bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sociodemographic and clinical risk factors for suicidal ideation and suicide attempt in functional/dissociative seizures and epilepsy: a large cohort study
Authors: Faiman Irene , Hodsoll John , Jasani Iman , Young Allan H. , Shotbolt Paul 
Published: November 2023

ABSTRACTObjectiveTo identify risk factors for first episodes of suicidal ideation and suicide attempt in people with functional/dissociative seizures (FDS) or epilepsy.MethodsRetrospective cohort study from the UK’s largest tertiary mental health care provider, with linked national admission data from the Hospital Episode Statistics (HES). Participants were 2383 people with a primary or secondary diagnosis of FDS or epilepsy attending between 01/01/2007 and 18/06/2021. Outcomes were a first report of suicidal ideation and a first hospital admission for suicide attempt (ICD-10 X60-X84). Demographic and clinical risk factors were assessed using multivariable bias-reduced binomial-response generalised linear models.ResultsIn both groups, ethnic minorities had significantly reduced odds of hospitalisations following a suicide attempt (OR: 0.45 – 0.49). Disorder-specific risk factors were gender, age, and comorbidity profile. In FDS, both genders had similar risk of suicidality; younger age was a risk factor for both outcomes (OR: 0.16 – 1.91) and a diagnosis of Depression or Personality Disorders was associated with higher odds of reporting suicidal ideation (OR: 1.91 and 3.01 respectively). In epilepsy, females had higher odds of being hospitalised following suicide attempt (OR: 1.64). Age had a quadratic association with both outcomes (OR: 0.88 – 1.06). A Substance Abuse Disorder was associated to higher suicidal ideation (OR: 2.67) whilst Developmental Disorders lowered the risk (OR: 0.16 – 0.24).ConclusionsThis is the first study systematically reporting risk factors for suicidality in people with FDS. Results for the large epilepsy cohort complement previous studies and will be useful in future meta-analyses.KEY MESSAGE BOXWhat is already known on this topicPeople with epilepsy and people with functional/dissociative seizures (FDS) are at elevated risk of suicideIdentification of risk factors for suicidal ideation and suicide attempt in high-risk groups is essential to inform risk prevention strategiesWhat this study addsSeveral factors are associated with suicidality in FDS, including age, ethnicity, comorbid Depression and Personality Disorders.In epilepsy, suicidality is associated with age, gender, ethnicity, comorbid Substance Misuse Disorder and Developmental Disorders.How this study might affect research, practice or policyWhilst disorder-specific factors will be useful to identify groups at higher risk in clinical settings, general risk factors can be target of population-based preventive strategies.
A Modified Mediterranean Ketogenic Diet mitigates modifiable risk factors of Alzheimer’s Disease: a serum and CSF-based metabolic analysis
Authors: Schweickart Annalise , Batra Richa , Neth Bryan J. , Martino Cameron , Shenhav Liat , Zhang Anru R. , Shi Pixu , Karu Naama , Huynh Kevin , Meikle Peter J. , Schimmel Leyla , Dilmore Amanda Hazel , Blennow Kaj , Zetterberg Henrik , Blach Colette , Dorrestein Pieter C , Knight Rob ,   Alzheimer’s Gut Microbiome Project Consortium, Craft Suzanne , Kaddurah-Daouk Rima , Krumsiek Jan 
Published: November 2023

AbstractAlzheimer’s disease (AD) is influenced by a variety of modifiable risk factors, including a person’s dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD’s metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean-ketogenic diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.
Housing insecurity and health: a marginal structural model analysis of the impact of housing payment problems and forced moves on mental health, sleep and hypertension in UK adults, 2009-2019
Authors: Mason Kate , Alexiou Alexandros , Li Ang , Taylor-Robinson David 
Published: November 2023

ABSTRACTBackgroundHousing insecurity is an escalating problem in the UK. Limited empirical evidence exists from which to draw reliable causal inferences about the impact of insecure housing on health. Using nationally representative panel data and causally focussed methods, we examined the effect of insecure housing on mental health, sleep disturbance and cardiovascular health, during a period of government austerity.MethodsWe used longitudinal survey data (2009-2019) from the UK Household Longitudinal Study. Health outcomes included probable common mental disorder; sleep disturbance due to worry; and new diagnoses of hypertension. The primary exposure was housing payment problems in the past 12 months. Using doubly robust marginal structural models) with inverse probability of treatment weights, we estimated absolute and relative health effects of housing payment problems, and population attributable fractions. We performed stratified analyses to assess potentially heterogeneous impacts across the population, and the potential modifying effects of austerity measures in the UK.FindingsThe average absolute effect of housing payment problems was a 2.5 percentage point increased risk of experiencing a common mental disorder (95% CI 1.1%, 3.8%) and 2.0% increased risk of sleep disturbance (95% CI 0.7%, 3.3%). Effects were larger among renters, younger people, less educated, and households with children. Effects were also larger among people living in areas most affected by austerity-related cuts to housing support services. Evidence for a cardiovascular health impact was weak (95% CI -0.1%, 1.2%).InterpretationHousing payment problems were associated with worse mental health and sleep disturbance in a large UK sample. Households at risk of falling into rent or mortgage arrears need more support, especially in areas where housing services have been diminished. Rapid and substantial investment is needed to improve supply of social and affordable housing.
Sex differences in health-related quality of life and poverty risk among older people living with HIV in Spain: a cross-sectional study
Authors: Nuño Néstor , Martínez Alberto , Martínez Susana , Cobos Marta , Hernández Juan Sebastián , Polo Rosa 
Published: November 2023

AbstractBackgroundCurrent antiretroviral therapies have increased the life expectancy of people living with HIV (PLHIV). There is, however, limited evidence regarding the health-related quality of life (HRQoL) and living conditions of older people living with HIV (OPLHIV) in Spain.MethodsWe implemented a self-administered online questionnaire to identify sex differences in HRQoL and poverty risk among Spanish OPLHIV (PLHIV ≥50 years). Participants were contacted through non-governmental organisations. We used the standardised WHOQoL-HIV BREF questionnaire and the Europe 2020 guidelines to estimate HRQoL and poverty risk respectively. The statistical analysis included multivariable generalised linear models with potential confounding variables and robust estimates.ResultsThe study included 247 OPLHIV (192 men and 55 women). On the WHOQoL-HIV BREF questionnaire, men scored higher on 84% of items and in all six domains. Women had significantly lower HRQoL in five domains: physical health (β: −1.5; 95% CI: −2.5, −0.5;p: 0.002), psychological health (β: −1.0; 95% CI: −1.9, −0.1;p: 0.036), level of independence (β: −1.1; 95% CI: −1.9, −0.2;p: 0.019), environmental health (β: −1.1; 95% CI: −1.8, −0.3;p: 0.008), and spirituality/personal beliefs (β: −1.4; 95% CI: −2.5, −0.3;p: 0.012). No statistical differences were found in the domain of social relations. Poverty risk was considerable for both men (30%) and women (53%), but women were significantly more likely to experience it (OR: 2.9; 95% CI: 1.3, 6.5;p: 0.009).ConclusionThe aging of PLHIV is a public health concern. Our findings indicate that HRQoL and poverty risk among Spanish OPLHIV differ significantly by sex. Spain should, therefore, implement specific policies and interventions to address OPLHIV needs. The strategies must place a high priority on the reduction of sex inequalities in HRQoL and the enhancement of the structural conditions in which OPLHIV live.
Investigating Dopaminergic Abnormalities in Psychosis with Normative Modelling and Multisite Molecular Neuroimaging
Authors: Giacomel A. , Martins D. , Nordio G. , Easmin R. , Howes O. , Selvaggi Pierluigi , Williams S.C.R. , Turkheimer F. , De Groot M. , Dipasquale O. , Veronese M. ,   the FDOPA PET imaging working group
Published: November 2023

AbstractMolecular neuroimaging techniques, like PET and SPECT, offer invaluable insights into the brain’s in-vivo biology and its dysfunction in neuropsychiatric patients. However, the transition of molecular neuroimaging into diagnostics and precision medicine has been limited to a few clinical applications, hindered by issues like practical feasibility and high costs. In this study, we explore the use of normative modelling (NM) for molecular neuroimaging to identify individual patient deviations from a reference cohort of subjects. NM potentially addresses challenges such as small sample sizes and diverse acquisition protocols that are typical of molecular neuroimaging studies. We applied NM to two PET radiotracers targeting the dopaminergic system ([11C]-(+)-PHNO and [18F]FDOPA) to create a normative model to reference groups of controls. The models were subsequently utilized on various independent cohorts of patients experiencing psychosis. These cohorts were characterized by differing disease stages, treatment responses, and the presence or absence of matched controls. Our results showed that patients exhibited a higher degree of extreme deviations (∼3-fold increase) than controls, although this pattern was heterogeneous, with minimal overlap in extreme deviations topology (max 20%). We also confirmed the value of striatal [18F]FDOPA signal to predict treatment response (striatal AUC ROC: 0.77-0.83). Methodologically, we highlighted the importance of data harmonization before data aggregation. In conclusion, normative modelling can be effectively applied to molecular neuroimaging after proper harmonization, enabling insights into disease mechanisms and advancing precision medicine. The method is valuable in understanding the heterogeneity of patient populations and can contribute to maximising cost efficiency in studies aimed at comparing cases and controls.
Baseline tumor-infiltrating lymphocyte patterns and response to immune checkpoint inhibition in metastatic cutaneous melanoma
Authors: van Duin Isabella A.J. , Schuiveling Mark , ter Maat Laurens S. , van Amsterdam Wouter A.C. , van den Berkmortel Franchette , Boers-Sonderen Marye , de Groot Jan Willem B. , Hospers Geke A.P. , Kapiteijn Ellen , Labots Mariette , Piersma Djura , Schrader Anne M.R. , Vreugdenhil Gerard , Westgeest Hans , Veta Mitko , Blokx Willeke A.M. , van Diest Paul J. , Suijkerbuijk Karijn P.M. 
Published: November 2023

AbstractIntroductionThe presence of tumor-infiltrating lymphocytes (TILs) in melanoma has been linked to survival. Their predictive capability for immune checkpoint inhibition (ICI) response remains uncertain. Therefore, we investigated the association between treatment response and TILs in the largest cohort to date and analyzed if this association was independent of known clinical predictors of response.MethodsIn this multicenter cohort study, patients who received first-line anti-PD1 ± anti-CTLA4 for advanced cutaneous melanoma were identified. TILs were scored as absent, non-brisk or brisk on hematoxylin and eosin (H&E) slides of primary melanoma and pre-treatment metastases. Scoring systems evaluating the infiltration and intensity patterns (‘MIA-score’) and the percentage of stromal TILs were also evaluated. The primary outcome was objective response rate (ORR), with PFS and OS being secondary outcomes. Univariable and multivariable logistic regression and Cox proportional hazard regression analyses were performed, adjusting.for age, sex, disease stage, ICI type, BRAF mutation, lactate dehydrogenase (LDH) level and WHO performance score.ResultsMetastatic melanoma specimens were available for 650 patients and primary specimens from 565 patients.. No association was found between TILs in primary melanoma specimens and response. In metastatic specimens, patients with non-brisk TILs (aOR 1.56, 95% CI 1.06-2.29) and brisk TILs (aOR 3.28, 95% CI 1.72-6.56) had a higher probability of response, longer median PFS (9.2 and 19.4 vs. 6.5months [p=0.009]) and median OS (49.5 and 40.9 vs 21.3 months [p=0.007]) when compared to absent TILs. Similar results were noted using the MIA- and stromal TIL scores.ConclusionIn advanced melanoma patients, TIL patterns on H&E slides of pre-treatment metastases are associated with ICI response. This is independent of known clinical predictors. TILs are easily scored on readily available H&Es, which facilitates the use of this biomarker for ICI outcomes in clinical practice.
Causality between Peripheral Immune Cell Counts and Membranous Nephropathy: A Bidirectional Mendelian Randomization Study
Authors: Su Zhihang , Wen Liu , Feng Xiangning , Wan Qijun 
Published: November 2023

AbstractBackgroundMembranous nephropathy (MN), an autoimmune disease, has not yet been fully elucidated regarding its relationship with immune cells.MethodsAs a primary method in this Mendelian randomization (MR) analysis, we employed the Inverse Variance Weighted (IVW), Wald Ratio (WR), Steiger filtering, Weighted Median, Weighted mode, MR-Egger, Mendelian randomization pleiotropy residual sum, and outlier (MR-PRESSO) and Leave-one-out sensitivity test. Reverse MR analysis was utilized to investigate whether MN affects immune cells.ResultsAfter False Discovery Rate multiple correction (threshold was 10%), it was determined that CD45RA+CD8+T cell (IVW OR=1.074, 95%CI: 1.034-1.114, P=0.0001, PFDR=0.036), Effector Memory CD8+T cell (IVW OR=0.929, 95%CI: 0.895-0.964, P=0.0001, PFDR=0.036), HLA DR+CD8+T cell (IVW OR=0.921, 95%CI: 0.884-0.960, P=0.0001, PFDR=0.036) are significantly affected by MN. CD28+CD45RA-CD8+T cell (WR OR=0.513, 95%CI: 0.357-0.793, P=0.0003, PFDR=0.061), CD8 on Terminally Differentiated CD8+T cell (WR OR=0.378, 95%CI: 0.219-0.652, P=0.0005, PFDR=0.061), and HVEM on Effector Memory CD4+T cell (WR OR=0.378, 95%CI: 0.219-0.652, P=0.0005, PFDR=0.065), among others, are considered immune cells that possess protective factors against MN. However, HLA DR on CD33+HLA DR+CD14-(WR OR=1.910, 95%CI: 1.269-2.876, P=0.002, PFDR=0.065), CD80 on granulocyte (WR OR=2.606, 95%CI: 1.417-4.792, P=0.002, PFDR=0.065), and CD62L-plasmacytoid Dendritic Cell (WR OR=1.508, 95%CI: 1.138-1.998, P=0.004, PFDR=0.071) pose a risk to MN. When increased by one standard deviation in peripheral blood, these immune cells positively or negatively impact the risk of MN with an odds ratio (OR).ConclusionsThe MR analysis unveiled the association between immune cells and MN. We have deepened our understanding of the pathogenic mechanisms linking MN and immune cells and also identified new targets for immunotherapy in MN.
Long-term survival, psychiatric, physiological, and functional outcomes of critically ill patients requiring prolonged mechanical ventilation: a systematic review
Authors: Ludski Jarryd , Honeywill Conor 
Published: November 2023

ABSTRACTPurposeInvasive mechanical ventilation is utilized in over 50% of Australian Intensive Care Unit patients, with rates increasing world-wide. Prolonged mechanical ventilation is associated with increased length of hospital stay and in-hospital mortality compared with patients ventilated under the time threshold. Previous studies have highlighted mortality rates, but much remains unknown regarding the long-term physiological, functional, and psychiatric effects of prolonged mechanical ventilation. With a greater understanding of these outcomes, models of care can be formulated to reduce long-term morbidity.MethodsMedline, CINAHL and the Cochrane Library were searched between 1998 and March 2019, for PMV, patients in ICU and long-term outcomes. Included studies had patients, that received greater than or equal to 14 days of IMV. Primary outcome was mortality rates with secondary outcomes clustered into physiological, functional, and psychiatric outcomes.Results1057 studies were identified, with 24 included. 73% of PMV patients were discharged from ICU, with mortality rates of 57% and 69% at 12 and 48 months. 30.2% were discharged home, 25% developed new onset ventilator acquired pneumonia and up to 39% experienced psychiatric complications.ConclusionDespite a high proportion of patients surviving to hospital discharge, subsequent outcomes are extremely poor for patients that require PMV.
Strength of spatial correlation between structural brain network connectivity and brain-wide patterns of proto-oncogene and neural network construction gene expression is associated with diffuse glioma survival
Authors: Kesler Shelli R. , Harrison Rebecca A. , Schultz Alexa De La Torre , Michener Hayley , Bean Paris , Vallone Veronica , Prinsloo Sarah 
Published: November 2023

AbstractLike other forms of neuropathology, gliomas appear to spread along neural pathways. Accordingly, our group and others have previously shown that brain network connectivity is highly predictive of glioma survival. In this study, we aimed to examine the molecular mechanisms of this relationship via imaging transcriptomics. We retrospectively obtained presurgical, T1-weighted MRI datasets from 669 adult patients, newly diagnosed with diffuse glioma. We measured brain connectivity using gray matter networks and coregistered these data with a transcriptomic brain atlas to determine the spatial co-localization between brain connectivity and expression patterns for 14 proto-oncogenes and 3 neural network construction genes. We found that all 17 genes were significantly co-localized with brain connectivity (p < 0.03, corrected). The strength of co-localization was highly predictive of overall survival in a cross-validated Cox Proportional Hazards model (mean area under the curve, AUC = 0.68 +/- 0.01) and significantly (p < 0.001) more so for a random forest survival model (mean AUC = 0.97 +/- 0.06). Bayesian network analysis demonstrated direct and indirect causal relationships among gene-brain co-localizations and survival. Gene ontology analysis showed that metabolic processes were overexpressed when spatial co-localization between brain connectivity and gene transcription was highest (p < 0.001). Drug-gene interaction analysis identified 84 potential candidate therapies based on our findings. Our findings provide novel insights regarding how gene-brain connectivity interactions may affect glioma survival.
Exploring the association between cannabis and opioid use among adults in Washington State: Estimates from a Cross-Sectional Survey
Authors: Abousamra Eslam , Andres Gabriel , Litman Alyson J 
Published: November 2023

ABSTRACTIntroductionCannabis and opioids are commonly used for pain management. However, studies examining the association between use of both substances conflict. Furthermore, disruptions to healthcare services and access due to COVID-19 may have affected opioid use in favor of cannabis because of accessibility. Our objective was to examine associations between cannabis and opioid use in Washington State (WA), COVID-19’s impact on these associations, and the association between frequency of cannabis use and misuse of opioids.MethodsWe pooled cross-sectional data from 2019 and 2021 WA Behavior Risk Factors Surveillance Systems surveys to examine associations between cannabis use in the past 30 days and prescription or non-prescription opioid use and misuse during the past 12 months among adults 18 and older. Survey-weighted adjusted prevalence ratios were estimated using multivariable Poisson regression. A proportion test and adjusted trend test were used to examine trends between cannabis use frequency (no use, 1-5 days, 6-9 days, 10-29 days, and 30 days) and opioid misuse among those reported opioid use.ResultsAmong 25,540 participants, the prevalence of opioid use was 19.2% among those who used cannabis and 13.8% among those who did not use cannabis (aPR=1.32; 95%CI: 1.20,1.46). COVID-19 did not modify the association between cannabis and opioid use. Among those who used opioids (n=2,168), daily cannabis use was associated with higher opioid misuse prevalence (aPR=2.64; 95% CI: 1.71,4.10), though less than daily use was not.ConclusionCannabis and opioid use were positively associated. Our findings emphasize the need for cautious policy decisions on cannabis regulations. Promoting cannabis use may not correlate with a reduction in other substance misuse. Further research is warranted to explore patterns of cannabis and opioid misuse.