Search Results (21,311)

Dietary sodium restriction is widely recommended in heart failure (HF) management; however, its benefits and risks remain a subject of ongoing debate. While moderate sodium reduction may improve symptoms and quality of life in selected patients, excessive restriction can trigger maladaptive neurohormonal activation, worsen renal function, and increase the risk of hyponatremia, malnutrition, and cachexia. Patient response is heterogeneous, influenced by clinical risk profile, salt sensitivity, comorbidities, and age, with some high-risk patients experiencing neutral or adverse outcomes. Additional challenges arise from hidden sodium in processed foods, medications, and meals, which complicate monitoring and adherence. Effective sodium management in HF therefore requires a nuanced, individualized approach that integrates risk stratification, dietary counseling, and public health measures targeting the food industry. Future research should refine patient selection criteria and establish optimal sodium targets to balance therapeutic efficacy with safety in real-world practice. Full article

Permethrin (PERM) is a synthetic pyrethroid insecticide initially regarded as low risk. However, evidence now indicates that misuse and prolonged exposure can damage multiple physiological systems by disrupting enzymatic functions in subcellular structures. In this study, male Wistar rats were administered PERM (75, 150, or 300 mg/kg/day) for 15 days to assess its effect on hematological and biochemical parameters, including oxidative stress markers in the liver, kidney, and heart. Subacute PERM administration induced significant, dose-dependent toxicological alterations in exposed animals. Hematological analysis revealed impaired hematopoiesis, characterized by increased erythrocytes and platelets alongside decreased hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width. Biochemical analysis revealed elevated liver enzymes and bilirubin, along with reduced albumin levels, indicating hepatic alterations associated with PERM. The assessment of oxidative stress revealed tissue-specific responses following PERM exposure. While GPx, CAT, and SOD levels remained unchanged, GR activity increased in the heart, and GST activity increased in the liver. Additionally, a substantial decrease in MDA was observed in both the liver and heart. These collective alterations found in PERM-subacute exposed rats suggest the potential for cellular damage with the possible development of chronic pathologies, warranting further investigation. Full article

Training not only enhances the athletic performance of horses but also improves cardiac structure and function, strengthens cardiovascular adaptability, and reduces the risk of cardiovascular diseases. However, the consequences of training on equine cardiac structure and function remain unclear. This study investigated the morphological, functional, genetic, and metabolic changes in the hearts of Yili horses divided into three groups: high athletic performance (agility group, AG), low athletic performance (ordinary group, OG), and untrained (untrained group, UN). The results showed remodeling of the cardiac structure and physiological adaptations in AG and OG compared to UN groups, with differences between AG and OG primarily in the left ventricle. To explore the molecular mechanisms underlying these phenotypic changes, transcriptomic and metabolomic analyses (particularly GO and KEGG pathway analyses) were performed to assess differences in gene expression and metabolite levels among the three groups. Our results show that miR-1842, miR-671, miR-106b and miR-18a were differentially expressed in the trained groups (AG group and OG group) compared with the control group that did not receive training. These regulatory factors would regulate PFKFB3 to affect the glycolytic activity mediated by HIF-1, there by promoting glycolysis and changing lactate level. This, in turn, would positively feedback to stabilize HIF-1, thus forming a closed loop for the reprogramming of myocardial energy metabolism. In the AG group, positive effects of cAMP signaling were noticeable. In conclusion, our findings offer new insights into physiological cardiac remodeling in Yili horses by highlighting genetic and metabolomic changes resulting from exercise training. Full article

Background: Sarcopenia and metabolic deterioration are major health concerns in adults aged ≥ 75 years with type 2 diabetes (T2DM), a population characterized by anabolic resistance, reduced dietary intake, and limited renal reserve. Optimizing protein nutrition may support muscle maintenance in this high-risk group, but clinical evidence for individualized high-protein guidance in the oldest-old population remains limited. Objective: We investigated whether an 18-month dietary intervention improves muscle mass and strength in adults aged ≥ 75 years with T2DM and whether serum amino acid (AA) and hormonal profiles reflect these changes. Methods: In this 18-month, single-arm, prospective intervention study, 44 community-dwelling adults aged ≥ 75 years with T2DM received individualized, dietitian-led nutritional guidance targeting a protein intake of approximately 1.4 g/kg ideal body weight (IBW)/day. Assessments at baseline and every 6 months included body composition, muscle strength, renal function, and fasting serum amino acid and hormonal profiles. Longitudinal changes were analyzed using paired t-tests and linear mixed-effects models. This trial was registered in the UMIN Clinical Trials Registry (UMIN000044687). Results: Skeletal muscle index and grip strength showed significant improvements at specific time points during follow-up (both p < 0.05), while gait speed improved at 6 months. Renal function remained clinically stable (eGFRcreat slope: +0.18 mL/min/1.73 m²/year; eGFRcys slope: −2.97 mL/min/1.73 m²/year), with no significant increase in CKD stage. Changes in glucagon correlated positively and C-peptide negatively with changes in skeletal muscle index, whereas glucagon was inversely associated with grip strength. Serum fibroblast growth factor 21 (FGF21) levels decreased over time, suggesting metabolic adaptation to the intervention. Conclusions: Individualized high-protein nutritional guidance for 18 months improved sarcopenia-related parameters, including skeletal muscle index and grip strength, without clinically significant deterioration of renal function in adults aged ≥ 75 years with T2DM. These findings support the feasibility and safety of protein-focused dietary counseling as a strategy to preserve muscle health in advanced age. Full article

Background and Objectives: NR5A1-related 46,XY differences of sex development (DSD) represent a heterogeneous group of conditions characterized by variable degrees of undervirilization, gonadal dysgenesis, and endocrine dysfunction. Mutations in the NR5A1 gene affect critical pathways of gonadal development and steroidogenesis, leading to complex diagnostic and management challenges. This narrative review aims to summarize the clinical spectrum, diagnostic algorithms, surgical management, and outcome data of pediatric NR5A1-related 46,XY DSD. Materials and Methods: A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted, using terms related to NR5A1 mutations, ambiguous genitalia, gonadal dysgenesis, tumor risk, and surgical management. A total of 26 studies were initially identified, of which 16 met the inclusion criteria for pediatric patients (≤18 years) with confirmed 46,XY karyotype, NR5A1 mutation, and available clinical or surgical data. Results: NR5A1 mutations are associated with phenotypes ranging from complete female external genitalia to apparently normal males with later infertility. While Sertoli cell function during fetal life is often preserved, Leydig cell dysfunction leads to incomplete masculinization. Spontaneous virilization during puberty has been reported. Management of gonadal dysgenesis remains controversial: while streak-like intra-abdominal gonads carry high germ cell tumor risk, warranting early gonadectomy, well-formed testes may be preserved under strict surveillance. Conclusions: NR5A1-related 46,XY DSD requires individualized, multidisciplinary management integrating genetic, endocrine, surgical, and psychosocial expertise. Gonadectomy decisions should be risk-stratified and, when possible, delayed to allow patients to participate in decision-making. Early psychological support and lifelong follow-up are essential to optimize physical and psychosocial outcomes. Full article

At present, ionic liquids (ILs) are increasingly being used to extract natural products as green solvents, but their residues can lead to risks in terms of further use for the extracted herbal materials. Therefore, it is necessary to remove them with simple and effective methods. For example, after the toxic anthraquinones in Polygonum multiflorum are removed by extraction with the IL of [C₄Bim][PTSA], it needs to be recovered and reused, and the useful stilbene glycosides should not suffer from obvious loss as they are the main functional components. In this study, an ultrasonic method with n-propanol was used to remove the residual [C₄Bim][PTSA] in the solid powders of Polygonum multiflorum that had been extracted for anthraquinones. After single-factor optimization, the removal conditions were as follows: the removal temperature was 303.15 K, the solid–liquid ratio was 1:200 (w (1 g):v (200 mL)), the ultrasonic time was 40 min, and there were four operations. Under these conditions, ILs could be completely removed with almost no loss of stilbene glycosides in solid powders. After that, the IL in the extracting solution and scrubbing solution was recovered by the back-extraction method, and an IL with high purity could be obtained for reuse. The total recovery efficiency of the IL reached more than 98%. Then gas chromatography (GC) was conducted for the determination of residual ethanol and n-propanol in the solid powders of Polygonum multiflorum, which could be used to quickly detect the contents of two organic solvents within three minutes. Besides that, the method could also be applied to the determination of residual organic solvents in the raw materials of Polygonum multiflorum, and the results showed that the residue of ethanol and n-propanol in the solid powders were in accordance with the general provisions of the current Chinese Pharmacopoeia. According to the developed procedures and optimized conditions, the recovered IL could be reused in five runs at least. General applicability and greenness assessment for the developed process also proved that it is an ideal method, which has potential in large-scale application. Full article

Protein–DNA and protein–RNA interactions are central to gene regulation and genetic disease, yet experimental identification remains costly and complex. Machine learning (ML) offers an efficient alternative, though challenges persist in representing protein sequences due to residue variability, dimensionality issues, and the risk of losing biological context. Traditional approaches such as k-mer counting or neural network encodings provide standardized sequence representations but often demand high computational resources and may obscure functional information. To address these limitations, a novel encoding method based on interpolation of physicochemical properties (PCPs) is introduced. Discrete PCPs values are transformed into continuous functions using logarithmic enhancement, highlighting residues that contribute most to nucleic acid interactions while preserving biological relevance across variable sequence lengths. Statistical features extracted from the resulting spectra via Tsfresh are then used for binary classification of DNA- and RNA-binding proteins. Six classifiers were evaluated, and the proposed method achieved up to 99% accuracy, precision, recall, and F1 score when amino acid highlighting was applied, compared with 66% without highlighting. Benchmarking against k-mer and neural network approaches confirmed superior efficiency and reliability, underscoring the potential of this method for protein interaction prediction. Our framework may be extended to multiclass problems and applied to the study of protein variants, offering a scalable tool for broader protein interaction prediction. Full article

Background: Radiation necrosis (RN) is a delayed and potentially debilitating complication of radiotherapy for central nervous system (CNS) tumors. It presents significant diagnostic and therapeutic challenges due to the variable clinical manifestations and overlap with tumor recurrence. Although advances in radiotherapy have improved tumor control, RN remains incompletely understood and inadequately addressed. This narrative review synthesizes current evidence on RN pathophysiology, risk factors, diagnostic strategies, and management approaches. Methods: A literature search was conducted for English-language literature published between January 1990 and December 2024. Studies were included if they addressed RN incidence, diagnosis, treatment, or novel preventive strategies in CNS tumor populations. Relevant findings were synthesized to produce a narrative review summarizing pathophysiology, diagnostic challenges, and treatment strategies. Results: RN results from radiation-induced neurovascular injury, inflammation, and vessel permeability, with incidence ranging from 3 to 26% depending on tumor type, location, and treatment parameters. Risk is influenced by dose, fractionation, cumulative exposure, re-irradiation, and adjuvant therapies. Advanced modalities such as SRS, HFSRT, brachytherapy, proton therapy, and IORT reduce but do not eliminate RN risk. Diagnosis remains challenging despite advanced MRI and PET techniques, with histopathology as the gold standard. Management includes corticosteroids, bevacizumab, surgery, LITT, and experimental therapies. Connectomics-based planning shows promise in minimizing RN by sparing critical brain networks. Conclusions: RN is a clinically significant and multifactorial complication of CNS radiotherapy. Precision treatment modalities and advanced imaging have improved prevention and detection, but diagnostic uncertainty and recurrence risk persist. Integration of connectomics into treatment planning may offer future promise of a reduction in RN-related morbidity by preserving structural and functional network integrity. Full article

Aim: Nephrotic syndrome (NS) represents a complex glomerular disorder with significant clinical heterogeneity across pediatric and adult populations. Although glucocorticosteroids have constituted the mainstay of therapeutic intervention for more than six decades, primary treatment resistance manifests in approximately 20% of pediatric patients and 50% of adult cohorts. Steroid-resistant nephrotic syndrome (SRNS) is associated with substantially greater morbidity compared to steroid-sensitive nephrotic syndrome (SSNS), characterized by both iatrogenic glucocorticoid toxicity and progressive nephron loss with attendant decline in renal function. Based on this, the current study aims to develop a robust machine learning (ML) model integrated with explainable artificial intelligence (XAI) to distinguish SRNS and identify important biomarker candidate metabolites. Methods: In the study, biomarker candidate compounds obtained from proton nuclear magnetic resonance (1 H NMR) metabolomics analyses on plasma samples taken from 41 patients with NS (27 SSNS and 14 SRNS) were used. We developed ML models to predict steroid resistance in pediatric NS using metabolomic data. After preprocessing with MICE-LightGBM imputation for missing values (<30%) and standardization, the dataset was randomly split into training (80%) and testing (20%) sets, repeated 100 times for robust evaluation. Four supervised algorithms (XGBoost, LightGBM, AdaBoost, and Random Forest) were trained and evaluated using AUC, sensitivity, specificity, F1-score, accuracy, and Brier score. XAI methods including SHAP (for global feature importance and model interpretability) and LIME (for individual patient-level explanations) were applied to identify key metabolomic biomarkers and ensure clinical transparency of predictions. Results: Among four ML algorithms evaluated, Random Forest demonstrated superior performance with the highest accuracy (0.87 ± 0.12), sensitivity (0.90 ± 0.18), AUC (0.92 ± 0.09), and lowest Brier score (0.20 ± 0.03), followed by LightGBM, AdaBoost, and XGBoost. The superiority of the Random Forest model was confirmed by paired t-tests, which revealed significantly higher AUC and lower Brier scores compared to all other algorithms (p < 0.05). SHAP analysis identified key metabolomic biomarkers consistently across all models, including glucose, creatine, 1-methylhistidine, homocysteine, and acetone. Low glucose and creatine levels were positively associated with steroid resistance risk, while higher propylene glycol and carnitine concentrations increased SRNS probability. LIME analysis provided patient-specific interpretability, confirming these metabolomic patterns at individual level. The XAI approach successfully identified clinically relevant metabolomic signatures for predicting steroid resistance with high accuracy and interpretability. Conclusions: The present study successfully identified candidate metabolomic biomarkers capable of predicting SRNS prior to treatment initiation and elucidating critical molecular mechanisms underlying steroid resistance regulation. Full article

Hyrox© is a hybrid competition that is gaining prominence in the competitive field due to its physical demanding nature and broad appeal to athletes from various backgrounds. Understanding athlete profiles and performance determinants in these events is essential to optimize training and recovery strategies. Objectives: This study aimed to examine and describe the profile of athletes participating in Hyrox© competitions, focusing on variables related to their sports background, training habits, recovery strategies, physical capacities, and motivational aspects. Methods: A descriptive analysis was conducted using an ad hoc questionnaire fulfilled by 80 active Hyrox© athletes. The questionnaire addressed aspects such as training frequency and structure, previous athletic experience, strength and endurance levels, recovery practices, and personal goals. Results: The findings revealed a predominantly male athlete profile with high physical demands and prior experience in functional or endurance-based sports. Participants generally exhibited well-developed strength and endurance capacities. However, recovery strategies were often unstructured or insufficient, potentially compromising performance and increasing injury risk. Conclusions: Athletes competing in Hyrox© share characteristics with those in other high-intensity or hybrid modalities, including strong aerobic and anaerobic capacities. Nonetheless, a gap remains in the implementation of structured recovery protocols. These results highlight the need to incorporate comprehensive recovery strategies alongside physical preparation to optimize performance and athlete longevity in hybrid events. Full article

Background: Crisponi/cold-induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by severe neonatal manifestations including paroxysmal muscle contractions, tendency for hyperthermia, and feeding and swallowing difficulties with high neonatal mortality. Pathogenic variants in the Cytokine Receptor-Like Factor 1 (CRLF1) gene have been associated with CS/CISS. These variants result in a loss of function of the encoded protein, which disrupts the formation of a functional heterodimer with Cardiotrophin-Like Cytokine Factor 1 (CLCF1). This complex is essential for the development of autonomic and sensory nervous systems, as well as for bone remodeling. We report two patients affected by CS harboring pathogenic variants in the CRLF1 gene. Methods—case reports: The first patient was diagnosed postnatally, presenting with non-epileptic paroxysmal events characterized by opisthotonus and orofacial contractions. He survived beyond infancy, later developing scoliosis and persistent episodes of hyperthermia. In the second patient, a prenatal ultrasound at 20 weeks of gestation revealed bilateral camptodactyly, also referred to as the ‘horn’s sign’, raising early suspicion of CS. The diagnosis was subsequently confirmed both clinically and genetically. After birth, the infant developed severe dysphagia, apnea, and paroxysmal events not associated with epileptiform activity on EEG. Sanger sequencing identified a homozygous c.708_709delinsT frameshift variant in the CRLF1 gene. The patient died at 30 days of age due to respiratory failure. Results and conclusions: With this manuscript, we aim to further delineate the phenotypic spectrum of this rare condition and propose the ‘horn’s sign’ as a targeted prenatal marker for early diagnosis in populations with known founder mutations or familial risk factors. Full article

Background: Childhood cancer survivors (CCSs) are at heightened risk of long-term neurocognitive and emotional difficulties that can affect educational attainment, social participation, and overall quality of life. These outcomes vary across developmental stages and are influenced by treatment modality, age at diagnosis, and central nervous system (CNS) involvement. Methods: A comprehensive literature search was conducted in PubMed, Scopus, PsycINFO, and Web of Science for articles published between January 2000 and June 2024. Search terms included combinations of “childhood cancer survivors,” “neurocognitive outcomes,” “executive function,” “emotional regulation,” and related MeSH terms. Inclusion criteria required peer-reviewed studies assessing CCS using standardized neuropsychological or emotional measures. Results: Evidence indicates persistent deficits in processing speed, working memory, and higher-order executive functions, with additional challenges in attention and memory. Emotional difficulties, including anxiety, depression, and social withdrawal, were prevalent and often co-occurred with cognitive impairments. Developmental timing of cancer and treatment was a key determinant of outcome. Family functioning, school reintegration support, and broader social environments emerged as important moderators of resilience. Conclusions: CCSs face complex, interrelated cognitive and emotional challenges that warrant early identification and ongoing, developmentally tailored intervention. Integrated approaches combining cognitive remediation and psychosocial support appear most effective. Future research should prioritize longitudinal designs, multi-informant assessments, and culturally sensitive frameworks to inform targeted prevention and rehabilitation strategies. Our synthesis highlights that deficits in processing speed and working memory are most pronounced following CNS-directed therapies during early developmental stages, whereas emotional vulnerabilities such as anxiety and social withdrawal often emerge later in adolescence. Interventions combining cognitive remediation, targeted psychosocial support, and structured school reintegration show the strongest evidence for improving adaptive outcomes. Coordinated survivorship care across healthcare, educational, and family systems is essential to sustain developmental recovery. Full article

The lower Mahanadi basin in eastern India is experiencing significant land and soil transformations that directly influence agricultural sustainability and ecosystem resilience. In this study, we used geospatial techniques to analyze the spatial-temporal variability of soil quality and land cover between 2011 and 2020 in the lower Mahanadi basin. The results revealed that the cropland decreased from 39,493.2 to 37,495.9 km², while forest cover increased from 12,401.2 to 13,822.2 km², enhancing soil organic carbon (>290 g/kg) and improving fertility. Grassland recovered from 4826.3 to 5432.1 km², wastelands declined from 133.3 to 93.2 km², and water bodies expanded from 184.3 to 191.4 km², reflecting positive land–soil interactions. Soil quality was evaluated using the Simple Additive Soil Quality Index (SQI), with core indicators bulk density, organic carbon, and nitrogen, selected to represent physical, chemical, and biological components of soil. These indicators were chosen as they represent the essential physical, chemical, and biological components influencing soil functionality and fertility. The SQI revealed spatial variability in texture, organic carbon, nitrogen, and bulk density at different depths. SQI values indicated high soil quality (SQI > 0.65) in northern and northwestern zones, supported by neutral to slightly alkaline pH (6.2–7.4), nitrogen exceeding 5.29 g/kg, and higher organic carbon stocks (>48.8 t/ha). In contrast, central and southwestern regions recorded low SQI (0.15–0.35) due to compaction (bulk density up to 1.79 g/cm³) and fertility loss. Clay-rich soils (>490 g/kg) enhanced nutrient retention, whereas sandy soils (>320 g/kg) in the south increased leaching risks. Integration of LULC with soil quality confirms forest expansion as a driver of resilience, while agricultural intensification contributed to localized degradation. These findings emphasize the need for depth-specific soil management and integrated land-use planning to ensure food security and ecological sustainability. Full article

This study integrates network toxicology with molecular docking technology to systematically elucidate the key molecular mechanisms and signaling pathways by which bisphenol A (BPA) induces obesity. By cross-referencing multiple databases—including the Comparative Toxicogenomics Database (CTD), SwissTarget prediction platform, and PharmMapper—potential BPA target genes were identified, yielding a total of 1326 candidate targets. Obesity-related genes were collected from GeneCards and OMIM databases, yielding 4570 disease-associated targets. Among these, 653 overlapping genes were identified as potential mediators linking BPA exposure to obesity. Protein interaction networks were constructed using STRING and Cytoscape, and the MCC algorithm identified five core hub genes: STAT3, MYC, TP53, IL6, and mTOR. Validation using random datasets demonstrated significant upregulation of these genes in the obesity group (p < 0.05), highlighting their potential central role in BPA-induced obesity effects. Functional enrichment analysis via GO and KEGG pathways indicated that BPA may promote obesity by interfering with endocrine signaling, activating lipid metabolism, and stimulating atherosclerosis pathways. Molecular docking analysis using CB-Dock2 confirmed strong binding affinity between BPA and core targets, providing structural evidence for their potential interactions. This study elucidates the potential biological mechanism by which BPA exacerbates obesity through endocrine disruption and metabolic reprogramming, employing a multidimensional approach encompassing cross-target analysis, pathway enrichment, and molecular interactions. It provides an innovative systems toxicology framework and empirical basis for assessing metabolic health risks induced by environmental pollutants. Full article

Background/Objectives: Open Notes—defined as patients’ electronic, portal-based access to clinicians’ narrative documentation within electronic health records (EHRs)—has become routine through policy and portal initiatives. In mental health (MH), transparency intersects with sensitive formulation and risk language, making outcomes contingent on documentation practices, release timing, and reader support. This scoping review mapped empirical evidence on experiences, perceived impacts, and implementation of Open Notes in MH across stakeholders and settings, deriving implications for practice, training, and policy. Methods: A PRISMA-ScR-guided review was conducted with a preregistered protocol on OSF. Eligible studies examined Open Notes in MH settings and reported stakeholder perspectives. Two reviewers independently screened and extracted data, analyzed through inductive narrative thematic synthesis. Results: Twenty-two studies (2012–2025) from the USA, Sweden, Germany, Canada, and international settings included surveys, qualitative interviews, mixed-methods designs, pilot and quasi-experimental implementations, and a Delphi consensus. Patients consistently reported improved comprehension, recall, empowerment, and—in some cases—greater trust. Large surveys identified error detection and patient-initiated corrections as safety mechanisms, while a minority reported worry or feeling judged by wording. Clinicians adapted documentation—modifying tone, wording, or candor—to minimize misinterpretation. Workload effects were generally modest, limited to occasional clarifications. Implementation and expert studies emphasize organizational readiness, training, patient preparation, and privacy-aware portal design as key enablers of safe transparency. Conclusions: In MH, Open Notes function as a communication and engagement tool that strengthens partnership, comprehension, and safety when implemented with attention to risk-sensitive documentation and privacy safeguards. Full article