Glioblastoma diagnostic models and therapeutic drug discovery based on GEO data and machine learning methods.

Beyond the urge to move: Impulsivity, aggression and impulse control disorders in restless legs syndrome.

From symptom to diagnosis: Gap between clinical observations and PTSD recognition in child protection.

Cytomegalovirus infection and coronary artery disease in liver transplant recipients: Nationwide study using protocolized cardiac computed tomography.

Depression and anxiety in adults with epilepsy. Systematic literature review and meta-analysis.

Psychosocial aspects in diabetes care: An observational study at an outpatient academic diabetes specialist centre in a metropolitan capital.

Alternative RNA splicing is a fundamental mechanism for enhancing proteomic diversity, and its dysregulation is a hallmark of cancer progression. However, the dynamic regulatory networks controlling oncogenic splicing events remain poorly understood. Our previous work identified the inclusion of CLSTN1 exon 11 as critical for the epithelial-to-mesenchymal transition (EMT). Here, we demonstrate that this splicing event promotes breast cancer metastasis by enhancing cell migration, invasion, and the generation of circulating tumor cells (CTCs) in vivo. To translate this finding into a therapeutic strategy, we developed splice-switching antisense oligonucleotides (ASOs) that effectively reverse exon 11 inclusion and suppress cancer cell migration. Furthermore, through systematic screening, we identified the RNA-binding protein TIA1 as a key suppressor of exon 11 inclusion. TIA1 inhibits EMT and metastasis, but its function is antagonized during EMT by phosphorylation mediated by the kinase DAPK3, which is upregulated in this process. This work defines a novel DAPK3-TIA1-CLSTN1 splicing axis that drives breast cancer metastasis, revealing new layers of post-transcriptional regulation and presenting promising therapeutic avenues for targeting pro-metastatic splicing.

Post-stroke insomnia and the risk of post-stroke cognitive impairment and dementia: A large retrospective cohort study.

Chronic kidney disease (CKD), although not infectious, has a sharply rising global incidence, alarming rates of death and disability, and the potential to disrupt health systems and economies. Thus, it demands the urgency and global attention of past pandemics. Over 850 million people are affected, disproportionately impacting people in low- and middle-income countries. Although CKD can be detected with simple and cost-effective testing, it is a silent condition, often remaining asymptomatic until it has progressed to advanced stages where effective treatment options are limited. Early detection relies on systematic population-level screening, especially among individuals with comorbidities. The global response to CKD has remained largely silent: There is limited evidence of prioritization within health agendas and inadequate infrastructure for screening, surveillance, and treatment. Coordinated global action is required to halt this silent "pandemic," especially given advances in care and policy: New effective disease modifying therapies may lead to remission of CKD for many individuals, and the 2025 World Health Organization's adoption of the Kidney Health Resolution at the 78th World Health Assembly prioritizes kidney health to reduce the burden of noncommunicable diseases through promoting early screening, strengthening disease prevention, and improving access to care. In this review, we examine the failure to address the escalating CKD "pandemic" and explore how the use of low-cost and cost-effective screening tools, such as simple urine dipstick testing, and applying lessons learned from the COVID-19 pandemic are critical to further reframing CKD as a public health emergency and prioritizing kidney health on the global agenda.

The increasing adoption of tenofovir (TXF)-sparing antiretroviral therapy (ART) raises concerns regarding hepatitis B virus (HBV) susceptibility and reactivation risk among people with HIV (PWH). We characterized HBV serological profiles and vaccination status according to ART composition in a real-world cohort. A cross-sectional study of all PWH in active follow-up at Hospital Clínic, Barcelona, as of 30 June 2025. ART regimens were categorized as TXF-containing or TXF-sparing, with or without lamivudine (3TC). HBV serological patterns were classified as chronic infection, serologically resolved infection, isolated HBV core antibody (anti-HBc), no exposure/immunity, and vaccine-induced immunity. Demographic and clinical characteristics were compared using nonparametric and chi-squared/Fisher's tests. Among the 6437 participants included (82% cisgender men; median age 48 years [IQR 39-58]), 3519 (55%) received TXF-containing and 2918 (45%) TXF-sparing regimens, of whom 1702/2918 (58%) were with 3TC. HBV serological distribution was: 2% chronic infection, 26% serologically resolved infection, 5% isolated anti-HBc, 52% vaccine-induced immunity, and 15% without exposure/immunity (50% documented prior vaccination attempts, 32% nonresponders, and 31% with prior anti-HBs detection). Overall, 1280 (20%) lacked protective HBV immunity (isolated anti-HBc or negative serology for all markers), including 530 (41%) on TXF-free regimens. TXF recipients were younger (47 versus 50 years, p < 0.001), more often migrants (58% versus 49%, p < 0.001), had lower suppression rates (91% versus 97%, p < 0.001), a higher proportion of previous virological failure(s) (26% versus 21%, p < 0.001), and a lower number of prior ART regimens (median 3 versus 4, p < 0.001). One in five PWH lacked effective HBV immunity, including 41% of whom were receiving TXF-sparing strategies. In the context of increasing use of TXF-sparing strategies, improvements in systematic HBV screening, vaccination, and risk-based monitoring are essential to prevent HBV-related morbidity.

Prevalence and clinical outcomes associated with proximal deep vein thrombosis at hospital admission detected by bedside ultrasound in patients hospitalized in a medical oncology ward: An exploratory prospective study.

Comprehensive VACTERL screening is crucial in children with esophageal atresia (EA), as undetected anomalies can delay diagnosis and treatments for these problems. Screening practices vary widely in the literature, however. This study aimed to assess the proportion of EA patients receiving comprehensive VACTERL screening, examine screening changes over time and determine the prevalence of additional anomalies, VACTERL association and genetic diagnoses. A retrospective cohort study was conducted at a single center, including all neonates born with EA between 2000 and 2024. Comprehensive VACTERL screening included vertebral x-ray, cardiac and renal ultrasound, and physical examination for limb deformities and anorectal malformation. VACTERL classification was based on EUROCAT definitions. A total of 240 patients were included. Comprehensive VACTERL screening was conducted in 180 (75%) patients, improving to 100% in the past four years (i.e. 2020-2024). In screened patients, vertebral (32%) and cardiac (28%) anomalies were most commonly identified. VACTERL association was present in 28% of comprehensive screened EA patients: 14% VACTERL-LIKE, 11% STRICT-VACTERL and 3% VACTERL-PLUS. A genetic association was identified in 13% of patients, most commonly trisomy 21. While 75% of EA patients underwent comprehensive VACTERL screening, a fourth of the patients were not fully assessed, potentially leading to unrecognized anomalies with possible clinical implications. Over the last four years 100% screening rate has successfully been attained. VACTERL association was identified in 28% of patients and a genetic diagnosis was established in 13%. These findings emphasize the importance to pursue systematic and comprehensive VACTERL screening for patients with EA to detect these anomalies.

Incidence, risk factors, and outcomes of opioid overdose after major gastrointestinal surgery.

In vitro digestion and fermentation characteristics of ethanol-extracted low molecular weight ginseng polysaccharide (AGP): Interactions with gut microbiota, metabolite regulation, and immunomodulatory effects.

Systematic reviews (SRs) of randomized controlled trials (RCTs) are crucial for shaping clinical practice, but are only as good as the RCTs on which they are based. We aimed to summarize tools to prevent untrustworthy RCTs from entering meta-analysis. We propose six checkpoints: prepublication checks, postpublication checks, checks during aggregate-data meta-analysis, checks of individual participant data (IPD), and checks for umbrella reviews and guidelines. We searched PubMed for tools assessing RCTs for trustworthiness. Before publication, trialists must guarantee trustworthiness by providing registration details, protocol, datasets, and code. Journals should enhance data-sharing policies for RCTs. Research users should evaluate trials postpublication and report concerns to journals or platforms like PubPeer. Journals should be automatically alerted to comments, mark retracted references, expedite investigations, and communicate findings transparently. We found seven tools for both prepublication and postpublication checks and an international consensus set of statements for postpublication checks. Four were piloted, while one has been published as preprint (INveStigating ProblEmatic Clinical Trials in SR [INSPECT-SR]). Three were achieved by non-Delphi consensus, while INSPECT-SR used a Delphi process. No tools were formally validated; one (IPD-Integrity) underwent preliminary validation. All address trial ethics, registration, follow-up plausibility, and baseline data; 6 of 7 tools assess the plausibility of the authors' group size relative to trial context, recruitment timelines, and outcome data. Three were recommended for research user and editor checks. Systematic reviewers should assess RCTs for trustworthiness. All seven tools were recommended for systematic reviewers. Positive systematic reviewer screening for major issues can eliminate trials after study selection but before data extraction. Studies with unresolved issues should be excluded; their count should appear in the flow diagram with reasons. All tools assess study-level data. IPD-level checks should detect unexpected values and data patterns; IPD-Integrity and a developing INSPECT-SR extension can do so. Umbrella reviews should check whether original reviews assessed trustworthiness and, if needed, perform primary RCT assessments or only include SRs that have conducted checks. Guidelines should evaluate the trustworthiness of included studies. Six levels of trustworthiness checks can prevent untrustworthy RCTs from influencing practice. At the SR level, trustworthiness assessments should be integrated in Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Establishment of a Methodology for PAX1 and CADM1 Methylation Detection and Preliminary Assessment of Its Clinical Value for Cervical Cancer Diagnosis.

Chronic hepatitis D is the most severe form of viral hepatitis. Despite recommendations for systematic screening of HBsAg-positive individuals, hepatitis D infection remains underdiagnosed. Standard HDV virological markers are classically assessed in serum or plasma specimens obtained through venous whole blood sampling. This approach is costly and challenging in resource-limited settings. Dried blood spot (DBS) sampling offers a practical alternative for large-scale screening, diagnosis, and monitoring of viral hepatitis. The goal of the study is to evaluate the performance of commercially available HDV diagnostic assays using DBS. Plasma and DBS-collected whole blood specimens from individuals chronically infected with HBV or coinfected with HBV and HDV were analysed for HDV antibody detection, HDV RNA quantification, HBsAg levels, and HDV genotyping. HDV antibodies were reliably detected in DBS after threshold adjustment, with the LIAISON XL Murex Anti-HDV assay showing superior sensitivity (99.3%) compared to HDV Ab DIA.PRO (90.3%), while both assays exhibited excellent specificity. HDV RNA was quantifiable in 86.8% of DBS specimens from patients with active infection, although levels were about 1.5 log10 lower than plasma, showing a strong correlation (r = 0.786; p < 0.0001). HBsAg was detectable and quantifiable in all DBS samples, correlating closely with plasma values (r = 0.98). DBS-based HDV genotyping was successful in 84.8% of samples and concordant with plasma results. DBS collection of whole blood from DBS appears to be a promising and practical alternative to conventional venous blood sampling for HDV screening, diagnosis, and monitoring.

Interpretable machine learning with SHAP analysis identifies redox-modulating dietary antioxidants for predicting accelerated biological aging.

Curcumin (CUR) is a bioactive polyphenol with significant health potential; however, its use in food systems is limited by poor aqueous solubility. Hetero-protein aggregation offers a promising encapsulation strategy; however, its performance is highly dependent on formulation conditions. Here, an experimental screening approach was used to evaluate the effects of pH (4–10), whey protein isolate (WPI): lysozyme (LYS) ratio (3:1–1:3), and CUR concentration (905–54 μM) on the formation and encapsulation performance of WPI–LYS hetero-protein aggregates. The screening identified pH, protein ratio, and CUR loading as interdependent drivers of aggregation behaviour, surface charge, particle size, crystallinity, and encapsulation efficiency. Maximum encapsulation efficiency (97.56 ± 0.50%) was achieved at pH 7, 494 μM, and a WPI: LYS ratio of 1:1.5; however, structural analyses revealed that high CUR loadings resulted in residual crystallinity despite the high apparent encapsulation efficiency. In contrast, lower CUR loading (106 μM; 1:50 CUR: protein) produced amorphous hetero-protein aggregates with high encapsulation efficiency and improved structural homogeneity. Spectroscopic evidence indicates that, in the ternary WPI–CUR–LYS system, CUR is stabilised within a reorganised protein network through localised hydrophobic interactions and hydrogen bonding. In contrast, single-protein systems rely on less restrictive associations. Overall, WPI–LYS hetero-protein aggregates outperformed single-protein systems, demonstrating that reliable CUR encapsulation cannot be inferred from encapsulation efficiency alone. This work highlights the critical role of systematic screening in establishing formulation-dependent design rules for hetero-protein-based delivery systems in food applications. • WPI–LYS hetero-protein aggregates enhanced curcumin encapsulation vs single proteins • Maximum encapsulation efficiency achieved at pH 7 and WPI:LYS ratio of 1:1.5 • Curcumin modulated protein–protein interactions, reducing aggregation and particle size • XRD and SEM revealed amorphous curcumin at ≤106 μM and saturation above 494 μM • FTIR showed α-helix/β-sheet increase correlates with higher curcumin encapsulation

Wilson disease (WD) is a rare autosomal recessive disorder. Although hepatic and neurologic manifestations are characterized, long-term cardiac outcomes remain poorly defined. We report the first longitudinal study systematically assessing cardiac symptoms and events over nearly a decade in WD. In 2016, 61 WD patients underwent prospective cardiac evaluation including echocardiography, MRI and 24-h ECG. Nine years later, we re-contacted all surviving participants by telephone and emailed standardized questionnaires. Baseline characteristics of respondents and non-respondents were compared to assess selection bias; mortality data were obtained from family interviews and medical records. Outcomes were available for 31 of 61 patients (27 interviewed, 4 deceased; no cardiac-related deaths) after a mean follow-up of 9.1 years. Respondents did not differ from those lost to follow-up, except for fewer disease exacerbations. General and cardiac health remained unchanged in about half (48% and 52%), worsened in ~40%, and improved in ≤ 15%. Palpitations were frequent (70%), whereas dizziness (26%), syncope (7%), and leg oedema (15%) were infrequent and comparable to general-population estimates. Daily activity was unrestricted in 44%, mildly to moderately restricted in 52% and severely restricted in 4%. Only six patients (22%) remained in routine cardiology care. Baseline imaging, strain, autonomic and laboratory parameters did not predict symptoms at follow-up. Over 9 years, cardiac symptoms in WD were common but mostly mild to moderate. These findings support a symptom-guided cardiological assessment within interdisciplinary care. Whether systematic screening of asymptomatic patients is warranted remains uncertain and requires dedicated prospective study.