bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of real-infection and immunity against SARS-CoV-2 in Indian populations
Authors: Singh Prajjval Pratap , Tamang Rakesh , Shukla Manoj , Pathak Abhishek , Srivastava Anshika , Gupta Pranav , Bhatt Alay , Shrivastava Abhishek K. , Upadhyay Sudhir K. , Singh Ashish , Maurya Sanjeev , Saxena Purnendu , Singh Vanya , Chaubey Akhilesh Kumar , Mishra Dinesh Kumar , Patel Yashvant , Pandey Rudra Kumar , Srivastava Ankit , Khanam Nargis , Das Debashruti , Bandopadhyay Audditiya , Chorol Urgyan , Pasupuleti Nagarjuna , Shrivastav Sachin Kumar , Prakash Satya , Mishra Astha , Dubey Pavan Kumar , Parihar Ajit , Basu Priyoneel , Sequeira Jaison J , Lavanya KC , Vijayalaxmi  , Vishnu Shreekara Bhat. K. , Ijinu Thadiyan Parambil , Aggarwal Dau Dayal , Prakash Anand , Yadav Kiran , Yadav Anupam , Upadhyay Vandana , Mukim Gunjan , Bhandari Ankan , Ghosh Ankita , Kumar Akash , Yadav Vijay Kumar , Nigam Kriti , Harshey Abhimanyu , Das Tanurup , Devadas Deepa , Mishra Surendra Pratap , Ashish  , Yadav Abhay Kumar , Singh Nitish Kumar , Kaur Manpreet , Kumar Sanjay , Srivastava Nikhil , Sharma Charu , Chowdhury Ritabrata , Jain Dharmendra , Kumar Abhai , Shukla Ritesh , Mishra Raghav Kumar , Singh Royana , Tripathi Yamini B , Mishra Vijay Nath , Mustak Mohammed S. , Rai Niraj , Rawat Sumit Kumar , Survajhala Prashanth , Singh Keshav K , Mallick Chandana Basu , Shrivastava Pankaj , Chaubey Gyaneshwer 
Published: February 2021

AbstractInfection born by Coronavirus SARS-CoV-2 has swept the world within a time of a few months. It has created a devastating effect on humanity with social and economic depressions. Europe and America were the hardest hit continents. India has also lost several lives, making the country fourth most deadly worldwide. However, the infection and death rate per million and the case fatality ratio in India were substantially lower than many of the developed nations. Several factors have been proposed including the genetics. One of the important facts is that a large chunk of Indian population is asymptomatic to the SARS-CoV-2 infection. Thus, the real infection in India is much higher than the reported number of cases. Therefore, the majority of people are already immune in the country. To understand the dynamics of real infection as well as level of immunity against SARS-CoV-2, we have performed antibody testing (serosurveillance) in the urban region of fourteen Indian districts encompassing six states. In our survey, the seroprevalence frequency varied between 0.01-0.48, suggesting high variability of viral transmission among states. We also found out that the cases reported by the Government were several fold lower than the real infection. This discrepancy is majorly driven by a higher number of asymptomatic cases. Overall, we suggest that with the high level of immunity developed against SARS-CoV-2 in the majority of the districts, it is less likely to have a second wave in India.
A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis
Authors: Miyano Takuya , Irvine Alan D , Tanaka Reiko J 
Published: February 2021

AbstractBackgroundSeveral biologics for atopic dermatitis (AD) have demonstrated good efficacy in clinical trials, but with a substantial proportion of patients being identified as poor responders. This study aims to understand the pathophysiological backgrounds of patient variability in drug response, especially for dupilumab, and to identify promising drug targets in dupilumab poor responders.MethodsWe conducted model-based meta-analysis of recent clinical trials of AD biologics and developed a mathematical model that reproduces reported clinical efficacies for nine biological drugs (dupilumab, lebrikizumab, tralokinumab, secukinumab, fezakinumab, nemolizumab, tezepelumab, GBR 830, and recombinant interferon-gamma) by describing systems-level AD pathogenesis. Using this model, we simulated the clinical efficacy of hypothetical therapies on virtual patients.ResultsOur model reproduced reported time courses of %improved EASI and EASI-75 of the nine drugs. The global sensitivity analysis and model simulation indicated the baseline level of IL-13 could stratify dupilumab good responders. Model simulation on the efficacies of hypothetical therapies revealed that simultaneous inhibition of IL-13 and IL-22 was effective, whereas application of the nine biologic drugs was ineffective, for dupilumab poor responders (EASI-75 at 24 weeks: 21.6% vs. max. 1.9%).ConclusionOur model identified IL-13 as a potential predictive biomarker to stratify dupilumab good responders, and simultaneous inhibition of IL-13 and IL-22 as a promising drug therapy for dupilumab poor responders. This model will serve as a computational platform for model-informed drug development for precision medicine, as it allows evaluation of the effects of new potential drug targets and the mechanisms behind patient variability in drug response.
Patterns of COVID-19 pandemic dynamics following deployment of a broad national immunization program
Authors: Rossman Hagai , Shilo Smadar , Meir Tomer , Gorfine Malka , Shalit Uri , Segal Eran 
Published: February 2021

AbstractStudies on the real-life impact of the BNT162b2 vaccine, recently authorized for the prevention of coronavirus disease 2019 (COVID-19), are urgently needed. Here, we analysed the temporal dynamics of the number of new COVID-19 cases and hospitalization in Israel following a rapid vaccination campaign initiated on December 20th, 2020. We conducted a retrospective descriptive analysis of data originating from the Israeli Ministry of Health (MOH) from March 2020 to February 2021. In order to distill the possible effect of the vaccinations from other factors, including a third lockdown imposed in Israel on January 2021, we compared the time-dependent changes in number of COVID-19 cases and hospitalizations between (1) individuals aged 60 years and older, eligible to receive the vaccine earlier, and younger age groups; (2) the latest lockdown (which was imposed in parallel to the vaccine rollout) versus the previous lockdown, imposed on September 2020; (3) early-vaccinated cities compared to late-vaccinated cities; and (4) early-vaccinated geographical statistical areas (GSAs) compared to late-vaccinated GSAs. In mid-January, the number of COVID-19 cases and hospitalization started to decline, with a larger and earlier decrease among older individuals, followed by younger age groups, by the order in which they were prioritized for vaccination. This fast and early decline in older individuals was more evident in early-vaccinated compared to late-vaccinated cities. Such a pattern was not observed in the previous lockdown. Our analysis demonstrates evidence for the real-life impact of a national vaccination campaign in Israel on the pandemic dynamics. We believe that our findings have major public health implications in the struggle against the COVID-19 pandemic, including the public ’s perception of the need for and benefit of nationwide vaccination campaigns. More studies aimed at assessing the effectiveness and impact of vaccination both on the individual and on the population level, with longer followup, are needed.
ACE: Explaining cluster from an adversarial perspective
Authors: Lu Yang Young , Yu Timothy C. , Bonora Giancarlo , Noble William Stafford 
Published: February 2021

AbstractA common workflow in single-cell RNA-seq analysis is to project the data to a latent space, cluster the cells in that space, and identify sets of marker genes that explain the differences among the discovered clusters. A primary drawback to this three-step procedure is that each step is carried out independently, thereby neglecting the effects of the nonlinear embedding and inter-gene dependencies on the selection of marker genes. Here we propose an integrated deep learning framework, Adversarial Clustering Explanation (ACE), that bundles all three steps into a single work-flow. The method thus moves away from the notion of “marker genes” to instead identify a panel of explanatory genes. This panel may include genes that are not only enriched but also depleted relative to other cell types, as well as genes that exhibit differences between closely related cell types. Empirically, we demonstrate that ACE is able to identify gene panels that are both highly discriminative and nonredundant, and we demonstrate the applicability of ACE to an image recognition task.1
Development and evaluation of a new methodology for Soft Tissue Artifact compensation in the lower limb
Authors: Lahkar Bhrigu K. , Rohan Pierre-Yves , Assi Ayman , Pillet Helene , Bonnet Xavier , Thoreux Patricia , Skalli Wafa 
Published: February 2021

AbstractSkin Marker (SM) based motion capture is the most widespread technique used for motion analysis. Yet, the accuracy is often hindered by Soft Tissue Artifact (STA). This is a major issue in clinical gait analysis where kinematic results are used for decision-making. It also has a considerable influence on the results of rigid body and Finite Element (FE) musculoskeletal models that rely on SM-based kinematics to estimate muscle, contact and ligament forces. Current techniques designed to compensate for STA, in particular multi-body optimization methods, assume anatomical simplifications to define joint constraints. These methods, however, cannot adapt to subjects’ bone morphology, particularly for patients with joint lesions, nor easily can account for subject- and location-dependent STA. In this perspective, we propose to develop a conceptual FE based model of the lower limb for STA compensation and evaluate it for 66 healthy subjects under level walking motor task.Both hip and knee joint kinematics were analyzed, considering both rotational and translational joint motion. Results showed that STA caused underestimation of the hip joint kinematics (up to 2.2°) for all rotational DoF, and overestimation of knee joint kinematics (up to 12°) except in flexion/extension. Joint kinematics, in particular the knee joint, appeared to be sensitive to soft tissue stiffness parameters (rotational and translational mean difference up to 1.5° and 3.4 mm). Analysis of the results using alternative joint representations highlighted the versatility of the proposed modeling approach. This work paves the way for using personalized models to compensate for STA in healthy subjects and different activities.
Next-generation sequencing-based bulked segregant analysis without sequencing the parental genomes
Authors: Zhang Jianbo , Panthee Dilip R. 
Published: February 2021

The genomic region(s) that controls a trait of interest can be rapidly identified using BSA-Seq, a technology in which next-generation se-quencing (NGS) is applied to bulked segregant analysis (BSA). We recently developed the significant structural variant method for BSA-Seq data analysis that exhibits higher detection power than standard BSA-Seq analysis methods. Our original algorithm was developed to analyze BSA-Seq data in which genome sequences of one parent served as the reference sequences in genotype calling, and thus required the availability of high-quality assembled parental genome sequences. Here we modified the original script to allow for the effective detection of the genomic region-trait associations using only bulk genome sequences. We analyzed a public BSA-Seq dataset using our modified method and the standard allele frequency and G-statistic methods with and without the aid of the parental genome sequences. Our results demonstrate that the genomic region(s) associated with the trait of interest could be reliably identified only via the significant structural variant method without using the parental genome sequences.Significance StatementBSA-Seq can be utilized to rapidly identify structural varianttrait associations, and our modified significant structural variant method allows the detection of such associations without sequencing the parental genomes, leading to further lower the sequencing cost and making BSA-Seq more accessible to the research community and more applicable to the species with a large genome.
Constructing smaller genome graphs via string compression
Authors: Qiu Yutong , Kingsford Carl 
Published: February 2021

AbstractThe size of a genome graph — the space required to store the nodes, their labels and edges — affects the efficiency of operations performed on it. For example, the time complexity to align a sequence to a graph without a graph index depends on the total number of characters in the node labels and the number of edges in the graph. The size of the graph also affects the size of the graph index that is used to speed up the alignment. This raises the need for approaches to construct space-efficient genome graphs.We point out similarities in the string encoding approaches of genome graphs and the external pointer macro (EPM) compression model. Supported by these similarities, we present a pair of linear-time algorithms that transform between genome graphs and EPM-compressed forms. We show that the algorithms result in an upper bound on the size of the genome graph constructed based on an optimal EPM compression. In addition to the transformation, we show that equivalent choices made by EPM compression algorithms may result in different sizes of genome graphs. To further optimize the size of the genome graph, we purpose the source assignment problem that optimizes over the equivalent choices during compression and introduce an ILP formulation that solves that problem optimally. As a proof-of-concept, we introduce RLZ-Graph, a genome graph constructed based on the relative Lempel-Ziv EPM compression algorithm. We show that using RLZ-Graph, across all human chromosomes, we are able to reduce the disk space to store a genome graph on average by 40.7% compared to colored de Bruijn graphs constructed by Bifrost under the default settings.The RLZ-Graph software is available athttps://github.com/Kingsford-Group/rlzgraph
CCG•CGG interruptions in high penetrance SCA8 families increase RAN translation and protein toxicity
Authors: Perez Barbara A. , Shorrock Hannah K. , Banez-Coronel Monica , Laboissonniere Lauren A. , Reid Tammy , Ikeda Yoshio , Reddy Kaalak , Gomez Christopher M. , Bird Thomas , Ashizawa Tetsuo , Schut Lawrence J. , Brusco Alfredo , Berglund J. Andrew , Hasholt Lis F. , Nielsen Jorgen E. , Subramony S.H. , Ranum Laura P.W. 
Published: February 2021

AbstractSpinocerebellar ataxia type 8 (SCA8), a dominantly inherited neurodegenerative disorder caused by a CTG•CAG expansion, is unusual because most individuals that carry the mutation do not develop ataxia. To understand the variable penetrance of SCA8 we studied the molecular differences between highly penetrant families and more common sporadic cases (82%) using a large cohort of SCA8 families (N=77). We show that repeat expansion mutations from individuals with two or more affected family members have CCG•CGG interruptions at a higher frequency than sporadic SCA8 cases and that the number of CCG•CGG interruptions correlates with age at onset. At the molecular level, CCG•CGG interruptions increase RNA hairpin stability and steady state levels of SCA8 RAN polyAla and polySer proteins. Additionally, the CCG•CGG interruptions, which encode arginine interruptions in the polyGln frame increase the toxicity of the resulting proteins. In summary, CCG•CGG interruptions increase polyAla and polySer RAN protein levels, polyGln protein toxicity and disease penetrance and provide novel insight into the molecular differences between SCA8 families with high vs. low disease penetrance.
An algal symbiont (Breviolum psygmophilum) responds more strongly to chronic high temperatures than its facultatively symbiotic coral host (Astrangia poculata)
Authors: Chan Andrea N. , González-Guerrero Luis A. , Iglesias-Prieto Roberto , Burmester Elizabeth M. , Rotjan Randi D. , Finnerty John R. , Baums Iliana B. 
Published: February 2021

AbstractScleractinian corals form the foundation of coral reefs by secreting skeletons of calcium carbonate. Their intracellular algal symbionts (Symbiodiniaceae) translocate a large proportion of photosynthate to the coral host, which is required to maintain high rates of calcification. Global warming is causing dissociation of coral host and algal symbiont, visibly presented as coral bleaching. Despite decades of study, the precise mechanisms of coral bleaching remain unknown. Separating the thermal stress response of the coral from the algal symbiont is key to understanding bleaching in tropical corals. The facultatively symbiotic northern star coral,Astrangia poculata, naturally occurs as both symbiotic and aposymbiotic (lacking algal symbionts) polyps – sometimes on the same coral colony. Thus, it is possible to separate the heat stress response of the coral host alone from the coral in symbiosis with its symbiontBreviolum psygmophilum. Using replicate symbiotic and aposymbiotic ramets ofA. poculata, we conducted a chronic heat stress experiment to increase our understanding of the cellular mechanisms resulting in coral bleaching. Sustained high temperature stress resulted in photosynthetic dysfunction inB. psygmophilum, including a decline in maximum photosynthesis rate, maximum photochemical efficiency, and the absorbance peak of chlorophylla. Interestingly, the metabolic rates of symbiotic and aposymbiotic corals were differentially impacted. RNAseq analysis revealed more differentially expressed genes between heat-stressed and control aposymbiotic colonies than heat-stressed and control symbiotic colonies. Notably, aposymbiotic colonies increased the expression of inflammation-associated genes such as nitric oxide synthases. Unexpectedly, the largest transcriptional response was observed between heat-stressed and controlB. psygmophilum, including genes involved in photosynthesis, response to oxidative stress, and meiosis. Thus, it appears that the algal symbiont suppresses the immune response of the host, potentially increasing the vulnerability of the host to pathogens. TheA. poculata-B. psygmophilumsymbiosis provides a tractable model system for investigating thermal stress and immune challenge in scleractinian corals.
Exosomes from COVID-19 patients carry tenascin-C and fibrinogen-β in triggering inflammatory signals in distant organ cells
Authors: Sur Subhayan , Khatun Mousumi , Steele Robert , Isbell T. Scott , Ray Ranjit , Ray Ratna B. 
Published: February 2021

AbstractSARS-CoV-2 infection causes cytokine storm and overshoot immunity in humans; however, it remains to be determined whether genetic material of SARS-CoV-2 and/or virus induced soluble mediators from lung epithelial cells as natural host are carried out by macrophages or other vehicles at distant organs causing tissue damage. We speculated that exosomes as extracellular vesicles are secreted from SARS-CoV-2 infected cells may transport messages to other cells of distant organs leading to pathogenic consequences. For this, we took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and SARS-CoV-2 infected patients. Our results revealed that tenascin-C (TNC) and fibrinogen-β (FGB) are highly abundant in exosomes from SARS-CoV-2 infected patient’s plasma as compared to that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via NF-κB pathway, we examined the status of TNF-α, IL-6 and CCL5 expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase when compared with that from healthy subjects. Together, our results demonstrated that soluble mediators, like TNC and FGB, are transported through plasma exosomes in SARS-CoV-2 infected patients and trigger pro-inflammatory cytokine expression in cells of distant organs in COVID-19 patients.ImportanceExosomes play an important role in intercellular communication by inducing physiological changes in recipient cells by transferring bioactive proteins. Little is known about exosomes from SARS-CoV-2 infected cells and their role in pathogenesis. Here, we have carefully examined and analyzed this aspect of SARS-CoV-2 infection. Our results uncovered the potential mechanisms by which SARS-CoV-2 communicates with other cells of distant organs and promotes pathogenesis. We expect to detect whether other factors are modulated in the presence of COVID-19 exosomes. Our exosomes related proteomic experiments prioritize after initial verification to further examine their role in SARS-CoV-2 associated other pathogenic mechanisms to target for therapeutic modalities.
SLC4A2 Anion Exchanger Promotes Tumor Cell Malignancy via Enhancing H+Leak across Golgi Membranes
Authors: Khosrowabadi Elham , Rivinoja Antti , Risteli Maija , Tuomisto Anne , Salo Tuula , Mäkinen Markus J , Kellokumpu Sakari 
Published: February 2021

AbstractProper functioning of each secretory and endocytic compartment relies on its unique pH micro-environment that is known to be dictated by the rates of V-ATPase-mediated H+pumping and its leakage back to the cytoplasm via an elusive “H+leak” pathway. Here, we show that this proton leak across Golgi membranes involves AE2a (SLC4A2a)-mediated bicarbonate-chloride exchange, as it is strictly dependent on both bicarbonate import (in exchange of chloride export) and the AE2a expression level in the cells. Imported bicarbonate anions and luminal protons then facilitate a common buffering reaction that yields carbon dioxide and water before their egress back to the cytoplasm via diffusion or water channels. The high surface-volume ratio of flattened Golgi cisternae helps this process, as their shape is optimal for water and gas exchange. Interestingly, this pathway is often upregulated in cancers and established cancer cell lines, and responsible for their markedly elevated Golgi resting pH and attenuated glycosylation potential. Accordingly, AE2 knockdown in SW-48 colorectal cancer cells was able to restore these two phenomena, and at the same time, to reverse cells’ invasive and anchorage-independent growth phenotype. These findings suggest that a malignant cell can be returned to a benign state by normalizing its Golgi resting pH.
Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro biofilm and in vivo implant infections
Authors: de Vor Lisanne , van Dijk Bruce , van Kessel Kok P.M. , Kavanaugh Jeffrey S. , de Haas Carla J.C. , Aerts Piet C. , Viveen Marco C. , Boel Edwin C.H. , Fluit Ad C. , Kwiecinski Jakub M. , Krijger Gerard C. , Ramakers Ruud M. , Beekman Freek J. , Dadachova Ekaterina , Lam Marnix G.E.H. , Vogely H. Charles , van der Wal Bart C.H. , van Strijp Jos A.G. , Horswill Alexander R. , Weinans Harrie , Rooijakkers Suzan H.M. 
Published: February 2021

AbstractImplant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and/or treatment of biofilm-related infections. Here we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. In a mouse model, we show that mAb 4497 (recognizing wall teichoic acid (WTA)) specifically localizes to biofilm-infected implants. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo. This is an important first step to develop mAbs for imaging or treating S. aureus biofilms.