bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated processing of thermal imaging to detect COVID-19
Authors: Brzezinski Rafael Y. , Rabin Neta , Lewis Nir , Peled Racheli , Kerpel Ariel , Tsur Avishai M. , Gendelman Omer , Naftali-Shani Nili , Gringauz Irina , Amital Howard , Leibowitz Avshalom , Mayan Haim , Ben-Zvi Ilan , Heler Eyal , Shechtman Liran , Rogovski Ori , Shenhar-Tsarfaty Shani , Konen Eli , Marom Edith M. , Ironi Avinoah , Rahav Galia , Zimmer Yair , Grossman Ehud , Ovadia-Blechman Zehava , Leor Jonathan , Hoffer Oshrit 
Published: December 2020

ABSTRACTRapid and sensitive screening tools for SARS-CoV-2 infection are essential to limit the spread of COVID-19 and to properly allocate national resources. Here, we developed a new point-of-care, non-contact thermal imaging tool to detect COVID-19, based on image-processing algorithms and machine learning analysis. We captured thermal images of the back of individuals with and without COVID-19 using a portable thermal camera that connects directly to smartphones. Our novel image processing algorithms automatically extracted multiple texture and shape features of the thermal images and achieved an area under the curve (AUC) of 0.85 in detecting COVID-19 with up to 92% sensitivity. Thermal imaging scores were inversely correlated with clinical variables associated with COVID-19 disease progression. We show, for the first time, that a hand-held thermal imaging device can be used to detect COVID-19. Non-invasive thermal imaging could be used to screen for COVID-19 in out-of-hospital settings, especially in low-income regions with limited imaging resources.HIGHLIGHTSAutomated processing of thermal images of the back can be used to detect COVID-19 with up to 92% sensitivity.The extracted texture features of the thermal image are associated with COVID-19 disease progression and lung injury.A portable thermal camera that connects directly to smartphones can be used to detect COVID-19.Non-invasive thermal imaging could be used to screen for COVID-19 in out-of-hospital settings and regions with limited imaging resources.GRAPHICAL ABSTRACT
Analysis of genome characteristics and transmission of SARS-CoV-2 strains in North-East of Romania during the first COVID-19 outbreak
Authors: Lobiuc Andrei , Dimian Mihai , Gheorghita Roxana , Sturdza Olga , Covasa Mihai 
Published: December 2020

AbstractRomania officially declared its first SARS-CoV-2 case on February 26, 2020. The first and largest COVID-19 outbreak in Romania was recorded in Suceava, N/E region of the country, and originated at the Suceava regional county hospital. Following sheltering-in-place measures, infection rates decreased, only to rise again after relaxation of measures. This study describes the incursion of SARS-CoV-2 in Suceava and other parts of Romania and analyzes the mutations and their association with clinical manifestation of the disease during the period of COVID-19 outbreak. Phylogenetic analysis indicated multiple sites of origin for SARS-CoV-2 strains in Suceava, specifically from Spain, Italy and Russia, but also other strains related to those from Czech Republic, Belgium and France. Most Suceava samples contained mutations common to European lineages, such as A20268G, however aproximately 10% of samples were missing such mutations, indicating a possible different origin. While overall genome regions ORF1ab, S and ORF7 were subject to most mutations, several recurring mutations such as C27707T were identified, and these were mainly present in severe forms of the disease. Non-synonymous mutations, such as C3225A (Thr987Asn in NSP3a domain), associated with changes in a protein responsible for decreasing viral tethering in human host were also present. Patients with diabetes and hypertension exhibited eight and three time,s respectively, higher odds ratios of acquiring severe forms of the disease and these were mainly related to C27707T mutation. These results will aid in tracing virus movement throughout Romania and identification of infectivity, virulence and pathogenicity.
Patterns of SARS-CoV-2 testing preferences in a national cohort in the United States
Authors: Romo Matthew L. , Zimba Rebecca , Kulkarni Sarah , Berry Amanda , You William , Mirzayi Chloe , Westmoreland Drew , Parcesepe Angela M. , Waldron Levi , Rane Madhura , Kochhar Shivani , Robertson McKaylee , Maroko Andrew R. , Grov Christian , Nash Denis ,   for the CHASING COVID Cohort Study Team
Published: December 2020

ABSTRACTIn order to understand preferences about SARS-CoV-2 testing, we conducted a discrete choice experiment among 4793 participants in the Communities, Households, and SARS-CoV-2 Epidemiology (CHASING COVID) Cohort Study from July 30-September 8, 2020. We used latent class analysis to identify distinct patterns of preferences related to testing and conducted a simulation to predict testing uptake if additional testing scenarios were offered. Five distinct patterns of SARS-CoV-2 testing emerged. “Comprehensive testers” (18.9%) ranked specimen type as most important and favored less invasive specimen types, with saliva most preferred, and also ranked venue and result turnaround time as highly important, with preferences for home testing and fast result turnaround time. “Fast track testers” (26.0%) ranked result turnaround time as most important and favored immediate and same day turnaround time. “Dual testers” (18.5%) ranked test type as most important and preferred both antibody and viral tests. “Non-invasive dual testers” (33.0%) ranked specimen type and test type as similarly most important, preferring cheek swab specimen type and both antibody and viral tests. “Home testers” (3.6%) ranked venue as most important and favored home-based testing. By offering less invasive (saliva specimen type), dual testing (both viral and antibody tests), and at home testing scenarios in addition to standard testing scenarios, simulation models predicted that testing uptake would increase from 81.7% to 98.1%. We identified substantial differences in preferences for SARS-CoV-2 testing and found that offering additional testing options, which consider this heterogeneity, would likely increase testing uptake.SIGNIFICANCEDuring the COVID-19 pandemic, diagnostic testing has allowed for early detection of cases and implementation of measures to reduce community transmission of SARS-CoV-2 infection. Understanding individuals’ preferences about testing and the service models that deliver tests are relevant in efforts to increase and sustain uptake of SARS-CoV-2 testing, which, despite vaccine availability, will be required for the foreseeable future. We identified substantial differences in preferences for SARS-CoV-2 testing in a discrete choice experiment among a large national cohort of adults in the US. Offering additional testing options that account for or anticipate this heterogeneity in preferences (e.g., both viral and antibody tests, at home testing), would likely increase testing uptake.ClassificationBiological Sciences (major); Psychological and Cognitive Sciences (minor)
The 100,000 most influential scientists rank: the underrepresentation of Brazilian women in academia
Authors: de Oliveira Leticia , Reichert Fernanda , Zandona Eugenia , Soletti Rossana C. , Staniscuaski Fernanda 
Published: December 2020

AbstractDespite the progress observed in recent years, women are still underrepresented in science worldwide, especially at top positions. Many factors contribute to women progressively leaving academia at different stages of their career, including motherhood, harassment and conscious and unconscious discrimination. Implicit bias plays a major negative role in recognition, promotions and career advancement of female scientists. Recently, a rank on the most influential scientists in the world was created based on several metrics, including the number of published papers and citations. Here, we analyzed the representation of Brazilian scientists in this rank, focusing on gender. Female Brazilian scientists are greatly underrepresented in the rank (11% in the Top 100,000; 18% in the Top 2%). Male scientists have more self-citation than female scientists and positions in the rank varied when self-citations were included, suggesting that self-citation by male scientists increases their visibility. Moreover, male scientists had more papers never cited than female scientists. Possible reasons for this observed scenario are related to the metrics used to rank scientists, since these metrics reproduce and amplify the well-known implicit bias in peer-review and citations. Discussions on the repercussions of such ranks are pivotal to avoid deepening the gender gap in science.
Platycodin D prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infectionin vitroby hindering membrane fusion
Authors: Kim Tai Young , Jeon Sangeun , Jang Youngho , Gotina Lizaveta , Won Joungha , Ju Yeon Ha , Kim Sunpil , Jang Minwoo Wendy , Won Woojin , Park Mingu Gordon , Pae Ae Nim , Han Sunkyu , Kim Seungtaek , Lee C. Justin 
Published: December 2020

AbstractAn ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to the global public health. Herbal medicines and their derived natural products have drawn much attention to treat COVID-19, but there has been no natural product showing inhibitory activity against SARS-CoV-2 infection with detailed mechanism. Here, we show that platycodin D (PD), a triterpenoid saponin abundant inPlatycodon grandiflorum(PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection-routes via lysosome- and transmembrane protease, serine 2 (TMPRSS2)-driven entry. Mechanistically, PD prevents host-entry of SARS-CoV-2 by redistributing membrane cholesterol to prevent membrane fusion, which can be reinstated by treatment with a PD-encapsulating agent. Furthermore, the inhibitory effects of PD are recapitulated by a pharmacological inhibition or gene-silencing ofNPC1, which is mutated in Niemann-Pick type C (NPC) patients displaying disrupted membrane cholesterol. Finally, readily available local foods or herbal medicines containing PG root show the similar inhibitory effects against SARS-CoV-2 infection. Our study proposes that PD is a potent natural product for preventing or treating COVID-19 and that a brief disruption of membrane cholesterol can be a novel therapeutic approach against SARS-CoV-2 infection.
Fitness selection of hyperfusogenic measles virus F proteins associated with neuropathogenic phenotypes
Authors: Ikegame Satoshi , Hashiguchi Takao , Hung Chuan-Tien , Dobrindt Kristina , Brennand Kristen J , Takeda Makoto , Lee Benhur 
Published: December 2020

AbstractMeasles virus (MeV) is resurgent and caused >200,000 deaths in 2019. MeV infection can establish a chronic latent infection of the brain that can recrudesce months to years after recovery from the primary infection. Recrudescent MeV leads to fatal subacute sclerosing panencephalitis (SSPE) or measles inclusion body encephalitis (MIBE) as the virus spreads across multiple brain regions. Most clinical isolates of SSPE/MIBE strains show mutations in the fusion (F) gene that result in a hyperfusogenic phenotypein vitroand allow for efficient spread in primary human neurons. Wild-type MeV receptor binding protein (RBP) is indispensable for manifesting these mutant F phenotypes, even though neurons lack canonical MeV receptors (CD150/SLAMF1 or Nectin-4). How such hyperfusogenic F mutants are selected for, and whether they confer a fitness advantage for efficient neuronal spread is unresolved. To better understand the fitness landscape that allows for the selection of such hyperfusogenic F mutants, we conducted a screen of ≥3.1×105MeV-F point mutants in their genomic context. We rescued and amplified our genomic MeV-F mutant libraries in BSR-T7 cells under conditions where MeV-F-T461I (a known SSPE mutant), but not wild-type MeV can spread. We recovered known SSPE mutants but also characterized at least 15 novel hyperfusogenic F mutations with a SSPE phenotype. Structural mapping of these mutants onto the pre-fusion MeV-F trimer confirm and extend our understanding of the fusion regulatory domains in MeV-F. Our list of hyperfusogenic F mutants is a valuable resource for future studies into MeV neuropathogenesis and the regulation of paramyxovirus fusion.SignificanceMeasles remains a major cause of infant death globally. On rare occasions, measles virus infection of the central nervous system (CNS) leads to a fatal progressive inflammation of the brain many years after the initial infection. MeV isolates from such CNS infections harbor fusion (F) protein mutations that result in a hyperfusogenic phenotype. The small number of hyperfusogenic MeV-F mutants identified thus far limits our ability to understand how these mutations are selected in the context of CNS infections. We performed a saturating mutagenesis screen of MeV-F to identify a large set of mutants that would mimic the hyperfusogenic phenotype of MeV-F in CNS infection. Characterization of these mutants shed light on other paramyxoviruses known to establish chronic CNS infections.
Multi-cellular communities are perturbed in the aging human brain and Alzheimer’s disease
Authors: Cain Anael , Taga Mariko , McCabe Cristin , Green Gilad , Hekselman Idan , White Charles C. , Lee Dylan I. , Gaur Pallavi , Rozenblatt-Rosen Orit , Zhang Feng , Yeger-Lotem Esti , Bennett David A. , Yang Hyun-Sik , Regev Aviv , Menon Vilas , Habib Naomi , De Jager Philip L. 
Published: December 2020

AbstractThe role of different cell types and their interactions in Alzheimer’s disease (AD) is an open question. Here we pursued it by assembling a high-resolution cellular map of the aging frontal cortex by single nucleus RNA-seq of 24 individuals with different clinicopathologic characteristics. We used the map to infer the neocortical cellular architecture of 638 individuals profiled by bulk RNA-seq, providing the sample size necessary for identifying statistically robust associations. We uncovered diverse cell populations associated with AD, including inhibitory neuronal subtypes and oligodendroglial states. We further recovered a network of multicellular communities, each composed of coordinated subpopulations of neuronal, glial and endothelial cells, and found that two of these communities are altered in AD. Finally, we used mediation analyses to prioritize cellular changes that might contribute to cognitive decline. Thus, our deconstruction of the aging neocortex provides a roadmap for evaluating the cellular microenvironments underlying AD and dementia.
Multiethnic Prediction of Nicotine Biomarkers and Association with Nicotine Dependence
Authors: Bergen Andrew W. , McMahan Christopher S. , McGee Stephen , Ervin Carolyn M. , Tindle Hilary A. , Marchand Loïc Le , Murphy Sharon E. , Stram Daniel O. , Patel Yesha M. , Park Sungshim L. , Baurley James W. 
Published: December 2020

ABSTRACTBackgroundThe nicotine metabolite ratio and nicotine equivalents are measures of metabolism rate and intake. Genome-wide prediction of these nicotine biomarkers will extend biomarker studies to cohorts without measured biomarkers and enable tobacco-related behavioral and exposure research.MethodsWe screened genetic variants genome-wide using marginal scans and applied statistical learning algorithms on top-ranked genetic variants and age, ethnicity and sex, and cigarettes per day (CPD) (in additional modeling) to build prediction models for the urinary nicotine metabolite ratio (uNMR) and creatinine-standardized total nicotine equivalents (TNE) in 2,239 current cigarette smokers in five ethnic groups. We predicted these nicotine biomarkers using model ensembles, and evaluated external validity using behavioral outcomes in 1,864 treatment-seeking smokers in two ethnic groups.ResultsThe genomic regions with the most selected and trained variants for measured biomarkers were chr19q13.2 (uNMR, without and with CPD) and chr15q25.1 and chr10q25.3 (TNE, without and with CPD). We observed ensemble correlations between measured and predicted biomarker values for the uNMR and TNE without (with CPD) of 0.67 (0.68), and 0.65 (0.72) in the training sample. We observed inconsistency in penalized regression models of TNE (with CPD) with fewer variants at chr15q25.1 selected and trained. In treatment-seeking smokers, predicted uNMR (without CPD) was significantly associated with CPD, and predicted TNE (without CPD) with CPD, Time-To-First-Cigarette, and Fagerström total score.ConclusionsNicotine metabolites, genome-wide data and statistical learning approaches develop novel robust predictive models for urinary nicotine biomarkers in multiple ethnic groups. Predicted biomarker associations help define genetically-influenced components of nicotine dependence.IMPLICATIONSWe demonstrate development of robust models and multiethnic prediction of the urinary nicotine metabolite ratio and total nicotine equivalents using statistical and machine learning approaches. Trained variants in models for both biomarkers include top-ranked variants in multiethnic genome-wide studies of smoking behavior, nicotine metabolites and related disease. Association of the two predicted nicotine biomarkers with Fagerstr□m Test for Nicotine Dependence items support models of nicotine biomarkers as predictors of physical dependence and nicotine exposure. Predicted nicotine biomarkers may facilitate tobacco-related disease and treatment research in samples with genomic data and limited nicotine metabolite or tobacco exposure data.
SARS-CoV-2 Testing in Florida, Illinois, and Maryland: Access and Barriers
Authors: Clipman Steven J. , Wesolowski Amy , Mehta Shruti H. , Agarwal Smisha , Cobey Sarah E. , Cummings Derek A.T. , Gibson Dustin G. , Labrique Alain B. , Kirk Gregory D. , Solomon Sunil S. 
Published: December 2020

AbstractObjectiveTo characterize the SARS-CoV-2 testing cascade and associated barriers in three US states.MethodsWe recruited participants from Florida, Illinois, and Maryland (∼1000/state) for an online survey September 16 – October 15, 2020. The survey covered demographics, COVID-19 symptoms, and experiences around SARS-CoV-2 PCR testing in the prior 2 weeks. Logistic regression was used to analyze associations with outcomes of interest.ResultsOverall, 316 (10%) of 3,058 respondents wanted/needed a test in the two weeks prior to the survey. Of these, 166 (53%) were able to get tested and 156 (94%) received results; 53% waited ≥ 8 days to get results from when they wanted/needed a test. There were no significant differences by state. Among those wanting/needing a test, getting tested was significantly less common among men (aOR: 0.46) and those reporting black race (aOR: 0.53) and more common in those reporting recent travel (aOR: 3.35).ConclusionsThere is an urgent need for a national communication strategy on who should get tested and where one can get tested. Additionally, measures need to be taken to improve access and reduce turn-around-time.
A Systematic Review of the Incubation Period of SARS-CoV-2: The Effects of Age, Biological Sex, and Location on Incubation Period
Authors: Daley Caitlin , Fydenkevez Megan , Ackerman-Morris Shari 
Published: December 2020

ABSTRACTA systematic review of the incubation period of COVID-19 was compiled and analyzed from 21 quantitative studies. We investigated the incubation period of COVID-19 with regard to age, biological sex, location, and severity of the disease. Based on the data extracted, we report an overall mean and median incubation period for SARS-CoV-2 of 5.894 days and 5.598 days, respectively. The incubation period did not statistically vary for biological sex or age, but some studies suggest a longer incubation period in the young and elderly. Cases of COVID-19 in Wuhan and Hubei Province of China may have a shorter incubation period for COVID-19 but the shorter incubation period may be due to an increase in viral load. In studying coronavirus strains such as SARS and MERS, researchers have discovered an inverse relationship between incubation period length and virus severity. Taking into consideration that SARS-CoV-2 is part of the beta-coronavirus family, as well as the study mentioned above, we suggest that people who experience more severe disease due to SARS-CoV-2 may have a shorter incubation period.
Selective Targeting of Ras Mutant Cancers via a New Small Molecule
Authors: Tolani Bhairavi , Celli Anna , Yao Yanmin , Tan Yong Zi , Fetter Richard , Liem Christina R. , de Smith Adam J. , Vasanthakumar Thamiya , Bisignano Paola , Seiple Ian B. , Rubinstetin John L. , Jost Marco , Weissman Jonathan S. 
Published: December 2020

ABSTRACTMutations in the Ras family of oncogenes are implicated in 33% of human cancers, making Ras an intensely pursued target in drug discovery. As an alternative to direct pharmacological inhibition of Ras, we looked for sensitivities in RAS mutant cells. Using a small molecule screen in cell lines with mutations in Ras and its effector Raf, we discovered 249C as a Ras-mutant selective cytotoxic agent against a spectrum of RAS-mutant cancers. By combining CRISPR chemical-genetic screening, comparative profiling and chemoproteomics, we identified that 249C binds to a unique subunit on vacuolar (V)-ATPase with nanomolar affinity, inhibiting its biochemical activity and, unexpectedly, altering V-ATPase translocation in Ras-induced macropinocytosis. Via binding to V-ATPase, 249C prevents lysosomal acidification and inhibits autophagy and macropinocytosis pathways that several Ras-driven cancers rely on for survival. In characterizing 249C’s mechanism, we show that potency varies with the identity of the RAS driver mutation highlighting a mutant-specific dependence on autophagy and macropinocytosis. Indeed, 249C potently inhibits tumor growth without adverse side effects in a mouse xenograft model ofKRAS-driven non-small cell lung cancer. These data establish proof-of-concept for targeting V-ATPase as a way to indirectly target specific Ras mutants, and provide a fundamental link between V-ATPase localization and specific Ras mutant tumor-related activity.
Partial spontaneous intersubunit rotations in actively translating ribosomes
Authors: Huang Tianhan , Choi Junhong , Prabhakar Arjun , Puglisi Joseph , Petrov Alexey 
Published: December 2020

SummaryThe ribosome is a molecular machine that adopts at least two global states during translation. Two main steps of translation, peptidyl transfer and translocation, are accompanied by counterclockwise and clockwise rotations of the two ribosomal subunits. However, when and why the ribosome alternates between these states remains unclear, with two well supported but conflicting hypotheses. Ribosomes may undergo a single cycle of forward and backward rotations per codon read. Alternatively, in addition to rotations caused by peptidyl transfer and translocation, ribosomes may undergo multiple full spontaneous rotations, with these rotations playing a critical role in elongation and specifically in translocation mechanism. We applied high-speed single-molecule TIRF microscopy to follow translation in real-time. Actively translating ribosomes undergopartialspontaneous rotations between three different rotational states. Spontaneous rotations are restricted prior to A-site tRNA decoding. Peptidyl transfer unlocks spontaneous rotations. Consequently, translocation proceeds via a novel rotational state induced by EF-G. Our results bridge both models and provide a coherent view of ribosome dynamics during translation.