Search Results (82,212)

Intramuscular fat (IMF) is a pivotal determinant of meat quality in yaks (Bos grunniens). While nutritional factors are well-documented, the epigenetic landscape, particularly the transcriptional architecture governed by super-enhancers (SEs), remains largely unexplored in the context of IMF deposition. To investigate SE-associated genes, Chromatin immunoprecipitation sequencing (ChIP-seq) assays using H3K27ac antibodies and RNA-sequencing (RNA-Seq) were conducted on longissimus dorsi (LD) muscle tissues with high and low IMF contents. Integrated multi-omics analysis identified 82 enhancer-associated genes exhibiting significant upregulation in high-IMF samples, with 63 loci characterized as SE-associated. In particular, H3K27ac signal distribution analysis indicated that SEs were distributed across functional regions such as promoters, gene bodies, exons, and introns. Among these SE-related genes, 3-hydroxybutyrate dehydrogenase 1 (BDH1) was further investigated to understand its function and regulatory mechanisms. To address this, overexpression or knockdown experiments were conducted, followed by CCK-8, EdU, Bodipy functional assays, and Real-time quantitative PCR (RT-qPCR) analysis. Functional experiments revealed that BDH1 acts as a key positive regulator of yak preadipocyte differentiation and is a prime SE-associated candidate regulatory gene. Furthermore, dual-luciferase reporter assays were performed to identify its SE region, revealing that the activity of 4 enhancer regions was significantly upregulated. Collectively, these findings implicate SE-associated genes in IMF deposition in yaks, provide a valuable resource for future research, and underscore the functional relevance of BDH1 in this process. Full article

Artificial intelligence (AI) and digital technology provide extensive possibilities for education. But focusing only on their implementation does not address the challenges associated with them and they may even have a negative impact on learners. So far, the disciplines of psychology and computer science have not provided a theoretical framework for the competence needed to develop and use AI and digital technology in education in order to prepare learners for successful participation in modern societies. The main aim of this paper is to theoretically specify competent use of AI and digital technology in education and to provide a standardized instrument to evaluate courses that teach this competence. Therefore, we (a) combine theoretical contributions from both scientific disciplines to formulate a theoretical framework with four levels for the “Competence to Use Artificial Intelligence and Digital Technology in Educational Processes” (AIEDTEC competence), (b) introduce a questionnaire to evaluate courses that teach AIEDTEC competence, and (c) present results regarding its psychometric properties ($N=240$). The questionnaire showed good to very good psychometric properties and the assumed factor structure was supported by confirmatory factor analyses. The paper connects research on systems thinking and learning and instruction with recent developments regarding AI and digital technology and thereby provides an essential base for creating effective, modern, and safe learning environments in the future as well as a psychometric evaluation instrument. Full article

Upper tract urothelial carcinoma (UTUC) presents distinct diagnostic and therapeutic challenges because of its rarity, anatomic constraints, frequent understaging at biopsy, and risk of systemic recurrence after radical nephroureterectomy. Current perioperative management is driven primarily by clinicopathologic risk factors, which may be insufficient to identify occult molecular residual disease (MRD) or to determine which patients are most likely to benefit from systemic therapy. This narrative review summarizes available evidence on circulating tumor DNA (ctDNA) in UTUC and related urothelial carcinoma settings, classifies the level of evidence supporting each application, and proposes a research framework for prospective evaluation. The strongest UTUC-specific evidence supports ctDNA as a prognostic biomarker associated with recurrence risk, whereas predictive validity for selecting chemotherapy, immune checkpoint inhibitors, antibody-drug conjugates, targeted therapy, or surveillance intensity remains unproven. Evidence from muscle-invasive bladder cancer, including ctDNA-correlative and ctDNA-guided perioperative trials, provides biologic rationale but should not be directly translated into routine UTUC care without disease-specific validation. We outline key implementation questions, including target population, assay selection, timing, false-positive and false-negative results, lead-time bias, and integration of plasma ctDNA with utDNA. Prospective UTUC-specific trials are needed to determine whether ctDNA-guided perioperative strategies improve survival, reduce unnecessary toxicity, and are cost-effective. 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

Background: Although guidelines emphasize proper insertion techniques and tip positioning, catheter-related thrombosis (CRT) remains a common and clinically significant complication of peripherally inserted central catheters (PICCs) and midline catheters (MCs). In this context, the use of pharmacological prophylaxis is still debated. This study aims to assess the incidence of CRT in patients receiving anticoagulant therapy (therapeutic or prophylactic) and antiplatelet therapy. Methods: This retrospective study was conducted at a tertiary care hospital and included adult patients from March 2021 to May 2023. Six potential confounders were analyzed: anticoagulation status (none, prophylaxis, therapeutic), antiplatelet therapy, tip position (PICCs vs. MCs), number of lumens, CRT risk factors, and drug infusion requiring central access. CRT was diagnosed in symptomatic patients using compression ultrasonography. Propensity score weighting and logistic regression were employed to estimate odds ratios (OR) and average treatment effects. Results: A total of 1431 patients were enrolled. PICCs and therapeutic anticoagulant therapy were highly protective against CRT (OR 0.068 [95% CI 0.013–0.2] and OR 0.007 [95% CI 0.001–0.046], respectively). Prophylactic anticoagulant therapy (OR 0.328 [95% CI 0.200–0.519]) and antiplatelet therapy (OR 0.342 [95% CI 0.182–0.595]) also showed protective effects. At the same time, neither the number of lumens, the presence of risk factors, nor the infusion of irritating drugs was independently associated with CRT. Conclusions: The use of anticoagulant drugs (both prophylactic and therapeutic), antiplatelet therapy, and PICC use significantly lowered the risk of CRT. The findings support personalized prevention strategies and underscore the need for a well-designed randomized controlled trial to validate these findings. 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

Background: Cancer is a chronic disease with significant health impacts and is a leading cause of mortality worldwide. Cancer patients often require frequent hospital visits to manage their condition effectively. Therefore, understanding the factors that influence their ability to access healthcare services—such as age, gender, citizenship, region of residence, educational level, and income—is crucial, as these factors can impact continuity of care and overall quality of life. Purpose: This study aims to identify the factors determining cancer patients’ healthcare access and to propose alternative solutions that will enhance their ability to access services. Methods: This cross-sectional quantitative study utilized the health belief model for data analysis. Data were collected randomly through an online questionnaire targeting cancer patients across Saudi Arabia. Results: The findings indicated that payment method, distance to healthcare facilities, tumor type, and willingness to use virtual appointments were significantly associated with access to healthcare services. A total of 391 participants were included, the majority of whom were female (n = 291), aged 39 to 48 (n = 111), Saudi citizens (n = 376), residing in the Eastern region (n = 210), holding a bachelor’s degree (n = 193), and reporting no monthly income (n = 110). Conclusions: Access to healthcare services for cancer patients in Saudi Arabia is challenged by several factors, including payment methods, travel distance, cancer type, and the acceptance of health applications. Promoting digital health tools and virtual appointments can significantly improve access to care and facilitate ongoing management for cancer patients. Full article

Background and Objectives: Pulmonary hypertension (PH) remains associated with substantial mortality despite advances in treatment. Although prognostic factors have been widely described at sea level, their behavior in populations living at high altitude remains insufficiently characterized. This study aimed to identify factors associated with mortality during follow-up in patients with Group 1 PH residing at high altitude. Materials and Methods: A retrospective cohort study was conducted including patients with confirmed Group I PH diagnosed by right heart catheterization and treated between 2017 and 2022. Clinical, functional, and hemodynamic variables were analyzed. A penalized logistic regression model using Elastic Net methodology was applied to identify variables associated with five-year mortality. Results: A total of 165 patients were included, with a mean age of 41 years (SD 13.93), and 84.2% were women. Among PH etiologies, congenital heart disease was the most frequent cause (50.3%), followed by idiopathic PH (33.3%) and connective tissue disease-associated PH (12.7%). Five-year mortality was 13.3% (22/165). Idiopathic pulmonary hypertension was significantly more frequent among deceased patients compared to survivors (13/22 [59.1%] vs. 42/143 [29.4%], p = 0.025). Mortality was associated with acute pulmonary embolism, greater smoking burden, worse functional class, and adverse hemodynamic parameters. In multivariable analysis, acute pulmonary embolism (coefficient 0.196; OR 1.216; 95% CI 1.16–1.27; p < 0.001), ESC/ERS risk stratification (coefficient 0.158; OR 1.171; 95% CI 1.08–1.26; p < 0.001), pulmonary vascular resistance > 25 wood units (coefficient 0.180; OR 1.198; 95% CI 1.13–1.26; p < 0.001), and age ≥ 65 years (coefficient 0.171; OR 1.187; 95% CI 1.10–1.27; p < 0.001) were identified as risk factors, while female sex showed a protective effect (coefficient −1.041; OR 0.353; 95% CI 0.33–0.37; p < 0.001). Conclusions: In patients with Group 1 PH living at high altitude, several clinical, functional, and hemodynamic variables were associated with increased mortality, including acute pulmonary embolism, elevated pulmonary vascular resistance, advanced age, and intermediate-high risk stratification. Female sex was associated with lower mortality. Full article

This study examined alterations in serum redox biomarkers before and one month after administration of the coronavirus disease 2019 (COVID-19) booster (third) doses across four vaccine regimens. A longitudinal cohort of 410 adults was analyzed following homologous Pfizer-BioNTech, Sinopharm [Vero Cell]-Inactivated, Sputnik V, or heterologous Sinopharm/Pfizer vaccination. Serum total proteins, albumin, total thiols, nitrites, ferric-reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity were measured, with DPPH interpreted as an ex vivo surrogate of serum radical-scavenging capacity. Additional analyses included stratification by prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, multivariable regression, correlation analysis, effect-size estimation, and sensitivity testing. Booster vaccination was associated with modest but consistent decreases in DPPH activity, albumin, and total proteins, whereas FRAP, nitrite, and total thiol levels remained stable. This pattern supports a transient shift in antioxidant buffering capacity but, by itself, does not exclude oxidative stress, as direct oxidative damage markers were not assessed. The most pronounced changes were observed in Sinopharm-based regimens, particularly in the heterologous Sinopharm/Pfizer group. Prior SARS-CoV-2 infection did not materially alter the qualitative response pattern, whereas older age and comorbidities were associated with greater declines in DPPH activity and albumin. Overall, the findings indicate a modest, transient redox-associated response following booster-induced immune activation and suggest that host-related factors, such as age and comorbidity burden, may accentuate short-term changes in antioxidant buffering capacity. Full article

Background and Objectives: Healthcare-associated infections (HAIs) remain a major cause of morbidity and mortality among hospitalized patients. During the COVID-19 pandemic, SARS-CoV-2 infection emerged as a major contributor to HAIs, alongside Clostridioides difficile infection (CDI) and other bacterial infections. This study aimed to evaluate the clinical characteristics and outcomes of HAIs in surgical departments and to identify factors associated with in-hospital mortality. Materials and Methods: We conducted a retrospective observational study including 170 patients with documented HAIs admitted between July 2018 and June 2022 in surgical departments of a county emergency hospital. Patients were categorized into SARS-CoV-2 infection (n = 85), CDI (n = 73), and other bacterial infections (n = 12), the latter being included for descriptive purposes only due to limited sample size. Clinical variables, comorbidities, prior antibiotic exposure, length of hospital stay, and in-hospital mortality were analyzed. Survival analysis and logistic regression were performed to identify predictors of mortality. Results: SARS-CoV-2 infection represented the largest subgroup, followed by CDI. Overall, in-hospital mortality was 15.9%, with comparable rates between SARS-CoV-2 infection (17.6%) and CDI (16.4%), while no deaths were observed in the small subgroup of other bacterial infections. CDI patients had a significantly higher burden of comorbidities (p = 0.004). Kaplan–Meier analysis did not show a statistically significant difference in survival between SARS-CoV-2 and CDI groups (log-rank p = 0.28). In univariate analysis, acute respiratory failure (OR ≈ 13.5, p < 0.001), chronic kidney disease (OR ≈ 4.4, p = 0.018), and number of comorbidities (p = 0.019) were associated with mortality, but none remained significant in multivariable analysis. Conclusions: In-hospital mortality was similar between SARS-CoV-2 infection and CDI, highlighting the persistent clinical impact of CDI in hospitalized patients. Comorbidity burden and acute complications, particularly respiratory failure, were key determinants of mortality. These findings highlight the persistent clinical impact of CDI and the role of comorbidity burden and acute complications, particularly respiratory failure, in shaping in-hospital mortality. The absence of independent predictors in multivariable analysis should be interpreted cautiously given the limited sample size. Full article

Background/Objectives: Food and nutritional insecurity (FNI) is a major social determinant of health that disproportionately affects older adults, with significant implications for their health, nutrition, and well-being. In this context, this scoping review aims to map and synthesize the available scientific evidence on the main determinants of FNI among older adults, considering socioeconomic, health-related, functional, psychosocial, and structural factors. Methods: A scoping review was conducted in accordance with the Joanna Briggs Institute methodology and reported following the PRISMA-ScR guidelines. A comprehensive search was performed across eight databases (PubMed/MEDLINE, EMBASE, Scopus, Web of Science, CINAHL, LILACS, ProQuest, and Google Scholar), up to November 2024. Original studies addressing FNI in individuals aged ≥60 years were included. Study selection and data extraction were conducted independently by two reviewers, with disagreements resolved by consensus. Results: Of 5897 records identified, 15 studies met the inclusion criteria. FNI in older adults was described as a multifactorial phenomenon associated with low income, limited education, social isolation, widowhood, chronic diseases, functional limitations, depressive symptoms, and poor housing conditions. Structural determinants, including institutional racism, gaps in social protection systems, and barriers to accessing food assistance programs, were also reported. Considerable heterogeneity in measurement instruments highlights the complexity of assessing FNI in this population. Conclusions: Addressing FNI in older adults requires moving beyond isolated interventions toward integrated, intersectoral strategies that tackle its underlying social and structural drivers. Strengthening social protection systems, reducing access barriers, and promoting equity-oriented policies are essential to ensure adequate nutrition and support healthy and dignified aging. Full article

Background: Autism spectrum disorder (ASD) is consistently associated with a high prevalence of sleep disturbances across the lifespan, with reported rates ranging from 60% to 86% depending on age and clinical characteristics. Although this issue has been widely described in the international literature, Spain currently lacks large-scale data to estimate the prevalence of sleep disturbances or to examine their relationship with factors such as age, intellectual disability, and co-occurring conditions. This study aims to estimate the prevalence and severity of sleep disturbances in individuals with autism spectrum disorder in Spain and to examine their associations with developmental stage, intellectual disability, affective symptoms, and contextual factors. Methods: This is a cross-sectional observational survey with nationwide dissemination approved by the Ethics Committee of the Universidad Católica San Antonio de Murcia. Data will be collected through an online survey (SurveyMonkey) including validated instruments: the Children’s Sleep Habits Questionnaire–Autism (CSHQ-Autism) and the Sleep Disturbance Scale for Children (SDSC) for pediatric participants; the Pittsburgh Sleep Quality Index (PSQI) for adolescents and adults without intellectual disability; and the Diagnostic Assessment for the Severely Handicapped–II (DASH-II) for adults with intellectual disability. Anxiety and depressive symptoms will be assessed using the Child Behavior Checklist (CBCL) in children and adolescents and the Hospital Anxiety and Depression Scale (HADS) and DASH-II. Statistical analyses will be conducted using SPSS v22 by applying parametric or non-parametric tests according to data distribution. Conclusions: This study represents one of the first survey protocols with nationwide dissemination designed to assess sleep disturbances in individuals with ASD in Spain. The resulting findings are expected to help identify vulnerability profiles, inform public health strategies, and support the development of multidisciplinary interventions aimed at improving sleep and, consequently, the quality of life of individuals with autism and their families. Full article

Background/Objectives: Mycophenolic acid (MPA) monitoring may improve organ transplant outcomes, yet clinical implementation is hindered by the complex pharmacokinetics of MPA and a lack of clarity regarding the influence of specific patient factors on drug exposure. While the area under the curve (AUC) is the gold standard for MPA monitoring, it is not easily validated or implemented in routine practice. This pilot project aimed to identify key clinical and biochemical covariates driving pharmacokinetic variability in a renal transplant population. Methods: This prospective study analyzed 103 samples from 66 kidney transplant recipients. To estimate total drug exposure (AUC), a limited sampling strategy was used with plasma samples collected at trough, and then 30 and 120 min post-dose. We performed linear univariate and multivariate regressions to evaluate the impact of patient characteristics (age, sex, body mass index (BMI)) and biochemical measurements (P-albumin, P-creatinine, estimated glomerular filtration rate (eGFR), B-tacrolimus) on MPA-AUC, peak concentrations (C_max) and trough levels. Results: At 750 mg twice daily, the median MPA-AUC was 43.5 mg·h/L (IQR: 34.5–53.5). After adjusting for dose, P-albumin and age were independent predictors of AUC: P-albumin levels were positively associated with AUC (β = 1.849, p < 0.001), while age showed a modest negative association (β = −0.282). BMI was significantly and inversely associated with trough concentrations (β = −0.137, p = 0.011), indicating that higher BMI is linked to lower trough concentrations. Male sex was associated with significantly lower AUC and C_max compared to females. Notably, eGFR and B-tacrolimus levels did not significantly influence MPA exposure in this cohort. Conclusions: The covariates BMI, sex, age, and P-albumin significantly influence MPA-AUC. LSS-based AUC monitoring, using 30–60 mg·h/L as a target and with consideration of a few patient-specific factors, could be a pragmatic and feasible approach to improve MMF dosing strategies in kidney transplant recipients. Full article

Purpose: Autopsy remains an important diagnostic and research modality in pediatric oncology. This study examined demographic and clinical factors associated with parental acceptance or decline of autopsy in childhood cancer. Patients and Methods: This study was a retrospective chart review of autopsy consent acceptance or decline patterns between 2007 and 2017 for inpatient pediatric oncology deaths in a large single-site oncology hospital. Demographic factors (age, race, gender), diagnostic factors (primary cancer, transplant history, and neurologic status 24 h prior to death), interventions (intensive care unit location, dialysis, ventilator, chemotherapy, medically administered nutrition), and code status in the 24 h prior to death were obtained. Analysis included descriptive and statistical correlations. Results: Among 344 inpatient decedents, 34% of families consented to autopsy. There was a difference in consent rate according to race (p = 0.015). Diagnosis, transplant status, age, and neurologic status showed no association. Use of dialysis (p < 0.001), ventilation (p < 0.001), and intensive care unit (ICU) location (p < 0.001) correlated with higher consent rates. Chemotherapy and assisted nutrition were not associated with decisions. Presence of a Do Not Resuscitate (DNR) order predicted lower consent (p < 0.001), while receipt of cardiopulmonary resuscitation (CPR) at death predicted higher consent (p < 0.001). Conclusion: One-third of families of inpatient pediatric oncology decedents with cancer agreed to autopsy. Demographic and diagnostic factors were not universally strong predictors, underscoring the personal nature of autopsy decisions. Further research should include multisite prospective designs and direct engagement with bereaved families. Full article

Background: Long-term survivors (LTS) after gynecological cancer may be cured but still face physical and psychological challenges. This multicenter study aimed to assess the long-term side effects, the received follow-up care, and the personal perspectives of survivors. Methods: Between 2019 and 2025, LTS from four European countries within the ENGOT (European Network of Gynecological Oncological Trial Groups) and GCIG (Gynecologic Cancer InterGroup) networks were recruited. Long-term survival was defined as surviving at least five years after the first diagnosis. LTS completed a questionnaire with 81 questions (patient’s characteristics, oncological history, current health status, lifestyle factors). Analyses were mainly descriptive. Results: A total of 677 LTS were enrolled, with a median age of 64.0 years (range: 26–92) and a median survival time of 7 years (range: 5–38). A total of 46.6% were diagnosed with cervical cancer, 32.9% with endometrial cancer, 4.4% with ovarian cancer, and 16.1% with other types of gynecological cancer. Moreover, 36.9% still suffer from physical and psychological symptoms, most frequently being lymphedema (36.2%), hot flashes (22.4%), difficulties with concentration (21.1%), fatigue (20.9%), vaginal dryness (20.1%), and urinary incontinence (18.9%). Median overall health status was ranked (scale 1–5; 1 = very good, 5 = very poor) as 2, while 13.5% rated their health as poor/very poor. Current symptoms were associated with poorer health status (p < 0.001) and a history of recurrent disease (p = 0.001). In addition, 13.6% reported not receiving follow-up care. CA-125 was determined in 80.8% of ovarian LTS, as well as in 30.7% of cervical and 28.9% of endometrial LTS. Pap smear follow-up was reported by 50.5% of endometrial LTS. A total of 33.7% did not exercise at all or exercised less than an hour per week, 13.4% smoke tobacco, and 51.2% drink alcohol more often than once a month. Conclusions: Our findings highlight the need for patient-centered follow-up care, addressing both long-term side effects and education on lifestyle and prevention. Follow-up procedures that do not follow guidelines should be avoided. Full article