bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independent of body mass index
Authors: Hartley April , Sanderson Eleanor , Granell Raquel , Paternoster Lavinia , Zheng Jie , Smith George Davey , Southam Lorraine , Hatzikotoulas Konstantinos , Boer Cindy G , van Meurs Joyce , Zeggini Eleftheria ,   The Genetics of Osteoarthritis consortium, Gregson Celia L , Tobias Jon H 
Published: March 2021

AbstractObjectivesObservational analyses suggest that high Bone Mineral Density (BMD) is a risk factor for osteoarthritis (OA); it’s unclear whether this represents a causal effect or shared aetiology and whether these relationships are body mass index (BMI)-independent. We performed bidirectional Mendelian randomization (MR) to uncover the causal pathways between BMD, BMI and OA.MethodsOne-sample (1S)MR estimates were generated by two-stage least-squares regression. Unweighted allele scores instrumented each exposure. Two-sample (2S)MR estimates were generated using inverse-variance weighted fixed-effects meta-analysis. Multivariable MR (MVMR), including BMD and BMI instruments in the same model, determined the BMI-independent causal pathway from BMD to OA. Latent causal variable (LCV) analysis, using weight-adjusted FN-BMD and hip/knee OA summary statistics, determined if genetic correlation explained the causal effect of BMD on OA.Results1SMR provided strong evidence for a causal effect of eBMD on hip and knee OA (ORhip =1.28[1.05,1.57],p=0.02, ORknee =1.40[1.20,1.63],p=3×10−5, OR per SD increase). 2SMR effect sizes were consistent in direction. Results suggested that the causal pathways between eBMD and OA were bidirectional (βhip=1.10[0.36,1.84],p=0.003, β knee =4.16[2.74,5.57],p=8×10−9, β=SD increase per doubling in risk). MVMR identified a BMI-independent causal pathway between eBMD and hip/knee OA. LCV suggested that genetic correlation (i.e. shared genetic aetiology) did not fully explain causal effects of BMD on hip/knee OA.ConclusionsThese results provide evidence for a BMI-independent causal effect of eBMD on OA. Despite evidence of bidirectional effects, the effect of BMD on OA did not appear to be fully explained by shared genetic aetiology, suggesting a direct action of bone on joint deterioration.
Localised community circulation of SARS-CoV-2 viruses with an increased accumulation of single nucleotide polymorphisms that adversely affect the sensitivity of real-time reverse transcription assays targeting Nucleocapsid protein
Authors: Moore Catherine , Davies Louise , Rees Rhiannydd , Gifford Laura , Lewis Heather , Plimmer Amy , Barratt Andrew , Pacchiarini Nicole , Southgate Joel ,   the COG-UK Consortium, Bull Matthew J. , Watkins Joanne , Corden Sally , Connor Thomas R. 
Published: March 2021

SummaryCurrently the primary method for confirming acute SARS-CoV-2 infection is through the use of molecular assays that target highly conserved regions within the viral genome. Many, if not most of the diagnostic targets currently in use were produced early in the pandemic, using genomes sequenced and shared in early 2020. As viral diversity increases, mutations may arise in diagnostic target sites that have an impact on the performance of diagnostic tests. Here, we report on a local outbreak of SARS-CoV-2 which had gained an additional mutation at position 28890 of the nucleocapsid protein, on a background of pre-existing mutations at positions 28881, 28882, 28883 in one of the main circulating viral lineages in Wales at that time. The impact of this additional mutation had a statistically significant impact on the Ct value reported for the N gene target designed by the Chinese CDC and used in a number of commercial diagnostic products. Further investigation identified that, in viral genomes sequenced from Wales over the summer of 2020, the N gene had a higher rate of mutations in diagnostic target sites than other targets, with 115 issues identified affecting over 10% of all cases sequenced between February and the end of August 2020. In comparison an issue was identified for ORFab, the next most affected target, in less than 1.4% of cases over the same time period. This work emphasises the potential impact that mutations in diagnostic target sites can have on tracking local outbreaks, as well as demonstrating the value of genomics as a routine tool for identifying and explaining potential diagnostic primer issues as part of a laboratory quality management system. This work also indicates that with increasing genomic sequencing data availability, there is a need to re-evaluate the diagnostic targets that are in use for SARS-CoV-2 testing, to better target regions that are now demonstrated to be of lower variability.
Racial/ethnic disparities in sleep in mothers and infants during the Covid-19 pandemic
Authors: Lucchini Maristella , Kyle Margaret , Pini Nicolò , Sania Ayesha , Babineau Vanessa , Firestein Morgan R. , Fernández Cristina R. , Shuffrey Lauren C. , Barbosa Jennifer R , Rodriguez Cynthia , Fifer William P. , Alcántara Carmela , Monk Catherine , Dumitriu Dani 
Published: March 2021

ABSTRACTStudy ObjectivesTo quantify the association between race/ethnicity and maternal and infant self-reported sleep health at 4 months, exploring the role of maternal depression, stress and symptoms of trauma related to the COVID-19 pandemic as potential mediators.MethodsParticipants were recruited as part of the COVID-19 Mother Baby Outcomes (COMBO) cohort at Columbia University (N=71 non-Hispanic White, N=14 African American (AA), N=113 Hispanic, N=40 other/declined). Data on infant sleep were collected at 4 months postpartum. A subset of 149 women also completed questionnaires assessing maternal mental health and sleep. Multivariable regressions were used to separately estimate associations of race/ethnicity and mental health with multiple sleep domains for infants and mothers adjusting for individual-level covariates.ResultsCompared to non-Hispanic White, Hispanic infants slept less at night (β=- 101.7±17.6, p<0.0001) and AA and Hispanic infants went to bed later (respectively β =1.9±0.6, p<0.0001, β=1.7±0.3, p<0.0001). Hispanic mothers were less likely to perceive infant sleep as a problem (β=1.0±0.3, p=0.006). Compared to non-Hispanic White mothers, Hispanic mothers reported worse maternal sleep latency (β=1.2±0.4, p=0.002), and efficiency (β=0.8±0.4, p=0.03), but better subjective sleep quality (β=-0.7±0.4, p=0.05), and less daytime dysfunction (β=-0.8±0.4, p=0.04). Maternal mental health scores were statistically significant predictors of multiple domains of maternal sleep but did not mediate the association between race/ethnicity and sleep.ConclusionsRacial/ethnic disparities in maternal and infant sleep are observable at 4 months post-partum. Maternal stress, depression and symptoms of trauma related to the COVID-19 pandemic did not mediate these associations.
Differential effect of corticosteroid treatment on Influenza, SARS, MERS, and SARS-CoV-2 patients: A meta-analysis and systematic review
Authors: Ali Sobur , Uddin Salman Zahir , Dewan Md. Nayem , Moniruzzaman M , Kabir Mir Himayet , Islam Mohammad Rafiqul , Monir Hossain , Hossan Shanewaz , Nafiz Tanvir Noor , Rashid Rumana , Imran Khan Mohammad 
Published: March 2021

ABSTRACTBackgroundCorticosteroid has been used to manage inflammation caused by many diseases including respiratory viral infections. Many articles are available to support the good and bad side of this steroid use but remain inconclusive. To find some evidence about the safety of the drug, we investigated the effect of corticosteroids on the mortality of patients with respiratory viral infections including SARS-CoV-2, SARS, MERS, and Influenza.MethodWe searched articles in PubMed, Scopus, Cochrane, Medline, Google Scholar, and Web of Science records using keywords “corticosteroid” or “viral infection” or “patients” or “control study”. Mortality was the primary outcome.ResultOur selected 24 studies involving 16633 patients were pooled in our meta-analysis. Corticosteroid use and overall mortality were not significantly associated (P=0.176), but in subgroup analysis, corticosteroid use was significantly associated with lower mortality in the case of SARS (P=0.003) but was not significantly associated with mortality for Influenza (H1N1) (P=0.260) and SARS-CoV-2 (P=0.554). Further analysis using study types of SARS-CoV-2, we found that corticosteroid use was not significantly associated with mortality in the case of retrospective cohort studies (P=0.256) but was significantly associated with lower mortality in the case of randomized control trials (P=0.005). Our findings uncover how the outcome of particular drug treatment for different diseases with comparable pathogenesis may not be similar and, RCTs are sometimes required for robust outcome data.ConclusionAt the beginning of the COVID-19 pandemic, data of corticosteroid use from other viral infections along with COVID-19 observational and retrospective cohort studies created confusion of its effect, but randomized control trials showed that corticosteroid can be used to treat COVID-19 patients.
Identification of Genetically Related HCV Infections Among Self-Described Injecting Partnerships
Authors: Tully Damien C. , Hahn Judith A. , Bean David J. , Evans Jennifer L. , Morris Meghan D. , Page Kimberly , Allen Todd M. 
Published: March 2021

ABSTRACTBackgroundThe current opioid epidemic across the United States has fueled a surge in the rate of new HCV infections among young persons who inject drugs (PWIDs). Paramount to interrupting transmission is targeting these high-risk populations and understanding the underlying network structures facilitating transmission within these communities.MethodsDeep sequencing data were obtained for 52 participants from 32 injecting partnerships enrolled in the UFO Partner Study which is a prospective study of self-described injecting dyad partnerships from a large community-based study of HCV infection in young adult PWIDs from San Francisco. Phylogenetically linked transmission events were identified using traditional genetic-distance measures and viral deep sequence phylogenies reconstructed to determine the statistical support of inferences and the direction of transmission within partnerships.ResultsUsing deep sequencing data, we found that 12 of 32 partnerships were genetically similar and clustered. Three additional phylogenetic clusters were found describing novel putative transmission links outside of the injecting relationship. Transmission direction was inferred correctly for five partnerships with the incorrect transmission direction inferred in more than 50% of cases. Notably, we observed that phylogenetic linkage was most often associated with a lower number of network partners and involvement in a sexual relationship.ConclusionsDeep sequencing of HCV among self-described injecting partnerships demonstrates that the majority of transmission events originate from outside of the injecting partnership. Furthermore, these findings caution that phylogenetic methods may be unable to routinely infer the direction of transmission among PWIDs especially when transmission events occur in rapid succession within high-risk networks.SummaryDeep sequencing of HCV from 32 self-described injecting partnerships revealed that only 37% were genetically similar and inferring the direction of transmission using phylogenetic tools is challenging as HCV transmission is complex and multifaceted.
Continuity of routine immunization programs in Canada during the COVID-19 pandemic
Authors: Sell Hannah , Assi Ali , Driedger S. Michelle , Dubé Eve , Gagneur Arnaud , Meyer Samantha B. , Robinson Joan , Sadarangani Manish , Tunis Matthew , MacDonald Shannon E. 
Published: March 2021

AbstractIntroductionIn Canada, the COVID-19 pandemic has interrupted many routine health services, placed additional strain on the health care system, and resulted in many Canadians being either unable or unwilling to attend routine immunization appointments. We sought to capture and synthesize information about changes to routine immunization programs in response to the pandemic and plans to catch-up any missed immunizations.MethodsProvincial/territorial (P/T) public health leaders were interviewed via teleconference between August-October 2020 to collect information on the following topics: how routine immunization delivery was affected during and after initial lockdown periods, plans to catch-up missed doses, and major challenges and achievements in continuing routine immunization programs. Data were coded and categorized according to common responses and descriptive analysis was performed.ResultsInterviews occurred with participants from 11 of 13 P/Ts. School immunization programs were reported to be most negatively affected by the pandemic (n=9). In the early pandemic period, infant, preschool, and maternal/prenatal programs were prioritized, with most P/Ts continuing these services with adaptations for COVID-19. After the initial lockdown period, all routine programs were continuing with adaptations in most P/Ts. Infant, preschool, and school programs were most often targeted for catch-up through measures such as appointment rebooking and making additional clinics and/or providers available. Major challenges included resource limitations (e.g., staff shortages, PPE shortages, limited infrastructure) (n=11), public health restrictions (n=8), and public hesitancy to attend appointments (n=5).ConclusionsCanadian routine immunization programs faced some disruptions due to the COVID-19 pandemic, particularly the school, adult, and older adult programs. Further research is needed to determine the measurable impact of the pandemic on routine vaccine coverage levels.
Testing and Vaccination to Reduce the Impact of COVID-19 in Nursing Homes: An Agent-Based Approach
Authors: Gómez-Vázquez Jose Pablo , García Yury , Schmidt Alec J. , Martínez-López Beatriz , Nuño Miriam 
Published: March 2021

AbstractBackgroundEfforts to protect residents in nursing homes involve non-pharmaceutical interventions, testing, and vaccine. We sought to quantify the effect of testing and vaccine strategies on the attack rate, length of the epidemic, and hospitalization.MethodsWe developed an agent-based model to simulate the dynamics of SARS-CoV-2 transmission in a nursing home with resident and staff agents. Interactions between 172 residents and 170 staff were assumed based on data from a nursing home in Los Angeles, CA. We simulated scenarios assuming different levels of non-pharmaceutical interventions, testing frequencies, and vaccine efficacy to block transmission.ResultsUnder the hypothetical scenario of widespread SARS-CoV-2 in the community, 3-day testing frequency minimized the attack rate and the time to eradicate an outbreak. Prioritization of vaccine among staff or staff and residents minimized the cumulative number of infections and hospitalization, particularly in the scenario of high probability of an introduction. Reducing the probability of a virus introduction reduced the demand on testing and vaccine to reduce infections and hospitalizations.ConclusionsImproving frequency of testing from 7-days to 3-days minimized the number of infections and hospitalizations, despite widespread community transmission. Vaccine prioritization of staff provides the best protection strategy, despite high risk of a virus introduction.
Characterizing the disproportionate burden of SARS-CoV-2 variants of concern among essential workers in the Greater Toronto Area, Canada
Authors: Chagla Zain , Ma Huiting , Sander Beate , Baral Stefan D. , Mishra Sharmistha 
Published: March 2021

ABSTRACTImportanceThe emergence of SARS-CoV-2 Variants of Concern (VOC) across North America has been associated with concerns of increased COVID-19 transmission. Characterizing the distribution of VOCs can inform development of policies and programs to address the prevention needs of disproportionately affected communities.ObjectiveWe compared per-capita rates of COVID-19 cases (overall and VOC) from February 3, 2021 to March 10, 2021, across neighborhoods in the health regions of Toronto and Peel, Ontario, by proportion of the population working in essential services and income.DesignDescriptive epidemiological analysis, integrating COVID-19 surveillance and census data. Per-capita daily epidemic curves were generated using 7-days rolling averages for cases and deaths. Cumulative per-capita rates were determined using census-reported population of each neighbourhood.SettingThe study setting was the city of Toronto and the region of Peel (the City of Brampton, Mississauga, and Caledon), Canada’s largest cities with a combined population of 4.3 million. This area of Canada has had one of the highest incident rates of COVID-19 throughout the pandemic.ParticipantsWe used person-level data on laboratory-confirmed COVID-19 community cases (N=22,478) and census data for neighborhood-level attributes.ExposuresWe stratified neighbourhoods, i.e., dissemination areas which represent geographic areas of approximately 400-700 individuals, into tertiles by ranking the proportion of population in each neighbourhood working in essential services (health, trades, transport, equipment, manufacturing, utilities, sales, services, agriculture); and the per-person equivalent household income.Main Outcome(s) and Measure(s)The primary outcomes were laboratory-confirmed COVID-19 cases overall and VOC positives by neighbourhood.ResultsDuring the study period, VOC cases emerged faster in groups with lowest income (growth rate 43.8%, 34.6% and 21.6% by income tertile from lowest to highest), and most essential work (growth rate 18.4%, 30.8% and 50.8% by tertile from lowest tertile of essential workers to highest tertile of essential workers).Conclusions and RelevanceThe recent introduction of VOC in a large urban area has disproportionately affected neighbourhoods with the most essential workers and lowest income levels. Notably, this is consistent with the increased burden of non-VOC COVID-19 cases suggesting shared risk factors. To date, restrictive public health strategies have been of limited impact in these communities suggesting the need for complementary and well-specified supportive strategies to address disparities and overall incidence of both VOC and non-VOC COVID-19.
Feasibility and effectiveness of daily temperature screening to detect COVID-19 in a large public university setting
Authors: Facente Shelley N. , Hunter Lauren A. , Packel Laura J. , Li Yi , Harte Anna , Nicolette Guy , McDevitt Shana , Petersen Maya , Reingold Arthur L. 
Published: March 2021

ABSTRACTBackgroundMany persons with active SARS-CoV-2 infection experience mild or no symptoms, presenting barriers to COVID-19 prevention. Regular temperature screening is nonetheless used in some settings, including University campuses, to reduce transmission potential. We evaluated the potential impact of this strategy using a prospective University-affiliated cohort.MethodsBetween June and August 2020, 2,912 participants were enrolled and tested for SARS-CoV-2 by PCR at least once (median: 3, range: 1-9). Participants reported temperature and symptoms daily via electronic survey using a previously owned or study-provided thermometer. We assessed feasibility and acceptability of daily temperature monitoring, calculated sensitivity and specificity of various fever-based strategies for restricting campus access to reduce transmission, and estimated the association between measured temperature and SARS-CoV-2 test positivity using a longitudinal binomial mixed model.ResultsMost participants (70.2%) did not initially have a thermometer for taking their temperature daily. Across 5481 total person months, the average daily completion rate of temperature values was 61.6% (IQR: 41.8%–86.2%). Sensitivity for SARS-CoV-2 ranged from 0% (95%CI 0–9.7%) to 40.5% (95%CI 25.6–56.7%) across all strategies for self-report of possible COVID-19 symptoms on day of specimen collection, with corresponding specificity of 99.9% (95%CI 99.8–100%) to 95.3% (95%CI 94.7–95.9%). An increase of 0.1°F in individual mean body temperature on the same day as specimen collection was associated with 1.11 increased odds of SARS-CoV-2 positivity (95%CI 1.06–1.17).ConclusionsDaily temperature monitoring was feasible and acceptable; however, the majority of potentially infectious individuals were not detected by temperature monitoring, suggesting that temperature screening is insufficient as a primary means of detection to reduce transmission of SARS-CoV-2.
Saliva testing as a means to monitor therapeutic lithium levels in patients
with psychiatric disorders: identification of clinical and environmental
covariates, and their incorporation into a prediction model
Authors: Parkin Georgia M. , McCarthy Michael J. , Thein Soe H. , Piccerillo Hillary L. , Warikoo Nisha , Granger Douglas A. , Thomas Elizabeth A. 
Published: March 2021

Abstract
The narrow therapeutic window of lithium medications necessitates frequent
serum monitoring, which can be expensive and inconvenient for the patient. The
use of saliva as a biofluid may have advantages over blood, as it is
non-invasive, easier to collect, requires less processing, and can be collected
without the need for trained personnel. This study investigated the utility of
saliva as a longitudinal means of monitoring lithium levels. We measured lithium
levels using Inductively-Coupled Plasma Optical Emission Spectrometry (ICP-OES)
in n=171 saliva samples collected via the passive drool method, from a
multi-center cohort consisting of n=75 patients with bipolar disorder or other
psychiatric conditions. We found that saliva and serum levels of lithium were
highly correlated (unadjusted Spearman r=0.74,
p<0.0001) and that consideration of daily lithium
dose, dosing schedule, cotinine-confirmed smoking status and diabetes status
could improve this relationship (adjusted Spearman r=0.77,
p<0.0001). Using this adjusted intersubject
equation to predict an individual’s serum lithium levels from their salivary
lithium value, we observed a strong linear correlation between the predicted vs.
actual serum lithium levels r=0.70; P<0.0001). Longitudinal samples were
collected from patients for up to 18 months from the initial assessment. The
saliva/serum ratios across these multiple visits were highly stable for most
patients. Variability in the saliva/serum ratios across observations was found
to be significantly associated with age. Using the intrasubject saliva/serum
ratio from a single prior observation was not better than using the interpatient
linear regression equation at predicting the serum lithium levels. However, the
using the mean intrasubject ratio calculated from three prior observations could
robustly predict serum levels with a predicted vs. actual serum correlation of
r=0.90 (p<0.0001). These findings strongly suggest
that saliva could be used for lithium monitoring and open the door for the
development and implementation of a point-of-care salivary lithium device that
could be used at home or in the clinic. We propose that the use of saliva will
dramatically improve treatment opportunities for patients with mood
disorders.

Data availability statement
Anonymized summary data will be shared by reasonable formal request from
qualified researchers, subject to a data sharing agreement and in compliance
with the requirements of the funding bodies and institutions.