bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trace, Quarantine, Test, Isolate and Treat: A Kerala Model of Covid-19 Response
Authors: Sulaiman KM , Muhammad T , A P Rishad Muhammad , Afsal K 
Published: June 2020

AbstractKerala reported the first three cases of coronavirus in India in late January. Kerala, one of the India’s most densely populated states, which makes its success in fighting the Covid-19 all the more commendable. Moreover, an estimated 17% of its 35 million population employed or lives elsewhere, more than 1 million tourists visit each year, and hundreds of students study abroad, including in China. All of this mobility makes the state more vulnerable to contagious outbreaks. What is the strategy behind the success story? This paper compares the situation of COVID-19 pandemic in major states and Kerala by the different phase of lockdown, and also highlights Kerala’s fight against the pandemic. We used publicly available data from https://www.covid19india.org/ and Covid-19 Daily Bulletin (Jan 31-May 31), Directorate of Health Services, Kerala (https://dashboard.kerala.gov.in/). We calculate the phase-wise period prevalence rate (PPR) and the case fatality rate (CFR) of the last phase. Compared to other major states, Kerala showed better response in preventing pandemic. The equation for the Kerala’s success has been simple, prioritized testing, widespread contact tracing, and promoting social distance. They also imposed uncompromising controls, were supported by an excellent healthcare system, government accountability, transparency, public trust, civil rights and importantly the decentralized governance and strong grass-root level institutions. The “proactive” measures taken by Kerala such as early detection of cases and extensive social support measures can be a “model for India and the world”.
Polyclonal epitope cartography reveals the temporal dynamics and diversity of human antibody responses to H5N1 vaccination
Authors: Han Julianna , Schmitz Aaron J. , Richey Sara T. , Dai Ya-Nan , Turner Hannah L. , Mohammed Bassem M. , Fremont Daved H. , Ellebedy Ali H. , Ward Andrew B. 
Published: June 2020

SUMMARYNovel influenza A virus (IAV) strains elicit recall immune responses to conserved epitopes, making them favorable antigenic choices for universal influenza virus vaccines. Evaluating these immunogens requires a thorough understanding of the antigenic sites targeted by the polyclonal antibody (pAb) response, which single particle electron microscopy (EM) can sensitively detect. Here, we employed EM polyclonal epitope mapping (EMPEM) to extensively characterize the pAb response to hemagglutinin (HA) after H5N1 immunization in humans. Cross-reactive pAbs originating from memory B cells immediately bound the stem of HA and persisted for over a year post vaccination. In contrast,de novopAb responses to multiple sites on the head of HA, which targeted previously determined key neutralizing sites on H5 HA, expanded after the second immunization and waned quickly. Thus, EMPEM provides a robust tool for comprehensively tracking the specificity and durability of immune responses elicited by novel universal influenza vaccine candidates.
Comparative Survival Analysis of Immunomodulatory Therapy for COVID-19 ‘Cytokine Storm’: A Retrospective Observational Cohort Study
Authors: Narain Sonali , Stefanov Dimitre G. , Chau Alice S. , Weber Andrew G. , Marder Galina , Kaplan Blanka , Malhotra Prashant , Bloom Ona , Liu Audrey , Lesser Martin L. , Hajizadeh Negin ,   Northwell COVID-19 Research Consortium
Published: June 2020

AbstractBackgroundCytokine storm is a marker of COVID-19 illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes.MethodsWe conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020 and April 15, 2020, were included. Cytokine storm was defined by inflammatory markers: ferritin >700ng/mL, C-reactive protein >30mg/dL, or lactate dehydrogenase >300U/L. Patients were subdivided into six groups -no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-interleukin 6 (IL-6) antibody (tocilizumab) or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality.ResultsThere were 3,098 patients who met inclusion criteria. The most common comorbidities were hypertension (40-56%), diabetes (32-43%) and cardiovascular disease (2-15%). Patients most frequently met criteria with high lactate dehydrogenase (74.8%) alone, or in combination, followed by ferritin (71.4%) and C-reactive protein (9.4%). More than 80% of patients had an elevated D-dimer. Patients treated with a combination of tocilizumab and corticosteroids (Hazard Ratio [HR]: 0.459, 95% Confidence Interval [CI]: 0.295-0.714; p<0.0001) or corticosteroids alone (HR: 0.696, 95% CI: 0.512-0.946; p=0.01) had improved hospital survival compared to standard of care. Corticosteroids and tocilizumab was associated with increased survival when compared to corticosteroids and anakinra (HR: 0.612, 95% CI: 0.391-0.958; p-value=0.02).ConclusionsWhen compared to standard of care, corticosteroid and tocilizumab used in combination, or corticosteroids alone, was associated with reduced hospital mortality for patients with COVID-19 cytokine storm.
PERSONAL PROTECTIVE EQUIPMENT (PPE) USING IN ANTALYA 112 EMERGENCY AMBULANCE SERVICES DURING OUTBREAK
Authors: Gulsen Mehmet Fatih , Kurt Münevver , Kaleli Isil , Ulasti Ayhan 
Published: June 2020

AbstractA new type of Coronavirus (SARS-CoV-2) was identified on January 7th, 2020, and the disease was named COVID-19 caused by this virus. The first confirmed COVID-19 (+) case in Antalya was detected on March 14th, 2020 and transferred by an Antalya 112 emergency ambulance to hospital.Using of Personal Protective Equipment (PPE) in ambulance work standards against COVID-19, was recommended by global health authorities. The aim of this descriptive, retrospective and cross-sectional study which is conducted between the dates of March 14th, 2020 – May 31st, 2020, is to evaluate the level of PPE usage, the risk analysis results of Antalya 112 ambulance teams during outbreak. There were 5344 possible and 787 confirmed COVID-19 (+) positive ambulance cases between the dates of study conducted. The majority of these cases were male (62%) and over the age of 65 (47%). The majority of cases were result in “transferred to healthcare facilities” (75.48%). The total 2361 ambulance team workers were taken to risk analysis measurements in terms of COVID-19. The majority of ambulance team members were assessed with no risk available. The ambulance team members who are assessed with no risk available, has preferred to use Level-4 PPE (N95/FPP-Goggle/face protection-Gloves-Apron/coverall) mostly (84.50%) during ambulance transfers. Using mask on patient and the level of PPE usage showed negative correlation with risk level of Healthcare Workers (HCWs). There have been detected only 2 HCWs diagnosed with COVID-19 with Computed Tomography. The follow-up procedures of two HCWs has been finalized, and both of them cured. The studies about easy-to-use, high-tech PPE with maximum protection, are recommended for further studies.
The King’s College London Coronavirus Health and Experiences of Colleagues at King’s Study (KCL CHECK) protocol paper: a platform for study of the effects of coronavirus pandemic on staff and postgraduate students
Authors: Davis Katrina A.S. , Stevelink Sharon A.M. , Al-Chalabi Ammar , Bergin-Cartwright Gabriella , Bhundia Rupa , Burdett Howard , Carr Ewan , Lavelle Grace , Leightley Daniel , Middleton Candice , Nicholson Timothy , O’Neill Lucy , Polling Catherine , Ruane Aoife , Wickersham Alice , Hotopf Matthew , Razavi Reza 
Published: June 2020

AbstractIntroductionWe will use an occupational sample to study the impact of COVID-19 on current staff and postgraduate research students at a large UK university. The cohort study will address some of the key questions about COVID-19 for the international community, while also providing feedback to the employer and educator.Methods and analysisParticipants were recruited via email to their University email address. Administrative records were available to compare the composition of volunteer participants to underlying staff and postgraduate student populations of the University. The study comprises a baseline survey, longitudinal follow-up surveys and a viral antibody study. Baseline information was collected in April 2020 including demographics, working situation, current stresses and worries, mental health and neurological symptoms. Personal experiences of COVID-19, indirect experiences and attitudes towards the pandemic were queried, as well as satisfaction with communication and support at work. Longitudinal surveys will assess changes in COVID-19 exposure and mental health. A viral antibody detection component is being planned and will also be longitudinal in nature.Ethics and disseminationEthical approval has been gained from KCL’s Psychiatry, Nursing and Midwifery Research Ethics Committee (HR-19/20-18247). Participants were provided with information and agreed to a series of consent statements before enrolment. Data are kept on secure servers with access to personally identifiable information limited. Researchers may apply to have access to pseudonymised data. Findings will be disseminated internally to the University and participants, and externally through scientific publications.
Multimodal FDG-PET and EEG assessment improves diagnosis and prognostication of disorders of consciousness
Authors: Hermann Bertrand , Stender Johan , Habert Marie-Odile , Kas Aurélie , Denis-Valente Mélanie , Raimondo Federico , Pérez Pauline , Rohaut Benjamin , Sitt Jacobo Diego , Naccache Lionel 
Published: June 2020

ABSTRACTThe complex diagnosis of disorders of consciousness (DoC) diagnosis increasingly relies on brain-imaging techniques for their ability to detect residual signs of consciousness in otherwise unresponsive patients. However, few of these techniques have been validated on external datasets. Here, we show that the FDG-PET glucose metabolic index of the best preserved hemisphere has robust in-sample and out-sample performances to diagnose DoC, slightly outperforming EEG-based classification. We further show that a multimodal assessment combining both FDG-PET and EEG not only improved diagnostic performances, but also allowed to identify covert cognition and to predict 6-month responsiveness in initially unresponsive patients. Lastly, we show that DoC heterogeneity reflects a sum of regional cortical metabolic differences, and their corresponding behavioral patterns, rather than a binary contrast between conscious and unconscious states. In total, we show that FDG-PET and EEG provide complementary information on DoC physiopathology and that their combination improves DoC diagnosis and prognostication.
A Counterfactual Graphical Model Reveals Economic and Sociodemographic Variables as Key Determinants of Country-Wise COVID-19 Burden
Authors: Sethi Tavpritesh , Kedia Saurabh , Awasthi Raghav , Lodha Rakesh , Ahuja Vineet 
Published: June 2020

AbstractImportanceInsights into the country-wise differences in COVID-19 burden can impact the policies being developed to control disease spread.ObjectivePresent study evaluated the possible socio-economic and health related factors (and their temporal consistency) determining the disease burden of COVID-19.DesignA retrospective analysis for identifying associations of COVID-19 burden.SettingData on COVID-19 statistics (number of cases, tests and deaths per million) was extracted from the website https://www.worldometers.info/coronavirus/ on 10th April and 12th May. Variables obtained to estimate the possible determinants for COVID-19 burden included economic-gross domestic product; socio-demographic-Sustainable Development Goals, SDGs indicators related to health systems, percentage Chinese diaspora; and COVID-19 trajectory-date of first case in each country, days between first reported case and 10th April, days between 100th and 1000th case, and government response stringency index (GRSI).Main outcomes and MeasuresCOVID-19 burden was modeled using economic and socio-demographic determinants. Consistency of inferences for two time points at three levels of increasing statistical rigor using (i) Spearman correlations, (ii) Bayesian probabilistic graphical model, and (iii) counterfactual impact was evaluated.ResultsCountries’ economy (reflected by GDP), mainly through the testing rates, was the major and temporally consistent determinant of COVID-19 burden in the model. Reproduction number of COVID-19 was lower where mortality due to water, sanitation, and hygiene (WaSH) was higher, thus strengthening the hygiene hypothesis. There was no association between vaccination status or tuberculosis incidence and COVID burden, refuting the claims over BCG vaccination as a possible factor against COVID-19 trajectory.Conclusion and RelevanceCountries’ economy, through testing power, was the major determinant of COVID-19 burden. There was weak evidence for hygiene hypothesis as a protective factor against COVID-19.
Common genetic associations between age-related diseases
Authors: Dönertaş Handan Melike , Fabian Daniel K. , Valenzuela Matías Fuentealba , Partridge Linda , Thornton Janet M. 
Published: June 2020

AbstractAge is a common risk factor in many diseases, but the molecular basis for this relationship is elusive. In this study we identified 4 disease clusters from 116 diseases in the UK Biobank data, defined by their age-of-onset profiles, and found that diseases with the same onset profile are genetically more similar, suggesting a common etiology. This similarity was not explained by disease categories, co-occurrences or disease cause-effect relationships. Two of the four disease clusters had an increased risk of occurrence from age 20 and 40 years respectively. They both showed an association with known aging-related genes, yet differed in functional enrichment and evolutionary profiles. We tested mutation accumulation and antagonistic pleiotropy theories of aging and found support for both. We also identified drug candidates for repurposing to target multiple age-dependent diseases with the potential to improve healthspan and alleviate multimorbidity and polypharmacy in the elderly.
Re-use of trial data in the first 10 years of the data-sharing policy of the Annals of Internal Medicine: a survey of published studies
Authors: Pellen Claude , Caquelin Laura , Bail Alexia Jouvance-Le , Gaba Jeanne , Vérin Mathilde , Moher David , Ioannidis John P. A. , Naudet Florian 
Published: June 2020

ABSTRACTBackgroundThe Annals of Internal Medicine (AIM) has adopted a policy encouraging data-sharing since 2007.ObjectiveTo explore the impact of the AIM data-sharing policy for randomized controlled trials (RCTs) in terms of output from data-sharing (i.e. publications re-using the data).DesignRetrospective study.SettingAIM.ParticipantsRCTs published in the AIM between 2007 and 2017 were retrieved on PubMed. Publications where the data had been re-used were identified on Web of Science. Searches were performed by two independent reviewers.InterventionsIntention to share data (or not) expressed in a data-sharing statement.MeasurementsThe primary outcome was any published re-use of the data (i.e. re-analysis, secondary analysis, or meta-analysis of individual participant data [MIPD]), where the first, last and corresponding authors were not among the authors of the RCT. Components of the primary outcome and analyses without any author restriction were secondary outcomes. Analyses used Cox (primary analysis) models adjusting for RCT characteristics.Results185 RCTs were identified. 106 (57%) mentioned willingness to share data and 79 (43%) did not. 208 secondary analyses, 67 MIPD and no re-analyses were identified. No significant association was found between intent to share and re-use where the first, last and corresponding authors were not among the authors of the primary RCT (adjusted hazard ratio = 1.04 [0.47-2.30]). Secondary outcomes also showed no association between intent to share and re-use.LimitationsPossibility of residual confounding and limited power.ConclusionOver ten years, RCTs published in AIM expressing an intention to share data were not associated with more extensive re-use of the data.Registrationhttps://osf.io/8pj5e/Funding SourceGrants from the Fondation pour la Recherche Médicale, Région Bretagne, and French National Research Agency.
Potent Neutralizing Antibodies Directed to Multiple Epitopes on SARS-CoV-2 Spike
Authors: Liu Lihong , Wang Pengfei , Nair Manoj S. , Yu Jian , Rapp Micah , Wang Qian , Luo Yang , Chan Jasper F-W. , Sahi Vincent , Figueroa Amir , Guo Xinzheng V. , Cerutti Gabriele , Bimela Jude , Gorman Jason , Zhou Tongqing , Chen Zhiwei , Yuen Kwok-Yung , Kwong Peter D. , Sodroski Joseph G. , Yin Michael T. , Sheng Zizhang , Huang Yaoxing , Shapiro Lawrence , Ho David D. 
Published: June 2020

AbstractThe SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that are overlapping with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.
The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins
Authors: Conceicao Carina , Thakur Nazia , Human Stacey , Kelly James T. , Logan Leanne , Bialy Dagmara , Bhat Sushant , Stevenson-Leggett Phoebe , Zagrajek Adrian K. , Hollinghurst Philippa , Varga Michal , Tsirigoti Christina , Hammond John A. , Maier Helena J. , Bickerton Erica , Shelton Holly , Dietrich Isabelle , Graham Stephen C. , Bailey Dalan 
Published: June 2020

AbstractSARS-CoV-2 emerged in late 2019, leading to the COVID-19 pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as well as related coronaviruses circulating in bats, SARS-CoV-2 is thought to have originated in Chiroptera species in China. However, whether the virus spread directly to humans or through an intermediate host is currently unclear, as is the potential for this virus to infect companion animals, livestock and wildlife that could act as viral reservoirs. Using a combination of surrogate entry assays and live virus we demonstrate that, in addition to human ACE2, the Spike glycoprotein of SARS-CoV-2 has a broad host tropism for mammalian ACE2 receptors, despite divergence in the amino acids at the Spike receptor binding site on these proteins. Of the twenty-two different hosts we investigated, ACE2 proteins from dog, cat and rabbit were the most permissive to SARS-CoV-2, while bat and bird ACE2 proteins were the least efficiently used receptors. The absence of a significant tropism for any of the three genetically distinct bat ACE2 proteins we examined indicates that SARS-CoV-2 receptor usage likely shifted during zoonotic transmission from bats into people, possibly in an intermediate reservoir. Interestingly, while SARS-CoV-2 pseudoparticle entry was inefficient in cells bearing the ACE2 receptor from bats or birds the live virus was still able to enter these cells, albeit with markedly lower efficiency. The apparently broad tropism of SARS-CoV-2 at the point of viral entry confirms the potential risk of infection to a wide range of companion animals, livestock and wildlife.
Small Non-coding RNAome of ageing chondrocytes
Authors: Balaskas Panagiotis , Green Jonathan A. , Haqqi Tariq M. , Dyer Philip , Kharaz Yalda A. , Fang Yongxiang , Liu Xuan , Welting Tim J.M. , Peffers Mandy J. 
Published: June 2020

ABSTRACTBackgroundAgeing is one of the leading risk factors predisposing cartilage to musculoskeletal diseases, including osteoarthritis. Cumulative evidence suggests that small non-coding RNAs play a role in cartilage-related pathological changes. However, little research has been conducted on the effect of ageing on the expression of small non-coding RNAs in cartilage. By using small RNA sequencing, we investigated changes in the expression of small non-coding RNAs between young and old equine chondrocytes.MethodsChondrocytes were extracted from five young (4±1 years) and five old (17.4±1.9 years) macroscopically normal equine metacarpophalangeal joints. Following RNA extraction cDNA libraries were prepared and subjected to small RNA sequencing using the Illumina MiSeq platform. Differential expression analysis was performed in R using package DESeq2. For tRNA fragment analysis, tRNA reads were aligned to horse tRNA sequences using Bowtie2 version 2.2.5. Selected microRNA and small nucleolar RNA findings were validated using qRT-PCR in an extended cohort of equine chondrocytes. tRNA fragments were further investigated in low and high grade OA human cartilage tissue.ResultsIn total, 83 sncRNAs were differentially expressed between young and old equine chondrocytes, including microRNAs, snoRNAs, snRNAs and tRNAs. Of these, 34 were expressed higher and 49 were expressed lower in old chondrocytes compared to young. qRT-PCR analysis confirmed findings in an extended cohort of equine chondrocytes. Ingenuity Pathway Analysis of differentially expressed microRNAs and their predicted target genes linked them to cartilage and OA-related pathways and diseases. tRNA fragment analysis revealed that tiRNA-5035-GluCTC and tiRNA-5031-GluCTC-1 were reduced in both high grade OA human cartilage and old equine chondrocytes.ConclusionFor the first time, we have measured the effect of ageing on the expression of small non-coding RNAs in equine chondrocytes. Changes were detected in a number of different sncRNA species, including microRNAs, small nucleolar RNAs and tRNA fragments. This study supports a role for small non-coding RNAs in ageing cartilage and their potential involvement in age-related cartilage diseases.