bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data Driven Monitoring in Community Based Management of SAM children using Psychometric Techniques: An Operational Framework
Authors: Joshi Ankur , Pakhare Abhijit P , Nair Sivaja K , Revadi G , Chouhan Manoj , Pandey Deepak , Kokane Arun M 
Published: June 2021

AbstractBackgroundThe success of the Community Based Management of Severe Malnutrition (CSAM)programme, largely depends on the knowledge and skills of Front-Line Workers (FLWs).A robust supportive supervision system in CSAM should be tailored to individualistic learning needs by distinguishing the FLWs as per their ability and simultaneously identifying the task domains to be emphasized more in supervisory visits.This paper details the ability assessment strategy developed and employed in the selected geographical locations in state of Madhya Pradesh (Central India) among the 197 Anganwadi workers (FLWs involved in CSAM implementation)MethodologyA 25 items tool was developed based on an analytical construct for ability estimation through Rasch Analysis (RA). RA models the probability of right/wrong answer as a function of person(participants) and item (questions) parameters and calculates the item difficulty in relation with person ability on same unidimensional linear scale. The fitting of the data to Rasch model (Rasch diagnostic) was tested by both numeric (Anderson LR and Wald test) and graphical method. Suitable visualization like Item Characteristic Curve (ICC) and Person Item Map (PIM) were plotted in RA.Further a quadratic allocation of all AWWs into 4 quadrants were done as per the ability estimation (Rasch score) and adjusted numbers of SAM/MAM children in her center.ResultsThe item easiness parameter (β) value related to Diarrhoeal assessment was lowest (−2.32, -2.91 to -1.73) and related to peer assessment consequential action (2.009, 1.669-2.348)) was highest (most difficult). Anderson LR test (LR=31.32, df=24, p=0.079) showed the absence of global outliers. Quadrant analysis using the permutations of ability score and adjusted burden of malnutrition further mapped 41/197 (20.8%) FLWs to low ability -high burden quadrant and 44/197(25%) as low ability low burden quadrant.ConclusionRASCH assessment may address the innate challenges to maintain homogeneity, discrimination capacity and linearity in a raw score-based measurement construct. The monitoring strategy developed on this thus may offer a judicious, pragmatic and thematic approach to supportive supervision in CSAM program.
Stable IgG-antibody levels in patients with mild SARS-CoV-2 infection
Authors: Åkerlund Thomas , Zakikhany Katherina , Löfström Charlotta , Lindmark Evelina , Källberg Henrik , Elofsson Ulla , Cederbrant Karin , Nygren Erik , Kallin Anders , Lagerqvist Nina , Nilsson Peter , Hober Sophia , Wollberg Anna Ridderstad , Björndal Åsa Szekely 
Published: June 2021

AbstractMore knowledge regarding persistence of antibody response to SARS-CoV-2 infections in the general population with mild symptoms is needed. We measured and compared levels of SARS-CoV-2 spike- and nucleocapsid-specific IgG-antibodies in serum samples from 145 laboratory-confirmed COVID-19 cases and 324 non-cases. The IgG-antibody levels against the spike protein in cases were stable over the time-period studied (14 to 256 days), while antibody levels against the nucleocapsid protein decreased over time.
Prevalence of different sleep problems in patients with respiratory diseases presented to a respiratory outdoor clinic: A Descriptive analysis
Authors: Haldar Arup Kumar , Chatterjee Arpita Halder 
Published: June 2021

AbstractIntroductionA patient with compromised respiratory system due to some diseases, may have disturbed sleep to a great extent. It has been proved in various community based epidemiologic studies. Though most of such studies available had concentrated on single respiratory disease like COPD or Asthma in the community. But such studies are hardly available for patients attending a respiratory clinic, where all respiratory ailments were evaluated with concurrent sleep problems. The present study is one such.MethodsTotal 163 patients were screened and among them 100 were selected as the study group. The patients were enquired with a standard questionnaire provided to them. In addition, they were given seperate questionnaire as STOP BANG, Insomnia Severity Index Score, RLS questionnaire. Those persons with STOP BANG > 5, were also advised for a Polysomnography (PSG), if not already done. Descriptive statistical analysis has been carried out in the present study.ResultsThe present study is a cross-sectional depiction of relationships between various respiratory diseases and sleep problems. As per this study, most patients were asthmatic and commonest sleep problem was OSA. A subgroup analysis was done to determine the significance of difference of various parameters between the three groups of asthmatic patients, patients having COPD and the ‘Other’ group.DiscussionSubjective sleep problems were significantly more in Asthma group than COPD group (p<0.0362). The mean STOP BANG was more in COPD group than the Asthma group (p<0.0301). Though OSA was the commonest sleep problem between the three groups, but the prevalence was not statistically significant between them. More patients in the COPD group had insomnia, but it was not statistically significantly more than in Asthma group. Sleeping pill use was significantly more in COPD group than the Asthma group (p<0.0039).ConclusionSleep problems are common in patients with respiratory diseases and OSA is the most common problem according to the present study. Asthma patients had more subjective sleep problems. Sleeping pill use is more common in COPD patients instead of having less subjective sleep complaints than asthma patients.
An Extended Susceptible-Exposed-Infected-Recovered (SEIR) Model with Vaccination for Predicting the COVID-19 Pandemic in Sri Lanka
Authors: Rajapaksha R. M. Nayani Umesha , Wijesinghe Millawage Supun Dilara , Thomas Toms K. , Jayasooriya Sujith P. , Gunawardana B. M. W. Indika , Weerasinghe W. M. Prasad Chathuranga , Bhakta Shalini , Assefa Yibeltal 
Published: June 2021

AbstractThe role of modelling in predicting the spread of an epidemic is important for health planning and policies. This study aimed to apply a compartmental model for predicting the variations of epidemiological parameters in Sri Lanka. We used a dynamic Susceptible-Exposed-Infected-Recovered-Vaccinated (SEIRV) model and simulated potential vaccine strategies under a range of epidemic conditions. The predictions were based on different vaccination coverages (5% to 90%), vaccination-rates (1%, 2%, 5%) and vaccine-efficacies (40%, 60%, 80%) under different R0 (2,4,6). We estimated the duration, exposed, and infected populations. When the R0 was increased, the days of reduction of susceptibility and the days to reach the peak of the infection were reduced gradually. At least 45% vaccine coverage is required for reducing the infected population to mitigate a disastrous situation in Sri Lanka. The results revealed that when R0 is increased in the SEIRV model along with the increase of vaccination efficacy and vaccination rate, the population to be vaccinated is reducing. Thus, the vaccination offers greater benefits to the local population by reducing the time to reach the peak, exposed and infected population through flattening the curves.
COVID-19 Vaccine Coverage Index: Identifying barriers to COVID-19 vaccine uptake across U.S. counties
Authors: Mishra Anubhuti , Sutermaster Staci , Smittenaar Peter , Stewart Nicholas , Sgaier Sema K. 
Published: June 2021

AbstractImportanceThe United States is in a race against time to vaccinate its population to contain the COVID-19 pandemic. With limited resources, a proactive, targeted effort is needed to reach widespread community immunity.ObjectiveIdentify county-level barriers to achieving rapid COVID-19 vaccine coverage and validate the index against vaccine rollout data.DesignEcological studySettingPopulation-basedParticipantsLongitudinal COVID-19 vaccination coverage data for 50 states and the District of Columbia and 3118 counties from January 12 through May 25, 2021.Exposure(s)The COVID-19 Vaccine Coverage index (CVAC) ranks states and counties on barriers to coverage through 28 indicators across 5 themes: historic undervaccination, sociodemographic barriers, resource-constrained health system, healthcare accessibility barriers, and irregular care-seeking behaviors. A score of 0 indicates the lowest level of concern, whereas a score of 1 indicates the highest level of concern.Main Outcome(s) and Measure(s)State-level vaccine administrations from January 12 through May 25, 2021, provided by the Centers for Disease Control and Prevention (CDC) and Our World In Data. County-level vaccine coverage as of May 25, 2021, provided by the CDC.ResultsAs of May 25, 2021, the CVAC strongly correlated with the percentage of population fully vaccinated against COVID-19 by county (r = -0.39, p=2.2×10−16) and state (r=-0.77, p=4.9×10−11). Low-concern states and counties have fully vaccinated 26.5% [t=6.8, p=1.7×10−7] and 26% (t=22.0, p=2.2×10−16) more people, respectively, compared to their high-concern counterparts. This vaccination gap is at its highest point since the start of vaccination and continues to grow. Higher concern on each of the five themes predicts a lower rate of vaccination at the county level (all p<.001). We identify five types of counties with distinct barrier profiles.Conclusions and RelevanceThe CVAC measures underlying barriers to vaccination and is strongly associated with the speed of rollout. As the coverage gap between high- and low-concern regions continues to grow, the CVAC can inform a precision public health response targeted to underlying barriers.Key PointsQuestionWhich U.S. counties face barriers to COVID-19 vaccine rollout, and are these communities vaccinating fewer individuals?FindingsThe COVID-19 Vaccine Coverage Index (CVAC) comprises five themes reflecting county-level concern for low coverage. We report rural, regional, and racial divides in exposure to these vaccination barriers. The top third of states and counties of highest concern have vaccinated 19% and 20% fewer people, respectively, compared to regions of least concern.MeaningThe CVAC can help contextualize progress to widespread COVID-19 vaccine coverage, identifying underlying community-level factors that could be driving suboptimal rollout to inform precision solutions.
No evidence of SARS-CoV-2 infection in Neotropical Primates sampled during COVID-19 pandemic in Minas Gerais and Rio Grande do Sul, Brazil
Authors: Abreu Filipe Vieira Santos de , Macedo Mariana Viana , Silva Alex Junio Jardim da , Oliveira Cirilo Henrique de , Ottone Vinícius de Oliveira , Almeida Marco Antônio Barreto de , Santos Edmilson dos , Cardoso Jader da Cruz , Campos Aline Scarpellini , Silva Claudia Maria Dornelles da , Silva Amanda Gonzales da , Andrade Miguel de Souza , Bernis Valéria Magro Octaviano , Bernis Filho Walter Octaviano , Trindade Giliane de Souza , Albuquerque George Rego , Sevá Anaiá da Paixão , Ribeiro Bergmann Morais , Teixeira Danilo Simonini , Campos Fabrício Souza , Franco Ana Cláudia , Roehe Paulo Michel , Oliveira Danilo Bretas de 
Published: June 2021

AbstractIn 2019, a new coronavirus disease (COVID-19) was detected in China. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was capable to infect domestic and captive mammals like cats, tigers and minks. Due to genetic similarities, concern about the infection of Non-Human Primates (NHPs) and the establishment of a sylvatic cycle has grown in the Americas. In this study, neotropical primates (NP) were sampled in different areas from Brazil to investigate whether they were infected by SARS-CoV-2. A total of 89 samples from 51 NP of four species were examined. No positive samples were detected via RT-qPCR, regardless of the NHP species, tissue or habitat tested. This work provides the first report on the lack of evidence of circulation of SARS-CoV-2 in NP. The expand of wild animals sampling is necessary to understand their role in the epidemiology of SARS-CoV-2.
Neural Regression, Representational Similarity, Model Zoology & Neural Taskonomy at Scale in Rodent Visual Cortex
Authors: Conwell Colin , Mayo David , Buice Michael A. , Katz Boris , Alvarez George A. , Barbu Andrei 
Published: June 2021

AbstractHow well do deep neural networks fare as models of mouse visual cortex? A majority of research to date suggests results far more mixed than those produced in the modeling of primate visual cortex. Here, we perform a large-scale benchmarking of dozens of deep neural network models in mouse visual cortex with both representational similarity analysis and neural regression. Using the Allen Brain Observatory’s 2-photon calcium-imaging dataset of activity in over 6,000 reliable rodent visual cortical neurons recorded in response to natural scenes, we replicate previous findings and resolve previous discrepancies, ultimately demonstrating that modern neural networks can in fact be used to explain activity in the mouse visual cortex to a more reasonable degree than previously suggested. Using our benchmark as an atlas, we offer preliminary answers to overarching questions about levels of analysis (e.g. do models that better predict the representations of individual neurons also predict representational similarity across neural populations?); questions about the properties of models that best predict the visual system overall (e.g. is convolution or category-supervision necessary to better predict neural activity?); and questions about the mapping between biological and artificial representations (e.g. does the information processing hierarchy in deep nets match the anatomical hierarchy of mouse visual cortex?). Along the way, we catalogue a number of models (including vision transformers, MLP-Mixers, normalization free networks, Taskonomy encoders and self-supervised models) outside the traditional circuit of convolutional object recognition. Taken together, our results provide a reference point for future ventures in the deep neural network modeling of mouse visual cortex, hinting at novel combinations of mapping method, architecture, and task to more fully characterize the computational motifs of visual representation in a species so central to neuroscience, but with a perceptual physiology and ecology markedly different from the ones we study in primates.
Single-molecule, full-length transcript isoform sequencing reveals disease mutation-associated RNA isoforms in cardiomyocytes
Authors: Zhu Chenchen , Wu Jingyan , Sun Han , Briganti Francesca , Meder Benjamin , Wei Wu , Steinmetz Lars M. 
Published: June 2021

AbstractAlternative splicing generates differing RNA isoforms that govern phenotypic complexity of eukaryotes. Its malfunction underlies many diseases, including cancer and cardiovascular diseases. Comparative analysis of RNA isoforms at the genome-wide scale has been difficult. Here, we established an experimental and computational pipeline that performs de novo transcript annotation and accurately quantifies transcript isoforms from cDNA sequences with a full-length isoform detection accuracy of 97.6%. We generated a searchable, quantitative human transcriptome annotation with 31,025 known and 5,740 novel transcript isoforms (http://steinmetzlab.embl.de/iBrowser/). By analyzing the isoforms in the presence of RNA Binding Motif Protein 20 (RBM20) mutations associated with aggressive dilated cardiomyopathy (DCM), we identified 121 differentially expressed transcript isoforms in 107 cardiac genes. Our approach enables quantitative dissection of complex transcript architecture instead of mere identification of inclusion or exclusion of individual exons, as exemplified by novel IMMT isoforms. Thereby we achieve a path to direct differential expression testing independent of an existing annotation of transcript isoforms as the functional unit, instead of genes or exons, providing more immediate biological interpretation and higher resolution transcriptome comparisons.
Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2
Authors: Liang Yu , Zhang Jing , Yuan Run Yu , Wang Mei Yu , He Peng , Su Ji Guo , Han Zi Bo , Jin Yu Qin , Hou Jun Wei , Zhang Hao , Zhang Xue Feng , Shao Shuai , Hou Ya Nan , Liu Zhao Ming , Du Li Fang , Shen Fu Jie , Zhou Wei Min , Tang Fang , Lei Ze Hua , Liu Shuo , Zhen Wei , Wu Jin Juan , Zheng Xiang , Liu Ning , Chen Shi , Ma Zhi Jing , Zheng Fan , Ren Si Yu , Hu Zhong Yu , Wu Gui Zhen , Huang Wei Jin , Ke Chang Wen , Li Qi Ming 
Published: June 2021

AbstractThe spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the “immune-escape” Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.
Higher order phosphatase-substrate contacts terminate the Integrated Stress Response
Authors: Yan Yahui , Harding Heather P. , Ron David 
Published: June 2021

ABSTRACTMany regulatory PPP1R subunits join few catalytic PP1c subunits to mediate phosphoserine and phosphothreonine dephosphorylation in metazoans. Regulatory subunits are known to engage PP1c’s surface, locally affecting flexible phosphopeptides access to the active site. However, catalytic efficiency of holophosphatases towards their natively-folded phosphoprotein substrates is largely unexplained. Here we present a Cryo-EM structure of the tripartite PP1c/PPP1R15A/G-actin holophosphatase that terminates signalling in the Integrated Stress Response (ISR) in pre-dephosphorylation complex with its substrate, translation initiation factor 2α (eIF2α). G-actin’s role in eIF2α dephosphorylation is supported crystallographically by the structure of the binary PPP1R15A-G-actin complex, and by biochemical and genetic confirmation of the essential role of PPP1R15A-G-actin contacts to eIF2αP dephosphorylation. In the pre-dephosphorylation CryoEM complex, G-actin aligns the catalytic and regulatory subunits, creating a composite surface that engages eIF2α’s N-terminal domain to position the distant phosphoserine-51 at the active site. eIF2α residues specifying affinity for the holophosphatase are confirmed here to make critical contacts with the eIF2α kinase PERK. Thus, a convergent process of higher-order substrate recognition specifies functionally-antagonistic phosphorylation and dephosphorylation in the ISR.
Persistent DNA Repair Signaling and DNA Polymerase Theta Promote Broken Chromosome Segregation
Authors: Clay Delisa E. , Bretscher Heidi S. , Jezuit Erin A. , Bush Korie B. , Fox Donald T. 
Published: June 2021

AbstractCycling cells must respond to double-strand breaks (DSBs) to avoid genome instability. Mis-segregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is incompletely understood. We previously showed that Drosophila papillar cells lack DSB checkpoints (as observed in many cancer cells). Here, we show that papillar cells still recruit early-acting repair machinery (Mre11 and RPA3) to DSBs. This machinery persists as foci on DSBs as cells enter mitosis. Repair foci are resolved in a step-wise manner during mitosis. Repair signaling kinetics at DSBs depends on both monoubiquitination of the Fanconi Anemia (FA) protein Fancd2 and the alternative end-joining protein DNA Polymerase Theta. Disruption of either or both of these factors causes micronuclei after DNA damage, which disrupts intestinal organogenesis. This study reveals a mechanism for how cells with inactive DSB checkpoints can respond to DNA damage that persists into mitosis.SummaryClay et. al. show that cells with DNA breaks that persist into mitosis activate sustained DNA repair signaling, regulated by Fanconi Anemia proteins and the alternative end-joining repair protein DNA Polymerase Theta. This signaling enables broken chromosome segregation and prevents micronuclei.
Stability of Polygenic Scores Across Discovery Genome-Wide Association Studies
Authors: Schultz Laura M. , Merikangas Alison K. , Ruparel Kosha , Jacquemont Sébastien , Glahn David C. , Gur Raquel E. , Barzilay Ran , Almasy Laura 
Published: June 2021

AbstractPolygenic scores (PGS) are commonly evaluated in terms of their predictive accuracy at the population level by the proportion of phenotypic variance they explain. To be useful for precision medicine applications, they also need to be evaluated at the individual patient level when phenotypes are not necessarily already known. Hence, we investigated the stability of PGS in European-American (EUR)- and African-American (AFR)-ancestry individuals from the Philadelphia Neurodevelopmental Cohort (PNC) and the Adolescent Brain Cognitive Development (ABCD) cohort using different discovery GWAS for post-traumatic stress disorder (PTSD), type-2 diabetes (T2D), and height. We found that pairs of EUR-ancestry GWAS for the same trait had genetic correlations > 0.92. However, PGS calculated from pairs of sameancestry and different-ancestry GWAS had correlations that ranged from <0.01 to 0.74. PGS stability was higher for GWAS that explained more of the trait variance, with height PGS being more stable than PTSD or T2D PGS. Focusing on the upper end of the PGS distribution, different discovery GWAS do not consistently identify the same individuals in the upper quantiles, with the best case being 60% of individuals above the 80th percentile of PGS overlapping from one height GWAS to another. The degree of overlap decreases sharply as higher quantiles, less heritable traits, and different-ancestry GWAS are considered. PGS computed from different discovery GWAS have only modest correlation at the level of the individual patient, underscoring the need to proceed cautiously with integrating PGS into precision medicine applications.