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PubMed2026

Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma.

BACKGROUND: Alternative polyadenylation (APA) is a key post-transcriptional mechanism that regulates gene expression by modulating 3'UTR length, its dysregulation has been implicated in carcinogenesis. How genetic variants influence APA to affect hepatocellular carcinoma (HCC) prognosis remains unclear. METHODS: Prognosis-APA quantitative trait loci (apaQTL) were performed using genotype and APA profiling from TCGA data. A two-stage survival analysis in 848 Chinese and 369 TCGA LIHC patients and functional validation were used to identify prognostic apaQTL in HCC progression. RESULTS: A total of 2,025 and 817 significant APA events were identified in Chinese and TCGA cohort, respectively. Besides, 859 events were associated with poor prognosis in HCC and enriched in RNA splicing / metabolism pathways. We detected 32,034 significant apaQTLs, predominantly enriched in 3'UTRs and RBP-binding regions. CPEB3 was prioritized as a key APA regulator RBP; its low expression correlated with poor patient survival and promoted proliferation, migration, and invasion in HCC cells. Notably, a functional apaQTL variant rs2037547, located in GSK3B and mediated by CPEB3, demonstrated a poor survival of HCC patients in both cohort (pooled HR=1.29, p=0.016). Mechanistically, rs2037547 promoted aberrant APA at proximal poly(A) sites of GSK3B through CPEB3, leading to increased expression of short 3'UTR isoform. This regulatory alteration enhanced HCC cell proliferation, invasion, and migration, and contributed to HCC progression. CONCLUSION: These findings elucidated the distinct role of apaQTL-mediated APA dysregulation in HCC prognosis, providing insights for prognostic stratification and potential targets for personalized therapy in HCC.

RNA-binding proteins↗

PubMed2026

Digital Structured Education With Behavioral Nudge Tools for Adults With Type 2 Diabetes: Multicenter Randomized Controlled Trial.

BACKGROUND: Digital interventions offer scalable alternatives to traditional face-to-face diabetes education, but often face challenges related to inconsistent clinical effectiveness, and declining user engagement. However, whether a digital structured education program integrated with behavioral nudge tools can improve metabolic, behavioral, and psychological outcomes in adults with type 2 diabetes remains unclear. OBJECTIVE: This study aimed to evaluate the effectiveness of a digital structured education program integrated with behavioral nudge tools in improving metabolic, behavioral, and psychological outcomes among adults with type 2 diabetes. METHODS: This multicenter randomized controlled trial was conducted in the endocrinology departments of 4 hospitals in China. Adults with type 2 diabetes were randomly assigned to an intervention group receiving a digital structured education program integrated with behavioral nudge tools (n=146) or a control group receiving standard digital diabetes education (n=147). Assessments were conducted at baseline and 12-week follow-up. The primary outcome was hemoglobin A1c (HbA1c) at 12 weeks, adjusted for baseline HbA1c, and study center. Secondary outcomes included fasting blood glucose (FBG), weight, BMI, waist circumference, blood pressure, lipid profiles, self-management behaviors, self-efficacy, and habit strength. RESULTS: Among 293 participants (mean age 49.19, SD 10.02 y), 287 (97.9%) completed follow-up. At 12 weeks, the intervention group demonstrated significantly greater improvements than the control group in HbA1c (adjusted mean difference -0.38%, 95% CI -0.68% to -0.09%; P=.01), FBG (adjusted mean difference -0.75, 95% CI -1.27 to -0.44 mmol/L; P<.001), weight (adjusted mean difference -0.84, 95% CI -1.61 to -0.07 kg; P=.03), BMI (adjusted mean difference -0.38, 95% CI -0.65 to -0.11 kg/m²; P=.01), systolic blood pressure (adjusted mean difference -2.71, 95% CI -4.62 to -0.79 mm Hg; P=.01), diastolic blood pressure (adjusted mean difference -2.92, 95% CI -4.47 to -1.37 mm Hg; P<.001), and total cholesterol (adjusted mean difference -0.27, 95% CI -0.48 to -0.05 mmol/L; P=.02). The intervention was also associated with significantly greater improvements in self-management behaviors, self-efficacy, and habit strength (all P<.05). CONCLUSIONS: Digital structured education integrated with behavioral nudge tools improved metabolic outcomes and strengthened psychological and behavioral determinants of self-management among adults with type 2 diabetes over a 12-week period. These findings suggest that a digital structured education program integrated with behavioral nudge tools may enhance diabetes self-management beyond standard digital diabetes education. Further studies with longer follow-up and real-world implementation are warranted to evaluate the sustainability, generalizability, and long-term clinical impact of this integrated intervention.

Humans↗

PubMed2026

Duration and characteristics of hypoglycemia with once-weekly insulin efsitora alfa versus once-daily basal insulins in adults with type 2 diabetes: Exploratory safety analysis of QWINT 2-4.

AIMS: Efsitora is a novel once-weekly basal insulin. Efsitora demonstrated similar efficacy and safety compared with once-daily basal insulin comparators across four phase 3 clinical trials for type 2 diabetes. This exploratory safety analysis further characterizes hypoglycemia events in the efsitora and once-daily treatment groups in three of these trials (QWINT-2, -3, and -4). METHODS: Median duration of hypoglycemia events was assessed with masked continuous glucose monitoring. Incidence of persistent-recurrent (PR) hypoglycemia was assessed by investigators and by a pre-specified algorithm using SMBG e-diary data. Factors contributing to hypoglycemia, characteristics of hypoglycemia, and treatment methods were reported by participants and assessed across groups. RESULTS: Across the three trials, durations of hypoglycemic events for efsitora vs once-daily basal insulin comparators were: Level 1 and 2 [<70 mg/dL]: 40-42.5 vs 40 min; Level 2 [<54 mg/dL]: 35-39.9 vs 35 min. Few incidences of PR hypoglycemia were reported for efsitora or once-daily comparators. No major descriptive differences were observed between hypoglycemia contributing factors, characteristics, or treatment methods in efsitora and once-daily treatment groups. CONCLUSIONS: No clinically relevant differences were observed between the duration or characteristics of hypoglycemic events in efsitora and once-daily treatment groups in the QWINT-2, -3, and -4 trials.

Adult↗

PubMed2026

Comparison of clinical efficacy and gut microbiota characteristics in children with ASD treated with fecal microbiota transplantation and ketogenic diet.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, along with restricted, repetitive patterns of behavior. It is often accompanied by gastrointestinal dysfunction and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) and the Ketogenic Diet (KD) are interventions targeting the gut microbiota for ASD. METHODS: 30 participants were diagnosed with ASD according to DSM-5 and ADOS-2. ASD core symptoms were evaluated with CARS and ABC. Gut microbiota composition was analyzed by shotgun metagenomic sequencing. RESULTS: Both groups demonstrated significant improvements in core symptoms. In the FMT group, the mean CARS score significantly decreased from 34.87 to 33.53 (p < 0.01); in the KD group, it declined from 35.13 to 33 (p < 0.01). The mean ABC score reduced from 79.93 to 69.33 (p = 0.064) in the FMT group and from 63.07 to 42.73 (p < 0.01) in the KD group. Following the intervention, no statistically significant changes were observed in α-diversity or β-diversity within either group. LEfSe analysis revealed distinct post-intervention microbial signatures: FMT significantly enriched butyrate-producing taxa (Wujia chipingensis, Eubacterium sp. MSJ-33, and Butyrivibrio crossotus), while KD elevated Blautia massiliensis and decreased propionate metabolism -associated taxa (Veillonella sp. S12025-13 and Veillonella nakazawae). KEGG enrichment analysis revealed that KD enriched propionate metabolism (Fold enrichment = 3.747, q = 0.010) and aromatic compound degradation (Fold enrichment = 3.591, q = 0.010). CONCLUSIONS: Both interventions significantly improved clinical symptoms among children with ASD, potentially through distinct patterns of gut microbiota modulation. CLINICAL TRIALS NUMBER: NCT06348433 (03/21/2024).

Child↗

PubMed2026

Maternal disease control and pregnancy outcomes with anti-CD20 therapy versus natalizumab in multiple sclerosis: a systematic review.

BACKGROUND: Management of multiple sclerosis (MS) during pregnancy requires balancing maternal disease control with fetal safety. Among high-efficacy disease-modifying therapies, anti-CD20 monoclonal antibodies and natalizumab are commonly used in women with active disease, yet their comparative effectiveness and safety during pregnancy remain incompletely defined. This systematic review evaluated maternal disease activity and pregnancy-related outcomes associated with anti-CD20 exposure compared with natalizumab in pregnant women with MS. METHODS: PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library were searched from inception through February 2026. Eligible studies included pregnant women with MS exposed to anti-CD20 before or during pregnancy and reporting maternal disease activity compared to natalizumab. RESULTS: Seven studies were included, comprising six observational cohort studies and one pharmacovigilance disproportionality analysis. Across studies, anti-CD20 exposure was consistently associated with lower relapse activity than natalizumab, particularly in the postpartum period. Anti-CD20 strategies were also associated with markedly lower postpartum MRI activity and more favorable disability-related outcomes where reported. Meta-analysis of three studies demonstrated a significant reduction in postpartum MRI activity with anti-CD20 therapy compared with natalizumab (RR 0.06, 95% CI 0.02-0.24; I² = 0%). No clear increase in major congenital anomalies was identified, although some data suggested higher odds of small for gestational age and maternal antibiotic use with anti-CD20 exposure. CONCLUSIONS: Anti-CD20 therapy was associated with lower maternal disease activity than natalizumab during pregnancy, especially for relapse prevention and postpartum MRI suppression. However, evidence regarding fetal and neonatal safety remains limited, warranting cautious individualized treatment decisions and further comparative research.

Humans↗

PubMed2026

Chemotherapy-Induced Nausea and Vomiting in Early Breast Cancer Patients Receiving Adjuvant Chemotherapy With Fluorouracil, Epirubicin, Cyclophosphamide Followed by Docetaxel Versus an Anthracycline-Free Regimen With Docetaxel, Cyclophosphamide-Results From a Randomized Clinical Trial.

Chemotherapy-induced nausea and vomiting (CINV) remains an important side effect despite new antiemetic drugs. This study tried to understand the occurrence of CINV in patients receiving two different chemotherapy regimens. As part of the randomized controlled clinical trial SUCCESS C (NCT00847444), 1582 of the 3463 patients completed CINV diaries. Patients were randomized to receive either chemotherapy with FEC (5-fluorouracil, epirubicin, cyclophosphamide followed by docetaxel) or TC (docetaxel, cyclophosphamide). CINV was evaluated hourly using a specially designed questionnaire. Endpoints of the study were complete response (no emesis) and total control (no nausea and no emesis) and were assessed with Kaplan-Meier curves and Cox regression analyses over three chemotherapy cycles. Eight hundred fourteen patients received FEC and 768 received TC; patients and tumor characteristics were similar in both groups. Patients receiving FEC had significantly more nausea and vomiting, with the main difference in the first 12 h. In the first cycle, the 0-12-h nausea/emesis-free rates were 70%/41% for FEC and 91/76% for TC. By 24 h after chemotherapy, the rates were 65%/33% (FEC) and 85%/60% (TC). The differences were similar in cycles 2 and 3. The detailed analysis of CINV in the study is unique and paves the way for modern CINV analysis of new therapeutics such as antibody-drug conjugates.

Adult↗

PubMed2026

Compliance With Ecological Momentary Assessment Among Patients With Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with cancer often experience substantial fluctuations in psychological states during disease management. Traditional research tools are limited in capturing these dynamic changes in real time, constraining clinicians' understanding of patients' true conditions. Ecological momentary assessment (EMA) enables high-frequency, real-time data collection, providing patient-reported data with greater ecological validity. However, the effectiveness of EMA studies critically depends on patient compliance, and reported compliance rates vary widely, with a lack of systematic quantitative synthesis. OBJECTIVE: This study aims to systematically review and quantitatively analyze compliance with EMA among patients with cancer, and to examine whether EMA design characteristics were associated with compliance. METHODS: Web of Science, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, and Wanfang databases were searched for literature published up to April 30, 2026. Compliance was defined as completed prompts divided by delivered prompts. Single-group proportions were pooled using logit transformation and random-effects models with the Hartung-Knapp-Sidik-Jonkman adjustment. Prediction intervals were calculated to describe the expected distribution of compliance in future comparable settings. Subgroup analyses, univariable meta-regressions, leave-one-out sensitivity analyses, and tests for small-study effects were performed. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, methodological reporting quality was assessed using a modified Checklist for Reporting EMA Studies, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twenty-three studies involving 13,565 participants were included. The pooled compliance rate was 78.55% (95% CI 73.48%-82.87%), with a prediction interval of 48.59%-93.41%. Subgroup analyses identified no robust differences across study characteristics. Although study length showed a statistically significant subgroup test, the result was not stable after excluding singleton categories. Meta-regression analyses similarly found no significant linear associations for study length, prompts per day, items per prompt, or assessment window. Leave-one-out analyses showed that no single study drove the pooled estimate. Regarding the risk of bias, 2 studies were judged as low, while 21 were judged as moderate risk. Quality scores ranged from 6.5 to 9.0, and the certainty of evidence for the pooled compliance rate was rated as very low according to the Grading of Recommendations Assessment, Development, and Evaluation approach. CONCLUSIONS: Overall compliance with EMA among patients with cancer was moderate to high, suggesting that repeated real-world assessment may be feasible in oncology research settings. Nevertheless, the very high heterogeneity, wide prediction interval, and very low certainty of evidence indicate that compliance is context-dependent. The pooled estimate should therefore be interpreted as an approximate benchmark rather than a universal expected rate. Future oncology EMA studies should use standardized compliance denominators, report missing prompts transparently, and prospectively evaluate patient-centered design strategies that reduce burden while preserving data quality.

Humans↗

PubMed2026

Effects of Exergame Balance Training with Variable Cognitive Motor Challenges on Serum BDNF, p-tau181, and Cognitive Functions in Adults with Mild Cognitive Impairment: A Randomized Trial.

INTRODUCTION: Cognitive-motor exergame balance training may increase attentional demands and neuronal processing, potentially affecting serum levels of brain-derived neurotrophic factor (BDNF), Aβ1-42, and p-tau181, as well as train cognitive abilities in adults with mild cognitive impairment (MCI). This study aimed to compare the effects of exergame balance training of mild, moderate, high-difficulty, and Wii Fit™ groups on blood serum levels of BDNF, Aβ1-42, p-tau181, and cognition function in adults with MCI. METHODS: In this four-arm, parallel group randomized clinical trial, 97 adults with MCI were randomly assigned to exergame balance training groups of mild, moderate, high-difficulty, and Wii Fit exergame as a control group. All participants received 40 min/session, 3 times/week for 8 weeks. Assessment of serum levels of p-tau181, Aβ1-42, BDNF, and cognitive functions was conducted at baseline, after weeks 4 and 8. A mixed-model analysis of covariance was used, with post-baseline measurements (weeks 4 and 8) specified as the within-subject factor and the corresponding baseline value entered as a covariate to adjust for initial between-group variability. RESULTS: A significant group × time interaction was found for BDNF, F(3,92) = 6.413, P = 0.017, ηp2 = 0.181; p-tau181, F(3,92) = 4.640, P = 0.040, ηp2 = 0.138; attention, F(3,92) = 4.171, P = 0.045, ηp2 = 0.057; abstraction, F(3,92) = 4.263, P = 0.043, ηp2 = 0.058; and visuospatial skills, F(3,92) = 6.931, P < 0.001, ηp2 = 0.234. CONCLUSION: Cognitive-motor challenge-based exergame balance training was associated with an increase in serum BDNF, a reduction in p-tau181. In contrast, the Aβ1-42 levels remained stable. These changes were accompanied by improvement in selective cognitive functions (attention, abstraction, and visuospatial skills) in individuals with MCI. Greater effects were observed in moderate and high-difficulty groups, suggesting the importance of intervention intensity in promoting cognitive and neurobiological outcomes in MCI.

Humans↗

PubMed2026

Characteristics of children with ureteroceles presenting for urological evaluation in the modern medical era.

INTRODUCTION: Historically, children with ureteroceles presented symptomatically and were managed surgically. It is unclear if this changed in the modern medical era of prenatal imaging and shared decision making. We aimed to describe the presentation and management of ureteroceles during initial urological evaluation of children in the era of widespread prenatal ultrasonography. PATIENTS AND METHODS: We retrospectively reviewed records of children (<18 years old [yo]) initially evaluated at our center with a ureterocele (2011-2020). We analyzed demographics, renal anatomy, initial presentation for evaluation, and initial management with non-parametric statistics. Febrile urinary tract infections (fUTIs, ≥ 38 °C) were classified as 1) urosepsis (positive urine culture admitted to pediatric intensive care), 2) documented (positive urine culture) or 3) family-reported. RESULTS: We identified 188 children (65% female). Median age at presentation was 1.2 months old (mo) (IQR 18 days-4.4 mo). Antenatally-detected congenital anomalies of the kidney and urinary tract (aCAKUT) were noted in 143 (76%) children with a confirmed postnatal diagnosis of ureterocele. Overall, 129/188 (69%) children presented without symptoms and 59 (31%) presented with symptoms. fUTI was the most common symptomatic presentation (46/188, 24%): urosepsis (6 children), documented (30), and family-reported (10). Children with aCAKUT presented earlier than those without aCAKUT (27 days vs. 1.6 yo, p < 0.0001). They were also less likely to present with symptoms (11% vs. 96%, p < 0.0001), including fUTIs (7% vs. 78%, p < 0.0001). In total, 108 children (57%) were initially managed with transurethral incision, 73 (39%) were observed, and 7 (4%) had reconstructive surgery. Asymptomatic children with aCAKUT (42%) and symptomatic children without aCAKUT (37%) were more likely to be observed than symptomatic children with aCAKUT (7%, p = 0.02). Among 143 children with aCAKUT, those on antibiotic prophylaxis were less likely to present with a history of a fUTI compared to those not on prophylaxis (4/106 vs. 6/37, 4% vs. 16%, p = 0.02). COMMENT: We present a large observational study describing clinical and anatomical characteristics of children presenting with ureteroceles in a medical era of ubiquitous prenatal ultrasonography. Our retrospective study was limited by incomplete documentation of all antenatal ultrasonography and adherence with antibiotic prophylaxis. Long-term clinical outcomes will be the focus of future work. CONCLUSION: In contrast to historical cohorts, most children presented to urologists with asymptomatic ureteroceles diagnosed with aCAKUT. Most children without aCAKUT presented with a fUTI. Overall, 39% of children were initially observed, indicating an increased use of observation in the modern medical era.

Humans↗

PubMed2026

Impaired toilet training and bladder and bowel dysfunction in children with developmental coordination disorder - an underreported issue.

BACKGROUND & OBJECTIVE: Children with Developmental Coordination Disorder (DCD) face significant, yet often overlooked, challenges beyond motor impairments, including difficulties with toilet training and bladder and bowel dysfunctions (BBD). This study aims to explore whether children with DCD exhibit greater difficulties in these areas compared to typically developing children (TDC). METHOD: This cross-sectional case-control study included 84 children aged 5-8 years (42 DCD, 42 TDC), matched by school-grade and sex (33 boys and 9 girls per group). Parents completed the Vancouver Symptom Score for Dysfunctional Elimination Syndrome (VSSDES) to assess BBD symptoms, the Dutch DCD-questionnaire (DCD-Q) to evaluate motor coordination, and additional questions regarding toilet training, elimination diagnosis, and co-occurring conditions. Correlations and exploratory group differences were analysed. RESULTS: Parents of children with DCD reported significantly more toilet training difficulties than parents of controls (p < 0.001), including persistent accidents (47.6% vs. 9.5%), prolonged training (45.2% vs. 4.8%), and difficulties recognizing urination urgency (40.5% vs. 2.4%). The parental report of delayed attainment of bowel and bladder control (p < 0.05) and BBD rates (p < 0.001) was also significantly higher in children with DCD. Exploratory analyses indicated that the prevalence of these outcomes was not significantly different between children with DCD with and without co-occurring ADHD or autism, suggesting a possible primary association with DCD. Additionally, across both children with DCD and TDC, poorer motor skills were associated with more BBD symptoms (r = -0.474, p < 0.001). CONCLUSION: Children with DCD have a higher prevalence of toilet training difficulties and BBD compared to TDC, potentially affecting their psychosocial well-being. Greater awareness is crucial for timely and targeted care. Notably, the study's design, directly comparing children diagnosed with DCD to matched TDC, provides new insights into the prevalence of elimination difficulties in this population.

Humans↗

PubMed2026

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials.

AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate ≥ 90; 60-< 90; 30-< 60; < 30 mL/min/1.73 m2) and liver (total bilirubin ≤ 21 μmol/L or aspartate aminotransferase [AST] ≤ 31/≤ 37 [female/male] U/L; total bilirubin > 21 μmol/L or AST > 31/> 37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p > 0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c < 7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p < 0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p < 0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229).

Humans↗

PubMed2026

Mortality of Individuals With PRNP Variants Associated With Prion Disease in the United States, 1998-2024.

BACKGROUND AND OBJECTIVES: To characterize the survival of individuals with pathogenic PRNP variants-including to estimate annual hazards, to judge the accuracy of previously reported survival data, and to evaluate the utility of public record searches in determining vital status. METHODS: In this single-center cohort study, we gathered data on individuals who received positive antemortem PRNP genetic tests at the US National Prion Disease Pathology Surveillance Center (NPDPSC), including both diagnostic tests in symptomatic individuals, and predictive tests in asymptomatic individuals. Genetic test and autopsy results were queried from the NPDPSC database, and public record searches were conducted using online tools. RESULTS: Four hundred four individuals received positive genetic test results. Of 206 cases symptomatic at the time of genetic testing, 188 are likely now deceased based on typical disease duration for their genetic variants. Combined autopsy and public record searches in combination confirmed 174 of these deaths, for an estimated 92.6% sensitivity. We evaluated the age-dependent penetrance of the reportedly highly penetrance variants D178N and E200K and the reportedly low-penetrance variant V210I. Among 99 initially asymptomatic individuals with the pathogenic E200K variant, more than 936 person-years of follow-up, 18 deaths were observed, significantly fewer than 27.4 expected according to life tables based on retrospective data. The age-dependent penetrance of E200K calculated from these longitudinal data was significantly lower than that from retrospective data, with 69% penetrance by age 80 and a median age at death of 75. For the pathogenic D178N variant, the median age at death was 57, which was numerically later, but not significantly different from, that seen in retrospective data. For V210I, just 2 deaths occurred, both after age 90, consistent with minimal penetrance. DISCUSSION: Our data support high penetrance of PRNP D178N and E200K variants and low penetrance of V210I. For E200K, the age at onset distribution appears to be shifted slightly later, and lifetime risk slightly lower, than previously reported. Autopsy data and public death records in combination were sensitive and concordant for determining long-term outcomes, but additional prospective data should be gathered to support future preventive trials.

Journal Article↗

PubMed2026

Association of Baloxavir Treatment Timing with Serial Interval and Household Transmission of Influenza through a Likelihood-Based Analysis.

BACKGROUND: Baloxavir treatment is associated with reduced influenza transmission within households, and the serial interval varies by treatment status. However, it remains unclear how baloxavir-induced changes in the serial interval relate to household transmission. We aimed to quantify the model-based association between baloxavir treatment timing and the serial interval and household transmission risk. METHODS: We conducted a household survey of influenza cases in Japan between October 2018 and February 2019. We defined the likelihood-based model integrating the serial interval distribution by treatment status and the secondary attack rate (SAR) using individual-level data from index cases. Using this model, we estimated the reduction in the serial interval associated with baloxavir treatment. RESULTS: Compared with untreated index cases, baloxavir-treated cases were estimated to have a serial interval density reduced by 21.42% following treatment. Treatment within 24 hours was associated with a 0.1685 reduction in the area under the curve, with smaller reductions as treatment was delayed. Earlier treatment was associated with a shorter, more concentrated distribution, whereas treatment 72 hours after onset resembled untreated cases. CONCLUSIONS: Our findings highlight that baloxavir treatment is associated with a shorter serial interval and lower estimated secondary household transmission risk. We provide model-based estimates suggesting that earlier administration is associated with a greater reduction in serial interval density and estimated transmission risk, which may inform public health strategies for infection control.

Influenza↗

PubMed2026

Intravenous thrombolysis for ischemic stroke in extended time window selected with CT perfusion: a systematic review and meta-analysis.

PURPOSE: Recent randomized controlled trials (RCTs) have provided new evidence regarding the efficacy and safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) presenting within the extended time window (ETW). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IVT, in patients treated within the ETW and selected with perfusion imaging criteria, predominantly computed tomography perfusion (CTP). METHODS: A systematic review and meta-analysis, registered in PROSPERO, was conducted including all available RCTs comparing IVT with best medical treatment (BMT) in patients with AIS within the ETW, selected using advanced perfusion imaging criteria. The predefined efficacy outcomes were excellent functional outcome and good functional outcome at 3 months. The safety endpoints included symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days. RESULTS: Six RCTs, including 1182 patients treated with IVT and 1176 patients receiving BMT, were included. IVT was associated with a higher likelihood of achieving excellent and good functional outcomes at 3 months. Exploratory subgroup analyses by treatment timing suggested consistent findings up to 24 hours. No significant difference in 90-day mortality was observed between groups, whereas IVT was associated with an increased risk of sICH. CONCLUSION: Treatment with IVT in the ETW (4.5-24 h) in patients selected using advanced perfusion imaging, predominantly CTP, may be associated with improved functional outcomes in patients with AIS. Although IVT was associated with an increased risk of sICH, no significant increase in 90-day mortality was observed. PROSPERO REGISTRATION: CRD420261304314.

Aged↗

PubMed2026

Novel Germline ELP1 Splice-Acceptor Variant in NF1-Negative Optic Pathway Glioma: Expanding the Clinical Spectrum Associated With ELP1 Variation.

We report a 7-year-old boy with NF1-negative optic pathway glioma harboring a novel germline ELP1 splice-acceptor variant (NM_003640.5:c.2205-2A>G) identified by whole-exome sequencing. The variant was likely pathogenic (ACMG/AMP: PVS1, PM2) and inherited from an asymptomatic father, consistent with incomplete penetrance, expanding the limited evidence linking germline ELP1 variation to gliomas.

Humans↗

PubMed2026

Efficacy of a high-frequency repetitive transcranial magnetic stimulation for craving reduction in adolescents with gaming disorder: a 4-week randomized control trial with 24-week follow-up.

BACKGROUND: With the widespread popularity of online gaming, gaming addiction has come under scrutiny. While there is ongoing research on the diagnosis and treatment of gaming disorder among adolescents, the clinical robustness and reliability of intervention strategies remain uncertain. METHODS: A 4-week, double-blind, randomized, sham-controlled clinical trial was conducted to evaluate the efficacy of noninvasive, high-frequency repetitive transcranial magnetic stimulation (rTMS) in alleviating psychological craving in adolescents diagnosed with gaming disorder. Sham rTMS was administered to the control group using the tilted-coil method. Both groups of participants were treated with SSRI medications. A total of 80 adolescents with gaming disorder participated in this study, and 73 ultimately completed the 24-week follow-up. The primary outcome was the change in craving levels before and after the rTMS intervention, as assessed by the Visual Analogue Scale (VAS). Secondary outcomes included changes in anxiety and depression levels before and after the intervention, as assessed by the HAMA and HAMD. RESULTS: We assessed levels of psychological craving, anxiety, and depression among adolescents with gaming disorder at baseline, after completing a 4-week intervention, and at a 24-week follow-up post-intervention. Our repeated-measures MANOVA results, adjusted for course variables, revealed a significant main effect of rTMS intervention on psychological craving levels in adolescents addicted to online games (F(11, 781) = 11.238, P < 0.001, partial η² = 0.142), as well as significant main effects on time (F(11, 781) = 6.809; P < 0.001, partial η² = 0.091) and group effects (F(1, 71) = 26.707, P < 0.001, partial η² = 0.282). In addition, repeated-measures ANOVA results showed significant time effects for anxiety (F(2, 142) = 20.747, P < 0.001, partial η² = 0.234) and depression levels (F(2, 142) = 22.277, P < 0.001, partial η² = 0.285) among adolescents with gaming disorder, with nonsignificant between-group effects and no intergroup interaction. In the active stimulation group, changes in psychological craving levels after 4 weeks of treatment were significantly and positively correlated with changes in anxiety levels after 4 weeks of treatment in adolescents addicted to online games (r = 0.335, P < 0.05). CONCLUSION: Our findings indicate that high-frequency rTMS targeting the left dorsolateral prefrontal cortex may be a promising approach for reducing psychological craving in adolescents with gaming disorder. TRIAL REGISTRATION: ChiCTR2500102979 in chictr.org.cn, registered on May 22, 2025.

Humans↗

PubMed2025

Global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD: a systematic review and meta-analysis.

BACKGROUND: The presence of diabetes increases the risk of adverse outcomes of patients with non-alcoholic fatty liver disease (NAFLD) even in those with lean or non-obese NAFLD. However, the epidemiological data regarding the prevalence of diabetes and prediabetes in lean or non-obese NAFLD populations remain limited. We assessed the global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD. METHODS: Published studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science databases from the inception of the databases to October 2024. The pooled global prevalence of diabetes or prediabetes in patients with NAFLD was evaluated using random-effects meta-analysis. Subgroup meta-analysis and meta-regression were used to investigate potential sources of heterogeneity. RESULTS: A total of 54 studies involving 146,714 patients with non-obese or lean NAFLD were included. The pooled global prevalence of diabetes among patients with lean or non-obese NAFLD was 15.6% (95% CI 10.8%-22.7%). Studies from South America reported the highest prevalence (41.3%, CI 39.1%-43.5%). Meta-regression models showed that geographic region and mean age (p < 0.05) were associated with the were associated with the prevalence of diabetes, jointly accounting for 51.61% of the heterogeneity. The global prevalence of prediabetes among patients with lean or non-obese NAFLD was 22.9% (95% CI 12.5%-41.9%) with the highest prevalence reported in studies from Europe (34.4%, CI 23.0%-51.4%). Meta-regression models showed that geographic region and country (p < 0.05) were associated with the prevalence of prediabetes, jointly accounting for 73.65% of the heterogeneity. CONCLUSION: The pooled global prevalence of diabetes and prediabetes were 15.6% and 22.9% in lean or non-obese patients with NAFLD, respectively. These findings suggest the importance of diabetes screening in these patients.

Humans↗

PubMed2026

Bipolar circumcision with mucocutaneous plane separation: A safe, precise, blood-sparing, dressing-free approach.

Conventional circumcision techniques may result in bleeding, limited control of the mucosal collar, and the need for dressings. We describe a modified bipolar technique enabling near-bloodless dissection with precise mucosal trimming. Following bipolar division of the preputial skin, the inner mucosa is separated using two forceps and retracted proximally, creating a protective plane for safe skin adjustment. The mucosal collar is trimmed with scissors. The wound is closed with sutures and 2-octyl cyanoacrylate, avoiding dressings. This technique has been performed in 55 consecutive cases (median age: 2 years and 2 months; range: 0 days-17 years and 5 months) with no reported complications over a median follow-up of 2 years and 7 months (range: 3 months-4 years and 1 month).

Humans↗