bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-depth Analysis of Laboratory Parameters Reveals the Interplay Between Sex, Age and Systemic Inflammation in Individuals with COVID-19
Authors: ten-Caten Felipe , Gonzalez-Dias Patrícia , Castro Ícaro , Ogava Rodrigo L T , Giddaluru Jeevan , Silva Juan Carlo S , Martins Felipe , Gonçalves André N A , Costa-Martins André G , Araujo José D. , Viegas Ana Carolina , Cunha Fernando Q , Farsky Sandra , Bozza Fernando A , Levin Anna S , Pannaraj Pia S , de Silva Thushan I , Minoprio Paola , Andrade Bruno B , da Silva Fabiano Pinheiro , Nakaya Helder I 
Published: August 2020

AbstractIntroductionThe progression and severity of the coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), varies significantly in the population. While the hallmarks of SARS-CoV-2 and severe COVID-19 within routine laboratory parameters are emerging, little is known about the impact of sex and age on these profiles.MethodsWe performed multidimensional analysis of millions of records of laboratory parameters and diagnostic tests for 178,887 individuals, of which 33,266 tested positive for SARS-CoV-2. These included complete blood cell count, electrolytes, metabolites, arterial blood gases, enzymes, hormones, cancer biomarkers, and others.ResultsCOVID-19 induced similar alterations in the laboratory parameters in males compared to females. Biomarkers of inflammation, such as C-reactive protein (CRP) and ferritin, were increased especially in older men with COVID-19, whereas other markers such as abnormal liver function tests were common across several age groups, except for young women. Low peripheral blood basophils and eosinophils were also more common in the elderly with COVID-19. Both male and female COVID-19 patients admitted to the intensive care unit (ICU) displayed alterations in the coagulation system, and higher levels of neutrophils, CRP, lactate dehydrogenase (LDH), among others.DiscussionOur study uncovers the laboratory profile of a large cohort of COVID-19 patients that underly discrepancies influenced by aging and biological sex. These profiles directly link COVID-19 disease presentation to an intricate interplay between sex, age and the immune response.One Sentence SummaryBig Data analysis of laboratory results from a large number of COVID-19 patients and controls reveals distinct disease profiles influenced by age and sex which may underly occurrence of severe disease.Key messages- What is the key question?Little is known about the impact of sex and age on the routine laboratory parameters measured in COVID-19 patients.- What is the bottom line?Our in-depth analysis unraveled distinct disease profiles influenced by age and sex which may underly occurrence of severe disease.- Why read on?This work will help physicians to interpret the disease presentation in COIVD-19 patients according to their age and sex.
Population perspective comparing COVID-19 to all and common causes of death in seven European countries
Authors: Olabi Bayanne , Bagaria Jayshree , Bhopal Sunil S. , Curry Gwenetta D. , Villarroel Nazmy , Bhopal Raj 
Published: August 2020

AbstractBackgroundMortality statistics on the COVID-19 pandemic have led to widespread concern and fear. To contextualise these data, we compared mortality related to COVID-19 with all and common causes of death, stratifying by age and sex. We also calculated deaths as a proportion of the population by age and sex.MethodsCOVID-19 related mortality and population statistics from seven European countries were extracted: England and Wales, Italy, Germany, Spain, France, Portugal and Netherlands. Available data spanned 14-16 weeks since the first recorded deaths in each country, except Spain, where only comparable stratified data over an 8-week time period was available. The Global Burden of Disease database provided data on all deaths and those from pneumonia, cardiovascular disease combining ischaemic heart disease and stroke, chronic obstructive pulmonary disease, cancer, road traffic accidents and dementia.FindingsDeaths related to COVID-19, while modest overall, varied considerably by age. Deaths as a percentage of all cause deaths during the time period under study ranged from <0.01% in children in Germany, Portugal and Netherlands, to as high as 41.65% for men aged over 80 years in England and Wales. The percentage of the population who died from COVID-19 was less than 0.2% in every age group under the age of 80. In each country, over the age of 80, these proportions were: England and Wales 1.27% males, 0.87% females; Italy 0.6% males, 0.38% females; Germany 0.13% males, 0.09% females; France 0.39% males, 0.2% females; Portugal 0.2% males, 0.15% females; and Netherlands 0.6% males, 0.4% females.InterpretationMortality rates from COVID-19 remains low including when compared to other common causes of death and will likely decline further while control measures are maintained. These data may help people contextualise their risk and policy makers in decision-making.
Compound risks of hurricane evacuation amid the COVID-19 pandemic in the United States
Authors: Pei Sen , Dahl Kristina A. , Yamana Teresa K. , Licker Rachel , Shaman Jeffrey 
Published: August 2020

AbstractCurrent projections and unprecedented storm activity to date suggest the 2020 Atlantic hurricane season will be extremely active and that a major hurricane could make landfall during the global COVID-19 pandemic. Such an event would necessitate a large-scale evacuation, with implications for the trajectory of the pandemic. Here we model how a hypothetical hurricane evacuation from four counties in southeast Florida would affect COVID-19 case levels. We find that hurricane evacuation increases the total number of COVID-19 cases in both origin and destination locations; however, if transmission rates in destination counties can be kept from rising during evacuation, excess evacuation-induced case numbers can be minimized by directing evacuees to counties experiencing lower COVID-19 transmission rates. Ultimately, the number of excess COVID-19 cases produced by the evacuation depends on the ability of destination counties to meet evacuee needs while minimizing virus exposure through public health directives.
Reproducibility in systems biology modelling
Authors: Tiwari Krishna , Kananathan Sarubini , Roberts Matthew G , Meyer Johannes P , Sharif Shohan Mohammad Umer , Xavier Ashley , Maire Matthieu , Zyoud Ahmad , Men Jinghao , Ng Szeyi , Nguyen Tung V N , Glont Mihai , Hermjakob Henning , Malik-Sheriff Rahuman S. 
Published: August 2020

AbstractThe reproducibility crisis has emerged as an important concern across many fields of science including life science, since many published results failed to reproduce. Systems biology modelling, which involves mathematical representation of biological processes to study complex system behaviour, was expected to be least affected by this crisis. While lack of reproducibility of experimental results and computational analysis could be a repercussion of several compounded factors, it was not fully understood why systems biology models with well-defined mathematical expressions fail to reproduce and how prevalent it is. Hence, we systematically attempted to reproduce455kinetic models of biological processes published in peer-reviewed research articles from152journals; which is collectively a work of about1400scientists from49countries. Our investigation revealed that about half (49%) of the models could not be reproduced using the information provided in the published manuscripts. With further effort, an additional 12% of the models could be reproduced either by empirical correction or support from authors. The other 37% remained non-reproducible models due to missing parameter values, missing initial concentration, inconsistent model structure, or a combination of these factors. Among the corresponding authors of the non-reproducible model we contacted, less than30%responded. Our analysis revealed that models published in journals across several fields of life science failed to reproduce, revealing a common problem in the peer-review process. Hence, we propose an 8-point reproducibility scorecard that can be used by authors, reviewers and journal editors to assess each model and address the reproducibility crisis.
Dach1 extends artery networks and protects against cardiac injury
Authors: Raftrey Brian , Williams Ian , Rios Coronado Pamela E. , Chang Andrew H. , Zhao Mingming , Roth Robert , Racelis Raquel , D’Amato Gaetano , Phansalkar Ragini , Gonzalez Karen M. , Zhang Yue , Bernstein Daniel , Red-Horse Kristy 
Published: August 2020

AbstractCoronary artery disease (CAD) is the leading cause of death worldwide, but there are currently no available methods to stimulate growth or regeneration of artery networks in diseased hearts. Studying how arteries are built during embryonic development could illuminate strategies for re-building these vessels in the setting of ischemic heart disease. We previously found, using loss-of-function experiments, that the transcription factorDach1is required for coronary artery development in mouse embryos. Here, we report thatDach1overexpression in endothelial cells (ECs) extended coronary arteries and improved survival and heart function in adult mice following myocardial infarction (MI).Dach1overexpression increased the length and number of arterial end branches, in both heart and retinal vasculature, by causing additional capillary ECs to differentiate into arterial ECs and contribute to growing arteries. Single-cell RNA sequencing (scRNAseq) of ECs undergoingDach1-induced arterial specification indicated that it potentiated normal artery differentiation, rather than functioning as a master regulator of artery cell fate. ScRNAseq also showed that normal arterial differentiation is accompanied by repression of lipid metabolism genes, which were also repressed by Dach1 prior to arterialization. Together, these results demonstrate that increasing the expression level ofDach1is a novel pathway for driving specification of artery ECs and extending arterial vessels, which could be explored as a means of increasing artery coverage to mitigate the effects of CAD.
Dynamics of infection in a novel group of promiscuous phages and hosts of multiple bacterial genera retrieved from river communities
Authors: Cazares Daniel , Cazares Adrian , Figueroa Wendy , Guarneros Gabriel , Edwards Robert A. , Vinuesa Pablo 
Published: August 2020

AbstractPhages are generally described as species- or even strain-specific viruses, implying an inherent limitation for some to be maintained and spread in diverse bacterial communities. Moreover, phage isolation and host range determination rarely consider the phage ecological context, likely biasing our notion on phage specificity. Here we identified and characterized a novel group of promiscuous phages existing in rivers by using diverse bacteria isolated from the same samples, and then used this biological system to investigate infection dynamics in distantly related hosts. We assembled a diverse collection of over 600 native bacterial strains and used them to isolate six podophages, named Atoyac, from different geographic origin and capable of infecting six genera in the Gammaproteobacteria. Atoyac phage genomes are highly similar to each other but not to those currently available in the genome and metagenome public databases. Detailed comparison of the phage’s infectivity in diverse hosts and trough hundreds of interactions revealed variation in plating efficiency amongst bacterial genera, implying a cost associated with infection of distant hosts, and between phages, despite their sequence similarity. We show, through experimental evolution in single or alternate hosts of different genera, that plaque production efficiency is highly dynamic and tends towards optimization in hosts rendering low plaque formation. Complex adaptation outcomes observed in the evolution experiments differed between highly similar phages and suggest that propagation in multiple hosts may be key to maintain promiscuity in some viruses. Our study expands our knowledge of the virosphere and uncovers bacteria-phage interactions overlooked in natural systems.ImportanceIn natural environments, phages co-exist and interact with a broad variety of bacteria, posing a conundrum for narrow-host-range phages maintenance in diverse communities. This context is rarely considered in the study of host-phage interactions, typically focused on narrow-host-range viruses and their infectivity in target bacteria isolated from sources distinct to where the phages were retrieved from. By studying phage-host interactions in bacteria and viruses isolated from river microbial communities, we show that novel phages with promiscuous host range encompassing multiple bacterial genera can be found in the environment. Assessment of hundreds of interactions in diverse hosts revealed that similar phages exhibit different infection efficiency and adaptation patterns. Understanding host range is fundamental in our knowledge of bacteria-phage interactions and their impact in microbial communities. The dynamic nature of phage promiscuity revealed in our study has implications in different aspects of phage research such as horizontal gene transfer or phage therapy.
A Validated Measure of Rigidity in Parkinson’s Disease Using Alternating Finger Tapping on an Engineered Keyboard
Authors: Trager Megan H , Wilkins Kevin B , Koop Mandy Miller , Bronte-Stewart Helen 
Published: August 2020

AbstractIntroductionReliable and accurate measures of rigidity have remained elusive in remote assessments of Parkinson’s disease (PD). This has severely limited the utility of telemedicine in the care and treatment of people with PD. It has also had a large negative impact on the scope of available outcomes, and on the costs, of multicenter clinical trials in PD. The goal of this study was to determine if quantitative measures from an engineered keyboard were sensitive and related to clinical measures of rigidity.MethodsSixteen participants with idiopathic PD, off antiparkinsonian medications, and eleven age-matched control participants performed a 30 second repetitive alternating finger tapping task on an engineered keyboard and were assessed with the Unified Parkinson’s Disease Rating Scale – motor (UPDRS-III).ResultsThe speed of the key release was significantly slower in the PD compared to control cohorts (p <0.0001). In the PD cohort key release speed correlated with the lateralized upper extremity UPDRS III rigidity score (r = - 0.58, p < 0.0001), but not with the lateralized upper extremity tremor score (r = 0.14, p = 0.43).ConclusionsThis validated measure of rigidity complements our previous validation of temporal metrics of the repetitive alternating finger tapping task with the UPDRS III, bradykinesia and with the ability to quantify tremor, arrhythmicity and freezing episodes, and suggests that thirty seconds of alternating finger tapping on a portable engineered keyboard could transform the treatment of PD with telemedicine and the precision of multicenter clinical trials.
Comparative Clinical Outcomes and Mortality in Prisoner and Non-Prisoner Populations Hospitalized with COVID-19: A Cohort from Michigan
Authors: Altibi Ahmed M. , Pallavi Bhargava , Liaqat Hassan , Slota Alexander A. , Sheth Radhika , Al Jebbawi Lama , George Matthew E. , LeDuc Allison , Abdallah Enas , Russel Luke R. , Jain Saniya , Shirvanian Nariné , Masri Ahmad , Kak Vivek 
Published: August 2020

ABSTRACTBackgroundPrisons in the United States have become a hotbed for spreading Covid-19 among incarcerated individuals. Covid-19 cases among prisoners are on the rise, with more than 46,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with Covid-19.MethodsAn observational study of all patients hospitalized with Covid-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were used to investigate primary outcomes.ResultsOf the 706 hospitalized Covid-19 patients (mean age 66.7 ± 16.1 years, 57% males, and 44% black), 108 were prisoners and 598 were non-prisoners. Compared to non-prisoners, prisoners were more likely to present with fever, tachypnea, hypoxemia, and markedly elevated inflammatory markers. Prisoners were more commonly admitted to the intensive care unit (ICU) (26.9% vs. 18.7%), required vasopressors (24.1% vs. 9.9%), and intubated (25.0% vs. 15.2%). Prisoners had higher unadjusted inpatient mortality (29.6% vs. 20.1%) and 30-day mortality (34.3% vs. 24.6%). In the adjusted models, prisoner status was associated with higher in-hospital death (odds ratio, 1.95; 95% confidence interval (CI), 1.07 to 3.57) and 30-day mortality (hazard ratio, 1.92; 95% CI, 1.24 to 2.98).ConclusionsIn this cohort of hospitalized Covid-19 patients, prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, inhospital mortality, and 30-day mortality.
An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation
Authors: Schoof Michael , Faust Bryan , Saunders Reuben A. , Sangwan Smriti , Rezelj Veronica , Hoppe Nick , Boone Morgane , Billesbølle Christian B. , Puchades Cristina , Azumaya Caleigh M. , Kratochvil Huong T. , Zimanyi Marcell , Deshpande Ishan , Liang Jiahao , Dickinson Sasha , Nguyen Henry C. , Chio Cynthia M. , Merz Gregory E. , Thompson Michael C. , Diwanji Devan , Schaefer Kaitlin , Anand Aditya A. , Dobzinski Niv , Zha Beth Shoshana , Simoneau Camille R. , Leon Kristoffer , White Kris M. , Chio Un Seng , Gupta Meghna , Jin Mingliang , Li Fei , Liu Yanxin , Zhang Kaihua , Bulkley David , Sun Ming , Smith Amber M. , Rizo Alexandrea N. , Moss Frank , Brilot Axel F. , Pourmal Sergei , Trenker Raphael , Pospiech Thomas , Gupta Sayan , Barsi-Rhyne Benjamin , Belyy Vladislav , Barile-Hill Andrew W. , Nock Silke , Liu Yuwei , Krogan Nevan J. , Ralston Corie Y. , Swaney Danielle L. , García-Sastre Adolfo , Ott Melanie , Vignuzzi Marco ,   QCRG Structural Biology Consortium, Walter Peter , Manglik Aashish 
Published: August 2020

ABSTRACTWithout an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. SARS-CoV-2 gains entry into host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. By screening a yeast surface-displayed library of synthetic nanobody sequences, we identified a panel of nanobodies that bind to multiple epitopes on Spike and block ACE2 interaction via two distinct mechanisms. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for SARS-CoV-2 Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains stability and function after aerosolization, lyophilization, and heat treatment. These properties may enable aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia, promising to yield a widely deployable, patient-friendly prophylactic and/or early infection therapeutic agent to stem the worst pandemic in a century.
Contrasting selection at multiple life stages maintains divergent adaptation between sunflower ecotypes
Authors: Goebl April M. , Kane Nolan C. , Doak Daniel F. , Rieseberg Loren H. , Ostevik Kate L. 
Published: August 2020

AbstractConspecific populations living in adjacent, but contrasting, microenvironments represent excellent systems for studying natural selection. These systems are valuable because gene flow maintains genetic homogeneity except at loci experiencing strong, divergent selection. A history of reciprocal transplant and common garden studies in such systems, and a growing number of genomic studies, have contributed to understanding how selection operates in natural populations. While selection can vary across different fitness components and life stages, few studies have investigated how this ultimately affects allele frequencies and persistence of divergent populations. Here, we study two sunflower ecotypes in distinct, adjacent habitats by combining demographic models with genome-wide sequence data to estimate fitness components, absolute fitness, and allele frequency change at multiple life stages. This framework allows us to demonstrate that only local ecotypes experience positive population growth (lambda>1) and that the maintenance of divergent adaptation is mediated via habitat- and life stage-specific selection. We identify genetic variation, significantly driven by loci in chromosomal inversions, associated with different life history strategies in neighbouring ecotypes that optimize different fitness components and contribute to the persistence of each ecotype in its respective habitat.
Bi-paratopic and multivalent human VH domains neutralize SARS-CoV-2 by targeting distinct epitopes within the ACE2 binding interface of Spike
Authors: Bracken Colton J. , Lim Shion A. , Solomon Paige , Rettko Nicholas J. , Nguyen Duy P. , Zha Beth Shoshana , Schaefer Kaitlin , Byrnes James R. , Zhou Jie , Lui Irene , Liu Jia , Pance Katarina ,   QCRG Structural Biology Consortium, Zhou Xin X. , Leung Kevin K. , Wells James A. 
Published: August 2020

AbstractNeutralizing agents against SARS-CoV-2 are urgently needed for treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domain binders with high affinity toward neutralizing epitopes without the need for high-resolution structural information. We constructed a VH-phage library and targeted a known neutralizing site, the angiotensin-converting enzyme 2 (ACE2) binding interface of the trimeric SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified 85 unique VH binders to two non-overlapping epitopes within the ACE2 binding site on Spike-RBD. This enabled us to systematically link these VH domains into multivalent and bi-paratopic formats. These multivalent and bi-paratopic VH constructs showed a marked increase in affinity to Spike (up to 600-fold) and neutralization potency (up to 1400-fold) on pseudotyped SARS-CoV-2 virus when compared to the standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with half-minimal inhibitory concentration (IC50) of 4.0 nM (180 ng/mL). A cryo-EM structure of the trivalent VH bound to Spike shows each VH domain bound an RBD at the ACE2 binding site, explaining its increased neutralization potency and confirming our original design strategy. Our results demonstrate that targeted selection and engineering campaigns using a VH-phage library can enable rapid assembly of highly avid and potent molecules towards therapeutically important protein interfaces.