Search Results (69,281)

Background: Breast cancer (BC) survivors frequently experience depression, which is associated with poorer quality of life (QoL), increased healthcare utilization, and worse prognosis. Although traditional Chinese medicine (TCM) is commonly used as an adjunctive therapy among Chinese populations for cancer-related symptom relief and supportive care, population-based evidence remains limited regarding whether integrated Chinese and Western medicine (ICWM) confers measurable benefits over Western medicine (WM) alone in terms of healthcare utilization and survival. Taiwan’s National Health Insurance (NHI) system offers a unique nationwide setting to address this gap because it reimburses patients for both WM and TCM services and captures care from a large number of TCM clinics across Taiwan, allowing evaluation of adjunctive TCM use in routine clinical practice at a scale rarely possible in prior studies. We used emergency department visits, hospitalization, and length of stay as pragmatic proxy indicators of patients’ daily functioning and disease burden. Leveraging a 10-year enrollment window (2004–2013) and up to 17 years of follow-up, we hypothesized that ICWM would be associated with a reduced risk of acute care events and lower healthcare expenditures compared with WM alone. This hypothesis was examined in a large cohort of breast cancer patients treated across nearly 4000 medical facilities nationwide, encompassing the entire Taiwanese population. Methods: A retrospective cohort study was performed to analyze Taiwan’s National Health Insurance Research Database and Cancer Registry. Women newly diagnosed with breast cancer between 2004 and 2013 who subsequently developed depression (≥3 outpatient diagnoses or 1 hospitalization) were followed until death or 31 December 2021. Patients receiving ≥30 cumulative days of TCM after diagnosis were classified as the ICWM group, whereas those receiving <30 days were classified as the WM group. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for all-cause mortality. Healthcare utilization, including emergency department visits, hospitalization, and medical expenditures, was analyzed on a per-person-year basis. Results: A total of 1193 patients were included, with 488 in the WM group and 705 in the ICWM group. Compared with WM users, ICWM users were younger, had lower body mass index, and were more likely to have stage 0–II disease. ICWM was associated with lower total, inpatient, and emergency healthcare expenditures per person-year, as well as fewer emergency visits per person-year, although outpatient and overall visits were higher. In stage-stratified multivariable analyses, ICWM was associated with lower all-cause mortality in both stage 0–II disease (aHR = 0.61, 95% CI: 0.39–0.94) and stage III–IV disease (aHR = 0.38, 95% CI: 0.21–0.67). Kaplan–Meier analyses likewise showed significantly better overall survival in the ICWM group in both early-stage and advanced-stage disease. Conclusions: In this nationwide retrospective cohort of breast cancer patients with depression, adjunctive ICWM was associated with better survival, lower acute care utilization, and lower healthcare expenditures compared with WM alone. However, because quality of life was not directly measured and the study was based on observational data, QoL-related interpretations should be made cautiously, with healthcare utilization outcomes viewed as indirect proxy indicators rather than direct evidence of improved daily QoL. Full article

Objective: Recent research has expanded the understanding of the potential role of sympathetic nervous system activation in the implications of sleep-related movement disorders, particularly in the mechanisms of dopaminergic dysfunction and iron deficiency. This multifactorial perspective aims to provide insights into disease mechanisms and opportunities for targeted interventions that address both neurological and autonomic contributors to sleep-related movements. Methods: To synthesize the current evidence on the role of sympathetic activation in sleep-related movement disorders, we conducted a review of the literature to identify studies exploring the intersection of autonomic nervous system activity and motor phenomena during sleep. Results: Studies indicate that sympathetic activation may contribute directly to the initiation and propagation of motor events during sleep. Evidence from electrophysiological studies and heart rate variability analyses in patients with sleep-related movement disorders shows that sympathetic bursts often precede or coincide with leg movements and arousals, suggesting a causal rather than reactive role. Moreover, iron deficiency appears to exacerbate both dopaminergic and autonomic dysfunction, providing a unifying mechanism that bridges these pathways. Conclusions: These findings support a shift from viewing sympathetic activity as a secondary response to arousal to recognizing it as a possible primary trigger of sleep-related motor events. Full article

Background: Since the advent of imatinib, more potent next-generation tyrosine kinase inhibitors (TKIs) and asciminib have expanded therapeutic options for chronic myeloid leukemia (CML). Treatment-free remission (TFR) is an important goal in CML management, but only ~30% of patients can achieve it, leaving many on lifelong therapy. TKIs are usually used in escalating order of potency, but in patients ineligible for or failing TFR, “downgrading” to safer, lower-potency agents may be advantageous. Methods: We analyzed this strategy in 157 patients across 29 Italian CML Campus centres. Data were collected via e-forms in July 2024. Prognostic scores at diagnosis did not influence downgrading. Results: The most downgraded TKIs were nilotinib (47%) and dasatinib (37%). Imatinib was the most frequent target agent (69.7%), followed by nilotinib and bosutinib. The majority underwent downgrading during first-line therapy and most after prior dose de-escalation. Adverse events were the leading reason for downgrading (79%). Notably, in 52.6% of cases, molecular responses improved afterwards. Twenty-one patients subsequently attempted TFR, with 17 (81%) remaining treatment-free at a median follow-up of 22 months. Conclusions: These results show that, beyond the known role of de-escalation, downgrading represents a new, feasible approach to maintaining long-term control, limiting toxicity and costs, and favouring TFR. Full article

Observed increases in wildfire activity across the contiguous United States (U.S.), together with continued warming and expanding development in fire-prone landscapes, highlight the need to anticipate near-term changes in fire regimes. We apply a Bayesian statistical model that integrates projected population density (SSP2) and downscaled climate simulations under a moderate emissions scenario (RCP 4.5) to estimate future wildfire occurrence, maximum fire size (using the 90th percentile of fire size distribution), and total area burned for large fires (>1000 acres) across all EPA Level III ecoregions for 2020–2060. Relative to 1984–2019, we project nationwide increases of 56% in fire occurrence and 59% in area burned, with larger increases in maximum fire size (63%) in 2020–2060. Spatial patterns vary substantially: fire occurrence increases most strongly in the eastern U.S., including regions where large fires have historically been rare, while western ecoregions experience the largest absolute increases in burned area and extreme fire size. The disproportionate growth in maximum fire size suggests that changes in fire weather will amplify extreme events beyond increases in ignition frequency alone. These projections indicate expanding wildfire risk across diverse U.S. landscapes and underscore the need for regionally tailored fire management and preparedness strategies. Full article

Membrane roofs with saddle geometry are widely used in stadiums and public facilities that are highly exposed to rainfall. However, current design practice typically considers rainfall only in terms of seepage effects, drainage requirements, or static stability checks, while the influence of extreme rainfall on dynamic behavior and prestress loss has not been comprehensively quantified. In this study, the behavior of a restored engineering-scale saddle-shaped membrane roof under three representative rainfall intensities (50, 300, and 550 mm/h) is investigated through combined laboratory experiments (span L = 2.52 m) and numerical simulations, with particular emphasis on how supporting conditions and pretension levels affect vertical displacement, vibration propagation, and rainfall-induced edge-cable pretension loss. The findings are intended to reveal response mechanisms and trends, while quantitative extrapolation to full-size roofs should be conducted with scaling considerations. The numerical model is validated against the experimental results through comparisons of cable forces and vertical displacements. The results indicate that while the maximum vertical displacement induced by heavy rainfall is small (millimeter-level) and does not cause immediate failure, the rainfall event induces a significant permanent loss of pretension (a maximum observed relaxation of 10.4% in the edge cables for the tested specimen) in the edge cables. This relaxation degrades the structural stiffness, potentially compromising aerodynamic stability under subsequent wind events. Consequently, for the tested configuration, post-rainfall pretension inspection is recommended for events exceeding 300 mm/h, with retensioning suggested if significant tension loss is detected. This recommendation should be interpreted as an indicative engineering reference for the present specimen rather than a universal criterion for all saddle membrane roofs. Full article

The goal of this paper is to present the design and preliminary development of a prototype for an inclusive evaluation tool aimed at gathering audience feedback in entertainment, cultural contexts and live events. The prototype consists of a flexible questionnaire and was designed as part of the SAFINA VITALITY research project. This research (“ACCESSMAP: design of a flexible system for feedback collection in accessibility to media, entertainment and cultural events”) was funded by PNRR ECS00000041 “Innovation, digitalisation and sustainability for the diffused economy in Central Italy”—PNRR—Missione 4, Componente 2—Investimento 1.5 “Creazione e rafforzamento di “ecosistemi dell’innovazione”—CUP D83C22000710005. Its aim consists of assessing visitors’ comprehension, appreciation and overall experience, with particular attention to accessibility. Building on the existing seminal research in reception studies and accessible design, this study reports on a pilot implementation of the questionnaire. The tool was adapted for being used at the Museo Tattile Statale Omero, a leading institution in tactile, multisensory and inclusive museum experiences. The questionnaire was designed to be accessible to a wide demographic, including visitors with and without disabilities. A preliminary site visit and consultation with the museum staff was made to inform the contextual adaptation of the tool, leading to a shift in focus to tactile engagement and reflecting the museum’s core strengths and needs of its audience. The instrument includes both quantitative and qualitative measures to explore, among others, memory retention, clarity of information, appreciation and perceived usefulness of accessibility features. This article discusses the rationale behind the tool’s design, its contextual adaptation, and its potential applications for museums and live events with an eye to accessibility. Rather than providing a definitive validation of the tool, this pilot study offers an initial exploration of its applicability to a multisensory museum context. In addition, it discusses the design rationale behind the tool, its contextual adaptation, and its potential for supporting accessible feedback collection in cultural settings. Full article

Background: Hypoplastic left heart syndrome (HLHS) is defined as “a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch”. Without treatment, HLHS is usually lethal in the neonate. Many hypotheses have been advanced to explain the etiology of HLHS; however, no single theory appears to fully explain the phenotypic variability seen in HLHS. Furthermore, many of these theories offer no explanations regarding the precipitating events which lead to the development of HLHS. Objective: This review considers and critically evaluates the strengths and weaknesses of the leading theories proposed to explain the pathogenesis of HLHS—including hemodynamic disturbances, primary myocardial structural defects, valvar malformations, and genetic or epigenetic alterations that may provoke developmental and anatomic abnormalities. After presenting each model, we propose a novel, comprehensive, and data-driven framework which may assist researchers in developing models for the pathogenesis of the various subtypes of HLHS. Methods: Key findings from human fetal imaging, histopathology, genetic studies, and animal models were considered, as well as the hypothetical contribution of each in observed HLHS phenotypes. The rationales for these findings as causal factors initiating individual HLHS patterns, as well as how they might contribute to HLHS in general, were critically analyzed. Results: The flow theory is strongly supported by animal models and in utero interventions that demonstrate the impact of altered hemodynamics on cardiac morphogenesis. However, the flow theory fails to identify initial causes of disturbed flow or related histological features of HLHS like endocardial fibroelastosis. The myocardial and valve-first models suggest an important role in developmental defects, but do not necessarily have a strong experimental basis that provides explanations for how they mediate HLHS. Genetic studies in patients with HLHS have identified several candidate causal mutations. However, such genetic causes of HLHS exhibit incomplete phenotypic penetrance and clinical impact. A multifactorial framework attempts to integrate these diverse mechanisms and may provide the most coherent explanation that can accommodate the heterogeneity and variable presentation of HLHS. Such a framework may identify multiple forces that drive disease but does not provide useful pathways for future research about HLHS. Conclusions: No single hypothesis has fully explained how HLHS is initiated, progresses, and presents with the clinical conditions that are encountered by cardiac surgeons and cardiologists. The most current models suggest that the spectrum of HLHS reflects acomplex interaction between genetic susceptibility, flow-dependent cardiac remodeling, and environmental factors in utero. A multifactorial model integrates these diverse mechanisms and may provide the most coherent explanation for the various phenotypic variations in HLHS. Based on our analysis of the most current data and the strengths and weaknesses of the current theoretical frameworks, we propose a novel research strategy aimed at identifying specific cardiac progenitor cell populations whose dysregulation may represent a unifying explanation for the etiology of the various phenotypes of HLHS. Based on the arguments made throughout this manuscript that evaluate the various genetic, structural, and hemodynamic models of initiation of disease, we believe that the significant phenotypic variability across the spectrum of HLHS (i.e., the different anatomic subtypes for “classic” HLHS) most likely reflects different underlying etiologies and mechanisms. At the very least, it is very likely that the timing of the insult is critical in determining anatomic subtype. Based on the published data and the arguments within this manuscript, it seems naive to think that there is a single unifying mechanism explain all forms of HLHLS. Full article

Background: Growth disorders, including central precocious puberty and delayed puberty, can significantly affect linear growth, skeletal maturation, metabolic regulation, and psychosocial development during childhood and adolescence. This systematic review synthesizes the current evidence regarding the effectiveness and safety of hormone-based therapies used in children with disorders of pubertal maturation. Methods: A PRISMA-guided systematic search was carried out between January 2016 and March 2026 in different databases, such as MEDLINE (PubMed), EMBASE, CENTRAL, Scopus, Web of Science, CINAHL, LILACS and OpenGrey; the protocol was previously registered in the PROSPERO database (CRD420251068048). Non-randomized, randomized controlled trials and observational research including participants aged 0–18 years receiving hormone therapies were eligible. Risk of bias was assessed using validated, design-specific tools. Results: Twenty studies involving 21,812 participants were included. GnRHa therapy improved final adult height (+3.5 to +4.5 cm) and reduced bone age advancement (−0.6 to −1.3 years) in children with central precocious puberty. rhGH therapy increased growth velocity (+3.0 to +5.0 cm/year) and height SDS (+0.3 to +0.9), particularly in idiopathic short stature and Prader–Willi syndrome. Combined GnRHa plus rhGH therapy showed greater short-term growth benefits than GnRHa alone. Both therapies showed favorable safety profiles, with predominantly mild adverse events and discontinuation rates below 2%. However, the evidence was limited by substantial heterogeneity and moderate-to-serious risk of bias. Conclusions: GnRHa and rhGH therapies are generally effective and safe for improving growth and pubertal outcomes in pediatric endocrine disorders. However, further long-term studies are needed to clarify their metabolic and psychosocial effects in adulthood. Nevertheless, these conclusions should be interpreted with caution due to the study’s moderate-to-serious risk of bias and heterogeneity. Full article

Due to randomness factors in the machine learning model construction process, reproducibility is compromised. This study investigates the impact of randomness on model stability and evaluates techniques for reducing this impact using the widely adopted shallow neural network model as a testbed. Randomness in this neural network model arises from three events: randomly initializing model parameters, randomly selecting a validation subset, and randomly sampling batches for parameter updates. Among these, batch randomness exerts a much weaker impact than the other two factors. In this study, the model training is stopped when the validation performance fails to improve or when a preset threshold for loss or epoch number is met. The final model stability is considerably better when using threshold criteria than when using validation criterion, as the former avoids the randomness associated with selecting a validation subset. Sensitivity experiments show that scaling the model’s initial parameters (i.e., weights) to 0.1 times their original values can mitigate the impact of initialization randomness, thereby markedly improving model stability while also substantially enhancing predictive skill. Furthermore, weight decay and multi-model ensembles, which are two commonly used techniques, can also markedly enhance model stability. From the perspective of this case study, the compression of model initial parameters yields better improvements in stability compared to weight decay, and unlike multi-model ensemble methods that entail substantial increases in computational cost, it serves as a preferable technique for improving model stability. Full article

Soil salinity is a major constraint on crop productivity, and plants rely on multilayered regulatory mechanisms to adapt to stress. Alternative splicing (AS) enhances transcriptome plasticity, yet how light modulates AS under salt stress remains unclear. Here, we performed a transcriptome-wide analysis to investigate light-dependent AS dynamics in sweet potato under salt stress. Plant treatments were initiated during daytime (SD) and nighttime (SN) conditions, and samples were collected at five time points (0–8 h). Intron retention (IR) was the predominant AS type (~36–37%), followed by A3SS, A5SS, and exon skipping (SE). Notably, light enhanced both the magnitude and temporal dynamic of AS, with a pronounced early response (0–2 h) under SD, where differential AS (DAS) events were nearly doubled compared with SN. This early AS response was accompanied by an increased prevalence of IR events and upregulation of spliceosome-related genes, suggesting dynamic splicing regulation under light. Enrichment of the mRNA surveillance pathway further indicates that IR-derived transcripts may be subject to RNA quality control. Although enriched pathways were largely conserved between SD and SN, including spliceosome and mRNA surveillance, more DAS genes under SD indicate enhanced responsiveness of conserved regulatory networks. These findings demonstrate that light reshapes the temporal dynamics of AS under salt stress, primarily through IR and its coupling with RNA surveillance, providing new insights into post-transcriptional regulation in crop stress adaptation. Full article

Introduction: Hyponatremia is a common electrolyte abnormality in heart failure and has been consistently associated with worse clinical outcomes. While its prognostic value is well established in heart failure with reduced ejection fraction, its significance in heart failure with preserved ejection fraction remains less clearly defined. Increasing evidence suggests that hyponatremia may reflect advanced neurohormonal activation, congestion, and cardiorenal dysfunction in this population. Methods: This study was conducted as a narrative review of the literature examining the pathophysiology, clinical implications, and management of hyponatremia in heart failure with preserved ejection fraction. Electronic databases including PubMed, EMBASE, Cochrane Library, Scopus, and Google Scholar were searched for relevant publications between 2010 and 2025. Eligible sources included clinical trials, observational studies, registry analyses, guideline documents, and review articles focusing on sodium disorders in heart failure populations. The findings were synthesized qualitatively to provide an integrated overview of the mechanisms, prognostic significance, and therapeutic considerations. Results: Available evidence indicates that hyponatremia occurs frequently in patients with heart failure with preserved ejection fraction and is associated with increased risks of mortality, rehospitalization, and cardiovascular events. The underlying mechanisms involve complex interactions between neurohormonal activation, impaired renal free water excretion, and therapeutic factors such as diuretic exposure. Hyponatremia appears to function primarily as a marker of disease severity rather than a direct mediator of adverse outcomes. Current management strategies primarily rely on general heart failure treatment principles, including optimizing diuretic therapy, managing fluid balance, and selectively using vasopressin antagonists. Conclusions: Hyponatremia represents an important biomarker of adverse prognosis in heart failure with preserved ejection fraction. Despite its clinical relevance, evidence guiding phenotype-specific management remains limited. Future research should focus on clarifying pathophysiologic mechanisms, improving risk stratification, and determining whether targeted correction of hyponatremia can improve clinical outcomes in this growing patient population. Full article

The assessment of non-stationarity in the rainfall process is still a major research topic in the field of applied hydrology. The water cycle is affected by several characteristics of this process: rainfall volume, wet weather duration, their mutual association, and the annual number of events. The method used to sample rainfall variables from the time series may or may not suitably account for their variability. Herein, the rainfall process is analyzed using a bivariate event-based approach, with reference to two rainfall time series recorded at short time steps in different Italian climates. Trends are also estimated. Full article

Background: Generative AI (GenAI) mental health chatbots are increasingly being developed to help address persistent barriers to mental healthcare. Unlike earlier rule-based and retrieval-based systems, GenAI chatbots generate open-ended outputs that can be inaccurate and unsafe. Documented harms from general-purpose GenAI chatbots have highlighted the need for purpose-built interventions with dedicated safeguards, yet how safety is implemented in such interventions remains poorly understood. Methods: This scoping review followed the Joanna Briggs Institute methodology and PRISMA-ScR guidelines, with a prospectively registered and peer-reviewed protocol. A systematic search of seven academic databases and search engines including MEDLINE, Scopus, PsycINFO, ACM Digital Library, IEEE Xplore, Google Scholar and Consensus was conducted in July 2025. Two reviewers independently screened records and extracted data. Safety mechanisms and risk mitigation strategies were narratively synthesised across three pre-specified domains: technical safeguards, pre-deployment safety considerations, and delivery-phase risk mitigation strategies. Results: Twenty-one studies across 11 countries were included. Most interventions incorporated at least one technical safety mechanism, most commonly fine-tuning and prompt engineering. A smaller subset implemented layered safety architectures combining retrieval systems, content filters or risk classifiers, and rule-based algorithms. Pre-deployment safeguards included clinical expert and user co-design approaches, research ethics procedures, and data privacy measures. During intervention delivery, detailed onboarding with role clarification was common, but human oversight was limited. Crisis referral protocols varied in rigour but were mostly underdeveloped, and systematic adverse event monitoring was sparse. Documented safety failures included missed suicidal ideation and provision of inaccurate clinical information. Conclusions: GenAI chatbot interventions require a robust sociotechnical approach that integrates technical safeguards with user co-design, procedural controls, and human oversight. Future research is needed to evaluate efficacy, improve safeguards and standardise safety outcome measurement. Regulatory oversight proportional to the risks these systems carry is required to enable integration into stepped or blended mental healthcare. Full article

The steno-endemic Verbascum rupicola faces a precarious future due to its extreme habitat specialization on tectonically active hydrothermal quartz veins. This study presents a long-term assessment based on periodic population censuses spanning 18 years (2007, 2016, and 2025) to assess the demographic and spatial trends of its global population in the Tahtalı Dam basin, Türkiye. Field surveys, GIS-based habitat mapping, and controlled pollination experiments were integrated with seed germination kinetics and ex situ cultivation trials. Results reveal a precipitous 69.12% global population decline, primarily driven by a 33.41% habitat loss from agricultural expansion in 2011 and the total extirpation of three sub-populations by a major wildfire in 2017. Furthermore, a “reproductive squeeze” was identified, where climate-induced reductions in flower production (18.87%) are compounded by intensifying floral predation by Pieris rapae. Reproductive analysis revealed random monomorphic enantiostyly—reported for the first time in the genus—which functions as a flexible mating system prioritizing outcrossing while providing reproductive assurance. Despite high intrinsic seed viability (69.12%), ex situ cultivation largely failed (3.5% survival; 1 out of 28 transplanted individuals), underscoring the species’ obligate chasmophytic nature. Consequently, V. rupicola meets the criteria for Critically Endangered (CR) status, necessitating urgent “micro-reserve” protection of its remaining habitat and in situ restoration efforts. Full article

Mass transfer–induced Marangoni convection in volatile binary liquids is commonly associated with the amplification of interfacial concentration disturbances, yet the localized evolution preceding the first visible convective cell remains difficult to quantify experimentally. Here, ethanol–water desorption in a confined quasi–two–dimensional cell with a 2 mm liquid thickness was investigated using quantitative Schlieren imaging. The apparent transient concentration field and interfacial concentration profiles were reconstructed to resolve the earliest observable stage of Marangoni onset. The early behavior depended strongly on the initial ethanol mass fraction. Low–concentration cases mainly exhibited Rayleigh plume structures, high–concentration cases developed Marangoni cellular structures too rapidly for reliable early–stage tracking, whereas intermediate–concentration cases provided a resolvable window before Marangoni cell formation. For an initial ethanol mass fraction of 8 wt.%, a localized interfacial onset site appeared before the first visible Marangoni convective cell. This event initiated two counter–propagating spreading fronts, enriched the swept interfacial region, and was followed shortly by visible Marangoni cellular structures within the redistributed region. The apparent surface tension gradient field exhibited a transient evolution, with an initial increase, followed by a decrease during spreading, and a subsequent increase upon front interaction. These results provide experimental reference data for the pre–cellular interfacial redistribution sequence associated with perturbation–driven Marangoni onset in confined ethanol–water desorption systems. Full article