bluuebunny/crossref_metadata_2025_split huggingface dataset:
One-Step Rapid Quantification of Serum Neutralizing Antibody after COVID-19 Vaccination by a High-Throughput Nanoplasmonic Sensor Platform
Authors: Huang Liping , Li Ying , Changyou Luo , Touil Nadia , Annaz Hicham el , Cheng Youqian , Zeng Shaoqi , Dang Tang , Liang Jiawei , Hu Wenjun , Xu Hao , Tu Jiasheng , Shen Yan , Liu Gang L. 
Published: April 2021

ABSTRACTThe COVID-19 vaccination efficacy depends on serum production level of the neutralizing IgG antibody (NA) specific to the receptor binding domain of SARS-Cov-2 spike protein. Therefore, a high-throughput rapid assay to measure the total SARS-CoV-2 NA level is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, vaccine development, and assessment. Here, we developed a nanoplasmonic immunosorbent assay (NanoPISA) platform for one-step rapid quantification of SARS-CoV-2 NAs in clinical serum samples for high-throughput evaluation of COVID-19 vaccine effectiveness. The NanoPISA platform enhanced by the use of nanoporous hollow gold nanoparticle coupling was able to detect SARS-CoV-2 NAs with a limit of detection of 0.1 ng/mL within 15 min. The one-step NanoPISA for SARS-CoV-2 NA detection in clinical specimens yielded good results, comparable to those obtained in the gold standard seroneutralization test and the surrogate virus neutralizing ELISA. Collectively, our findings indicate that the one-step NanoPISA may offer a rapid and high-throughput NA quantification platform for evaluating the effectiveness of COVID-19 vaccines.
A Generalizable Data Assembly Algorithm for Infectious Disease Outbreaks
Authors: Majumder Maimuna S. , Rose Sherri 
Published: April 2021

AbstractBackground & ObjectiveDuring infectious disease outbreaks, health agencies often share text-based information about cases and deaths. This information is usually text-based and rarely machine-readable, thus creating challenges for outbreak researchers. Here, we introduce a generalizable data assembly algorithm that automatically curates text-based, outbreak-related information and demonstrate its performance across three outbreaks.MethodsAfter developing an algorithm with regular expressions, we automatically curated data from health agencies via three information sources: formal reports, email newsletters, and Twitter. A validation data set was also curated manually for each outbreak.FindingsWhen compared against the validation data sets, the overall cumulative missingness and misidentification of the algorithmically curated data were ≤2% and ≤1%, respectively, for all three outbreaks.ConclusionsWithin the context of outbreak research, our work successfully addresses the need for generalizable tools that can transform text-based information into machine-readable data across varied information sources and infectious diseases.
Evaluation of Different Types of Face Masks to Limit the Spread of SARS-CoV-2 – A Modeling Study
Authors: Gurbaxani Brian M. , Hill Andrew N. , Paul Prabasaj , Prasad Pragati V. , Slayton Rachel B. 
Published: April 2021

AbstractWe updated a published mathematical model of SARS-CoV-2 transmission with laboratory-derived source and wearer protection efficacy estimates for a variety of face masks to estimate their impact on COVID-19 incidence and related mortality in the United States. When used at already-observed population rates of 80% for those ≥65 years and 60% for those <65 years, face masks are associated with 69% (cloth) to 78% (medical procedure mask) reductions in cumulative COVID-19 infections and 82% (cloth) to 87% (medical procedure mask) reductions in related deaths over a 6-month timeline in the model, assuming a basic reproductive number of 2.5. If cloth or medical procedure masks’ source control and wearer protection efficacies are boosted about 30% each to 84% and 60% by cloth over medical procedure masking, fitters, or braces, the COVID-19 basic reproductive number of 2.5 could be reduced to an effective reproductive number ≤ 1.0, and from 6.0 to 2.3 for a variant of concern similar to delta (B.1.617.2).Article Summary LineAdapting a published SARS-CoV-2 transmission model together with updated, laboratory-derived source control and wearer protection efficacy estimates for a variety of face coverings as well as N95 respirators, we demonstrate that community masking as currently practiced has likely reduced cases and deaths and that this benefit can be increased with wider adoption of better performing masks.
Geographic clusters of objectively measured physical activity and the characteristics of their built environment in a Swiss urban area
Authors: Vallarta-Robledo Juan R , Joost Stéphane , André Vieira Ruas Marco , Gubelmann Cédric , Vollenweider Peter , Marques-Vidal Pedro , Guessous Idris 
Published: April 2021

AbstractIntroductionEvidence suggests that the built environment can influence the intensity of physical activity. However, despite the importance of the geographic context, most of the studies do not consider the spatial framework of this association. We aimed to assess individual spatial dependence of objectively measured moderate and vigorous physical activity (MVPA) and describe the characteristics of the built environment among spatial clusters of MVPA.MethodsCross-sectional data from the second follow-up (2014-2017) of CoLaus|PsyCoLaus, a longitudinal population-based study of the Lausanne area (Switzerland), was used to objectively measure MVPA using accelerometers. Local Moran’s I was used to assess the spatial dependence of MVPA and detect geographic clusters of low and high MVPA. Additionally, the characteristics of the built environment observed in the clusters based on raw MVPA and MVPA adjusted for socioeconomic and demographic factors were described.ResultsData from 1,889 participants (median age 63, 55% women) were used. The geographic distribution of MVPA and the characteristics of the built environment among clusters were similar for raw and adjusted MVPA. In the adjusted model, we found a low concentration of individuals within spatial clusters of high MVPA (median: 36.9 mins; 3% of the studied population) and low MVPA (median: 10.1 mins; 2% of the studied population). Yet, clear differences were found in both models between clusters regarding the built environment; high MVPA clusters were located in areas where specific compositions of the built environment favor physical activity.ConclusionsOur results suggest the built environment may influence spatial patterns of MVPA independently of socioeconomic and demographic factors. Interventions in the built environment should be considered to promote physically active behaviors in urban areas.
Penetrance of breast cancer genes from the eMERGE III Network
Authors: Fan Xiao , Wynn Julia , Shang Ning , Liu Cong , Fedotov Alexander , Hallquist Miranda L.G. , Buchanan Adam H. , Williams Marc S. , Smith Maureen E. , Hoell Christin , Rasmussen-Torvik Laura J. , Peterson Josh F. , Wiesner Georgia L. , Murad Andrea M. , Jarvik Gail P. , Gordon Adam S. , Rosenthal Elisabeth A. , Stanaway Ian B. , Crosslin David R. , Larson Eric B. , Leppig Kathleen A. , Henrikson Nora B. , Williams Janet L. , Li Rongling , Hebbring Scott , Weng Chunhua , Shen Yufeng , Crew Katherine D. , Chung Wendy K. 
Published: April 2021

AbstractWe studied the penetrance and clinical outcomes of seven breast cancer susceptibility genes (BRCA1, BRCA2, TP53, CHEK2, ATM, PALB2 and PTEN) in almost 25,000 participants unselected for personal or family history of breast cancer. We identified 420 participants with pathogenic or likely pathogenic variants, and 147 were women who did not previously know their genetic results. Out of these 147 women, 32 women were diagnosed with breast cancer at an average age of 52.8 years. Estimated penetrance by age 60 years ranged from 18-44%, depending on the gene. Within the first twelve months after genetic results disclosure, 42% of women had taken actions related to their genetic results and two new breast cancer cases were identified. Our study provides population-based penetrance estimates for the understudied genes, CHEK2, ATM, and PALB2, and highlights the importance of using unselected populations for penetrance studies. It also demonstrates the potential clinical impact of genetic testing to improve healthcare through early diagnosis and preventative screening.
A Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men
Authors: Manikpurage Hasanga D. , Eslami Aida , Perrot Nicolas , Li Zhonglin , Couture Christian , Mathieu Patrick , Bossé Yohan , Arsenault Benoit J. , Thériault Sébastien 
Published: April 2021

ABSTRACTBackgroundSeveral risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established.MethodsA PRSCAD including the weighted effects of >1.14 million SNPs associated with CAD was calculated in UK Biobank (n=408,422), using LDPred. Cox regressions were performed, stratified by age quartiles and sex, for incident MI and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRSCAD to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI0.02) and continuous NRI (NRI>0).ResultsFrom 7,746 incident MI cases and 393,725 controls, hazard ratio (HR) for MI reached 1.53 (95% CI [1.49-1.56], p=2.69e-296) per standard deviation (SD) increase of PRSCAD. PRSCAD was significantly associated with MI in both sexes, with a stronger association in men (interaction p=0.002), particularly in those aged between 40-51 years (HR=2.00, 95% CI [1.86-2.16], p=1.93e-72). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI0.02=0.199, 95% CI [0.157-0.248] and NRI>0=0.602, 95% CI [0.525-0.683]). From 23,982 deaths, HR for mortality was 1.08 (95% CI [1.06-1.09], p=5.46e-30) per SD increase of PRSCAD, with a stronger association in men (interaction p=1.60e-6).ConclusionOur PRSCAD predicts MI incidence and all-cause mortality, especially in men aged between 40-51 years. PRS could optimize the identification and management of individuals at risk for CAD.
The genome of New Zealand trevally (Carangidae: Pseudocaranx georgianus) uncovers a XY sex determination locus
Authors: Ruigrok Mike , Catanach Andrew , Bowatte Deepa , Davy Marcus , Storey Roy , Valenza-Troubat Noémie , López-Girona Elena , Hilario Elena , Wylie Matthew J. , Chagné David , Wellenreuther Maren 
Published: April 2021

AbstractBackgroundThe genetic control of sex determinism in teleost species is poorly understood. This is partly because of the diversity of sex determining mechanisms in this large group, including constitutive genes linked to sex chromosomes, polygenic constitutive mechanisms, environmental factors, hermaphroditism, and unisexuality. Here we use ade novogenome assembly of New Zealand silver trevally (Pseudocaranx georgianus) together with whole genome sequencing to detect sexually divergent regions, identify candidate genes and develop molecular makers.ResultsThede novoassembly of an unsexed trevally (Trevally_v1) resulted in an assembly of 579.4 Mb in length, with a N50 of 25.2 Mb. Of the assembled scaffolds, 24 were of chromosome scale, ranging from 11 to 31 Mb. A total of 28416 genes were annotated after 12.8% of the assembly was masked with repetitive elements. Whole genome re-sequencing of 13 sexed trevally (7 males, 6 females) identified sexually divergent regions located on two scaffolds, including a 6 kb region at the proximal end of chromosome 21. Blast analyses revealed similarity between one region and the aromatase genescyp19 (a1a/b). Males contained higher numbers of heterozygous variants in both regions, while females showed regions of very low read-depth, indicative of deletions. Molecular markers tested on 96 histologically-sexed fish (42 males, 54 females). Three markers amplified in absolute correspondence with sex.ConclusionsThe higher number of heterozygous variants in males combined with deletions in females support a XY sex-determination model, indicating the trevally_v1 genome assembly was based on a male. This sex system contrasts with the ZW-type sex system documented in closely related species. Our results indicate a likely sex-determining function of thecyp19b-like gene, suggesting the molecular pathway of sex determination is somewhat conserved in this family. Our genomic resources will facilitate future comparative genomics works in teleost species, and enable improved insights into the varied sex determination pathways in this group of vertebrates. The sex marker will be a valuable resource for aquaculture breeding programmes, and for determining sex ratios and sex-specific impacts in wild fisheries stocks of this species.
The neuroinflammatory interleukin-12 signaling pathway drives Alzheimer’s disease-like pathology by perturbing oligodendrocyte survival and neuronal homeostasis
Authors: Schneeberger Shirin , Kim Seung Joon , Eede Pascale , Boltengagen Anastasiya , Braeuning Caroline , Andreadou Myrto , Becher Burkhard , Karaiskos Nikos , Kocks Christine , Rajewsky Nikolaus , Heppner Frank L. 
Published: April 2021

AbstractAlzheimer’s disease (AD) is characterized by deposition of pathological amyloid-β (Aβ) and tau protein aggregates and involves chronic neuroinflammation, ultimately leading to neurodegeneration and cognitive decline. Central in AD-related neuroinflammation is the proinflammatory interleukin-12 (IL-12)/IL-23 signaling pathway whose inhibition has been shown to attenuate pathology and cognitive defects in AD-like mice. In order to explore which cell types are involved in this neuroinflammatory cascade, we used single-nuclei RNA sequencing in AD-like APPPS1 mice lacking or harboring IL-12/IL-23 signaling. We foundIl12btranscripts encoding the common p40 subunit of IL-12/IL-23 signaling to be expressed preferentially, but not exclusively, in microglia in an AD-specific manner. In contrast, transcripts for the other subunits of the IL-12 signaling pathway were expressed constitutively in neurons and oligodendrocytes irrespective of AD pathology, while transcripts for IL-23 were almost undetectable. Notably, genetic ablation of IL-12/IL-23 signaling did not affect the inflammatory gene expression profile of the AD-specific disease associated microglia (DAM), but reversed the loss of mature myelin-producing oligodendrocytes and alterations in neuronal homeostasis in APPPS1 mice. Taken together, our results reveal that IL-12, but not IL-23 is the main driver of AD-specific IL-12/IL-23 neuroinflammation, which alters neuronal and oligodendrocyte functions. Given that drugs targeting IL-12 already exist, our data may foster first clinical trials in AD subjects using this novel neuroimmune target.
Using Human Induced Pluripotent Stem Cell Derived Organoids to Identify New Pathologies in Patients with PDX1 Mutations
Authors: Krishnamurthy Mansa , Kechele Daniel O , Broda Taylor , Zhang Xinghao , Enriquez Jacob R , McCauley Heather A , Sanchez J Guillermo , Palermo Joseph , Collins Margaret , Thomas Inas H , Neef Haley C , Heider Amer , Dauber Andrew , Wells James M 
Published: April 2021

SummaryTwo patients with mutations inPDX1presented with pancreatic agenesis, chronic diarrhea and poor weight gain, the causes of which were not identified through routine clinical testing. We generated patient derived organoids as a novel diagnostic strategy and observed thatPDX1188delC/188delCantral organoids convert to an intestinal phenotype, while intestinal organoids undergo gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsies from bothPDX1188delC/188delCpatients, which recapitulated organoid phenotypes. Antral biopsies had increased parietal cells and lacked G-cells suggesting loss of antral identity. These patients will now be monitored for the progression of metaplasia. This study demonstrates the utility of organoids for patient diagnoses and treatment.
Conserved in 186 countries the RBD fraction of SARS CoV-2 S-protein with in-silicoT500S mutation strongly blocks ACE2 rejecting the viral spike; A Molecular-docking analysis
Authors: Banerjee Amrita , Kanwar Mehak , Santra Dipannita , Maiti Smarajit 
Published: April 2021

AbstractSARS-CoV-2 developed global-pandemic with millions of infections/deaths. Blocker/inhibitor of ACE2 and viral-spikes Receptor-Binding-Domain RBD-blockers are helpful. Here, conserved RBD (CUTs) from 186-countries were compared with WUHAN-Hu-1 wild-type by CLUSTAL-X2 and Structural-alignment using Pymol. The RBD of ACE2-bound nCOV2 crystal-structure (2.68Å) 6VW1 was analyzed by Haddock-PatchDock. Extensive structural study/trial to introduce point/double/triple mutations in the following locations (Y489S/Y453S/T500S/T500Y)/(Y489S,Y453S/Y489S,T500S/Y489S,T500Y/Y453S,T500S/Y453S, T500Y)/ (Y489S,Y453S,T500S/Y489S,Y453S,T500Y) of CUT4 (most-effective) were tested with Swiss-Model-Expacy. Blind-docking of mutated-CUTs to ACE2 (6VW1) by Haddock-Hawkdock was performed and optimally complete-rejection of nCOV2 to ACE2 was noticed. Further, competitive-docking/binding-analyses were done by PRODIGY. Present results suggest that compared to the wild-spike, CUT4 showed extra LYS31-PHE490/GLN42-GLN498 bonding and lack of TYR41-THR500 interaction (in wild H-bond:2.639Å) with ACE2 RBD. Mutated-CUT4 strongly binds with the ACE2-RBD, promoting TYR41-T500S (H-bond: 2.0Å and 1.8Å)/T500Y (H-bond:2.6Å) interaction and complete inhibition of ACE2 RBD-nCOV2. Mutant combinations T500S,Y489S,T500S and Y489S,Y453S,T500Y mostly blocked ACE2. Conclusively, CUT4-mutant rejects whole glycosylated-nCoV2 pre-dock/post-dock/competitive-docking conditions.
Patterns of SARS-CoV-2 Aerosol Spread in Typical Classrooms
Authors: Rencken Gerhard K. , Rutherford Emma K. , Ghanta Nikhilesh , Kongoletos John , Glicksman Leon 
Published: April 2021

AbstractAlthough current industry guidelines to control the spread of SARS-CoV-2 (COVID-19) have adopted a six-foot (∼1.8m) spacing between individuals indoors, recent evidence suggests that longer range spread is also responsible for infections in public spaces. The vehicle for long-range spread is smaller droplets or particles, termed bio-aerosols, or aerosols for short, which have a large surface area to volume ratio such that aerodynamic drag is much larger than gravity forces. The aerosols remain suspended in air for extended time periods and they essentially move with air currents. Prediction of the danger to occupants in a closed room when exposed to an infected individual requires knowledge of the period of exposure and the concentration level of aerosols in the breathing zone of an occupant. To obtain an estimate of the concentration level, a common assumption is well-mixed conditions within an interior space. This is obtained from a mass balance between the level of aerosol produced by an infected individual along with the airflow rate into and out of the entire space. In this work, we use computational fluid dynamics, verified by experimental results, to explore the aerosol concentration distribution in a typical classroom for several common conditions and compare these results to the well-mixed assumption. We use a tracer gas to simulate the flow and dispersion of the aerosol-air mixture. The two ventilation systems examined, ceiling diffusers and open windows, yield average concentrations at occupant breathing level 50% greater than the well mixed case, and some scenarios yield concentrations that are 150% greater than the well mixed concentration at specific breathing-level locations. Of particular concern are two conditions: horizontal air flow from an open window in line with a row of seating and, second, an infected individual seated near a sealed cold window. For the former, conditions are improved if a baffle is placed inside the open window to direct the air toward the floor, creating a condition similar to displacement ventilation. In the latter, the cold air flowing down along the cold window recirculates aerosols back into the breathing zone. Adding window covers or a portable heater below the window surface will moderate this condition.
Single-cell dissection of the human cerebrovasculature in health and disease
Authors: Garcia Francisco J. , Sun Na , Lee Hyeseung , Godlewski Brianna , Galani Kyriaki , Mantero Julio , Bennett David A. , Sahin Mustafa , Kellis Manolis , Heiman Myriam 
Published: April 2021

SummaryDespite the importance of the blood-brain barrier in maintaining normal brain physiology and in understanding neurodegeneration and CNS drug delivery, human cerebrovascular cells remain poorly characterized due to their sparsity and dispersion. Here, we perform the first single-cell characterization of the human cerebrovasculature using bothex vivofresh-tissue experimental enrichment andpost mortem in silicosorting of human cortical tissue samples. We capture 31,812 cerebrovascular cells across 17 subtypes, including three distinct subtypes of perivascular fibroblasts as well as vasculature-coupled neurons and glia. We uncover human-specific expression patterns along the arteriovenous axis and determine previously uncharacterized cell type-specific markers. We use our newly discovered human-specific signatures to study changes in 3,945 cerebrovascular cells of Huntington’s disease patients, which reveal an activation of innate immune signaling in vascular and vasculature-coupled cell types and the concomitant reduction to proteins critical for maintenance of BBB integrity. Finally, our study provides a comprehensive resource molecular atlas of the human cerebrovasculature to guide future biological and therapeutic studies.
The encapsulin fromThermatoga maritimais a flavoprotein with a symmetry matched ferritin-like cargo protein
Authors: LaFrance Benjamin , Cassidy-Amstutz Caleb , Nichols Robert J , Oltrogge Luke M , Nogales Eva , Savage David F 
Published: April 2021

AbstractBacterial nanocompartments, also known as encapsulins, are an emerging class of protein-based ‘organelles’ found in bacteria and archaea. Encapsulins are virus-like icosahedral particles comprising a ∼25-50 nm shell surrounding a specific cargo enzyme. Compartmentalization is thought to create a unique chemical environment to facilitate catalysis and isolate toxic intermediates. Many questions regarding nanocompartment structure-function remain unanswered, including how shell symmetry dictates cargo loading and to what extent the shell facilitates enzymatic activity. Here, we explore these questions using the modelT. maritimananocompartment known to encapsulate a redox-active ferritin-like protein. Biochemical analysis revealed the encapsulin shell to possess a flavin binding site located at the interface between capsomere subunits, suggesting the shell may play a direct and active role in the function of the encapsulated cargo. Furthermore, we used cryoEM to show that cargo proteins use a form of symmetry-matching to facilitate encapsulation and define stoichiometry. In the case of theT. maritimaencapsulin, the decameric cargo protein with 5-fold symmetry preferentially binds to the pentameric-axis of the icosahedral shell. Taken together, these observations suggest the shell is not simply a passive barrier—it also plays a significant role in the structure and function of the cargo enzyme.