incubated with primary antibody (1:400 dilutions) overnight at 4 °C and then washed with PBS three times. After incubation with secondary antibodies (16 h), the sections were subjected to a DAB reaction. The sections were photographed using a digitalized microscope camera (Nikon, Tokyo, Japan).

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For analysis of cell migration, the Oris Assembly Kit (Platypus Technologies, Madison, WI, USA) was used. Cell seeding stoppers were inserted into the wells of a 96-well plate for creating a cell-free area. 5 × 104 MDA-MB-231, 7.5 × 104 MDA-MB-468, 7.5 × 104 MCF-7, 1 × 105 SKBR-3, 1 × 105 BT-474, or 1 × 105 MCF-10A were seeded in technical triplicate in their standard cell culture medium and incubated for 24 h at 37 °C and 5% CO2. After 24 h, the stoppers were removed carefully. The medium was removed, the cells were washed twice with PBS and medium was changed accordingly to the experimental groups (Table 1). Every 24 h, the medium was replaced according to the experimental groups, thus, including fresh LPA. Images in the central region were taken in 40-fold magnification at 0 h, 24 h, 48 h, and 72 h (Olympus IX83, cellSens Software, Olympus Corporation, Tokio, Japan). Migrated cells were semi-automatically measured using Fiji Is Just ImageJ (Fiji)22. For quantification, control at 24 h was set 1. The assay was performed three times for all cell lines.

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Borrelia burgdorferi, causative agent of Lyme disease, is a bacterial spirochete transmitted by Ixodes scapularis and Ixodes pacificus in North America . Dogs are incidental hosts for Bo. burgdorferi and not part of the transmission cycle . In North America, canine Lyme disease has been significantly associated with Bo. burgdorferi sensu stricto (ss) strains, whereas in Europe, most cases are associated with sensu lato (sl) species (Bo. garinii and Bo. afzelii) .

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Figure S1. Analysis of purity of primary cultured astrocytes or microglia. Primary glial cells were prepared, astrocytes and microglial cells were prepared and purified. (A1) Cells were stained with anti-CD11b-FITC antibody and detected with flow cytometry. The staining showed that < 0.1% of the cultured cells were microglia; (A2) Immunofluorescent staining revealed astrocytes stained with GFAP (green). Nuclei were stained with DAPI (blue). The GFAP staining showed that > 98% of the cultured cells were astrocytes. For microglial cells separated from the mix culture, both flow cytometry analysis and immunofluorescent staining showed that > 99% of the cultured cells were microglia in (B1-B2). Scale bar = 50 μm. Figure S2. MTT assay for cell viability of astrocytes undergone OGD/R injury. Primary astrocytes were prepared from newborn mice and subjected to OGD/R injury. (A) MTT assay to measure cell viability in astrocytes after treatment with SalB at 5 to 100 μg/mL concentrations. Con: control; (B) MTT assay to measure cell viability in astrocytes after treatment with CBX at 10 to 5000 μM concentrations. Con: control; (C) MTT assay to measure cell viability in astrocytes after treatment with CBX at 10 μM, SalB at 20 μg/mL, Gap19 at 100 μM, Gap26 at 100 μM; Also, Gap19, Gap26 or CBX pretreatment followed by SalB incubation and SalB pretreatment for 30 min followed by Gap19, Gap26 or CBX incubation with the above indicated concentrations; All error bars:±SEM. We evaluated the statistical significance with ANOVA and Duncan’s multiple comparisons test. *p < 0.05, **p < 0.01, and ***p < 0.001. Figure S3. Standard curve for ATP detection. ATP levels in conditioned medium were determined. The fluorescence levels from five serial ATP dilutions—0, 10, 30, 60, 100, 300, and 1000 nM are shown. Figure S4 (A-B) Western blotting were performed to evaluate the M2 marker arginase-1. Arginase-1 protein expression was decreased in the OGD/R group’s activated microglia, but SalB reversed this effect; (C-D) Arginase-1 expression was decreased in OGD/R-ACM-treated microglia while increased in microglia treated with OGD/R-SalB-ACM or OGD/R-CBX-ACM. We evaluated the statistical significance with ANOVA and Duncan’s multiple comparisons test. *p < 0.05, **p < 0.01, and ***p < 0.001. (PPTX 11400 kb)

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ZBED6 (zinc finger, BED-type containing 6) is a transcriptional modulator that is unique to placental mammals and has evolved from a DNA transposon that integrated in an ancestor of mammals more than 200 million years ago . The fact that the DNA-binding domain of ZBED6 was found to show 100% sequence identity among 25 placental mammals implies that it serves an essential function. ZBED6 acts as a repressor of Igf2 expression in multiple tissues through the binding of the GCTCG motif located in an intron of Igf2 [1, 2]. The ZBED6-mediated lowering of Igf2 expression results not only in decreased muscle mass, but also affects the size of organs such as the liver, kidney and heart . ZBED6 is also expressed in insulin-producing beta cells, where it has been shown to modulate reactive oxygen species (ROS) production, insulin production, proliferation and cell death . In vitro, ZBED6 seems to maintain the capacity of beta cells to proliferate at the expense of specialised function, negatively affecting cell-to-cell interactions , stimulus-secretion coupling involving cAMP and Ca2+ signalling events, and neuronal/beta cell differentiation pathways . Thus, it is possible that ZBED6 controls the balance between proliferation and function/differentiation of beta cells, thereby preventing either process from unwanted domination. Indeed, in early stages of the pathogenesis of type 2 diabetes, beta cells are often hyperactivated in response to hyperglycaemia, hyperlipidaemia or inflammatory signals , leading to hyperinsulinaemia . Later, as peripheral insulin resistance develops and the insulin requirement augments further, the beta cell mass fails to adapt by proliferation , and instead de- or transdifferentiate , or even undergo apoptosis , leading to a worsened glucose homeostasis. This may suggest that initial activation traps the beta cells in a non-proliferative state, which does not allow expansion of the beta cell mass under conditions of continued and intensified stimulation, subsequently causing beta cell damage . Therefore, ZBED6 may be a factor that modulates the balance between proliferation and function. Consequently, in this study we aimed to evaluate the effects of the transcriptional modulator ZBED6 on beta cell proliferation and function in vivo and in vitro.

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In this study, we improved the sensitivity of the AAO chip by pore-area control and reduced the manufacturing time of the device compared with a previous report using hard anodization (HA). The anodizing time was reduced to by approximately 10-fold to form an aluminum oxide layer of the same thickness, provided higher AAO chip production efficiency, and reduced the unit cost of the AAO chip . We optimized the pore-area of AAO chip by controlling the fabrication parameters (applied voltage, electrolyte, anodizing time) to enhance the sensitivity of the optical biosensor. The measured limit of detection for the serum amyloid A1 (SAA1) antigen was 11.8 ag/mL. SAA1 is a member of a family of proteins synthesized in a multigene complex and is a well-known acute-phase reactant. Additionally, SAA1 is considered the most sensitive protein indicating inflammatory activity and is a lung and gastric cancer biomarker that is difficult to detect using previously-described measurement techniques and, thus, secondary data analysis is typically required.

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In the second scenario, participants only passed by the observation area to check whether the system would correctly recognize that none of the detected pedestrians intends to cross the street and, therefore, should not trigger any change in traffic signalization. Again, in this scenario, only one participant was simultaneously present in the observation area at a time. If a green signal was given despite none of the participants stopping to cross the street, it would only disrupt traffic flow in a real-life scenario, which we counted as incorrect system response.

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Differences existed in the mean scores of miners with different levels of education as follows. Miners with only a junior school education had scores that were significantly lower on E-I, M-I, S-I, and W-I than that with other miners (E-I: junior college (p = 0.004); M-I: high school (p = 0.000); junior college (p = 0.005), senior technical (p = 0.035); S-I: junior college (p = 0.049); undergraduate (p = 0.015); postgraduate (p = 0.000); and W-I: junior college (p = 0.012); postgraduate (p = 0.012). Additionally, for E-I, there was a significant difference between the mean scores of miners with a junior college and postgraduate education (p = 0.001); the latter was lower than the mean score. For S-I, the miners with a primary school education had significantly lower mean scores than miners with postgraduate education (p = 0.024).

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The first group works according to the physiological principles of Moens and Korteweg , Young’s modulus of elasticity , and the Bramwell–Hill model ; the common link is the PWV, which depends on the blood pressure and blood volume flow, as well as the elasticity of the examined vessel and the viscosity of the blood.

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Baseline clinical data on demographic characteristics, cardiovascular risk factors, cardiac symptoms and previous non-invasive exams were recorded. Follow-up was performed by reviewing medical records and telephone interviews with patients and referring physicians as needed. Additionally, vital status data was also collected from medical national platform records and/or civil registries. The primary combined endpoint was the first major adverse cardiac event (MACE), defined as cardiac death, non-fatal myocardial infarction (MI) or urgent/non-urgent revascularization of the anomalous vessel (either percutaneous coronary intervention—PCI—or coronary artery bypass grafting—CABG). Cardiac death was defined as either sudden death with probable cardiac origin or death caused by acute MI, ventricular arrhythmias or refractory heart failure. Non-fatal MI was defined based on symptoms, EKG and biomarkers of ischemia.

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Cross-talk between GAs and auxins has proven to play an important role during fruit set in tomato via the activation of GA biosynthtetic enzyme GA20 oxydase by auxin (de Jong et al., 2009) two transcripts coding for GA20ox are over-expressed in compact clones (Figure 6). In grapevine crosstalk beween these two hormones is also critical in flower set initiation and parthenocarpy (Jung et al., 2014; Lu et al., 2016).

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Five months after sevoflurane exposure, spatial and related forms of learning and memory were assessed by MWM, as previously described (Zhang et al., 2016). Briefly, a 10-cm diameter platform was placed 1 cm above the water surface in a circular tank (diameter, 150 cm; depth, 50 cm). A flag was placed on the platform to increase its visibility. Rat was gently released in the water and emerged from the water onto the platform within 120 s. If the rat failed to find the platform, place the rat on the raised platform and allow it to stay there for 20 s before being removed from the pool. A different platform location was used for each subsequent trial. This cueing procedure enables the rats to acknowledge that they can escape the water by finding a platform.

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Additionally, higher PaCO2 was an important factor for mortality. A previous retrospective study of patients with IPF in a single center yielded similar results . The present prospective study corroborated these findings among heterogenous patients waiting for transplantation, not limited to IPF. In the future, we wish to investigate the potential usefulness of PaCO2 as a new biomarker for risk stratification.

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The information content within MFC data revealed in a quantitative model strongly depends on the specific choices made in collecting the data and in data processing that precedes modelling. The analysed sample may consist of a relatively homogeneous cell population or can interrogate a much broader mixture of cells, such as the whole blood and bone marrow analysed in the asthma and AML studies presented here, respectively. The results on the FLOWCAP 2 data show how the quantitative potential of DAMACY is on par with the most advanced methods benchmarked in this challenge. The discriminatory Top model may extract the response-related information on cell variability in marker expression from the Base model histograms, both for a priori gated homogeneous neutrophil populations (LPS) and in peripheral blood (asthma). DAMACY shows to be also very informative for other sample types, like bone marrow samples from the AML study.

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We observed an association between tobacco cigarette use before pregnancy and during pregnancy with age, which was consistent with previous studies (Schneider and Schütz 2008). However, regarding dual use, a different picture emerged, as dual use before pregnancy was not significantly associated with age. Nevertheless, we could identify tendencies that showed that younger women were more commonly dual users before pregnancy. This finding supports a previous study by Ashford et al. (2017), who identified a younger age as a predictor of e-cigarette use in a U.S. collective of women of childbearing age. In addition, educational level was an important predictor of dual use before pregnancy and tobacco cigarette use before and during pregnancy. While research on the predictors of dual use before or during pregnancy is scarce, our results are in line with previous studies on tobacco cigarette use (Graham et al. 2010; Kharkova et al. 2016). Moreover, we identified that having a smoking partner (exclusively or dual) was associated with smoking before and during pregnancy, which was consistent with previous studies (Murin et al. 2011).

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To date, the underlying mechanism of CDWs in cuprates still remains elusive. Unveiling the nature of the quasistatic CDWs as well as their dynamical excitations is crucial for understanding the CDW’s origin––similar to the study of AFM in cuprates. Although the quasistatic properties of CDWs have been investigated extensively, their dynamics (i.e., the collective CDW excitations) are largely unexplored due to the limited availability of suitable experimental tools. RIXS is one of the few techniques that directly probe quasistatic CDWs, their excitations, and electron-phonon coupling, which are important elements for identifying the CDW mechanism.

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