bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopaenia
Authors: Xu Min , Liu Jiachen , Huang Linlin , Shu Jinhui , Wei Qiuzhe , Hu Yu , Mei Heng 
Published: July 2024

SummaryDespite diverse therapeutic options for immune thrombocytopaenia (ITP), drug efficacy and selection challenges persist. This study systematically identified potential indicators in ITP patients and followed up on subsequent treatment. We initially analysed 61 variables and identified 12, 14, and 10 candidates for discriminating responders from non‐responders in glucocorticoid (N = 215), thrombopoietin receptor agonists (TPO‐RAs) (N = 224), and rituximab (N = 67) treatments, respectively. Patients were randomly assigned to training or testing datasets and employing five machine learning (ML) models, with eXtreme Gradient Boosting (XGBoost) area under the curve (AUC = 0.89), Decision Tree (DT) (AUC = 0.80) and Artificial Neural Network (ANN) (AUC = 0.79) selected. Cross‐validated with logistic regression and ML finalised five variables (baseline platelet, IP‐10, TNF‐α, Treg, B cell) for glucocorticoid, eight variables (baseline platelet, TGF‐β1, MCP‐1, IL‐21, Th1, Treg, MK number, TPO) for TPO‐RAs, and three variables (IL‐12, Breg, MAIPA−) for rituximab to establish the predictive model. Spearman correlation and receiver operating characteristic curve analysis in validation datasets demonstrated strong correlations between response fractions and scores in all treatments. Scoring thresholds SGlu ≥ 3 (AUC = 0.911, 95% CI, 0.865–0.956), STPO‐RAs ≥ 5 (AUC = 0.964, 95% CI 0.934–0.994), and SRitu = 3 (AUC = 0.964, 95% CI 0.915–1.000) indicated ineffectiveness in glucocorticoid, TPO‐RAs, and rituximab therapy, respectively. Regression analysis and ML established a tentative and preliminary predictive scoring model for advancing individualised treatment.
Azacitidine combined with interferon‐α for pre‐emptive treatment of AML/MDS after allogeneic peripheral blood stem cell transplantation: A prospective phase II study
Authors: Huang Chongmei , Jia Yannan , Yang Jun , Cai Yu , Tong Yin , Qiu Huiying , Zhou Kun , Xia Xinxin , Zhang Ying , Shen Chang , Wan Liping , Song Xianmin 
Published: July 2024

SummaryThis prospective clinical study aimed to evaluate the efficacy and safety of the pre‐emptive treatment modality of azacitidine in combination with interferon‐α (IFN‐α) in AML/MDS patients post‐transplantation. Forty‐seven patients aged 17–62 were enrolled with 14 patients having completed the planned 12 cycles. Following initiation, 72.3% responded positively after the first cycle, peaking at 77.2% by the fifth cycle. Notably, 24 patients maintained sustained responses throughout a median follow‐up of 1050 days (range, 866–1234). Overall survival, leukaemia‐free survival and event‐free survival probabilities at 3 years were 69.5%, 60.4% and 35.7% respectively. Cumulative incidences of relapse and non‐relapse mortality were 36.5% and 4.3% respectively. Multivariate analysis identified that receiving pre‐emptive treatment for fewer than six cycles and the absence of chronic graft‐versus‐host disease after intervention was significantly associated with poorer clinical outcomes. The combination of azacitidine with IFN‐α was well‐tolerated with no observed severe myelotoxicity, and the majority of adverse events were reversible and manageable. In conclusion, the use of azacitidine in conjunction with IFN‐α as pre‐emptive therapy is a safe and effective treatment to prevent disease progression in AML/MDS patients with MRD positivity post‐allo‐HSCT.
Inhibition of proline‐rich tyrosine kinase 2 restores cardioprotection by remote ischaemic preconditioning in type 2 diabetes
Authors: Erkens Ralf , Duse Dragos Andrei , Brum Amanda , Chadt Alexandra , Becher Stefanie , Siragusa Mauro , Quast Christine , Müssig Johanna , Roden Michael , Cortese‐Krott Miriam , Ibáñez Borja , Lammert Eckhard , Fleming Ingrid , Jung Christian , Al‐Hasani Hadi , Heusch Gerd , Kelm Malte 
Published: July 2024

AbstractBackground and PurposeRemote ischaemic preconditioning (rIPC) for cardioprotection is severely impaired in diabetes, and therapeutic options to restore it are lacking. The vascular endothelium plays a key role in rIPC. Given that the activity of endothelial nitric oxide synthase (eNOS) is inhibited by proline‐rich tyrosine kinase 2 (Pyk2), we hypothesized that pharmacological Pyk2 inhibition could restore eNOS activity and thus restore remote cardioprotection in diabetes.Experimental ApproachNew Zealand obese (NZO) mice that demonstrated key features of diabetes were studied. The consequence of Pyk2 inhibition on endothelial function, rIPC and infarct size after myocardial infarction were evaluated. The impact of plasma from mice and humans with or without diabetes was assessed in isolated buffer perfused murine hearts and aortic rings.Key ResultsPlasma from nondiabetic mice and humans, both subjected to rIPC, caused remote tissue protection. Similar to diabetic humans, NZO mice demonstrated endothelial dysfunction. NZO mice had reduced circulating nitrite levels, elevated arterial blood pressure and a larger infarct size after ischaemia and reperfusion than BL6 mice. Pyk2 increased the phosphorylation of eNOS at its inhibitory site (Tyr656), limiting its activity in diabetes. The cardioprotective effects of rIPC were abolished in diabetic NZO mice. Pharmacological Pyk2 inhibition restored endothelial function and rescued cardioprotective effects of rIPC.Conclusion and ImplicationsEndothelial function and remote tissue protection are impaired in diabetes. Pyk2 is a novel target for treating endothelial dysfunction and restoring cardioprotection through rIPC in diabetes.
Effectiveness of therapeutic interventions on participation in children with cerebral palsy: A systematic review and meta‐analysis
Authors: Dimakopoulos Rigas , Vakalaki Theodora , Spinou Arietta , Michopoulos Ioannis , Papadopoulou Μarianna 
Published: July 2024

AbstractBackgroundParticipation in life activities is an integral part of health and a main outcome of rehabilitation services for children and adolescents with disabilities. However, there is still no consensus on the most effective way to improve participation. The aim of this systematic review is to determine the effectiveness of therapeutic interventions on participation outcomes of children with cerebral palsy (CP).MethodsA systematic review was conducted, searching the databases PubMed, Cochrane Library, Science Direct, Web of Science and Scopus for randomized controlled trials (RCTs), between 2001 and 2023. Studies were eligible for inclusion if they evaluated children with CP undergoing any intervention and using any tool measuring participation as an outcome measure. A meta‐analysis of treatment effect was conducted. A sensitivity analysis was conducted to identify the effect on participation when intervention targeted different International Classification of Functioning (ICF) domains.ResultsA total of 1572 records were identified. Eight RCTs including 384 children (195 in the intervention group and 189 in the control group) were included in the systematic review and in the meta‐analysis. A sensitivity analysis showed that interventions focusing on participation significantly improved participation; standardized mean difference (1.83; 95% CI: 1.33–2.32; Z = 7.21; P < 0.00001). When other types of interventions, that is, focusing on body functions and structures or activities, were used, then participation was not favourably affected.InterpretationInterventions primarily targeting barriers to participation across several ICF domains have a greater influence on enhancing participation. Interventions aimed at enhancing specific motor skills, including gross and fine motor function or strength, do not necessarily have a positive impact on participation.
Whole genome sequencing identifies a homozygous splicing variant in TDRKH segregating with non‐obstructive azoospermia in an Iranian family
Authors: Amiri‐Yekta Amir , Sen Sharanya , Hazane‐Puch Florence , Tebbakh Célia , Roux‐Buisson Nathalie , Cazin Caroline , Thierry‐Mieg Nicolas , Bouras Ahmed , Mohammad Ali Sadighi‐Gilani , Hosseini Seyedeh‐Hanieh , Goodarzian Maedeh , Gourabi Hamid , Ray Pierre F. , Kherraf Zine‐Eddine 
Published: July 2024

AbstractNon‐obstructive azoospermia (NOA) resulting from primary spermatogenic failure represents one of the most severe forms of male infertility, largely because therapeutic options are very limited. Beyond their diagnostic value, genetic tests for NOA also hold prognostic potential. Specifically, genetic diagnosis enables the establishment of genotype‐testicular phenotype correlations, which, in some cases, provide a negative predictive value for testicular sperm extraction (TESE), thereby preventing unnecessary surgical procedures. In this study, we employed whole‐genome sequencing (WGS) to investigate two generations of an Iranian family with NOA and identified a homozygous splicing variant in TDRKH (NM_001083965.2: c.562‐2A>T). TDRKH encodes a conserved mitochondrial membrane‐anchored factor essential for piRNA biogenesis in germ cells. In Tdrkh knockout mice, de‐repression of retrotransposons in germ cells leads to spermatogenic arrest and male infertility. Previously, our team reported TDRKH involvement in human NOA cases through the investigation of a North African cohort. This current study marks the second report of TDRKH's role in NOA and human male infertility, underscoring the significance of the piRNA pathway in spermatogenesis. Furthermore, across both studies, we demonstrated that men carrying TDRKH variants, similar to knockout mice, exhibit complete spermatogenic arrest, correlating with failed testicular sperm retrieval.
The global burden of disease attributable to high body mass index in 204 countries and territories: Findings from 1990 to 2019 and predictions to 2035
Authors: Chen Yuhan , Ma Li , Han Zhigang , Xiong Peng 
Published: July 2024

AbstractAimOur study aims to provide an updated estimate of age‐ and sex‐specific deaths and disability‐adjusted life years (DALYs) associated with high body mass index (BMI) from 1990 to 2019 at the global, regional and national levels, and to forecast the global burden of disease attributed to high BMI from 2020 to 2035.MethodsWe used the data for the number of deaths, DALYs, age‐standardized rate (per 100 000 population), percentage change and population attributable fraction from the Global Burden of Disease Study 2019 (GBD 2019) to examine the disease burden attributable to high BMI. We further applied an autoregressive integrated moving average (ARIMA) model to predict the disease burden for the period 2020‐2035.ResultsFrom 1990 to 2019, the deaths and DALYs attributable to high BMI increased by 148% and 155.86% for men, and by 111.67% and 121.78% for women, respectively. In 2019, high BMI directly accounted for 8.52% [95% uncertainty intervals (UI) 0.05, 0.12] of all‐cause deaths and 5.89% (95% UI 0.04, 0.08) of global DALYs. The highest death rates were observed in men aged 65‐69 and women aged 75‐79. The highest DALY rates were observed in the age group of 60‐64 for both sexes. In 2019, the highest age‐standardized deaths and DALY rates were observed in the Central Asia region [163.15 (95% UI 107.72, 223.58) per 100 000 people] and the Oceania region [4643.33 (95% UI 2835.66, 6902.6) per 100 000 people], respectively. Fiji [319.08 (95% UI 213.77, 444.96) per 100 000 people] and Kiribati [10 000.58 (95% UI 6266.55, 14159.2) per 100 000 people] had the highest age‐standardized deaths and DALY rates, respectively. In 2019, the highest age‐standardized rates of high BMI‐related deaths and DALYs were observed in the middle‐high socio‐demographic index quintile and in the middle socio‐demographic index quintile. The age‐standardized deaths and DALY rates attributable to high BMI are projected to increase in both sexes from 2020 to 2035. The death rates are projected to rise from 62.79 to 64.31 per 100 000 people, while the DALY rates are projected to rise from 1946 to 2099.54 per 100 000 people.ConclusionsHigh BMIs significantly contribute to the global disease burden. The projected rise in deaths and DALY rates attributable to high BMI by 2035 highlights the critical need to address the impact of obesity on public health. Our study provides policymakers with up‐to‐date and comprehensive information.
Portfolio construction using explainable reinforcement learning
Authors: Cortés Daniel González , Onieva Enrique , Pastor Iker , Trinchera Laura , Wu Jian 
Published: July 2024

AbstractWhile machine learning's role in financial trading has advanced considerably, algorithmic transparency and explainability challenges still exist. This research enriches prior studies focused on high‐frequency financial data prediction by introducing an explainable reinforcement learning model for portfolio management. This model transcends basic asset prediction, formulating concrete, actionable trading strategies. The methodology is applied in a custom trading environment mimicking the CAC‐40 index's financial conditions, allowing the model to adapt dynamically to market changes based on iterative learning from historical data. Empirical findings reveal that the model outperforms an equally weighted portfolio in out‐of‐sample tests. The study offers a dual contribution: it elevates algorithmic planning while significantly boosting transparency and interpretability in financial machine learning. This approach tackles the enduring ‘black‐box’ issue and provides a holistic, transparent framework for managing investment portfolios.
The β2‐adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress‐induced cardiac injury
Authors: Naryzhnaya Natalia V. , Logvinov Sergey V. , Kurbatov Boris K. , Derkachev Ivan A. , Mustafina Liliia R. , Gorbunov Aleksandr S. , Sirotina Maria A. , Kilin Mikhail , Gusakova Svetlana V. , Maslov Leonid N. 
Published: July 2024

AbstractBackgroundCurrently, there is no effective therapy for takotsubo syndrome (stress‐induced cardiac injury in humans) in the clinics. It has previously been shown that β2‐adrenergic receptor (β2‐AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.ObjectivesThe aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress‐induced cardiomyopathy.MethodsStress‐induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.ResultsThe myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase‐MB, syndecan‐1, and thrombomodulin after 24 hours of stress. Administration of β2‐AR agonist formoterol (50 μg/kg) four times during 24‐hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL‐positive cardiomyocytes, serum creatine kinase‐MB, syndecan‐1, and thrombomodulin levels.ConclusionPresent data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress‐induced cardiac injury can be mitigated by activation of the β2‐AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.
Consultations With Muslims From Minoritised Ethnic Communities Living in Deprived Areas: Identifying Inequities in Mental Health Care and Support
Authors: Tannerah Ashraf , Hazel Oluwalolami , Desson Sheree , Farah Rahima , Kamil‐Thomas Zalihe , Iqbal Halima , Eames Catrin , Saini Pooja , Bifarin Oladayo 
Published: July 2024

ABSTRACTBackgroundLimited research concerning existing inequities in mental health care and support services in the United Kingdom captures perceptions and lived experiences of the significantly underrepresented Muslim population.MethodsUnderpinned by social constructivist theory, we used consultation to facilitate public and patient involvement and engagement (PPIE) to identify inequities in mental health care and support experienced by Muslims from minoritised ethnic communities living in deprived areas in Liverpool, UK. The rationale was to (a) better inform standards and policies in healthcare and (b) provide a psychologically safe space to members of the Muslim community to share perceptions and experiences of mental health care and support services. To ensure trustworthiness of the data, member checking was adopted. This paper describes the procedure to achieving this consultation, including our recruitment strategy, data collection and analysis as well as key findings.FindingsTwenty‐seven consultees attended the women's consultation and eight consultees attended the men's consultation. Consultees were from Yemeni, Somali, Sudanese, Egyptian, Algerian, Pakistani and Moroccan communities and share the Islamic faith. Four key interlinked themes were identified from consultees' narratives: (1) broken cycle of trust; (2) an overmedicalised model of care; (3) community mental health prevention initiatives; and (4) culturally conscious training and education.ConclusionsThe Muslim population has identified numerous barriers to accessing mental health support and there is a need to resource activities that would aid deeper understanding of mental health support needs through continuous and meaningful community initiatives. This would afford mental health practitioners and organisations opportunities for developing realistic anti‐racism strategies, effectively adopting social prescription, strengthening partnerships and collaborations aimed at supporting delivery of evidence‐based mental health care provisions to tackle mental health inequities.Patient and Public InvolvementThis paper reports on the involvement and engagement of Muslims from minoritised ethnic communities living in the Liverpool city region.
Integrating machine learning and single‐cell analysis to uncover lung adenocarcinoma progression and prognostic biomarkers
Authors: Zhang Pengpeng , Feng Jiaqi , Rui Min , Xie Jiping , Zhang Lianmin , Zhang Zhenfa 
Published: July 2024

AbstractThe progression of lung adenocarcinoma (LUAD) from atypical adenomatous hyperplasia (AAH) to invasive adenocarcinoma (IAC) involves a complex evolution of tumour cell clusters, the mechanisms of which remain largely unknown. By integrating single‐cell datasets and using inferCNV, we identified and analysed tumour cell clusters to explore their heterogeneity and changes in abundance throughout LUAD progression. We applied gene set variation analysis (GSVA), pseudotime analysis, scMetabolism, and Cytotrace scores to study biological functions, metabolic profiles and stemness traits. A predictive model for prognosis, based on key cluster marker genes, was developed using CoxBoost and plsRcox (CPM), and validated across multiple cohorts for its prognostic prediction capabilities, tumour microenvironment characterization, mutation landscape and immunotherapy response. We identified nine distinct tumour cell clusters, with Cluster 6 indicating an early developmental stage, high stemness and proliferative potential. The abundance of Clusters 0 and 6 increased from AAH to IAC, correlating with prognosis. The CPM model effectively distinguished prognosis in immunotherapy cohorts and predicted genomic alterations, chemotherapy drug sensitivity, and immunotherapy responsiveness. Key gene S100A16 in the CPM model was validated as an oncogene, enhancing LUAD cell proliferation, invasion and migration. The CPM model emerges as a novel biomarker for predicting prognosis and immunotherapy response in LUAD patients, with S100A16 identified as a potential therapeutic target.
Factors influencing the reimbursement of cancer drugs in Europe: A scoping review
Authors: Nieto‐Gómez Pelayo , Castaño‐Amores Celia 
Published: July 2024

AbstractRationaleReimbursement process of oncology drugs in Europe occurs within a complex decision‐making process that varies between Member States. Distinctions between the States trigger societal debates since it is necessary to balance access to medicines and health systems sustainability.Aims and ObjectivesWe aimed to review the evidence concerning factors associated with the reimbursement decision or Health Technology Agency recommendation of oncology drugs in Europe.MethodsA systematic literature search was performed in two databases from inception to august 2023. Screening and data extraction were performed by pairs.ResultsThirteen articles were included and encompassed data from 11 nations. Seven articles showed that cost‐effective (C‐E) drugs and lower Incremental Cost‐Effectiveness Ratios (ICERs) had higher likelihood of reimbursement. Disease severity might influence the reimbursement decision with financial agreements. Improvement in clinical outcomes, substantial clinical benefit (p < 0.01) or overall survival gains (p < 0.05) were positively associated. Orphan drug designation impact varies between countries but positive decisions are usually achieved under specific conditions. Clinical and C‐E uncertainty frequently led to reimbursement with financial agreements or outcomes‐based conditions. Sociodemographic factors as: social health insurance system, higher Gross Domestic Product and larger elderly population were positively associated with reimbursement (p < 0.01).ConclusionThere is a need for further research into key determinants of reimbursement decisions in Europe and the development of drug access models that can effectively address and overcome costs and effectiveness uncertainties.