Inter-individual variability in drug efficacy and toxicity remains a major obstacle to precision therapeutics. Candidate-gene pharmacogenomics and star-allele-based guidelines have established clinically useful examples, but they cannot capture the full spectrum of mechanisms that shape drug response. Pharmacogenomic genome-wide association studies (pharmacoGWAS) extend this framework by enabling discovery beyond known pharmacogenes and can identify human genetic variants associated with efficacy, adverse drug reactions, dose requirements, pharmacokinetics, and pharmacodynamics. This mini-review aims to summarize practical principles for human pharmacoGWAS, with emphasis on study design, phenotype and exposure definition, reproducible bioinformatics pipelines, gene-expression-based functional interpretation, and clinical translation. This review discusses randomized trials, prospective cohorts, biobanks, electronic health records, claims databases, and rare adverse-event designs, highlighting the specific biases that arise because drug response is defined among exposed individuals. It then outlines core analytical steps, including genotype quality control, imputation, ancestry-aware association testing, mixed models, survival and longitudinal analyses, rare-variant aggregation, replication, and meta-analysis. Particular attention is given to expression quantitative trait loci, splicing quantitative trait loci, and protein quantitative trait loci, tissue prioritization informed by the Genotype-Tissue Expression project, transcriptome-wide association studies, and colocalization as tools for prioritizing candidate genes and plausible mechanisms. Finally, we propose a translation framework connecting discovery to clinical validity, guideline development, electronic health record decision support, and equitable implementation across diverse populations. When combined with rigorous epidemiology and functional genomics, pharmacoGWAS may help translate genome-wide signals into safer and more effective prescribing.

Ferroptosis, an iron-dependent form of regulated cell death, serves as an important mechanism associated with cancer progression. Natural compounds, particularly alkaloids, have emerged as attractive candidates for regulating ferroptotic cell death, thereby providing a promising anticancer strategy. However, the molecular mechanisms underlying their antitumor effects remain poorly understood. In this study, we aimed to investigate the antitumor effects and underlying mechanisms of natural alkaloids against HCC.

An alkaloid library was used to screen alkaloids with anti-hepatocellular carcinoma (HCC) activity. A combination of proteomic profiling, in vitro functional assays, and in vivo animal experiments was performed to explore the biological roles and molecular mechanisms of the lead compound.

Through high-throughput screening of an alkaloid library, we identified palmatine (PAL), an active component isolated from Fibraurea recisa Pierre, as a potential ferroptosis sensitizer in HCC cells. PAL treatment triggered typical ferroptotic features in HCC cells, including elevated ferrous iron, reactive oxygen species, and lipid peroxidation, along with decreased glutathione levels. Importantly, the pro-ferroptotic effect of PAL was significantly abolished by two ferroptosis inhibitors, ferrostatin-1 and deferoxamine. Mechanistically, PAL directly interacted with troponin T1 (TNNT1) to trigger its K48-linked polyubiquitination and subsequent protein degradation. Ectopic TNNT1 overexpression significantly rescued PAL-mediated ferroptosis and abrogated its tumor-suppressive effects. In vivo animal models further confirmed that PAL suppressed tumor growth by downregulating TNNT1, with a favorable safety profile.

Therefore, this study reveals a previously unrecognized role of PAL as a ferroptosis sensitizer and highlights its translational potential for anti-HCC therapy.

Anti-anxiety medications may cause adverse effects and can be associated with long-term health risks. Rooibos tea (Aspalathus linearis) contains polyphenolic compounds that may confer health benefits. This study aims to investigate the effects of green rooibos extract supplementation on anxiety levels in adults with mild-to-moderate anxiety.

This double-blind, placebo-controlled, randomized controlled trial will enroll 60 adults aged 18-65 years with mild-to-moderate anxiety. Participants will receive either green rooibos extract (19.25 mg aspalathin per capsule; n = 30) or placebo (n = 30). They will take one capsule each morning during the first week and two capsules each morning during the subsequent 7 weeks. The anxiety subscale of the 21-item Depression, Anxiety and Stress Scale will be the primary outcome and will be assessed from baseline to post-intervention. Secondary outcomes will include salivary biomarkers, heart rate variability, sleep quality, and dietary intake. Measurements will be collected at baseline, mid-intervention, and post-intervention.

The findings may help determine whether green rooibos extract supplementation is associated with reduced anxiety and improvements in related health markers in adults with mild-to-moderate anxiety.

Bilateral above-knee amputation stump ulcers with poor arterial inflow, multidrug-resistant infection, and bone involvement are rare and difficult to manage. We report a 52-year-old man who developed nonhealing bilateral stump ulcers more than one month after emergency bilateral amputation for extensive aortoiliac and lower-extremity arterial thrombosis. On admission on January 6, 2026, the right stump wound measured approximately 16.0 × 13.0 cm, with exposed femoral bone, purulent medullary drainage, and necrotic tissue; the left measured 18.0 × 12.0 cm, with slough and persistent exudation. Wound culture yielded carbapenem-resistant Klebsiella pneumoniae, and right femoral bone pathology supported chronic necrotizing osteomyelitis. Because immediate revascularization was not feasible, we used a staged debridement strategy—repeated selective debridement preserving viable tissue, with negative pressure wound therapy (NPWT) as a bridge between operations—combined with delayed stump repair, culture-guided antimicrobial therapy, anticoagulation, analgesia, vascular protection, and nutritional support. NPWT was applied in seven cycles over approximately 54 days. The wounds achieved complete closure by discharge on March 16, 2026. At follow-up on March 30, 2026, there was no exudation, sinus tract, recurrent dehiscence, exposed bone, recurrent infection, or significant stump pain, although prosthetic fitting was not yet possible. This case suggests that NPWT combined with serial staged debridement may offer short-term salvage for selected complex infected amputation stumps when arterial inflow is poor and one-stage closure is unsafe; however, durability and generalizability remain uncertain.

Eosinophilic esophagitis (EoE) is characterized by esophageal dysfunction and ≥15 eosinophils/high-power field on biopsy. The specific clinicopathologic characteristics and therapeutic outcomes of patients with concurrent gastric Helicobacter pylori infection and EoE remain poorly defined. This observational cohort study reexamines this relationship and evaluates the clinicopathologic features and outcomes of patients with concurrent diseases.

We retrospectively reviewed esophageal and gastric biopsies obtained between January 1, 2022, and December 30, 2025. Patients with a first-time diagnosis of EoE and concurrent treatment-naive gastric H. pylori infection were identified and confirmed by morphology and immunohistochemistry. Patients with a history of prior H. pylori eradication therapy or eosinophilic gastrointestinal disease were excluded. Clinical, pathologic, and follow-up data were analyzed.

Among 5,443 patients undergoing concurrent esophageal and gastric biopsy evaluation, 197 (3.6%, 95% confidence interval [CI], 3.1–4.1%) met the diagnostic criteria for EoE, and 286 (5.3%, 95% CI, 4.7–5.9%) had gastric H. pylori infection. Twenty-eight patients with concurrent EoE and gastric H. pylori infection were initially identified, corresponding to an H. pylori prevalence of 14.2% (28/197) among patients with EoE. A significant association was identified between EoE and H. pylori infection (odds ratio, 3.20; 95% CI, 2.11–4.87; Fisher’s exact test, P < 0.001). After exclusion of 1 patient with eosinophilic gastrointestinal disease and 3 patients with prior H. pylori treatment, 24 patients met the study inclusion criteria for the subsequent clinicopathologic analysis. Among these 24 patients (M:F = 7:1; mean age, 29.5 years; range, 8–82 years), 8 (33%) were children. The most common presentations (n = 18, 75%) were abdominal pain in children and dysphagia in adults. Atopy was present in 7 (29%) patients. Histologically, 5 (21%) cases exhibited classic features, while 19 (79%) showed nonclassic features with lower eosinophil density and a more uniform distribution of eosinophils within the epithelium. Among 10 patients with follow-up, 3/10 (30%) achieved resolution of both H. pylori infection and EoE after H. pylori eradication therapy with or without steroids; 5/10 (50%) had persistent H. pylori infection and persistent or recurrent EoE; 2(20%) achieved H. pylori-negative status but had persistent EoE; and fungal infection developed in 2 of 4 patients (50%) treated with steroids.

H. pylori infection may be associated with a nonclassic pattern of EoE. Recognition of this pattern may have implications for diagnosis and management.

The selectivity of chemotherapy remains limited by systemic toxicity. pH-sensitive polymeric nanocarriers exploit the acidic extracellular environment of solid tumors as a drug-release trigger, but they respond passively to a pre-existing pH gradient that is modest and heterogeneous. We hypothesize that controlled glucose priming, temporally coordinated with nanocarrier administration, may transiently widen the tumor-to-normal extracellular pH differential sufficiently to trigger release from a sharply tuned ultra-pH-sensitive (UPS) carrier in responsive tumor regions. Historical animal studies and limited human observations report tumor-associated extracellular pH decreases of approximately 0.17–0.20 units under selected conditions, while UPS micelles can dissociate cooperatively across a window narrower than 0.25 units and have tunable transition pH thresholds (pHt). The carrier would be tuned below the baseline extracellular pH (pHe) of the target tumor (with a pHt of approximately 6.5–6.6), remaining assembled where local pHe remains above pHt until a priming-induced pH excursion crosses the threshold. The central uncertainty is the accompanying effect on tumor perfusion and carrier delivery: tumor blood flow was unchanged at 1 g/kg in one animal study and reduced by 31% at 4 g/kg, while perfusion at 2 g/kg and the net effect across the proposed 1–2 g/kg testing range remain insufficiently characterized. Human evidence is limited and heterogeneous. Recent intracellular pH imaging associated glucose-induced pH changes with the lactate-to-pyruvate ratio but not with fluorodeoxyglucose standardized uptake value; fluorodeoxyglucose positron emission tomography avidity is therefore retained only as an exploratory candidate biomarker. A previous pH-low insertion peptide (pHLIP)-modified liposomal study supports the general principle of glucose-enhanced pH-responsive delivery but uses a mechanistically distinct carrier. The present work formulates a class-level, falsifiable framework for conformational UPS polymers. The essential next step is simultaneous measurement of tumor extracellular pH, perfusion, nanocarrier accumulation, and cargo release across glucose doses and administration sequences in tumor-bearing animals. Until those variables are measured together, the strategy should be regarded as a falsifiable preclinical proposal rather than a clinically feasible protocol.

Biliary atresia (BA) is the leading cause of pediatric obstructive cholestasis and a major indication for liver transplantation in infants. Organoid models are increasingly used to investigate BA pathogenesis and therapeutic responses, but incomplete methodological and clinical reporting may limit cross-study comparison and translational interpretation. This study aimed to map the landscape of BA-related organoid research, identify major reporting gaps, and propose Biliary Atresia Minimum Reporting Standard (BA-MRS) as a preliminary framework for improving reporting completeness.

PubMed, Scopus, and Web of Science Core Collection were searched on March 8, 2026, in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) and the 2024 Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. Reporting completeness was assessed using a 36-item BA-MRS across six domains, scored as fully reported, partially reported, not reported, or not applicable.

Twenty-six studies published between 2020 and 2026 were included. Fibrosis and epithelial–mesenchymal transition were the most frequently studied themes, whereas only one study linked organoid findings to post-Kasai outcomes. BA case/model definition, ethics approval, and differentiation protocols were fully reported in all applicable studies (100%). In contrast, contamination monitoring (3.8%), core biliary function assays (34.6%), and clinical outcome linkage (26.3%) were poorly reported. Culture System and Sample Acquisition showed the lowest domain-level fully reported rates (58.1% and 63.2%, respectively).

BA organoid research has progressed beyond early model development, but reporting remains insufficient for robust comparison, reproducibility, and clinically meaningful interpretation. BA-MRS may serve as a preliminary framework for improving standardized reporting in future studies.

Celiac disease remains underdiagnosed despite an established diagnostic pathway, reflecting phenotypic heterogeneity, delayed recognition, and dependence on resource-intensive testing. This narrative review synthesizes evidence on artificial intelligence and phenomics in celiac disease (CD) across four operational layers: electronic health record phenotyping, Human Phenotype Ontology-based semantic encoding, machine-learning pre-screening from routine clinical data, and deep-learning-assisted histopathology. A targeted literature search of PubMed/MEDLINE, Embase, and Google Scholar covered publications from January 2010 through December 2025, using combinations of CD/coeliac disease with artificial intelligence, machine learning, deep learning, phenomics, Human Phenotype Ontology, computable phenotype, electronic health records, and natural language processing, supplemented by targeted searches and citation chaining. We present a curated minimum viable CD phenome and discuss clinical actionability, age-specific considerations, and current pediatric validation gaps. Selected models have demonstrated promising CD detection or pre-screening performance in specific datasets, but prospective, multicenter evidence with external validation remains insufficient to establish clinical utility. Artificial intelligence should augment expert clinical care rather than replace it.