bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of COVID-19 and Case Fatality Rate in Pune India: An Analysis of First and Second Wave of the Pandemic
Authors: Bogam Prasad , Joshi Aparna , Nagarkar Sanket , Jain Divyashri , Gupte Nikhil , Shashidhara LS , Monteiro Joy Merwin , Mave Vidya 
Published: June 2021

AbstractBackgroundThe recent second wave in India in April-May 2021 placed an unprecedented burden on the Indian health systems. However, limited data exist on the epidemiology of the COVID-19 pandemic from the first wave through the second wave in India. With detailed epidemiologic data, we aimed to assess trends in incident cases and case fatality, its risk between pandemic waves in Pune, an epicenter of COVID-19 cases in India, a country with the second-largest absolute burden worldwide.MethodsProgrammatic COVID-19 data from Pune city between the first wave (March 09th 2020-October 31st, 2020), maintenance phase (November 01st 2020-February 14th, 2021), the second wave (February 15th, 2021-May 31st, 2021) were assessed for trends of incident cases, time-to-death, and case fatality rate (CFR). In addition, Poisson regression models adjusted for age and gender were used to determine the independent effect of pandemic waves on mortality.ResultsOf 465,192 COVID-19 cases, 162,182 (35%) were reported in the first wave, and 4,146 (2.5%) died among them; Maintenance period registered 27,517 (6%) cases with 590 (2.1%) deaths; Second wave reported 275,493 (59%) cases and 3184 (1.1%) deaths (p<0.01). The overall CFR was 1.16 per 1000 person-days (PD), which declined from 1.80 per 1000 PD during the first wave to 0.77 per 1000 PD in the second wave. The risk of death was 1.49 times higher during the first wave (adjusted case fatality rate ratio-aCFRR,1.49; 95% CI: 1.37–1.62) and 35% lower in the second wave (aCFRR, 0.65; 95% CI: 0.59 – 0.70), compared to the maintenance phase.InterpretationThe absolute burden of COVID-19 cases and deaths were more significant in the second wave in Pune, India; however, the CFR declined as the pandemic progressed. Nevertheless, investigating newer therapies and implementing mass vaccinations against COVID-19 are urgently needed.
Dietary practices, physical activity and social determinants of non-communicable diseases in Nepal: a systemic analysis
Authors: Sharma Sudesh Raj , Matheson Anna , Lambrick Danielle , Faulkner James , Lounsbury David W. , Vaidya Abhinav , Page Rachel 
Published: June 2021

AbstractBackgroundThe objective of this paper was to describe the role of dietary practices and physical activity in the interaction of the social determinants of non-communicable diseases (NCDs) in Nepal.MethodThe study was a qualitative study design guided by systemic intervention methodology. Qualitative data were collected through key informant interviews (n=63) and focus group discussions (n= 12), and case study-based thematic analysis was carried out. Causal loop diagram was utilised to illustrate the dynamic interactions of the social determinants based on the themes. The study also involved sense-making sessions with policy level and local stakeholders.FindingsFour key interacting themes emerged from the study. Dietary and physical activity practices have shifted significantly at community level contributing to increased risk of NCDs. The practice of healthy and locally produced meals was gradually being displaced by junk food and linked to junk food availability and declining agricultural activities. Health system was ineffective in preventing unhealthy practices. Gender and social economic factors were driving the poor dietary practices and physical inactivity.ConclusionWhile the current dietary and physical activity-related practices within communities were poor, the broader determinants such as socio-economic circumstances and gender further fuelled such practices. The health system has potential to play an effective role in the prevention of the behavioural and social determinants of NCDs.
Development of quantitative high-throughput screening methods for identification of antifungal biocontrol strains
Authors: Kjeldgaard Bodil , Neves Ana Rute , Fonseca César , Kovács Ákos T. , Domínguez- Cuevas Patricia 
Published: June 2021

AbstractLarge screens of bacterial strain collections to identify potential biocontrol agents are often time consuming, costly, and fail to provide quantitative results. In this study, we present two quantitative and high-throughput methods to assess the inhibitory capacity of bacterial biocontrol candidates against fungal phytopathogens. One method measures the inhibitory effect of bacterial culture supernatant components on the fungal growth, while the other accounts for direct interaction between growing bacteria and the fungus by co-cultivating the two organisms. The antagonistic supernatant method quantifies the culture components’ antifungal activity by calculating the cumulative impact of supernatant addition relative to a non-treated fungal control, while the antagonistic co-cultivation method identifies the minimal bacterial cell concentration required to inhibit fungal growth by co-inoculating fungal spores with bacterial culture dilution series. Thereby, both methods provide quantitative measures of biocontrol efficiency and allow prominent fungal inhibitors to be distinguished from less effective strains. The combination of the two methods shed light on the type of inhibition mechanisms and provide the basis for further mode of action studies. We demonstrate the efficacy of the methods usingBacillus spp. with different levels of antifungal activities as model antagonists and quantify their inhibitory potency against classic plant pathogens.ImportanceFungal phytopathogens are responsible for tremendous agricultural losses on annual basis. While microbial biocontrol agents represent a promising solution to the problem, there is a growing need for high-throughput methods to evaluate and quantify inhibitory properties of new potential biocontrol agents for agricultural application. In this study, we present two high-throughput and quantitative fungal inhibition methods that are suitable for commercial biocontrol screening.
Viral detection and identification in 20 minutes by rapid single-particle fluorescence in-situ hybridization of viral RNA
Authors: Hepp Christof , Shiaelis Nicolas , Robb Nicole C. , Kapanidis Achillefs N 
Published: June 2021

AbstractThe increasing risk from viral outbreaks such as the ongoing COVID-19 pandemic exacerbates the need for rapid, affordable and sensitive methods for virus detection, identification and quantification; however, existing methods for detecting virus particles in biological samples usually depend on multistep protocols that take considerable time to yield a result. Here, we introduce a rapid fluorescence in situ hybridization (FISH) protocol capable of detecting influenza virus, avian infectious bronchitis virus and SARS-CoV-2 specifically and quantitatively in approximately 20 minutes, in both virus cultures and combined throat and nasal swabs without previous purification. This fast and facile workflow is applicable to a wide range of enveloped viruses and can be adapted both as a lab technique and a future diagnostic tool.
Pulmonary thromboembolism in patients after COVID-19 - predictive indicators for correct diagnosis
Authors: Yakova-Hristova D. , Simova I. , Pavlov P. , Hristov M. , Kundurzhiev T. , Dimitrov N. , Vekov T. 
Published: June 2021

AbstractIntroductionInfection caused by SARS-CoV-2 has been shown to lead to significant procoagulant events, in some cases involving life-threatening pulmonary thromboembolism (PE). Additional conditions complicating the diagnosis are the presence of risk factors for PE in almost all patients with COVID-19, as well as the overlap of the clinical presentation between PE and COVID-19. Materials and Methods: Тherefore we conducted a single-center study at the Heart and Brain Hospital, Pleven in the period December 2020-February 2021. It included 27 consecutively hospitalized patients with recent pneumonia caused by Covid-19 and clinical presentation referring to PE. The cohort was divided into two groups - with and without a definitive diagnosis of PE, proven by CT pulmoangiography. The aim was to find the indicators that predict the presence of PE in patients with acute or Post-acute COVID-19 conditions. Results: Our results show that part of the ECG criteria - S-wave over 1.5 mm in I lead and aVL (p = 0.007), Q-wave in III and aVF (p = 0.020), as well as the D-dimer as quantitative variable (p = 0.025) proved to be independent predictors of PE. The RV/ LV diameter ratios ≥1.0 as well as right ventricular dysfunction showed sensitivity 62.5%, specificity 100%, positive predictive value 100% and negative such 86.4% to verify the PE diagnosisЛ We suggest that the cut-off value of D-dimer of 1032 ng/ml has an optimal sensitivity (Se) of 87.5%, specificity (Sp) 57.9%, positive a predictive value (PPV) 46.7% and negative predictive value (NPV) of 91.7% for the diagnosis of PE (p = 0.021). Conclusion: Against the background of acute and Post-acute COVID-19 conditions ECG and EchoCG criteria remain predictive of PE. We suggest that a higher D-dimer cut-off value should be applied in COVID-19 and post-COVID-19 patients in order to confirm/dismiss the diagnosis PE.
Long-term course of humoral and cellular immune responses in outpatients after SARS-CoV-2 infection
Authors: Schiffner Julia , Backhaus Insa , Rimmele Jens , Schulz Sören , Möhlenkamp Till , Klemens Julia Maria , Zapf Dorinja , Solbach Werner , Mischnik Alexander 
Published: June 2021

AbstractCharacterisation of the naturally acquired B and T cell immune responses to SARS-CoV-2 is important for the development of public health and vaccination strategies to manage the burden of COVID-19 disease. We conducted a prospective, longitudinal analysis in COVID-19 recovered patients at various time points over a 10-month period in order to determine how circulating antibody levels and interferon-gamma (IFN-γ) release by peripheral blood cells change over time following natural infection.From March 2020 till January 2021, we enrolled 412 adults mostly with mild or moderate disease course. At each study visit, subjects donated peripheral blood for testing of anti-SARS-CoV-2 IgG antibodies and IFN-γ release after SARS-CoV-2 S-protein stimulation. Anti-SARS-CoV-2 IgG antibodies were identified in 316/412 (76.7%) of the patients and 215/412 (52.2%) had positive neutralizing antibody levels. Likewise, in 274/412 (66.5 %) positive IFN-γ release and IgG antibodies were detected. With respect to time after infection, both IgG antibody levels and IFN-γ concentrations decreased by about half within three hundred days. Statistically, IgG and IFN-γ production were closely associated, but on an individual basis we observed patients with high antibody titres but low IFN-γ levels and vice versa.Our data suggest that immunological reaction is acquired in most individuals after infection with SARS-CoV-2 and is sustained in the majority of patients for at least 10 months after infection. Since no robust marker for protection against COVID-19 exists so far, we recommend utilizing both, IgG and IFN-γ release for an individual assessment of immunity status.
Efficacy of recombinant NP-M1 and NP-M1-CRT DNA vaccines against Influenza A viruses in mice C57/BL6
Authors: Attaran Hamidreza , He Wen , Wang Wei 
Published: June 2021

AbstractEffective vaccination against the influenza virus remains a challenge because of antigenic shift and drift in influenza viruses. Conservation is an important feature of the Nucleoprotein (NP) and Matrix protein 1(M1) qualifying them as potential candidates for developing a universal vaccine against the influenza A virus. Carliticulin (CRT), a member of heat shock protein (HSP) family, are conserved and widely distributed in many microorganisms and mammalian cells. In this study, a plasmid vector encoding the NP-M1-CRT sequence was constructed and compared with the NP-M1 sequence with respect to immunogenicity and protective efficacy in a murine model. The potency of the created construct for provoking humoral, cellular immune responses, and its protective immunity against the lethal influenza virus infection were then compared with commercial split vaccine and then evaluated in a murine model system. NP-M1-CRT as a DNA vaccine combined with in vivo electroporation could significantly improve the immunogenicity of constructed vectors. Serological evaluations demonstrated the potency of our approach to provoke strong anti-NP specific antibody responses. Furthermore, our strategy of immunization in prime-boost groups were able to provide protection against lethal viral challenge using H1N1 subtype. The ease of production of these types of vectors and the fact that they would not require annual updating and manufacturing may provide an alternative cost-effective approach to limit the spread of potential pandemic influenza viruses.
Distinct modes of action of IAPP oligomers on membranes
Authors: Sepehri Aliasghar , Nepal Binod , Lazaridis Themis 
Published: June 2021

AbstractIslet Amyloid Polypeptide (IAPP, also known as amylin) is a peptide hormone which is co-secreted with insulin by pancreatic β-cells and forms amyloid aggregates in type II diabetes. Various lines of evidence indicate that oligomers of this peptide may induce toxicity by disrupting or forming pores in cell membranes but the structures of these pores are unknown. Here we create models of pores for both helical and β-structured peptides using implicit membrane modeling and test their stability using multimicrosecond all-atom simulations. We find that the helical peptides behave similarly to antimicrobial peptides; they remain stably inserted in a highly tilted or partially unfolded configuration creating a narrow water channel. Parallel helix orientation creates a somewhat larger pore. An octameric β barrel of parallel β-hairpins is highly stable in the membrane, whereas the corresponding barrel made of antiparallel hairpins is not. We propose that certain experiments probe the helical pore state while others probe the β-structured pore state; this provides a possible explanation for lack of correlation that is sometimes observed between in vivo toxicity and in vitro liposome permeabilization experiments.
Phylourny: Predicting the Knock-out-phase of Tournaments via Phylogenetic Methods by example of the UEFA EURO 2020
Authors: Bettisworth Ben , Stamatakis Alexandros 
Published: June 2021

AbstractThe prediction of knock-out tournaments represents an area of large public interest and active academic as well as industrial research. Here, we leverage the computational analogies between calculating the so-called phylogenetic likelihood score used in the area of molecular evolution and efficiently calculating, instead of approximating via simulations, the exact per-team winning probabilities, given a pairwise win probability matrix P. We implement and make available our method as open-source code and deploy it to calculate the winning probabilities for all teams participating at the knock-out phase of the UEFA EURO 2020 football tournament. We use three different P matrices to conduct predictions, two inferred via our own simple method and one computed by experts in the field. According to this expert P matrix which we trust most, we find that the most probable final is France versus England and that England has a slightly higher probability to win the title. The ability to efficiently and exactly compute winning probabilities, apart from improving and accelerating predictions, might allow for the development of novel methods to compute P.
Two evolutionary distinct effectors from a nematode and virus target RanGAP1 and 2 via the WPP domain to promote disease
Authors: Sukarta Octavina C. A , Diaz-Granados Amalia , Slootweg Erik J , Overmars Hein , van Schaik Casper , Pokhare Somnath , Roosien Jan , Pomp Rikus , Elashry Abdelnaser , Smant Geert , Goverse Aska 
Published: June 2021

ABSTRACTThe Gpa2 and Rx1 intracellular immune receptors are canonical CC-NB-LRR proteins belonging to the same R gene cluster in potato. Despite sharing high sequence homology, they have evolved to provide defence against unrelated pathogens. Gpa2 detects Gp-RBP-1 effectors secreted by the potato cyst nematode Globodera pallida whereas Rx1 recognizes the viral coat protein (CP) of Potato Virus X (PVX). How Gpa2 and Rx1 perceive their matching effectors remains unknown. Using a combination of in planta Co-Immunoprecipitation and cellular imaging, we show that both Gp-RBP-1 and PVX-CP physically interact with RanGAP2 and RanGAP1 in the cytoplasm of plant cells. Interestingly, this was also demonstrated for the eliciting variants of Gp-RBP-1 and PVX-CP indicating a role for RanGAP1 and RanGAP2 in pathogenicity independent from Gpa2 and Rx1 recognition. Indeed, knocking down both RanGAP homologs reduce cyst nematode and PVX infection. These findings show that RanGAP1/2 act as common host targets of evolutionary distinct effectors from two plant pathogens with different lifestyles. The involvement of RanGAP1/2 to pathogen virulence is a novel role not yet reported for these key host cell components and as such, their possible role in cyst nematode parasitism and viral pathogenicity are discussed. Moreover, from these findings a model emerges for their possible role as co-factor in pathogen recognition by the potato immune receptors Gpa2/Rx1.
A Robust and Scalable Graph Neural Network for Accurate Single Cell Classification
Authors: Zeng Yuansong , Zhou Xiang , Pan Zixiang , Lu Yutong , Yang Yuedong 
Published: June 2021

ABSTRACTMotivationSingle-cell RNA sequencing (scRNA-seq) techniques provide high-resolution data on cellular heterogeneity in diverse tissues, and a critical step for the data analysis is cell type identification. Traditional methods usually cluster the cells and manually identify cell clusters through marker genes, which is time-consuming and subjective. With the launch of several large-scale single-cell projects, millions of sequenced cells have been annotated and it is promising to transfer labels from the annotated datasets to newly generated datasets. One powerful way for the transferring is to learn cell relations through the graph neural network (GNN), while vanilla GNN is difficult to process millions of cells due to the expensive costs of the message-passing procedure at each training epoch.ResultsHere, we have developed a robust and scalable GNN-based method for accurate single cell classification (GraphCS), where the graph is constructed to connect similar cells within and between labelled and unlabelled scRNA-seq datasets for propagation of shared information. To overcome the slow information propagation of GNN at each training epoch, the diffused information is pre-calculated via the approximate Generalized PageRank algorithm, enabling sublinear complexity for a high speed and scalability on millions of cells. Compared with existing methods, GraphCS demonstrates better performance on simulated, cross-platform, and cross-species scRNA-seq datasets. More importantly, our model can achieve superior performance on a large dataset with one million cells within 50 minutes.
Membraneless organelles formed by liquid-liquid phase separation increase bacterial fitness
Authors: Jin Xin , Lee Ji-Eun , Schaefer Charley , Luo Xinwei , Wollman Adam J. M. , Tian Tian , Zhang Xiaowei , Chen Xiao , Li Yingxing , McLeish Tom C. B. , Leake Mark C. , Bai Fan 
Published: June 2021

AbstractLiquid-liquid phase separation is emerging as a crucial phenomenon in several fundamental cell processes. A range of eukaryotic systems exhibit liquid condensates. However, their function in bacteria, which in general lack membrane-bound compartments, remains less clear. Here, we used high-resolution optical microscopy to observe single bacterial aggresomes, nanostructured intracellular assemblies of proteins, to undercover their role in cell stress. We find that proteins inside aggresomes are mobile and undergo dynamic turnover, consistent with a liquid state. Our observations are in quantitative agreement with phase-separated liquid droplet formation driven by interacting proteins under thermal equilibrium that nucleate following diffusive collisions in the cytoplasm. We have discovered aggresomes in multiple species of bacteria, and show that these emergent, metastable liquid-structured protein assemblies increase bacterial fitness by enabling cells to tolerate environmental stresses.One Sentence SummaryBacteria use subcellular proteinaceous liquid droplets to survive stress
Rational engineering of an erythropoietin fusion protein to treat hypoxia
Authors: Lee Jungmin , Vernet Andyna , Gruber Nathalie G. , Kready Kasia M. , Burrill Devin R. , Way Jeffrey C. , Silver Pamela A. 
Published: June 2021

AbstractErythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.
Pyrimidine biosynthesis inhibitors synergize with nucleoside analogs to block SARS-CoV-2 infection
Authors: Schultz David C. , Johnson Robert M. , Ayyanathan Kasirajan , Miller Jesse , Whig Kanupriya , Kamalia Brinda , Dittmar Mark , Weston Stuart , Hammond Holly L. , Dillen Carly , Castellana Lauren , Lee Jae Seung , Li Minghua , Lee Emily , Constant Samuel , Ferrer Marc , Thaiss Christoph A. , Frieman Matthew B. , Cherry Sara 
Published: June 2021

AbstractThe ongoing COVID-19 pandemic has highlighted the dearth of approved drugs to treat viral infections, with only ∼90 FDA approved drugs against human viral pathogens. To identify drugs that can block SARS-CoV-2 replication, extensive drug screening to repurpose approved drugs is underway. Here, we screened ∼18,000 drugs for antiviral activity using live virus infection in human respiratory cells. Dose-response studies validate 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Amongst these drug candidates are 16 nucleoside analogs, the largest category of clinically used antivirals. This included the antiviral Remdesivir approved for use in COVID-19, and the nucleoside Molnupirivir, which is undergoing clinical trials. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral, and we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogs synergistically inhibits SARS-CoV-2 infection in vitro and in vivo suggesting a clinical path forward.