bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of 200 000 exome-sequenced UK Biobank subjects fails to identify genes influencing probability of developing a mood disorder resulting in psychiatric referral
Authors: Curtis David 
Published: May 2021

Background
Depression is moderately heritable but there is no common genetic variant which has a major effect on susceptibility. A previous analysis of 50 000 exome-sequenced subjects failed to implicate any genes or sets of genes in which rare variants were associated with risk of affective disorder requiring specialist treatment. A much larger exome-sequenced dataset is now available.

Methods
Data from 200 632 exome-sequenced UK Biobank participants was analysed. Subjects were treated as cases if they had reported having seen a psychiatrist for ‘nerves, anxiety, tension or depression’. Gene-wise weighted burden analysis was performed to see if there were any genes or sets of genes for which there was an excess of rare, functional variants in cases.

Results
There were 22 886 cases and 176 486 controls. There were 22 642 informative genes but no gene or gene set produced a statistically significant result after correction for multiple testing. None of the genes or gene sets with the lowest P values appeared to be an obvious biological candidate.

Conclusions
The results conform exactly with the expectation under the null hypothesis. It seems unlikely that the use of common, poorly defined phenotypes will produce useful advances in understanding genetic contributions to affective disorder and it might be preferable to focus instead on obtaining large exome-sequenced samples of conditions such as bipolar 1 disorder and severe, recurrent depression. This research has been conducted using the UK Biobank Resource.
The real-life impact of vaccination on COVID-19 mortality in Europe and Israel
Authors: Jabłońska Katarzyna , Aballéa Samuel , Toumi Mondher 
Published: May 2021

AbstractOBJECTIVESThis study aimed at estimating the real-life impact of vaccination on COVID-19 mortality, with adjustment for SARS-CoV-2 variants spread and other factors across Europe and Israel.METHODSTime series analysis of daily number of COVID-19 deaths was performed using non-linear Poisson mixed regression models. Variants’ frequency, demographic, climate, health and mobility characteristics of thirty-two countries were considered as potentially relevant adjustment factors between January 2020 and April 2021.RESULTSThe analysis revealed that vaccination efficacy in terms of protection against deaths was equal to 72%, with a lower reduction of number of deaths for B.1.1.7 versus non-B.1.1.7 variants (70% and 78%, respectively). Other factors significantly related to mortality were arrivals at airports, mobility change from the pre-pandemic level and temperature.CONCLUSIONSOur study confirms a strong effectiveness of COVID-19 vaccination based on real-life public data, although lower than expected from clinical trials. This suggests the absence of indirect protection for non-vaccinated individuals. Results also show that vaccination effectiveness against mortality associated with the B.1.1.7 variant is slightly lower compared with other variants. Lastly, this analysis confirms the role of mobility reduction, within and between countries, as an effective way to reduce COVID-19 mortality and suggests the possibility of seasonal variations in COVID-19 incidence.
Looking for crumbs in the obesity forest: anti-obesity interventions in the Mexican population. History, and systematic review with Meta-Analysis
Authors:   The Síntevi Group, Garcia-Oropesa Esperanza M. , Martinez-Lopez Yoscelina E. , Ruiz-Cejudo Sonia María , Martínez-Ezquerro José Darío , Diaz-Badillo Alvaro , Ramirez-Pfeiffer Carlos , Bustamante-Fuentes Alejandra , Lopez-Sosa Elena B. , Moctezuma-Chavez Oscar O. , Nava-Gonzalez Edna J. , Perales-Torres Adriana L. , Perez-Navarro Lucia M. , Rosas-Diaz Marisol , Carter Kathleen , Tapia Beatriz , Lopez-Alvarenga Juan C. 
Published: May 2021

AbstractMexicans and Mexican Americans share culture, genetic background, and predisposition for chronic complications associated with obesity and diabetes making imperative efficacious treatments and prevention. Obesity has been treated for centuries focused-on weight loss while other treatments on associated conditions like gout, diabetes (T2D), and hypertriglyceridemia. To date, there is no systematic review that synthetize the origin of obesity clinics in Mexico and the efforts to investigate treatments for obesity tested by randomized clinical trials (RCT).We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve anti-obesity RCT through 2019 and without inferior temporal limit. The systematic review included RCT of anti-obesity treatments in the Mexican adult population, including alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions reporting biometric outcomes such as BMI, weight, waist circumference, triglycerides, glucose, among others. Studies with at least three months of treatment were included in the meta-analysis.We found 634 entries, after removal of duplicates and screening the studies based on eligibility criteria, we analyzed 43, and 2 multinational-collaborative studies. Most of the national studies have small sample sizes, and the studied strategies do not have replications in the population. The nutrition/behavioral interventions were difficult to blind, and most studies have medium to high risk of bias. Nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like plain water instead of sweet beverages decrease triglycerides and systolic blood pressure. Participants with obesity and hypertension can have benefic effects with antioxidants, and treatment with insulin increase weight in those with T2D.The study of obesity in Mexico has been on-going for more than four decades, but the interest on RCT just increased until this millennium, but with small sample sizes and lack of replication. The interventions affect different metabolic syndrome components, which should be analyzed in detail with the population living on the U.S.-Mexico border; therefore, bi-national collaboration is desirable to disentangle the cultural effects on this population’s treatment response.
Injustices in pandemic vulnerability: A spatial-statistical analysis of the CDC Social Vulnerability Index and COVID-19 outcomes in the U.S.
Authors: Song Jamie , South Eugenia , Solomon Sara , Wiebe Douglas 
Published: May 2021

AbstractBackgroundThe COVID-19 pandemic has exacerbated health injustices in the U.S. driven by racism and other forms of structural violence. Research has shown the disproportionate impacts of COVID-19 morbidity and mortality in the most marginalized communities.ObjectivesWe examined the associations between COVID-19 cumulative incidence (CI) and case-fatality risk (CFR) and the CDC’s Social Vulnerability Index (SVI), a composite score assessing historical marginalization and thus vulnerability to disaster events.MethodsUsing county-level data from national databases, we used population density, Gini index, percent uninsured, and average annual temperature as covariates, and employed negative binomial regression to evaluate relationships between SVI and COVID-19 outcomes. Optimized hot spot analysis identified hot spots of COVID-19 CI and CFR, which were compared in terms of SVI using logistic regression.ResultsAs of 2/3/21, 26,452,031 cases of and 448,786 deaths from COVID-19 had been reported in the U.S. Negative binomial regression showed that counties in the top SVI quintile reported 13.7% higher CI (p<0.001) than those in the bottom SVI quintile. Additionally, each unit increase in a county’s SVI score was associated with a 0.2% increase in CFR (p<0.001). Logistic regression analysis showed that counties in the lowest SVI quintile had significantly greater odds of being in a CI hot spot than all other counties, yet counties in the highest SVI quintile had 63% greater odds (p=0.008) of being in a CFR hot spot than counties in the lowest SVI quintile.ConclusionWe demonstrated a significant relationship between SVI and CFR, but the relationship between SVI and CI is complex and warrants further investigation. SVI may help elucidate unequal impacts of COVID-19 and guide prioritization of vaccines to communities most impacted by structural injustices.
How can we increase notification of exposure to STIs between gay and bisexual men?: intervention development using stakeholder engagement, qualitative methods and behavioural science
Authors: Flowers Paul , Gerressu Makeda , McLeod Julie , McQueen Jean , Vojt Gabriele , Symonds Merle , Woode-Owusu Melvina , Estcourt Claudia 
Published: May 2021

AbstractRationaleThe first key step in contact tracing for sexually transmitted infections (STIs) is tonotifyrecent exposed sex partners. Gay and bisexual men and other men who have sex with men (GBMSM) bear a high burden of STIs and one-off partners contribute disproportionately to community transmission, posing a particular challenge to contact tracing. Here we explore and theorise the barriers and facilitators of GBMSM telling their ‘one-off’ sexual partners about their exposure to STIs.DesignUsing focus groups with diverse GBMSM from Leeds, Glasgow, London and on-line (n=28) we used a multi-level approach to intervention development to enhance contact tracing. This framework included initial stakeholder engagement; deductive thematic analysis to identify key barriers and facilitators to contact tracing with one-off partners; the use of the theoretical domains framework (TDF) to theorise these barriers and facilitators and subsequently the use of the behaviour change wheel (BCW), incorporating the behaviour change technique taxonomy (BCTT), to suggest intervention content to enhance the key step of notifying partners; and final stakeholder input to ensure this content was fit for purpose and satisfied the APEASE criteria.ResultsIn relation to the TDF, the barriers and facilitators primarily related to ‘beliefs about consequences’. Having used the BCW and further stakeholder engagement, our final intervention recommendations related to focussed efforts to change the culture and corresponding norms and social practice of notifying sex partners about the risk of infection in GBMSM communities. This could usefully be achieved through dedicated community engagement and partnership work, through focussed mass and social media interventions twinned with focussed peer-led work to normalise and destigmatise contact tracing.ConclusionThrough systematically working with key stakeholders, GBMSM communities and using a range of tools from the behavioural sciences, we have developed a suite of evidence-based and theoretically informed intervention content which, if developed further, could enhance GBMSM’s willingness to notify sex partners about their risk of infection.
Trends in medical and surgical admission length of stay by race/ethnicity and socioeconomic status: a time series analysis
Authors: Ghosh Arnab K. , Unruh Mark A. , Soroka Orysya , Shapiro Martin 
Published: May 2021

ABSTRACTLength of stay, a metric of hospital efficiency, differs by race/ethnicity and socioeconomic status (SES). Longer LOS is associated with adverse health outcomes. We assessed differences in average adjusted length of stay (aALOS) over time by race/ethnicity, and SES stratified by discharge destination (home or non-home). Using the 2009-2014 State Inpatient Datasets from three states, we examined trends in aALOS differences by race/ethnicity, and SES (defined first vs fourth quartile of median income by zip code) controlling for patient, disease and hospital characteristics. For those discharged home, racial/ethnic and SES aALOS differences remained stable. Notably, for those discharged to non-home destinations, Black vs White, and low vs high SES aALOS differences increased significantly from 2009 to 2013, more sharply after Q3 2011, the Affordable Care Act’s (ACA) introduction. Further research to understand the ACA’s policy impact on hospital efficiencies, and relationship to racial/ethnic and SES differences in LOS is warranted.
Estimates of cases and hospitalizations averted by COVID-19 case investigation and contact tracing in 14 health jurisdictions in the United States
Authors: Jeon Seonghye , Rainisch Gabriel , Lash R. Ryan , Moonan Patrick K. , Oeltmann John E. , Greening Bradford , Adhikari Bishwa B. ,   Contact Tracing Impact Group, Meltzer Martin I. 
Published: May 2021

ABSTRACTContextThe implementation of case investigation and contact tracing (CICT) for controlling COVID-19 (caused by SARS-Cov-2 virus) has proven challenging due to varying levels of public acceptance and initially constrained resources, especially enough trained staff. Evaluating the impacts of CICT will aid efforts to improve such programs.ObjectivesEstimate the number of COVID-19 cases and hospitalizations averted by CICT and identify CICT processes that could improve overall effectiveness.DesignWe used data on proportion of cases interviewed, contacts notified or monitored, and days from testing to contact notification from 14 jurisdictions to model the impact of CICT on cumulative cases counts and hospitalizations over a 60-day period. Using the Centers for Disease Control and Prevention (CDC)’s COVIDTracer tool, we estimated a range of impacts by assuming either contacts would quarantine only if monitored or would do so upon notification of potential exposure. We also varied the observed program metrics to assess their relative influence.ResultsPerformance by jurisdictions varied widely. Jurisdictions isolated between 12 and 86% of cases (including contacts which became cases) within 6 to 10 days after exposure-and-infection. We estimated that CICT-related reductions in transmission ranged from 0.4% to 32%. For every 100 cases prevented by nonpharmaceutical interventions, CICT averted between 4 and 97 additional cases. Reducing time to case isolation by one day increased averted case estimates by up to 15 percentage points. Increasing the proportion of cases interviewed or contacts notified by 20 percentage points each resulted in at most 3 or 6 percentage point improvements in averted cases.ConclusionsWe estimated that case investigation and contact tracing reduced the number of COVID-19 cases and hospitalizations among all jurisdictions studied. Reducing time to isolation produced the greatest improvements in impact of CICT.
Modeling the impact of COVID-19 vaccination in Lebanon: A call to speed-up vaccine roll out
Authors: Mumtaz Ghina R. , El-Jardali Fadi , Jabbour Mathilda , Harb Aya , Abu-Raddad Laith J. , Makhoul Monia 
Published: May 2021

AbstractBackgroundAmidst a very difficult economic and political situation, and after a large first SARS-CoV-2 wave near the end of 2020, Lebanon launched its vaccination campaign on 14 February 2021. To date, only 6.7% of the population have received at least one dose of the vaccine, raising serious concerns over the speed of vaccine roll-out and its impact in the event of a future surge.ObjectiveUsing mathematical modeling, we assessed the short-term impact (by end of 2021) of various vaccine roll-out scenarios on SARS-CoV-2 epidemic course in Lebanon.ResultsAt current immunity levels in the population, estimated by the model at 40% on 15 April 2021, a large epidemic wave is predicted if all social distancing restrictions are gradually eased and variants of concern are introduced. Reaching 80% vaccine coverage by end of 2021 will flatten the epidemic curve and will result in a 37% and 34% decrease in the peak daily numbers of severe/critical disease cases and deaths, respectively; while reaching intermediate coverage of 40% will result in only 10-11% decrease in each. Reaching 80% coverage by end of 2021 will avert 3 times more hospitalizations and deaths over the course of this year compared with 40% coverage. Impact of vaccination was substantially enhanced with rapid scale-up. Reaching 80% vaccine coverage by August would prevent twice as many severe/critical disease cases and deaths than if it were reached by December. Finally, a longer duration over which restrictions are eased resulted in a more favorable impact of vaccination.ConclusionFor vaccination to have an impact on the predicted epidemic course and associated disease burden in Lebanon, vaccination has to be rapid and reach high coverage (at least 70%), while sustaining social distancing measures during roll-out. At current vaccination pace, this is unlikely to be achieved. Concerted efforts need to be put to overcome local challenges and substantially scale up vaccination to avoid a surge that the country, with its multiple crises and limited health-care capacity, is largely unprepared for.
Immune transcriptomes from hospitalized patients infected with the SARS-CoV-2 variants B.1.1.7 and B.1.1.7 carrying the E484K escape mutation
Authors: Lee Hye Kyung , Knabl Ludwig , Knabl Ludwig , Wieser Manuel , Mur Anna , Zabernigg August , Schumacher Jana , Kaiser Norbert , Furth Priscilla A. , Hennighausen Lothar 
Published: May 2021

AbstractFast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. B.1.1.7 (VOC-202012/01) has become the predominant variant in many countries and a new lineage (VOC-202102/02) harboring the E484K escape mutation in the B.1.1.7 background emerged in February 20211. This variant is of concern due to reduced neutralizing activity by vaccine-elicited antibodies2,3. However, it is not known whether this single amino acid change leads to an altered immune response. Here, we investigate differences in the immune transcriptome in hospitalized patients infected with either B.1.1.7 (n=28) or B.1.1.7+E484K (n=12). RNA-seq conducted on PBMCs isolated within five days after the onset of COVID symptoms demonstrated elevated activation of specific immune pathways, including JAK-STAT signaling, in B.1.1.7+E484K patients as compared to B.1.1.7. Longitudinal transcriptome studies demonstrated a delayed dampening of interferon-activated pathways in B.1.1.7+E484K patients. Prior vaccination with BNT162b vaccine (n=8 one dose; n=1 two doses) reduced the transcriptome inflammatory response to B.1.1.7+E484K infection relative to unvaccinated patients. Lastly, the immune transcriptome of patients infected with additional variants (B.1.258, B.1.1.163 and B.1.7.7) displayed a reduced activation compared to patients infected with B.1.1.7. Acquisition of the E484K substitution in the B.1.1.7 background elicits an altered immune response, which could impact disease progression.
Predicting EGFR mutation status in lung adenocarcinoma presenting as ground-glass opacity: utilizing radiomics model in clinical translation
Authors: Cheng Bo , Deng Hongsheng , Zhao Yi , Xiong Junfeng , Liang Peng , Li Caichen , Liang Hengrui , Shi Jiang , Li Jianfu , Xiong Shan , Lai Ting , Chen Zhuxing , Wu Jianrong , Qian Tianyi , Huan Wenjing , Alexander Ng Man Tat , Wang Guotai , He Jianxing , Liang Wenhua 
Published: May 2021

AbstractObjectivesThis study aimed to establish a noninvasive radiomics model based on computed tomography (CT), with favorable sensitivity and specificity to predict EGFR mutation status in GGO-featured lung adenocarcinoma that subsequently guiding the administration of targeted therapy.MethodClinical-pathological information and preoperative CT-images of 636 lung adenocarcinoma patients (464, 100, and 72 in the training, internal, and external validation sets, respectively) that underwent GGO lesions resection were included. A total of 1476 radiomic features were extracted with gradient boosting decision tree (GBDT).ResultsThe established radiomics model containing 252 selected features showed an encouraging discrimination performance of EGFR mutation status (mutant or wild-type), and the predictive ability was superior to that of the clinical model (AUC: 0.901 vs. 0.674, 0.813 vs. 0.730, and 0.801 vs. 0.746 the training, internal, and external validation sets, respectively). The combined radiomics plus clinical model showed no additional benefit over the radiomics model in predicting EGFR status (AUC: 0.909 vs. 0.901, 0.803 vs. 0.813, 0.808 vs. 0.801, respectively, in three cohorts). Uniquely, this model was validated in a cohort of lung adenocarcinoma patients who undertaken adjuvant EGFR-TKIs and harbored unresected GGOs, leading to a significantly improved potency of EGFR-TKIs (response rate: 33.9% vs. 62.5%, P =0.04; before- and after-prediction, respectively).ConclusionThis presented radiomics model can be served as a noninvasive and time-saving approach for predicting the EGFR mutation status in lung adenocarcinoma presenting as GGO.Key pointsWe developed a GGO-specific radiomics model containing 252 radiomics features for EGFR mutation status differentiation.An AUC of 0.813 and 0.801 in the internal and external validation cohort, respectively, were achieved.The radiomics model was utilized in clinical translation in an adjuvant EGFR-TKIs cohort with unresected GGOs. A significant improvement in the potency of EGFR-TKIs was achieved (response rate: 33.9% vs. 62.5%, P =0.04; before- and after-prediction).
Effectiveness of the Covid-19 vaccines in preventing infection in dental practitioners – results of a cross-sectional ‘questionnaire-based’ survey
Authors: Kumar Sanjeev , Saxena Susmita , Atri Mansi , Chamola Sunil Kumar 
Published: May 2021

AbstractIndia started its vaccination program at the beginning of 2021, the main beneficiaries being health workers and frontline workers including police, paramilitary forces, sanitation workers, and disaster management volunteers in the first phase. By the time, the second wave of Covid-19 impacted India, approximately 14 million healthcare and frontline workers, including dentists had been vaccinated.AimTo study the effectiveness of vaccination on a subset of high-risk healthcare workers i.e. dentists in preventing Covid-19 during the second wave of the pandemic.Study designA questionnaire based pan-India online survey was carried out to record the Covid-related experiences of dentists prior to and after vaccination.ResultThe sample size for this survey was 4493 respondents from across India. During the second wave, 9.18% (n=364) respondents became positive in spite of the vaccine, while 14.69%(n=78) became positive in the unvaccinated group. A chi-square test of independence was performed to examine the relation between vaccination and the Covid positivity rate in all age groups. The relation between these variables was highly significant, [X2 (1, N = 4493) = 15.9809, p=.000064].ConclusionOur pan-India online survey inferred that vaccination has a definitive role to play in reducing the positivity rate amongst dentists during the second wave of the pandemic across all age groups.