bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post SARS-CoV-2 cell mediated Immune profiles; Case studies
Authors: Singh Rajveer , Ravichandiran Velayutham , Ghosh Dipanjan , Ray Ujjaini , Dasgupta Sarbani , Dutta Soma , Saha Aditi , Roy Debabrota , Ghosh Srinika , Somasundaram A. , Dutta Pallab , Ganguly N K , Datta Debatosh 
Published: July 2022

AbstractCell-mediated immunity (CMI), which includes T-cells (both T helper and cytotoxic), is critical for effective antiviral defenses against coronavirus disease-2019 (COVID-19). To better understand the immunological characteristics of CD markers on T-cells in post-COVID-19 patients, we investigated the expression of differential CD markers in the patient groups in this study.Flow cytometry was used to quantify total lymphocyte count and assess the levels of expression of CD markers in the samples. The percentage of Lymphocytes decreased significantly in the post-SARS-COV-2 patients in comparison to normal subjects, which is usually happening in any viral infection. In contrast to that, expression of CD8 was increased in the patient group having long SARS-COV-2 infection with comorbid complications with respect to the normal individuals and long SARS-COV-2 infection without comorbid complications. This data revealed that the cellular immunological responses corroborated with an earlier report of COVID-19 infection were mediated by CD8 upregulation and cytotoxic T lymphocyte hyperactivation.
Using machine learning probabilities to identify effects of COVID-19
Authors: Ramlall Vijendra , May Benjamin , Tatonetti Nicholas P 
Published: July 2022

AbstractCOVID-19, the disease caused by the SARS-CoV-2 virus, has had and continues to have extensive economic, social and public health impacts in the United States and around the world. To date, there have been more than 500 million reported cases of SARS-CoV-2 infection worldwide with more than 6 million reported deaths, more than 80 million of those cases and more than 1 million of those deaths have been reported in the United States. Retrospective analysis throughout the pandemic, which identified comorbidities, risk factors and treatments, has underpinned the response COVID-19. As the situation transitions from a pandemic to an endemic, retrospective analyses using electronic health records will be increasingly important to identify long term effects of COVID-19. However, these analyses can be complicated by the incompleteness of electronic health records, which in turns makes it difficult to differentiate visits where the patient has COVID-19. To address this, we trained a random forest classifier to assign a probability of a patient having been diagnosed with COVID-19 during each visit using demographic data, temporal data and visit-specific diagnoses (Training AUROC = 0.9867, Training OOB AUROC = 0.8957, Evaluation AUROC = 0.8958). Using these probabilities, we identified conditions associated with higher COVID-19 probabilities irrespective of clinical history and when accounting for previous diagnosis and estimated the hazards ratio for myocardial infarction (Hazards ratio = 121.736 (87.375, 169.611),p= 3.796E-177 and Hazards ratio = 80.262 (4.134, 4.637),p= 4.543E-256, respectively), urinary tract infection (Hazards ratio = 72.021 (58.116 - 89.253),p< 2.225E-308 and Hazards ratio = 61.380 (51.273 - 73.479),p< 2.225E-308, respectively), acute renal failure (Hazards ratio = 1.264E4 (9.278E4 - 1.724E4),p< 2.225E-308 and Hazards ratio = 6.333E3 (4.947E3 - 8.108E3),p< 2.225E-308, respectively) and type 2 diabetes (Hazards ratio = 345.730 (283.180 - 422.098),p< 2.225E-308 and Hazards ratio = 217.271 (187.898 - 251.235),p= 1.39E-22, respectively) when accounting for demographics and the ten most common clinical conditions.
Environmental surveillance of poliovirus in four districts within two regions of Ghana
Authors: Obese-Djomoah Ernest , Obodai Evangeline , Gberbi Emmanuel , Duker Ewurabena , Attiku Keren , Eshun Miriam , Boahene Bismarck , Nuvor Samuel Victor , Odoom John Kofi 
Published: July 2022

AbstractThe eradication of poliovirus is at its last phase through the efforts and strategies of Global Polio Eradication Initiation (GPEI). There are very few countries that are still endemic with wild poliovirus (WPV) and others with circulating vaccine derived poliovirus (cVDPV). The aim of the study was to detect silent circulation of WPV and VDPV in four districts within the Eastern and Volta region of Ghana. A systematic longitudinal design was used for the study. The convenient sampling technique was used to collect the samples every four weeks from two open and close sewage systems. The open sewage systems were located in New Juabeng and Ho districts while the close sewage systems were located in Asuogyaman and Ketu South districts. A total of 35 sewage samples were collected from September 2018 to May 2019. L20B and RD cell lines were used for the purification of poliovirus (PV) while real-time reverse transcriptase polymerase chain reaction (rRT-PCR) was use to characterize the serotypes of the PVs. The findings of the study showed that the prevalence of non-polio enterovirus (NPEV) and Sabin were 65.71% and 14.29% respectively. The characterized Sabins were serotype 1 and serotype 3 which were circulating in the two districts within the Eastern Region. The study did not detect any WPV and VDPV but isolated Sabin strains of the poliovirus. This necessitates the need for continuous environmental surveillance for poliovirus nationwide.
Membrane curvature sensing and symmetry breaking of the M2 proton channel from Influenza A
Authors: Helsell Cole V. M. , Marcoline Frank V. , Lincoff James , Natale Andrew M. , Grabe Michael 
Published: July 2022

AbstractThe M2 proton channel aids in the exit of mature influenza viral particles from the host plasma membrane through its ability to stabilize regions of high negative gaussian curvature (NGC) that occur at the neck of budding virions. The channels are homo-tetramers that contain a cytoplasm-facing amphipathic helix (AH) that is necessary and sufficient for NGC generation; however, constructs containing the transmembrane spanning helix, which facilitates tetramerization, exhibit enhanced curvature generation. Here we used all-atom molecular dynamics (MD) simulations to explore the conformational dynamics of M2 channels in lipid bilayers revealing that the AH is dynamic, quickly breaking the 4-fold symmetry observed in most structures. Next, we carried out MD simulations with the protein restrained in 4-fold and 2-fold symmetric conformations to determine the impact on the membrane shape. While each pattern was distinct, all configurations induced pronounced curvature in the outer leaflet with rather subtle lipid tilt, while conversely, the inner leaflets adjacent to the AHs showed minimal curvature and significant lipid tilt. The MD-generated profiles at the protein-membrane interface were then extracted and used as boundary conditions in a continuum elastic membrane model to calculate the membrane bending energy of each conformation embedded in different membrane surfaces characteristic of a budding virus. The calculations show that all three M2 conformations are stabilized in concave spherical caps and destabilized in convex spherical caps, the latter reminiscent of a budding virus. Only C2-broken symmetry conformations are stabilized in NGC surfaces, by 1-3 kBT depending on the AH domain arrangement. The most favored conformation is stabilized in saddles with curvatures corresponding to 33 nm radii. In total, our work provides atomistic insight into the curvature sensing capabilities of M2 channels and how enrichment in the nascent viral particle depends on protein shape and membrane geometry.
Clinical characteristics and factors associated with COVID-19-related mortality and hospital admission in 5 rural provinces in Indonesia: a retrospective cohort study
Authors: Surendra Henry , Praptiningsih C Yekti , Ersanti Arina M , Rahmat Mariati , Noviyanti Widia , Harmani Joshua AD , Mansur Erni NA , Suleman Yana Y , Sudrani Sitti , Rosalina Rosalina , Mukhtar Ismen , Rosadi Dian , Fauzi Lukman , Elyazar Iqbal RF , Hawley William A , Wibisono Hariadi 
Published: July 2022

AbstractBackgroundData on COVID-19 clinical characteristics and severity from resource-limited settings are limited. This study examined clinical characteristics and factors associated with COVID-19 mortality and hospitalisation in rural settings of Indonesia, from 1 January to 31 July, 2021.MethodsThis retrospective cohort included individuals diagnosed with COVID-19 based on polymerase chain reaction or rapid antigen diagnostic test, from Lampung, Gorontalo, Central Sulawesi, Southeast Sulawesi, and East Nusa Tenggara Provinces. We extracted demographic and clinical data, including hospitalisation and mortality from COVID-19 surveillance records. We used mixed-effect logistic regression to examine factors associated with COVID-19-related mortality and hospitalisation.ResultsOf 6,583 confirmed cases, 205 (3.1%) died, and 1,727 (26%) were hospitalised. The median age was 37 years (IQR 26-52), with 825 (12·53%) under 20 years, and 3,371 (51.21%) females. 4,533 (68.86%) cases were symptomatic, 319 (4.85%) had a clinical diagnosis of pneumonia, and 945 (14.36%) with at least one pre-existing comorbidity. The mortality and hospitalisation rate ranged from 2.0% and 13.4% in East Nusa Tenggara to 4.3% and 36·1% in Lampung. Age-specific mortality rates were 0.9% (2/340) for 0-4 years; 0% (0/112) for 5-9 years; 0.2% (1/498) for 10-19 years; 0.8% (11/1,385) for 20-29 years; 0.9% (12/1,382) for 30-39 years; 2% (23/1,095) for 40-49 years; 5% (57/1,064) for 50-59 years; 11% (62/576) for 60-69 years; 16% (37/232) for ≥70 years. Older age, pre-existing diabetes, liver diseases, malignancy, and pneumonia were associated with higher risk of mortality and hospitalisation. Pre-existing hypertension, cardiac diseases, chronic kidney disease, COPD, and immunocompromised condition were associated with risk of hospitalisation but not with mortality.ConclusionClinical characteristics and risk factors of severe COVID-19 outcomes in rural provinces were broadly similar to those in urban settings. The risk of COVID-19-related mortality and hospitalisation was associated with higher age, pre-existing chronic comorbidities, and clinical presentation of pneumonia.
Tissue confinement regulates cell growth and size in epithelia
Authors: Devany John , Falk Martin J , Holt Liam J , Murugan Arvind , Gardel Margaret L 
Published: July 2022

SummaryCell proliferation is a central process in tissue development, homeostasis and disease. Yet how proliferation is regulated in the tissue context remains poorly understood. Here, we introduce a quantitative framework to elucidate how tissue growth dynamics regulate cell proliferation. We show that tissue growth causes confinement that suppresses cell growth; however, this confinement does not directly affect the cell cycle. This leads to uncoupling between rates of cell growth and division in epithelia and, thereby, reduces cell size. Division becomes arrested at a minimal cell size, which is consistent across diverse epithelia in vivo. Here, the nucleus approaches a volume limit set by the compacted genome. The loss of Cyclin D1-dependent cell size regulation results in an abnormally high nuclear-to-cytoplasmic volume ratio and DNA damage. Overall, we demonstrate how epithelial proliferation is regulated by the interplay between tissue confinement and cell size regulation.Highlights-In epithelia, regulation of cell growth and cycle are uncoupled-Cell growth is regulated by tissue-scale dynamics, which determine confinement-Cell volume in epithelial tissue is described by G1 sizer model with a tunable growth rate-Volume of cells in epithelial tissues is near a minimum set by genome size
Spatial and Temporal Origin of The Third SARS-Cov-2 Outbreak in Taiwan
Authors: Tai Jui-Hung , Low Yu Ken , Wang Selina Cai-Ling , Lin Hsin-Fu , Wang Tzi-Yuan , Wang Jann-Tay , Liu Yu-Shu , Lin You-Yu , Foster Charles S.P. , van Hal Sebastiaan J. , Lai Ya-Yun , Yeh Shiou-Hwei , Chang Sui-Yuan , Chen Pei-Jer , Chaw Shu-Miaw 
Published: July 2022

ABSTRACTSince the first report of SARS-CoV-2 in December 2019, Taiwan has gone through three local outbreaks. Unlike the first two outbreaks, the spatial and temporal origin of the third outbreak (April 20 to November 5, 2021) is still unclear. We assembled and analyzed a data set of more than 6,000 SARS-CoV-2 genomes, including 300 from Taiwan and 5812 related sequences downloaded from GISAID as of 2021/12/08. We found that the third outbreak in Taiwan was caused by a single virus lineage belonging to Alpha (B.1.1.7) strain. This lineage, T-III (the third outbreak in Taiwan), carries a distinct genetic fingerprint, consisting of spike M1237I (S-M1237I) and three silent mutations, C5812T, C15895T, and T27869C. The T-III is closest to the sequences derived from Turkey on February 8, 2021. The estimated age of the most recent common ancestor (TMRCA) of T-III is March 23, 2021 (95% highest posterior density [HPD] February 24 - April 13, 2021), almost one month before the first three confirmed cases on April 20, 2021. The effective population size of the T-III showed approximately 20-fold increase after the onset of the outbreak and reached a plateau in early June 2021. Our results reconcile several unresolved observations, including the occurrence of two infection clusters at the same time without traceable connection and several airline pilots who were PCR negative but serum IgM-/IgG+ for SARS-CoV-2 in late April. Therefore, in contrast to the general notion that the third SARS-CoV-2 outbreak in Taiwan was sparked by two imported cases from USA on April 20, 2021, which, in turn, was caused by the partial relaxation of entry quarantine measures in early April 2021, our comprehensive analyses demonstrated that the outbreak was most likely originated from Europe in February 2021.
Large-scale expansions and replication stalling of Friedreich’s ataxia GAA repeats in an experimental mammalian system
Authors: Rastokina Anastasia , Cebrián Jorge , Mandel Nicholas , Zain Rula , Lopes Massimo , Mirkin Sergei M. 
Published: July 2022

1AbstractHuman disease Friedreich’s ataxia (FRDA) is caused by large-scale expansions of (GAA)n repeats in the first intron of the FXN gene. While repeat expansions during intergenerational transmissions are causative for the disease development, somatic expansions additionally contribute to the disease progression. We and others have previously shown that (GAA)n repeats transiently pause the replication fork progression in cultured human cells. However, whether and by which mechanisms fork stalling underlies repeat expansions remained unclear. Here we developed a new genetically tractable experimental system to simultaneously analyze repeat-mediated fork stalling and large-scale repeat expansions in cultured human cells. It is based on a mammalian/yeast shuttle vector that can transiently replicate from the SV40 replication origin in human HEK-293T cells or be stably maintained in S. cerevisiae utilizing ARS4-CEN6; it also contains a cassette for selecting repeat expansions in yeast. Repeat expansions accumulate in mammalian cells and are then detected upon plasmid transformation into yeast. We found that large-scale expansions of (GAA)n repeats do occur in this experimental mammalian system. Further, we observed that repeat expansions’ frequency depends on several previously implicated proteins in replication fork stalling, reversal, and restart. These proteins include SHPRH, RAD52, ZRANB3, DDX11, SMARCAL1, HLTF, RECQ1 and WRN. Therefore, we propose that GAA repeat expansions might occur as a consequence of deregulated replication fork regression and restoration process.
Point-of-care thermal imaging tool assisting in the development of imaging biomarker as pre-diagnostics of graves’ disease
Authors: Sharma Vaishali , Dhingra Vandana K , Kumar Ashok , Shakya Snehlata , Goswami Mayank 
Published: July 2022

AbstractThis article presents the development of a tool to address the scarcity of clinically validated datasets for Thyroid related abnormalities. Infrared thermography Images are taken from each of the sixty persons of different age groups and gender. Scintigraphy and standard thyroid blood test results are used to categorize these persons into thirty-three females and thirteen males suffering from graves’ disease. Eleven females and three males are found to be in healthy conditions and used as control. An Artificial Intelligence algorithm is used to automatically segment and extract the histogram-associated information within the thyroid and cheek region from the collected images. A very simple and novel imaging biomarker is found to be moderately correlated w.r.t age and gender. A smartphone app integrated with a dedicated smartphone-based compact IR camera add-on is developed and deployed in a clinical environment to enrich the analysis. This point-of-care tool is expected to categorize healthy cases from patients automatically. It is to reduce the ethical burden on clinicians’ shoulders before recommending radioactive contamination-prone Scintigraphy and/or expensive and relatively slower thyroid blood tests. If adopted, such preliminary tests will save costs on patients’ end and burden at pathology labs, especially in densely populated countries such as India.
Proximity to livestock farms and COVID-19 in the Netherlands, 2020-2021
Authors: Hogerwerf Lenny , Post Pim M. , Bom Ben , van der Hoek Wim , van de Kassteele Jan , Stemerding Annette M. , de Vries Wilco , Houthuijs Danny 
Published: July 2022

AbstractObjectivesIn the Netherlands, during the first phase of the COVID-19 epidemic, the hotspot of COVID-19 overlapped with the country’s main livestock area, while in subsequent phases this distinct spatial pattern disappeared. Previous studies show that living near livestock farms influence human respiratory health and immunological responses. This study aimed to explore whether proximity to livestock was associated with SARS-CoV-2 infection.MethodsThe associations between residential (6-digit postal-code) distance to the nearest livestock farm and individuals’ SARS-CoV-2 status was studied in multilevel logistic regression models, comparing individuals notified with a positive SARS-CoV-2 test to the general population in the Netherlands. Data included all reported Dutch laboratory-confirmed patients with disease onset before 1 January 2022. Individuals living in strongly urbanised areas and border areas were excluded. Models were adjusted for individuals’ age categories, the social status of the postal code area, particulate matter (PM10)-and nitrogen dioxide (NO2)-concentrations. We analysed data for the entire period and population as well as separately for eight time periods (Jan-Mar, Apr-Jun, Jul-Sep and Oct-Dec in 2020 and 2021), four geographic areas of the Netherlands (north, east, west and south), and for five age categories (0-14, 15-24, 25-44, 45-64 and > 65 years).ResultsOver the period 2020-2021, individuals’ SARS-CoV-2 status was associated with living closer to livestock farms. This association increased from an Odds Ratio (OR) of 1.01 (95% Confidence Interval [CI] 1.01-1.02) for patients living at a distance of 751-1000 m to a farm to an OR of 1.04 (95% CI 1.04-1.04), 1.07 (95% CI 1.06-1.07) and 1.11 (95% CI 1.10-1.12) for patients living in the more proximate 501-750 m, 251-500m and 0-250 m zones around farms, all relative to patients living further than 1000 m around farms. This association was observed in three out of four quarters of the year in both 2020 and 2021, and in all studied geographic areas and age groups.ConclusionsIn this exploratory study with individual SARS-CoV-2 notification data and high-resolution spatial data associations were found between living near livestock farms and individuals’ SARS-CoV-2 status in the Netherlands. Verification of the results in other countries is warranted, as well as investigations into possible underlying mechanisms.
Real-world experience with molnupiravir during the period of SARS-CoV-2 Omicron variant dominance
Authors: Flisiak Robert , Zarębska-Michaluk Dorota , Rogalska Magdalena , Kryńska Justyna Anna , Kowalska Justyna , Dutkiewicz Ewa , Dobrowolska Krystyna , Jaroszewicz Jerzy , Moniuszko-Malinowska Anna , Rorat Marta , Podlasin Regina , Tronina Olga , Rzymski Piotr 
Published: July 2022

AbstractBackgroundThe real-world effectiveness of molnupiravir (MOL) during the dominance of Omicron SARS-CoV-2 lineage is urgently needed since the available data relates to the period of circulation of other viral variants. Therefore, this study assessed the efficacy of MOL in patients hospitalized for COVID-19 in a real-world clinical practice during the wave of Omicron infections.MethodsAmong 11822 patients hospitalized after 1 March 2020 and included in the SARSTer national database, 590 were treated between 1 January and 31 April 2022, a period of dominance of the Omicron SARS-CoV-2 variant. MOL was administered to 203 patients, whereas 387 did not receive any antiviral regimen. Both groups were similar in terms of sex, BMI and age allowing for direct comparisonsResultsPatients who did not receive antiviral therapy significantly more often required the use of Dexamethasone and Baricitinib. Treatment with MOL resulted in a statistically significant reduction in mortality during the 28-day follow-up (9.9 vs. 16.3%), which was particularly evident in the population of patients over 80 years of age treated in the first 5 days of the disease (14.6 vs. 35.2%). MOL therapy did not affect the frequency of the need for mechanical ventilation, but patients treated with MOL required oxygen supplementation less frequently than those without antivirals (31.7 vs. 49.2%). The time of hospitalization did not differ between groups.ConclusionsThe use of molnupiravir in patients hospitalized for COVID-19 during the dominance of Omicron variant reduced mortality. This effect is particularly evident in patients over 80 years of age.
The causal effect of cigarette smoking on healthcare costs
Authors: Dixon Padraig , Sallis Hannah , Munafo Marcus , Smith George Davey , Howe Laura 
Published: July 2022

ABSTRACTKnowledge of the impact of smoking on healthcare costs is important for establishing the external effects of smoking and for evaluating policies intended to modify this behavior. Conventional analysis of this association is difficult because of omitted variable bias, reverse causality, and measurement error. We approached these challenges using a Mendelian Randomization study design, in which genetic variants associated with smoking behaviors were used as instrumental variables. We undertook genome wide association studies to identify genetic variants associated with smoking initiation and a composite index of lifetime smoking on up to 300,045 individuals in the UK Biobank cohort. These variants were used in two-stage least square models and a variety of sensitivity analyses. All results were concordant in indicating a substantial impact of each smoking exposure on annual inpatient hospital costs Our results indicate a substantial impact of smoking on hospital costs. Genetic liability to initiate smoking – ever versus never having smoked – was estimated to increase mean per-patient annual hospital costs by £477 (95% confidence interval (CI): £187 to £766). A one unit change in genetic liability a composite index reflecting the cumulative health impacts of smoking was estimated to increase these costs by £204 (95% CI: £105 to £303). Models conditioning on the causal effect of risk tolerance were not robust to weak instruments for this exposure. Our findings have implications for the scale of external effects that smokers impose on others, and on the probable cost-effectiveness of smoking interventions.