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PubMed2026

Time to subsequent therapy (TTST) as an endpoint in clinical studies: development of standardized documentation of subsequent therapy through systematic literature review, expert interviews, and Delphi survey.

BACKGROUND: The endpoint Time to Subsequent Therapy (TTST) is an intermediate endpoint used in research and regulatory assessments. TTST denotes initiation of subsequent therapy and is a clearly definable, clinically relevant event for healthcare professionals. However, it has not been systematically established to which extent TTST is subjectively meaningful to patients. The objective of this study was to define TTST as a patient-relevant intermediate endpoint. METHODS: The study examined five oncological indications (breast cancer, prostate cancer, melanoma, multiple myeloma, and non-small cell lung cancer) using a systematic literature review, analysis of case report forms used in international randomized controlled trials, review of German Federal Joint Committee (G-BA) documents, semi-structured interviews and a two-stage Delphi survey with healthcare professionals, patients, and relatives. RESULTS: A total of 35 individuals participated in qualitative interviews. Most of them rated TTST as particularly significant. The Delphi Survey included 264 interviewees in round one, and 117 in round two. Patient-relevance of TTST was confirmed by 81% of respondents (95% confidence interval 76%, 85%). Nine treatment scenarios that justify TTST were identified. To capture patient-relevance, prospective collection of reasons for and consequences of therapy change are required. A checklist with standardized response formats plus free-text fields was developed: a comprehensive master checklist for flexible, complete documentation and a short version focused on therapy change-specific items. CONCLUSIONS: TTST is an intermediate endpoint whose systematic documentation of characteristics demonstrating patient-relevance can be standardized in research and clinical practice using the developed checklists.

Humans↗

PubMed2025

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1‑chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals↗

PubMed2026

Rhinoplasty Difficulty Scale: Development and Psychometric Analysis of a Surgeon's Assessment of Rhinoplasty Technique and Nasal Deformity Correction.

BACKGROUND: Rhinoplasty surgeons lack a universal scale of the relative difficulty of rhinoplasty techniques and rhinoplasty deformities. OBJECTIVE: To compare the expert opinion of the difficulty of rhinoplasty techniques and rhinoplasty deformities among international rhinoplasty surgeons, as measured by a scale of difficulty. METHODS: A cross-sectional survey of rhinoplasty surgeons collected training levels, experience, case volume, and perceived expertise. Rhinoplasty techniques/deformities (n = 64) were rated from 1-10, representing the least to most technically demanding. Rasch analysis was used to examine the fit of the observed data to Rasch model requirements, assess rating scale functioning, and provide estimates of internal consistency. RESULTS: Respondents (n = 63) were in practice (<5 years, 14%; 5-10, 20%; 10-20, 20%; 20-30, 26%; >30, 20%), and rhinoplasty volume ranged from <25 (14%) to >100 cases/year (32%). Self-reported expertise was comfortably novice (32%), intermediate (10%), advanced (28%), and expert (30%). Otolaryngology (42%), facial plastic surgery (30%), and plastic surgery (28%) were represented. Rasch estimates of internal consistency reliability were excellent (0.96 for surgeons and 0.99 for items); the item difficulties were more heterogeneous (mean: 0, SD: 1.23) than the distribution of surgeons (mean: -0.09, SD: 0.58). Survey items were ordered by difficulty, ranging from least difficult (inferior turbinate reduction = 1.01) to most difficult (contracted nose repair post-infection = 8.24). CONCLUSION: The newly developed Rhinoplasty Difficulty Scale provides ratings of common rhinoplasty techniques and deformities with a high correlation among experts using this rating scale.

Humans↗

PubMed2026

Longitudinal associations between family factors and the neurodevelopmental and psychosocial outcomes of children with congenital heart disease: A systematic review.

Family factors have been gaining increased attention in understanding adverse neurodevelopmental and psychosocial outcomes for children with congenital heart disease (CHD). To clarify relevance, we undertook a systematic review of only longitudinal studies which assessed such associations. Comparisons with the contribution of disease/surgical factors were also made where included studies considered such. We included longitudinal studies which assessed dynamic family factors (e.g. parent mental health, attachment, family functioning) and later child outcomes. Searches were conducted across CINAHL, Medline-Pubmed, PsychInfo and SCOPUS Web of Science. The NIH Quality Assessment Tool was used to evaluate study quality and risk of bias. Eighteen studies, utilizing data from 11 study samples and 2109 participants, met inclusion criteria. These studies included samples from infancy, with follow-up periods stretching into young adulthood, and with various degrees of CHD severity. The quality of studies was "good" to "fair", with key limitations of attrition and limited sociocultural diversity in samples. Findings suggested that family factors predicted later child psychosocial outcomes and more consistently than severity of disease indicators. This contrasted with a much smaller number of studies examining family factors and child neurodevelopmental outcomes, where no reliable conclusions could be reached. Findings highlight the importance of screening and family focused interventions for this population.

Child↗

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↗

PubMed2026

Multi-Omics Genome-Wide to Explore the Formation and Development Targets for Intracranial Aneurysms.

Intracranial aneurysms (IAs) represent a significant and potentially life-threatening category of disease, and there is currently a lack of effective treatment options aimed at preventing the progression of the disease. Accordingly, this study is dedicated to exploring and identifying effective drug targets that can help in the prevention of both the formation and rupture of IAs, along with a detailed examination of the underlying potential mechanisms involved in these processes. The data related to IAs for this research was obtained from the ISGC Biobank and UK Biobank. Then, we investigated the possible biological functions and unintended consequences of targeting the specific genes that were highlighted in IAs by using mediation analysis, virtual knockout experiments, and PW-MR studies. A total of 5 unique potential drug targets for IAs (FKTN, MAP3K1, PSMA4, SLC22A4, ADAM17), 4 unique potential drug targets for SAH (PSMA4, ADAM17, GPR160, SLC22A4), and 2 unique potential drug targets for UIA (SLC22A4, PRCP) were identified across brain or blood samples. Among the various candidates identified, SLC22A4 has emerged as a promising potential drug target, showing significant expression levels in both blood and brain tissues. Additionally, phenome-wide MR of SLC22A4 across 32 selected phenotypes did not identify statistically significant adverse associations after FDR correction. Virtual knockout (KO) experiments on SLC22A4 revealed that SLC22A4 KO disrupted 81 genes, all of which are involved in IAs-related pathways. Besides, we recognized BRD-K85337334 as potential candidates for targeting SLC22A4. This research indicates that an increase in SLC22A4 gene expression within the blood or brain is directly linked to a heightened risk of IAs rupture, which will aid in prioritizing the development of drugs for IAs.

Humans↗

PubMed2026

Mechanisms linking the gut microbiota to colorectal cancer development and progression.

Colorectal cancer remains a leading cause of global cancer mortality, with a concerning rise in early-onset cases driven by complex interactions between environmental exposures, lifestyle factors, and host genetics. Mounting evidence indicates that gut microbiota dysbiosis critically modulates this oncogenic process, acting as an active participant rather than a passive bystander. This review systematically synthesizes the dichotomous roles of the intestinal microbiome in colorectal tumorigenesis through the conceptual framework of the driver-passenger model. We discuss how early initiating driver bacteria, such as Polyketide synthase-positive Escherichia coli and enterotoxigenic Bacteroides fragilis, compromise mucosal barriers, induce chronic mucosal inflammation, and inflict direct genomic instability. As the local tumor microenvironment undergoes profound metabolic remodeling, opportunistic passenger pathogens, notably Fusobacterium nucleatum, become enriched, further promoting cellular proliferation and facilitating tumor immune evasion. Conversely, protective commensals, exemplified by Clostridium butyricum and Streptococcus thermophilus, exert robust tumor-suppressive effects through multifaceted mechanisms. These beneficial microbes actively antagonize malignant progression by redirecting tumor metabolic fluxes toward oxidative stress, orchestrating deep epigenetic reprogramming, and degrading core oncoproteins to reverse chemoresistance. Transitioning from fundamental mechanisms to clinical application, we evaluate a comprehensive spectrum of microbiota-targeted interventions, encompassing non-invasive diagnostic biomarkers, fecal microbiota transplantation, engineered bacteria, phage therapy, and postbiotics. Finally, we critically address the formidable translational challenges associated with microbial heterogeneity, long-term safety, and regulatory standardization, aiming to provide a balanced perspective on integrating microbiome-based strategies into next-generation precision oncology for colorectal cancer.

Humans↗

PubMed2026

Evolutionary conservation of heat shock proteins in Blattodea and their roles in wing morphogenesis and ovarian development of Blattella germanica.

Heat shock proteins (Hsps) are essential molecular chaperones for protein homeostasis and stress responses. However, the Hsp repertoires and functions in Blattodea remain underexplored. Our genome-scale survey of nine Blattodea species revealed 37-46 conserved Hsp90, Hsp70, and DNAJ (Hsp40) genes, with DNAJ the most abundant and Hsp90 the least. Phylogenetic analysis confirmed the evolutionary conservation of three Hsp90, seven Hsp70, and 29 DNAJ subclades in Blattodea. Selection pressure analysis revealed predominant purifying selection (dN/dS ≪ 1) across lineages, strongest in DNAJ and highest in Hsp90 conservation. In Blattella germanica, expression of six representative BgHsp genes progressively increased during development, peaking in fifth-instar nymphs. Tissue expression profiling revealed that BgHspA1-2/3/4 were predominantly expressed in legs, BgDNAJB5 and BgHsp90AB1-2 were enriched in the fat body, and BgHsp90AB1 was highly expressed in the head. dsRNA injection targeting conserved Hsp gene regions achieved 61.9-94.1% knockdown of all six target genes. RNAi knockdown of six BgHsp genes disrupted wing morphogenesis, causing distinct phenotypes: wing whitening (56.7%, dsBgHspA1-4), unequal length (66.7%, dsBgHspA1-3; 76.7%, dsBgDNAJB5), and wing wrinkling (70%, dsBgHspA1-2; 63.3%, dsBgHsp90AB1; 76.7%, dsBgHsp90AB1-2). During ovarian formation, the developmental delay was most severe in the dsBgHsp90AB1 group, moderate in the dsBgHsp90AB1-2 and dsBgHspA1-2/3/4 groups, and weakest in the dsBgDNAJB5 group. Besides, knockdown significantly downregulated key developmental genes (apterous-a, nubbin, scalloped, ultrabithorax, wingless, and vitellogenin). These findings provide a reference for understanding the evolutionary patterns of Hsps in Blattodea, and offer mechanistic insights into the developmental regulation mediated by Hsps in this important public-health pest.

Animals↗

PubMed2026

Development of a core descriptor set for studies assessing interventions for diabetes-related foot ulceration.

AIMS/HYPOTHESIS: Foot ulceration is a common complication of diabetes and is associated with high mortality and costs. The quality of evidence to inform clinical practice is limited, partly because clinical studies do not consistently report baseline participant characteristics. This study aimed to develop a core descriptor set (CDS), a minimum set of descriptors to be measured in all studies evaluating interventions for people with diabetes-related foot ulceration. METHODS: A longlist of descriptors was generated through a systematic review of studies assessing interventions for diabetes-related foot ulcers, pre-registered with PROSPERO (CRD42019128250). The identified descriptors were then ranked based on perceived importance by healthcare professionals from different fields and geographical locations using a nine-point Likert scale in the first round of a Delphi survey. Using standardised criteria, descriptors without consensus were re-ranked in round two. Critical descriptors and those without consensus after the Delphi process were discussed in the consensus meeting to finalise the CDS. RESULTS: The systematic review yielded 95 candidate descriptors. The two Delphi rounds were completed by 102 and 69 healthcare professionals, respectively. The Delphi process identified 34 critically important descriptors and 13 descriptors without consensus, which were discussed in the consensus meeting. The ratified CDS included 28 descriptors across nine domains: demographic variables; individual factors; ulcer characteristics; limb characteristics; ongoing medical interventions; previous surgical interventions; medication history; biochemical measurements; and quality of life/function/symptoms. CONCLUSIONS/INTERPRETATION: This CDS reflects characteristics important to health professionals and researchers when reporting clinical studies on diabetes-related foot ulceration. Its use will aid the reporting of future studies.

Humans↗

PubMed2026

Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantification of twenty-five steroids in equine serum.

Steroids are potential biomarkers for monitoring equine pregnancy. However, immunoassays currently used for their quantification suffer from cross-reactivity and limited specificity, thus requiring more accurate methods. This study reports the development and validation of a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 25 steroids covering the main biosynthetic pathways of progestogens, corticosteroids, androgens, and estrogens. Steroids were extracted by protein precipitation followed by evaporation, derivatization, and reconstitution before LC-MS/MS analysis. A surrogate matrix was used for calibration and validation to avoid endogenous interference. Validation was performed according to and partly adapted from Clinical and Laboratory Standards Institute guidelines (CLSI), including linearity, trueness, precision, limits of detection and quantification, measurement uncertainty, recovery, matrix effects, carryover, selectivity, and stability. Calibration curves were fitted using the best-performing weighted linear or quadratic regression model, yielding excellent linearity (R2 > 0.990), trueness between -9.0% and 2.3%, and intra- and inter-day precision <6.3%. Lower limits of quantification ranged from 2.07 to 2250 pg/mL depending on physiological analytes concentration. Extraction recovery averaged 24.3-114.9%, matrix effects were acceptable, and accuracy ranged from 94.4% to 98.9%. No carryover or interferences were detected. Measurement uncertainty remained <15%. This study presents the first LC-MS/MS method partially validated per CLSI criteria for the quantification of 24 steroids in equine serum. The method offers a sensitive and specific alternative to immunoassays and provides a robust tool for equine steroid profiling with potential applications in pregnancy monitoring, placentitis diagnosis, and fetal sex determination.

Animals↗

PubMed2026

Development, feasibility, acceptability, and preliminary impact of NutriSOS®: A behavioral mobile app to promote sustainable diets.

The primary objective of this study was to describe the development of the NutriSOS® app and to evaluate its feasibility and acceptability for its use in the NutriSOS® Randomized Controlled Trial (RCT) to promote sustainable diets. A secondary objective was to explore preliminary changes in dietary and physical activity behaviors and environmental impact following app use. The NutriSOS® app integrates personalized dietary advice, educational content, self-monitoring, and social interaction features. A single-arm, pre-post pilot study was conducted in 37 young Mexican adults over four weeks. Feasibility, acceptability, quality, and usability were assessed using online surveys, alongside exploratory changes in dietary and physical activity behaviors, environmental indicators, and their association with perceived behavioral determinants. Feasibility and acceptability were high overall, with favorable responses reaching up to 100% in key components such as the nutritional guide and learning modules, and above 90% for messaging, registration, and design. Greater variability was observed in some sections, particularly the 24-h recall (41-86%). Reductions in red and processed meat and ultra-processed food consumption were observed (from 3 to 1 times/week, p < 0.01), with ∼60% decreases in their related environmental footprints (p < 0.01) and favorable self-reported behavioral determinants (p < 0.0001). Physical activity type and intensity changed (p < 0.05). These findings support NutriSOS® as a feasible and acceptable tool, while highlighting areas for refinement, particularly those related to the time and effort required for data entry, prior to its implementation in the NutriSOS® RCT, in which its effectiveness will be formally evaluated.

Humans↗

PubMed2026

Development and Crossover Evaluation of an Artificial Intelligence-Assisted System for Solid Pancreatic Lesion Detection and Pancreatic Parenchyma Recognition in Endoscopic Ultrasonography (With Video).

BACKGROUND AND STUDY AIMS: Pancreatobiliary endoscopic ultrasonography (EUS) is technically demanding, and supervised training opportunities are limited. We developed an artificial intelligence (AI) overlay system for detecting solid pancreatic lesions (SPL) and recognizing pancreatic parenchyma (PP) and evaluated its effect on reader performance. PATIENTS AND METHODS: Across six centers, two deep learning-based models were trained using expert-annotated EUS frames. We then conducted a randomized, two-sequence, two-period crossover reader study in which eight endosonographers (five novices and three experts) interpreted image sets with and without AI assistance. The primary endpoint was superiority of sensitivity for SPL detection among novices; key secondary endpoints included specificity and PP recognition. RESULTS: From 118 patients, 120 SPL-positive/negative image sets and 160 PP-positive/negative image sets were constructed. Among novices, AI assistance improved SPL detection sensitivity (88.7% vs. 76.8%, p < 0.001) and accuracy (86.4% vs. 78.7%), while specificity met the predefined noninferiority criterion (84.2% vs. 80.5%, p < 0.001). For PP recognition, sensitivity increased numerically (86.3% vs. 83.3%) but did not meet the predefined superiority criterion (p = 0.095); specificity met the noninferiority criterion (87.8% vs. 81.0%), and accuracy increased from 82.1% to 87.0%. Among experts, sensitivity was maintained for both tasks, whereas specificity increased with AI assistance. CONCLUSIONS: AI assistance improved SPL detection among novice endosonographers. For PP recognition, sensitivity increased without reaching statistical superiority, whereas specificity met the predefined noninferiority criterion. These findings support a potential adjunctive role for AI in EUS interpretation.

Humans↗

PubMed2026

Community-driven advances in computational mass spectrometry: The perspective of EuBIC-MS members.

Advances in data acquisition, artificial intelligence, and integrative bioinformatics are driving the rapid evolution of computational mass spectrometry, and in turn, transforming modern proteomics, metabolomics, and lipidomics. These developments have greatly increased the scale and complexity of mass spectrometry data, underscoring the importance of evolving accurate, transparent, efficient and reproducible data processing workflows. Addressing these challenges requires collaborative innovation that brings together expertise in software engineering, statistics, and biology. The European Bioinformatics Community for Mass Spectrometry (EuBIC-MS), an initiative of the European Proteomics Association (EuPA), fosters a culture of open, community-driven development through its biennial Developers Meetings and Winter Schools. This commentary summarizes the scientific background and outcomes of the EuBIC-MS Developers Meeting 2025, which took place in Novacella, Italy. Three keynote presentations highlighted major frontiers in the field: deep proteome and phosphoproteome profiling, text mining for protein-protein interaction extraction, and scalable proteomics for AI-driven drug discovery. Seven community-selected hackathons addressed emerging challenges such as single-cell proteomics data analysis, FAIR metadata extraction, deep learning frameworks, R-Python interoperability, and DIA validation. Together, these efforts demonstrate the potential for scientific and technical innovation to arise from open collaboration, and highlight how community-driven initiatives can accelerate progress in computational mass spectrometry. SIGNIFICANCE: Modern proteomics increasingly depends on computational advances to translate complex, high-dimensional data into biological knowledge. The EuBIC-MS Developers Meeting 2025 exemplifies how community-driven collaboration can directly accelerate this process by bringing together experts from bioinformatics, statistics, and experimental proteomics to co-develop open, interoperable, and reproducible analytical tools. By fostering shared software frameworks, transparent benchmarking, and collaborative problem solving, the EuBIC-MS community helps ensure that technological innovation translates into reliable biological insights. This collaborative model strengthens the foundation for quantitative, system-level understanding of proteomes and establishes a sustainable path for integrating artificial intelligence and next-generation data acquisition into routine biological discovery. This commentary shows some current highlights in the field of computational mass spectrometry and community-based approaches undertaken during the most recent Developers Meeting to solve these challenges. The approaches discussed and initiated during the meeting - ranging from deep proteome profiling and phosphosite mapping to text mining, single-cell data analysis, and FAIR metadata extraction - address key bottlenecks that currently limit the biological interpretability and comparability of proteomics data.

Mass Spectrometry↗

PubMed2026

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5 min). Salivary chromogranin A and α-amylase were measured at baseline and 1 min post-task. Only VA% and chromogranin A showed significant condition × time interactions (p = 0.027-0.039). VA% significantly decreased from before to immediately after the task and 1 min post-task in both conditions (p ≤ 0.002), with significantly higher values in the CP condition than in placebo immediately after and 1 min post-task (p ≤ 0.037). Chromogranin A significantly increased from baseline to 1 min post-task in the placebo condition (p < 0.001) but not in the CP condition (p = 0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans↗

PubMed2026

Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.

BACKGROUND: Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS: CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS: Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30·9% (114 of 369 patients) with HD-WL versus 33·8% (123 of 364 patients) with CADe assistance (odds ratio 1·14 [95% CI 0·83-1·57], p=0·41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85·9% (95% CI 82·0-89·1) and specificity was 91·4% (89·4-93·0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION: CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING: Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Humans↗

PubMed2026

Co-Use of Some Substances Associated With Higher Doses in Adolescents: Findings From the Adolescent Brain Cognitive Development Study.

PURPOSE: Adolescence is a critical developmental period marked by heightened vulnerability to initiating substance use, with long-term implications for health and behavior. Nicotine, alcohol, and cannabis are the most commonly used substances among adolescents. Their use often co-occurs but few studies have described or quantified the patterns and doses of substance co-use in this vulnerable population. METHODS: We used data from six waves of the Adolescent Brain Cognitive Development study. Substance use was measured through a web-based timeline followback interview, and outcomes are operationalized into substance use quantity (in standard units), single use, and co-use (use of two substances on the same day) of alcohol, cannabis, and nicotine. Group differences of average dose in standard units between single use and co-use for each substance class were analyzed using linear mixed-effects modeling in years 4-6. RESULTS: The average dose of nicotine was significantly higher when co-used with alcohol (4.32; 95% confidence interval [CI]: 2.55-6.09; p < .001) or when co-used with cannabis (4.41; 95% CI: 2.76-6.05; p < .001) in year 6; nicotine trends were similar in years four and five. In year 6, the average dose of alcohol was higher when co-used with cannabis (1.87; 95% CI: 0.37-3.36; p = .004) or co-used with nicotine (1.64; 95% CI: 0.06-3.22; p = .03) compared to single use of alcohol. The average dose of cannabis was not significantly different when used singularly or co-used with either alcohol or nicotine in our study years. DISCUSSION: During adolescence, the co-use of substances (namely alcohol and nicotine) may lead to higher average doses compared to single-substance use.

Humans↗

PubMed2026

Somatic mutations: recent advances in brain aging and neurodegeneration.

Somatic mutations are genetic variants that occur after the single-cell phase of development and have been implicated in disease pathogenesis. While most DNA lesions are detected and repaired, examination of healthy tissue has revealed that some lesions escape repair, leading to somatic mutations that accumulate at a consistent rate, including in human brain tissue and postmitotic neurons. Emerging methodological and analytical advances have revealed the presence of persistent mutagenic mechanisms during healthy brain aging as well as mutational pattern shifts in the context of neurodegenerative diseases. Here, we highlight recent methodological advances, summarize our current understanding of somatic mutagenesis in neurotypical brain aging, and examine the role of somatic mutations in neurodegenerative diseases.

Humans↗

PubMed2026

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans↗