bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic propensity to mental health traits and their associations with social connection phenotypes: evidence from the English Longitudinal Study of Ageing
Authors: Finn Saoirse , Ajnakina Olesya , Bu Feifei , Fancourt Daisy 
Published: November 2024

AbstractThere is a wealth of phenotypic literature on the interplay between mental health and social connections. However, how genetic propensity to mental health traits may be associated with distinct social connections phenotypes (i.e., structural, functional and quality aspects) is largely unexplored. Using polygenic scores (PGSs), we explored the associations between genetic propensity for five mental health traits (PGSdepressive-symptoms,PGSanxiety,PGSbipolar- disorder,PGSschizophrenia,PGSwellbeing) and four social connection phenotypes (social isolation, loneliness, social support and relationship strain). Linear regressions were conducted in a representative sample of unrelated older adults living in the UK, and analyses were controlled for age, sex, and principal components to account for population stratification. The results show that higherPGSdepressive-symptomswas associated with greater loneliness (B=0.11, CI-95%=0.07, 0.15) and relationship strain (B=0.09, CI-95%=0.05, 0.13) and lower social support (B=-0.07, CI-95%=-0.13, -0.01). Higher PGSanxietywas associated with higher social isolation (B=0.05, CI-95%=0.00, 0.10) and greater relationship strain (B=0.05, CI-95%=0.01, 0.09). HigherPGSbipolar-disorderwas associated with greater loneliness (B=0.05, CI-95%=0.01, 0.09) and relationship strain (B=0.06, CI-95%=0.02, 0.10). HigherPGSwellbeingwas associated with lower loneliness (B=-0.07, CI-95%=-0.11, -0.03), relationship strain (B=- 0.07, CI-95%=-0.11, -0.03), and social isolation (B=-0.07, CI-95%=-0.12, -0.02), and greater social support (B=0.14, CI-95%=0.08, 0.21). This suggests differential associations between different mental health PGSs and distinct aspects of social connections, indicating a nuanced picture. Our findings confirm that genetics play a role in having adequate social connections, which can be supported through social, community, and cultural schemes. They also highlight that genetic confounding is important when using observational data assessing the associations between mental health and social connections.
Disparities in cancer genomics by ancestry in the 100,000 Genomes Project
Authors: Nguyen T. , Tallman Sam , Cho Yoonsu , Sosinsky Alona , Ambrose John , Thorn Steve , Mackintosh Maxine , Brown Matthew A. , Moutsianas Loukas , Silver Matt J. , Kuchenbaecker Karoline 
Published: November 2024

AbstractPurposeMost research on genetic screening and precision oncology is based on participants of European ancestry, making it vital to evaluate the performance of these approaches in diverse populations. We analysed data from the 100,000 Genomes Project (100kGP) to assess ancestry-related differences in cancer variant prioritisation.Patients and MethodsTo assess the representativeness of the 14,775 participants with cancer from the 100kGP, we compared recruitment ratios for self-reported ethnicities to those in England. For genetic ancestry groups we analysed differences in detection rates for potential pathogenic variants (PVs) in the germline and somatic mutations in genes with treatment implications and investigated possible causes of observed disparities.ResultsRecruitment rates for Black and Asian ethnicities compared with White ethnicity in the 100kGP were consistent with rates in England, except for bladder and prostate (Black and Asian) and breast (Asian only) where Black and Asian ethnicities were recruited at higher rates than expected compared to White ethnicity.Patients with non-European genetic ancestry were more likely to carry variants classified as potential pathogenic compared to European ancestry (p=0.006). PVs were identified in 4.6% of South Asian (adjusted model: odds ratio=1.88, 95%CI=1.21-2.93) and 5.3% of African ancestry patients (odds ratio=2.24, 95%CI=1.44-3.48) compared with 2.2% in European.Fewer non-synonymous somatic mutations in actionable genes were identified in patients of non-European ancestry (p=0.004). WGS failed to identify treatment-relevant findings for 26% of patients of South Asian ancestry compared with 16% of European ancestry.ConclusionThe excess germline variants classified as PVs in patients with non-European ancestry may impede the diagnostic process. Our analysis demonstrates the need for better variant classification across diverse ancestries to ensure equitable implementation of genomics in cancer care.
Consequences of Acute Presentations of Functional Neurological Disorders in Neuro-oncology patients: Case Series and Systematic Review
Authors: Innes Stuart C. , Joe Dorothy K. , Cikurel Katia , Lavrador José P. , Vergani Francesco , Bhangoo Ranjeev , Ashkan Keyoumars , Finnerty Gerald T. 
Published: November 2024

ABSTRACTObjectiveNew neurological symptoms in neuro-oncology patients are usually attributed to the tumour or its treatment. A diagnosis of functional neurological disorder (FND) is often only considered when investigations do not reveal a cause and medical management fails. Here, we investigate the consequences of acute FND in neuro-oncology patients.MethodsWe performed a single-centre retrospective case study of adult neuro-oncology patients with an intracranial tumour who presented acutely with FND. Data recorded were: tumour type, investigations, adverse life events, medical interventions and outcomes. This was combined with a systematic literature review of articles in English peer-reviewed journals on adults with brain or meningeal tumours and concomitant FND.ResultsTen patients met our study criteria. Six had functional seizures, two had functional hemiparesis and two had functional speech disorders. FND symptoms started: prior to tumour diagnosis in three patients; between diagnosis and treatment in four; and after treatment commenced in three patients. Two patients were thrombolysed for presumed stroke. Three patients had their tumour surgery or chemoradiotherapy delayed. Diagnosis and management of FND enabled tumour treatment to restart. The systematic review identified 37 patients. 33 had functional seizures and four had motor FND. All FND diagnoses except one started after tumour treatment commenced.ConclusionAcute FND may lead to unnecessary medical interventions and disrupt tumour treatment. Although acute FND improved with diagnosis and explanation, many neuro-oncology patients require a multi-disciplinary tumour-FND pathway to manage their FND, prevent acute FND symptoms becoming chronic and to avoid delays to tumour treatment.What is already known on this topicCase reports have documented functional neurological disorders (FND) in brain tumour patients, but almost invariably after their tumour treatment has commenced.What this study addsFND can present acutely at any stage of the brain tumour illness and may result in inappropriate interventions and/or treatment. Tumour treatment may be delayed.How this study might affect research, practice or policyBrain tumour patients require a multi-disciplinary FND pathway, not only to manage their FND symptoms, but to prevent delays to tumour treatment, which is proscribed by government guidance on timely treatment of cancer.
Genetic Insights into Cardiac Conduction Disorders from Genome-Wide Association Studies
Authors: Li Bingxun , Xu Hongxuan , Wu Lin 
Published: November 2024

ABSTRACTBACKGROUNDSubstantial data support a heritable basis for cardiac conduction disorders (CCDs), but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood, therefore, we sought to identify genetic loci associated with CCDs.METHODSWe performed meta-analyses of genome-wide association studies to identify genetic loci for atrioventricular block (AVB), left bundle branch block (LBBB), and right bundle branch block (RBBB) from public data from the UK Biobank and FinnGen consortium. We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and ECG-wide phenome-wide associations for each indexed SNP.RESULTSAnalysis comprised over 700,000 individuals for each trait. We identified 10, 4 and 0 significant loci for AVB (PLEKHA3, TTN, FNDC3B, SENP2, SCN10A, RRH, PPARGC1A, PKD2L2, NKX2-5andTBX20), LBBB (PPARGC1A, HAND1, TBX5, andADAMTS5) and RBBB, respectively. Transcriptome-wide association analysis supported an association between reduced predicted cardiac expression ofSCN10Aand AVB. Phenome-wide associations identified traits with both cardiovascular and non-cardiovascular traits with indexed SNPs.CONCLUSIONSOur analysis highlight gene regions associated with channel function, cardiac development, sarcomere function and energy modulation as important potential effectors of CCDs susceptibility.
Distribution of Smoking and Hypertension: A Cross-Sectional Study of Bangladeshi Beverage Company Staff
Authors: Md. Saleh Abu Sayeed , Shaharin Tilat , Shafiullah Afnan , Rahman Mashreky S M Saidur 
Published: November 2024

ABSTRACTNon-communicable diseases, especially hypertension, are disproportionately problematic in low- and middle-income countries such as Bangladesh, where they have become one of the leading causes of death among its population. The present study compares both the prevalence of hypertension and smoking in employees of Bangladeshi beverage industries to that of the general population. By capitalizing on data from various sources, this research evinces that the prevalence of the preceding issues is disturbingly high, particularly among certain demographics. This, despite the efforts the National Heart Foundation put in place to address the challenges in hypertension screening and management, reflects the need for healthcare delivery. The connection between smoking with health in this sense is confirmed; thus, it will be of crucial necessity to understand the link between these threats, especially within the beverage industry. This study has, therefore, tried to shed light on the nexus, to inform targeted interventions aimed at promoting healthier work environments for the ultimate reduction of NCD-related deaths within the country.
Trends and the Prevalence of Metabolic Syndrome and its Associated Factors among Nepalese Adults in Ecological regions of Nepal-A Nationwide Cross - Sectional Survey
Authors: Bhandari Bhawana , Bista Bihumgum , Karmacharya Suna Laxmi , Ojha Anil Babu , Nizaruddin Datin Mariani Ahmad , Mehata Suresh 
Published: November 2024

AbstractGlobally, there is an increase in the Prevalence of Metabolic Syndrome. The rise in prevalence of Metabolic Syndrome suggests burden of Cardiovascular related morbidity and mortality which is also prevalent in Nepal. Metabolic Syndrome confers a 5-fold increase in the risk of Type 2 Diabetes Mellitus (T2DM) and 2-fold the risk of developing Cardiovascular Disease (CVD) over the next 5 to 10 years. Routine surveillance and registry system in Nepal related to Metabolic Syndrome are bare in Nepal which is imperative to determine the prevalence of MetS and its associated factors. This study used multistage cluster sampling considering the three ecological zones as strata. 259 Primary Sampling Units were selected randomly and a total of 5593 population were surveyed where 5051 population met the criteria for determining the Prevalence of MetS. A STEPwise Surveillance was conducted using WHO Steps survey questionnaire 3.2 version by interview technique, physical and biochemical measurements. The result concluded that there was a decrease in trend of Prevalence of Metabolic Syndrome from 14.1% to 6.69%. from 2013 to 2019.The overall Prevalence of MetS was found to be 6.69%, nearly double in women than in men (8.62% and 4.57% respectively). Waist circumference was found to be the most prevalent component of Metabolic Syndrome among women. Age, Sex, Education, Marital status, Wealth quintile and Ecological region were significantly associated with MetS and there was no significant association of MetS with behavioral factors.
Long-Term Coronary Microvascular and Cardiac Dysfunction Following Severe COVID-19 Hospitalization
Authors: Johansson Rebecka Steffen , Loewenstein Daniel , Lodin Klara , Bruchfeld Judith , Runold Michael , Ståhlberg Marcus , Xue Hui , Kellman Peter , Caidahl Kenneth , Engblom Henrik , Nickander Jannike 
Published: November 2024

AbstractBackgroundCoronavirus disease 2019 (COVID-19) can lead to long-term cardiopulmonary symptoms and is associated to coronary microvascular dysfunction (CMD). However, long-term data on CMD following severe COVID-19 are lacking.ObjectiveTo determine long-term left ventricular (LV) function and presence of CMD after severe COVID-19, utilizing cardiovascular magnetic resonance (CMR) and stress perfusion mapping.MethodsHospitalized COVID-19 patients underwent CMR at 10 months follow-up (1.5T Aera, Siemens Healthineers) including cine imaging, native T1 and T2, extracellular volume, and adenosine stress perfusion mapping. Clinical data were obtained from patient records. Patients were compared to volunteers without symptomatic ischemic heart disease (IHD).ResultsCOVID-19 patients (n=37, age 56±12 years, 76% male) and volunteers (n=22, age 51±13 years, 55% male, p=ns for both) were included. COVID-19 patients demonstrated reduced stress perfusion (2.8±0.81 vs 3.4±0.69 ml/min/g,p=0.003), impaired global longitudinal strain (GLS, −17±2 vs −19±2 %,p=0.003) and global circumferential strain (GCS, −16±3 vs −19±3 %,p=0.001). There were no differences in stress perfusion or myocardial perfusion reserve between COVID-19 patients with or without cardiovascular risk factors or cardiac symptoms.ConclusionCOVID-19 patients exhibit long-term reduced stress perfusion indicating CMD, and impaired LV function by GLS and GCS. Lack of variation in stress perfusion between patients with and without cardiovascular risk factors suggests that CMD may be a consequence of severe COVID-19, warranting further investigation to elucidate mechanisms, and guide potential therapeutic interventions.
A Cross-Sectional Analysis of Disparities in Biopsy Result Disclosure for Patients with Limited English Proficiency
Authors: Nguyen Joseph Dan Khoa , Mark Erica , Martin Seth , Flowers R. Hal 
Published: November 2024

AbstractPatients with limited English proficiency (LEP) receiving care from language-discordant providers experience worse outcomes in healthcare quality, safety, and satisfaction, so optimizing medical care for patients with LEP is an integral topic for quality improvement. At our institution, biopsy results are disclosed via telephone unless discussed during an appointment. In this retrospective cohort study, we aimed to quantify the relative lag time in telephone-based biopsy result disclosure when interpretation services were utilized compared to when they were not. A total of 12,372 patient interactions were analyzed; 250 patients (2.02%) required interpreters, and most of these patients spoke Spanish (196, 78.4%). Other languages spoken included Tagalog, Ukrainian, Serbian, Russian, Punjabi, Mandarin, Kurdish, Farsi, Nepali Arabic, and American Sign Language. The mean delay from provider result release to disclosure for patients who required an interpreter was 55.0 hours compared to 36.6 hours for those who did not, respectively (p<0.001). For those requiring a Spanish interpreter, this delay was 60.2 hours (p<0.001). For non-Spanish interpretation, the delay was 36.6 hours (p=0.99). Patients requiring a Spanish interpreter experienced increased mean wait times for receiving biopsy results compared to those who spoke English. Possible reasons include increased communication burden for clinicians when using interpreters, insufficient provider awareness of delays, and patient socioeconomic factors. Future research may analyze the impact of delayed result disclosure, optimal disclosure methods, and initiatives to reduce disparities in time to result disclosure for LEP patients.
Development and Validation of a Nomogram for Predicting Survival in Patients With Cardiogenic Shock
Authors: Fang Dingfeng , Chen Huihe , Geng Hui , Chen Xiahuan , Liu Meilin 
Published: November 2024

AbstractBackgroundThere is currently a lack of easy-to-use tools for assessing the severity of cardiogenic shock (CS) patients. This study aims to develop a nomogram for evaluating severity in CS patients regardless of the underlying cause.Methods and ResultsThe MIMIC-IV database was used to identify 1923 CS patients admitted to the ICU. A multivariate Cox model was developed in the training cohort (70%) based on LASSO regression results. Factors such as age, systolic blood pressure, arterial oxygen saturation, hemoglobin, serum creatinine, blood glucose, arterial pH, arterial lactate, and norepinephrine use were incorporated into the final model. This model was visualized as a Cardiogenic Shock Survival Nomogram (CSSN) to predict 30-day survival rates. The model’s c-statistic was 0.75 (95% CI 0.73–0.77) in the training cohort and 0.73 (95% CI 0.70– 0.77) in the validation cohort, demonstrating good predictive accuracy. The AUC of the CSSN for 30-day survival probabilities was 0.76 in the training cohort and 0.73 in the validation cohort. Calibration plots showed strong concordance between predicted and actual survival rates, and decision curve analysis (DCA) affirmed the model’s clinical utility. The CSSN outperformed the Cardiogenic Shock Score (CSS) in various metrics, including c-statistic, time-dependent ROC, calibration plots, and DCA (c-statistic: 0.75 versus 0.72; AUC: 0.76 versus 0.73). Sensitivity analyses confirmed the model’s robustness across both AMI-CS and non-AMI-CS subgroups.ConclusionsThe CSSN was developed to predict 30-day survival rates in CS patients irrespective of the underlying cause, showing good performance and potential clinical utility in managing CS.CLINICAL PERSPECTIVEWhat Is New?This study presents the development and validation of a novel nomogram, the Cardiogenic Shock Survival Nomogram (CSSN), specifically designed for predicting 30-day survival rates in patients with cardiogenic shock (CS), regardless of the underlying cause.Utilizing a large cohort from the MIMIC-IV database, this research integrates multiple available clinical factors—such as age, systolic blood pressure, arterial oxygen saturation, hemoglobin levels, serum creatinine, blood glucose, arterial pH, arterial lactate, and norepinephrine use—into a convenient and easy to use the prognostic tool.What Are the Clinical Implications?Enhanced Decision-Making: Clinicians can utilize the CSSN as a practical tool to assess the severity and prognosis of CS patients, enabling more informed decision-making regarding treatment strategies.Improved Risk Stratification: By incorporating easily obtainable clinical parameters such as age, systolic blood pressure, arterial oxygen saturation, and biochemical markers, the CSSN provides a straightforward method for risk stratification, facilitating the identification of high-risk patients who may benefit from more intensive monitoring or advanced therapeutic interventions.
Trends in Prescription Fills for Blood Pressure-Elevating and Antihypertensive Medications, 2017–2023
Authors: Kumar Ashutosh , Therrien Nicole L. , Ogwuegbu John I. , Lee Jun Soo , Wall Hilary K. , Flack John M. , Jackson Sandra L. 
Published: November 2024

AbstractBackgroundMany medications can have blood pressure (BP)-elevating effects, which might negatively impact BP control among persons with hypertension. This study examines trends in prescription fills for BP-elevating and antihypertensive medications, individually and concurrently, among US individuals.MethodsQuarterly trends of concurrent and individual fills for BP-elevating and antihypertensive medications were reported using the national sample from IQVIA’s Total Patient Tracker database, covering 94% of all retail prescription fills in the US. We identified 1,387 products containing BP-elevating medications and 240 products containing antihypertensive medications. Percentage change from Q1/2017 and average quarterly percent change from Joinpoint regression were used to present trends overall and by sex and age group (0–17, 18–44, 45–64, 65–74, and ≥75 years).ResultsDuring 2017–2023, fills remained stable for BP-elevating medications alone and increased for antihypertensive medication alone (9.5% increase; from 10.1% to 11.0%; p<0.001). Concurrent fills for antihypertensive and BP-elevating medications increased by 15.9% (from 5.4% to 6.2%; p<0.001). Prescription fills for BP-elevating medications were higher among adult women compared to men; among women aged 18 to 44 years, this was primarily due to the use of combined oral contraceptives. In Q4/2023, prescription fills for BP-elevating medications were most common among those aged 65–74 years (females=30.7% vs males = 20.4%).ConclusionsThese results provide the first national trends in concurrent prescription fills for BP-elevating and antihypertensive medications, indicating an increasing trend. Our findings might inform clinicians in their decision-making regarding medication selection for patients with hypertension.
Lipid composition differentiates ferroptosis sensitivity betweenin vitroandin vivosystems
Authors: Park Vivian S. , Pope Lauren E. , Ingram Justin , Alchemy Grace A. , Purkal Julie , Andino-Frydman Eli Y. , Jin Sha , Singh Sanjana , Chen Anlu , Narayanan Priya , Kongpachith Sarah , Phillips Darren C. , Dixon Scott J. , Popovic Relja 
Published: November 2024

ABSTRACTFerroptosis is a regulated non-apoptotic cell death process characterized by iron-dependent lipid peroxidation. This process has recently emerged as a promising approach for cancer therapy. Peroxidation of polyunsaturated fatty acid-containing phospholipids (PUFA-PLs) is necessary for the execution of ferroptosis. Ferroptosis is normally suppressed by glutathione peroxidase 4 (GPX4), which reduces lipid hydroperoxides to lipid alcohols. Some evidence indicates that GPX4 may be a useful target for drug development, yet factors that govern GPX4 inhibitor sensitivityin vivoare poorly understood. We find that pharmacological and genetic loss ofGPX4function was sufficient to induce ferroptosis in multiple adherent (“2D”) cancer cell cultures. However, reducing GPX4 protein levels did not affect tumor xenograft growth when these cells were implanted in mice. Furthermore, sensitivity to GPX4 inhibition was markedly reduced when cells were cultured as spheroids (“3D”). Mechanistically, growth in 3D versus 2D conditions reduced the abundance of PUFA-PLs. 3D culture conditions upregulated the monounsaturated fatty acid (MUFA) biosynthetic gene stearoyl-CoA desaturase (SCD). SCD-derived MUFAs appear to protect against ferroptosis in 3D conditions by displacing PUFAs from phospholipids. Various structurally related long chain MUFAs can inhibit ferroptosis through this PUFA-displacement mechanism. These findings suggest that growth-condition-dependent lipidome remodeling is an important mechanism governing GPX4 inhibitor effects. This resistance mechanism may specifically limit GPX4 inhibitor effectivenessin vivo.