bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Review of Computerised Cognitive Remediation interventions in Early Psychosis: Do we Still Need “Somebody with a Human Touch”?
Authors: Avila Alessia , Novais Filipa 
Published: August 2024

Abstract
Purpose of the Review
Several computerized cognitive remediation (CCR) programs have been developed in recent years, although their efficacy in First Episode Psychosis (FEP) remains unclear, particularly regarding the benefits in terms of functional improvement. This review article provides a systematic evaluation of the efficacy, mechanisms, and implementation characteristics of CCR in FEP and critically reflects on the role of human supervision.

Recent Findings
Studies indicates that CCR is effective in improving neurocognition. Evidence for the effects of CCR in social cognition remain less strong and delivery characteristics do not seem to influence this outcome. CCR showed some effects on both clinical symptoms and functional outcomes, with neurocognition being a strong mediator of improvement in social functioning.

Summary
Computer-assisted CR programs can offer standardized, scalable interventions and are effective in improving neurocognition, even with limited supervision from trainers. Human supervision seems, however, crucial to ensuring proper development and transferring of skills to everyday functioning.
Understanding healthy ageing in India: insights from multivariate regression trees
Authors: Das Ayushi , Dhillon Preeti 
Published: August 2024

Abstract
Background
Population ageing represents a significant global challenge, particularly pronounced in countries like India.

Aims
This study aims to explore how factors such as socio-economic status, behaviour, and health influence healthy ageing across the Indian older population.

Methods
In this study, we utilized the Longitudinal Ageing Study in India – wave 1 dataset for analysis purposes. Scores were generated for five dimensions of healthy aging, including physical, functional, mental, cognitive, and social aspects and these scores were treated as the target variables. Multivariate Regression Trees analysis was employed to identify the behavioural and socio-demographic factors associated with each dimension of healthy ageing.

Results
Years of education emerge as crucial across all dimensions, positively impacting cognitive health and mitigating age-related decline in healthy ageing. Marital status, engagement in household activities, spiritual practices, and living arrangements impacts the scores of different aspects of healthy ageing. Gender disparities in healthy aging are noticeable in the 60–74 age group, with women generally having lower scores. Safety of the living environment is a crucial determinant of the mental health of the elderly across all age groups.These findings highlight the complex interplay of factors in healthy ageing outcomes.

Conclusion
Our study emphasizes the pivotal role of education in fostering healthy ageing in India. Factors such as environmental safety and social participation also influence well-being. Targeted interventions addressing education, gender equality, safety, and healthcare access are vital for enhancing the ageing experience and overall well-being of older adults.
Influence of serum uric acid on bone and fracture risk in postmenopausal women
Authors: Gómez-de-Tejada-Romero María-Jesús , Murias-Henríquez Carmen , Saavedra-Santana Pedro , Sablón-González Nery , Abreu Delvys Rodríguez , Sosa-Henríquez Manuel 
Published: August 2024

Abstract
Aims
Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture.

Methods
An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray.

Results
Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures.

Conclusions
In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures.
An exceptionally well-preserved Jurassic plateau-top to marginal escarpment in the Northern Apennines (Central Italy): sedimentological, palaeontological and palaeostructural features
Authors: Santantonio Massimo , Innamorati Giulia , Cipriani Angelo , Antonelli Matteo , Fabbi Simone 
Published: August 2024

AbstractSubmarine palaeo-escarpment tracts at the basin margins commonly border isolated drowned carbonate platforms in the Jurassic rifted margins of the Western Tethys and bear fundamental structural and palaeogeographic significance. These tectonically generated escarpments, rooted in late Hettangian-early Sinemurian master faults, provide key information on the regional architecture of the rift, and on the nature and timespan of activity of the faults which define them. An isolated drowned carbonate platform (the Sabina Plateau) in the Northern Apennines of Central Italy exhibits a wealth of peculiar details on the Jurassic submarine topography. The deposits covering this escarpment host multiple unconformities related to a margin-failure episode, documented by breccias resting on a submarine-scar surface, perched with respect to the basin bottom and draped discontinuously by condensed ammonite-rich pelagites. Thin lenses of graded and laminated oolitic limestones in the condensed pelagic succession of the Sabina Plateau are interpreted as likely produced by the overbanking of turbidity currents, which were shed into the basin by a neighbouring productive carbonate platform. The final leveling of the submarine rift bathymetry occurred in the earliest Cretaceous, as documented by the onlap of the aggrading basinal succession against the palaeo-escarpment, and the burial of the plateau-top condensed succession. This complex onlap surface exhibits a distinctive overprint, such as diffuse silicification driven by the transit of silica-rich diagenetic fluids sourced by the radiolarian-rich basinal units.
CliqueFluxNet: Unveiling EHR Insights with Stochastic Edge Fluxing and Maximal Clique Utilisation Using Graph Neural Networks
Authors: Molaei Soheila , Bousejin Nima Ghanbari , Ghosheh Ghadeer O. , Thakur Anshul , Chauhan Vinod Kumar , Zhu Tingting , Clifton David A. 
Published: August 2024

AbstractElectronic Health Records (EHRs) play a crucial role in shaping predictive are models, yet they encounter challenges such as significant data gaps and class imbalances. Traditional Graph Neural Network (GNN) approaches have limitations in fully leveraging neighbourhood data or demanding intensive computational requirements for regularisation. To address this challenge, we introduce CliqueFluxNet, a novel framework that innovatively constructs a patient similarity graph to maximise cliques, thereby highlighting strong inter-patient connections. At the heart of CliqueFluxNet lies its stochastic edge fluxing strategy — a dynamic process involving random edge addition and removal during training. This strategy aims to enhance the model’s generalisability and mitigate overfitting. Our empirical analysis, conducted on MIMIC-III and eICU datasets, focuses on the tasks of mortality and readmission prediction. It demonstrates significant progress in representation learning, particularly in scenarios with limited data availability. Qualitative assessments further underscore CliqueFluxNet’s effectiveness in extracting meaningful EHR representations, solidifying its potential for advancing GNN applications in healthcare analytics.
Gene Regulatory Network Analysis of Decidual Stromal Cells and Natural Killer Cells
Authors: Rytkönen Kalle T. , Adossa Nigatu , Zúñiga Norman Sebastián , Lönnberg Tapio , Poutanen Matti , Elo Laura L. 
Published: August 2024

AbstractHuman reproductive success relies on the proper differentiation of the uterine endometrium to facilitate implantation, formation of the placenta, and pregnancy. This process involves two critical types of decidual uterine cells: endometrial/decidual stromal cells (dS) and uterine/decidual natural killer (dNK) cells. To better understand the transcription factors governing the in vivo functions of these cells, we analyzed single-cell transcriptomics data from first-trimester terminations of pregnancy, and for the first time conducted gene regulatory network analysis of dS and dNK cell subpopulations. Our analysis revealed stromal cell populations that corresponded to previously described in vitro decidualized cells and senescent decidual cells. We discovered new decidualization driving transcription factors of stromal cells for early pregnancy, including DDIT3 and BRF2, which regulate oxidative stress protection. For dNK cells, we identified transcription factors involved in the immunotolerant (dNK1) subpopulation, including IRX3 and RELB, which repress the NFKB pathway. In contrast, for the less immunotolerant (dNK3) population we predicted TBX21 (T-bet) and IRF2-mediated upregulation of the interferon pathway. To determine the clinical relevance of our findings, we tested the overrepresentation of the predicted transcription factors target genes among cell type-specific regulated genes from pregnancy disorders, such as recurrent pregnancy loss and preeclampsia. We observed that the predicted decidualized stromal and dNK1-specific transcription factor target genes were enriched with the genes downregulated in pregnancy disorders, whereas the predicted dNK3-specific targets were enriched with genes upregulated in pregnancy disorders. Our findings emphasize the importance of stress tolerance pathways in stromal cell decidualization and immunotolerance promoting regulators in dNK differentiation.
Antibiotic practice and stewardship in the management of neutropenic fever: a survey of US institutions
Authors: Wang Xiao , Arya Swarn V. , Patel Sonal , Saw Stephen , Decena Mary A. , Hirsh Rebecca , Pegues David A. , Ziegler Matthew J. 
Published: August 2024

AbstractObjective:To describe neutropenic fever management practices among healthcare institutions.Design:Survey.Participants:Members of the Society for Healthcare Epidemiology of America Research Network (SRN) representing healthcare institutions within the United States.Methods:An electronic survey was distributed to SRN representatives, with questions pertaining to demographics, antimicrobial prophylaxis, supportive care, and neutropenic fever management. The survey was distributed from fall 2022 through spring 2023.Results:40 complete responses were recorded (54.8% response rate), with respondent institutions accounting for approximately 15.7% of 2021 US hematologic malignancy hospitalizations and 14.9% of 2020 US bone marrow transplantations. Most entities have institutional guidelines for neutropenic fever management (35, 87.5%) and prophylaxis (31, 77.5%), and first-line treatment included IV antipseudomonal antibiotics (35, 87.5% cephalosporin; 5, 12.5% penicillin; 0, 0% carbapenem).We observed significant heterogeneity in treatment course decisions, with roughly half (18, 45.0%) of respondents continuing antibiotics until neutrophil recovery, while the remainder having criteria for de-escalation prior to neutrophil recovery. Respondents were more willing to de-escalate prior to neutrophil recovery in patients with identified clinical (27, 67.5% with pneumonia) or microbiological (30, 75.0% with bacteremia) sources after dedicated treatment courses.Conclusions:We found substantial variation in the practice of de-escalation of empiric antibiotics relative to neutrophil recovery, highlighting a need for more robust evidence for and adoption of this practice. No respondents use carbapenems as first-line therapy, comparing favorably to prior survey studies conducted in other countries.
Forecasting Inundation of Catastrophic Landslides From Precursory Creep
Authors: Xu Y. , Bürgmann R. , George D. L. , Fielding E. J. , Solis‐Gordillo G. X. , Yanez‐Borja D. B. 
Published: August 2024

AbstractForecasting landslide inundation upon catastrophic failure is crucial for reducing casualties, yet it remains a long‐standing challenge owing to the complex nature of landslides. Recent global studies indicate that catastrophic hillslope failures are commonly preceded by a period of precursory creep, motivating a novel scheme to foresee their hazard. Here, we showcase an approach to hindcast landslide inundation by linking satellite‐captured precursory displacements to modeling of consequent granular‐fluid flows. We present its application to the 2021 Chunchi, Ecuador landslide, which failed catastrophically and evolved into a mobile debris flow after four months of precursory creep, destroying 68 homes along its lengthy flow path. Underpinned by uncertainty quantification and in situ validations, we highlight the feasibility and potential of forecasting landslide inundation damage using observable precursors. This forecast approach is broadly applicable for flow hazards initiated from geomaterial failures.
Comprehensive molecular characterization of TFE3-rearranged renal cell carcinoma
Authors: Lee Cho-Rong , Suh Jungyo , Jang Dongjun , Jin Bo-Yeong , Cho Jaeso , Lee Moses , Sim Hyungtai , Kang Minyong , Lee Jueun , Park Ju Hyun , Lee Kyoung-Hwa , Hwang Geum-Sook , Moon Kyung Chul , Song Cheryn , Ku Ja Hyeon , Kwak Cheol , Kim Hyeon Hoe , Cho Sung-Yup , Choi Murim , Jeong Chang Wook 
Published: August 2024

AbstractTFE3-rearranged renal cell cancer (tRCC) is a rare form of RCC that involves chromosomal translocation of the Xp11.2 TFE3 gene. Despite its early onset and poor prognosis, the molecular mechanisms of the pathogenesis of tRCC remain elusive. This study aimed to identify novel therapeutic targets for patients with primary and recurrent tRCC. We collected 19 TFE3-positive RCC tissues that were diagnosed by immunohistochemistry and subjected them to genetic characterization to examine their genomic and transcriptomic features. Tumor-specific signatures were extracted using whole exome sequencing (WES) and RNA sequencing (RNA-seq) data, and the functional consequences were analyzed in a cell line with TFE3 translocation. Both a low burden of somatic single nucleotide variants (SNVs) and a positive correlation between the number of somatic variants and age of onset were observed. Transcriptome analysis revealed that four samples (21.1%) lacked the expected fusion event and clustered with the genomic profiles of clear cell RCC (ccRCC) tissues. The fusion event also demonstrated an enrichment of upregulated genes associated with mitochondrial respiration compared with ccRCC expression profiles. Comparison of the RNA expression profile with the TFE3 ChIP-seq pattern data indicated that PPARGC1A is a metabolic regulator of the oncogenic process. Cell proliferation was reduced when PPARGC1A and its related metabolic pathways were repressed by its inhibitor SR-18292. In conclusion, we demonstrate that PPARGC1A-mediated mitochondrial respiration can be considered a potential therapeutic target in tRCC. This study identifies an uncharacterized genetic profile of an RCC subtype with unique clinical features and provides therapeutic options specific to tRCC.
A programmable microfluidic platform to monitor calcium dynamics in microglia during inflammation
Authors: Shebindu Adam , Kaveti Durga , Umutoni Linda , Kirk Gia , Burton Michael D. , Jones Caroline N. 
Published: August 2024

AbstractNeuroinflammation is characterized by the elevation of cytokines and adenosine triphosphate (ATP), which in turn activates microglia. These immunoregulatory molecules typically form gradients in vivo, which significantly influence microglial behaviors such as increasing calcium signaling, migration, phagocytosis, and cytokine secretion. Quantifying microglial calcium signaling in the context of inflammation holds the potential for developing precise therapeutic strategies for neurological diseases. However, the current calcium imaging systems are technically challenging to operate, necessitate large volumes of expensive reagents and cells, and model immunoregulatory molecules as uniform concentrations, failing to accurately replicate the in vivo microenvironment. In this study, we introduce a novel calcium monitoring micro-total analysis system (CAM-μTAS) designed to quantify calcium dynamics in microglia (BV2 cells) within defined cytokine gradients. Leveraging programmable pneumatically actuated lifting gate microvalve arrays and a Quake valve, CAM-μTAS delivers cytokine gradients to microglia, mimicking neuroinflammation. Our device automates sample handling and cell culture, enabling rapid media changes in just 1.5 s, thus streamlining the experimental workflow. By analyzing BV2 calcium transient latency to peak, we demonstrate location-dependent microglial activation patterns based on cytokine and ATP gradients, offering insights contrasting those of non-gradient-based perfusion systems. By harnessing advancements in microsystem technology to quantify calcium dynamics, we can construct simplified human models of neurological disorders, unravel the intricate mechanisms of cell-cell signaling, and conduct robust evaluations of novel therapeutics.
Neuroserpin normalization by mesenchymal stem cell therapy after encephalopathy of prematurity in neonatal rats
Authors: Wang Lan-Wan , Hsiung Chien-Wei , Chang Ching-Ping , Lin Mao-Tsun , Chen Shyi-Jou 
Published: August 2024

Abstract
Background
Hypoxic-ischemia (HI), infection/inflammation and reperfusion injury are pathogenic factors of encephalopathy of prematurity, which involves maturational/neurotrophic disturbances in oligodendrocyte progenitor cells (OPC) and neurons/axons. Mesenchymal stem cells (MSCs) might facilitate neuroserpin production, which is neurotrophic for OPC/neurons. This study investigated MSC effects on developmental disturbances after lipopolysaccharide (LPS)-sensitized HI/reperfusion (LHIR) injury and the relation to neuroserpin expression.

Methods
Postnatal day 2 (P2) rat pups received intraperitoneal LPS (5 µg/kg) injection followed by HI (unilateral common-carotid-artery ligation and 6.5% oxygen exposure for 90 min) and post-HI reperfusion (release of ligation). MSCs (5 × 104 cells) were injected into the left lateral ventricle at 24 h post-LHIR. Neurological tests and brain tissue examinations were performed between P5 and P56.

Results
After LHIR injury, MSC therapy significantly reduced cell death in subplate neurons, attenuated axonal damage, and facilitated synaptophysin synthesis in the cortex. It also alleviated OPC maturation arrest and preserved the complexity of myelinated axons in the white matter, leading to cognitive, motor and behavioral functional improvements. These beneficial effects were linked to restored neuroserpin expression in subplate neurons.

Conclusions
MSC therapy ameliorated developmental disturbances after LHIR injury through protection of neuroserpin expression, serving as a promising approach for treating encephalopathy of prematurity.

Impact

Neuroserpin is secreted by subplate neurons and may regulate the development of neurons and oligodendrocyte-axon contact for myelination in the premature brain.

LPS-sensitized hypoxic-ischemia/reperfusion (LHIR) injury caused the developmental disturbances of neurons/axons and oligodendrocytes, and lowered neuroserpin levels in a neonatal rat model simulating encephalopathy of prematurity.

Mesenchymal stem cell therapy alleviated the developmental disturbances after LHIR injury through protection of neuroserpin expression in subplate neurons, offering a new perspective on potential treatment for encephalopathy of prematurity.
Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors
Authors: Sablin Marie-Paule , Gestraud Pierre , Jonas Sarah Flora , Lamy Constance , Lacroix-Triki Magali , Bachelot Thomas , Filleron Thomas , Lacroix Ludovic , Tran-Dien Alicia , Jézéquel Pascal , Mauduit Marjorie , Barros Monteiro Janice , Jimenez Marta , Michiels Stefan , Attignon Valery , Soubeyran Isabelle , Driouch Keltouma , Servant Nicolas , Le Tourneau Christophe , Kamal Maud , André Fabrice , Bièche Ivan 
Published: August 2024

Abstract
Background
Copy number alterations (CNA) are acquired during the evolution of cancers from their early stage to metastatic stage. This study aims at analysing the clinical value of the identified metastasis-associated CNAs both in metastatic breast cancers (mBCs) and early breast cancers (eBCs).

Methods
Single-nucleotide polymorphism (SNP)-array was performed on 926 biopsies from mBC patients, enrolled in SAFIR02-BREAST prospective trial. CNA profiles of eBCs from The Cancer Genome Atlas Breast Invasive Carcinoma (n = 770), Molecular Taxonomy of Breast Cancer International Consortium (n = 1620) and PACS04 trial (n = 243) cohorts were used as references for comparing mBCs and eBCs CNA profiles. Overall survival was the considered survival endpoint.

Results
Among the twenty-one genes frequently altered in ER + /HER2− mBCs: focal amplification of TERT was associated with poor outcome in the ER + /HER2− mBC population. Among the ER + /HER2− mBCs patients for whom CDK4/6 inhibitors information before biopsies collection was available: we identified seven genes on post-treatment biopsies, including the cyclin-dependent kinase 4 (CDK4), which was amplified in 9.8% of the ER + /HER2− mBCs pretreated population, as compared to 1.5% in the ER + /HER2− mBCs unpretreated population (P = 2.82E-04) as well as the 3 eBC populations. CDK4 amplification was associated with poor outcome in the ER + /HER2− eBCs.

Conclusions
This study provides insights into the biology of mBCs and identifies clinically useful genomic features for future improvement of breast cancer patient management.
Oxidative cell death in cancer: mechanisms and therapeutic opportunities
Authors: An Xiaoqin , Yu Wenfeng , Liu Jinbao , Tang Daolin , Yang Li , Chen Xin 
Published: August 2024

AbstractReactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse cellular functions, including cell signaling and immune responses. However, a disturbance in the balance between ROS production and cellular antioxidant defenses can lead to an excessive ROS buildup, causing oxidative stress. This stress damages essential cellular components, including lipids, proteins, and DNA, potentially culminating in oxidative cell death. This form of cell death can take various forms, such as ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis, each displaying distinct genetic, biochemical, and signaling characteristics. The investigation of oxidative cell death holds promise for the development of pharmacological agents that are used to prevent tumorigenesis or treat established cancer. Specifically, targeting key antioxidant proteins, such as SLC7A11, GCLC, GPX4, TXN, and TXNRD, represents an emerging approach for inducing oxidative cell death in cancer cells. This review provides a comprehensive summary of recent progress, opportunities, and challenges in targeting oxidative cell death for cancer therapy.