bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global and Regional Estimate of HIV-Associated Stroke Burden: A Meta-Analysis and Population Attributable Modeling Study
Authors: Yang Yumei , Yao Xiaoqin , Liu Yuping , Zhao Jianhui , Sun Ping , Zhang Yixuan , Li Kangning , Chen Yan , Zheng Jinxin , Deng Ling , Fan Song , Ma Xiaoxiang , Guo Shujin , Shuai Ping , Wan Zhengwei 
Published: July 2023

BACKGROUND:
This study aimed to determine the correlation between human-immunodeficiency-virus (HIV) infection and stroke, as well as to estimate the global, regional, and national burden of HIV-associated stroke.

METHODS:
A registered meta-analysis was performed by searching PubMed, Embase, and Web of Science for relevant literature up to October 31, 2022. The pooled relative risk of stroke in HIV-infected people was calculated using a random-effects model. HIV prevalence and disability-adjusted life years (DALYs) datasets were obtained from the Joint United Nations Program on HIV and AIDS, and the Global Health Data Exchange, respectively. The population attributable fraction was estimated and delivered to calculate the HIV-associated DALYs of stroke from 1990 to 2019, at the global, regional, and national levels. Pearson correlation analysis were conducted to assess the correlation between the age-standardized rate or estimated annual percentage changes and the sociodemographic index.

RESULTS:
Out of 10 080 identified studies, 11 were included in this meta-analysis. Compared with individuals without HIV-infection, the pooled relative risk of stroke in HIV-infected individuals was 1.40 (95% CI, 1.18–1.65). From 1990 to 2019, the global population attributable fraction of HIV-associated stroke increased almost 3-fold, while the HIV-associated DALYs increased from 18 595 (95% CI, 7485–31 196) in 1990 to 60 684 (95% CI, 24 281–101 894) in 2019. Meanwhile, HIV-associated DALYs varied by region, with Eastern and Southern Africa having the highest value of 126 160 in 2019. Moreover, countries with middle social development index were shouldering the highest increase trend of the HIV-associated DALYs age-standardized rates.

CONCLUSIONS:
HIV-infected individuals face a significantly higher risk of stroke, and the global burden of HIV-associated stroke has increased over the past 3 decades, showing regional variations. Eastern and Southern Africa bear the highest burden, while Eastern Europe and Central Asia have seen significant growth. Health care providers, researchers, and decision-makers should give increased attention to stroke prevention and management in HIV-endemic areas.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: CRD42022367450.
Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders
Authors: Eratne Dhamidhu , Kang Matthew , Malpas Charles , Simpson-Yap Steve , Lewis Courtney , Dang Christa , Grewal Jasleen , Coe Amy , Dobson Hannah , Keem Michael , Chiu Wei-Hsuan , Kalincik Tomas , Ooi Suyi , Darby David , Brodtmann Amy , Hansson Oskar , Janelidze Shorena , Blennow Kaj , Zetterberg Henrik , Walker Adam , Dean Olivia , Berk Michael , Wannan Cassandra , Pantelis Christos , Loi Samantha M , Walterfang Mark , Berkovic Samuel F , Santillo Alexander F , Velakoulis Dennis 
Published: July 2023

Objective: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. Methods: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD ( n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). Results: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. Conclusions: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
Resilience in Newly Diagnosed Breast Cancer Women: The Predictive Role of Diurnal Cortisol and Social Support
Authors: Aizpurua-Perez Ibane , Arregi Amaia , Gonzalez David , Macia Patricia , Ugartemendia Gurutze , Labaka Ainitze , Zabalza Nerea , Perez-Tejada Joana 
Published: July 2023

Background Breast cancer is currently the most prevalent malignancy among women. Psychological resilience is an important factor that diminishes the stress-related emotional and psychosocial disturbances triggered when receiving the diagnosis. Furthermore, resilience appears to be associated with cortisol, the hormonal end-product of the hypothalamic-pituitary-adrenal axis; however, further studies are needed due to the mixed results reported. Thus, we aim to examine the predictive role of social support and cortisol in resilience among breast cancer patients. Methods A total of 132 women with primary breast cancer completed the Medical Outcomes Study-Social Support Survey (MOS-SSS) and the Resilience Scale (RS-14) and provided four salivary samples for the estimation of participants’ total daily cortisol production, for which the formula of the area under the curve with respect to the ground (AUCg) was applied. Moderation analyses were performed to study the influence of social support and AUCg on psychological resilience levels. Results The regression analyses showed a direct significant effect for the emotional support subscale of MOS-SSS on resilience and the interaction between emotional support and AUCg was also found to be statistically significant. Specifically, the conditional effect of emotional support on resilience was found to be significant at middle ( M = 3.08; p < .05) and low levels ( M = .59; p < .001) of AUCg. Conclusions Our results suggest that newly diagnosed breast cancer women with middle and low diurnal cortisol profiles may benefit more from emotional support based-interventions while women with high diurnal cortisol may need more individualized therapies.
Are clinical registries an effective tool for hospital health services to address unwarranted clinical variation?
Authors: Bessen Taryn , O’Callaghan Gerry 
Published: July 2023

Objective: To map clinical registries within the Central Adelaide Local Health Network (CALHN); and to identify how these registries were currently used for addressing unwarranted clinical variation in care. Method: An online survey was sent to all Heads of Units (HoUs) within CALHN. The survey addressed participation, type of data, reporting processes and use of the clinical registries for research, quality assurance (QA), quality improvement (QI) and clinical variation in health care. Results: Twenty-six HoUs responded (26%); 25 contributed to a clinical registry (96%); all provided data to more than one registry, but only 34.6% had an existing financial and governance arrangement with the network. Health outcomes were the most common datapoints; 77% of all data were collected manually; and 38.5% of data analysis was risk adjusted. Access to aggregated data varied across the registries; and 65.4% of reports included benchmarks and outliers. Clinical registries were used for research in 65.4%, and QA and QI in 73.1 and 69.2%, respectively. Most used external comparators and measured clinical variation, but there was marked inconsistency in the exploring clinical variation, improving care and reporting activities. Conclusion: Based on this sample, clinical registries within CALHN did not currently appear to be a reliable resource to consistently address unwarranted clinical variation but were shown to be valuable resources for research and quality initiatives at a high level. Further research is required to facilitate effective integration of clinical registries with administrative and quality systems.
Cardiac surgery risk prediction using ensemble machine learning to incorporate legacy risk scores: A benchmarking study
Authors: Dong Tim , Sinha Shubhra , Zhai Ben , Fudulu Daniel P , Chan Jeremy , Narayan Pradeep , Judge Andy , Caputo Massimo , Dimagli Arnaldo , Benedetto Umberto , Angelini Gianni D 
Published: July 2023

Objective The introduction of new clinical risk scores (e.g. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II) superseding original scores (e.g. EuroSCORE I) with different variable sets typically result in disparate datasets due to high levels of missingness for new score variables prior to time of adoption. Little is known about the use of ensemble learning to incorporate disparate data from legacy scores. We tested the hypothesised that Homogenenous and Heterogeneous Machine Learning (ML) ensembles will have better performance than ensembles of Dynamic Model Averaging (DMA) for combining knowledge from EuroSCORE I legacy data with EuroSCORE II data to predict cardiac surgery risk. Methods Using the National Adult Cardiac Surgery Audit dataset, we trained 12 different base learner models, based on two different variable sets from either EuroSCORE I (LogES) or EuroScore II (ES II), partitioned by the time of score adoption (1996–2016 or 2012–2016) and evaluated on holdout set (2017–2019). These base learner models were ensembled using nine different combinations of six ML algorithms to produce homogeneous or heterogeneous ensembles. Performance was assessed using a consensus metric. Results Xgboost homogenous ensemble (HE) was the highest performing model (clinical effectiveness metric (CEM) 0.725) with area under the curve (AUC) (0.8327; 95% confidence interval (CI) 0.8323–0.8329) followed by Random Forest HE (CEM 0.723; AUC 0.8325; 95%CI 0.8320–0.8326). Across different heterogenous ensembles, significantly better performance was obtained by combining siloed datasets across time (CEM 0.720) than building ensembles of either 1996–2011 ( t-test adjusted, p = 1.67×10−6) or 2012–2019 ( t-test adjusted, p = 1.35×10−193) datasets alone. Conclusions Both homogenous and heterogenous ML ensembles performed significantly better than DMA ensemble of Bayesian Update models. Time-dependent ensemble combination of variables, having differing qualities according to time of score adoption, enabled previously siloed data to be combined, leading to increased power, clinical interpretability of variables and usage of data.
Missed Cardiac Amyloidosis: A Potentially Treatable Disease
Authors: Vivek B.S. , Jain Ashish Kumar , Sawhney J.P.S. , Jain Rajneesh , Passey Rajiv , Mohanty Arun 
Published: July 2023

Aim To highlight the prevailing lack of suspicion of cardiac amyloidosis (CA) amongst physicians, leading to preventable delay in management of patients of heart failure (HF). Methods Six patients of CA diagnosed in 6 months were retrospectively analyzed. Clinical history, investigations, treatment, and follow-up data is analyzed. Result A speckled interventricular septum on echo favored CA. Speckle tracking showed reduced global longitudinal strain with typical left ventricular apical sparing in all patients. Bone marrow study confirmed light chain amyloidosis (AL) in all patients. Conclusion CA, a frequently missed diagnosis, can be detected early with the help of clinical red flag signs, echocardiogram, serum and urine immune electrophoresis and bone scan.
EASIX-1year and late mortality after allogeneic stem cell transplantation
Authors: Kordelas Lambros , Terzer Tobias , Gooley Ted , Davis Chris , Sandmaier Brenda M. , Sorror Mohamed , Penack Olaf , Schaeper Nigel D. E. , Blau Igor W. , Beelen Dietrich , Radujkovic Aleksandar , Dreger Peter , Luft Thomas 
Published: July 2023

Abstract
Patients with hematological malignancies who survive the first year after allogeneic stem cell transplantation (allo-SCT) without relapse have a substantial risk of nonrelapse mortality (NRM) and missing predictive markers. The Endothelial Activation and Stress Index (EASIX) predicts endothelial complications and NRM early after allo-SCT. We hypothesized that EASIX assessed 1 year after allo-SCT in survivors who were disease free may predict late NRM. Survivors who were relapse-free at 1 year after allo-SCT were retrospectively studied in 2 independent cohorts (training cohort, n = 610; merged validation cohort, n = 852). EASIX determined 1 year after allo-SCT correlated with the overall survival (OS), NRM, and relapse. Serum endothelial and inflammatory markers were measured in the training cohort and correlated with EASIX-1year, which predicted OS and NRM but not relapse risk in both the training and validation cohorts in univariable and multivariable Cox regression analyses. Brier score and c-index analyses validated the univariable EASIX effects. There was no significant interaction between EASIX-1year and incidence of chronic graft-versus-host disease (GVHD) on OS. EASIX-1year predicted the outcome irrespective of preexisting comorbidities. Principal causes of NRM in both training and validation cohorts were infections with and without GVHD as well as cardiovascular complications. EASIX-1year correlated with sCD141 and interleukin-18 but not with C-reactive protein, suppressor of tumorigenicity-2, angiopoietin-2, CXCL9, or CXCL8. To our knowledge, EASIX-1year is the first validated predictor of late overall and NRM. Patients who are high risk as defined by EASIX-1year might be considered for intensified surveillance and prophylactic measures.
The mixture assessment or allocation factor: conceptual background, estimation algorithms and a case study example
Authors: Backhaus Thomas 
Published: July 2023

AbstractCurrent approaches for the prospective regulatory assessment of chemicals do not account sufficiently for elevated mixture risks. The Mixture Assessment Factor (MAF, better labeled a Mixture Allocation Factor) has been suggested for mixtures of industrial chemicals in the EU’s Chemicals Strategy for Sustainability, as a pragmatic tool to account for potential mixture risks already during the risk and safety assessment of individual chemicals. The MAF is to be applied in scenarios in which specific mixture risk assessments are not possible, due to a lack of data and/or the complexity of the relevant exposure scenarios. Several approaches and algorithms for calculating a MAF have been suggested in the literature. The MAFexact, which is a member of the larger MAFceiling class, is defined as the maximum fraction of the risk quotient of each chemical that is still acceptable to occur in a mixture, without the sum of risk quotients exceeding 1. This paper provides a comparative overview of the different MAF types discussed in the literature. It argues that the MAFexact is the most promising approach in the context of chemical registration and authorization under regulatory frameworks such as REACH because this approach ensures a protection level that is similar to the protection level used in the current safety assessment of individual chemicals under REACH. Other MAF approaches either disproportionally impact low-risk substances, without leading to any appreciable risk reduction, or hamper risk communication because they lead to fluctuating residual risks after the MAF application. The paper also presents a case study comparing the different MAF approaches and finally discusses the MAF concept in the wider context of chemical regulation.
The impact of supported accommodation on health and criminal justice outcomes of people released from prison: a systematic literature review
Authors: Gibbs Daisy , Stockings Emily , Larney Sarah , Bromberg Daniel J. , Shakeshaft Anthony , Farnbach Sara 
Published: July 2023

Abstract
Background
Supported accommodation intends to address challenges arising following release from prison; however, impact of services, and of specific service components, is unclear. We describe key characteristics of supported accommodation, including program components and outcomes/impact; and distil best-evidence components.

Methods
We conducted a systematic review, searching relevant databases in November 2022. Data were synthesised via effect direction plots according to the Synthesis Without Meta-analysis guidelines. We assessed study quality using the McGill Mixed Methods Appraisal Tool, and certainty in evidence using the GRADE framework.

Results
Twenty-eight studies were included; predominantly cross-sectional. Program components which address life skills, vocational training, AOD use, and mental health appear to positively impact criminal justice outcomes. Criminal justice outcomes were the most commonly reported, and while we identified a reduction in parole revocations and reincarceration, outcomes were otherwise mixed. Variable design, often lacking rigour, and inconsistent outcome reporting limited assessment of these outcomes, and subsequently certainty in findings was low.

Conclusion
Post-release supported accommodation may reduce parole revocations and reincarceration. Despite limitations in the literature, the findings presented herein represent current best evidence. Future studies should clearly define program components and measure their impact; use analyses which reflect the high risk of adverse outcomes, such as time-to-event analyses; and consider outcomes which reflect the range of challenges faced by people leaving prison.
Registration: PROSPERO registration CRD42020189821.
N-glycosylation acts as a switch for FGFR1 trafficking between the plasma membrane and nuclear envelope
Authors: Gregorczyk Paulina , Porębska Natalia , Żukowska Dominika , Chorążewska Aleksandra , Gędaj Aleksandra , Malinowska Agata , Otlewski Jacek , Zakrzewska Małgorzata , Opaliński Łukasz 
Published: July 2023

AbstractFibroblast growth factor receptor 1 (FGFR1) is a heavily N-glycosylated cell surface receptor tyrosine kinase that transmits signals across the plasma membrane, in response to fibroblast growth factors (FGFs). Balanced FGF/FGFR1 signaling is crucial for the development and homeostasis of the human body, and aberrant FGFR1 is frequently observed in various cancers. In addition to its predominant localization to the plasma membrane, FGFR1 has also been detected inside cells, mainly in the nuclear lumen, where it modulates gene expression. However, the exact mechanism of FGFR1 nuclear transport is still unknown. In this study, we generated a glycosylation-free mutant of FGFR1, FGFR1.GF, and demonstrated that it is localized primarily to the nuclear envelope. We show that reintroducing N-glycans into the D3 domain cannot redirect FGFR1 to the plasma membrane or exclude the receptor from the nuclear envelope. Reestablishment of D2 domain N-glycans largely inhibits FGFR1 accumulation in the nuclear envelope, but the receptor continues to accumulate inside the cell, mainly in the ER. Only the simultaneous presence of N-glycans of the D2 and D3 domains of FGFR1 promotes efficient transport of FGFR1 to the plasma membrane. We demonstrate that while disturbed FGFR1 folding results in partial FGFR1 accumulation in the ER, impaired FGFR1 secretion drives FGFR1 trafficking to the nuclear envelope. Intracellular FGFR1.GF displays a high level of autoactivation, suggesting the presence of nuclear FGFR1 signaling, which is independent of FGF. Using mass spectrometry and proximity ligation assay, we identified novel binding partners of the nuclear envelope-localized FGFR1, providing insights into its cellular functions. Collectively, our data define N-glycosylation of FGFR1 as an important regulator of FGFR1 kinase activity and, most importantly, as a switchable signal for FGFR1 trafficking between the nuclear envelope and plasma membrane, which, due to spatial restrictions, shapes FGFR1 interactome and cellular function.
Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy
Authors: Yan Meng , Li Wenwen , Wei Rui , Li Shuwen , Liu Yan , Huang Yuqian , Zhang Yunye , Lu Zihao , Lu Qian 
Published: July 2023

Abstract
Background
Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus (DM). A growing body of research has demonstrated that the inflammatory state plays a critical role in the incidence and development of DN. Pyroptosis is a new way of programmed cell death, which has the particularity of natural immune inflammation. The inhibition of inflammatory cytokine expression and regulation of pathways related to pyroptosis may be a novel strategy for DN treatment. The aim of this study is to identify pyroptosis-related genes and potential drugs for DN.

Methods
DN differentially expressed pyroptosis-related genes were identified via bioinformatic analysis Gene Expression Omnibus (GEO) dataset GSE96804. Dataset GSE30528 and GSE142025 were downloaded to verify pyroptosis-related differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a pyroptosis-related gene predictive model. A consensus clustering analysis was performed to identify pyroptosis-related DN subtypes. Subsequently, Gene Set Variation Analysis (GSVA), Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the differences between DN clusters. A protein–protein interaction (PPI) network was used to select hub genes and DGIdb database was utilized to screen potential therapeutic drugs/compounds targeting hub genes.

Results
A total of 24 differentially expressed pyroptosis-related genes were identified in DN. A 16 gene predictive model was conducted via LASSO regression analysis. According to the expression level of these 16 genes, DN cases were divided into two subtypes, and the subtypes are mainly associated with inflammation, activation of immune response and cell metabolism. In addition, we identified 10 hub genes among these subtypes, and predicted 65 potential DN therapeutics that target key genes.

Conclusion
We identified two pyroptosis-related DN clusters and 65 potential therapeutical agents/compounds for DN, which might shed a light on the treatment of DN.