bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-polygenic scores in psychiatry: from disorder-specific to transdiagnostic perspectives
Authors: Shi Yingjie , Sprooten Emma , Mulders Peter , Vrijsen Janna , Bralten Janita , Demontis Ditte , Børglum Anders D. , Walters G. Bragi , Stefansson Kari , van Eijndhoven Philip , Tendolkar Indira , Franke Barbara , Mota Nina Roth 
Published: June 2022

AbstractThe dense co-occurrence of psychiatric disorders questions the categorical classification tradition and motivates efforts to establish dimensional constructs with neurobiological foundations that transcend diagnostic boundaries. In this study, we examined the genetic liability for eight major psychiatric disorder phenotypes under both a disorder-specific and a transdiagnostic framework. In a deeply-phenotyped sample (n=513) consisting of 452 patients from tertiary care with mood disorders, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and/or substance use disorders (SUD) and 61 unaffected comparison individuals, we derived subject-specific multi-base polygenic risk score (PRS) profiles and assessed their associations with psychiatric diagnoses, comorbidity status, as well as cross-disorder behavioral dimensions. High PRS for depression was unselectively associated with the diagnosis of SUD, ADHD, anxiety disorders, mood disorders, and the comorbidities among them. In the dimensional approach, four distinct functional domains were uncovered, namely the negative valence, social, cognitive, and regulatory systems, closely matching the major functional domains proposed by the Research Domain Criteria (RDoC) framework. Critically, the genetic predisposition for depression was selectively reflected in the functional aspect of negative valence systems but not others. This study highlights a misalignment between current psychiatric nosology and the underlying psychiatric genetic etiology, and underscores the effectiveness of the dimensional approach in both the functional characterization of psychiatric patients and the delineation of the genetic liability for psychiatric disorders.
The role of adolescent lifestyle habits in biological aging: A prospective twin study
Authors: Kankaanpää Anna , Tolvanen Asko , Heikkinen Aino , Kaprio Jaakko , Ollikainen Miina , Sillanpää Elina 
Published: June 2022

ABSTRACTAdolescence is a stage of fast growth and development. Exposures during puberty can have long-term effects on health in later life. This study aims to investigate the role of adolescent lifestyle in biological aging. The study participants originated from the longitudinal FinnTwin12 study (n = 5114). Adolescent lifestyle-related factors, including body mass index (BMI), leisure-time physical activity, smoking and alcohol use, were based on self-reports and measured at ages 12, 14 and 17 years. For a subsample, blood-based DNA methylation (DNAm) was used to assess biological aging with six epigenetic aging measures in young adulthood (21–25 years, n = 824). A latent class analysis was conducted to identify patterns of lifestyle behaviors in adolescence, and differences between the subgroups in later biological aging were studied. Genetic and environmental influences on biological aging shared with lifestyle behavior patterns were estimated using quantitative genetic modelling.We identified five subgroups of participants with different adolescent lifestyle behavior patterns. When DNAm GrimAge, DunedinPoAm and DunedinPACE estimators were used, the class with the unhealthiest lifestyle and the class of participants with high BMI were biologically older than the classes with healthier lifestyle habits. The differences in lifestyle-related factors were maintained into young adulthood. Most of the variation in biological aging shared with adolescent lifestyle was explained by common genetic factors. These findings suggest that an unhealthy lifestyle during pubertal years is associated with accelerated biological aging in young adulthood. Genetic pleiotropy can largely explain the observed associations.
Comparative efficacy of different eating patterns in the management of type 2 diabetes and prediabetes: An arm-based Bayesian network meta-analysis
Authors: Zeng Ben-tuo , Pan Hui-qing , Li Feng-dan , Ye Zhen-yu , Liu Yang , Du Ji-wei 
Published: June 2022

AbstractAims/IntroductionDiet therapy is a vital approach to manage type 2 diabetes and prediabetes. However, the comparative efficacy of different eating patterns is not clear enough. We aimed to compare the efficacy of various eating patterns for glycemic control, anthropometrics, and serum lipid profiles in the management of type 2 diabetes and prediabetes.Materials and MethodsWe conducted a network meta-analysis using arm-based Bayesian methods and random effect models, and drew the conclusions using the partially contextualized framework. We searched twelve databases and yielded 9,534 related references, where 107 studies were eligible, comprising 8,909 participants.ResultsEleven diets were evaluated for fourteen outcomes. Caloric restriction was ranked as the best pattern for weight loss (SUCRA 86.8%) and waist circumference (82.2%), low-carbohydrate diets for body mass index (81.6%) and high-density lipoprotein (84.0%), and low-glycemic-index diets for total cholesterol (87.5%) and low-density lipoprotein (86.6%). Other interventions showed some superiorities, but were of imprecision due to insufficient participants and needed further investigation. The attrition rates of interventions were similar. Meta-regression suggested that macronutrients, energy intake, and weight may modify outcomes differently. The evidence was of moderate-to-low quality, and 38.2% of the evidence items met the minimal clinically important differences.ConclusionsThe selection and development of dietary strategies for diabetic/prediabetic patients should depend on their holistic conditions, i.e., serum lipids profiles, glucometabolic patterns, weight and blood pressures. It is recommended to identify the most critical and urgent metabolic indicator to control for one specific patient, and then choose the most appropriate eating pattern accordingly.
Using a design-based research approach to develop a technology-supported physical education course to increase the physical activity levels of university students: Study protocol paper
Authors: Sultoni Kuston , Peralta Louisa , Cotton Wayne 
Published: June 2022

AbstractBackgroundPromoting physical activity (PA) for university students is essential as PA levels decrease during the transition from secondary to higher education. Providing technology-supported university courses targeting students’ PA levels may be a viable option to combat the problem. However, it is still unclear how and what technologies should be implemented in university courses to promote PA. This study aims to create a series of design principles for technology-supported physical education courses that aim to increase university students’ PA knowledge, motivation and levels.MethodThe proposed methodology underpinning the research program is a seven-phase design-based research (DBR) approach, with the seven phases encompassed in four sequential studies. These four studies are a systematic review, a qualitative focus group study, a pilot study, and a randomised controlled trial (RCT) study. The protocol paper aims to detail the plan for conducting the four studies in a comprehensive and transparent manner, thus contributing to the methodological evidence base in this field.DiscussionDesign principles generated from this project will contribute to the growing evidence focusing on effective design and implementation features. Future practitioners can also use these to develop physical education courses that aim to promote university students’ physical activity levels, knowledge, and motivation.Ethical considerationThis project has obtained ethical approval from the University of Sydney Human Research Ethics Committee (Project No. 2021/071; Project No. 2021/935). The randomised controlled trial protocol is registered at the Australian New Zealand Clinical Trials Registry (ANZCTR).Trial registrationthe RCT registry number: ACTRN12622000712707, 18/05/2022
Diagnostic delay of sarcoidosis: protocol for an integrated systematic review
Authors: Namsrai Tergel , Desborough Jane , Gregory Dianne , Kelly Elaine , Cook Matthew , Phillips Christine , Parkinson Anne 
Published: June 2022

AbstractSarcoidosis is a rare systemic inflammatory granulomatous disease with broad manifestation ranging from acute epileptic seizures to fatigue and pain syndromes that are subject to the organ involved. Delays in the diagnosis of sarcoidosis are attributed to the lack of a single diagnostic test or unified commonly used diagnostic criteria, and diagnosis based on exclusion of possible alternative diagnoses. We aim to systematically review the evidence about diagnostic delay in sarcoidosis to elucidate the causes and consequences of diagnostic delay, including people with sarcoidosis’ experiences. This will inform the development of interventions, tools, and health policies aiming to improve diagnostic efficiency and patients’ experiences of sarcoidosis.Methods and analysisA systematic search of the literature will be conducted using PubMed/Medline, Scopus, and ProQuest databases, and sources of grey literature, up to 25th of May 2022, with no limitations on publication date. We will include all study types (qualitative, quantitative, and mixed methods) except review articles, examining diagnostic delay, incorrect diagnosis, missed diagnosis or slow diagnosis of all types of sarcoidosis across all age groups. We will also examine evidence of patients’ experiences associated with diagnostic delay. Only studies in English, German and Indonesian will be included. The outcomes we examine will be diagnostic delay time, patients’ experiences, and causes and consequences associated with diagnostic delay in sarcoidosis. Two people will independently screen the titles and abstracts of search results, and then the remaining full-text documents against the inclusion criteria. Disagreements will be resolved with a third reviewer until consensus is reached. Selected studies will be appraised using the Mixed Methods Appraisal Tool (MMAT). A meta-analysis and subgroup analysis of quantitative data will be conducted. Meta-aggregation methods will be used to analyse qualitative data. If there is insufficient data for these analyses, a narrative synthesis will be conducted.Ethics and disseminationEthical approval will not be required as no human recruitment or participation will be involved. Findings of the study will be disseminated through publications in peer-reviewed journals, conferences, and symposia.Trial registrationPROSPERO Registration number: CRD42022307236 URL of the PROSPERO registration: https://www.crd.york.ac.uk/PROSPEROFILES/307236_PROTOCOL_20220127.pdf
Local genetic correlations exist among neurodegenerative and neuropsychiatric diseases
Authors: Reynolds Regina H. , Wagen Aaron Z. , Lona-Durazo Frida , Scholz Sonja W. , Shoai Maryam , Hardy John , Taliun Sarah A. Gagliano , Ryten Mina 
Published: June 2022

AbstractGenetic correlation (rg) between traits can offer valuable insight into underlying shared biological mechanisms. Neurodegenerative diseases overlap neuropathologically and often manifest comorbid neuropsychiatric symptoms. However, globalrganalyses show minimalrgamong neurodegenerative and neuropsychiatric diseases. Importantly, localrgs can exist in the absence of global relationships. To investigate this possibility, we applied LAVA, a tool for localrganalysis, to genome-wide association studies of 3 neurodegenerative diseases (Alzheimer’s disease, Lewy body dementia and Parkinson’s disease) and 3 neuropsychiatric disorders (bipolar disorder, major depressive disorder and schizophrenia). We identified several localrgs missed in global analyses, including between (i) all 3 neurodegenerative diseases and schizophrenia and (ii) Alzheimer’s and Parkinson’s disease. For those localrgs identified in genomic regions containing disease-implicated genes, such asSNCA, CLUandAPOE, incorporation of expression quantitative trait loci identified genes that may drive genetic overlaps between diseases. Collectively, we demonstrate that complex genetic relationships exist among neurodegenerative and neuropsychiatric diseases, highlighting putative pleiotropic genomic regions and genes. These findings imply sharing of pathogenic processes and the potential existence of common therapeutic targets.
A series of pulses vaccination in SIR model – Understanding periodic orbits and irregular trajectories
Authors: Yang Hyun Mo 
Published: June 2022

AbstractWhen a Susceptible-Infective-Recovered (SIR) model with a constant contact rate is used to describe the dynamics of directly transmitted infections, oscillations, which decay exponentially with time, are obtained. Due to damped oscillations, intermittent vaccination schemes can be designed in order to reduce or even eliminate the infection. A simple intermittent vaccination can be described by a series of pulses, i.e., a proportion of susceptible individuals is vaccinated intermittently at every fixed period of time. Analysis of the model is done by numerical simulations in order to determine the trajectories in the phase space. It is observed that as the proportion of vaccinated individuals increases, closed orbits with multiple cycles appear, even irregular trajectories arise occasionally. These results can be understood by comparing with bifurcations occurring in a discrete logistic model describing a single population. Further, bifurcations occurring in epidemiological models that use periodic functions to mimic seasonal variations in the disease transmission are discussed.
Preserved cognition in elderly with intact rhinal cortex
Authors: Sepehrband Farshid , Lynch Kirsten M. , Gasperi Andrea Sotelo , Bienkowski Michael S. , Wang Xinhui , Chui Helena C. , Toga Arthur W ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2022

AbstractAlzheimer’s disease pathology leads to neurodegeneration within the memory-related structures of the medial temporal cortex and hippocampus. Neurodegeneration also occurs as a part of normative aging and it is unclear whether medial temporal lobe subregions are selectively intact in older adults with preserved cognitive function in comparison to adults who are cognitively impaired. In this study, we used T1-weighted and high-resolution T2-weighted magnetic resonance images to assess age-related volumetric changes to medial temporal lobe regions, including the hippocampal formation and rhinal cortex, in patients with mild cognitive impairment and cognitively normal controls in two independent cohorts. Our results show age was significantly associated with regional atrophy in the hippocampus, but not the rhinal cortex. Additionally, variability in regional medial temporal lobe volume was associated with tau uptake in the rhinal cortex, but not the hippocampus. Together, these results suggest that the rhinal cortex may be more indicative of Alzheimer’s disease pathology and can help differentiate from age-related neurodegeneration.
SARS-CoV-2 genomic surveillance in Rwanda: Introductions and local transmission of the B.1.617.2 (Delta) variant of concern
Authors: Butera Yvan , Hong Samuel L. , Semakula Muhammed , Bollen Nena , Hill Verity , O’Toole Áine Niamh , Potter Barney I. , Mutangana Dieudonné , Sindayiheba Reuben , Rutayisire Robert , Artesi Maria , Bours Vincent , Rujeni Nadine , Dellicour Simon , Durkin Keith , Mutesa Leon , Baele Guy 
Published: June 2022

AbstractThe emergence of the SARS-CoV-2 Delta variant of concern (lineage B.1.617.2) in late 2020 resulted in a new wave of infections in many countries across the world, where it often became the dominant lineage in a relatively short amount of time. We here report on a novel genomic surveillance effort in Rwanda in the time period from June to September 2021, leading to 201 SARS-CoV-2 genomes being generated, the majority of which were identified as the Delta variant of concern. We show that in Rwanda, the Delta variant almost completely replaced the previously dominant A.23.1 and B.1.351 (Beta) lineages in a matter of weeks, and led to a tripling of the total number of COVID-19 infections and COVID-19-related fatalities over the course of only three months. We estimate that Delta in Rwanda had an average growth rate advantage of 0.034 (95% CI 0.025-0.045) per day over A.23.1, and of 0.022 (95% CI 0.012-0.032) over B.1.351. Phylogenetic analysis reveals the presence of at least seven local Delta transmission clusters, with two of these clusters occurring close to the border with the Democratic Republic of the Congo, and another cluster close to the border with Tanzania. A smaller Delta cluster of infections also appeared close to the border with Uganda, illustrating the importance of monitoring cross-border traffic to limit the spread between Rwanda and its neighboring countries. We discuss our findings against a background of increased vaccination efforts in Rwanda, and also discuss a number of breakthrough infections identified during our study. Concluding, our study has added an important collection of data to the available genomes for the Eastern Africa region, with the number of Delta infections close to the border with neighboring countries highlighting the need to further strengthen genomic surveillance in the region to obtain a better understanding of the impact of border crossings on lowering the epidemic curve in Rwanda.
Estimating the replicability of highly cited clinical research (2004-2018)
Authors: da Costa Gabriel Gonçalves , Neves Kleber , Amaral Olavo B. 
Published: June 2022

AbstractIntroductionPrevious studies about the replicability of clinical research based on the published literature have suggested that highly cited articles are often contradicted or found to have inflated effects. Nevertheless, there are no recent updates of such efforts, and this situation may have changed over time.MethodsWe searched the Web of Science database for articles studying medical interventions with more than 2000 citations, published between 2004 and 2018 in high-impact medical journals. We then searched for replications of these studies in PubMed using the PICO (Population, Intervention, Comparator and Outcome) framework. Replication success was evaluated by the presence of a statistically significant effect in the same direction and by overlap of the replication’s effect size confidence interval (CIs) with that of the original study. Evidence of effect size inflation and potential predictors of replicability were also analyzed.ResultsA total of 89 eligible studies, of which 24 had valid replications (17 meta-analyses and 7 primary studies) were found. Of these, 21 (88%) had effect sizes with overlapping CIs. Of 15 highly cited studies with a statistically significant difference in the primary outcome, 13 (87%) had a significant effect in the replication as well. When both criteria were considered together, the replicability rate in our sample was of 20 out of 24 (83%). There was no evidence of systematic inflation in these highly cited studies, with a mean effect size ratio of 1.03 (95% CI [0.88, 1.21]) between initial and subsequent effects. Due to the small number of contradicted results, our analysis had low statistical power to detect predictors of replicability.ConclusionAlthough most studies did not have eligible replications, the replicability rate of highly cited clinical studies in our sample was higher than in previous estimates, with little evidence of systematic effect size inflation.
An in vivo biomarker to characterize ototoxic compounds and novel protective therapeutics
Authors: Bellairs Joseph A. , Redila Van A. , Wu Patricia , Tong Ling , Webster Alyssa , Simon Julian A. , Rubel Edwin W. , Raible David W. 
Published: June 2022

AbstractThere are no approved therapeutics for the prevention of hearing loss and vestibular dysfunction from drugs like aminoglycoside antibiotics. While the mechanisms underlying aminoglycoside ototoxicity remain unresolved, there is considerable evidence that aminoglycosides enter inner ear mechanosensory hair cells through the mechanoelectrical transduction (MET) channel. Inhibition of MET-dependent uptake with small molecules or modified aminoglycosides is a promising otoprotective strategy. To better characterize mammalian ototoxicity and aid in the translation of emerging therapeutics, a biomarker is needed. In the present study we propose that neonatal mice systemically injected with the aminoglycosides G418 conjugated to Texas Red (G418-TR) can be used as a histologic biomarker to characterize in vivo aminoglycoside toxicity. We demonstrate that postnatal day 5 mice, like older mice with functional hearing, show uptake and retention of G418-TR in cochlear hair cells following systemic injection. When we compare G418-TR uptake in other tissues, we find that kidney proximal tubule cells show similar retention. Using ORC-13661, an investigational hearing protection drug, we demonstrate in vivo inhibition of aminoglycoside uptake in mammalian hair cells. This work establishes how systemically administered fluorescently labeled ototoxins in the neonatal mouse can reveal important details about ototoxic drugs and protective therapeutics.