bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasopressin 1a receptor antagonist disrupts male-male affiliative relationships formed by triadic cohabitation in large-billed crows
Authors: Seguchi Akiko , Izawa Ei-Ichi
Published: February 2024

Same-sex affiliative relationships are common in humans and some social animals, forming one of the bases of group living. The neuropeptide vasopressin (VP) and its receptors mediate these relationships and behaviours in mammals and birds with gregarious and colonial social structures. In some species, affiliative relationships between dominant and subordinate individuals can be maintained while still retaining strict dominance hierarchies where three or more individuals interact. However, it is unclear whether triadic interaction promotes these relationships, and whether the VP system is also involved in such affiliations due to the lack of suitable animal models and experimental settings. This study addresses these questions with two experiments. In Experiment 1, two-week cohabitation among three male crows facilitated affiliative relationships in particular dyads within each triad. In Experiment 2, vasopressin 1a receptor (V1aR) antagonism disrupted affiliative behaviours and led to the resurgence of agonistic behaviours in affiliated males but not in unaffiliated ones by peripherally administering a V1aR antagonist. These findings suggest that the VP system might universally mediate same-sex affiliative relationships, despite differences in inherent aggression levels among individuals. The triadic cohabitation paradigm established here could advance our understanding of animal societies and be applied across various species, sexes, and social structures.

Impact statement

This study provides evidence that a triadic interactive environment facilitates the formation of affiliative relationship between specific dominant and subordinate males in large-billed crows, with crucial involvement of vasopressin 1a receptor in maintaining this affiliation.
A genetically modulated Toll-like-receptor-tolerant phenotype in peripheral blood cells of children with multisystem inflammatory syndrome
Authors: Khan Rehan , Ji Weizhen , Guzman-Rivera Jeisac , Madhvi Abhilasha , Andrews Tracy , Richlin Benjamin , Suarez Christian , Gaur Sunanda , Cuddy William , Singh Aalok R. , Bukulmez Hulya , Kaelber David , Kimura Yukiko , Ganapathi Usha , Michailidis Ioannis E. , Ukey Rahul , Moroso-Fela Sandra , Kuster John K. , Casseus Myriam , Roy Jason , Kleinman Lawrence C. , Horton Daniel B. , Lakhani Saquib A. , Gennaro Maria Laura
Published: February 2024

Dysregulated innate immune responses contribute to multisystem inflammatory syndrome in children (MIS-C), characterized by gastrointestinal, mucocutaneous, and/or cardiovascular injury occurring weeks after SARS-CoV-2 exposure. To investigate innate immune functions in MIS-C, we stimulatedex vivoperipheral blood cells from MIS-C patients with agonists of Toll-like receptors (TLR), key innate immune response initiators. We found severely dampened cytokine responses and elevated gene expression of negative regulators of TLR signaling. Increased plasma levels of zonulin, a gut leakage marker, were also detected. These effects were also observed in children enrolled months after MIS-C recovery. Moreover, cells from MIS-C children carrying rare genetic variants of lysosomal trafficking regulator (LYST) were less refractory to TLR stimulation and exhibited lysosomal and mitochondrial abnormalities with altered energy metabolism. Our results strongly suggest that MIS-C hyperinflammation and/or excessive or prolonged stimulation with gut-originated TLR ligands drive immune cells to a lasting refractory state. TLR hyporesponsiveness is likely beneficial, as suggested by excess lymphopenia among rareLYSTvariant carriers. Our findings point to cellular mechanisms underlying TLR hyporesponsiveness; identify genetic determinants that may explain the MIS-C clinical spectrum; suggest potential associations between innate refractory states and long COVID; and highlight the need to monitor long-term consequences of MIS-C.
Evaluating the causal impact of reproductive factors on breast cancer risk: a multivariable mendelian randomization approach
Authors: Prince Claire , Howe Laura D , Sanderson Eleanor , Sharp Gemma C , Fraser Abigail , Lloyd-Lewis Bethan , Richmond Rebecca C
Published: February 2024

Background

Observational evidence proposes a protective effect of having children and an early age at first birth on the development of breast cancer, however the causality of this association remains uncertain. In this study we assess whether these reproductive factors impact breast cancer risk independently of age at menarche, age at menopause, adiposity measures and other reproductive factors that have been identified as being causally related to or genetically correlated with the reproductive factors of interest.

Methods

We used genetic data from UK Biobank (273,238 women) for reproductive factors, age at menarche and menopause, and adiposity measures, and the Breast Cancer Association Consortium for risk of overall, estrogen receptor (ER) positive and negative breast cancer as well as breast cancer subtypes. We applied univariable and multivariable Mendelian randomization (MR) to estimate direct effects of ever parous status, ages at first birth and last birth, and number of births on breast cancer risk.

Results

We found limited evidence of an effect of age at first birth on overall or ER positive breast cancer risk in either the univariable or multivariable analyses. While the univariable analysis revealed an effect of later age at first birth decreasing ER negative breast cancer risk (Odds ratio (OR): 0.76, 95% confidence interval:0.61-0.95 per standard deviation (SD) increase in age at first birth), this effect attenuated with separate adjustment for age at menarche and menopause (e.g., OR 0.83, 0.62-1.06 per SD increase in age at first birth, adjusted for age at menarche). In addition, we found evidence for an effect of later age at first birth on decreased human epidermal growth factor receptor 2 enriched breast cancer risk but only with adjustment for number of births (OR 0.28 (0.11-0.57) per SD increase in age at first birth).

We found little evidence for direct effects of ever parous status, age at last birth or number of births on breast cancer risk, however, analyses of ever parous status and age at last birth were limited by weak instruments in the multivariable analysis.

Conclusions

This study found minimal evidence of a protective effect of earlier age at first birth on breast cancer risk, while identifying some evidence for an adverse effect on ER negative breast cancer risk. However, multivariable MR of ever parous status and age at last birth is limited by weak instruments which might be improved in future studies with larger sample sizes and when additional genetic variants related to reproductive factors are identified.
Unreliability in Simulations of COVID-19 Cases and Deaths Based on Transmission Models
Authors: Kakeya Hideki , Itoh Makoto , Kamijima Yukari , Nitta Takeshi , Umeno Yoshitaka
Published: February 2024

Two papers authored by the same research group were published in academic journals in October 2023, both of which simulate counterfactual COVID-19 cases and deaths using transmission models. One paper estimates that the COVID-19 cases and deaths from Feb 17 to Nov 30, 2021 in Japan would have been as many as 63.3 million and 364 thousand respectively had the vaccination not been implemented, where the 95% confidence interval is claimed to be less than 1% of the estimated value. It also claims that the cases and deaths could have been reduced by 54% and 48% respectively had the vaccination been implemented 14 days earlier. The other paper estimates that the number of cases in early 2022, Tokyo would have been larger than the number of populations in the age group under 49 in the absence of the vaccination program. In this paper, we reexamine the results given by these papers to find that the simulation results do not explain the real-world data in Japan including prefectures with early/late vaccination schedules. The cause of discrepancy is identified as low reliability of model parameters that immensely affect the simulation results of case and death counts. Leaders of public healthcare are required to discern the reliability and credibility of simulation studies and to prepare for variety of possible scenarios when reliable predictions are not available.
Plasma proteomic evidence for increased Alzheimer’s disease-related brain pathology after SARS-CoV-2 infection
Authors: Duff Eugene P , Zetterberg Henrik , Heslegrave Amanda , Dehghan Abbas , Elliot Paul , Allen Naomi , Runz Heiko , Laban Rhiannon , Veleva Elena , Whelan Christopher D , Sun Benjamin B , Matthews Paul M
Published: February 2024

Prior studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for SARS-CoV-2 virus infections remains uncertain but is of great consequence for predicting future dementia rates. We examined this by comparing changes in plasma biomarkers in UK Biobank participants before and after serology confirmed SARS-CoV-2 infections. We discovered biomarker changes associated with increased AD risk within this population. SARS-CoV-2 infection was associated with reduced plasma Aβ42:Aβ40 concentration ratios, and in more vulnerable participants, lower plasma Aβ42 and higher plasma pTau-181. These biomarker changes, which have been associated with brain beta-amyloid accumulation in prodromal AD, were associated here with increased brain imaging signatures of AD, poorer cognitive scores, and worse assessments of overall health. Changes were greater in participants who had been hospitalised with COVID-19 or had previously reported hypertension. Our data provide evidence for the hypothesis that SARS-CoV-2 can be associated with accelerating brain pathology related to prodromal AD.
European Survey on Citizens’ Attitudes towards Personalized Medicine, Genetic Testing, and Health Data Sharing: Design and Delivery
Authors: Causio Francesco Andrea , Beccia Flavia , Kreeftenberg Loes Lindiwe , Calabrò Giovanna Elisa , Pastorino Roberta , Boccia Stefania , van El Carla
Published: February 2024

Personalized medicine leverages genetic, environmental, and lifestyle information to enhance the efficacy and safety of medical interventions. The shift from traditional one-size-fits-all approaches to a more individualized strategy signifies a major evolution in healthcare systems globally, promising improved patient outcomes and cost-effectiveness. A critical aspect of implementing personalized medicine is the role of public participation and their attitudes toward sharing health data. With growing concerns over data privacy, understanding and addressing public perceptions is essential. For this purpose, we designed and conducted a cross-sectional survey in Europe to gather public attitudes toward personalized medicine and health data sharing. The addressed issues range from knowledge and views to means of data sharing, e.g., via digital health instruments and electronic health care records. These insights are crucial for developing policies and practices that can help build trust and foster a secure environment for healthcare data sharing.
Acupuncture for fatigue in parkinson’s disease: A protocol for systematic review and meta-analysis
Authors: Li Yibo , Zhang Jingxin , Liu Xiaohan , Li Tengteng , Zhang Bingbing , Wang Xiting , Lu Tao
Published: February 2024

Background

Parkinson’s disease (PD) is a common movement disorder characterized by bradykinesia, rigidity, and resting tremors. Fatigue is a common disabling symptom but is easily ignored in PD. Half of the PD patients were influenced by fatigue. Acupuncture is one of the conservative treatments for fatigue related to other conditions, especially in China. Therefore, we perform a systematic review and meta-analysis to evaluate the evidence for acupuncture’s effectiveness, safety, and cost benefits for the treatment.

Methods

This protocol is based on the previously published randomized controlled trial (RCT) studies. A literature search will be performed on the following database: PubMed, the Cochrane Library, Chinese BioMedical Literature Database, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Data. According to the Cochrane Risk of Bias Tool and the level of evidence for results, we will assess the quality of the included studies by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. The Review Manager (v5.3) software will be applied to statistical analysis.

Results

From the study, we will assess the effectiveness, safety, and cost-benefit of acupuncture on fatigue relief and functional improvement in patients with Parkinson’s Disease.

PROSPERO registration number

CRD42020163155

Strengths and limitations of this study

This paper emphasizes the importance of assessing acupuncture in treating Parkinson’s fatigue symptoms and provides methodological guidance for the evaluation of clinical evidence. This study 1) provides a research protocol, 2) facilitates the reasonable evaluation for acupuncture in the treatment of Parkinson’s fatigue symptoms, and 3) raises the potential importance of acupuncture in Parkinson’s fatigue symptoms. Due to the lack of acupuncture reports, there may be a limitation of the small sample size.
Identifying factors related to nondisclosure during clinical supervision among Chinese supervisees: Study protocol
Authors: Stefana Alberto , Youngstrom Eric A.
Published: February 2024

Psychoanalysis is gaining widespread popularity as a therapeutic model in China. However, the absence of local accredited psychoanalytic training institutes necessitates that Chinese trainees and clinicians often receive supervision from European or American supervisors through online platforms. A key component of effective supervision is the willingness of the supervisees to disclose. This openness not only solidifies the supervisory alliance but also improves the supervisee’s self-awareness, self-efficacy, knowledge, and therapeutic skills. Emerging research highlights the significant role of cultural factors in shaping supervisory relationships. Our study aims to: (a) compare the disclosure and nondisclosure rates in clinical supervision between Chinese supervisees and their counterparts from Western cultures, and (b) examine the association between these behaviors and variables related to the therapeutic process among Chinese supervisees. We will employ a cross-sectional design, targeting Chinese psychoanalytic clinicians, both trainees and licensed professionals, engaged in individual clinical supervision. Recruitment will be primarily through the China American Psychoanalytic Alliance mailing list, complemented by snowball sampling. Data will be collected through an online survey hosted on the REDCap platform, focusing on the primary clinical supervisor of the participants and their supervisory experience. This research aims to provide insights that could enable supervisors of Chinese trainees to better understand and adapt to the relational dynamics in supervisory contexts. Additionally, it will lay the foundation for more detailed qualitative investigations into the experiences of Chinese psychoanalytic supervisees, potentially informing future supervisory practices and training methodologies.
Investigating the changing taxonomy and antimicrobial resistance of bacteria isolated from door handles in a new infectious disease ward pre- and post-patient admittance
Authors: Ackers-Johnson Gavin , Pulmones Ralfh , McLaughlan Danielle , Doyle Amy , Lewis Joseph M , Neal Tim , Todd Stacy , Roberts Adam P.
Published: February 2024

Background

Healthcare associated infections (HAIs) are a significant burden to health systems, conferring increased morbidity, mortality and financial costs to hospital admission. Antimicrobial resistance (AMR) further compounds the issue as viable treatment options are constrained. The hospital environment plays a significant role in the development of HAIs, with effective microbial monitoring providing the foundation for targeted interventions and improved infection prevention and control strategies.

Methods

This project sampled door handles in an infectious disease ward at the newly built Royal Liverpool University Hospital, Liverpool, UK. Sampling was performed prior to the first patients being admitted to the ward and then six and twelve months after this date. In addition to identifying all isolates, we also investigated the phenotypic antibiotic resistance of allStaphylococcusspp. identified, with further whole genome sequencing analysis of multidrug resistant isolates.

Results

Prior to patient admission, the majority of isolates identified (57%) wereStaphylococcusspp., reducing to 32% and 29% at six and twelve months respectively whereBacillusspp. accounted for 51% of isolates. No ESKAPE pathogens were identified. Antibiotic susceptibility testing of theStaphylococcusspp. showed the rates of resistance were relatively low for all isolates prior to patient admittance, with the exception of cefoxitin (56%). Overall, resistance was highest after six months of ward use, with only tetracycline showing a consistent increase in resistance at each consecutive time point. Despite an increase in isolates susceptible to all antibiotics after 12 months, the rate of multi-drug resistance remained high. Whole genome sequencing revealed the most abundant resistance genes present amongst multidrug resistant staphylococci wereblaZ(25/26),mecA(22/26) andaac6-aph2(20/26) respectively, followed byermC(15/26) which was identified in allStaphylococcus hominisisolates anddfrC(11/26) which was identified in allStaphylococcus epidermidis isolates. No isolates believed to be clonal were observed across the three time points assessed.

This study highlighted the prevalence of a resistant reservoir of bacteria recoverable on high touch surfaces. However, given all the isolates identified were unique, it would suggest that the cleaning protocols in place are sufficient, and that the observed bacteria are a result of subsequent recolonisation events. This study emphasises the importance of frequent cleaning and efficient, ongoing, environmental surveillance.
Problem-based Learning Curriculum Disconnect on Diversity, Equity, and Inclusion
Authors: Brondani Mario , Barlow Grace , Liu Shuwen , Kalsi Pavneet , Koonar Annika , Chen Jialin (Lydia) , Murphy Peter , Broadbent Jonathan , Brondani Bruna
Published: February 2024

Background

Diversity, equity, and inclusion (DEI) mission statements continue to be adopted by academic institutions in general, and by dental schools around the globe in particular. But DEI content seems to be under-developed in dental education.

Objectives

The objectives of this study were two-fold: to extract information from all the PBL cases at University of British Columbia’s Faculty of Dentistry curriculum in terms of the diversity, equity, and inclusion of patient and provider characteristics, context, and treatment outcomes; and; to compare these findings with the composition of the British Columbia census population, dental practice contextual factors, and the evidence on treatment outcomes within patient care.

Methods

Information from all the 58 PBL cases was extracted focusing on patient and provider characteristics (e.g., age, gender, ethnicity), context (e.g., type of insurance), and treatment outcomes (e.g., successful/unsuccessful). This information was compared with the available literature.

Results

From all the 58 PBL cases, 0.4% included non-straight patients, while at least 4% of BC residents self-identify as non-straight; there were no cases involving First Nations patients although they make up 6% of the British Columbia population. Less than 10% of the cases involved older adults who make up almost 20% of the population. Only Treatments involving patients without a disability were 5.74 times more likely to be successful compared to those involving patients with a disability (p<0.05).

Conclusions

The characteristics of the patients, practice context, and treatment outcomes portrayed in the existing PBL cases seem to differ from what is known about the composition of the British Columbia population, treatment outcome success, and practice context; a curriculum disconnect seems to exist. The PBL cases should be revised to better represent the population within which most students will practice.
Effects of COVID-19 on the provision of Water, Sanitation, and Hygiene (WASH) services in health care facilities in the Far-North Region of Cameroon
Authors: Nounkeu Carole Debora , Noumbissi Massop Giequel Corniche , Koyalta Donato , Ndongo Chanceline Bilounga , Ouabo Florent Kamkumo , Nono Bertin , Ngoufack Marie Nicole , Dharod Jigna Morarji , Juillard Catherine , Chichom-Mefire Alain , Nguefack-Tsague Georges
Published: February 2024

Worldwide, the Joint Monitoring Program reports that one in four health care facilities (HCFs) lack functional water supply on premises, one in three lack hand hygiene facilities, and one in three lack adequate infectious waste disposal. The COVID-19 pandemics shed light on the lack of investments, the absence of infrastructures, education and policies related to WASH as well as revealed insufficient investment in healthcare safety and has brought WASH services as non-negotiable for HCFs. This study used a cross-sectional pre-post COVID-19 framework to determine the proportion of HCFs: meeting basic WASH services and, which WASH services improved post-COVID-19 in the Far-North Region of Cameroon. A total of 97 (23.04%) HCFs among the 421 that are found in the Far-North region were surveyed and located in eight (25%) of the 32 Health Districts. They corresponded to the integrated health centers category (79.4%) and the survey’s respondent was the chief of the HCF (92.8%). Approximately 75.3%, 0.0%, 48.5%, 46.4%, and 6.2% of HCFs respectively met thresholds for basic water, sanitation, hygiene, waste management, and environment cleaning services. When comparing pre- vs. post COVID-19 periods, a significant increase (8%) was noted in the proportion of HCFs as of optimal handwashing practices-related services (P=0.0026). There was also a significant increase (p=0.007) in the proportion of HCFs with cleaning protocols available. Further, none of the HCFs fulfilled all the criteria to meet basic services for all the five WASH services. In conclusion, the response to the COVID-19 pandemics only partially improved WASH services-related infrastructures in HCFs of the Far-North Region of Cameroon. The COVID-19 pandemics was a missed opportunity to strengthen WASH services. There should be a continuing encouragement of governments and funding agencies in planning and budgeting WASH in healthcare-related research and issues, and enabling the maintenance of existing WASH infrastructures in healthcare settings.
Impact of continuous labour companion- who is the best: A comprehensive meta-analysis on familiarity, training, temporal association, and geographical location
Authors: Jayasundara DMCS , Jayawardane IA , Weliange SDS , Jayasingha TDKM , Madugalle TMSSB
Published: February 2024

Background

Continuous labour support is widely acknowledged for potentially enhancing maternal and neonatal outcomes and smoothing the labour process. However, existing literature lacks a comprehensive analysis of the optimal characteristics of labour companions, particularly in comparing the effects of trained versus untrained and familiar versus unfamiliar labour companions across diverse geographical regions and pre and post-millennial. This meta-analysis addresses these research gaps by providing insights into the most influential aspects of continuous labour support.

Methodology

A thorough search of PubMed, Google Scholar, Science Direct, International Clinical Trials Registry Platform (ICTRP),ClinicalTrials.gov, Research4Life, and Cochrane Library was conducted. Study selection utilised the semi-automated tool Rayyan. The Cochrane risk-of-bias (RoB2) tool and funnel plots gauged the risk of bias. Statistical analysis employed RevMan 5.4, using Mantel-Haenszel statistics and random effects models to calculate risk ratios with 95% confidence intervals. Subgroup analyses were performed for different characteristics, including familiarity, training, temporal associations, and geographical locations. The study was registered in INPLASY. (Registration number: INPLASY202410003)

Results

Thirty-five randomised controlled trials (RCTs) were identified from 5,346 studies. The meta-analysis highlighted significant positive effects of continuous labour support across various outcomes. There was a substantial improvement in the 5-minute APGAR score < 7, with an effect size of 1.52 (95% CI 1.05, 2.20). Familiar labour companions showed a higher effect size in reducing tocophobia, 1.73 (95% CI 1.49, 2.42), compared to unfamiliar companions, 1.34 (95% CI 1.14, 1.58). Differences were noted between trained and untrained companions, favouring untrained companions in reducing tocophobia and the cesarean section rate. Studies conducted after 2000 had a more significant impact on decreasing labour duration. Geographical variations indicated more pronounced effects in Asia and Africa than in Europe.

Discussion and Conclusion

The meta-analysis underscores the benefits of labour companionship, particularly in facilitating the parturient experience of spontaneous labour. The impact is more pronounced in specific subgroups, such as familiar companions, untrained companions, recent studies, and studies conducted in Asia and Africa. The study recommends integrating labour companionship into obstetric care pending further research, standardisation, and awareness initiatives to enhance maternal and neonatal outcomes. Challenges such as study heterogeneity, insufficient data on companion training, and temporal outcome variations are acknowledged.
Racial and ethnic associations with interstitial lung disease and healthcare utilization in patients with systemic sclerosis
Authors: Tukpah Ann-Marcia C. , Rose Jonathan A. , Seger Diane L. , Hunninghake Gary Matt , Bates David W.
Published: February 2024

Rationale

Racial and ethnic differences in presentation and outcomes have been reported in systemic sclerosis (SSc) and SSc-interstitial lung disease (ILD). However, diverse cohorts and additional modeling can improve understanding of risk features and outcomes, which is important for reducing associated disparities.

Objective(s)

To determine if there are racial/ethnic differences associated with SSc-ILD risk and age; time intervals between SSc and ILD, and with emergency department (ED) visit or hospitalization rates.

Methods

A retrospective cohort study using electronic health record data from an integrated health system, over a 5.5 year period was conducted using clinical and sociodemographic variables, models were generated with sequential adjustments for these variables. Logistic regression models were used to examine the association of covariates with ILD and age at SSc-ILD. Healthcare outcomes were analyzed with complementary log-log regression models.

Results

The cohort included 756 adults (83.6% female, 80.3% non-Hispanic White) with SSc with a mean age of 59 years. Overall, 33.7% of patients in the cohort had an ILD code, with increased odds for Asian (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.29, 5.18;P=.007) compared to White patients. The age in years of patients with SSc-ILD was younger for Hispanic (mean difference, −6.5; 95% CI, −13, −0.21;P= 0.04) and Black/African American patients (−10; 95% CI −16, −4.9;P<0.001) compared to White patients. Black/African American patients were more likely to have an ILD code before an SSc code (59% compared to 20.6% of White patients), and had the shortest interval from SSc to ILD (3 months). Black/African American (HR, 2.59; 95% CI 1.47, 4.49;P=0.001) and Hispanic patients (HR 2.29; 95% CI 1.37, 3.82;P=0.002) had higher rates of an ED visit.

Conclusion

In this study, SSc-ILD presentation and outcomes differed by racial/ethnic group (increased odds of SSc-ILD, younger age at SSc-ILD, and preceding diagnosis with respect to SSc, rates of ED visit), some of which was attenuated with adjustment for clinical and sociodemographic characteristics. Differing presentation may be driven by social drivers of health (SDOH), autoantibody profiles, or other key unmeasured factors contributing to susceptibility and severity.
Confounder control in biomedicine necessitates conceptual considerations beyond statistical evaluations
Authors: Komeyer Vera , Eickhoff Simon B. , Grefkes Christian , Patil Kaustubh R. , Raimondo Federico
Published: February 2024

Machine learning (ML) models hold promise in precision medicine by enabling personalized predictions based on high-dimensional biomedical data. Yet, transitioning models from prototyping to clinical applications poses challenges, with confounders being a significant hurdle by undermining the reliability, generalizability, and interpretability of ML models. Using hand grip strength (HGS) prediction from neuroimaging data from the UK Biobank as a case study, we demonstrate that confounder adjustment can have a greater impact on model performance than changes in features or algorithms. An ubiquitous and necessary approach to confounding is by statistical means. However, a pure statistical viewpoint overlooks the biomedical relevance of candidate confounders, i.e. their biological link and conceptual similarity to actual variables of interest. Problematically, this can lead to biomedically not-meaningful confounder-adjustment, which limits the usefulness of resulting models, both in terms of biological insights and clinical applicability. To address this, we propose a two-dimensional framework, theConfound Continuum, that combines both statistical association and biomedical relevance, i.e. conceptual similarity, of a candidate confounder. The evaluation of conceptual similarity assesses on a continuum how much two variables overlap in their biological meaning, ranging from negligible links to expressing the same underlying biology. It thereby acknowledges the gradual nature of the biological link between candidate confounders and a predictive task. Our framework aims to create awareness for the imperative need to complement statistical confounder considerations with biomedical, conceptual domain knowledge (without going into causal considerations) and thereby offers a means to arrive at meaningful and informed confounder decisions. The position of a candidate confoudner in the two-dimensional grid of theConfound Continuumcan support informed and context-specific confounder decisions and thereby not only enhance biomedical validity of predictions but also support translation of predictive models into clinical practice.
Age Prediction From 12-lead Electrocardiograms Using Deep Learning: A Comparison of Four Models on a Contemporary, Freely Available Dataset
Authors: Barros Andrew , German-Mesner Ian , Rich Nguyen N. , Moorman J. Randall
Published: February 2024

Objective

The 12-lead electrocardiogram (ECG) is routine in clinical use and deep learning approaches have been shown to have the identify features not immediately apparent to human interpreters including age and sex. Several models have been published but no direct comparisons exist.

Approach

We implemented three previously published models and one unpublished model to predict age and sex from a 12-lead ECG and then compared their performance on an open-access data set.

Main results

All models converged and were evaluated on the holdout set. The best preforming age prediction model had a hold-out set mean absolute error of 8.06 years. The best preforming sex prediction model had a hold-out set area under the receiver operating curve of 0.92.

Significance

We compared performance of four models on an open-access dataset.
Genome-wide association analysis of composite sleep health scores in 413,904 individuals
Authors: Goodman Matthew O , Faquih Tariq , Paz Valentina , Nagarajan Pavithra , Lane Jacqueline M , Spitzer Brian , Maher Matthew , Chung Joon , Cade Brian E , Purcell Shaun M , Zhu Xiaofeng , Noordam Raymond , Phillips Andrew J. K. , Kyle Simon D. , Spiegelhalder Kai , Weedon Michael N , Lawlor Deborah A. , Rotter Jerome I , Taylor Kent D , Isasi Carmen R , Sofer Tamar , Dashti Hassan S , Rutter Martin K , Redline Susan , Saxena Richa , Wang Heming
Published: February 2024

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, and together may provide a more complete picture of sleep health, while also illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p<8.3e-9), along with 341 previously reported loci (p<5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2=0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections to behavioral, psychological, and cardiometabolic traits.
Comparing surveyed adults with long COVID and those with just a positive test helps put COVID into perspective
Authors: Adams Mary L. , Grandpre Joseph
Published: February 2024

Introduction

Among adults who test positive for COVID-19, some develop long COVID (symptoms lasting ≥3 months), and some do not. We compared 3 groups on selected measures to help determine strategies to reduce COVID impact.

Methods

Using Stata and data for 385,617 adults from the 2022 Behavioral Risk Factor Surveillance System, we compared adults reporting long COVID, those with just a positive test, and those who never tested positive, on several health status and risk factor measures plus vaccination rates (data for 178,949 adults in 29 states).

Results

Prevalence of just COVID was 26.5% (95% CI 26.2-26.8) and long COVID was 7.4% (7.3-7.6). Compared with adults with just COVID those with long COVID had worse rates for 13 of 17 measures of chronic disease, disability, and poor health status, while those with just COVID had the best results for 15 of the 17 measures among all 3 groups. The 5 risk factors (obesity, diabetes, asthma, cardiovascular disease, and COPD) previously associated with COVID deaths, increased long COVID but not just COVID rates, which were highest among younger and higher income adults. Adults with long COVID had the highest rate among the 3 groups for any COVID risk factors and data from 29 states showed they had the lowest rates for ≥3 vaccine doses of 35.6%, vs. 42.7% and 50.3% for those with just a positive test, and neither, respectively. Vaccination with ≥3 vaccines vs. <3 reduced long COVID rates by 38%, and just COVID rates by 16%.

Conclusions

Results show the seriousness of long COVID vs. just a positive test and that increasing vaccine coverage by targeting adults with risk factors shows promise for reducing COVID impact.
Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections
Authors: Rivera Luis Felipe , Lezcano-Coba Carlos , Galué Josefrancisco , Rodriguez Xacdiel , Juarez Yelissa , de Souza William M. , Capitan-Barrios Zeuz , Valderrama Anayansi , Abrego Leyda , Cedeño Hector , Jackman Carmela , Waggoner Jesse J. , Aguilar Patricia V. , Guzman Hilda , Weaver Scott C. , Tesh Robert B. , López-Vèrges Sandra , Donnelly Christl A. , Estofolete Cassia F. , Nogueira Mauricio L. , Faria Nuno R. , Vasilakis Nikos , Vittor Amy Y. , Smith Darci R. , Carrera Jean-Paul
Published: February 2024

Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, there are limited clinical and epidemiological reports available, and outbreaks are occurring at an increasing frequency. We addressed this gap by analyzing all the available clinical and epidemiological data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 of human alphavirus encephalitis cases were detected in Panama from 1961 to 2023. Here we describe the clinical signs and symptoms and epidemiological characteristics of these cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection when compared to those of other arbovirus infections occurring in the region. Our results highlight the challenges clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.
Distinguishing different psychiatric disorders using DDx-PRS
Authors: Peyrot Wouter J. , Panagiotaropoulou Georgia , Olde Loohuis Loes M. , Adams Mark J. , Awasthi Swapnil , Ge Tian , McIntosh Andrew M. , Mitchell Brittany L. , Mullins Niamh , O’Connell Kevin S , Penninx Brenda W.J.H. , Posthuma Danielle , Ripke Stephan , Ruderfer Douglas M. , Uffelmann Emil , Vilhjalmsson Bjarni J. , Zhu Zhihong ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium,   Bipolar Disorder Working Group of the Psychiatric Genomics Consortium,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Smoller Jordan W. , Price Alkes L.
Published: February 2024

Despite great progress on methods for case-control polygenic prediction (e.g. schizophrenia vs. control), there remains an unmet need for a method that genetically distinguishes clinically related disorders (e.g. schizophrenia (SCZ) vs. bipolar disorder (BIP) vs. depression (MDD) vs. control); such a method could have important clinical value, especially at disorder onset when differential diagnosis can be challenging. Here, we introduce a method, Differential Diagnosis-Polygenic Risk Score (DDx-PRS), that jointly estimates posterior probabilities of each possible diagnostic category (e.g. SCZ=50%, BIP=25%, MDD=15%, control=10%) by modeling variance/covariance structure across disorders, leveraging case-control polygenic risk scores (PRS) for each disorder (computed using existing methods) and prior clinical probabilities for each diagnostic category. DDx-PRS uses only summary-level training data and does not use tuning data, facilitating implementation in clinical settings. In simulations, DDx-PRS was well-calibrated (whereas a simpler approach that analyzes each disorder marginally was poorly calibrated), and effective in distinguishing each diagnostic category vs. the rest. We then applied DDx-PRS to Psychiatric Genomics Consortium SCZ/BIP/MDD/control data, including summary-level training data from 3 case-control GWAS (N=41,917-173,140 cases; totalN=1,048,683) and held-out test data from different cohorts with equal numbers of each diagnostic category (totalN=11,460). DDx-PRS was well-calibrated and well-powered relative to these training sample sizes, attaining AUCs of 0.66 for SCZ vs. rest, 0.64 for BIP vs. rest, 0.59 for MDD vs. rest, and 0.68 for control vs. rest. DDx-PRS produced comparable results to methods that leverage tuning data, confirming that DDx-PRS is an effective method. True diagnosis probabilities in top deciles of predicted diagnosis probabilities were considerably larger than prior baseline probabilities, particularly in projections to larger training sample sizes, implying considerable potential for clinical utility under certain circumstances. In conclusion, DDx-PRS is an effective method for distinguishing clinically related disorders.
The effect of health insurance coverage on antenatal care utilization in Cambodia: A secondary analysis of Cambodia Demographic and Health Survey 2021-2022
Authors: Um Samnang , Phan Channnarong , Dany Leng , Veha Khun , Pay Soklim , Chau Darapheak
Published: February 2024

Health insurance is essential in reducing or eliminating the financial constraint to accessing maternal health services caused by out-of-pocket payments. Also, it has a beneficial effect in minimizing the number of maternal and child mortality. However, limited studies in Cambodia examined the association between health insurance coverage on antenatal care (ANC) utilization. Therefore, this study have examined the effect of health insurance coverage on ANC utilization in Cambodia. The study utilized data from the 2021-2022 Cambodia Demographic and Health Surveys (CDHS). A total of 3,162 weighted women who gave birth within two years were included in the study. Multiple logistic regression analysis was explored to assess the association between health insurance coverage with women who attended four or more ANC visits. About 24.9% of the women had health insurance coverage during 2021-2022. Most (86.1%) of women attended four or more ANC visits. Women with health insurance coverage were statistically significantly associated with attending four or more ANC visits with an adjusted odds ratio (AOR = 1.6; 95% CI: 1.1–2.4). Other factors significantly associated with attending four or more ANC visits include women with higher education (AOR = 3.1; 95% CI: 1.2–7.7), secondary education (AOR = 2.3; 95% CI: 1.5–3.5), richest households (AOR = 3.2; 95% CI: 1.5-6.8), and richer households (AOR = 1.9;95% CI: 1.2-2.8). Pregnant women with health insurance coverage, who had completed at least secondary education and had a better wealth index were more likely to attend at least four ANC visits. Thus, providing health insurance coverage and improving women’s economic and educational may be essential to improving women’s access to maternal health services in Cambodia.
Proteome-Wide Assessment of Clustering of Missense Variants in Neurodevelopmental Disorders Versus Cancer
Authors: Ng Jeffrey K. , Chen Yilin , Akinwe Titilope M. , Heins Hillary B. , Mehinovic Elvisa , Chang Yoonhoo , Payne Zachary L. , Manuel Juana G. , Karchin Rachel , Turner Tychele N.
Published: February 2024

Missense de novo variants (DNVs) and missense somatic variants contribute to neurodevelopmental disorders (NDDs) and cancer, respectively. Proteins with statistical enrichment based on analyses of these variants exhibit convergence in the differing NDD and cancer phenotypes. Herein, the question of why some of the same proteins are identified in both phenotypes is examined through investigation of clustering of missense variation at the protein level. Our hypothesis is that missense variation is present in different protein locations in the two phenotypes leading to the distinct phenotypic outcomes. We tested this hypothesis in 1D protein space using our software CLUMP. Furthermore, we newly developed 3D-CLUMP that uses 3D protein structures to spatially test clustering of missense variation for proteome-wide significance. We examined missense DNVs in 39,883 parent-child sequenced trios with NDDs and missense somatic variants from 10,543 sequenced tumors covering five TCGA cancer types and two COSMIC pan-cancer aggregates of tissue types. There were 57 proteins with proteome-wide significant missense variation clustering in NDDs when compared to cancers and 79 proteins with proteome-wide significant missense clustering in cancers compared to NDDs. While our main objective was to identify differences in patterns of missense variation, we also identified a novel NDD protein BLTP2. Overall, our study is innovative, provides new insights into differential missense variation in NDDs and cancer at the protein-level, and contributes necessary information toward building a framework for thinking about prognostic and therapeutic aspects of these proteins.
Predicting post-stroke cognitive impairment using electronic health record data
Authors: Ashburner Jeffrey M. , Chang Yuchiao , Porneala Bianca , Singh Sanjula D. , Yechoor Nirupama , Rosand Jonathan M. , Singer Daniel E. , Anderson Christopher D. , Atlas Steven J.
Published: February 2024

Importance

Secondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification.

Objective

To develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records.

Design

Cohort study with patients enrolled between 2003-2016 with follow-up through 2022.

Setting

Primary care practices affiliated with two academic medical centers.

Participants

Individuals 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003-2016 (development/internal validation cohort) or 2010-2022 (external validation cohort).

Exposures

Predictors of PSCI were ascertained from the electronic health record.

Main Outcome

The outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using ICD-9/10 codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included.

Results

The analysis included 332 incident diagnoses of PSCI in the development cohort (n=3,741), and 161 and 128 incident diagnoses in the internal (n=1,925) and external (n=2,237) validation cohorts. The c-statistic for predicting PSCI was 0.731 (95% CI: 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-35 points) risk groups. The hazard ratios for incident PSCI were significantly different by risk categories in internal (High, HR: 6.2, 95% CI 4.1-9.3; Intermediate, HR 2.7, 95% CI: 1.8-4.1) and external (High, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR 2.8, 95% CI: 1.9-4.3) validation cohorts.

Conclusions and Relevance

Five-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts.