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PubMed2026

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12 cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B) ≈ 9, coefficient of variance (CV) < 10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus↗

PubMed2025

Comparison of three tracking methods to assess usage of two pediatric powered mobility devices for young children with cerebral palsy.

Powered mobility devices are underutilized for promoting self-initiated mobility in young children with cerebral palsy due to prioritization of walking, caregiver effort, device characteristics, and environmental factors. Understanding device usage patterns is important to assess the impact of powered mobility interventions on child outcomes. As part of clinical trial (NCT04684576), three objective tracking methods including integrated loggers, Global Positioning System trackers (GPST), and caregiver reported activity logs (CRAL) were compared to provide insights into device usage patterns. Metrics included play session frequency, session duration, total usage minutes, and unique usage days for two powered mobility devices: Modified Ride-on Cars (MROC) and the Permobil Explorer Mini (EM). Twelve children with cerebral palsy used each device for eight consecutive weeks in home and community settings (16 weeks total), with device ordered randomized. Results showed no significant differences among tracking methods for the MROC. For the EM, only session duration differed between GPST and CRAL. Correlation analysis revealed variable relationships amongst tracking methods for both devices. The EM was used more frequently than the MROC, with significantly greater total usage minutes and session duration via CRAL, not GPST. The findings highlight the need for reliable tracking technologies that can be used across powered mobility devices.

Child, Preschool↗

PubMed2026

Rates, Timing, and Predictors of Retreatment Across Risk-Cohorts in Retinopathy of Prematurity: Intravitreal Bevacizumab Injection Versus Laser.

OBJECTIVE: To characterize rates, timing, and predictors of retinopathy of prematurity (ROP) retreatment among infants treated with primary laser or intravitreal bevacizumab injection. DESIGN: Retrospective consecutive, comparative clinical study. PARTICIPANTS: Infants who underwent initial treatment for treatment-warranted ROP (TW-ROP) with either intravitreal bevacizumab or laser photocoagulation between 2017 and 2023. METHODS: Patients were stratified into two treatment groups: primary laser group vs primary bevacizumab group. MAIN OUTCOME MEASURES: Retreatment within the first 3 months (0-90 days) was assessed and classified as early (≤30 days) or late (31-90 days). RESULTS: Two hundred and thirty eight eyes of 122 infants were treated for ROP; of those, 181 (76.1%) eyes of 93 (76.2%) patients were included. There were 116 (64.1%) eyes in the bevacizumab group, and 65 (35.9%) eyes in the laser group. Thirty-three (18.2%) eyes-all micro- or nano-premature (<27 weeks GA and/or <800 grams)-required retreatment for TW-ROP. Sixteen (8.8%) required early retreatment at a median postmenstrual age (PMA) of 40.4 weeks (IQR, 38.44-43.3). There were differences in the proportion of early retreated infants (21.5% for laser vs 1.7% for injection, P < .001). Seventeen (9.4%) eyes required late retreatment. The median PMA at late retreatment was 45.6 weeks (IQR, 43.7-47.4). Infants in the bevacizumab group had lower odds of retreatment within three months than those with laser (OR, 0.23; 95% CI, 0.06-0.82). Similarly, patients in the bevacizumab group had lower odds of requiring early retreatment compared to those with laser (OR, 0.08; 95% CI, 0.04-0.18). Within eyes with retreatment, infants in the bevacizumab group had a later PMA at retreatment than those in the laser group (B = 6.81; 95% CI: 4.68-8.93). AROP was associated with earlier PMA at retreatment (B = -7.72; 95% CI, -9.36 to -6.10). CONCLUSION: In this study, early retreatment was low (8.8%), with most eyes initially treated with laser (21.5%) rather than bevacizumab (1.7%). Aggressive ROP was associated with earlier retreatment, highlighting its role as a marker of more severe disease. Compared to laser, bevacizumab was associated with lower overall and early retreatment, and delayed need for additional intervention when necessary. All retreatments occurred in micro- or nano-premature infants, suggesting that medium-to-low risk infants may require less strict post-treatment monitoring.

Humans↗

PubMed2026

Systematic review of the mutations in the active antigenic site Ø of the prefusion F protein of the Respiratory Syncytial Virus (RSV) following the implementation of monoclonal antibody prophylaxis.

BACKGROUND: Monoclonal antibody (mAb) nirsevimab, which targets the antigenic site Ø of the prefusion F protein (pre-F) of RSV, was introduced for RSV prophylaxis in several countries. METHODS: A systematic search was conducted between January 1, 2022, and July 31, 2026 for studies analyzing substitutions within the epitope of pre-F RSV protein, which is the target of nirsevimab, after the implementation of the mAb. We searched across PubMed, Scopus, Web of Science and ClinicalTrial.gov for studies involving children with confirmed RSV infection, that conducted genomic analysis. RESULTS: Seven studies (five observational and two randomized controlled trials) including 2156 RSV-positive samples (RSV-A: 1347, RSV-B: 809) were analyzed. RSV-A strains showed limited variability within antigenic site Ø, with K65R being the most common substitution and K209E being the only intermediate-resistance RSV-A substitution. RSV-B strains demonstrated substantially higher substitution frequencies, particularly involving I206M, Q209R, and S211N. Most identified substitutions appeared to represent naturally occurring polymorphisms and retained susceptibility to nirsevimab, while multiple RSV-B substitutions and combinations involving residues 64-68 and 204-208 demonstrated reduced susceptibility or high-level resistance. Resistance-associated variants were detected in 28 of 2156 (1.3%) RSV-positive samples and exclusively among nirsevimab breakthrough infections. In a sub-analysis restricted to nirsevimab-treated individuals, resistance-associated variants were significantly more frequent among RSV-B than RSV-A (9.8% vs 0.5%; p < 0.001). CONCLUSION: Most substitutions that were detected within the nirsevimab antigenic site reflect ongoing natural RSV evolution and do not significantly affect nirsevimab susceptibility. However, detection of resistance-associated variants highlights the importance of continuous genomic and phenotypic surveillance.

Humans↗

PubMed2026

Lower urinary tract evaluation in children with cerebral palsy: A crossectional study.

INTRODUCTION: Cerebral palsy (CP) is a chronic, non-progressive motor disorder affecting voluntary movement and posture. Lower urinary tract (LUT) dysfunction is highly prevalent in children with CP. This study aims to evaluate LUT function in children with CP. MATERIAL AND METHODS: This cross-sectional study was conducted at a tertiary care hospital. Patients aged 5-18 years with established CP diagnosis were included. Evaluation included clinical history, physical examination, urinary ultrasonography with post-void residual (PVR) measurement, and urodynamic studies when indicated. Patients were categorized into three groups; group-1 (LUT dysfunction), group-2 (symptomatic), and group-3 (asymptomatic) for analysis. RESULTS: The study included 97 children with CP (41 girls, 56 boys; median age 8 years). Of the patients, 61.8% were ambulatory (GMFCS I-III) and 38.2% were non-ambulatory (GMFCS IV-V). At least one LUT symptom was detected in 75.3% of patients. Incontinence was the most common symptom at 69.1%. Incontinence prevalence was significantly higher in non-ambulatory patients (81.1% vs 61.7%, p = 0.044). Invasive urodynamics was performed in 19 patients, and LUT dysfunction was diagnosed in 89.5% of them (19.3% of the entire population). Prematurity rate was significantly higher in patients with LUT dysfunction (94.1% vs 64.8%, p = 0.017). Binary logistic regression analysis identified elevated PVR as the strongest independent risk factor for LUT dysfunction (OR = 108, p < 0.001). Abnormal urinary frequency (OR = 14.9, p = 0.022) and quadriplegia (OR = 10.3, p = 0.016) were other independent risk factors. ROC analysis determined the optimal cut-off value for PVR as 19 mL (sensitivity 58.82%, specificity 94.92%). In the intergroup analysis, multinomial logistic regression identified elevated PVR as the strongest predictor (Group-1 vs Group-2: OR = 101; Group-1 vs Group-3: OR = 24, both p < 0.003). Lower gestational age was also an independent risk factor in both comparisons (OR = 1.25-1.26, p < 0.020). DISCUSSION: This study demonstrates LUT dysfunction affects 19.3% of children with CP, strongly correlating with motor impairment severity. Elevated PVR emerged as the strongest independent predictor (OR = 108), offering a practical non-invasive screening tool. Our proposed urodynamic criteria achieved 94.7% diagnostic yield, enabling selective evaluation. Limitations include single-center design and cross-sectional methodology without longitudinal follow-up. These findings support integrating systematic urological assessment into standard CP care for early intervention. CONCLUSION: LUT dysfunction prevalence is high in children with CP, and symptom frequency increases with higher GMFCS levels. Elevated PVR is the strongest predictor, with a clinically applicable cut-off value of 19 mL. Particularly in quadriplegic, non-ambulatory, and premature patients, close follow-up and urodynamic evaluation when necessary should be performed with a multidisciplinary approach.

Humans↗

PubMed2026

Relationships between cannabis and cocaine use in a randomized trial of combined buprenorphine and naltrexone for DSM-IV cocaine dependence.

BACKGROUND: Cannabis is the most commonly used drug in the United States, and among people who use cannabis, polysubstance use is common and understudied. We aimed to examine the association of tetrahydrocannabinol (THC) positive urine drug screen (+UDS) with the odds of submitting a cocaine + UDS during cocaine use disorder treatment. METHODS: We conducted a secondary data analysis of a previously reported double-blind, placebo-controlled clinical trial, CTN0048. Participants meeting criteria for opioid abuse/dependence were assigned to receive extended-release naltrexone and one of three conditions of buprenorphine (placebo, 4 mg/day, 16 mg/day) for 8 weeks. Generalized estimating equations (GEE) were used to analyze urine samples (Liu et al., 2018) collected over time, examining the association between THC + UDS and cocaine + UDS during treatment. RESULTS: Participants (n = 301) averaged 46 (SD = 8.64) years of age, were majority male (78.41 %), non-Hispanic (89.70 %), and African American (66.45 %). GEE results indicated that patients who submitted THC + UDS had significantly higher odds of submitting cocaine + UDS compared to participants who submitted THC-negative UDS across the 25 time points examined (OR = 1.47, 95 % CI = 1.21-1.79, p = 0.00). Time (OR = 0.9998, 95 % CI: 0.9997, 0.9999, p = 0.018) and the covariate of sex assigned at birth (OR = 1.77, 95 % CI = 1.13-2.77, p = 0.013) were also significant in the model, indicating very small decreases in the odds of submitting a cocaine + UDS over time for all patients and 77 % higher odds of submitting cocaine + UDS for females. CONCLUSION: THC + UDS was associated with increased odds of submitting a cocaine + UDS during treatment. Further investigation is needed to discern whether decreasing THC use will result in reduced cocaine use; however, these results suggest that it may be beneficial to counsel patients on cannabis use cessation both before and during treatment for cocaine use, as it is related to cocaine use treatment outcomes. TRIAL REGISTRATION: Secondary data analysis of ClinicalTrials.gov, TRN: NCT01402492 ("A randomized study to test the safety and effectiveness of buprenorphine in the presence of naltrexone for the treatment of cocaine dependence"; National Drug Abuse Treatment Clinical Trials Network (CTN) clinical trial: CTN0048), Registration date: 27 July 2011.

Humans↗

PubMed2026

Smartphone Apps for Preventing Adolescent Health Problems Among Health Care Professionals: Systematic Search and Quality Assessment.

BACKGROUND: Health care professionals must consider multiple dimensions of prevention when consulting with adolescents. Identifying risky behaviors early in adolescence is crucial for reducing both morbidity and mortality. General practitioners are increasingly eager to incorporate digital tools for prevention into their consultations with adolescents; however, the relevance and clinical validity of these digital tools are not always established or well-known. Consequently, primary care professionals require guidance and support in selecting relevant mobile health (mHealth) tools. OBJECTIVE: The aim of this study is to identify relevant and useful digital apps to help primary care professionals detect at-risk adolescents across all recommended areas of prevention: orthopedics, mental health, substance abuse, risk behaviors, sexual health, vaccinations, social relationships, and nutrition. METHODS: A systematic review of smartphone apps, with an analysis of content quality, was carried out by 4 researchers using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. The App Store and Google Play Store platforms were surveyed. The inclusion criteria were as follows: free of charge, date of last update, availability in French or English, relevance of the preventive approach to adolescents, and scientific validation. Four health care professionals assessed the apps: 2 selected the apps relevant to health care professionals, then 3 analyzed these apps using the French version of the Mobile App Rating Scale (MARS-F). Intraclass correlation coefficient, model (2,1) (2-way random effects, absolute agreement, single measures); standard error of measurement; and mean absolute error were also calculated. RESULTS: A total of 976 apps were identified, 49 of which had disappeared from the platforms prior to analysis. Nine apps were retained. Seven (0.72%) were included after evaluation using the MARS-F: 2 on mental health and 5 on sexual health (including 3 on contraception only). The mean MARS-F interrater score ranged from 2.5/5 to 3.8/5. The global MARS-F score demonstrated a pooled SD of 0.60 and an intraclass correlation coefficient (2,1) of 0.0003, resulting in a calculated standard error of measurement of 0.60. The average discrepancy between raters was a mean absolute error of 0.53. CONCLUSIONS: No similar studies have been identified in the literature that specifically focus on mobile apps designed to support health care professionals in delivering preventive care to adolescents. Of the 8 areas of prevention identified as relevant for adolescents, only 3 are addressed by the apps validated through our methodology (5 focus on sexual health). Consequently, current apps are insufficient to support health care professionals in their overall preventive work with adolescents. Such a review should be conducted systematically prior to the development of any new tool to prevent duplication and channel creative efforts toward truly innovative digital solutions. Furthermore, a thorough analysis of relevant, recommended websites is essential, as these resources complement the use of mobile apps designed for health care professionals.

Humans↗

PubMed2026

Incidence of silent cerebral lesions during pulsed field ablation for paroxysmal atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is a first-line treatment for paroxysmal atrial fibrillation (PAF). Complications such as silent cerebral lesion (SCL) may occur during ablation. Pulsed field ablation (PFA) is a non-thermal method thatablates cardiac tissue via irreversible electroporation. Limited studies have reported the incidence of SCL during PFA, with highly variable results. However, randomized controlled trials (RCTs) remain scarce. The objective of this study was to compare perioperative SCL incidence between PFA and RFCA, and to identify risk factors for SCL during PFA. METHODS: In this prospective pilot RCT (ChiCTR2400088774), 62 patients with PAF were randomized 1:1 to undergo PFA or RFCA. Cerebral MRI (3.0 T) was performed preoperatively and 24-48h postoperatively. SCL was defined as a new acute brain lesion on MRI without neurological deficits. Baseline and surgical data of the patients were collected. RESULTS: SCL was detected post-procedure in 6.45% (2/31) in the RFCA group, 12.90% (4/31) in the PFA group. No statistically significant difference in the incidence of postoperative SCL was detected between the two groups (p = 0.67). Left atrium dimension (LAD), left atrial operation time (LAOT), left ventricular end-diastolic dimension (LVEDD), and total operation time (TOT) were significantly higher in SCL group than those in no-SCL group (p < 0.05) through univariate analyses. CONCLUSIONS: SCL incidence was 12.90% in the PFA group versus 6.45% in the RFCA group. While no statistically significant difference was detected between two groups, the numerically higher rate in the PFA group warrants larger studies to evaluate cerebral safety associated with PFA.

Humans↗

PubMed2026

A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (≥18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).

Humans↗

PubMed2026

High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial.

IMPORTANCE: Severe burn injury triggers systemic inflammation that can lead to multiple organ dysfunctions and death. High-dose intravenous vitamin C has been proposed to mitigate these effects, but strong evidence in patients with burn injury is lacking. OBJECTIVE: To evaluate the efficacy of high-dose intravenous vitamin C in patients with severe burn injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled phase 3 trial conducted across 24 burn centers in North, Central, and South America; Europe; and Asia. Adults (≥18 years) with deep second- and/or third-degree burns covering 20% or more of total body surface area and requiring skin grafting were enrolled between August 18, 2020, and September 12, 2025. Final follow-up was completed in March 2026. The trial was stopped early after the first prespecified interim analysis for futility/harm. INTERVENTIONS: Patients were randomly assigned (1:1) to receive intravenous vitamin C (50 mg/kg every 6 hours for 96 hours) or matched placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of 28-day mortality and persistent organ dysfunction (defined as dependence on mechanical ventilation, kidney replacement therapy, or vasopressor/inotrope support at day 28). The main secondary outcome was time to discharge alive from hospital within 90 days. RESULTS: Among 238 patients enrolled (mean age, 48.9 [SD, 19.1] years; 79% male; mean total body surface area, 37.0% [SD, 14.6%]), 120 were assigned to vitamin C and 118 to placebo. The primary composite outcome occurred in 49 patients (40.8%) in the vitamin C group and 35 patients (29.7%) in the placebo group (adjusted risk ratio [RR], 1.28 [95% CI, 0.99-1.65]; P = .06), crossing the prespecified futility/harm threshold and prompting early trial termination. Time to discharge alive from hospital within 90 days was not improved (adjusted subdistribution hazard ratio, 0.85 [95% CI, 0.62-1.16]; P = .31). Twenty-eight-day mortality was higher in the vitamin C group (15.0% vs 7.6%; adjusted RR, 1.96 [95% CI, 1.32-2.90]; P = .001), as was hospital mortality (23.3% vs 16.1%; adjusted RR, 1.44 [95% CI, 1.03-2.00]; P = .03). CONCLUSIONS AND RELEVANCE: Among patients with severe burn injury, high-dose intravenous vitamin C did not reduce 28-day mortality and persistent organ dysfunction and is possibly harmful. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04138394.

Humans↗

PubMed2026

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as ≥ 50% reduction in MADRS score, and remission as MADRS ≤ 10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans↗

PubMed2026

Association of Age at Menarche With Depression in Adulthood in NHANES 2015-2023: A Cross-Sectional Study.

PURPOSE: The primary objective of this study is to elucidate the role of age at menarche in depression in adulthood and explore the implications of this association. METHODS: We conducted a study involving 9,826 adult female participants from the National Health and Nutrition Examination Survey (NHANES) between 2015 and August 2023. Age at menarche was categorized as early (<12 years), normal (12-14 years), or late (≥15 years). Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and clinical diagnoses. Logistic regression and restricted cubic spline analyses were performed to address the study objectives. In addition, subgroup analyses were conducted based on demographic, lifestyle, and clinical characteristics. RESULTS: The depression group had a significantly higher proportion of young adults (aged 18-30 years) compared to the nondepression group (26.46% vs. 20.52%, p < .001). Conversely, the nondepression group included a greater proportion of older adults (over 60 years) than the depression group (29.53% vs. 23.98%, p < .001). After comprehensive adjustments, early menarche was significantly associated with increased depression risk (adjusted odds ratio [aOR] = 1.224, 95% confidence interval [CI]: 1.003-1.493, p = .047). Restricted cubic spline analyses revealed an L-shaped nonlinear pattern (p for nonlinearity = 0.006), with optimal age at menarche around 12 years. Subgroup analyses confirmed consistent associations without significant interactions. DISCUSSION: Early menarche is linked to increased depression risk, especially among women aged 18-30 years. Menarche at 12 years may serve as a key point for early intervention to prevent depression in young women.

Humans↗

PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗

PubMed2026

Artificial intelligence (AI) uses in stereotactic radiosurgery (SRS): diagnosis with brain metastasis (BM) - A systematic review.

BACKGROUND: Brain metastases (BM) are the most common intracranial tumors in adults, and stereotactic radiosurgery (SRS) has become a mainstay of management. However, several diagnostic challenges persist in the SRS pathway, particularly the differentiation of radiation necrosis (RN) from true tumor progression, which conventional MRI and even advanced imaging techniques often cannot reliably resolve. Recent advances in artificial intelligence (AI) offer the potential to address these diagnostic limitations. This systematic review synthesizes current literature on AI applications for MRI-based diagnostic decision support in BM patients undergoing SRS, with a focus on radiomics and deep learning tools for distinguishing RN from progression, classifying molecular and histologic subtypes, and predicting treatment response. METHODS: A systematic review was performed in accordance with PRISMA guidelines. PubMed, Web of Science, and Scopus were searched using a targeted query combining terms related to AI, brain metastasis, diagnosis or imaging, and SRS. After screening 483 records and applying strict inclusion and exclusion criteria, 18 studies published between 2015 and 2025 were included. Data were extracted on study design, cohort characteristics, imaging modality, AI methodology, validation strategy, and reported diagnostic performance. RESULTS: Among the 18 included studies, AI models demonstrated strong performance across diagnostic tasks in the BM-SRS pathway. The differentiation of RN from true tumor progression was the most extensively studied application, addressed by 14 of 18 studies, with reported AUCs ranging from 0.71 to 0.94. Support vector machines, random-forest ensembles, convolutional neural networks, and transformer-based multimodal architectures were widely used. The literature evolved from single-sequence radiomic classifiers in 2018 to multimodal deep learning frameworks fusing imaging with clinical and genomic data in 2025. Contrast-enhanced T1-weighted MRI was the dominant imaging input, and texture-based radiomic features (GLCM, GLSZM, GLDM, and wavelet-derived features) were the most consistently predictive. The highest-performing models reached AUCs of 0.85-0.91 through multimodal integration of imaging with clinical and genomic features, and consistently outperformed expert neuroradiologist read on matched cases. Remaining studies addressed longitudinal segmentation-based detection of local failure and adverse radiation effects, BRAF mutation status in melanoma BM, early Gamma Knife treatment response, and primary tumor histology classification, with more variable performance. CONCLUSION: AI models, particularly those integrating MRI-derived radiomic features with clinical and genomic data, show high accuracy in supporting diagnostic decisions for BM patients treated with SRS. The post-SRS differentiation of radiation necrosis from true tumor progression has reached the greatest level of maturity and is closest to clinical translation, with potential to reduce unnecessary biopsies, personalize surveillance intervals, and rationalize treatment-pathway decisions. Other diagnostic applications, including molecular subtyping and primary tumor histology classification, remain exploratory and require further multicenter validation. Integration of AI tools into multidisciplinary tumor-board workflows, combined with prospective validation and standardized reporting, will be essential to realize the full clinical benefits of AI in SRS for brain metastases.

Humans↗

PubMed2026

Comprehensive study on pesticide residues and mycotoxins in freeze-dried strawberries and raspberries.

Freeze-dried fruit has gained popularity because it preserves the flavour and nutritional value of fresh fruit while providing extended shelf life. Despite this, there are concerns regarding its chemical safety. This study evaluated 58 freeze-dried fruit products from the Czech retail market, focusing on potential contamination. Pesticide residues and mycotoxins were determined using LC-MS/MS and GC-MS/MS. Overall, 111 pesticide residues (or their metabolites) and 3 mycotoxins were quantified. After applying processing factors, 12 pesticide residues exceeded EU maximum residue limits. Prohibited substances, including carbofuran, omethoate, and haloxyfop, were detected. Tenuazonic acid was found in 71% of samples, while alternariol and tentoxin were detected less frequently. More than half (54%) of strawberry samples contained 10 or more pesticide residues, indicating potential cumulative exposure concerns, particularly for children with lower body weight. These findings highlight the need for continued monitoring of freeze-dried fruits and further assessment of dietary exposure.

Pesticide Residues↗

PubMed2026

Clinical characteristics and outcomes of post-stroke seizures following reperfusion therapy: a retrospective single-center study.

BACKGROUND: Post-stroke seizures (PSS) are a recognized complication of ischemic stroke and may adversely affect functional outcomes and survival; however, their characteristics in patients receiving contemporary reperfusion therapy remain incompletely defined. We aimed to describe the clinical characteristics, treatment patterns, and outcomes of patients who developed PSS following reperfusion therapy and to compare early- and late-onset seizure subgroups. METHODS: This single-center retrospective study included adult patients with acute ischemic stroke treated with intravenous thrombolysis (IV-tPA), mechanical thrombectomy (MT), or combined therapy between January 2020 and September 2025. Early seizures were defined as occurring within 7 days of stroke onset. Clinical, radiological, and treatment-related variables were analyzed, and functional outcome was assessed using the modified Rankin Scale at 3 months. RESULTS: Of 1242 patients who received reperfusion therapy, 53 (4.27 %; 95 % CI 3.28-5.54) developed PSS. Observed seizure rates were 3.39 % in the MT group, 4.06 % in the IV-tPA group, and 7.02 % in the combined therapy group; these observed rates did not differ significantly across treatment modalities. Early seizures occurred in 23 patients and late seizures in 30. No significant differences were found between early- and late-onset seizure subgroups in demographic characteristics, vascular risk factors, stroke severity, reperfusion success, or clinical outcomes, with the exception of an isolated, exploratory difference in stroke laterality. Three-month mortality among patients with PSS was 45.28 % (95 % CI 32.66-58.55), and in-hospital mortality was 20.75 %. CONCLUSIONS: In this single-center cohort, the incidence of PSS after reperfusion therapy was comparable to previously reported rates, with no marked differences across treatment modalities. The high mortality among patients with PSS likely reflects underlying stroke severity rather than a treatment-specific risk.

Humans↗

PubMed2026

The hidden threat from food-derived carbon dots: Formation, biodistribution, and potential health risks.

Food-derived carbon dots (CDs) are a new class of carbon-based nanoparticles generated during the thermal processing of food matrices. These nanomaterials have been extensively studied for their unique fluorescence, good biocompatibility, and tunable surface chemistry in food detection, intelligent packaging, and biomedical applications. However, their nanoscale size and high surface activity have raised safety concerns regarding biological interactions, in vivo biodistribution, and potential long-term health hazards. Although CDs have traditionally been regarded as low-toxicity materials due to their favorable biocompatibility, the potential hidden risks of CDs have not received sufficient attention. CDs exhibit dose-dependent toxicity, not only accumulating in various tissues and organs but also potentially inducing oxidative stress and interfering with cellular metabolic functions. Therefore, this review summarizes the advances in sources, synthetic strategies, and core properties of CDs, with a special focus on in vivo biological interactions, fates, and potential safety challenges. In addition, it is proposed that the standardized detection and risk assessment system should be established to further explore the long-term health effects of CDs under real dietary exposure, thereby ensuring their safety and sustainable application.

Carbon Quantum Dots↗

PubMed2026

Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 × 3 factorial trial.

BACKGROUND: Evidence is limited regarding whether assigned protein targets modify responses to resistance training (RT) alone or to the same RT program plus cycling (concurrent training [CT]) in middle-aged and older women. This randomized 2 × 3 factorial trial examined bioelectrical impedance analysis (BIA)-derived skeletal muscle mass (SMM; primary outcome), other body composition outcomes, muscular and functional performance, and cycle-derived estimated VO₂max. METHODS: In this randomized 2 × 3 factorial trial, 108 women aged 40-77 years were assigned to 12 weeks of supervised RT or CT (identical RT followed by cycling) and protein targets of 0.8, 1.6, or 2.2 g·kg-1·d-1. Baseline-adjusted ANCOVA tested training × protein interactions and marginal training and protein effects. Complete-case analyses included 83 participants. RESULTS: For SMM, no training-condition × protein-target interaction (p = 0.856), marginal protein-target effect (p = 0.726), or marginal training-condition effect (p = 0.273) was detected. CT had a lower baseline-adjusted week-12 BFP than RT (adjusted difference, -2.04 percentage points; 95% CI, -2.94 to -1.14; p < 0.001). RT had a higher baseline-adjusted week-12 leg-press estimated 1-RM than CT (CT - RT: -6.68 kg; 95% CI, -8.32 to -5.04; p < 0.001), whereas CT had a higher baseline-adjusted week-12 cycle-derived estimated VO₂max (adjusted difference, 4.53 mL·kg-1·min-1; 95% CI, 3.80 to 5.25; p < 0.001). No detectable marginal protein-target effects or training-condition × protein-target interactions were observed for the key secondary outcomes. CONCLUSIONS: No detectable differences in SMM or key secondary outcomes were attributable to assigned protein target. Compared with RT, CT favored estimated aerobic fitness and BFP, whereas RT favored leg-press strength. Because CT included additional cycling and greater exercise exposure, these differences cannot be attributed solely to training modality. Null protein findings do not establish equivalence among doses.

Humans↗