bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of contact tracing on COVID-19 mortality: An impact evaluation using surveillance data from Colombia
Authors: Vecino-Ortiz Andres I. , Villanueva Congote Juliana , Zapata Bedoya Silvana , Cucunuba Zulma M 
Published: August 2020

AbstractBackgroundContact tracing is a key part of the public health surveillance toolkit. However, it is labor intensive and costly to carry it out. Some countries have faced challenges implementing contact tracing, and no impact evaluations to our knowledge have assessed its impact on COVID-19 mortality. This study assesses the impact of contact tracing in a middle-income country and provides data to support the expansion of contact tracing strategies with the aim of improving infection control.MethodsWe obtained publicly available data on all confirmed COVID-19 cases in Colombia between March 2 and June 16, 2020. (N=54,931 cases over 135 days of observation). We proxied contact tracing performance as the proportion of cases identified through contact tracing out of all cases identified, as suggested by WHO guidelines. We calculated the daily proportion of cases identified through contact tracing across 37 geographical units (32 departments and five districts). Further, we used a sequential log-log fixed-effects model to estimate the 21-days, 28-days, 42-days and 56-days lagged impact of the proportion of cases identified through contact tracing on the daily number of COVID-19 deaths. Both the proportion of cases identified through contact tracing and the daily number of COVID-19 deaths are smoothed using 7-day moving averages. Models control for prevalence of active cases, second-degree polynomials, and mobility indices. Robustness checks to include supply-side variables were performed.ResultsWe found that a 10 percent increase in the proportion of cases identified through contact tracing is related to COVID-19 mortality reductions between 0.8% and 3.4%. Our models explain between 47%-70% of the variance in mortality. Results are robust to changes of specification and inclusion of supply-side variables.ConclusionContact tracing is instrumental to contain infectious diseases and its prioritization as a surveillance strategy will have a substantial impact on reducing deaths while minimizing the impact on the fragile economic systems of lower and middle-income countries. This study provides lessons for other LMIC.
Robust, reproducible clinical patterns in hospitalised patients with COVID-19
Authors: Millar Jonathan E , Neyton Lucile , Seth Sohan , Dunning Jake , Merson Laura , Murthy Srin , Russell Clark D , Keating Sean , Swets Maaike , Sudre Carole , Spector Timothy , Ourselin Sebastien , Steves Claire , Wolf Jonathan ,   ISARIC-4C Investigators, Docherty Annemarie , Harrison Ewen , Openshaw Peter , Semple Calum , Baillie J. Kenneth 
Published: August 2020

AbstractBackgroundSevere COVID-19 is characterised by fever, cough, and dyspnoea. Symptoms affecting other organ systems have been reported. However, it is the clinical associations of different patterns of symptoms which influence diagnostic and therapeutic decision-making. In this study, we applied simple machine learning techniques to a large prospective cohort of hospitalised patients with COVID-19 identify clinically meaningful sub-groups.MethodsWe obtained structured clinical data on 59 011 patients in the UK (the ISARIC Coronavirus Clinical Characterisation Consortium, 4C) and used a principled, unsupervised clustering approach to partition the first 25 477 cases according to symptoms reported at recruitment. We validated our findings in a second group of 33 534 cases recruited to ISARIC-4C, and in 4 445 cases recruited to a separate study of community cases.FindingsUnsupervised clustering identified distinct sub-groups. First, a core symptom set of fever, cough, and dyspnoea, which co-occurred with additional symptoms in three further patterns: fatigue and confusion, diarrhoea and vomiting, or productive cough. Presentations with a single reported symptom of dyspnoea or confusion were common, and a subgroup of patients reported few or no symptoms. Patients presenting with gastrointestinal symptoms were more commonly female, had a longer duration of symptoms before presentation, and had lower 30-day mortality. Patients presenting with confusion, with or without core symptoms, were older and had a higher unadjusted mortality. Symptom clusters were highly consistent in replication analysis using a further 35446 individuals subsequently recruited to ISARIC-4C. Similar patterns were externally verified in 4445 patients from a study of self-reported symptoms of mild disease.InterpretationThe large scale of the ISARIC-4C study enabled robust, granular discovery and replication of patient clusters. Clinical interpretation is necessary to determine which of these observations have practical utility. We propose that four patterns are usefully distinct from the core symptom groups: gastro-intestinal disease, productive cough, confusion, and pauci-symptomatic presentations. Importantly, each is associated with an in-hospital mortality which differs from that of patients with core symptoms. These observations deepen our understanding of COVID-19 and will influence clinical diagnosis, risk prediction, and future mechanistic and clinical studies.FundingMedical Research Council; National Institute Health Research; Well-come Trust; Department for International Development; Bill and Melinda Gates Foundation; Liverpool Experimental Cancer Medicine Centre.
Analysis of cardiomyocyte nuclei in human cardiomyopathy reveals orientation dependent defects in shape
Authors: Brayson Daniel , Ehler Elisabeth , dos Remedios Cristobal G. , Shanahan Catherine M. 
Published: August 2020

AbstractCardiomyopathies are progressive diseases of heart muscle often caused by mutations in genes encoding sarcomeric, cytoskeletal and nucleoskeletal proteins though in many cases the cause of disease is not identified. Whilst nucleus hypertrophy has been described, it is not known whether nucleus shape changes are a general feature of cardiomyopathy. Due to the rod-shaped nature of cardiomyocytes and their elliptical nuclei we hypothesised that orientation of analysis would be an important determinant of any changes observed between patients exhibiting primarily unexplained cardiomyopathy and control samples from non-failing donors. To investigate this we performed image analysis of cardiomyocyte nuclei in myocardial cryosections from a cohort of cardiomyopathy patients. We discovered that circularity, solidity and aspect ratio were sensitive to orientation of the myocardium and that in the transverse plane only circularity was reduced in cardiomyocyte nuclei of cardiomyopathy patients. These findings show that orientation dependent changes in nucleus shape may be a property of cardiomyopathy and with appropriate follow up studies, may prove to have mechanistic and diagnostic value.
Proportion of idiopathic pulmonary fibrosis risk explained by known genetic loci
Authors: Leavy Olivia C , Ma Shwu-Fan , Molyneaux Philip L , Maher Toby M , Oldham Justin M , Flores Carlos , Noth Imre , Jenkins R Gisli , Dudbridge Frank , Wain Louise V , Allen Richard J 
Published: August 2020

AbstractGenome-wide association studies have identified 14 genetic loci associated with susceptibility to idiopathic pulmonary fibrosis (IPF), a devastating lung disease with poor prognosis. Of these, the variant with the strongest association, rs35705950, is located in the promoter region of the MUC5B gene and has a risk allele (T) frequency of 30-35% in IPF cases. Here we present estimates of the proportion of disease liability explained by each of the 14 IPF risk variants as well as estimates of the proportion of cases that can be attributed to each variant. We estimate that rs35705950 explains 5.9-9.4% of disease liability, which is much lower than previously reported estimates. Of every 100,000 individuals with the rs35705950_GG genotype we estimate 30 will have IPF, whereas for every 100,000 individuals with the rs35705950_GT genotype 152 will have IPF. Quantifying the impact of genetic risk factors on disease liability improves our understanding of the underlying genetic architecture of IPF and provides insight into the impact of genetic factors in risk prediction modelling.
Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine
Authors: Peters EJG , Collard D , Van Assen S , Beudel M , Bomers MK , Buijs J , De Haan LR , De Ruijter W , Douma RA , Elbers PWG , Goorhuis A , Gritters van den Oever NC , Knarren GHH , Moeniralam HS , Mostard RLM , Quanjel MJR , Reidinga AC , Renckens R , Van Den Bergh JPW , Vlasveld IN , Sikkens JJ 
Published: August 2020

AbstractObjectiveTo compare survival of subjects with COVID-19 treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine.MethodsWe analysed data of COVID-19 patients treated in 9 hospitals in the Netherlands. Inclusion dates ranged from February 27th 2020, to May 15th, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated subjects with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox-regression with adjustment for age, sex and covariates based on premorbid health, disease severity, and the use of steroids for adult respiratory distress syndrome, including dexamethasone.ResultsAmong 1893 included subjects, 21-day mortality was 23.4% in 1552 subjects treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 17.0% in 341 subjects that were treated in hospitals that did not. In the adjusted Cox-regression models this difference disappeared, with an adjusted hazard ratio of 1.17 (95%CI 0.88-1.55). When stratified by actually received treatment in individual subjects, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95%CI 1.25-2.01) in the full model.ConclusionsAfter adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine, compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in patients with COVID-19.
Impacts of bariatric surgery on costs and health outcomes of patients in Brazil: Interrupted time series analysis of multi-panel data
Authors: Turri José Antonio Orellana , Baraccat Edmund Chada , Soarez José Maria , Santos Lionai Lima dos , Santo Marco Aurélio , Sarti Flavia Mori , Anokye Nana Kwame 
Published: August 2020

AbstractStudy designOriginal researchObesity is one of the most important public health problems worldwide, presenting significant socioeconomic impacts in health systems. Considering the rising costs of health care and the escalating burden of obesity in diverse countries, there has been increasing trends in examination of cost-effectiveness of health interventions towards prevention and treatment of obesity and its effects on comorbidities. Bariatric surgery has been considered an effective intervention for reducing moderate to severe obesity and improvement of obesity-related morbidities.MethodologyInterrupted Time-Series Analysis (ITSA) on costs and health outcomes from retrospective cohort of 114 patients who had bariatric surgery at the Hospital of Clinics from the University of Sao Paulo. Medical records encompassing complete data on anthropometric, hemodynamic and biochemical parameters, utilization of resources and costs for health care procedures and regular assessments of patients’ health status associated with bariatric surgery at individual level were included in the study. Data on utilization of resources during outpatient and inpatient health care were used for estimation of patient’s direct costs referring to bariatric surgery, and 6-month pre- and post-intervention periods, adopting health system perspective in micro-costing approach.ResultsMean direct costs of hospitalization (-US$2,762.22; −23.2%), image exams (-US$7.53; −0.8%) and medication (-US$175.37; −25,7%) presented decrease after bariatric surgery, and total direct cost (US$1,375.37; +138%), consultations (US$0.42; +2.4%) and laboratory exams (US$68.96; +63.4%) had increase. Reduction in weight, BMI, LDL, triglycerides, insulin, glucose-linked hemoglobin, and glucose showed improvements in patients’ health status after bariatric surgery. Cholesterol, VLDL, and HDL presenting increase after surgery.ConclusionBariatric surgery represents an effective intervention for treatment of moderate to severe obesity with extensive benefits regarding health promotion and reduction of burden of disease. Trends in direct costs and multiple health outcomes showed post-intervention improvements in patients’ health status and reduction of health care needs of individuals.
Covid-19 related stress and coping strategies among adults with chronic disease in Southwest Ethiopia
Authors: Girma Abel , Ayalew Ermias 
Published: August 2020

AbstractBackgroundCoronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus which are a large family of viruses that are common in people and many different species of animals which can affect people physically and psychologically. The older people and those with underlying medical problems are more likely to develop serious illness and death.Objectivethe aim of this study was to determine Covid-19 related stress and coping strategies among adults with chronic disease in Bench-Sheko,West Omo and Keffa Zones, southwest EthiopiaMethodsInstitutional based cross-sectional study was applied among 613 adults with chronic disease. A simple sampling technique was applied. Correlational analysis was used to determine the relationship between the COVID-19 related stress score and coping strategy types. To measure the strength of association between dependent variables and independent variables and Pearson coefficients (r) with 95% Confidence interval (CI) were calculated. Finally, the variable, which shows statistical significance (p-value < 0.05 cut point) were used to quantify the associations among variables.ResultsAround 613 participants of 96% response rate were participated. About 68.4% were moderately stressed; low stress was 17.8% and severe stress was 13.9 %. Covid-19 related perceived stress score were positively associated with coping strategies types of like sell-distraction, active coping, denial, emotional support, behavioral disengagement, venting, and use of instrument, positive reframing, self-blaming, planning, humoring and religion. The most preferable types of coping strategies were religious, instrumental and active coping strategies and while the least used were substance used.ConclusionSignificant numbers of participants were suffered from severe perceived stress due to covid-19 outbreak in this study area. Both adaptive and maladaptive Coping strategy types were significantly associated with stress. Substance use and self-blaming were the types coping strategies which were not associated with perceived stress.
Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure
Authors: Ripperger Tyler J. , Uhrlaub Jennifer L. , Watanabe Makiko , Wong Rachel , Castaneda Yvonne , Pizzato Hannah A. , Thompson Mallory R. , Bradshaw Christine , Weinkauf Craig C. , Bime Christian , Erickson Heidi L. , Knox Kenneth , Bixby Billie , Parthasarathy Sairam , Chaudhary Sachin , Natt Bhupinder , Cristan Elaine , Aini Tammer El , Rischard Franz , Campion Janet , Chopra Madhav , Insel Michael , Sam Afshin , Knepler James L. , Capaldi Andrew P. , Spier Catherine M. , Dake Michael D. , Edwards Taylor , Kaplan Matthew E. , Scott Serena Jain , Hypes Cameron , Mosier Jarrod , Harris David T. , LaFleur Bonnie J. , Sprissler Ryan , Nikolich-Žugich Janko , Bhattacharya Deepta 
Published: August 2020

ABSTRACTWe conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.
Widespread testing, case isolation and contact tracing may allow safe school reopening with continued moderate physical distancing: a modeling analysis of King County, WA data
Authors: Bracis Chloe , Burns Eileen , Moore Mia , Swan David , Reeves Daniel B , Schiffer Joshua T. , Dimitrov Dobromir 
Published: August 2020

AbstractBackgroundIn late March 2020, a “Stay Home, Stay Healthy” order was issued in Washington State in response to the COVID-19 pandemic. On May 1, a 4-phase reopening plan began. If implemented without interruptions, all types of public interactions were planned to resume by July 15. We investigated whether adjunctive prevention strategies would allow less restrictive physical distancing to avoid second epidemic waves and secure safe school reopening.MethodsWe developed a mathematical model, stratifying the population by age (0-19 years, 20-49 years, 50-69 years, and 70+ years), infection status (susceptible, exposed, asymptomatic, pre-symptomatic, symptomatic, recovered) and treatment status (undiagnosed, diagnosed, hospitalized) to project SARS-CoV-2 transmission during and after the reopening period. The model was parameterized with demographic and contact data from King County, WA and calibrated to confirmed cases, deaths (overall and by age) and epidemic peak timing. Adjunctive prevention interventions were simulated assuming different levels of pre-COVID physical interactions (pC_PI) restored. We made several predictions related to adjunctive interventions or changes in pC_PI.ResultsThe best model fit estimated ~35% pC_PI under lockdown. Gradually restoring 75% pC_PI for all age groups between May 15-July 15 resulted in ~350 daily deaths by early September 2020. Maintaining less than 45% pC_PI was required with current testing practices to ensure low levels of daily infections and deaths. If widespread community transmission persisted, isolating the elderly does not lower daily death rates significantly. Increased testing, isolation of symptomatic infections, and contact tracing permitted 60% pC_PI without significant increases in daily deaths before September, although this strategy may not be sufficient to eliminate community transmission. This combination strategy also allowed opening of schools with <15 daily deaths. Inpatient antiviral treatment reduces deaths significantly without lowering cases or hospitalizations.ConclusionsWe predict that widespread implementation of “test and isolate” policy alone is insufficient to prevent the rapid re-emergence of SARS CoV-2 without moderate physical distancing. However, widespread testing, contact tracing and case isolation would allow relaxation of physical distancing, as well as opening of schools, without a surge in local cases and deaths.
Integrative transcriptome analysis of malignant pleural mesothelioma reveals a clinically relevant immune-based classification
Authors: Alay Ania , Cordero David , Hijazo-Pechero Sara , Aliagas Elisabet , Lopez-Doriga Adriana , Marín Raúl , Palmero Ramón , Llatjós Roger , Escobar Ignacio , Ramos Ricard , Padrones Susana , Moreno Víctor , Nadal Ernest , Solé Xavier 
Published: August 2020

AbstractBackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive neoplasia affecting the lung mesothelium. Immune checkpoint inhibitors (ICI) in MPM have not been extremely successful, likely due to poor identification of suitable candidate patients for the therapy. We aimed to identify cellular immune fractions associated with clinical outcome and classify MPM patients based on their immune contexture. For each defined group, we sought for molecular specificities that could help further define our MPM classification at the genomic and transcriptomic level, as well as identify differential therapeutic strategies based on transcriptional signatures predictive of drug response.MethodsThe abundance of 20 immune cell fractions in 516 MPM samples from 7 gene expression datasets was inferred using Gene Set Variation Analysis. Identification of clinically relevant fractions was performed with Cox Proportional-Hazards Models adjusted for age, stage, sex, and tumor histology. Immune-based groups were identified using unsupervised classification.ResultsT-Helper 2 (TH2) and cytotoxic T (TC) cells were found to be consistently associated with overall survival. Three immune clusters (IG) were subsequently defined based on TH2 and TC immune infiltration levels: IG1 (54.5%) was characterized by high TH2 and low TC levels, IG2 (37%) had either low or high levels of both fractions, and IG3 (8.5%) was defined by low TH2 and high TC levels. IG1 and IG3 groups were associated with worse and better overall survival, respectively. The three groups showed differential molecular profiles, with IG1 enriched for CDKN2A and IFN-related genes deletions. At the transcriptional level, IG1 samples showed upregulation of proliferation signatures, while IG3 samples presented upregulation of immune and inflammation-related pathways. Finally, the integration of gene expression with functional signatures of drug response showed that IG3 patients might be more likely to respond to ICI, while IG1 patients could be more sensitive to PARP inhibitors.ConclusionsThis study identifies a novel immune-based signature with potential clinical relevance based on TH2 and TC levels, unveiling a fraction of MPM patients with better prognosis and who might benefit from immune-based therapies. Genomic and transcriptomic specificities of the different groups could be used to tailor potential therapies in the future.