bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of undetected COVID-19 infections in India
Authors: Mukhopadhyay Siuli , Chakraborty Debraj 
Published: April 2020

Background and ObjectivesWhile the number of detected COVID-19 infections are widely available, an understanding of the extent of undetected COVID-19 cases is urgently needed for an effective tackling of the pandemic and as a guide to lifting the lockdown. The aim of this work is to estimate and predict the true number of COVID-19 (detected and undetected) infections in India for short to medium forecast horizons. In particular, using publicly available COVID-19 infection data up to 28th April 2020, we forecast the true number of infections in India till the end of lockdown (3rd May) and five days beyond (8th May).MethodsThe high death rate observed in most COVID-19 hit countries is suspected to be a function of the undetected infections existing in the population. An estimate of the age weighted infection fatality rate (IFR) of the disease of 0.41%, specifically calculated by taking into account the age structure of Indian population, is already available in the literature. In addition, the recorded case fatality rate (CFR= 1%) of Kerala, the first state in India to successfully flatten the curve by consistently reporting single digit new infections from 12-20 April, is used as a second estimate of the IFR. These estimates are used to formulate a relationship between deaths recorded and the true number of infections and recoveries. The estimated undetected and detected cases time series based on these two IFR estimates are then used to fit a discrete time multivariate infection model to predict the total infections at the end of the formal lockdown period.ResultsOver three consecutive fortnight periods during the lockdown, it was noted that the rise in detected infections has decreased by 8.2 times. For an IFR of 0.41%, the rise in undetected infections decreased 2.5 times, while for the higher IFR value of 1%, undetected cases decreased by 2.4 times. The predicted number of total infections in India on 3rd May for both IFRs varied from 2.8 - 6.8 lakhs.Interpretation and ConclusionsThe behaviour of the undetected cases over time effectively illustrates the effects of lockdown and increased testing. From our estimates, it is found that the lockdown has brought down the undetected to detected cases ratio, and has consequently dampened the increase in the number of total cases. However, even though the rate of rise in total infections has fallen, the lifting of the lockdown should be done keeping in mind that 2.3 to 6.4 lakhs undetected cases will already exist in the population by 3rd May.
Clinical features of coronavirus disease 2019 (COVID-19) in a cohort of patients with disability due to spinal cord injury
Authors: Rodríguez-Cola Miguel , Jiménez-Velasco Irena , Gutiérrez-Henares Francisco , López-Dolado Elisa , Gambarrutta-Malfatti Claudia , Vargas-Baquero Eduardo , Gil-Agudo Ángel 
Published: April 2020

ABSTRACTStudy designCohort study of patients with spinal cord injury (SCI)ObjectivesTo describe the clinical and analytical features of a Covid-19 infected cohort with SCI to contribute new knowledge for a more accurate diagnosis and to outline prevention measures.SettingThis study was conducted at the National Hospital for Paraplegics (Toledo, Spain).MethodsA cohort analysis of seven patients with SCI infected by Covid-19 was carried out. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical and radiographic findings were registered.ResultsRT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (5 out 7). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (6 out of 7). The second most common symptom was asthenia (4 out of 7), followed by dyspnea, cough and expectoration (3 out of 7 for each symptom). The MEWS score for Covid-19 severity rating was classified as severe in 5 out of 7. All but one patient showed radiological alterations evident in chest X-Rays at the time of diagnosis. All patients recovered gradually.ConclusionOur patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.
Characterization of a high-resolution breath acetone meter for ketosis monitoring
Authors: Suntrup Donald J. , Ratto Timothy V. , Ratto Matt , McCarter James P. 
Published: April 2020

ABSTRACTBackgroundThe ketone bodies beta-hydroxybutyrate (BHB) and acetone are endogenous products of fatty acid metabolism. Although ketone levels can be monitored by measuring either blood BHB or breath acetone, determining the precise correlation between these two measurement methods has been challenging. The purpose of this study is to characterize the performance of a novel portable breath acetone meter (PBAM) developed by Readout, Inc., to compare single versus multiple daily ketone measurements, and to compare breath acetone (BrAce) and blood BHB measurements.MethodsWe conducted a 14-day prospective observational cohort study of 21 subjects attempting to follow either a low-carbohydrate/ketogenic or a standard diet. Subjects were asked to concurrently measure both blood BHB and BrAce five times per day and report the results using an online data entry system. We evaluated the utility of multiple daily measurements by calculating the coefficient of variation (CV) for each daily group of measurements. We calculated the correlation between coincident BrAce and blood BHB measurements using linear ordinary least squares regression analysis. We assessed the ability of the BrAce measurement to accurately predict blood BHB states using receiver operating characteristic (ROC) analysis. Finally, we calculated a daily ketone exposure (DKE) using the area under the curve (AUC) of a ketone concentration versus time graph and compared the DKE of BrAce and blood BHB using linear ordinary least squares regression.ResultsBrAce and blood BHB varied throughout the day by an average of 44% and 46%, respectively. The BrAce measurement accurately predicted whether blood BHB was greater than or less than the following thresholds: 0.3 mM (AUC = 0.898), 0.5 mM (AUC = 0.854), 1.0 mM (AUC = 0.887), and 1.5 mM (AUC = 0.935). Coincident BrAce and blood BHB measurements were moderately correlated withR2= 0.57 (P< 0.0001), similar to literature reported values. However, daily ketone exposures, or areas under the curve, for BrAce and blood BHB were highly correlated withR2= 0.83 (P< 0.0001).ConclusionsThe results validated the performance of the PBAM. The BrAce/BHB correlation was similar to literature values where BrAce was measured using highly accurate lab instruments. Additionally, BrAce measurements using the PBAM can be used to predict blood BHB states. The relatively high daily variability of ketone levels indicate that single blood or breath ketone measurements are often not sufficient to assess daily ketone exposure for most users. Finally, although single coincident blood and breath ketone measurements show only a moderate correlation, possibly due to the temporal lag between BrAce and blood BHB, daily ketone exposures for blood and breath are highly correlated.
Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries
Authors: Delatorre Edson , Mir Daiana , Gräf Tiago , Bello Gonzalo 
Published: April 2020

ABSTRACTThe SARS-CoV-2 rapidly spread around the world during 2020, but the precise time in which the virus began to spread locally is currently unknown for most countries. Here, we estimate the probable onset date of the community spread of SARS-CoV-2 from the cumulative number of deaths reported during the early stage of the epidemic in Western Europe and the Americas. Our results support that SARS-CoV-2 probably started to spread locally in all western countries analyzed between the middle of January and early February 2020, thus long before community transmission was officially recognized and control measures were implemented.
Measuring Icebergs: Using Different Methods to Estimate the Number of COVID-19 Cases in Portugal and Spain
Authors: Baquero Carlos , Casari Paolo , Anta Antonio Fernández , Frey Davide , Garcia-Agundez Augusto , Georgiou Chryssis , Menezes Raquel , Nicolaou Nicolas , Ojo Oluwasegun , Patras Paul 
Published: April 2020

AbstractThe world is suffering from a pandemic called COVID-19, caused by the SARS-CoV-2 virus. The different national governments have problems evaluating the reach of the epidemic, having limited resources and tests at their disposal. Hence, any means to evaluate the number of persons with symptoms compatible with COVID-19 with reasonable level of accuracy is useful. In this paper we present the initial results of the @CoronaSurveys project. The objective of this project is the collection and publication of data concerning the number of people that show symptoms compatible with COVID-19 in different countries using open anonymous surveys. While this data may be biased, we conjecture that it is still useful to estimate the number of infected persons with the COVID-19 virus at a given point in time in these countries, and the evolution of this number over time. We show here the initial results of the @CoronaSurveys project in Spain and Portugal.
Detection of Tuberculosis by The Analysis of Exhaled Breath Particles with High-resolution Mass Spectrometry
Authors: Chen Dapeng , Bryden Wayne A. , Wood Robin 
Published: April 2020

AbstractTuberculosis remains a global health threat killing over 1 million peopleperyear. Current sputum-based diagnostics are specific but lack sensitivity resulting in treatment of many sputum negative cases. In this proof-of-concept study, we used high-resolution mass spectrometry to identify specific lipids in peripheral lung fluid samples of TB patients and controls, captured using a novel non-invasive sampling system. Exhaled respiratory particles were collected in liquid and after concentration and lipid extraction directly infused into a high-resolution mass spectrometer. High-resolution mass spectrometric data collection was conducted in a dual ion mode and chemical compositions were constructed using accurate mass measurement. Over 400 features with high segregating capacity were extracted and optimized using feature selection algorithm and machine learning, from which the accuracy of detection of positive tuberculosis patients was estimated. This current strategy provides sensitivity offered by high-resolution mass spectrometry and can be readily susceptible for developing a novel clinical assay exploring peripheral lung fluid for the detection of active TB cases.
Convergent evolution of p38/MAPK activation in hormone resistant prostate cancer mediates pro-survival, immune evasive, and metastatic phenotypes
Authors: Ware Kathryn E. , Gupta Santosh , Eng Jared , Kemeny Gabor , Puviindran Bhairavy J. , Foo Wen-Chi , Crawford Lorin A. , Garland Almquist R. , Runyambo Daniella , Thomas Beatrice C. , Sheth Maya U. , Agarwal Anika , Pierobon Mariaelena , Petricoin Emanuel F. , Corcoran David L. , Freedman Jennifer , Patierno Steven R. , Zhang Tian , Gregory Simon , Sychev Zoi , Drake Justin M. , Armstrong Andrew J. , Somarelli Jason A. 
Published: April 2020

SummaryAdaptation of cancer cells to targeted therapy follows ecological paradigms observed in natural populations that encounter resource depletion and changing environments, including activation of pro-survival mechanisms, migration to new locations, and escape of predation. We identified the p38 MAPK pathway as a common molecular driver of these three responses during the adaptation to hormone therapy resistance in prostate cancer. The p38 pathway is activated in therapy-resistant cells and mechanistically drives these three convergent responses through sustained AR activity, enhanced invasion and metastasis, and immune evasion. Targeting p38 signaling may represent a new therapeutic strategy to treat men with metastatic, hormone therapy-resistant prostate cancer.
Anti-EGFR Fibronectin Bispecific Chemically Self-Assembling Nanorings (CSANs) Induce Potent T cell Mediated Anti-Tumor Response and Downregulation of EGFR Signaling and PD-1/PD-L1 Expression
Authors: Kilic Ozgun , de Souza Marcos R. Matos , Almotlak Abdulaziz A. , Siegfried Jill M. , Wagner Carston R. 
Published: April 2020

ABSTRACTNumerous approaches have targeted the Epidermal Growth Factor Receptor (EGFR) for the development of anti-cancer therapeutics, since it is over-expressed on a variety of cancers. Recently, αEGFR chimeric antigen receptor (CAR)-T cells have shown potential promise for the immunological control of tumors. Our laboratory has recently demonstrated that bispecific chemically self-assembled nanorings (CSANs) can modify T cell surfaces and function as prosthetic antigen receptors (PARs). This technology allows selective targeting of tumor antigens due to high avidity of the multimeric rings, while incorporating a mechanism to dissociate the rings to prevent further T cell stimulation. Previously, PARs with single-chain variable fragments (scFvs) have been successfulin vitroandin vivo, activating T cells selectively at the tumor site. Alternatively, here we report fibronectin (FN3)-based PARs with improved properties such as increased protein yield, rapid protein production, increased protein stability and predicted low immunogenicity due to the human origin of fibronectins. We examined the cytotoxicity of EGFR-targeting PARsin vitroin which the affinities of the αEGFR fibronectins, the αEGFR/ αCD3 valency of the CSANs and the antigen expression levels were varied. Based on these selectivein vitrocytotoxicity results, we conducted anin vivostudy of FN3-PARs using an orthotopic breast cancer model. The FN3-PARs demonstrated potent tumor growth suppression with no adverse effects. Furthermore, these results demonstrated that FN3-PARs modulated the tumor microenvironment by downregulating EGFR signaling resulting in decreased PD-L1 expression. In addition, the expression of PD-1 was also found to be reduced. Collectively, these results demonstrate that FN3-PARs have the potential to direct selective T cell targeted tumor killing and that αEGFR FN3-PARs may enhance anti-tumor T cell efficacy by modulating the tumor microenvironment.
Tension causes structural unfolding of intracellular intermediate filaments
Authors: Fleissner Frederik , Kumar Sachin , Klein Noreen , Wirth Daniel , Dhiman Ravi , Schneider Dirk , Bonn Mischa , Parekh Sapun H. 
Published: April 2020

AbstractIntermediate filament (IF) proteins are a class of proteins that constitute different filamentous structures in mammalian cells. As such, IF proteins are part of the load-bearing cytoskeleton and support the nuclear envelope. Molecular dynamics simulations have shown that IF proteins undergo secondary structural changes to compensate mechanical loads, which has been confirmed by experimentalin vitrostudies on IF hydrogels. However, the structural response of intracellular IF to mechanical load has yet to be elucidatedin cellulo. Here, we usein situnonlinear Raman imaging combined with multivariate data analysis to quantify the intracellular secondary structure of the IF cytoskeletal protein vimentin under different states of cellular tension. We find that cells under native cellular tension contain more unfolded vimentin than chemically or physically relaxed specimens. This indicates that unfolding of IF proteins occurs intracellularly when sufficient forces are applied, suggesting that IF structures act as local force sensors in the cell to mark locations under large mechanical tension.
Local adaptation ofLegionella pneumophilawithin a hospital hot water system increases tolerance to copper
Authors: Bédard Emilie , Trigui Hana , Liang Jeffrey , Doberva Margot , Paranjape Kiran , Lalancette Cindy , Faucher Sebastien P. , Prévost Michèle 
Published: April 2020

AbstractIn large-building water systems,Legionella pneumophilais exposed to common environmental stressors such as copper. The aim of this study was to evaluate the susceptibility to copper ofL. pneumophilaisolates recovered from various sites: two clinical and seven environmental from hot water systems biofilm & water, and from cooling tower water. After one-week acclimation in simulated drinking water, strains were exposed to various copper concentrations (0.8 to 5 mg/L) for over 672 hours. Complete loss of culturability was observed for three isolates, following copper exposure to 5 mg/L for 672h. Two ST1427-like isolates were highly sensitive to copper, while the other two, isolated from biofilm samples, were resistant. The expression of the copper resistance genecopAevaluated by RT-qPCR was significantly higher for the biofilm isolates. All four ST1427-like isolates were recovered from the same water system during an outbreak. Whole genome sequencing results confirmed that the four isolates are very close phylogenetically, differing by only 29 single nucleotide polymorphisms, suggestingin situadaptation to microenvironmental conditions, possibly due to epigenetic regulation. These results indicate that the immediate environment within a building water distribution system influences the tolerance ofL. pneumophilato copper. Increased contact ofL. pneumophilabiofilm strains with copper piping or copper alloys in the heat exchanger might lead to local adaptation. The phenotypic differences observed between water and biofilm isolates from the hot water system of a healthcare facility warrants further investigation to assess the relevance of evaluating disinfection performances based on water sampling alone.ImportanceLegionella pneumophilais a pathogen indigenous to natural and large building water systems in the bulk and the biofilm phases. The immediate environment within a system can impact the tolerance ofL. pneumophilato environmental stressors, including copper. In healthcare facilities, copper levels in water can vary, depending on water quality, plumbing materials and age. This study evaluated the impact of the isolation site (water vs biofilm, hot water system vs cooling tower) within building water systems. Closely related strains isolated from a healthcare facility hot water system exhibited variable tolerance to copper stress shown by differential expression ofcopA, with biofilm isolates displaying highest expression and tolerance. Relying on the detection ofL. pneumophilain water samples following exposure to environmental stressor such as copper may underestimate the prevalence ofL. pneumophila, leading to inappropriate risk management strategies and increasing the risk of exposure for vulnerable patients.
Area-specific Biased Global Efficiency in Functional Connectivity Provides Features Negatively Correlated with Age
Authors: Akama Hiroyuki , Ota Airi 
Published: April 2020

AbstractIt has been acknowledged that graph-theoretical coefficients computed from the adjacency matrix of cerebral resting-state functional connectivity (RSFC) represent aging of the brain and its plasticity facilitating cognitive reserve. In particular, global efficiency (GE) has been recognized as a crucial graph index for age-dependent RSFC. Using the dataset of the Nathan Kline Institute-Rockland Sample [NKI-RS], we found that the regions of the brain in which GE values decay with age were located in the subcortical zone and the cerebellum, whereas an opposite relationship was found in many frontal and parietal regions. Based on this systematic tendency, a new coefficient was proposed that corrects GE, referred to as biased GE (BGE); BGE is calculated by changing the sign of the weight between the superior and the inferior parts of the brain before separately averaging the respective sign groups of area-specific corrected GE values, to influence the raw global network GE. The BGE showed a significant negative correlation with age, irrespective of the scan condition, and strong consistency as an information source of a subject’s identity. We propose that this new index could play an important role in the clinical context of preventive medicine and the maintenance of healthy brains.
Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3
Authors: Finogenova Ksenia , Bonnet Jacques , Poepsel Simon , Schäfer Ingmar B. , Finkl Katja , Schmid Katharina , Litz Claudia , Strauss Mike , Benda Christian , Müller Jürg 
Published: April 2020

ABSTRACTRepression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and trimethylated H3K36 inhibit PRC2. Here, the cryo-EM structure of PRC2 on dinucleosomes reveals how binding of its catalytic subunit EZH2 to nucleosomal DNA orients the H3 N-terminus via an extended network of interactions to place H3K27 into the active site. Unmodified H3K36 occupies a critical position in the EZH2-DNA interface. Mutation of H3K36 to arginine or alanine inhibits H3K27 methylation by PRC2 on nucleosomesin vitro. Accordingly,DrosophilaH3K36A and H3K36R mutants show reduced levels of H3K27me3 and defective Polycomb repression of HOX genes. The relay of interactions between EZH2, the nucleosomal DNA and the H3 N-terminus therefore creates the geometry that permits allosteric inhibition of PRC2 by methylated H3K36 in transcriptionally active chromatin.
Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis
Authors: Powell Victoria , Martin Joanna , Thapar Anita , Rice Frances , Anney Richard J. L. 
Published: April 2020

AbstractAttention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p=5×10−8) SNPs in the meta-analysis that were also strongly associated (p=5×10−4) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were identified that were associated with each disorder separately (p=5×10−4) and in the cross-disorder meta-analysis (p=5×10−8). Nine of these SNPs had not been reported previously in either individual GWAS and can be considered as novel signals. Evidence supported nine of the fourteen SNPs acting as eQTL and two of the SNPs as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel regions of the genome that may be implicated in this overlap.