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PubMed2026

Neoplasms in prune belly syndrome: A novel case of early-onset metastatic bladder carcinoma and systematic review of reported tumors.

PURPOSE: Prune Belly Syndrome (PBS) is a rare congenital malformation complex characterized by cryptorchidism, urinary tract abnormalities and deficiency of the abdominal wall musculature. Although advances in neonatal and reconstructive care have substantially improved survival, the long-term risk of malignancy in this population remains poorly defined. We report a novel case of early-onset metastatic bladder carcinoma in a patient with PBS and perform a systematic review of all tumors described in association with the syndrome. METHODS: A systematic literature review was performed according to PRISMA guidelines and registered in PROSPERO (CRD420251072086). Databases searched through April 2025 included PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane, and SciELO. Reported tumor cases in PBS patients were identified and classified as either PBS-associated or not. We additionally describe a new case of invasive bladder carcinoma. RESULTS: Seventeen studies comprising 20 patients met inclusion criteria. Tumors directly related to the genitourinary tract accounted for half of the cases. Bladder carcinoma was the most frequent neoplasm (35%), followed by hepatoblastoma (25%). Bladder tumors occurred at markedly younger ages and often presented as advanced diseases. Our index case involved a 33-year-old man with PBS who developed metastatic muscle-invasive urothelial carcinoma and died shortly after diagnosis. DISCUSSION: Improved survival in PBS has led to recognition of new late complications, including malignancy. Tumorigenesis may be influenced by chronic urinary stasis, infection, catheterization, cryptorchidism, and underlying genitourinary developmental abnormalities. These findings should be interpreted as hypothesis-generating given the limited number of reported cases. CONCLUSION: Although uncommon, malignancies in PBS may occur earlier and behave more aggressively than in the general population. Given the current level of evidence, careful long-term follow-up with clinical awareness is warranted, rather than routine invasive screening for all patients.

Humans↗

PubMed2026

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4 days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9 ± 12.7; active/sham 50/54). The model yielded a Time × Novelty Seeking interaction (β = -1.70, p = 0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p = 0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans↗

PubMed2026

Sulfonic Ion-Exchange Resins as Versatile Tools for the Oxidative Degradation of Chemical and Biological Hazardous Agents.

Commercial sulfonic styrene-divinylbenzene ion-exchange resins are activated with aqueous H2O2 to generate metal-free decontamination systems that combine strong Brønsted acidity with immobilized oxidizing capability. Among five tested materials, Amberlyst 15 dry showed the best performance in terms of oxidant immobilization capacity and promoting the oxidative degradation of the sulfur mustard simulant (2-chloroethyl)ethyl sulfide, CEES, and the organophosphorus pesticide malathion under very mild conditions. Control experiments with K2CO3-exchanged resin demonstrate that efficient decontamination requires the synergy between surface acidity and peroxide functionality. The activated resins also display rapid biocidal activity, strongly reducing viable Escherichia coli and Staphylococcus aureus and completely suppressing the infectivity of HSV-1 and SARS-CoV-2 within min. These findings identify peroxide-activated sulfonic resins as simple, sustainable, regenerable, and versatile tools for efficient combined hazardous chemical and biological decontamination.

Oxidation-Reduction↗

PubMed2026

The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.

BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC. METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening. DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies. CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.

Humans↗

PubMed2026

Virtual Reality Mastoidectomy as Precadaver Training for Novices: A Randomized Crossover Study.

OBJECTIVES: To compare cognitive load during virtual reality (VR) simulation and cadaveric dissection (CD) mastoidectomy training in novice learners. To determine whether training order influences cognitive load, characterize cognitive load progression during the procedure, and assess whether VR training improves subsequent cadaveric performance. METHODS: In this randomized crossover study, 24 core surgical trainees with no prior mastoidectomy experience performed a cortical mastoidectomy in both VR and CD settings. Participants were randomized to either VR-first or CD-first training sequences. Cognitive load was measured using a bespoke auditory reaction-time device at baseline and 10, 30, and 50 min. Relative reaction time (RRT) served as an objective index of cognitive load. Cadaveric performance was assessed using the Modified Welling Scale by two blinded otologists. RESULTS: Cognitive load was significantly lower during VR than CD, with mean RRT rising 26% from baseline in VR versus 60% in CD (p < 0.001). Training order did not affect cognitive load in either modality, and RRT increased progressively throughout mastoidectomy in both VR and CD. Participants who began with VR achieved significantly higher cadaveric performance scores than those who began with CD (mean 9.50 vs. 4.96; p < 0.001), and inter-rater reliability for performance scoring was high. CONCLUSION: VR mastoidectomy reduces cognitive load and enhances subsequent cadaveric performance in novice trainees, supporting its role as a cognitively optimized precadaver training modality that complements, rather than replaces, cadaveric dissection. These findings suggest VR enhances early learning efficiency and resource utilization in novice otolaryngology training. LEVEL OF EVIDENCE: N/A.

Humans↗

PubMed2026

Transcriptomic insights into thermal stress reveal physiological trade-off between thermal stress adaptation and reproductive investment in Spodoptera litura.

Spodoptera litura, a highly polyphagous lepidopteran pest, poses a major threat to agricultural productivity due to its remarkable adaptability to diverse environmental conditions. Although heat stress is known to trigger transcriptional reprogramming in insects, the molecular mechanisms underlying thermal stress responses in S. litura remain poorly understood. In the present study, fourth-instar larvae were exposed to acute heat stress (44 °C) and compared with control conditions (27 ± 1 °C) to investigate heat-induced transcriptional alterations affecting physiology and reproduction. High-quality RNA-Seq data achieved more than 80% mapping efficiency, with a total of 15,782 transcripts were identified. Transcriptome analysis of S. litura larvae showed 323 differentially expressed genes (DEGs), of which 262 genes were significantly upregulated and 61 were downregulated in heat-stressed larvae compared to the control group. The DEGs were associated with stress response, reproduction, signalling, proteostasis, detoxification, oxidative stress, metabolism, development, and chromatin regulation. Heat shock proteins genes, including HSP70, HSP90, and HSP27, together with co-chaperones such as TRET-1, STIP1, and Starvin, were strongly upregulated, indicating enhanced cellular protection against protein damage and oxidative stress under heat stress. Conversely, key reproductive and cell cycle-related genes, including BARR, CAPD2, FEO, CDK2 and MORULA, were significantly downregulated, suggesting reproductive impairment and developmental arrest. RT-qPCR validation corroborated the RNA-Seq findings, demonstrating a heat-induced physiological trade-off that prioritizes survival over reproduction. Consistent with these molecular responses, heat-stressed insects exhibited marked reproductive impairment, including significant reductions in gonadosomatic index, eupyrene sperm bundle count, mating frequency, mating success, female calling behaviour, copulation duration, fecundity, and egg fertility. Collectively, these findings provide comprehensive insights into the molecular basis of thermal adaptation in S. litura and demonstrate that acute heat stress compromises reproductive fitness while activating conserved stress-response pathways that promote short-term survival.

Animals↗

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

Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.

BACKGROUND: Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation. METHODS: We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking. RESULTS: In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing. CONCLUSIONS: Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.

Animals↗

PubMed2026

Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in HARS1-Related Autosomal Recessive Disorder Associated With Usher-Like Symptoms.

Autosomal recessive HARS1-related disorder (originally described as Usher syndrome type 3B) caused by a homozygous Y454S variant in the histidyl-tRNA synthetase gene (HARS1) is characterized by progressive sensorineural hearing and vision loss and respiratory deterioration with risk for sudden death following febrile illnesses. In-vitro studies have previously shown that histidine can rescue a humanized yeast model for pathogenic HARS alleles. Fourteen children homozygous for HARS Y454S were treated with supplemental oral histidine (50 mg/kg BID) and monitored with bloodwork and physical, visual, and audiometry assessments during a 3-year clinical trial, then followed for more than 4 years on histidine in the post-trial period. Patient fibroblasts were assessed for response to histidine. Hearing and vision remained stable, and growth improved significantly. Children remained healthy, with no severe deteriorations despite exposure to bacterial and viral infections, including COVID-19. Gains in growth were maintained in the post-trial period on varying levels of histidine supplementation. Daily oral histidine supplementation in children with autosomal recessive HARS1-related disorder can ameliorate or slow the progression of disease and is safe, inexpensive, and well tolerated. This study adds to the growing list of autosomal recessive ARSopathies (aminoacyl-tRNA synthetase disorders) that are amenable to amino acid supplementation.

Humans↗

PubMed2026

Extender-dependent effects of reduced glutathione on post-thaw boar sperm quality: A systematic review and meta-analysis.

Supplementation of reduced glutathione (GSH) in freezing media has been proposed to improve post-thaw boar sperm quality, although reported findings remain inconsistent. This study aimed to quantitatively evaluate the effects of reduced glutathione on post-thaw sperm quality through a systematic review and meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Scopus, PubMed, CAB Direct, EBSCOhost, and Google Scholar were systematically searched. Based on predefined inclusion and exclusion criteria, 15 in vitro studies comprising 19 experiments were included. Four outcomes were analyzed: total motility, progressive motility, viability, and acrosome integrity. Standardized mean differences (SMD) were calculated using random-effects models. Heterogeneity was assessed using Cochran's Q test, and the I2 statistic. Publication bias was evaluated using funnel plots, Egger's test, and trim-and-fill analysis, while sensitivity analyses were performed using Baujat plots and leave-one-out analysis. Reduced glutathione was positively associated with total motility (SMD = 0.74; 95% CI: 0.42-1.05; P<0.001), progressive motility (SMD = 0.90; 95% CI: 0.21-1.58; P=0.014), viability (SMD = 0.67; 95% CI: 0.11-1.23; P=0.022), and acrosome integrity (SMD = 0.72; 95% CI: 0.32-1.12; P=0.002). Low to high heterogeneity was observed across outcomes, indicating variability in the estimated effects across studies. Significant subgroup differences were identified according to GSH concentration, freezing media, and thawing media. Overall, the available evidence suggests a possible positive association between GSH supplementation and several post-thaw sperm quality parameters, although these subgroup findings are exploratory and require confirmation in well-standardized experimental studies.

Animals↗

PubMed2026

Toward real-time quantification of driving risks: a systematic review and research agenda of risk field theory.

In complex traffic systems, driving risk often evolves in a continuous and progressive manner prior to crash occurrence. How to effectively represent and analyze such latent risk states remains a central challenge in traffic safety research. In recent years, risk field-based approaches have introduced spatial and spatiotemporal continuous modeling paradigms, providing new perspectives for characterizing the distribution of traffic risk and its dynamic evolution. Motivated by the rapid growth of this research area and the lack of a systematic synthesis, this paper presents a comprehensive review of studies applying risk field theory to driving safety and traffic risk analysis. Following the PRISMA guidelines, relevant literature was collected through multi-database searches and analyzed using a combination of bibliometric analysis and qualitative review. The review systematically summarizes the theoretical foundations, modeling elements, data sources, analytical methods, and application domains of risk field-related research. Particular attention is given to studies that conceptualize traffic risk as a continuous field, complemented by a broader review of traffic risk factor literature to identify key elements and analytical dimensions involved in risk field modeling. On this basis, the paper synthesizes research progress in major application areas, including traffic safety state representation, driving behavior analysis, traffic conflict assessment, and autonomous driving and human-machine cooperative systems. Differences and commonalities among existing studies are compared in terms of modeling strategies, data support, and application scenarios. Through this systematic review, the paper clarifies the main research themes and methodological trends of risk field-based studies, providing a structured framework for understanding the evolution and application of this approach and offering methodological insights for risk perception modeling and safety-oriented decision support in intelligent transportation systems (ITS).

Humans↗

PubMed2025

Quantitative Outcomes for Shared Assessment and Management in Forensic Mental Health: A Meta-Analysis and Systematic Review.

Despite leading models of mental health care encouraging user involvement, users in forensic mental health (FMH) report poor involvement given the difficulty in reconciling shared approaches with risk-averse and legally mandated settings. While previous research has demonstrated qualitative benefits to shared approaches in FMH and has led to a proliferation of self-rated assessment tools, there remains to quantify agreement on self-rated tools and to clarify the impact of shared approaches on care. This meta-analysis examines (1) the correlation between clinician and user ratings, (2) the predictive validity of self-ratings for violence, and (3) the effects of shared risk management on violence and restriction in FMH. Five databases were searched from inception to April 2024, selecting for adult FMH inpatients, shared risk assessment, needs assessment or violence management as interventions, and quantitative outcomes (correlation, agreement, predictive validity, and effect on violence or restriction rates). Fifteen quantitative evaluations were retained. One of three planned meta-analyses could be conducted, with seven records providing paired clinician-user t-tests. Eleven more records provided clinical recommendations on operationalizing shared approaches. Random-effects meta-analysis showed a significant and large paired standard difference of .95 (95% CI = [.49,1.42]) across tools, with significant differences in DUNDRUM-3, DUNDRUM-4, and CANFOR sub-models. While acknowledging between-study heterogeneity, results substantiate quantitative differences where clinicians generally rate more needs and lesser progress than users across tools, showing that self-ratings can and should be used to broach collaborative discussions on needs and progress during FMH treatment. There remains an evidence gap for quantitative benefits in care outcomes and a need to standardize agreement measures for future comparisons and clinical sub-group analyses.

Humans↗

PubMed2026

Spore-forming Clostridia as overlooked determinants of microbial risk in wastewater reuse systems.

Using treated municipal wastewater for crop irrigation is a key strategy to combat drought-induced water scarcity. However, current wastewater reclamation standards systematically underestimate risks from spore-forming pathogens. As highlighted in a recent minireview by A. Mrozinski, C. Le Maréchal, and E. Topp in Applied and Environmental Microbiology (92:e00173-26, 2026, https://doi.org/10.1128/aem.00173-26), Clostridioides difficile and Clostridium perfringens survive conventional disinfection, persist indefinitely in agricultural soils, and harbor critical antibiotic resistance genes. To safeguard the food supply and protect public health, regulatory frameworks must shift from relying solely on standard vegetative bacterial indicators and include monitoring resilient, spore-forming pathogens.

Clostridium↗

PubMed2026

Molecular mechanisms of natural de novo shoot organogenesis and their applications.

Natural de novo shoot organogenesis (DNSO) is the spontaneous regeneration of shoots from wound sites outside the shoot apical region through endogenous developmental programs. This regenerative capacity enables plants to recover from severe tissue damage by re-establishing the shoot-root axis. Here, we review current knowledge about the molecular mechanisms of natural DNSO, focusing on transcriptomic and physiological studies in model plants. Accumulating evidence suggests that natural DNSO proceeds through three sequential phases: (i) early wound responses, characterized by the activation of the WIND1-ESR1 module and the establishment of apical-basal auxin asymmetry; (ii) cellular proliferation driven by metabolic and cell-cycle reprogramming; and (iii) cytokinin-mediated establishment of shoot apical meristem identity. We also discuss how these mechanistic insights have been harnessed for practical applications, including tissue culture-free transformation systems such as the cut-dip-budding (CDB) method, and developmental reprogramming strategies that employ ectopic expression of developmental regulator (DR) genes to induce DNSO in otherwise recalcitrant species. Together, these advances illustrate how understanding natural regeneration can guide the development of simplified, broadly applicable plant transformation technologies.

Plant Shoots↗

PubMed2026

Beyond predictive performance: A systematic review and critical methodological appraisal of AI/ML and conventional modelling strategies in breast, colorectal, and pancreatic Cancer.

BACKGROUND: Predictive modelling for cancer risk, treatment-related complications, and survival is central to precision oncology. Conventional logistic regression (LR) and Cox proportional hazards (CoxPH) regression remain widely used but are limited when modelling nonlinear interactions, high-dimensional imaging features, and multimodal clinical-metabolic predictors. Artificial intelligence (AI) and machine learning (ML) methods offer expanded capability through automated feature extraction, ensemble learning, and flexible survival modelling, but the evidence on when AI/ML adds value over conventional models across cancer sites and predictive tasks remains fragmented. OBJECTIVE: To systematically evaluate the methodological performance, validation strategies, and translational limitations of AI/ML models compared with conventional statistical models in published predictive-modelling studies for breast, colorectal, or pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for studies published between January 2019 and March 2025. Two reviewers independently conducted title-and-abstract screening, full-text eligibility assessment, and PROBAST risk-of-bias assessment. Sixty-five studies (n = 907,567 participants) were narratively synthesised by cancer site, predictive task, model family, comparator, validation strategy, predictor modality, and calibration or explainability reporting. RESULTS: The 65 studies comprised breast cancer (n = 35), colorectal cancer (n = 21), and pancreatic cancer (n = 9). AI/ML superiority over LR and CoxPH was task- and data-dependent. CNN- and U-Net-based models predominated in imaging and body-composition tasks, tree-based ensembles consistently outperformed LR for tabular perioperative complication prediction, and CoxPH remained competitive, and in the largest pancreatic risk study, superior to XGBoost (C-index 0.802 vs 0.723) in well-structured datasets. PROBAST analysis-domain risk was moderate in 54 of 65 studies (83%), driven by limited external validation, sparse calibration reporting (11/65), and few decision-curve analyses (7/65). CONCLUSION: AI/ML adds the most methodological value in imaging-derived feature extraction and nonlinear perioperative prediction, while conventional regression remains preferable in large, structured datasets with linear predictors. Clinical translation requires standardised body-composition definitions, external validation, calibration assessment, decision-curve analysis, and explainability, in line with TRIPOD+AI and CLAIM standards.

Humans↗

PubMed2026

Evolution of Precision Oncology, Personalized Medicine, and Molecular Tumor Boards.

With multiple molecular targeted therapies available for patients with cancer that correspond to a specific genetic alteration, the selection of the best treatment is essential to ensure therapeutic efficacy. Molecular tumor boards (MTBs) play a key role in this process to deliver personalized medicine to patients with cancer in a multidisciplinary manner. Historically, personalized medicine has been offered to patients with advanced cancer, but the incorporation of molecular targeted therapies and immunotherapy into the perioperative setting requires clinicians to understand the role of the MTB. Evidence is accumulating to support feasibility and survival benefit in patients treated with matched therapy.

Humans↗

PubMed2026

A narrative review of what cohorts have taught us and how they have laid the foundation for much of our understanding of type 2 diabetes.

This narrative review provides a historical perspective on how observational research on type 2 diabetes has been developed and consolidated over the last 50 years and how well-designed cohort studies will provide us with knowledge for research and practice in the future and aid guideline development. We have included data from a large number of cohorts from every continent that have been used to study the development and/or progression of type 2 diabetes, including cohorts that are general population-based, disease-based, intervention-based and registry-based. We have structured the results from the past 50 years based on the following themes: diagnosis and screening, complications, risk factors and pathophysiology. We also discuss the strengths and weaknesses of observational research when compared with other research designs. Finally, we discuss the emerging and future directions for type 2 diabetes research using cohorts, which include novel developments, such as artificial intelligence, precision health and the exposome. We conclude that cohort research has significantly advanced our understanding of type 2 diabetes and aided guideline development, and complements experimental work, such as human randomised controlled trials and animal studies. Both approaches are essential and complementary in our pursuit to provide a more comprehensive understanding of the development and progression of type 2 diabetes, and to change dogma, practice and policies for better outcomes.

Humans↗

PubMed2026

Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.

INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.

Humans↗