bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically-proxied therapeutic inhibition of antihypertensive drug targets and risk of common cancers
Authors: Yarmolinsky James , Díez-Obrero Virginia , Richardson Tom G , Pigeyre Marie , Sjaarda Jennifer , Paré Guillaume , Walker Venexia M , Vincent Emma E , Tan Vanessa Y , Obón-Santacana Mireia , Albanes Demetrius , Hampe Jochen , Gsur Andrea , Hampel Heather , Kampman Ellen , Pai Rish K , Jenkins Mark , Gallinger Steven , Casey Graham , Zheng Wei , Amos Christopher I ,   the International Lung Cancer Consortium,   the PRACTICAL consortium, Smith George Davey , Martin Richard M , Moreno Victor 
Published: March 2021

AbstractBackgroundEpidemiological studies have reported conflicting findings on the potential adverse effects of long-term antihypertensive medication use on cancer risk. Naturally occurring variation in genes encoding antihypertensive drug targets can be used as proxies for these targets to examine the effect of their long-term therapeutic inhibition on disease outcomes.MethodsSingle-nucleotide polymorphisms (SNPs) in ACE, ADRB1, and SLC12A3 associated (P < 5.0 x 10-8) with systolic blood pressure in genome-wide association studies (GWAS) were used to proxy inhibition of angiotensin-converting enzyme (ACE), β-1 adrenergic receptor (ADRB1), and sodium-chloride symporter (NCC), respectively. Summary genetic association estimates for these SNPs were obtained from GWAS consortia for the following cancers: breast (122,977 cases, 105,974 controls), colorectal (58,221 cases, 67,694 controls), lung (29,266 cases, 56,450 controls), and prostate (79,148 cases, 61,106 controls). Replication analyses were performed in the FinnGen consortium (1,573 colorectal cancer cases, 120,006 controls). Inverse-variance weighted random- effects models were used to examine associations between genetically-proxied inhibition of these drug targets and risk of cancer. Multivariable Mendelian randomization and colocalisation analyses were employed to examine robustness of findings to violations of Mendelian randomization assumptions.ResultsGenetically-proxied ACE inhibition equivalent to a 1 mmHg reduction in systolic blood pressure was associated with increased odds of colorectal cancer (OR 1.13, 95% CI 1.06-1.22; P = 3.6 x 10-4). This finding was replicated in the FinnGen consortium (OR 1.40, 95% CI 1.02-1.92; P = 0.035). There was little evidence of association of genetically-proxied ACE inhibition with risk of breast cancer (OR 0.98, 95% CI 0.94-1.02, P = 0.35), lung cancer (OR 1.01, 95% CI 0.92-1.10; P = 0.93), or prostate cancer (OR 1.06, 95% CI 0.99-1.13; P = 0.08). Genetically-proxied inhibition of ADRB1 and NCC were not associated with risk of these cancers.ConclusionGenetically-proxied long-term ACE inhibition was associated with an increased risk of colorectal cancer, warranting comprehensive evaluation of the safety profiles of ACE inhibitors in clinical trials with adequate follow-up. There was little evidence to support associations across other drug target-cancer risk analyses, consistent with findings from short-term randomised controlled trials for these medications.
Evolution of antibodies against SARS-CoV-2 over seven months: experience of the Nationwide Seroprevalence ENE-COVID Study in Spain
Authors: Pérez-Olmeda Mayte , Saugar José María , Fernández-García Aurora , Pérez-Gómez Beatriz , Pollán Marina , Avellón Ana , Pastor-Barriuso Roberto , Fernández-de Larrea Nerea , Martín Mariano , Cruz Israel , Sanmartín Jose L , Fedele Giovanni , León Paniagua Jose , Muñoz-Montalvo Juan F , Blanco Faustino , Yotti Raquel , Oteo-Iglesias Jesús 
Published: March 2021

AbstractObjectivesTo analyse temporal trends in SARS-CoV-2 anti-nucleocapsid IgG throughout the four rounds of the nationwide seroepidemiologic study ENE-COVID (April-November 2020), and to compare the fourth-round results of two immunoassays detecting antibodies against nucleocapsid and to S protein receptor-binding domain (RBD).MethodsA chemiluminescent microparticle immunoassay (CMIA) was offered to all participants in the first three rounds (Abbott; anti-nucleocapsid IgG). In the fourth round we offered this test and a chemiluminescence immunoassay (CLIA) (Beckman; anti-RBD IgG) to i) a randomly selected sub-cohort, ii) participants who were IgG-positive in any of the three first rounds; and iii) participants who were IgG-positive in the fourth round by point-of-care immunochromatography.ResultsImmunoassays involving 10,153 participants (82.2% of people invited to donate samples) were performed in the fourth round. A total of 2595 participants (35.1% of participants with immunoassay results in the four rounds) were positive for anti-nucleocapsid IgG in at least one round. Anti-nucleocapsid IgG became undetectable in 43.3% of participants with positive first-round results. Pneumonia was more frequent in participants with anti-nucleocapsid IgG in all four rounds (11.2%) than those in which IgG became undetectable (2.4%).In fourth round, anti-nucleocapsid and anti-RBD IgG were detected in 5.5% and 5.4% participants of the randomly selected sub-cohort, and in 26.6% and 25.9% participants with at least one previous positive result, respectively. Agreement between techniques was 90.3% (kappa: 0.72).ConclusionsThe response of IgG to SARS-CoV-2 is heterogeneous and conditioned by infection severity. A substantial proportion of the SARS-CoV-2 infected population may have negative serologic results in the post-infection months.
Quantifying Contact Patterns in Response to COVID-19 Public Health Measures in Canada
Authors: Brankston Gabrielle , Merkley Eric , Fisman David N. , Tuite Ashleigh R. , Poljak Zvonimir , Loewen Peter J. , Greer Amy L. 
Published: March 2021

AbstractBackgroundA variety of public health measures have been implemented during the COVID-19 pandemic in Canada to reduce contact between individuals.ObjectiveThe objective of this study was to construct contact patterns to evaluate the degree to which social contacts rebounded to normal levels, as well as direct public health efforts toward age- and location-specific settings.DesignFour population-based cross-sectional surveys.SettingCanada.ParticipantsMembers of a paid panel representative of Canadian adults by age, gender, official language, and region of residence.MethodsRespondents provided information about the age and setting for each direct contact made in a 24-hour period. Contact matrices were constructed and contacts for those under the age of 18 years imputed. The next generation matrix approach was used to estimate the reproduction number (Rt) for each survey. Respondents with children estimated the number of contacts their children made in school and extracurricular settings.ResultsEstimated Rt values were 0.49 (95% CI: 0.29-0.69) for May, 0.48 (95% CI: 0.29-0.68) for July, 1.06 (95% CI: 0.63-1.52) for September, and 0.81 (0.47-1.17) for December. The highest proportion of reported contacts occurred within the home (51.3% in May), in ‘other’ locations (49.2% in July) and at work (66.3% and 65.4% in September and December). Respondents with children reported an average of 22.7 (95% CI: 21.1-24.3) (September) and 19.0 (95% CI 17.7-20.4) (December) contacts at school per day per child in attendance.ConclusionThe skewed distribution of reported contacts toward workplace settings in September and December combined with the number of reported school-related contacts suggest that these settings represent important opportunities for transmission emphasizing the need to ensure infection control procedures in both workplaces and schools.
SARS-CoV-2 specific immune-signature in direct contacts of COVID-19 cases protect them from contracting disease: A Retrospective Study
Authors: Raghav Sunil K. , Sen Kaushik , Ghosh Arup , Datta Sudeshna , Ahad Abdul , Jha Atimukta , Chatterjee Sanchari , Suranjika Sandhya , Sengupta Soumya , Bhattacharya Gargee , Shriwas Omprakash , Avula Kiran , Kshatri Jayasingh , Prasad Punit , Parida Ajay K. 
Published: March 2021

AbstractThe response to SARS-CoV-2 is largely impacted by the level of exposure and the status of immunity. The nature of protection shown by direct contacts of COVID-19 positive patients is quite intriguing to note. We aimed to study the immune differences reinforcing contact individuals in circumventing the disease. Our observation showed direct contacts of PCR positive patients developed elevated neutralizing antibody titres and cytokine levels. On the other hand, single cell data revealed differential usage of V(D)J genes and unique BCR clonotypes imparting protective immune signatures.Topicsserologic tests, immunoglobulin a, immunoglobulin g, immunoglobulin m, antibody titre; cytokine levels; virus neutralization; V(D)J sequencing; BCR clonotypes
Comparing COVID-19 risk factors in Brazil using machine learning: the importance of socioeconomic, demographic and structural factors
Authors: Baqui Pedro , Marra Valerio , Alaa Ahmed M. , Bica Ioana , Ercole Ari , van der Schaar Mihaela 
Published: March 2021

BackgroundThe COVID-19 pandemic continues to have a devastating impact on Brazil. Brazil’s social, health and economic crises are aggravated by strong societal inequities and persisting political disarray. This complex scenario motivates careful study of the clinical, socioeconomic, demographic and structural factors contributing to increased risk of mortality from SARS-CoV-2 in Brazil specifically.MethodsWe consider the Brazilian SIVEP-Gripe catalog, a very rich respiratory infection dataset which allows us to estimate the importance of several non-laboratorial and socio-geographic factors on COVID-19 mortality. We analyze the catalog using machine learning algorithms to account for likely complex interdependence between metrics.FindingsThe XGBoost algorithm achieved excellent performance, producing an AUC-ROC of 0.813 (95%CI 0.810–0.817), and outperforming logistic regression. Using our model we found that, in Brazil, socioeconomic, geographical and structural factors are more important than individual comorbidities. Particularly important factors were: The state of residence and its development index; the distance to the hospital (especially for rural and less developed areas); the level of education; hospital funding model and strain. Ethnicity is also confirmed to be more important than comorbidities but less than the aforementioned factors.InterpretationSocioeconomic and structural factors are as important as biological factors in determining the outcome of COVID-19. This has important consequences for policy making, especially on vaccination/non-pharmacological preventative measures, hospital management and healthcare network organization.FundingNone.
Airborne Transmission of COVID-19 and Mitigation Using Box Fan Air Cleaners in a Poorly Ventilated Classroom
Authors: He Ruichen , Liu Wanjiao , Elson John , Vogt Rainer , Maranville Clay , Hong Jiarong 
Published: March 2021

ABSTRACTMany indoor places, including aged classrooms and offices, prisons, homeless shelters, etc., are poorly ventilated but resource-limited to afford expensive ventilation upgrade or commercial air purification systems, raising concerns on the safety of opening activities in these places in the era of COVID-19 pandemic. To address this challenge, using computational fluid dynamics, we conducted a systematic investigation of airborne transmission in a classroom equipped with a single horizontal unit ventilator (HUV) and evaluate the performance of low-cost box fan air cleaner for risk mitigation. Our study shows that placing box fan air cleaners in the classroom results in a substantial reduction of airborne transmission risk across the entire space. The air cleaner can achieve optimal performance when placed near the asymptomatic patient. However, without knowing the location of the patient, the performance of the cleaner is optimal near the HUV with the air flowing downwards. In addition, we find that it is more efficient in reducing aerosol concentration and spread in the classroom by adding air cleaners in comparison with raising the flow rate of HUV alone. The number and placement of air cleaners need to be adjusted to maintain its efficacy for larger classrooms and to account for the thermal gradient associated with human thermal plume and hot ventilation air during cold seasons. Overall, our study shows that box fan air cleaners can serve as an effective low-cost alternative for mitigating airborne transmission risks in poorly ventilated spaces.
A rapid review of COVID-19 vaccine prioritization in the U.S.: alignment between Federal guidance and State practice
Authors: Jain Vageesh , Schwarz Lara , Lorgelly Paula 
Published: March 2021

AbstractBackgroundPopulation groups to be prioritized for COVID-19 vaccinations in the U.S. have been determined at the Federal level. Evidence suggests that there is variation in how States have implemented this guidance. This review examines how the position of population groups in vaccine priority lists varies between Federal guidance and State practice.MethodsAn online search of State vaccination prioritization plans was conducted. Data were extracted on each population group included and their relative position. A standardized ranking method was applied to provide a directional measure of variability in prioritization between State and Federal guidance, for each population group.ResultsHealthcare workers and those in long-term care facilities were largely prioritized in line with Federal guidance. Aside from early education staff, essential workers were often excluded at State level. Of the 37 States including frontline essential workers, 12 assigned them to a lower priority than recommended. Almost all States included the 65-74 year age group and most assigned them to a higher position than recommended in Federal guidance. Those with underlying medical conditions were similarly highly prioritized, although there was more variability across States. Some socially vulnerable groups (not included in Federal guidance) were highly prioritized by many States.ConclusionsAcross the U.S, the prioritization of groups for COVID-19 vaccination has been highly variable. Essential workers were the most often excluded or less highly prioritised group compared to Federal guidance. Some socially vulnerable groups were highly prioritized in State plans, whilst others were mentioned in only a few States. Future guidance must be relevant to local needs and values, to minimise any unwarranted heterogeneity in vaccine access across populations.
Exposure to SARS-CoV-2 within the household is associated with greater symptom severity and stronger antibody responses in a community-based sample of seropositive adults
Authors: Schrock Joshua M. , Ryan Daniel T. , Saber Rana , Benbow Nanette , Vaught Lauren A. , Reiser Nina , Velez Matthew P. , Hsieh Ryan , Newcomb Michael , Demonbreun Alexis R. , Mustanski Brian , McNally Elizabeth M. , D’Aquila Richard , McDade Thomas W. 
Published: March 2021

AbstractMagnitude of SARS-CoV-2 virus exposure may contribute to symptom severity. In a sample of seropositive adults (n=1101), we found that individuals who lived with a known COVID-19 case exhibited greater symptom severity and IgG concentrations compared to individuals who were seropositive but did not live with a known case (P<0.0001).
Sex ratios and ‘missing women’ among Asian minority and migrant populations in Aotearoa/New Zealand: A retrospective cohort analysis
Authors: Simon-Kumar Rachel , Paynter Janine , Chiang Annie , Chabba Nimisha 
Published: March 2021

ABSTRACTBackgroundRecent research from the UK, USA, Australia, and Canada point to male-favouring Sex Ratios at Birth (SRB) among their Asian minority populations, attributed to son preference and sex-selective abortion within these cultural groups. The present study conducts a similar investigation of SRBs among New Zealand’s Asian minority and migrant populations, who comprise 15% of the population.MethodsThe New Zealand historical census series between 1976-2013 was used to examine SRBs between ages 0-5 by ethnicity. A retrospective birth cohort in New Zealand was created using the Stats NZ Integrated Data Infrastructure from 2003-2018. A logistic regression was conducted and adjusted for selected variables of interest including visa group, parity, maternal age and deprivation. Finally, associations between family size, ethnicity and family gender composition were examined in a subset of this cohort (families with 2 or 3 children).ResultsThere was no evidence of ‘missing women’ or gender bias as indicated by a deviation from the biological norm in New Zealand’s Asian population. However, Indian and Chinese families were significantly more likely to have a third child if their first two children were females compared to two male children.ConclusionThe analyses did not reveal male-favouring SRBs or any conclusive evidence of sex-selective abortion among Indian and Chinese populations. Based on this data, we conclude that in comparison to other western countries, New Zealand’s Asian migrant populations presents as an anomaly. The larger family sizes for Indian and Chinese populations where the first two children were girls suggested potentially ‘soft’ practices of son preference.WHAT IS ALREADY KNOWN ON THIS SUBJECT-There are discrepancies in Sex Ratios at Birth (SRB) among the Asian minority migrant populations – particularly Indian and Chinese populations –in countries like Canada, UK, USA. SRBs show a pronounced number of males over female children, suggesting a widespread practice of sex-selective abortions in these communities since the 1970s.-These trends implicitly reflect social norms of gender bias through son preference, and daughter devaluation.WHAT IS BEING ADDED-The present study did not find evidence of skewed SRBs that favour boys over girls among Asian ethnicities. The analyses however did find a tendency for Indian and Chinese families to have larger families especially when the first two children were girls.-Overall, the findings suggest the absence of widespread practices of sex-selective abortion making New Zealand an anomaly relative to other migrant-receiving countries. However, there are still vestiges of son preference that are seen through decisions around family size and gender composition.
Ancestrally and Temporally Diverse Analysis of Penetrance of Clinical Variants in 72,434 Individuals
Authors: Forrest Iain S. , Chaudhary Kumardeep , Vy Ha My T. , Bafna Shantanu , Jordan Daniel M. , Rocheleau Ghislain , Loos Ruth J.F. , Cho Judy H. , Do Ron 
Published: March 2021

ABSTRACTA major goal of genomic medicine is to quantify the disease risk of genetic variants. Here, we report the penetrance of 37,772 clinically relevant variants (including those reported in ClinVar1 and of loss-of-function consequence) for 197 diseases in an analysis of exome sequence data for 72,434 individuals over five ancestries and six decades of ages from two large-scale population-based biobanks (BioMe Biobank and UK Biobank). With a high-quality set of 5,359 clinically impactful variants, we evaluate disease prevalence in carriers and non-carriers to interrogate major determinants and implications of penetrance. First, we associate biomarker levels with penetrance of variants in known disease-predisposition genes and illustrate their clear biological link to disease. We then systematically uncover large numbers of ClinVar pathogenic variants that confer low risk of disease, even among those reviewed by experts, while delineating stark differences in variant penetrance by molecular consequence. Furthermore, we ascertain numerous variants present in non-European ancestries and reveal how increasing carrier age modifies penetrance estimates. Lastly, we examine substantial heterogeneity of penetrance among variants in known disease-predisposition genes for conditions such as familial hypercholesterolemia and breast cancer. These data indicate that existing categorical systems for variant classification do not adequately capture disease risk and warrant consideration of a more quantitative system based on population-based penetrance to evaluate clinical impact.
Prediction of severe COVID-19 cases requiring a ventilator in Tokyo, Japan
Authors: Kurita Junko , Sugawara Tamie , Ohkusa Yasushi 
Published: March 2021

SummaryBackgroundTo avoid exhaustion of medical resources by COVID-19, policy-makers must predict care needs, specifically the proportion of severe cases likely to need ventilator care.ObjectiveThis study was designed to use a statistical model to elucidate dynamics of severe cases in Tokyo and to discuss the timing of effective policy activation.MethodsThe study extended from April 27 through October 18, 2020 in Japan’s Tokyo Metropolitan area. Medical exhaustion was defined as use of more than half of the ventilator capacity available before the COVID-19 outbreak. We regressed the number of severe cases on the newly onset patients of more than 14 days prior. As earlier research indicated, the COVID-19 severity changed at the end of May. Therefore, we added dummy variables to reflect changing severity from June and its product with newly onset patients as the explanatory variable. Then we calculated the threshold using R(t): R(t)=0.99 for the number of patients 14 days prior was used as a threshold at which strong countermeasures should be activated to keep to avoid medical exhaustion.ResultsThe critical number signaling medical exhaustion in Tokyo was defined as 655 cases. We selected 15, 30, 60 and 90 days prior as explanatory variables for explaining the number of severe cases. A coefficient of determination larger than 0.95 was inferred as indicating good fit. The threshold was estimated as more than 4500 cases for R(t)=1.1 and monotonically decreasing by R(t) to be 600 cases for R(t)=2.5.Discussion and ConclusionResults showed that newly onset patients reported more than 14 days prior can explain the number of severe cases very well. We also confirmed the threshold number of patients 14 days prior by R(t) for which strong countermeasures should be activated to avoid medical exhaustion with R(t)=0.99. This method is expected to be useful for countermeasure activation policies for Tokyo.
Relationships Between Parental Involvement and Suicidal Ideation among In-school Adolescents in Vietnam: A Multilevel Analysis of the Global School-Based Student Health Survey 2019
Authors: Long Khuong Quynh , Hanh Tran Thi Tuyet , Anh Hoang Thi Ngoc , Park Kidong , Takeuchi Momoe , Lam Nguyen Tuan , Nga Pham Thi Quynh , Anh Le Phuong , Van Tuan Le , Bao Tran Quoc , Nguyet Van Nguyen Hang , Thanh Pham Quoc , Phi Nguyen Hong , Anh Le Duong Minh , Phuong Nguyen Hong , Van Minh Hoang 
Published: March 2021

AbstractYouth suicide is a leading cause of death among adolescents, but evidence about the influences of parental involvement on adolescent suicidal behaviors is inconsistent and have not been well studied. We used nationally representative data from the Vietnam Global School-based Student Health Survey (GSHS) 2019 (n = 7796 students aged 13–18 years). Using the 2-level random intercept logistic regressions, we evaluated the relationship between parental involvement (high expectation, monitoring, and understanding) and suicidal ideation and identified related factors of suicidal ideation. The overall prevalence of suicidal ideation was 15.6%. While high level of parental monitoring and understanding were associated with lower odds of suicidal ideation among adolescents (OR: 0.63; 95% CI: 0.52–0.77 and OR: 0.60; 95% CI: 0.49–0.73, respectively), high parental expectation was linked to higher odds of suicidal ideation (OR: 1.42; 95% CI: 1.24–1.63). Other risk factors at the individual- and school-level for suicidal ideation included being girls, living in urban areas, having mental health problems, involving in risk behaviors, suffering from bullying and violence, and poor school quality. Targeted suicide prevention initiatives should take into account comprehensive aspects of parent-child bonding, student, and school factors to mitigate the burden of suicidal behaviors among adolescents.