bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of COVID-19 patients to understand the key predictors of mortality in the non-vaccinated groups in remote settings
Authors: Jain Neha L. , Parekh Karishma , Saigal Rishi , Alyusuf Amal , Kelly Gabrielle , Jha Alokkumar 
Published: January 2022

AbstractVarious studies have looked into the impact of the COVID-19 vaccine on large populations. However, very few studies have looked into the remote setting of hospitals where vaccination is challenging due to social structure, myths, and misconceptions. There is a consensus that elevated inflammatory markers such as CRP, ferritin, D-dimer correlate with increased severity of COVID-19 and are associated with worse outcomes. In the present study, through retrospective meta-analysis, we have looked into ∼20 months of SARS-COV2 infected patients with known mortality status and identified predictors of mortality concerning their comorbidities, various clinical parameters, inflammatory markers, superimposed infections, length of hospitalization, length of mechanical ventilation and ICU stay. Studies with larger sample sizes have covered the outcomes through epidemiological, social, and survey-based analysis—however, most studies cover larger cohorts from tertiary medical centers. In the present study, we assessed the outcome of non-vaccinated COVID 19 patients in a remote setting for 20 months from January 1, 2020, to August 30, 2021, at CHI Mercy Health in Roseburg, Oregon. We also included two vaccinated patients from September 2021 to add to the power of our cohort. The study will provide a comprehensive methodology and deep insight into multi-dimensional data in the unvaccinated group, translational biomarkers of mortality, and state-of-art to conduct such studies in various remote hospitals.
The impact of Mendelian sleep and circadian genetic variants in a population setting
Authors: Weedon Michael N. , Jones Samuel E. , Lane Jacqueline. M. , Lee Jiwon , Ollila Hanna M. , Dawes Amy , Tyrrell Jess , Beaumont Robin N. , Partonen Timo , Merikanto Ilona , Rich Stephen S. , Rotter Jerome I. , Frayling Timothy M. , Rutter Martin K , Redline Susan , Sofer Tamar , Saxena Richa , Wood Andrew R. 
Published: January 2022

ABSTRACTRare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants of these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts.We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data.We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. We found no association of any of these variants with extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being “definitely a morning person”, P=4×10−8; and had a 57-minute earlier midpoint sleep, P=5×10−7).Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.
Evaluation of Commercial Anti-SARS-CoV-2 Neutralizing Antibody Assays in seropositive subjects
Authors: Saker Kahina , Pozzetto Bruno , Escuret Vanessa , Pitiot Virginie , Massardier-Pilonchéry Amélie , Mokdad Bouchra , Langlois-Jacques Carole , Rabilloud Muriel , Alfaiate Dulce , Guibert Nicolas , Fassier Jean-Baptiste , Bal Antonin , Trouillet-Assant Sophie , Trabaud Mary-Anne 
Published: January 2022

ABSTRACTThe virus neutralization test (VNT) is the reference for the assessment of the functional ability of neutralizing antibodies (NAb) to block SARS-CoV-2 entry into cells. New competitive immunoassays measuring antibodies preventing interaction between the spike protein and its cellular receptor are proposed as surrogate VNT (sVNT). We tested three commercial sVNT (a qualitative immunochromatographic test and two quantitative immunoassays named YHLO and TECO) together with a conventional anti-spike IgG assay (bioMérieux) in comparison with an in-house plaque reduction neutralization test (PRNT50) using the original 19A strain and different variants of concern (VOC), on a panel of 306 sera from naturally-infected or vaccinated patients. The qualitative test was rapidly discarded because of poor sensitivity and specificity. Areas under the curve of YHLO and TECO assays were, respectively, 85.83 and 84.07 (p-value >0.05) using a positivity threshold of 20 for PRNT50, and 95.63 and 90.35 (p-value =0.02) using a threshold of 80. However, the performances of YHLO and bioMérieux were very close for both thresholds, demonstrating the absence of added value of sVNT compared to a conventional assay for the evaluation of the presence of NAb in seropositive subjects. In addition, the PRNT50 assay showed a reduction of NAb titers towards different VOC in comparison to the 19A strain that could not be appreciated by the commercial tests. Despite the good correlation between the anti-spike antibody titer and the titer of NAb by PRNT50, our results highlight the difficulty to distinguish true NAb among the anti-RBD antibodies with commercial user-friendly immunoassays.
COVID-19-Associated Hospitalizations Among Children Less Than 12 Years of Age in the United States
Authors: Di Fusco Manuela , Vaghela Shailja , Moran Mary M , Lin Jay , Atwell Jessica E , Malhotra Deepa , Sforzolini Thomas Scassellati , Cane Alejandro , Nguyen Jennifer L , McGrath Leah J 
Published: January 2022

AbstractObjectivesTo describe the characteristics, healthcare resource use and costs associated with initial hospitalization and readmissions among pediatric patients with COVID-19 in the US.MethodsHospitalized pediatric patients, 0-11 years of age, with a primary or secondary discharge diagnosis code for COVID-19 (ICD-10 code U07.1) were selected from 1 April 2020 through 30 September 2021 in the US Premier Healthcare Database Special Release (PHD SR). Patient characteristics, hospital length of stay (LOS), in-hospital mortality, hospital costs, hospital charges, and COVID-19-associated readmission outcomes were evaluated and stratified by age groups (0-4, 5-11), four COVID-19 disease progression states based on intensive care unit (ICU) and invasive mechanical ventilation (IMV) usage, and three sequential calendar periods. Sensitivity analyses were performed using the US HealthVerity claims database and restricting the analyses to primary discharge code.ResultsAmong 4,573 hospitalized pediatric patients aged 0-11 years, 68.0% were 0-4 years and 32.0% were 5-11 years, with a mean (median) age of 3.2 (1) years; 56.0% were male, and 67.2% were covered by Medicaid. Among the overall study population, 25.7% had immunocompromised condition(s), 23.1% were admitted to the ICU and 7.3% received IMV. The mean (median) hospital LOS was 4.3 (2) days, hospital costs and charges were $14,760 ($6,164) and $58,418 ($21,622), respectively; in-hospital mortality was 0.5%. LOS, costs, charges, and in-hospital mortality increased with ICU admission and/or IMV usage. In total, 2.1% had a COVID-19-associated readmission. Study outcomes appeared relatively more frequent and/or higher among those 5-11 than those 0-4. Results using the HealthVerity data source were generally consistent with main analyses.LimitationsThis retrospective administrative database analysis relied on coding accuracy and inpatient admissions with validated hospital costs.ConclusionsThese findings underscore that children aged 0-11 years can experience severe COVID-19 illness requiring hospitalization and substantial hospital resource use, further supporting recommendations for COVID-19 vaccination.
Effects of Varying Approaches to Lifting COVID-19 Pandemic Restrictions in the United States
Authors: Galarraga Jessica E. , Popovsky Daniel , Delijani Kevin , Hanson Hannah , Hanlon Mark 
Published: January 2022

ABSTRACTBackgroundPolicy approaches to lifting COVID-19 restrictions have varied significantly across the United States. An evaluation of the effects of state reopening policies on population health outcomes can inform ongoing and future pandemic responses. This study evaluates the approaches to lifting social distancing restrictions based on adherence to the Centers for Disease Control and Prevention (CDC) guidance established during the first wave of the COVID-19 pandemic.MethodsWe performed a retrospective study using difference-in-differences analyses to examine the effects of reopening policies on COVID-19 outcomes with risk-adjustment for population density, temporal changes, and concurrent mask policy implementation. We examined the effects of reopening policies on per capita case rates and rates of severe COVID-19 outcomes, including hospitalizations and deaths.ResultsAdherence to the CDC’s reopening gating metrics and phased social distancing guidelines resulted in fewer COVID-19 cases, hospitalizations, and deaths. Phase one adherent states exhibited a 50-fold reduction in daily new cases and a 3-fold reduction in daily new deaths after reopening. Phase two adherent states experienced improvements in COVID-19 outcomes after reopening, while non-adherent states had a resurgence of worsening outcomes after lifting restrictions.ConclusionsOur study findings indicate that adherence to the CDC’s reopening guidance after implementing social distancing restrictions during the COVID-19 pandemic substantially prevents new cases, hospitalizations, and deaths. Following a stepwise reopening strategy and ensuring a sustained decline in case rates and test positivity rates before lifting restrictions can mitigate on a large scale the negative effects of a pandemic on population health outcomes.
Mandatory coupling of zygotic transcription to DNA replication in early Drosophila embryos
Authors: Cho Chun-Yi , Kemp James P. , Duronio Robert J. , O’Farrell Patrick H. 
Published: January 2022

SUMMARYCollisions between transcribing RNA polymerases and DNA replication forks are disruptive. The threat of collisions is particularly acute during the rapid early embryonic cell cycles of Drosophila when S phase occupies the entirety of interphase. We hypothesized that collision-avoidance mechanisms safeguard the onset of zygotic transcription in these cycles. To explore this hypothesis, we used real-time imaging of transcriptional events at the onset of each interphase. Endogenously tagged RNA polymerase II (RNAPII) abruptly formed clusters before nascent transcripts accumulated, indicating recruitment prior to transcriptional engagement. Injection of inhibitors of DNA replication prevented RNAPII clustering, blocked formation of foci of the pioneer factor Zelda, and largely prevented expression of transcription reporters. Knockdown of Zelda or the histone acetyltransferase CBP prevented RNAPII cluster formation except at the replication-dependent (RD) histone gene locus. We suggest a model in which the passage of replication forks allows Zelda and a distinct pathway at the RD histone locus to reconfigure chromatin to nucleate RNAPII clustering and promote transcriptional initiation. The replication dependency of these events defers initiation of transcription and ensures that RNA polymerases transcribe behind advancing replication forks. The resulting coordination of transcription and replication explains how early embryos circumvent collisions and promote genome stability.
The bounded coalescent model: conditioning a genealogy on a minimum root date
Authors: Carson Jake , Ledda Alice , Ferretti Luca , Keeling Matt , Didelot Xavier 
Published: January 2022

AbstractThe coalescent model represents how individuals sampled from a population may have originated from a last common ancestor. The bounded coalescent model is obtained by conditioning the coalescent model such that the last common ancestor must have existed after a certain date. This conditioned model arises in a variety of applications, such as speciation, horizontal gene transfer or transmission analysis, and yet the bounded coalescent model has not been previously analysed in detail. Here we describe a new algorithm to simulate from this model directly, without resorting to rejection sampling. We show that this direct simulation algorithm is more computationally efficient than the rejection sampling approach. We also show how to calculate the probability of the last common ancestor occurring after a given date, which is required to compute the probability of realisations under the bounded coalescent model. Our results are applicable in both the isochronous (when all samples have the same date) and heterochronous (where samples can have different dates) settings. We explore the effect of setting a bound on the date of the last common ancestor, and show that it affects a number of properties of the resulting phylogenies. All our methods are implemented in a new R package called BoundedCoalescent which is freely available online.
ABRIDGE: An ultra-compression software for SAM alignment files
Authors: Banerjee Sagnik , Andorf Carson 
Published: January 2022

ABSTRACTAdvancement in technology has enabled sequencing machines to produce vast amounts of genetic data, causing an increase in storage demands. Most genomic software utilizes read alignments for several purposes including transcriptome assembly and gene count estimation. Herein we present, ABRIDGE, a state-of-the-art compressor for SAM alignment files offering users both lossless and lossy compression options. This reference-based file compressor achieves the best compression ratio among all compression software ensuring lower space demand and faster file transmission. Central to the software is a novel algorithm that retains non-redundant information. This new approach has allowed ABRIDGE to achieve a compression 16% higher than the second-best compressor for RNA-Seq reads and over 35% for DNA-Seq reads. ABRIDGE also offers users the option to randomly access location without having to decompress the entire file. ABRIDGE is distributed under MIT license and can be obtained from GitHub (https://github.com/sagnikbanerjee15/Abridge) and docker hub. We anticipate that the user community will adopt ABRIDGE within their existing pipeline encouraging further research in this domain.
A Wake-Up Call: Determination of Antibiotics Residue Level in Raw Meat in Abattoir and Selected Slaughterhouses in Five Local Government in Kano State, Nigeria
Authors: Lateefat Habeeb Modupe , Olaniyi Opasola Afolabi , Misbahu Garba , Raimi Olalekan Morufu 
Published: January 2022

AbstractThe frequent use of antibiotics may result in drug residues that can be discovered at varying quantities in animal products such as milk or meat. The presence of pharmaceutical residues in food above the MRLs has been perceived globally by various persons. Antibiotics residues are present in food, which can endanger human health by causing antibiotic sensitivity, allergic reactions, microflora imbalance, bacterial resistance to antibiotics in microorganisms, and financial loss to the food industry. Farmers around the world utilize them on a sporadic basis for both preventative and curative purposes. This study assessed the antibiotics residues in raw meat sold in 6 slaughter houses in Kano States. The study is a descriptive cross-sectional study involving six (6) major slaughter house in Kano state. Muscle, Kidney and liver samples were collected from each slaughterhouse. The antibiotic residues in the meat samples were analysed using high performance liquid chromatography (HPLC) for tetracycline, ciprofloxacin and oxytetracycline residue results were presented in charts and tables. Out of a total of 18 beef samples analyzed during this study, 15 (83%) of the total samples had detectable levels of tetracycline residues from which 6(33.3%) had tetracycline residues at violative levels above the WHO/FAO maximum residue limits (MRLs), out of those 18 beef samples analyzed during this study, 6(33%) of the total samples had detectable levels of oxytetracycline residues from which 3(17%) had oxytetracycline residues at violative levels above the WHO/FAO maximum residue limits (MRLs) and out of those 18 beef samples analyzed during this study, 12(67%) of the total samples had detectable levels of ciprofloxacin, all levels are below the WHO/FAO maximum residue limits (MRLs). This high level of tetracycline and oxytetracycline residues in greater proportion of meat destined for human consumption at violative levels could be as a result of the indiscriminate use and misuse of veterinary drugs as commonly practiced among livestock producers and marketers without observing withdrawal period prior to slaughter. These results indicate that consumers may be predisposed to health hazards and hinder international meat trade from Nigeria. Regulatory authorities should therefore ensure compliance with good agricultural practices including withdrawal period of drugs used for treatment of food animals.
Elixirs of Life, threats to Human and Environmental Well-being: Assessment of Antibiotic Residues in Raw Meat Sold Within Central Market Kaduna Metropolis, Kaduna State, Nigeria
Authors: Lateefat Habeeb Modupe , Olaniyi Opasola Afolabi , Yusuf Adiama Babatunde , Azaman Ibrahim , Raimi Morufu Olalekan 
Published: January 2022

AbstractAntibiotics, which are commonly used to treat human illnesses, are also used in animals for therapy, prophylaxis, and growth promotion. Sub-therapeutic antibiotic doses have typically been utilized for the last-mentioned purpose, which has contributed to resistance development. According to scientific data, certain antibiotic applications in food-producing animals can result in antibiotic resistance in intestinal bacteria, which can then be passed to the general population, causing treatment-resistant sickness. These antibiotic applications can also result in antibiotic resistance in non-pathogenic bacteria, whose resistance genes can be passed to disease-causing bacteria, resulting in antibiotic-resistant illnesses in people. Thus, this study assessed the antibiotics residues in raw meat sold in 6 slaughter houses in Kaduna State. The study is a descriptive cross-sectional study involving 6 slaughter houses in Central market Kaduna. Muscle, Kidney and liver samples were collected from each slaughterhouse. The antibiotic residues in the meat samples were analyzed using high performance liquid chromatography (HPLC) for tetracycline, ciprofloxacin and oxytetracycline residue results were presented in charts and tables. 18 different samples of beef (6 Muscles, 6 Liver and 6 Kidney) collected from abattoirs and meat vendors, the results shown that all beefs use three or more antimicrobial drugs. This research result revealed that 4(67%) tetracycline (oxytetracycline)were detected in meat samples at higher concentration), Oxytetraxycline (352.88 ± 221.58) of muscles is higher than (332.2± 217.05 of Liver and (263.33 ± 153.98) of Kidney is lower to muscles and liver. The Concentration of oxytetracycline were highest in muscles in samples 2. 3 and 6 which is above the WHO maximum residual limit. The concentration of streptomycin in the muscle, liver and kidney were detected (182.78 ± 56.23), (169.2 ± 58.39), (155.1 ± 50.20) but were within WHO Maximum residual limit. These high level of oxytetracycline residues in greater proportion of muscle samples destined for human consumption beyond MRLs could be as a result of the abuse of veterinary drugs as commonly practiced among livestock producers and vendors without observing withdrawal period prior to slaughter. The high-contamination rate of beef meat in the study areas is likely that consumers experience a high risk of exposure to drug residues.
Combination therapy of metformin with sodium selenite reverses effects of monotherapy on nitric oxide production, IL-1β and TNF-α release, and upregulates relative expression of Bcl-2 by LPS-activated human primary monocytes in T-cell acute lymphoblastic leukemia
Authors: Rostane Fella , Sari Nidel , Bali Ilyes , Messali Rabia , Hadjidj Zeyneb , Miliani Maroua , Belhassena Imène , El Mezouar Charazed , Aribi Mourad 
Published: January 2022

AbstractObjectivesWe examined the influence of the ex vivo combination therapy of metformin (Met, 1,1-dimethylbiguanide hydrochloride) with sodium selenite (Ss, Na2SeO3) on the changes in the production of nitric oxide (NO) and selected cytokines by circulating monocytes (MOs) during T-cell acute lymphoblastic leukemia (T-ALL).MethodsAssays were performed on MO cell samples isolated from children with T-ALL.ResultsMet+Ss combination therapy reversed the Ss effect on the upregulation of NO production. Both Met+Ss and Ss treatment alone induced a significant downregulation of extracellular calcium ions consumption (ecCa2+) levels. Additionally, Met treatment induced a significant upregulation of IL-1β and TNF-α production; such effects were significantly reversed after combination with Ss treatment. Moreover, Met+Ss induced no significant effect on the production of IL-10, IL-6 and TNF-α, but a slight increase in IFN-γ levels. Furthermore, treatment with Ss alone induced a slight increase of IFN-γ. Finally, Met+Ss induced a marked upregulation of relative Bcl-2 expression in MOs.ConclusionsMet+Ss combination therapy results in downregulation of NO production, IL-1β and TNF-α release as well as in upregulation of the relative expression levels of Bcl-2-associated survival of primary MOs in human T-ALL.