bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of Individualised Polygenic Risk Score Analysis: A Test Case of a Family of Four
Authors: Corpas Manuel , Megy Karyn , Metastasio Antonio , Lehmann Edmund 
Published: July 2021

AbstractPolygenic risk scores (PRS) have been widely applied in research studies, showing how population groups can be stratified into risk categories for many common conditions. As healthcare systems consider applying PRS to keep their populations healthy, little work has been carried out demonstrating their implementation at an individual level. We performed a systematic curation of PRS sources from established data repositories, selecting 27 phenotypes, comprising almost 40 million SNPs related to cancer, cardiovascular, metabolic and autoimmune diseases. We tested selected phenotypes using whole genome sequencing data for a family of four family related individuals, with the 1000 Genomes Project (1000G) Phase III participants as background populations. Over 98 billion allele effects were calculated in order to obtain the PRS for each of the individuals analysed here. PRS calculation for the 1000G cohort of 2,504 participants allows us to develop a methodology for risk inference and general PRS deployment. Our approach for PRS implementation advances the discussion on the adoption of PRS in a preventative healthcare setting.
Longitudinal Risk Factors For Developing Depression in Parkinson’s Disease
Authors: Antar Tarek , Morris Huw R , Faghri Faraz , Leonard Hampton , Nalls Mike , Singleton Andrew , Iwaki Hirotaka 
Published: July 2021

AbstractBackgroundDespite the established importance of identifying depression in Parkinson’s disease, our understanding of the factors which place the Parkinson’s disease patient at future risk of depression is limited.MethodsOur sample consisted of 874 patients from two longitudinal cohorts, PPMI and PDBP, with median follow-up durations of 7 and 3 years respectively. Risk factors for depression at baseline were determined using logistic regression. A Cox regression model was then used to identify baseline factors that predisposed the non-depressed patient to develop depressive symptoms that were sustained for at least one year, while adjusting for antidepressant use and cognitive impairment. Common predictors between the two cohorts were identified with a random-effects meta-analysis.ResultsWe found in our analyses that the majority of baseline non-depressed patients would develop sustained depressive symptoms at least once during the course of the study. Probable REM sleep disorder (pRBD), age, duration of diagnosis, impairment in daily activities, mild constipation, and antidepressant use were among the baseline risk factors for depression in either cohort. Our Cox regression model indicated that pRBD, impairment in daily activities, hyposmia, and mild constipation could serve as longitudinal predictors of sustained depressive symptoms.ConclusionsWe identified several potential risk factors to aid physicians in the early detection of depression in Parkinson’s disease patients. Our findings also underline the importance of adjusting for multiple covariates when analyzing risk factors for depression.
Characterization and Mitigation of Model Bias in Parametric Mapping of Dopamine Response to Behavioral Challenge
Authors: Levine Michael A. , Mandeville Joseph B. , Calabro Finnegan , Izquierdo-Garcia David , Price Julie C. , Luna Beatriz , Catana Ciprian 
Published: July 2021

AbstractCompartmental modeling of 11C-raclopride (RAC) is commonly used to measure dopamine response to intra-scan behavioral tasks. Bias in estimates of binding potential (BPND) and its dynamic changes (ΔBPND) can arise when the selected compartmental model deviates from the underlying biology. In this work, we characterize the bias associated with assuming a single target compartment and propose a model for reducing this bias by selectively discounting the contribution of the initial uptake period.Methods69 healthy young adult participants were scanned using RAC PET/MR while simultaneously performing a rewarded behavioral task. BPND and ΔBPND were estimated using an extension of the Multilinear Reference Tissue Model (MRTM2) with the task challenge encoded as a Heaviside step function. Bias was estimated using simulations designed to match the acquired data and was reduced by introducing a new model (DE-MRTM2) that reduces the biasing influence of the initial uptake period in the modeled estimation of BPND for both simulations and participant data.ResultsBias in ΔBPND was observed to vary both spatially with BPND and with the assumed value of k4. At the most likely value of k4 (0.13 min-1), the average bias and the maximum voxel bias magnitude in the nucleus accumbens were estimated to be 1.2% and 3.9% respectively. Simulations estimated that debiasing the contribution of the first 27 minutes of acquired data reduced average bias and maximum voxel bias in the nucleus accumbens ΔBPND to -0.3% and 2.4% respectively. In the acquired participant data, DE-MRTM2 produced modest changes in the experimental estimates of striatal ΔBPND, while extrastriatal bias patterns were greatly reduced. DE-MRTM2 also considerably reduced the dependence of ΔBPND upon the first-pass selection of k2’.ConclusionSelectively discounting the contribution of the initial uptake period can help mitigate BPND- and k4-dependent bias in single compartment models of ΔBPND, while also reducing the dependence of ΔBPND on the first-pass estimation of k2’.
A national survey of attitudes towards and intentions to vaccinate against COVID-19: implications for communications
Authors: Stead Martine , Jessop Curtis , Angus Kathryn , Bedford Helen , Ussher Michael , Ford Allison , Eadie Douglas , MacGregor Andy , Hunt Kate , MacKintosh Anne Marie 
Published: July 2021

AbstractBackgroundHesitancy about COVID-19 vaccination threatens comprehensive vaccination. It is important to examine vaccination acceptance when people are making real rather than hypothetical decisions, to identify whether targeted support is needed, and to identify implications for communications.MethodsCross-sectional online and telephone survey with probability-based sample (n=4,978) of British adults, conducted January-February 2021. Measures: socio-demographic characteristics (age, gender, ethnicity, education, financial status), COVID-19 status, vaccine acceptance, trust in COVID-19 vaccination information sources, perceptions of vaccination priority groups, and perceptions of importance of second dose.FindingsAmong 5,931 individuals invited, survey response rate was 84%. COVID-19 vaccine acceptance (83%) was associated with increasing age, higher level of education and having been invited for vaccination. Acceptance decreased with unconfirmed past COVID-19, greater financial hardship, and non-White British ethnicity; Black/Black British participants had lowest acceptance. Overall, healthcare and scientific sources of information were most trusted. Compared with White British participants, other ethnicities had lower trust in healthcare and scientific sources. Those with lower educational attainment or financial hardship had lower trust in healthcare and scientific sources. Those with no qualifications had higher trust in media and family/friends. While trust was low overall in community or faith leaders it was higher among those with Asian/Asian British and Black/Black British ethnicity compared with White British participants. Views of vaccine prioritisation were mostly consistent with UK official policy but there was support for prioritising additional groups. There was high support for having the second vaccine dose.ConclusionsTargeted engagement is needed to address COVID-19 vaccine hesitancy in non-White British ethnic groups, in younger adults, and among those with lower education, greater financial hardship and unconfirmed past infection. Healthcare professionals and scientific advisors should play a central role in communications and tailored messaging is needed for hesitant groups. Careful communication around vaccination prioritisation continues to be required.
Tracing and testing multiple generations of contacts to COVID-19 cases: cost-benefit tradeoffs
Authors: Kim Jungyeol , Chen Xingran , Nikpey Hesam , Rubin Harvey , Bidokhti Shirin Saeedi , Sarkar Saswati 
Published: July 2021

AbstractTraditional contact tracing for COVID-19 tests the direct contacts of those who test positive even if the contacts do not show any symptom. But, by the time an infected individual is tested, the infection starting from the person may have infected a chain of individuals. Hence, why should the testing stop at direct contacts, and not test secondary, tertiary contacts or even contacts further down? One deterrent in testing long chains of individuals right away may be that it substantially increases the testing load, or does it? We investigate the costs and benefits of such multi-hop contact tracing for different number of hops. Considering a large number of contact topologies, spanning synthetic networks of divergent characteristics and those constructed from recorded interactions, we show that the cost-benefit tradeoff can be characterized in terms of a single measurable attribute, the initial epidemic growth rate. Once this growth rate crosses a threshold, multi-hop contact tracing substantially reduces the outbreak size compared to traditional contact tracing. Multi-hop even incurs a lower cost compared to the traditional contact tracing for a large range of values of the growth rate. The cost-benefit tradeoffs and the choice of the number of hops can be classified into three phases, with sharp transitions between them, depending on the value of the growth rate. The need for choosing a larger number of hops becomes greater as the growth rate increases or the environment becomes less conducive toward containing the disease.Author summaryThe COVID-19 pandemic has wrecked havoc on lives and livelihoods worldwide. Other epidemics may well emerge in future and one needs a preparedness to prevent their growth into another pandemic. During the early stages of a new epidemic, or even a mutated version of an earlier epidemic, pharmaceutical interventions may not be available but contact tracing and timely quarantine are among the few available control measures. We show that 1) traditional contact tracing may not successfully contain the outbreak depending on the rate of growth of the epidemic, but 2) the cost-benefit tradeoffs may be substantially enhanced through the deployment of a natural multi-hop generalization which tests contact chains starting from those who test positive.
Prominent Spatiotemporal Waves of COVID-19 Incidence in the United States: Implications for Causality, Forecasting, and Control
Authors: Jalal Hawre , Lee Kyueun , Burke Donald S. 
Published: July 2021

AbstractBetter understanding of the spatiotemporal structure of the COVID-19 epidemic in the USA may help inform more effective prevention and control strategies. By analyzing daily COVID-19 case data in the United States, Mexico and Canada, we found four continental-scale epidemic wave patterns, including travelling waves, that spanned multiple state and even international boundaries. These major epidemic patterns co-varied strongly with continental-scale seasonal temperature change patterns. Geo-contiguous states shared similar timing and amplitude of epidemic wave patterns irrespective of similarities or differences in state government political party affiliations. These analyses provide evidence that seasonal factors, probably weather changes, have exerted major effects on local COVID-19 incidence rates. Seasonal wave patterns observed during the first year of the epidemic may become repeated in the subsequent years.One Sentence SummaryThe COVID-19 epidemic in the United States has consisted of four continental-scale spatiotemporal waves of case incidence that have spanned multiple states and even international boundaries.
Uptake of SARS-CoV-2 workplace testing programs, March 2020 to March 2021
Authors: Duarte Nathan , D’Mello Sean , Duarte Natalie A , Rocco Simona , Van Wyk Jordan , Pillai Abhinav Arun , Liu Michael , Williamson Tyler , Arora Rahul K 
Published: July 2021

Structured AbstractObjectiveTo track uptake of workplace SARS-CoV-2 testing programs using publicly-available data (e.g., press releases), supplementing findings from employer surveys.MethodsWe tracked testing programs reported by 1,159 Canadian and 1,081 international employers across sectors from March 1, 2020 to March 31, 2021. We analyzed trends in uptake of testing programs, including over time and by workplace setting.Results9.5% (n=110) of Canadian employers and 24.6% (n=266) of international employers tracked reported testing. The prevalence of reported testing programs was less than 20% in some settings associated with high risk of transmission including retail and customer-facing environments, and indoor and mixed blue collar workplaces.ConclusionsPublicly-available data suggest that fewer employers are testing than indicated by surveys. Workplace safety in high-risk workplaces could be further improved by implementing testing strategies that deploy both screening and diagnostic tests.
Temozolomide sensitivity of malignant glioma cell lines – a systematic review assessing consistencies between in vitro studies
Authors: Poon Michael TC , Bruce Morgan , Simpson Joanne E , Hannan Cathal J , Brennan Paul M 
Published: July 2021

AbstractMalignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that these models are reliable and consistent. We assessed this by examining the reporting of experimental conditions and sensitivity to temozolomide in glioma cells lines.We searched Medline and Embase (Jan 1994-Jan 2021) for studies that evaluated the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Studies using a drug-resistant cell line or a modified preparation of temozolomide were excluded. Key data items included type of cell lines, temozolomide exposure duration, and cell viability measure (IC50).We included 212 eligible studies from 2,789 non-duplicate records that reported 248 distinct cell lines. The commonest cell line was U87 (60.4%). Only 10.4% studies used a patient-derived cell line. The proportion of studies not reporting each experimental condition ranged from 8.0-27.4%, including base medium (8.0%), serum supplementation (9.9%) and number of replicates (27.4%). In studies reporting IC50 the median value for U87 cell line at 24 hours, 48 hours and 72 hours was 123.9μM (IQR 75.3-277.7μM), 223.1μM (IQR 92.0-590.1μM) and 230.0μM (IQR 34.1-650.0μM), respectively (Figure 2A). The median IC50 at 72 hours for patient-derived cell lines was 220μM (IQR 81.1-800.0μM).Temozolomide sensitivity reported in comparable studies was not consistent between and within individual malignant glioma cell lines. Drug discovery science performed on these models cannot reliably inform clinical translation. A consensus model of reporting can maximise reproducibility and consistency among in vitro studies.Key pointsThere is a wide variety of study designs for malignant glioma cell line studies.Reporting of experimental designs of cell line studies was suboptimal.Temozolomide sensitivity was inconsistent between and within individual cell lines.Importance of the studyThere is a wide variety of experimental designs for malignant glioma cell line studies but the reporting of these is suboptimal.Temozolomide sensitivity reported in comparable studies was not consistent between and within individual malignant glioma cell lines.While there will be variations of opinion on what the optimal design is, a consensus model of a reporting structure is the only rational way to maximise the yield from in vitro studies to find novel therapies for our patients.
Machine learning identifies six genetic variants and alterations in the Heart Atrial Appendage as key contributors to PD risk predictivity
Authors: Ho Daniel , Schierding William , Farrow Sophie , Cooper Antony A. , Kempa-Liehr Andreas W. , O’Sullivan Justin M. 
Published: July 2021

AbstractParkinson’s disease (PD) is a complex neurodegenerative disease with a range of causes and clinical presentations. Over 76 genetic loci (comprising 90 SNPs) have been associated with PD by the most recent GWAS meta-analysis. Most of these PD-associated variants are located in non-coding regions of the genome and it is difficult to understand what they are doing and how they contribute to the aetiology of PD. We hypothesised that PD-associated genetic variants modulate disease risk through tissue-specific expression quantitative trait loci (eQTL) effects. We developed and validated a machine learning approach that integrated tissue-specific eQTL data on known PD-associated genetic variants with PD case and control genotypes from the Wellcome Trust Case Control Consortium, the UK Biobank, and NeuroX. In so doing, our analysis ranked the tissue-specific transcription effects for PD-associated genetic variants and estimated their relative contributions to PD risk. We identified roles for SNPs that are connected with INPP5P, CNTN1, GBA and SNCA in PD. Ranking the variants and tissue-specific eQTL effects contributing most to the machine learning model suggested a key role in the risk of developing PD for two variants (rs7617877 and rs6808178) and eQTL associated transcriptional changes of EAF1-AS1 within the heart atrial appendage. Similarly, effects associated with eQTLs located within the brain cerebellum were also recognized to confer major PD risk. These findings warrant further mechanistic investigations to determine if these transcriptional changes could act as early contributors to PD risk and disease development.
Feeding Activated Bifidobacterium infantis EVC001 to Very Low Birth Weight Infants is Associated with Significant Reduction in Rates of Necrotizing Enterocolitis
Authors: Tobias Joseph , Olyaei Amy , Laraway Bryan , Jordan Brian K. , Dickinson Stephanie , Arroyo Lilian G. , Fialkowski Elizabeth , Owora Arthur , Scottoline Brian 
Published: July 2021

ABSTRACTObjectivesTo assess the effects of Bifidobacterium infantis EVC001 administration on the rate of necrotizing enterocolitis (NEC) in preterm infants in a single Level IV NICU.Study DesignThis was a retrospective observational analysis of 2 cohorts of VLBW infants (+/-B. infantis EVC001 probiotic) at OHSU from 2014 to 2020. Outcomes included NEC rates and NEC-associated mortality, including subgroup analysis of ELBW infants. Fisher’s exact test and log binomial models were used to determine differences between cohorts and risk reduction of NEC. Adjusted number needed to treat was calculated from the cohort coefficient of the model.ResultsIn this analysis of 483 infants, the difference in rates of NEC between cohorts was statistically significant (11.0% vs. 2.7%, P = 0.0008). The EVC001-fed cohort had a 73% risk reduction of NEC compared to the No EVC001 cohort (adjusted risk ratio 0.270, 95% CI 0.094, 0.614, P = 0.0054) resulting in an adjusted number needed to treat of 12.4 (95% CI 10.0, 23.5) for B. infantis EVC001. There was no NEC-related mortality in the EVC001-fed cohort, yielding statistically significant differences from the No EVC001 cohort overall (0% vs. 2.7%, P = 0.0274) and the ELBW subgroup (0% vs. 5.6%, P = 0.0468).Conclusion(s)B. infantis EVC001 feeding was associated with a significant reduction in the rate of NEC and NEC-related mortality in an observational study of 483 VLBW infants. B. infantis EVC001 supplementation may be considered safe and effective for reducing morbidity and mortality in the NICU.
Perceptions and acceptance of COVID-19 vaccine among pregnant and lactating women in Singapore: A cross-sectional study
Authors: Jayagobi Pooja A , Ong Chengsi , Thai Yeo Kee , Lim Caleb CW , Jiun Seet Meei , Koon Kwek Lee , Wai Ku Chee , Chan Jerry KY , Mathur Manisha , Chien Chua Mei 
Published: July 2021

AbstractIntroductionVaccination is critical in controlling the coronavirus disease 19 (COVID-19) pandemic. However, vaccine perception and acceptance among pregnant and lactating women is unknown in Singapore. We aimed to determine the acceptance of COVID-19 vaccination among these two groups of women in Singapore, and factors associated with vaccine acceptance.MethodsWe conducted an anonymous, online survey on the perception and acceptance of the COVID-19 vaccine in pregnant and lactating women at a tertiary hospital in Singapore from 1st March to 31st May 2021. Information on demographics and knowledge were collected, and these factors were assessed for their relationship with vaccine acceptance.ResultsA total of 201 pregnant and 207 lactating women participated. Vaccine acceptance rates in pregnant and lactating women were 30.3% and 16.9% respectively. Pregnant women who were unsure or unwilling to take the vaccine cited concerns about safety of the vaccine during pregnancy (92.9%), while lactating women were concerned about potential long-term negative effects on the breastfeeding child (75.6%). Other factors significantly associated with vaccine acceptance included a lower monthly household income or education level, appropriate knowledge regarding vaccine mechanism and higher perceived maternal risk of COVID-19. Most pregnant (70.0%) and lactating women (83.7%) were willing to take the vaccine only when more safety data during pregnancy and breastfeeding were available.ConclusionsCOVID-19 vaccine acceptance was low among pregnant and lactating women in Singapore. Addressing safety concerns when more data is available and education on mechanism of vaccine action will likely improve acceptance among these women.