bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human primary visual cortex shows larger population receptive fields for binocular disparity-defined stimuli
Authors: Alvarez Ivan , Hurley Samuel A. , Parker Andrew J. , Bridge Holly 
Published: March 2021

1AbstractThe visual perception of 3D depth is underpinned by the brain’s ability to combine signals from the left and right eyes to produce a neural representation of binocular disparity for perception and behavior. Electrophysiological studies of binocular disparity over the past two decades have investigated the computational role of neurons in area V1 for binocular combination, while more recent neuroimaging investigations have focused on identifying specific roles for different extrastriate visual areas in depth perception. Here we investigate the population receptive field properties of neural responses to binocular information in striate and extrastriate cortical visual areas using ultra-high field fMRI. We measured BOLD fMRI responses while participants viewed retinotopic-mapping stimuli defined by different visual properties: contrast, luminance, motion, correlated and anti-correlated stereoscopic disparity. By fitting each condition with a population receptive field model, we compared quantitatively the size of the population receptive field for disparity-specific stimulation. We found larger population receptive fields for disparity compared with contrast and luminance in area V1, the first stage of binocular combination, which likely reflects the binocular integration zone, an interpretation supported by modelling of the binocular energy model. A similar pattern was found in region LOC, where it may reflect the role of disparity as a cue for 3D shape. These findings provide insight into the binocular receptive field properties underlying processing for human stereoscopic vision.
Winter rye cover cropping changes squash (Cucurbita pepo) phyllosphere microbiota and reduces Pseudomonas syringae symptoms
Authors: Maglione Rémi , Ciotola Marie , Cadieux Mélanie , Toussaint Vicky , Laforest Martin , Kembel Steven W. 
Published: March 2021

AbstractCover cropping is a soil conservation practice that may reduce the impacts of the economically important pathogen Pseudomonas syringae on crops including squash (Cucurbita pepo). To date, no studies have directly quantified the effect of rye cover crops on P. syringae populations, nor on the bacterial community of squash leaves. In this work, we tested the hypothesis that the protective effects of cover cropping on squash may be mediated by cover cropping effects on the plant’s microbiota that in turn protects against P. syringae. Using combined 16S sequencing and culture-based approaches, we showed that rye cover cropping protects squash against P. syringae, by decreasing pathogen population size on squash leaves and increasing fruit health and marketability at harvest. We also found evidence of a strong effect of rye cover crops on bacterial communities of the squash phyllosphere. Those findings were more striking early in the growing season. Finally, we identified numerous phyllosphere bacteria belonging to the genera Sphingomonas, Methylobacterium and Pseudomonas that were promoted by rye cover crops. Overall, our findings suggest cover cropping is effective for the sustainable management of P. syringae on squash and may provide a reservoir of potential microbial biocontrol agents colonizing the phyllosphere.
Single-trial-based Temporal Principal Component Analysis on Extracting Event-related Potentials of Interest for an Individual Subject
Authors: Zhang Guanghui , Li Xueyan , Lu Yingzhi , Tiihonen Timo , Chang Zheng , Cong Fengyu 
Published: March 2021

AbstractTemporal principal component analysis (t-PCA) has been widely used to extract event-related potentials (ERPs) at the group level of multiple subjects’ ERP data. The t-PCA is, however, poorly employed to isolate ERPs from single-trial data of an individual subject. Additionally, the effects of varied trial numbers on the yields of t-PCA have not been systematically examined. To fill both gaps, in an emotional experiment (22 subjects), we use t-PCA and Promax rotation to extract interesting P2/N2 from single-trial data of each subject with consecutive increasingly trial numbers (from 10 to 42) and all trials, respectively. Besides, time-domain analysis and other two group t-PCA strategies (trial-averaged and single-trial) are also employed to isolate ERPs of interest from all subjects. The results indicate that the proposed technique produces the internal consistent measure of N2 from few trials (i.e., 19) as from all trials compared with the other three approaches (more than 30 trials). As for P2, all approaches yield internal-subject consistent effect after approximately 33 trials are included in the average, but Cronbach’s alpha values for the proposed technique are higher than the other two group PCA strategies over varied trials. Combined, the yields provide evidence that the proposed approach may efficiently temporally filter the data to extract more reliable and stable ERPs for an individual subject.
Release, rescue and recycling: termination of translation in mammalian mitochondria
Authors: Kummer Eva , Schubert Katharina Noel , Schönhut Tanja , Scaiola Alain , Ban Nenad 
Published: March 2021

SummaryThe mitochondrial translation system originates from a bacterial ancestor but has substantially diverged in the course of evolution. Here, we use single particle cryo-EM as a screening tool to identify mitochondrial translation termination mechanisms and to describe them in molecular detail. We show how mitochondria release factor 1a releases the nascent chain from the ribosome when it encounters the canonical stop codons UAA and UAG. Furthermore, we define how the peptidyl-tRNA hydrolase ICT1 acts as a rescue factor on mitoribosomes that have stalled on truncated messages to recover them for protein synthesis. Finally, we present near-atomic models detailing the process of mitochondrial ribosome recycling, to explain how a dedicated elongation factor, mtEFG2, has specialized for cooperation with the mitochondrial ribosome recycling factor to dissociate the mitoribosomal subunits at the end of the translation process. (134 words)
Natural spring water gargle and direct RT-PCR for the diagnosis of COVID-19 (COVID-SPRING study)
Authors: Dumaresq Jeannot , Coutlée François , Dufresne Philippe J. , Longtin Jean , Fafard Judith , Bestman-Smith Julie , Bergevin Marco , Vallières Emilie , Desforges Marc , Labbé Annie-Claude 
Published: March 2021

AbstractWe prospectively compared natural spring water gargle to combined oro-nasopharyngeal swab (ONPS) for the diagnosis of coronavirus disease 2019 (COVID-19) in paired clinical specimens (1005 ONPS and 1005 gargles) collected from 987 unique early symptomatic as well as asymptomatic individuals from the community. Using a direct RT-PCR method with the Allplex™ 2019-nCoV Assay (Seegene), the clinical sensitivity of the gargle was 95.3% (95% confidence interval [CI], 90.2 to 98.3%) and was similar to the sensitivity of the ONPS (93.8%; 95% CI, 88.2 to 97.3%), despite significantly lower viral RNA concentration in gargles, as reflected by higher cycle threshold values. No single specimen type detected all COVID-19 cases. SARS-CoV-2 RNA was stable in gargles at room temperature for at least 7 days. The simplicity of this sampling method coupled with the accessibility of spring water are clear advantages in a pandemic situation where testing frequency, turnaround time and shortage of consumables and trained staff are critical elements.
A survey of current anticoagulation patient education practices and development
Authors: Jones Aubrey E. , Saunders John , Vazquez Sara , Fagerlin Angela , Witt Daniel M. 
Published: March 2021

AbstractIntroductionAnticoagulants are high-risk medications widely used to prevent and treat thrombotic events, resulting in a need for adequate patient education to minimize harm. While anticoagulant patient education interventions can improve knowledge and surrogate outcomes, they may not represent current practice. Our objective was to determine provider perceptions of anticoagulation patient education at their institution.MethodsA quantitative survey was distributed through a national professional organization and across several health systems. Questions included educational delivery methods, perceived effectiveness, evaluation of patient knowledge, development of patient education, and demographics.ResultsThe 61 survey respondents were 79.0% female, 86.2% white, and an average age of 43. Most respondents (95%) complete patient education interventions in one session. Providers reviewed educational topics in 37% of daily patient interactions. 59% of respondents reported reasons for not performing patient knowledge checks included no formal process requiring knowledge checks, lack of time, and forgetting. The majority (93.4%) reported their patient education process was somewhat or very effective. The main reason underlying perceived less effective patient education was too much information in one session. Thirty-four respondents had some knowledge of patient education development at their institution. Most of these (82.9%) indicated their educational process’s development relied on expert opinion. In comparison, 22.9% indicated utilizing user-based design, and 10 (28.9%) respondents used learning theories.ConclusionWhile most providers felt patient education was effective, they reported reviewing education with patients daily. The lack of formal knowledge checks and best practices in developing patient education tools are significant gaps to address.
Reducing the Cost of Rapid Antigen Tests through Swab Pooling and Extraction in a Device
Authors: Berking Tim , Lorenz Sabrina G. , Ulrich Alexander , Greiner Joachim , Richert Clemens 
Published: March 2021

AbstractThe COVID-19 pandemic places a significant stress on the viral testing capabilities of many countries. The value of rapid point-of-care (PoC) antigen tests is becoming increasingly clear, but implementing frequent large scale testing is costly. We have developed an inexpensive device for pooling swabs, extracting specimens, and detecting viral antigens with a commercial lateral flow assay detecting the nucleocapsid protein of SARS-CoV-2 as antigen. The holder of the device can be produced locally through 3D printing. The extraction and the elution can be performed with the entire set-up encapsulated in a transparent bag, minimizing the risk of infection for the operator. With 6 swabs holding approx. 0.1 mL specimen each and 0.35 mL extraction buffer, 43±6 % (n= 8) of the signal for an individual extraction of a positive control standard was obtained. Image analysis still showed a signal-to-noise ratio of ≥ 7 upon further eight-fold dilution. Our current total cost of materials is below $ 2 per tested person or 20% of our cost for an individual PoC test. These findings suggest that pooling can make frequent testing more affordable for schools, universities and other institutions, without decreasing sensitivity to an unacceptable level. Further validation of the method is required.
Magnesium Treatment on Methylation Changes of Transmembrane Serine Protease 2 (TMPRSS2)
Authors: Fan Lei , Zhu Xiangzhu , Zheng Yinan , Zhang Wei , Seidner Douglas L , Ness Reid , Murff Harvey J , Yu Chang , Huang Xiang , Shrubsole Martha J , Hou Lifang , Dai Qi 
Published: March 2021

AbstractBackgroundThe viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike (S) protein priming.ObjectivesTo test the hypothesis that Mg treatment leads to DNA methylation changes in TMPRSS2.MethodsThis study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2×2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized.ResultsWe found that 12-week of personalized Mg treatment significantly increased 5-mC methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to placebo arm (decreased by 0.1%) in those aged < 65 years old. The difference remained statistically significant after adjusting for age, sex and baseline methylation as well as FDR correction (FDR-adjusted P =0.014). Additionally, Mg treatment significantly reduced 5-hmC level at cg26337277 (close proximity to TSS200 and 5’UTR, promoter) by 2.3% compared to increases by 7.1% in the placebo arm after adjusting for covariates in those aged < 65 years old (P=0.003). The effect remained significant at FDR of 0.10 (adjusted P value=0.088).ConclusionAmong individuals aged younger than 65 years with the Ca:Mg intake ratios equal to or over 2.6, reducing Ca:Mg ratios to around 2.3 increased 5-mC modifications (i.e. cg16371860) and reduced 5-hmC modifications (i.e. cg26337277) in the TMPRSS2 gene. These findings, if confirmed, provide another mechanism for the role of Mg intervention for the prevention of COVID-19 and treatment of early and mild disease by modifying the phenotype of the TMPRSS2 genotype.
Immunodominant B cell epitope in a hotspot mutation site and mechanism of immune escape for SARS-CoV-2
Authors: Oliveira Jamille Ramos , Machado Rafael Rahal G. , Arcuri Helen Andrade , Magawa Jhosiene Yukari , Daher Isabela Pazotti , Urbanski Alysson Henrique , Händel Schmitz Gabriela Justamante , Silva Roberto Carlos Vieira , Durigon Edison Luiz , Boscardin Silvia Beatriz , Rosa Daniela Santoro , Schechtman Deborah , Nakaya Helder I , Cunha-Neto Edecio , Gadermaier Gabriele , Coelho Verônica , Santos Keity Souza , Kalil Jorge 
Published: March 2021

AbstractRecent SARS-CoV-2 variants pose important concerns due to their higher transmissibility (1) and escape (2) from previous infections or vaccine-induced neutralizing antibodies (nAb). The receptor binding domain (RBD) of the Spike protein is a major nAb target (3), but data on its B cell epitopes are still lacking. Using a peptide microarray, we identified an immunodominant epitope (S415-429) recognized by 68% of sera from 71 convalescent Brazilians infected with the ancestral variant. In contrast with previous studies, we have identified a linear IgG and IgA antibody binding epitope within the RBD. IgG and IgA antibody levels for this epitope positively correlated with nAb titers, suggesting a potential target of antibody neutralizing activity. Interestingly, this immunodominant RBD region harbors the mutation hotspot site K417 present in P.1 (K417T) and B.1.351 (K417N) variants. In silico simulation analyses indicate impaired RBD binding to nAb in both variants and that a glycosylation in the B.1.351 417N could further hinder antibody binding as compared to the K417T mutation in P.1. This is in line with published data showing that nAb from either convalescents or anti-CoV-2 vaccinees are less effective towards B.1.351 than for P.1. Our data support the occurrence of immune pressure and selection involving this immunodominant epitope that may have critically contributed to the recent COVID-19 marked rise in Brazil and South Africa, and pinpoint a potential additional immune escape mechanism for SARS-CoV-2.
The Use/Abuse of Oral Contraceptive Pills Among Males: A Mixed-Method Explanatory Sequential Study Over Jordanian Community Pharmacists
Authors: Barakat Muna M. , Al-Qudah Raja’a A. , Akour Amal , Abu-Asal Mona , Thiab Samar , Dallal Bashi Yahya H. 
Published: March 2021

AbstractBackgroundOral contraceptive pills (OCPs) are considered one of the most important birth control methods in the world. However, these pills were designed for female administration rather than males. This study was designed to investigate patterns of OCPs use and abuse among Jordanian males, according to the community pharmacists’ observations.MethodA mixed-method explanatory sequential study was conducted using an online self - administered survey and semi-structured in-depth interviews for community pharmacists. The interviews were utilized using a conceptual framework. Inductive thematic analysis and descriptive/regression analyses were completed using Nvivo and SPSS, respectively.ResultsA total of 158 questionnaire responses and 22 interviews were included in our analysis. Around half (48.4%) of the questionnaire responses confirmed that males could use OCPs for hair growth enhancement, muscle gain and acne treatment 12.7%, 31.7% and 4.4%, respectively. Through the interviews, the majority of the pharmacists highlighted that most of the males use OCPs for bodybuilding purposes, according to recommendations by their coaches at the gym. The most abused OCPs containing estrogen (Ethinyl estradiol) and progestins (Drospirenone or Levonorgestrel).ConclusionThis study provided insight into unexpected uses of OCPs by males in Jordan. Community pharmacists have a crucial role in the management of OCPs use and abuse, However, restricted regulations and monitoring must be released and implemented on the community to limit such practices.
Population Impact and Efficiency of Improvements to HIV PrEP Under Conditions of High ART Coverage among San Francisco Men Who Have Sex with Men
Authors: Le Guillou Adrien , Buchbinder Susan , Scott Hyman , Liu Albert , Havlir Diane , Scheer Susan , Jenness Samuel M. 
Published: March 2021

ABSTRACTBackgroundKey components of Ending the HIV Epidemic (EHE) plan include increasing HIV antiretroviral therapy (ART) and HIV preexposure prophylaxis (PrEP) coverage. One complication to addressing this service delivery challenge is the wide heterogeneity of HIV burden and healthcare access across the U.S. It is unclear how the effectiveness and efficiency of expanded PrEP will depend on different baseline ART coverage.MethodsWe used a network-based model of HIV transmission for men who have sex with men (MSM) in San Francisco. Model scenarios increased varying levels of PrEP coverage relative under current empirical levels of baseline ART coverage and two counterfactual levels. We assessed the effectiveness of PrEP with the cumulative percent of infections averted (PIA) over the next decade and efficiency with the number needed to treat (NNT) by PrEP required to avert one HIV infection.ResultsIn our projections, only the highest levels of combined PrEP and ART coverage achieved the EHE goals. Increasing PrEP coverage up to 75% showed that PrEP effectiveness was higher at higher baseline ART coverage with the PIA ranging from 61% in the lowest baseline ART coverage population to 75% in the highest ART coverage. The efficiency declined with increasing ART (NNT range from 41 to 113).ConclusionsImproving both PrEP and ART coverage would have a synergistic impact on HIV prevention even in a high baseline coverage city like San Francisco. Efforts should focus on narrowing the implementation gaps to achieve higher levels of PrEP retention and ART sustained viral suppression.
An international comparison of age and sex dependency of COVID-19 Deaths in 2020 - a descriptive analysis
Authors: Bauer Peter , Brugger Jonas , König Franz , Posch Martin 
Published: March 2021

SummaryCOVID-19 mortality, the number of reported COVID-19 deaths per 100,000 persons observed so far, is described in 15 European countries and the USA depending on age groups and sex for the full year 2020. It is contrasted to the corresponding historic all-cause mortality per year depending on age and sex observed in these countries. Although there are substantial differences in the age and sex dependency of COVID-19 mortality between countries, there are some common features: Exponential increase with age is a good model to describe and analyse both COVID-19 and all-cause mortality above an age of 40 years, where almost all COVID-19 death occur. Age dependency is stronger for COVID-19 mortality than for all-cause mortality, males have an excess risk compared to women which flattens off with increasing age. Also with regard to calendar time, there were differences in the age and sex dependency between countries with the common tendency that male excess risk of COVID-19 mortality was smaller in the second half of the year.
mTOR-activating mutations inRRAGDcause kidney tubulopathy and cardiomyopathy (KICA) syndrome
Authors: Schlingmann Karl P. , Jouret François , Shen Kuang , Nigam Anukrati , Arjona Francisco J. , Dafinger Claudia , Houillier Pascal , Jones Deborah P. , Kleinerüschkamp Felix , Oh Jun , Godefroid Nathalie , Eltan Mehmet , Güran Tülay , Burtey Stéphane , Parotte Marie-Christine , König Jens , Braun Alina , Bos Caro , Serra Maria Ibars , Rehmann Holger , Zwartkruis Fried J.T. , Renkema Kirsten Y. , Klingel Karin , Schulze-Bahr Eric , Schermer Bernhard , Bergmann Carsten , Altmüller Janine , Thiele Holger , Beck Bodo B. , Dahan Karin , Sabatini David , Liebau Max C. , Vargas-Poussou Rosa , Knoers Nine V.A.M. , Konrad Martin , Baaij Jeroen H.F. de 
Published: March 2021

ABSTRACTBackgroundOver the last decaces, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, ±20% of all tubulopathy patients remain without genetic diagnosis. Here, we explore a large multicentric patient cohort with a novel inherited salt-losing tubulopathy, hypomagnesemia and dilated cardiomyopathy (DCM).MethodsWhole exome and genome sequencings were performed with various subsequent functional analyses of identifiedRRAGDvariants in vitro.ResultsIn 8 children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt-wasting, and nephrocalcinosis, we identified heterozygous missense variants inRRAGDthat mostly occurredde novo. Six of these patients additionally suffered from DCM requiring heart transplantation in 3 of them. An additional dominant variant inRRAGDwas simultaneously identified in eight members of a large family with a similar renal phenotype.RRAGDencodes GTPase RagD mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron include the thick ascending limb and the distal convoluted tubule. The identifiedRRAGDvariants were shown to induce a constitutive activation of mTOR signalingin vitro,ConclusionsOur findings establish a novel disease phenotype combining kidney tubulopathy and cardiomyopathy (KICA) caused by an activation of mTOR signaling suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.SIGNIFICANCE STATEMENTHere, we report on heterozygous variants inRRAGDin patients with profound hypomagnesemia, renal salt wasting, nephrocalcinosis, and dilated cardiomyopathy. The identified RagD variants induce a constitutive activation of mTOR signalingin vitro. These findings not only establish a novel monogenic disorder of the kidney tubule, but demonstrate the essential role of mTOR signaling for distal tubular electrolyte handling and cardiac function.