bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tocilizumab Effect in COVID-19 Hospitalized Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials
Authors: Abdulrahman Basheer , Aletreby Waleed , Mady Ahmed , Noor Alfateh Mohammed , Lhmdi Mohammed , Faqihi Fahad , Alharthy Abdulrahman , Al-Odat Mohammed , Karakitsos Dimitrios , Memish Ziad 
Published: March 2021

AbstractSince the emergence of the first cases of COVID-19 viral pneumonia late 2019 several studies evaluated the benefits of different treatment modalities. Early in the pandemic, the interleukin 6 (IL-6) receptor antibody Tocilizumab was considered in view of the cytokine release syndrome associated with COVID-19 infection. Several early observational studies showed beneficial effect of treatment with Tocilizumab on mortality, however, results from well-designed randomized clinical trials (RCT) were contradicting.ObjectivesTo perform a systematic literature review and meta-analysis of RCTs utilizing Tocilizumab in the treatment of COVID-19 pneumonia, with in-hospital mortality as a primary objective, while secondary objectives included composite outcome of mortality, intubation, or ICU admission, another secondary outcome was super added infection.MethodThis was a random effects model (DerSimonian and Laird) model of relative risk (RR), along with corresponding 95% confidence intervals, p values, and forest plots of both primary and secondary outcomes. A fixed effect sensitivity test was performed for the primary outcome, in addition to subgroup and meta-regression analyses with predefined criteria.ResultsThe primary outcome of mortality showed statistically insignificant reduction of mortality with Tocilizumab (RR = 0.9, 95% CI: 0.8 – 1.01; p = 0.09) although with an unmistakable apparent clinical benefit. There was a significant reduction in the RR of the secondary composite outcome (RR = 0.83, 95% CI: 0.76 – 0.9; p < 0.001), and no difference between groups in super-added infection (RR = 0.77, 95% CI: 0.51 – 1.19; p = 0.24). Treatment protocol allowing a second dose was the only significant predictor of improved mortality in the meta-regression analysis. Certainty of evidence was reduced to moderate for the primary outcome and the secondary outcome of clinical deterioration, while it was reduced to low for the secondary outcome of super-added infection.ConclusionModerate certainty of evidence suggest no statistically significant improvement of 28-30 day all-cause mortality of hospitalized COVID-19 patients treated with TCZ, although there may be clinically important value. Moderate certainty of evidence suggest lowered relative risk of a composite outcome of death or clinical deterioration, while, low grade evidence indicate no increase in the risk of super-added infection associated with TCZ treatment. A protocol allowing two doses of TCZ shows evidence of improved mortality as compared to a strictly single dose protocol.
Electronic health record enabled track and trace in an urban hospital network: implications for infection prevention and control
Authors: Pi Li , Expert Paul , Clarke Jonathan M , Jauneikaite Elita , Costelloe Céire E 
Published: March 2021

ABSTRACTHealthcare-associated infections represent one of the most significant challenges for modern medicine as they can significantly impact patients’lives. Carbapenemase-producing Enterobacteriaceae (CPE) pose the greatest clinical threat, given the high levels of resistance to carbapenems, which are considered as agents of ‘last resort’ against life-threatening infections. Understanding patterns of CPE infection spreading in hospitals is paramount to design effective infection control protocols to mitigate the presence of CPE in hospitals. We used patient electronic health records from three urban hospitals to: i) track microbiologically confirmed carbapenemase producingEscherichia coli(CP-Ec) carriers and ii) trace the patients they shared place and time with until their identification. We show that yearly contact networks in each hospital consistently exhibit a core-periphery structure, highlighting the presence of a core set of wards where most carrier-contact interactions occured before being distributed to peripheral wards. We also identified functional communities of wards from the general patient movement network. The contact networks projected onto the general patient movement community structure showed a comprehensive coverage of the hospital. Our findings highlight that infections such as CP-Ec infections can reach virtually all parts of hospitals through first-level contacts.
A bibliometric analysis of COVID-19 research in Africa
Authors: Guleid Fatuma H , Oyando Robinson , Kabia Evelyn , Mumbi Audrey , Akech Samuel , Barasa Edwine 
Published: March 2021

ABSTRACTBackgroundThe ongoing COVID-19 pandemic has led to an unprecedented global research effort to build a body of knowledge that can inform mitigation strategies. We carried out a bibliometric analysis to describe the COVID-19 research output in Africa.MethodsWe searched for articles published between 1st December 2019 and 3rd January 2021 from various databases including PubMed, African Journals Online, MedRxiv, BioRxiv, Collabovid, the World Health Organisation global research database and Google for grey literature. Editorial type publications and papers reporting original research done in Africa and were included. Data analysis was done using Microsoft Excel.ResultsA total of 1296 articles were retrieved. 46.6% were primary research articles, 48.6% were editorials type articles while 4.6% were secondary research articles. 20.3% articles used the entire continent of Africa as their study setting while South Africa (15.4%) was the most common country focused setting. 90.3% of the articles had at least one African researcher as author, 78.5% had an African researcher as first author, while 63.5% had an African researcher as last author. The University of Cape Town tops the list with the greatest number of first and last authors. Over 13% of the articles were published in MedRxiv and of the studies that declared funding, the Wellcome Trust was the top funding body. The most common research topics include “country preparedness and response” (24.9%) and “the direct and indirect health impacts of the pandemic” (21.6%). However, only 1.0% of articles focus on therapeutics and vaccines.ConclusionsThis study sheds light on the contribution of African researchers to COVID-19 research in Africa and highlights Africa’s existing capacity to carry out research that addresses local problems. However, the uneven distribution of research productivity amongst African countries emphasizes the need for increased investment where needed.
Seroreactivity to SARS-CoV-2 in individuals attending a university campus in Bogotá Colombia
Authors: Gonzalez John M. , Santos-Barbosa Juan Carlos , Jaller Catherine , Otalora German , Hernandez Luis J. , Guevara-Suarez Marcela , Restrepo Silvia 
Published: March 2021

AbstractMost community-specific serological surveys for SARS-CoV-2 antibodies have been performed in healthcare workers and institutions. In this study, IgG antibodies specific to the virus were evaluated in individuals working at a university campus in Bogotá, Colombia. The aim of this work was to determine previous exposure to SARS-CoV-2 in those attending the campus during city lockdown. A total of 237 individuals, including 93 women and 144 men were evaluated using chemiluminescent detection of IgG anti N-viral protein between November and December 2020. There were 32 positives individuals corresponding to a seroprevalence of 13.5% (10 women and 22 men) and mostly asymptomatic (68.75%) and three cluster of seropositive individuals were identified. Only 13 of the seropositive individuals had previous positive detection of SARS-CoV-2 RNA by RT-qPCR performed in average 91 days before serological test. Seropositive individuals did not come from boroughs having higher percentages of SARS-CoV-2 cases in the city. This survey was carried out after the first peak of SARS-CoV-2 transmission in the city, and before the preparedness to reopening the campus for students in 2021, demonstrating a low seroprevalence in high percentage of asymptomatic. These results will help to evaluate some of the strategies stablished to control virus spread in the campus or other similar communities.
Long-term sequelae of Pneumococcal Sepsis in children: a systematic review
Authors: Ogunbameru Adeteju , Miranda Rafael Neves , Bielecki Joanna , Sander Beate 
Published: March 2021

ABSTRACTBackgroundLong-term sequelae associated with pneumococcal sepsis (PS) in pediatric patients in existing literature is currently unclear.AimTo review the evidence on sequelae and prognostic factors associated with PS among pediatric patients.MethodWe conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We screened six databases from their inception to January 15, 2021. Study population were neonates, infants, children and adolescents less than 18 years old with suspected or confirmed PS disease. Outcomes included sequelae types, prognostic factors, pooled death estimate and length of hospital stay (LOS) for survivors and deceased patients. Quality of studies was assessed using Joanna Briggs Institute appraisal checklists.ResultsWe screened 981 abstracts, and 24 full-text articles for final review. Septic shock was the most prevalent physical sequelae reported (13%, n=1492 patients). No functional, cognitive or neurological sequelae were reported in included studies. Meta-analysis of pooled mortality estimate was 14.6% (95%CI: 9.9 −19.4%). Prognostic factors associated with increased risk of PS sequelae and death included pediatric risk of mortality score ≥ 10 and co-infection with meningitis. LOS for survivors and non-survivors ranged between 5-30 days and 1-30 days. Nine included studies met at least 50% of the quality assessment criteria.ConclusionPhysical sequelae and death are the PS sequelae types currently identified in existing literature. Lack of information about other possible sequelae types suggests the long-term consequences of PS disease maybe underreported, especially in resource-limited settings. Future studies should consider exploring reasons for the existing of this knowledge gap.
OCD.py - Characterizing immunoglobulin inter-domain orientations
Authors: Hoerschinger Valentin J. , Fernández-Quintero Monica L. , Waibl Franz , Kraml Johannes , Bujotzek Alexander , Georges Guy , Liedl Klaus R. 
Published: March 2021

AbstractSummaryInter-domain orientations between immunoglobulin domains are important for the modeling and engineering of novel antibody therapeutics. Previous tools to describe these orientations are applicable only to the variable domains of antibodies and T-cell receptors. We present the “Orientation of Cylindrical Domains (OCD)” tool, which employs a transferable approach to calculate inter-domain orientations for all immunoglobulin domains. Based on a reference structure, the OCD tool automatically builds a suitable reference coordinate system for each domain. Through alignment, the reference coordinate systems are transferred onto the sample to calculate six measures which fully characterize the inter-domain orientation.Availability and implementationThe OCD approach is implemented as a stand-alone Python script, OCD.py, which can handle multiple types of data input for the analysis of single structures and molecular dynamics trajectories alike. OCD.py is available athttps://github.com/liedllab/OCDunder MIT license.Supplementary InformationSupplementary information and data are available atBioinformaticsonline.
The inflammasome-activated cytokine IL-1β is targeted for ubiquitylation and proteasomal degradation to limit its inflammatory potential
Authors: Vijayaraj Swarna L. , Feltham Rebecca , Rashidi Maryam , Frank Daniel , Liu Zhengyang , Simpson Daniel S. , Ebert Gregor , Vince Angelina , Herold Marco J. , Kueh Andrew , Pearson Jaclyn S. , Dagley Laura F. , Murphy James M. , Webb Andrew I. , Lawlor Kate E. , Vince James E. 
Published: March 2021

AbstractInterleukin-1β (IL-1β) is activated by inflammasome-associated caspase-1 in rare autoinflammatory conditions and in wide-spread diseases. Therefore, IL-1β activity must be fine-tuned to enable antimicrobial responses whilst limiting collateral damage. Here we report that precursor IL-1β is rapidly turned over by the proteasome and this correlates with its decoration by K11-, K63- and K48-linked ubiquitin chains. The ubiquitylation of IL-1β is not just a degradation signal triggered by inflammasome priming and activating stimuli, but also limits IL-1β cleavage by caspase-1. We further demonstrate that IL-1β K133 is modified by ubiquitin and forms a salt bridge with IL-1β D129. Loss of IL-1β K133 ubiquitylation, or disruption of the K133:D129 electrostatic interaction, stabilizes IL-1β. Accordingly,IL-1βK133R/K133Rmice display increased precursor IL-1β upon inflammasome priming and increased bioactive IL-1β, bothin vitroand following LPS injectionin vivo. These findings reveal new mechanisms for limiting IL-1β activity and safeguarding against damaging inflammation.
Immunoinformatic Approach for the identification of T Cell and B Cell Epitopes in the Surface Glycoprotein and Designing a Potent Multiepitope Vaccine Construct Against SARS-CoV-2 including the new UK variant
Authors: Selvaraj Gracy Fathima , Ramesh Kiruba , Padmanabhan Padmapriya , Gopalan Vidya , Govindan Karthikeyan , Chandran Aswathi , Srinivasan Sivasubramanian , Krishnasamy Kaveri 
Published: March 2021

AbstractThe emergence of a novel coronavirus in China in late 2019 has turned into a SARS-CoV-2 pandemic affecting several millions of people worldwide in a short span of time with high fatality. The crisis is further aggravated by the emergence and evolution of new variant SARS-CoV-2 strains in UK during December, 2020 followed by their transmission to other countries. A major concern is that prophylaxis and therapeutics are not available yet to control and prevent the virus which is spreading at an alarming rate, though several vaccine trials are in the final stage. As vaccines are developed through various strategies, their immunogenic potential may drastically vary and thus pose several challenges in offering both arms of immunity such as humoral and cell-mediated immune responses against the virus. In this study, we adopted an immunoinformatics-aided identification of B cell and T cell epitopes in the Spike protein, which is a surface glycoprotein of SARS-CoV-2, for developing a new Multiepitope vaccine construct (MEVC). MEVC has 575 amino acids and comprises adjuvants and various cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes that possess the highest affinity for the respective HLA alleles, assembled and joined by linkers. The computational data suggest that the MEVC is non-toxic, non-allergenic and thermostable with the capability to elicit both humoral and cell-mediated immune responses. The population coverage of various countries affected by COVID-19 with respect to the selected B and T cell epitopes in MEVC was also investigated. Subsequently, the biological activity of MEVC was assessed by bioinformatic tools using the interaction between the vaccine candidate and the innate immune system receptors TLR3 and TLR4. The epitopes of the construct were analyzed with that of the strains belonging to various clades including the new variant UK strain having multiple unique mutations in S protein. Due to the advantageous features, the MEVC can be testedin vitrofor more practical validation and the study offers immense scope for developing a potential vaccine candidate against SARS-CoV-2 in view of the public health emergency associated with COVID-19 disease caused by SARS-CoV-2.
Comparative Genomics of two Inbred Lines of the Potato Cyst NematodeGlobodera rostochiensisreveals disparate Effector Family-specific Diversification Patterns
Authors: van Steenbrugge Joris J.M. , van den Elsen Sven , Holterman Martijn , Sterken Mark G. , Thorpe Peter , Goverse Aska , Smant Geert , Helder Johannes 
Published: March 2021

AbstractBackgroundPotato cyst nematodes belong to the most harmful pathogens in potato, and durable management of these soil-borne parasites largely depends on host-plant resistances. These resistances are pathotype specific. The currentGlobodera rostochiensispathotype scheme that defines five pathotypes (Ro1 - Ro5) is for fundamental and practical reasons barely useful. As a result, resistant potato varieties are worldwide used in a non-informed manner.ResultsWe generated two novel reference genomes ofG. rostochiensisinbred lines derived from a Ro1 and a Ro5 population. These genome sequences comprise 173 and 189 scaffolds respectively, marking a ≈ 24-fold reduction in fragmentation as compared to the current reference genome. We provide copy number variations for 18 effector families. Four dorsal gland effector families were investigated in more detail. SPRYSECs, known to be implicated in immune suppression, constitute by far the most diversified family with 60 and 99 variants in Ro1 and Ro5 distributed over 18 and 26 scaffolds. In contrast, CLEs, effectors involved in feeding site induction, show strong physical clustering. The 10 and 16 variants cluster on respectively 2 and 1 scaffolds. Given that pathotypes are defined by their effectoromes, we pinpoint the disparate nature of the contributing effector families in terms of sequence diversification and loss and gain of variants.ConclusionTwo novel reference genomes allow for nearly complete inventories of effector diversification and physical organisation within and between pathotypes. Combined with insights we provide on effector family-specific diversification patterns, this constitutes a solid basis for an effectorome-based virulence scheme for this notorious pathogen.
scite: a smart citation index that displays the context of citations and classifies their intent using deep learning
Authors: Nicholson J.M. , Mordaunt M. , Lopez P. , Uppala A. , Rosati D. , Rodrigues N.P. , Grabitz P. , Rife S.C. 
Published: March 2021

AbstractCitation indices are tools used by the academic community for research and research evaluation which aggregate scientific literature output and measure scientific impact by collating citation counts. Citation indices help measure the interconnections between scientific papers but fall short because they only display paper titles, authors, and the date of publications, and fail to communicate contextual information about why a citation was made. The usage of citations in research evaluation without due consideration to context can be problematic, if only because a citation that disputes a paper is treated the same as a citation that supports it. To solve this problem, we have used machine learning and other techniques to develop a “smart citation index” called scite, which categorizes citations based on context. Scite shows how a citation was used by displaying the surrounding textual context from the citing paper, and a classification from our deep learning model that indicates whether the statement provides supporting or disputing evidence for a referenced work, or simply mentions it. Scite has been developed by analyzing over 23 million full-text scientific articles and currently has a database of more than 800 million classified citation statements. Here we describe how scite works and how it can be used to further research and research evaluation.
Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models
Authors: Bauer Lisa , Lendemeijer Bas , Leijten Lonneke , Embregts Carmen W. E. , Rockx Barry , Kushner Steven A. , de Vrij Femke M.S. , van Riel Debby 
Published: March 2021

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a wide variety of neurological complications. Even though SARS-CoV-2 is rarely detected in the central nervous system (CNS) or cerebrospinal fluid, evidence is accumulating that SARS-CoV-2 might enter the CNS via the olfactory nerve. However, what happens after SARS-CoV-2 enters the CNS is poorly understood. Therefore, we investigated the replication kinetics, cell tropism, and associated immune responses of SARS-CoV-2 infection in different types of neural cultures derived from human induced pluripotent stem cells (hiPSCs). SARS-CoV-2 was compared to the neurotropic and highly pathogenic H5N1 influenza A virus. SARS-CoV-2 infected a minority of individual mature neurons, without subsequent virus replication and spread, despite ACE2, TMPRSS2 and NPR1 expression in all cultures. However, this sparse infection did result in the production of type-III-interferons and IL-8. In contrast, H5N1 virus replicated and spread very efficiently in all cell types in all cultures. Taken together, our findings support the hypothesis that neurological complications might result from local immune responses triggered by virus invasion, rather than abundant SARS-CoV-2 replication in the CNS.
Early Spring Snowmelt and Summer Droughts Strongly Impair the Resilience of Key Microbial Communities in Subalpine Grassland Ecosystems
Authors: Hafeez Farhan , Bernard Lionel , Poly Franck , Clément Jean-Christophe , Pommier Thomas 
Published: March 2021

ABSTRACTSubalpine grassland ecosystems are important from biodiversity, agriculture, and touristic perspectives but their resilience to seasonally occurring climatic extremes is increasingly challenged with climate change, accelerating their vulnerability to tipping points. Microbial communities, which are central in ecosystem functioning, are usually considered as more resistant and highly resilient to such extreme events due to their functional redundancy and strong selection in residing habitats. To investigate this, we explored soil microbial responses upon recurrent summer droughts associated with early snowmelt in subalpine grasslands mesocosms set-up at the Lautaret Pass (French Alps). Potential respiration, nitrification and denitrification were monitored over a period of two growing seasons along with quantification of community gene abundances of total bacteria as well as (de)nitrifiers. Results revealed that droughts had a low and short-term adverse impact on bacterial total respiration supporting their hypothesized high resilience, i.e., resistance and ability to recover. Nitrification and abundances of the corresponding functional guilds showed relatively strong resistance to summer droughts but declined in response to early snowmelt. This triggered a cascading effect on denitrification but also on abundances of denitrifying communities which recovered from all climatic extremes except from the summer droughts where nitrifiers were collapsed. Denitrification and respective functional groups faced high impact of applied stresses with strong reduction in abundance and activity of this specialized community. Although, consequently lower microbial competition for nitrate may be positive for plant biomass production, warnings exist when considering the potential nitrogen leaching from these ecosystems as well as risks of greenhouses gases emission such as N2O.