bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines
Authors: Narasimhan Madhusudhanan , Mahimainathan Lenin , Clark Andrew E. , Usmani Amena , Cao Jing , Araj Ellen , Torres Fernando , Sarode Ravi , Kaza Vaidehi , Lacelle Chantale , Muthukumar Alagarraju 
Published: May 2021

AbstractThe immunological effectiveness of SARS-CoV-2 mRNA vaccines in lung transplant (LT) recipients is largely unknown. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines’ two-dose (2D) regimen on humoral responses in immunocompromised lung transplant (LT) recipients. About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited significantly lesser median IgGSP response (1.7 AU/mL, 95% CI: 0.6-7.5 AU/mL) compared to non-transplanted, uninfected naïve subjects (14209 AU/mL, 95% CI: 11261-18836 AU/mL) (p<0.0001). In LT patients, Moderna-evoked seropositivity trend was higher by 23-fold than Pfizer. 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation.
A recurrentSHANK3frameshift variant in Autism Spectrum Disorder
Authors: Loureiro Livia O , Howe Jennifer L , Reuter Miriam , Iaboni Alana , Calli Kristina , Roshandel Delnaz , Pritisanac Iva , Moses Alan , Forman-Kay Julie D. , Trost Brett , Zarrei Mehdi , Rennie Olivia , Lau Lynette , Marshall Christian R , Srivastava Siddharth , Godlewski Brianna , Buttermore Elizabeth , Sahin Mustafa , Hartley Dean , Frazier Thomas , Vorstman Jacob , Georgiades Stelios , Lewis Suzanne ME , Szatmari Peter , Bradley Lisa , Delorme Richard , Bourgeron Thomas , Anagnostou Evdokia , Scherer Stephen W. 
Published: May 2021

AbstractAutism Spectrum Disorder (ASD) is genetically complex, but specific copy number variants (CNVs; e.g., 1q21.1, 16p11.2) and genes (e.g.,NRXN1, NLGN4) have been identified as penetrant susceptibility factors, and all of these demonstrate pleiotropy. Many ASD-associated CNVs are, in fact, genomic disorder loci where flanking segmental duplications lead to recurrent deletion and duplication events of the same region in unrelated individuals, but these lesions are large and involve multiple genes. To identify opportunities to establish a more specific genotype and phenotype correlation in ASD, we searched genomic data, and the literature, for recurrent predicted damaging sequence-level variants affecting single genes. We identified 17 individuals from 15 unrelated families carrying a heterozygous guanine duplication (rs797044936; NM_033517.1; c.3679dup; p.Ala1227Glyfs*69) occurring within a string of 8 guanines (at genomic location [hg38]g.50,721,512dup) affectingSHANK3, a prototypical ASD gene (6/7,521 or 0.08% of ASD-affected individuals studied by whole genome sequencing carried the p.Ala1227Glyfs*69 variant). This variant, which is predicted to cause a frameshift leading to a premature stop codon truncating the C-terminal region of the corresponding protein, was not reproducibly found in any of the control groups we analyzed. All probands identified carriedde novomutations with the exception of five individuals in three families who inherited it through somatic mosaicism. This same heterozygous variant in published mouse models leads to an ASD-like phenotype. We scrutinized the phenotype of p.Ala1227Glyfs*69 carriers, and while everyone (16/16) formally tested for ASD carried a diagnosis, there was variable expression of core ASD features both within families and between families, underscoring the impact of as yet unknown modifiable factors affecting expressivity in autism.
Cesarean section prevalence at a baby-friendly hospital in southern Brazil: current context in the face of COVID-19
Authors: de Azevedo Bicho Manoela , Fernandes Mayra Pacheco , Vidaletti Luís Paulo , Santos Vaz Juliana dos 
Published: May 2021

AbstractObjectiveTo analyze cesarean prevalence at a baby-friendly hospital in Southern Brazil between 2017 and 2020 and possible annual and monthly changes due to the novel coronavirus (COVID-19) pandemic.MethodsDescriptive cross-sectional study using secondary data retrieved from the electronic information system of a Baby-Friendly Hospital in the municipality of Rio Grande, RS, Brazil. Data was retrieved for all hospitalizations at the obstetric center between January 1st 2017 and December 31st 2020. Data on COVID-19 deaths were obtained from the municipal government website. Annual and monthly cesarean prevalence rates were calculated in comparison to the same periods in 2017, 2018 and 2019. Differences in prevalence rates were tested using a chi-square test, taking a significance level of less than 5%. Prevalence ratios were estimated for 2018/2017, 2019/2018, and 2020/2019.Results7,294 childbirths were included. Cesarean prevalence was 42.6% in 2017, 44.3% in 2018, 40.2% in 2019, and 51.0% in 2020. In 2018/2017, there was no statistically significant difference in cesarean prevalence (95%CI: 0.90-1.20). Between 2019/2018, there was a reduction of approximately 20% in prevalence (95%CI: 0.69-0.93). The scenario changes between 2020/2019 with a 40% increase in cesareans (95%CI: 1.20-1.62). The period comprising July to December 2020 was the only period in which over half the deliveries were done by cesarean section, exceeding 60% in July.ConclusionCesarean prevalence rates increased in 2020 in relation to the three preceding years. The data highlight the need to reinforce compliance with childbirth protocols to reduce cesarean sections in baby-friendly hospitals.
Monotreme middle ear is not primitive for Mammalia
Authors: Meng Jin , Mao Fangyuan 
Published: May 2021

AbstractThe study on evolution of the mammalian middle ear has been fueled by continuous discoveries of Mesozoic fossils in the last two decades. Wang et al.1recently reported a specimen ofVilevolodon diplomylos(IMMNH-PV01699)2that adds to the increasing knowledge about the auditory apparatus of ‘haramiyidans’, an extinct Mesozoic group of mammaliaforms. The authors hypothesized that a middle ear with a monotreme-like incus and malleus and incudomallear articulation was primitive for mammals, which challenges the convention that the monotreme middle ear is specialized3or autapomorphic4in mammals. We raise concerns about terminology and identification of the incus presented by Wang et al. and show that their analysis does not support their hypothesis; instead, it supports the one by Mao et al.5,6.
COVID-19 VACCINE PERCEPTIONS AND DIFFERENCES BY SEX, AGE, AND EDUCATION: FINDINGS FROM A CROSS-SECTIONAL ASSESSMENT OF 1367 COMMUNITY ADULTS IN ONTARIO
Authors: Syan Sabrina K. , Gohari Mahmood , Levitt Emily E. , Belisario Kyla , Gillard Jessica , DeJesus Jane , MacKillop James 
Published: May 2021

ABSTRACTBackgroundCOVID-19 is a global pandemic and vaccination efforts may be impeded by vaccine hesitancy. The present study examined willingness to receive COVID-19 vaccine, the associated reasons for willingness/unwillingness, and vaccine safety perceptions in a cross-sectional assessment of community adults in Ontario.Methods1367 individuals (60.3% female, M age = 38.6) completed an online assessment between January 15, 2021 and February 15, 2021. Perceptions were investigated in general and by age, sex and education.ResultsOverall, 82.8% sample reported they were willing to receive a COVID-19 vaccine and 17.2% reported they were unwilling. The three most common reasons for unwillingness were long-term side effects (65.5%), immediate side effects (60.5%), and lack of trust in the vaccine (55.2%). Vaccine willingness significantly differed by sex and education level, with female participants and those with less than a bachelor’s degree being more likely to report unwillingness. Perception of COVID-19 vaccine safety was significantly lower (−10.7%) than vaccines in general and differed by age, sex and education, with females, older adults, and individuals with less than a bachelor’s degree reporting lower perceived COVID-19 vaccine safety.ConclusionIn this sample of community adults, under one in five individuals was unwilling to receive a COVID-19 vaccine, but with higher rates in population subgroups. Targeting public health messaging to females and individuals with less than Bachelor’s degree, and addressing concerns about long-term and immediate side effects may increase vaccine uptake.
Distinct patterns of blood cytokines beyond a cytokine storm predict mortality in COVID-19
Authors: Herr Christian , Mang Sebastian , Mozafari Bahareh , Günther Katharina , Speer Thimoteus , Seibert Martina , Srikakulam Sanjay Kumar , Beisswenger Christoph , Ritzmann Felix , Keller Andreas , Müller Rolf , Smola Sigrun , Eisinger Dominic , Zemlin Michael , Danziger Guy , Volk Thomas , Hörsch Sabrina , Krawczyk Marcin , Lammert Frank , Adams Thomas , Wagenpfeil Gudrun , Kindermann Michael , Marcu Constantin , Ataya Zuhair Wolf Dietrich , Mittag Marc , Schwarzkopf Konrad , Custodis Florian , Grandt Daniel , Schäfer Harald , Eltges Kai , Lepper Philipp M. , Bals Robert ,   CORSAAR study group
Published: May 2021

AbstractBackgroundCOVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements.Patients and methodsPatients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed.FindingsThe biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers.InterpretationSeveral newly identified blood markers were increased in patients with severe COVID-19 (AAT, EN-RAGE, ICAM-1, myoglobin, SAP, TIMP-1, vWF, decorin, HGF, MMP7, PECAM-1) or in patients that died (FRTN, SCF, TIMP-1, CA-9, CEA, decorin, HGF). The use of established assay technologies allows for rapid translation into clinical practice.FundingNo role of the funding source.
Early pre-exposure prophylaxis (PrEP) discontinuation among pregnant and postpartum women: Implications for maternal PrEP roll out in South Africa
Authors: Joseph Davey Dvora Leah , Mvududu Rufaro , Mashele Nyiko , Lesosky Maia , Khadka Nehaa , More Jessica , Bekker Linda-Gail , Gorbach Pamina , Coates Thomas J. , Myer Landon 
Published: May 2021

AbstractIntroductionOral pre-exposure prophylaxis (PrEP) is a safe and effective prevention strategy to reduce women’s risk of HIV in pregnancy and postpartum. Effective PrEP requires daily PrEP adherence, but little is known about maternal PrEP continuation and risk factors that influence optimal PrEP use.MethodsThe PrEP in pregnancy and postpartum (PrEP-PP) study is an ongoing cohort study that enrolled consenting pregnant, HIV-uninfected women at first antenatal care (ANC) visit, followed through 12-months postpartum. HIV-uninfected women and girls ≥16-years who were eligible for the study received HIV prevention counseling and were offered PrEP. Interviewers collected socio-demographic, behavioral data from participants at each visit. We analyzed the proportion of women who initiated PrEP and the proportion who continued on PrEP after 3-months with associated correlates, including side effects whilst on PrEP, by estimating the prevalence ratio (95% CI) adjusting for a priori confounders.ResultsBetween Aug’19 and Feb’21, we enrolled 891 pregnant women (median gestation=21wks; age=26yrs). Following PrEP counseling, 90% of women initiated PrEP at their first ANC visit (n=801); 60% were married or cohabiting. Three-quarters of women on PrEP returned for a repeat prescription at 1-month; 62% returned at 3-months. One-third of women on PrEP reported a side effect, mostly nausea/vomiting, dizziness, and headache. Women on PrEP in the 1st or 2nd trimester had higher odds of reporting side effects (aOR=2.61; 95%CI=1.17-5.84) vs. postpartum women. Women who reported side effects continued with PrEP less than those who did not report side effects (aPR=0.88; 95% CI=0.78-0.99) adjusting for covariates. Women who had ≥1 previous pregnancy (aPR=0.76;95%CI=0.59-1.00) or were postpartum (aPR=0.86;95%CI=0.75-0.99) continued less than women who were primigravid or pregnant. Women who reported having an HIV+ partner (aPR= 1.70;95% CI=1.55-1.86) or unknown partner serostatus (aPR=1.14;95%CI=1.01-1.29) were more likely to continue on PrEP than those who had HIV-negative partners.ConclusionPrEP initiation and early continuation were high in ANC in this setting. Being postpartum and experiencing side effects were associated with lower PrEP continuation, presenting an opportunity for improved clinical management and counseling during pregnancy of nausea/vomiting to address early, transient side effects. Interventions for postpartum women on PrEP are urgently needed.Clinical Trial NumberNCT03826199
DUX4 induces a homogeneous sequence of molecular changes, culminating in the activation of a stem-cell-like transcriptional network and induction of apoptosis in somatic cells
Authors: Ashoti Ator , Alemany Anna , Sage Fanny , Geijsen Niels 
Published: May 2021

AbstractFacioscapulohumeral muscular dystrophy (FSHD) is a muscle degenerative disease that disproportionally affects the muscles of the face, shoulder girdle and upper arms. FSHD is caused by the misexpression of Double Homeobox 4 (DUX4), a transcription factor that is normally expressed during early embryonic development. Ectopic expression of DUX4 in somatic cells is cytotoxic and leads to rapid apoptosis. To elucidate the mechanism by which DUX4 induces apoptosis, we determined the temporal transcriptional changes induced by Dux4 at the single-cell level. We observed that induction of DUX4 expression induces a non-random, consecutive sequence of transcriptional changes. DUX4 homogenously induces the activation of a stem cell signature and activates a network of transcription factors that is typically expressed during early embryogenesis and in pluripotent stem cells. Ultimately, these transcriptional changes trigger the induction of apoptosis, suggesting that the induction of this early stemness program is incompatible with a somatic cell program. Our findings shed new light on the timing and dynamic of DUX4-mediated transcriptional reprogramming and may help elucidate why the DUX4 stemness program is required during early embryogenesis, but incompatible with somatic cell viability.
An interpretable connectivity-based decoding model for classification of chronic marijuana use
Authors: Kulkarni Kaustubh R. , Schafer Matthew , Berner Laura , Fiore Vincenzo G. , Heflin Matt , Hutchison Kent , Calhoun Vince , Filbey Francesca , Pandey Gaurav , Schiller Daniela , Gu Xiaosi 
Published: May 2021

ABSTRACTBackgroundPsychiatric neuroimaging typically proceeds with one of two approaches: encoding models, which aim to model neural mechanisms, or decoding models, which aim to predict behavioral or clinical characteristics from brain imaging data. In this study, we seek to combine these aims by developing interpretable decoding models that offer both accurate prediction and novel neural insights. We demonstrate the effectiveness of this combined approach in a case study of chronic marijuana use.MethodsChronic marijuana (MJ) users (n=195) and non-using healthy controls (n=128) completed a cue-elicited craving task during functional magnetic resonance imaging. Linear machine learning methods were used to classify individuals into chronic MJ users and non-users based on task-evoked, whole-brain functional connectivity. We then used graph theoretic analyses to identify ‘predictive functional connectivities’ among brain regions that contributed most substantially to the classification of chronic marijuana use.ResultsWe obtained high (~80% out-of-sample) accuracy across four different classification models, demonstrating that task-evoked, whole-brain functional connectivity can successfully differentiate chronic marijuana users from non-users. Subsequent network analyses revealed key predictive regions (e.g., anterior cingulate cortex, dorsolateral prefrontal cortex, and precuneus) that are often implicated in neuroimaging studies of substance use disorders, as well as some key exceptions. We also identified a core set of networks of brain regions that contributed to successful classification, comprised of many of the same predictive regions.ConclusionsOur dual aims of accurate prediction and interpretability were successful, producing a predictive model that also provides interpretability at the neural level. This novel approach may complement other predictive-exploratory approaches for a more complete understanding of neural mechanisms in drug use and other neuropsychiatric disorders.
CFTR corrector efficacy is associated with occupancy of distinct binding sites
Authors: Baatallah Nesrine , Elbahnsi Ahmad , Mornon Jean-Paul , Chevalier Benoit , Pranke Iwona , Servel Nathalie , Zelli Renaud , Décout Jean-Luc , Edelman Aleksander , Sermet-Gaudelus Isabelle , Callebaut Isabelle , Hinzpeter Alexandre 
Published: May 2021

AbstractCFTR misfolding due to cystic fibrosis causing mutations can be corrected with small molecules designated as correctors. VX-809, an investigational corrector compound, is believed to bind CFTR directly to either the first membrane-spanning domain (MSD1) and/or the first nucleotide-binding domain (NBD1). Blind docking onto the 3D structures of these domains, followed by molecular dynamics (MD) simulations, revealed the presence of two potential VX-809 binding sites which, when mutated, abrogated corrector rescue. Mutations altering protein maturation are also shown to be not equally sensitive to the occupancy of the two sites by VX-809, with the most frequent mutation F508del requiring integrity of both sites and allosteric coupling with the F508del region while L206W only requires the integrity of the MSD1 site. A network of charged amino acids in the lasso Lh2 helix and the intracellular loops ICL1 and ICL4 is involved in the allostery between MSD1 and NBD1. Corrector VX-445, which is used in combination in clinics with VX-661, a structurally close analog of VX-809, to fully correct F508del, is also shown to occupy two potential binding sites on MSD1 and NBD1, the latter being shared with VX-809. In conclusion, VX-809 and VX-445 appear to bind different CFTR domains to alleviate specific folding defects. These results provide new insights into therapeutics understanding and may help the development of efficient corrector combinations.
TISON: a next-generation multi-scale modeling theatre forin silicosystems oncology
Authors: Gondal Mahnoor N , Sultan Muhammad U , Arif Ammar , Rehman Abdul , Awan Hira A , Arshad Zainab , Ahmed Waleed , Chaudhary Muhammad FA , Khan Salaar , Tanveer Zain B , Butt Rida Nasir , Hussain Risham , Khawar Huma , Amina Bibi , Akbar Rida , Abbas Fatima , Jami Misha N , Nasir Zainab , Shah Osama S , Hameed Hadia , Butt Muhammad FA , Mustafa Ghulam , Ahmad Muhammad M , Ahmed Sameer , Qazi Romena , Ahmed Fayyaz , Ishaq Omer , Nabi Syed W , Vanderbauwhede Wim , Wajid Bilal , Shehwana Huma , Uddin Emad , Safdar Muhammad , Javed Irfan , Tariq Muhammad , Faisal Amir , Chaudhary Safee U 
Published: May 2021

AbstractMulti-scale models integrating biomolecular data from genetic, transcriptional, and translational levels, coupled with extracellular microenvironments can assist in decoding the complex mechanisms underlying system-level diseases such as cancer. To investigate the emergent properties and clinical translation of such cancer models, we present Theatre forin silicoSystems Oncology (TISON,https://tison.lums.edu.pk), a next-generation web-based multi-scale modeling and simulation platform forin silicosystems oncology. TISON provides a “zero-code” environment for multi-scale model development by seamlessly coupling scale-specific information from biomolecular networks, microenvironments, cell decision circuits,in silicocell lines, and organoid geometries. To compute the temporal evolution of multi-scale models, a simulation engine and data analysis features are also provided. Furthermore, TISON integrates patient-specific gene expression data to evaluate patient-centric models towards personalized therapeutics. Several literature-based case studies have been developed to exemplify and validate TISON’s modeling and analysis capabilities. TISON provides a cutting-edge multi-scale modeling pipeline for scale-specific as well as integrative systems oncology that can assist in drug target discovery, repositioning, and development of personalized therapeutics.
Capacity to erase gene occlusion is a defining feature distinguishing naive from primed pluripotency
Authors: Foshay Kara M. , Lee Jae Hyun , Zhang Li , Fernandes Croydon J. , Wu Bohou , Gaetz Jedidiah , Baker Samuel W. , Looney Timothy J. , Xiang Andy Peng , Fan Guoping , Lahn Bruce T. 
Published: May 2021

SUMMARYPluripotent stem cells can exist in either the naive state representing a developmental blank slate or the downstream primed state poised for differentiation. Currently, known differences between these two states are mostly phenomenological, and none can adequately explain why the two states should differ in developmental priming. Gene occlusion is a mode of epigenetic inactivation that renders genes unresponsive to their cognate transcriptional activators. It plays a crucial role in lineage restriction. Here, we report that a defining feature distinguishing the two pluripotent states lies in the ability of naive but not primed cells to erase occlusion. This “deocclusion” capacity requires Esrrb, a gene expressed only in the naive but not primed state. Notably, Esrrb silencing in the primed state is itself due to occlusion. Collectively, our data argue that the Esrrb-dependent deocclusion capacity in naive cells is key for sustaining naive pluripotency, and the loss of this capacity in the primed state via the occlusion of Esrrb poises cells for differentiation.