bluuebunny/crossref_metadata_2025_split huggingface dataset:
REACT-1 round 9 interim report: downward trend of SARS-CoV-2 in England in February 2021 but still at high prevalence
Authors: Riley Steven , Walters Caroline E. , Wang Haowei , Eales Oliver , Haw David , Ainslie Kylie E. C. , Atchison Christina , Fronterre Claudio , Diggle Peter J. , Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul 
Published: February 2021

AbstractBackground and MethodsEngland entered its third national lockdown of the COVID-19 pandemic on 6th January 2021 with the aim of reducing the daily number of deaths and pressure on healthcare services. The real-time assessment of community transmission study (REACT-1) obtains throat and nose swabs from randomly selected people in England in order to describe patterns of SARS-CoV-2 prevalence. Here, we report data from round 9a of REACT-1 for swabs collected between 4th and 13th February 2021.ResultsOut of 85,473 tested-swabs, 378 were positive. Overall weighted prevalence of infection in the community in England was 0.51%, a fall of more than two thirds since our last report (round 8) in January 2021 when 1.57% of people tested positive. We estimate a halving time of 14.6 days and a reproduction number R of 0.72, based on the difference in prevalence between the end of round 8 and the beginning of round 9. Although prevalence fell in all nine regions of England over the same period, there was greater uncertainty in the trend for North West, North East, and Yorkshire and The Humber. Prevalence fell substantially across all age groups with highest prevalence among 18- to 24-year olds at 0.89% (0.47%, 1.67%) and those aged 5 to12 years at 0.86% (0.60%, 1.24%). Large household size, living in a deprived neighbourhood, and Asian ethnicity were all associated with increased prevalence. Healthcare and care home workers were more likely to test positive compared to other workers.ConclusionsThere is a strong decline in prevalence of SARS-CoV-2 in England among the general population five to six weeks into lockdown, but prevalence remains high: at levels similar to those observed in late September 2020. Also, the number of COVID-19 cases in hospitals is higher than at the peak of the first wave in April 2020. The effects of easing of social distancing when we transition out of lockdown need to be closely monitored to avoid a resurgence in infections and renewed pressure on health services.
Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial
Authors: Gonzalez Jose Lenin Beltran , González Gámez Mario , Enciso Emanuel Antonio Mendoza , Maldonado Ramiro Josue Esparza , Hernández Palacios Daniel , Dueñas Campos Samuel , Robles Itzel Ovalle , Macías Guzmán Mariana Jocelyn , García Díaz Andrea Lucia , Gutiérrez Peña César Mauricio , Medina Lucila Martinez , Colin Victor Antonio Monroy , Manuel Arreola Guerra Jose 
Published: February 2021

AbstractBackgroundIn the search for active drugs against COVID-19, the indications of many have been redirected. Ivermectin and Hydroxychloroquine are drugs that inhibit viral replication in vitro and that have been used in several medical centers.ObjectivesThis clinical trial analyzes the efficacy of Ivermectin and Hydroxychloroquine in patients with moderate COVID-19 and in need of hospitalization.MethodsThis a controlled, clinical, randomized, double-blind trial that included patients with COVID-19-induced pneumonia and hospitalization criteria, but no severe respiratory failure. Patients were randomized to one of three groups: Group1-hydroxychloroquine, 400 mg every 12 hours on the first day and subsequently, 200 mg every 12 hours for 4 days, Group 2-ivermectin, 12 mg or 18 mg, according to patient weight and, Group 3-placebo. At inclusion, blood samples for arterial blood gases and biochemical markers associated with a poor prognosis were obtained. The primary outcome was established as the duration of hospitalization until discharge due to patient improvement, the total duration of hospitalization, and the safety outcomes were either respiratory deterioration or death.ResultsDuring the month of August, the admission of patients requiring hospitalization mostly encompassed cases with severe respiratory failure, so we ended the recruitment process and analyzed the data that was available at the time. One hundred and six (106) patients with an average age of 53 yrs. (±16.9) were included, with a greater proportion of males (n=66, 62.2 %). Seventy-two percent (72%) (n= 76) had an associated comorbidity. Ninety percent (90 %) of patients were discharged due to improvement (n=96). The average duration of hospitalization was 6 days (IQR, 3 – 10). No difference in hospitalization duration was found between the treatment groups (Group1: 7 vs Group 2: 6 vs Group 3: 5, p=0.43) nor in respiratory deterioration or death (Group 1: 18 % vs Group 2: 22.2 % vs Group 3: 24.3 %, p =0.83).ConclusionsIn non-critical hospitalized patients with COVID-19 pneumonia, neither ivermectin nor hydroxychloroquine decreases the number of in-hospital days, respiratory deterioration, or deaths.ClinicalTrials identifier NCT04391127
Cohort profile: 10K - a large-scale prospective longitudinal study in Israel
Authors: Shilo Smadar , Bar Noam , Keshet Ayya , Talmor-Barkan Yeela , Rossman Hagai , Godneva Anastasia , Aviv Yaron , Edlitz Yochai , Reicher Lee , Kolobkov Dmitry , Wolf Bat Chen , Lotan-Pompan Maya , Levi Kohava , Cohen Ori , Saranga Hila , Weinberger Adina , Segal Eran 
Published: February 2021

AbstractThe 10K is a large-scale prospective longitudinal cohort and biobank that was established in Israel. The primary aims of the study include development of prediction models for disease onset and progression and identification of novel molecular markers with a diagnostic, prognostic and therapeutic value. The recruitment was initiated in 2018 and is expected to complete in 2021. Between 28/01/2019 and 13/12/2020, 4,629 from the expected 10,000 participants were recruited (46%). Follow-up visits are scheduled every year for a total of 25 years. The cohort includes individuals between the age of 40 and 70 years old. Predefined medical conditions were determined as exclusions. Information collected at baseline includes medical history, lifestyle and nutritional habits, vital signs, anthropometrics, blood tests results, Electrocardiography (ECG), Ankle–brachial pressure index (ABI), liver US and Dual-energy X-ray absorptiometry (DXA) tests. Molecular profiling includes transcriptome, proteome, gut and oral microbiome, metabolome and immune system profiling. Continuous measurements include glucose levels using a continuous glucose monitoring (CGM) device for 2 weeks and sleep monitoring by a home sleep apnea test (HSAT) device for 3 nights. Blood and stool samples are collected and stored at −80 °C in a storage facility for future research. Linkage is being established with national disease registries.
Differential effects of brain maintenance and cognitive reserve on age-related cognitive decline
Authors: Gazes Yunglin , Lee Seonjoo , Fang Zhiqian , Mensing Ashley , Noofoory Diala , Nazario Geneva Hidalgo , Babukutty Reshma , Chen Bryan , Habeck Christian , Stern Yaakov 
Published: February 2021

AbstractAge-related cognitive changes can be influenced by both brain maintenance (BM), which refers to the relative absence over time of changes in neural resources or neuropathologic changes, and cognitive reserve (CR), which encompasses brain processes that allow for better-than-expected behavioral performance given the degree of life-course related brain changes. This study evaluated the effects of age, BM, and CR on longitudinal changes over two visits, 5 years apart, in four reference cognitive abilities that capture most of age-related variability. Participants included 254 healthy adults aged 20–80 years at recruitment. Potential BM was estimated using whole brain cortical thickness and white matter mean diffusivity at both visits. Education and IQ (estimated with AMNART) were tested as moderating factors for cognitive changes in the four reference abilities. Consistent with BM, after accounting for age, sex, and baseline performance, individual differences in the preservation of mean diffusivity were associated with relative preservation in the four abilities; differential preservation of cortical thickness was associated with preservation of reasoning, processing speed, and memory. Consistent with CR, after accounting for structural brain changes, higher IQ, but not education, was associated with reduced 5-year decline in reasoning. A similar marginal association was seen for memory but not for processing speed. These results demonstrate that both CR and BM can moderate cognitive changes in healthy aging and that the two mechanisms can make differential contributions to preserved cognition.SignificanceThe theoretical constructs of brain maintenance (BM) and cognitive reserve (CR) are postulated to account for individual differences in age-related cognitive decline. To further understand BM and CR mechanisms, this study used a lifespan sample to examine 5-year changes in four cognitive abilities that comprehensively capture cognitive aging. Education has been the most used life exposure when studying CR, but recent studies suggest that education does not moderate age-related changes in brain and cognition in healthy aging so IQ was also considered. The results demonstrated that BM and CR can both exert unique influences on the same cognitive ability and that the two mechanisms differentially moderate change in the four reference abilities.
Temporal and geographical variation of COVID-19 in-hospital fatality rate in Brazil
Authors: Portella Tatiana Pineda , Mortara Sara Ribeiro , Lopes Rafael , Sánchez-Tapia Andrea , Donalísio Maria Rita , Castro Marcia C. , Venturieri Vito Ribeiro , Estevam Camila Genaro , Ribeiro Ana Freitas , Coutinho Renato Mendes , Sousa Mascena Veras Maria Amélia de , Inácio Prado Paulo , André Kraenkel Roberto 
Published: February 2021

AbstractBackgroundPrevious studies have shown that COVID-19 In-Hospital Fatality Rate (IHFR) varies between regions and has been diminishing over time. It is believed that the continuous improvement in the treatment of patients, age group of hospitalized, and the availability of hospital resources might be affecting the temporal and regional variation of IHFR. In this study, we explored how the IHFR varied over time and among age groups and federative states in Brazil. In addition, we also assessed the relationship between hospital structure availability and peaks of IHFR.MethodsA retrospective analysis of all COVID-19 hospitalizations with confirmed outcomes in 22 states between March 01 and September 22, 2020 (n=345,281) was done. We fit GLM binomial models with additive and interaction effects between age groups, epidemiological weeks, and states. We also evaluated the association between the modeled peak of IHFR in each state and the variables of hospital structure using the Spearman rank correlation test.ResultsWe found that the temporal variation of the IHFR was heterogeneous among the states, and in general it followed the temporal trends in hospitalizations. In addition, the peak of IHFR was higher in states with a smaller number of doctors and intensivists, and in states in which a higher percentage of people relied on the Public Health System (SUS) for medical care.ConclusionsOur results suggest that the pressure over the healthcare system is affecting the temporal trends of IHFR in Brazil.Key MessagesTemporal variation of age adjusted In-Hospital Fatality Rate (IHFR) was markedly heterogeneous among Brazilian states from March to September of 2020.In several states, the IHFR increased in association with the increase in the number of hospitalizations, which suggests that the overload of the healthcare system might be affecting the temporal trends of IHFR in Brazil.The IHFR remained low in the states with higher rates of hospital resources, even with the high demand for hospitalization.The number of doctors and intensivist physicians per habitant was more strongly correlated with the peak of IHFR in the Brazilian states than the number of ICU beds.
The U-shaped association of serum iron level with disease severity in adult hospitalized patients with COVID-19
Authors: Tojo Kentaro , Sugawara Yoh , Oi Yasufumi , Ogawa Fumihiro , Higurashi Takuma , Yoshimura Yukihiro , Miyata Nobuyuki , Hayami Hajime , Yamaguchi Yoshikazu , Ishikawa Yoko , Takeuchi Ichiro , Tachikawa Natsuo , Goto Takahisa 
Published: February 2021

AbstractCoronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.
CIITA G-286A promoter polymorphism impairs monocytes HLA-DR expression in septic shock and is rescued by interferon-γ
Authors: Miatello Jordi , Lukaszewicz Anne-Claire , Faivre Valérie , Hua Stéphane , Martinet Kim Zita , Bourgeois Christine , Quintana-Murci Lluis , Payen Didier , Boniotto Michele , Tissières Pierre 
Published: February 2021

ABSTRACTMonocyte HLA-DR is an increasingly recognized markers of sepsis-induced immunodepression, but its regulatory mechanisms remain poorly understood in sepsis. Several evidence for positive selection on the 5’ promoter region of HLA class II transactivator (CIITA) gene, the master regulator of MHC class II, have been gathered in the European population, and its role in sepsis has never been demonstrated, whilst suggested in autoimmune disease. We aim to describe the effect of rs3087456 polymorphism, localized on CIITA promoter III (pIII), on mortality of patients with septic shock, and investigate the mechanisms regulating HLA-DR expression. Genotyping of 203 patients with septic shock showed that, in A dominant model, GG genotype was associated with 28-day mortality (OR 2.29; 95%CI: 1.01 to 5.22; P = 0.043). Monocyte HLA-DR remained low in patients with GG genotype whereas it increases as early as at the end of the first week in intensive care in patients with AA or AG genotype. Using site-directed mutagenesis, in vitro reporter gene promoter activity of the pIII was decreased in GG genotype in monocyte cell line. Interferon-γ (IFN-γ) restored pIII activity in GG genotype as well as restore, in ex vivo experiment in healthy volunteers, CIITA pIII expression of GG genotype. Hereby, we demonstrated that rs3087456, a positively selected polymorphism of CIITA proximal promoter, significantly impact monocyte HLA-DR expression in patients with septic shock through CIITA promoter activity, that can be rescued using IFN-γ, offering a new perspective in genetic susceptibility to sepsis and targeted immunomodulatory therapy.KeypointsCIITA G-286A polymorphism reduces promotor activity and significantly impact monocyte HLA-DR expression and mortality in septic shockDownregulatory effects of CIITA G-286A polymorphism on monocyte HLA-DR expression can be reverse by IFN-γ in patients with septic shock
SARS-CoV-2 disinfection in aqueous solution by UV222 from a krypton chlorine excilamp
Authors: Robinson Richard T. , Mahfooz Najmus , Rosas-Mejia Oscar , Liu Yijing , Hull Natalie M. 
Published: February 2021

ABSTRACTThere is an urgent need for evidence-based development and implementation of engineering controls to reduce transmission of SARS-CoV-2, the etiological agent of COVID-19. Ultraviolet (UV) light can inactivate coronaviruses, but the practicality of UV light as an engineering control in public spaces is limited by the hazardous nature of conventional UV lamps, which are Mercury (Hg)-based and emit a peak wavelength (254 nm) that penetrates human skin and is carcinogenic. Recent advances in the development and production of Krypton Chlorine (KrCl) excimer lamps hold promise in this regard, as these emit a shorter peak wavelength (222 nm) and are recently being produced to filter out emission above 240 nm. However, the disinfection kinetics of KrCl UV excimer lamps against SARS-CoV-2 are unknown. Here we provide the first dose response report for SARS-CoV-2 exposed to a commercial filtered KrCl excimer light source emitting primarily 222 nm UV light (UV222), using multiple assays of SARS-CoV-2 viability. Plaque infectivity assays demonstrate the pseudo-first order rate constant of SARS-CoV-2 reduction of infectivity to host cells to be 0.64 cm2/mJ (R2 = 0.95), which equates to a D90 (dose for 1 log10 or 90% inactivation) of 1.6 mJ/cm2. Through RT-qPCR assays targeting the nucleocapsid (N) gene with a short (<100 bp) and long (∼1000 bp) amplicon in samples immediately after UV222 exposure, the reduction of ability to amplify indicated an approximately 10% contribution of N gene damage to disinfection kinetics. Through ELISA assay targeting the N protein in samples immediately after UV222 exposure, we found no dose response of the ability to damage the N protein. In both qPCR assays and the ELISA assay of viral outgrowth supernatants collected 3 days after incubation of untreated and UV222 treated SARS-CoV-2, molecular damage rate constants were similar, but lower than disinfection rate constants. These data provide quantitative evidence for UV222 doses required to disinfect SARS-CoV-2 in aqueous solution that can be used to develop further understanding of disinfection in air, and to inform decisions about implementing UV222 for preventing transmission of COVID19.ABSTRACT ART / TOC GRAPHIC
Nosocomial outbreak of SARS-CoV-2 in a “non-COVID-19” hospital ward: virus genome sequencing as a key tool to understand cryptic transmission
Authors: Borges Vítor , Isidro Joana , Macedo Filipe , Neves José , Silva Luís , Paiva Mário , Barata José , Catarino Judite , Ciobanu Liliana , Duarte Sílvia , Vieira Luís , Guiomar Raquel , Gomes João Paulo 
Published: February 2021

ABSTRACTBackgroundDissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare institutions affects both patients and health-care workers (HCW), as well as the institutional capacity to provide essential health services.MethodsWe conducted an investigation of a cluster of SARS-CoV-2 positive cases detected in a “non-COVID-19” hospital ward during Summer 2020. The magnitude of the nosocomial outbreak was disclosed by massive testing, challenging the retrospective reconstruction of the introduction and transmission events. An in-depth contact tracing investigation was carried out to identify the contacts network during the 15-day period before the screening. In parallel, positive SARS-CoV-2 RNA samples were subjected to virus genome sequencing.ResultsOf the 245 tested individuals, 48 (21 patients and 27 HCWs) tested positive for SARS-CoV-2. HCWs were mostly asymptomatic, but the mortality among the vulnerable patient group reached 57.1% (12/21). Phylogenetic reconstruction revealed that all cases were part of the same transmission chain, thus confirming a single origin behind this nosocomial outbreak. By combining vast epidemiological and genomic data, including analysis of emerging minor variants, we unveiled a scenario of silent SARS-CoV-2 dissemination within the hospital ward, mostly driven by the close contact within the HCWs group and between HCWs and patients. This investigation triggered enhanced prevention and control measures, leading to a more timely detection and containment of novel nosocomial outbreaks.ConclusionsThe present study shows the benefit of combining genomic and epidemiological data for the investigation of complex nosocomial outbreaks, and provides valuable data to minimize the risk of transmission of COVID-19 in healthcare facilities.Short summarySARS-CoV-2 nosocomial outbreaks are of utmost public health concern. Here, we performed an in-depth investigation of a high-fatality rate nosocomial outbreak by combining vast genomic and epidemiological data, providing valuable information to understand cryptic transmission of SARS-CoV-2 within healthcare institutions.
Prediction of type 1 diabetes at birth: cord blood metabolites versus genetic risk score in the MoBa cohort
Authors: Tapia German , Suvitaival Tommi , Ahonen Linda , Lund-Blix Nicolai A. , R. Njølstad Pål , Joner Geir , Skrivarhaug Torild , Legido-Quigley Cristina , Størdal Ketil , Stene Lars C. 
Published: February 2021

AbstractBackground and aimGenetic markers are established as predictive of type 1 diabetes, but unknown early life environment is believed to be involved. Umbilical cord blood may reflect perinatal metabolism and exposures. We studied whether selected polar metabolites in cord blood contribute to prediction of type 1 diabetes.MethodsUsing a targeted UHPLC-QQQ-MS platform, we quantified 27 low molecular weight metabolites (including amino acids, small organic acids and bile acids) in 166 children, who later developed type 1 diabetes, and 177 random control children in the Norwegian Mother, Father and Child (MoBa) cohort. We analysed the data using logistic regression (estimating odds ratios per standard deviation [aOR]), area under the receiver operating characteristic curve (AUC) and k-means clustering. Metabolites were compared to a genetic risk score based on 51 established non-HLA SNPs, and a four-category HLA risk group.ResultsThe strongest associations for metabolites were aminoadipic acid (aOR=1.23,95%CI:0.97–1.55), indoxyl sulfate (aOR=1.15,95%CI:0.87–1.51), and tryptophan (aOR=0.84,95%CI:0.65–1.10), with other aORs close to 1.0, and none significantly associated with type 1 diabetes. K-means clustering identified six clusters, none of which were associated with type 1 diabetes. Cross-validated AUC showed no predictive value of metabolites (AUC 0.49), while the non-HLA genetic risk score AUC was 0.56 and the HLA risk group AUC was 0.78.ConclusionsIn this large study, we found no support of a predictive role of cord blood concentrations of selected bile acids and other small polar metabolites in the development of type 1 diabetes.TweetPredicting childhood type 1 diabetes with cord blood biomarkers: genetic risk score works but metabolites do not@OsloDiabetes #T1D