bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between early-life mental health and abnormal sleep duration in midlife: findings from a prospective cohort study in Great Britain
Authors: Metherell Thomas E. , Ploubidis George B. , Moreno-Agostino Darío 
Published: December 2023

AbstractObjectivesTo quantify the association between the state of mental health in childhood and sleep duration at age 46-48 in the 1970 British Cohort Study (BCS70).DesignBCS70 is a prospective birth cohort study of a population-representative sample.SettingData collection was conducted in participants’ homes across Great Britain.ParticipantsAll individuals born in one week in April 1970 and resident in the UK are eligible to take part, including those born outside the UK who subsequently immigrated. The study has more than 17,000 participants, of whom 8,581 responded at the last available sweep at age 46-48.Main outcome measuresAverage nightly sleep duration at age 46-48, as assessed by five separate methods: self-report, inference from a sleep diary and three algorithms used to process accelerometry data collected using a thigh-worn activPAL™ 3 device.ResultsAll seven measures of childhood mental ill-health were positively associated with abnormal self-reported sleep duration. Five were associated with abnormal diary-derived estimates and four were associated with abnormal estimates from an accelerometry-based algorithm. Strengths of associations vary. Adjusting for adult mental health symptoms partially attenuated the associations with self-reported sleep duration but not with the more objective estimates.ConclusionsPoor mental health in childhood is associated with abnormal nightly sleep duration at age 46-48. Post-hoc analyses suggest that this association might not be entirely mediated by poor mental health in adulthood. Future research should attempt to replicate these results in diverse samples and assess whether stronger interventions in early-life mental health might have substantial and long-lasting positive impacts on sleep.SummaryWhat is already known on this topicThe state of a person’s mental health in their early life is associated with a range of adult health outcomes.There exists a bidirectional and multifaceted relationship between the state of a person’s mental health and their sleep.The longitudinal association between early-life mental health and sleep in adulthood was not well understood.What this study addsOur study demonstrates that early-life mental health is associated with an abnormal average nightly sleep duration at age 46 in this sample.Associations between early-life mental health and abnormal average nightly sleep at age 46 were not fully mediated by adult mental health.
Socioeconomic inequities in care experienced by women with breast cancer in England: An intersectional cross-sectional study
Authors: de Mesa Mar Estupiñán Fdez , Marcu Afrodita , Ream Emma , Whitaker Katriina L 
Published: December 2023

AbstractPurposeGuided by the intersectionality framework, we examined the differential in breast cancer care experience across population subgroups in England.MethodsSecondary data analysis using the 2017/2018 English National Cancer Patient Experience Survey (NCPES). We applied disaggregated descriptive statistics (mean, standard errors, 95% confidence interval) to analyse 26,030 responses from female breast cancer patients to a question relating to overall care experience categorised by age, ethnicity, and sexual orientation in their intersection with deprivation status. We then applied multivariable logistic regression (odds ratios, 95% confidence intervals) to ascertain the relationship of reporting a positive care experience adjusting for patient, clinical, and trust-level factors.ResultsPoorer breast cancer care experience was mostly reported by the most deprived younger and minoritised ethnic groups. Similar findings were observed in adjusted multivariable analyses. Younger respondents were less likely than older patients to rate their care favourably. Pakistani, Indian, Chinese, and Black African women were less likely than White British women to rate their care favourably. Respondents from the most socioeconomic deprived backgrounds were less likely than the most affluent ones to rate their care favourably.ConclusionThere is evidence of inequity in overall cancer care experience among female breast cancer patients in England, particularly among women living at the specific intersection of age, ethnicity and socioeconomic position. Future research is necessary to understand the mechanisms underlying breast cancer inequities. Policymakers, commissioners, and providers should consider the existence of multiple forms of marginalization to inform improvement initiatives targeting patients at higher risk of vulnerability.
Physiotherapists’ use of aerobic exercise during stroke rehabilitation: a qualitative study using chart-stimulated recall
Authors: Barzideh Azadeh , Devasahayam Augustine Joshua , Tang Ada , Inness Elizabeth , Marzolini Susan , Munce Sarah , Sibley Kathryn M , Mansfield Avril 
Published: December 2023

ABSTRACTPurposeWe aimed to explore the factors that affect physiotherapists’ use of AE during stroke rehabilitation for people with stroke.Material and methodsWe conducted a qualitative descriptive study using thematic analysis informed by a pragmatic worldview. Physiotherapists attended one on one semi-structured interviews to answer some general questions about aerobic exercise and then discussed the charts of their 4 most recently discharged patients. Both deductive and inductive coding were used for analysis.ResultsTen physiotherapists participated. Healthcare policies and limited resources were mostly discussed in general questions while specific profiles of patients with stroke, their goals and preferences were mostly discussed in patient specific questions. Three themes were identified:1) physiotherapists’ perspectives and practices around aerobic exercise; 2) profiles of people with stroke, as well as their goals and their exercise modality preferences; and 3) influence of health system priorities, rehabilitation intensity policy, and resources.ConclusionsPhysiotherapists’ behaviours regarding use of aerobic exercise for people with stroke are not a binary behaviour of prescribing or not prescribing aerobic exercise. Their behaviours are better understood on a continuum; between two ends of not prescribing aerobic exercise, and prescribing aerobic exercise with defined intensity, duration, and frequency.
Types and timing of trauma exposure across the life course and maternal hypertension
Authors: Stanhope Kaitlyn K , Michopoulos Vasiliki , Powers Abigail , Boulet Sheree L , Kramer Michael R , Suglia Shakira F 
Published: December 2023

AbstractObjectiveTo estimate associations between types and timing (first occurrence and time since) of trauma exposure and hypertension experienced during pregnancy in a safety-net hospital in Atlanta, Georgia.MethodsParticipants completed a 14-item trauma screener. We linked that information to data from the medical record on hypertension (inclusive of chronic hypertension, gestational hypertension, or preeclampsia). We fit logistic regression models and used the estimates to calculate risk ratios for each trauma type and each critical window (0-9 years, 10-19, and 20+). We fit unadjusted models and adjusted for age, parity, and education.ResultsWe included 704 individuals with a delivery within 12 months of screening. The majority (94%, 661) reported at least one traumatic event, most commonly witnessing violence (79.4%). Overall, 18% experienced gestational hypertension, 10.8% chronic hypertension, and 11.9% preeclampsia. Among individuals who reported trauma, 31.5% screened positive for probable posttraumatic stress disorder and 30.9% for probable depression compared to 0 and 2.3% among those without reported trauma. No trauma type (violence, witnessing violence, non-interpersonal, or sexual assault) was associated with increased hypertensive risk, regardless of timing. Similarly, time between trauma and delivery (0-3 years, 3-10 years, 10+ years) was not associated with increased hypertensive risk.ConclusionsIn this sample with a high trauma and hypertension burden, trauma was not associated with elevated risk of hypertension during pregnancy, despite a high burden of PTSD and depressive symptoms among people with trauma exposure. Future research should consider how community-level exposure may modify the impact of trauma on adverse pregnancy outcomes.
Integrated bioinformatics and wet-lab analysis revealed prominent inflammatory genes of Extracellular Matrix as prognostic biomarkers in patients with advance IBD requiring early surgery
Authors: Dehghani Mahmoudabadi Farzad , Khanabadi Binazir 
Published: December 2023

AbstractBackgroundThe number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Due to the fact that at the age of 20 to 30 years, this autoimmune disease is very common; Investigating and identifying prognostic biomarkers in advanced IBD is very important; Because according to the identification of these biomarkers, patients who need early surgery can be nominated and undergo surgery without wasting time and treatment costs. In this study, with the aim of identifying effective biomarkers involved in the inflammatory part of extracellular matrix (ECM) in the early surgery of IBD, separately from Crohns disease and ulcerative colitis.MethodIn this study, we examined 50 patients in both patient groups as well as the normal group. The expression of the nominated genes MASP2, DKC1, HNF4A, and STAT3 was analyzed using quantitative polymerase chain reaction (Q-PCR) and relative quantification was determined using the 2-ΔΔCtmethod. ROC curve analysis was performed to compare IBD (UC & CD) and normal for the investigated genes. The correlation between adhesion molecule gene expression and immunophenotype was analyzed. Also we comprehensively analyzed the genetic alteration, prognostic value and gene regulatory networks using multiple databases.ResultThe obtained results showed that MASP2 and DKC1 genes were significantly expressed in advanced UC patients, as well as HNF4A and STAT3 in advanced CD patients.ConclusionIt can be stated that the biomarker panel MASP2, DKC1, HNF4A, and STAT3 related to them have a significant prognostic role in the candidates of IBD patients for early surgery.Graphical abstract
Genome-wide CRISPRi Screen in Human iNeurons to Identify Novel Focal Cortical Dysplasia Genes
Authors: Tidball Andrew M. , Luo Jinghui , Clayton Walker J. , Takla Taylor N. , Carvill Gemma L. , Parent Jack M. 
Published: December 2023

AbstractFocal cortical dysplasia (FCD) is a common cause of focal epilepsy that typically results from brain mosaic mutations in the mTOR cell signaling pathway. To identify new FCD genes, we developed anin vitroCRISPRi screen in human neurons and used FACS enrichment based on the FCD biomarker, phosphorylated S6 ribosomal protein (pS6). Using whole-genome (110,000 gRNAs) and candidate (129 gRNAs) libraries, we discovered 12 new genes that significantly increase pS6 levels. Interestingly, positive hits were enriched for brain-specific genes, highlighting the effectiveness of using human iPSC-derived induced neurons (iNeurons) in our screen. We investigated the signaling pathways of six candidate genes:LRRC4,EIF3A, TSN, HIP1, PIK3R3,andURI1. All six genes increased phosphorylation of S6. However, only two genes,PIK3R3andHIP1,caused hyperphosphorylation more proximally in the AKT/mTOR/S6 signaling pathway. Importantly, these two genes have recently been found independently to be mutated in resected brain tissue from FCD patients, supporting the predictive validity of our screen. Knocking down each of the other four genes (LRRC4, EIF3A, TSN, and URI1) in iNeurons caused them to become resistant to the loss of growth factor signaling; without growth factor stimulation, pS6 levels were comparable to growth factor stimulated controls. Our data markedly expand the set of genes that are likely to regulate mTOR pathway signaling in neurons and provide additional targets for identifying somatic gene variants that cause FCD.Significance StatementFocal cortical dysplasia (FCD) is a common cause of focal epilepsy due to somatic variants in mTOR pathway genes in FCD brain tissue. Unbiased sequencing to identify novel FCD genes is challenging since these variants are often in a small subset of neurons. To overcome this challenge, we used anin vitrogenetic screen in human neurons using an FCD biomarker, uncovering genes that increase neuronal mTOR signaling when their expression is lost. Two candidate genes were mutated in patient FCD brain tissues in a recent study, supporting a causative role for these genes in FCD. Our work suggests gene candidates for somatic variant analysis in FCD tissue and indicates added value for genetic screening in neurons over cell lines.
Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative
Authors: Huang Zeyu , Bucklin Mary A. , Guo Weihua , Martin John T. 
Published: December 2023

AbstractThe prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual’s diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.
Genetic implication of prenatal GABAergic and cholinergic neuron development in susceptibility to schizophrenia
Authors: Cameron Darren , Vinh Ngoc-Nga , Prapaiwongs Parinda , Perry Elizabeth A. , Walters James T. R. , Li Meng , O’Donovan Michael C. , Bray Nicholas J. 
Published: December 2023

AbstractBackgroundThe ganglionic eminences are fetal-specific structures that give rise to gamma- aminobutyric acid (GABA)- and acetylcholine- releasing neurons of the forebrain. Given evidence for GABAergic and cholinergic disturbances in schizophrenia, as well as an early neurodevelopmental component to the disorder, we tested the potential involvement of developing cells of the ganglionic eminences in mediating genetic risk for the condition.Study DesignWe combined data from a recent large-scale genome-wide association study of schizophrenia with single cell RNA sequencing data from the human ganglionic eminences to test enrichment of schizophrenia risk variation in genes with high expression specificity for particular developing cell populations within these structures. We additionally performed the single nuclei Assay for Transposase-Accessible Chromatin with Sequencing (snATAC-Seq) to map potential regulatory genomic regions operating in individual cell populations of the human ganglionic eminences, using these to additionally test for enrichment of schizophrenia common genetic variant liability and to functionally annotate non-coding variants associated with the disorder.Study ResultsSchizophrenia common variant liability was enriched in genes with high expression specificity for developing neuron populations that are predicted to form dopamine D1 and D2 receptor expressing GABAergic medium spiny neurons of the striatum, cortical somatostatin-positive GABAergic interneurons, calretinin-positive GABAergic neurons and cholinergic neurons. Consistent with these findings, schizophrenia genetic risk was also concentrated in predicted regulatory genomic sequence mapped in developing neuronal populations of the ganglionic eminences.ConclusionsOur study provides evidence for a role of prenatal GABAergic and cholinergic neuron development in later susceptibility to schizophrenia.
Increased Donor Inhibitory KIR Are Associated with Reduced GVHD and Improved Survival Following HLA Matched Unrelated Donor HCT in Pediatric Acute Leukemia
Authors: Krieger Elizabeth , Qayyum Rehan , Toor Amir 
Published: December 2023

AbstractKiller immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after hematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity in the adult transplant setting.Pediatric acute leukemia patients were retrospectively analyzed and KIR-KIRL combinations and maximal inhibitory KIR ligand (IM-KIR) scores determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints.The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints, remained significant for relevant downstream events. KIR-KIRL combinations were significantly predictive for reduced grade 3-4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM-KIR=5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse-free survival, GRFS, and overall survival.This study demonstrates that NK cell KIR HLA interactions may be relevant to the pediatric acute leukemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in pediatric recipients with acute leukemia to optimize clinical outcomes.
Variation in ambulance pre-alert process and practice: Cross-sectional survey of ambulance clinicians
Authors: Coster Joanne , Sampson Fiona , O’Hara Rachel , Long Jaqui , Bell Fiona , Goodacre Steve 
Published: December 2023

AbstractBackgroundAmbulance clinicians use pre-alerts calls to alert emergency departments (EDs) about the arrival of critically ill patients. We explored ambulance clinician’s views and experiences of pre-alert practice and processes using a national online survey.MethodsAmbulance clinicians involved in pre-alert decision-making were recruited via ambulance trusts and social media to complete an anonymous online survey during May-July 2023. Quantitative data was analysed descriptively using SPSS and text data was analysed thematically to illustrate quantitative findings.ResultsWe included 1298 valid responses from across 10 ambulance services. Analysis identified variation in practice at all stages of the pre-alert process, including reported frequency of pre-alert (7.1% several times a shift, 14.9% once/twice a month).Most respondents reported that pre-alerts were delivered directly to the ED but 32.8% reported pre-alerting via an ambulance control room. Personal mobile phones were used to make a pre-alert by 46.8% of respondents, with 30% using ambulance radio. A third of respondents always used mnemonics (e.g. ATMIST/SBAR) but 10.2% reported not using any fixed format.Guidance used to identify patients for pre-alert varied between clinicians and ambulance service, with local ambulance service guidance most commonly used and 20% stating they never use national guidelines. Respondents reported variable understanding of appropriate conditions for pre-alert and particularly students wanted further guidance on silver trauma and medical pre-alerts.Only 29% or respondents reported receiving specific pre-alert training and 50% reported never receiving feedback. Fewer than 9% reported always being listened to and having the call taken seriously.ConclusionWe identified variation in pre-alert processes and practice that may result in inconsistent pre-alert practice and challenges for clinicians providing time critical care. Guidance and training on the use of pre-alerts may promote more consistent processes and practices.WHAT IS ALREADY KNOWN ON THIS TOPIC⍰ Pre-alerts can enable EDs to prepare for the arrival of a critically ill patient.⍰ There is variation in local ambulance trust pre-alert guidance, in terms of variation in the conditions suitable for pre-alert and alignment with the ACCE/RCEM pre-alert criteria.WHAT THIS STUDY ADDS⍰ The study identifies variation in reported practice in how pre-alerts are delivered across ambulance services and between individual clinicians.⍰ The study identifies a lack of formal training and feedback around pre-alerts and that a majority of ambulance clinicians would find additional training and feedback useful.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY⍰ Training and guidance in the use of pre-alerts could promote more consistent processes and practices⍰ Further research is needed to better understand how to improve pre-alert practice and increase consistency.
Empirical phenotyping in coupled patient+care systems: Generating low-dimensional categories for hypothesis-driven investigation of mechanically-ventilated patients
Authors: Stroh J.N. , Sottile Peter D. , Wang Yanran , Smith Bradford J. , Bennett Tellen D. , Moss Marc , Albers David J. 
Published: December 2023

AbstractBackgroundAnalyzing patient data under current mechanical ventilation (MV) management processes is essential to develop hypotheses about improvements and to understand MV consequences over time. How-ever, progress is complicated by the complexity of lung-ventilator system (LVS) interactions, patient-care and patient-ventilator heterogeneity, and a lack of classification schemes for observable behavior.MethodVentilator waveform data arise from patient-ventilator interactions within the LVS while care processes manage both patient and ventilator settings. This study develops a computational pipeline that segments these joint waveform data and care settings timeseries to phenotype the data generating process. The modular method supports many methodological choices for representing waveform data and unsuper-vised clustering.ResultsApplied to 35 ARDS patients including 8 with COVID-19, typcially 8[6.8] (median[IQR]) phenotypes capture 97[3.1]% of data using naive similarity assumptions on waveform and MV settings data. Individual phenotypes organized around ventilator mode, PEEP, and tidal volume with additional segmentation reflecting waveform behaviors. Few (<10% of) phenotype changes tie to ventilator settings, indicating considerable dynamics in LVS behaviors. Evaluation of phenotype heterogeneity reveals LVS dynamics that cannot be discretized into sub-phenotypes without additional data or alternate assumptions. Suitably normalized individual phenotypes may be aggregated into coherent groupings suitable for analysis of cohort data.ConclusionsThe pipeline is generalizable although empirical output is data- and algorithm-dependent. Further, output phenotypes compactly discretize the data for longitudinal analysis and may be optimized to resolve features of interest for specific applications.