PubMed Trending Research Digest — August 29, 2026

Automated digest · 92 articles · 15 research areas · August 29, 2026

Overview

Across this week’s set of studies, a dominant theme is mechanism-to-clinic translation: from targeted molecular pathways (e.g., cGAS–STING activation by obesity-derived extracellular vesicles in osteoarthritis; TREM2 shedding linked to TRL metabolism; DIXDC1–DLAT control of cuproptosis sensitivity; miR-4485-3p/RPRD1B synthetic lethality in BRCA1-deficient cancer) to clinical trials and risk models that aim to improve outcomes through more precise patient selection and longer-term follow-up. Several cardiovascular papers similarly emphasize durable, clinically meaningful endpoints—such as extended event analyses in transthyretin amyloid cardiomyopathy and new evidence for cardiac myosin inhibition in nonobstructive hypertrophic cardiomyopathy—while diabetes/kidney studies refine when and how SGLT2 inhibitors should be used and uncover additional cardioprotective mechanisms (PANK1/CoA synthesis).

A second major thread is “personalization” beyond single biomarkers: dynamic risk stratification (MRD-informed CLL indices; time-updated prognostic modeling in MDS; lesion-level WMH subtyping in brain aging), and tailored management strategies (response-tailored antibiotics for infective endocarditis; individualized diet macronutrient composition effects on hepatic insulin sensitivity; prehabilitation standardization efforts). In parallel, multiple reviews and consensus/guideline-type contributions address implementation gaps—spanning stroke rehabilitation updates, long-term surveillance after gene therapy, and diagnostic algorithms for invasive pulmonary fungal disease in high-burden settings.

Finally, the digest highlights a broad movement toward safer or more targeted interventions: nonpharmacologic approaches (CBT-I/bright light during chemotherapy; pain neuroscience education plus stabilization for low back pain; VR-based digital defocus training for myopia), next-generation therapeutics (KLHL12-recruiting PROTACs, nonviral sup-tRNA delivery for nonsense CF, and CAR-T/CAR-Treg concepts in IBD), and careful attention to adverse effects and misuse (delayed Parkinsonism-like neurotoxicity after CAR T, and medically inappropriate GLP-1 use). Together, these articles reflect a field increasingly focused on coupling biological specificity with practical, real-world decision tools.

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Pediatric obesity, insulin resistance, and metabolic inflammation

Effects of Omega-3 and Omega-9 Fatty Acid Supplementation on HOMA-IR and Inflammatory Markers in Children with Obesity and Insulin Resistance: A Triple-Blind RCT with Post-Intervention Follow-Up.

This triple-blind, multicenter randomized controlled trial studied omega-3 and omega-9 fatty acid supplementation (independent and combined arms) in 97 children aged 8–17 years with overweight/obesity and baseline insulin resistance, assessing metabolic outcomes including HOMA-IR and inflammatory markers during active treatment and after discontinuation. The study found that omega-3 and/or omega-9 supplementation improved insulin resistance and inflammatory profiles, with effects persisting into the post-intervention follow-up period (as reported in the prespecified secondary analysis). These findings support omega-3/omega-9 dietary supplementation as a potentially durable adjunct strategy to improve metabolic and inflammatory risk in pediatric obesity-associated insulin resistance.

Campos-González JA, Vasquez-Solorio DF, Flores-Huerta S et al. · Nutrients · (2026) · View on PubMed ↗ · Free PDF ↗

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Nutritional supplements, micronutrients, and diet effects on health

Beyond wrinkles.

This Science commentary discusses whether the skin microbiome could influence healthy aging, framing the question of how microbial communities might affect age-related biology. The key point is that emerging evidence suggests microbiome composition and function may modulate aging-related processes, but causal mechanisms and clinical relevance remain to be established. The significance is that it highlights a potentially actionable aging lever while emphasizing the need for rigorous mechanistic and interventional studies.

Jalili S, Oh J · Science (New York, N.Y.) · (2026) · View on PubMed ↗

An in vivo resource of age-regulated C. elegans intestinal secretory-pathway proteins highlights secreted enzymes associated with lifespan regulation.

The study used proximity labeling followed by quantitative proteomics to map age-regulated proteins along the C. elegans intestinal secretory pathway, focusing on intestine-secreted factors such as ACP7. It identified intestine-secreted proteins whose secretion changes with age and showed that overexpressing the conserved secreted enzyme ACP7 extends lifespan in a secretion-dependent manner. These findings establish an in vivo secretory-pathway resource linking extracellular intestinal enzymes to lifespan regulation and suggest ACP7 as a candidate target for aging interventions.

Miklas JW, Papsdorf K, Sun ED et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

The Potential of Cannabidiol for the Treatment of Psychosis: Endocannabinoid Regulation of Serotonergic Neurotransmission via Serotonin 5-HT1A/2A Receptors.

This review assessed cannabidiol (CBD) as a potential treatment for psychosis by focusing on endocannabinoid regulation of serotonergic neurotransmission through serotonin 5-HT1A/2A receptors, contrasting CBD with Δ9-tetrahydrocannabinol (Δ9-THC). It argues that receptor-level mechanisms underlying CBD’s effects may contribute to therapeutic benefits with lower addiction liability than Δ9-THC. The significance is translational: it supports mechanistically informed, safer CBD-containing approaches for schizophrenia-spectrum conditions.

Yonemura K, Kitanaka N, Tomita K et al. · Neurochemical research · (2026) · View on PubMed ↗

Inappropriate use of GLP-1-based antiobesity medications: beyond appropriate drug use toward appropriate weight reduction.

This article studied medically inappropriate use of GLP-1-based antiobesity medications, focusing on how misuse extends beyond regulatory issues like off-label prescribing and illegal acquisition. It highlights that serious harms reported with inappropriate tirzepatide use may stem not only from drug effects but also from inappropriate dietary restriction and related behaviors. The significance is a shift toward promoting appropriate weight reduction strategies and safer clinical use of GLP-1 receptor agonists and GLP-1/GIP dual agonists.

Ogawa W, Nishikage S, Nomura K et al. · Diabetology international · (2026) · View on PubMed ↗ · Free PDF ↗

GLP-1 and GLP-1/GIP receptor agonist medication use and self-reported outcomes in individuals with lipedema: Results from a large online survey.

This cross-sectional online survey studied self-reported outcomes and medication use patterns of GLP-1 receptor agonists and GLP-1/GIP receptor agonists in individuals with lipedema, a condition primarily affecting women. The study assessed associations between reported symptom severity and prior use of these agents, providing real-world patient-reported data on potential benefits and outcomes. The findings are significant for informing evidence gaps in lipedema pharmacotherapy and guiding future controlled studies of GLP-1-based treatments.

Srinivasan A, Kartt J, Daftuar F et al. · Obesity pillars · (2026) · View on PubMed ↗ · Free PDF ↗

Is There a Better Day of the Week to Administer Semaglutide or Tirzepatide? A Systematic Literature Review.

This systematic literature review studied whether the day of the week affects clinical outcomes, adherence, and tolerability of once-weekly GLP-1 receptor agonists semaglutide and tirzepatide in type 2 diabetes mellitus and obesity. The abstract describes the rationale and methods but truncates before reporting the review’s conclusions. If evidence is limited or absent, the finding would be significant for clinicians by suggesting that dosing day may not be a meaningful personalization lever for these incretin therapies.

La Vignera S, Condorelli RA · Medicina (Kaunas, Lithuania) · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond Bone Health: Exploring the “Heart-Brain-Bone” Axis Modulated by Lipid-Soluble Nutrients (Omega-3, Vitamin D3, and Vitamin K2).

This narrative review explored the proposed “heart–brain–bone” axis and how lipid-soluble nutrients—omega-3, vitamin D3, and vitamin K2—might modulate shared regulators of calcium handling, inflammation resolution, vascular integrity, and inflammaging. It synthesizes mechanistic and evidence-based links across cardiovascular, neurocognitive, and bone health domains rather than presenting new experimental results. The significance lies in framing integrative, nutrient-focused hypotheses that could guide future trials testing whether these nutrients can beneficially modulate interconnected cardiometabolic and neuro-skeletal outcomes.

Fang SC, Huang MK, Shen HE et al. · Nutrients · (2026) · View on PubMed ↗ · Free PDF ↗

Coffee and Physical Performance: What Is Driven by Caffeine and What Is Not.

This narrative review examined how coffee consumption affects physical performance in athletes and physically active individuals, focusing on what is driven by caffeine versus other coffee components. It discusses variability in responses based on factors such as circadian rhythm, habitual intake, and genetic variability, and reviews effects on fatigue, muscle pain, recovery, and performance. The significance is practical for sports nutrition by clarifying which performance benefits are likely caffeine-mediated and which depend on individual and training-related modifiers.

Grzelczyk J, Ziętala J, Budryn G et al. · Nutrients · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond Weight Loss: Skeletal Muscle Health During Incretin-Based Therapy in Patients with Diabesity.

This narrative review synthesized evidence on skeletal muscle health during incretin-based therapy in patients with diabesity, focusing on semaglutide and tirzepatide (GLP-1 RA and GIP/GLP-1 RA classes). It addresses concerns that, despite metabolic benefits, incretin therapies may affect muscle mass and function—especially in older adults at risk for sarcopenia and functional decline. The significance is that it frames how incretin-based weight-loss regimens might need monitoring or adjunct strategies to preserve skeletal muscle outcomes.

Mollero ELM, Dozzani I, Biamonte E et al. · Nutrients · (2026) · View on PubMed ↗ · Free PDF ↗

Anti-Androgenic Potential of Plant Extracts: Molecular Mechanisms, Synergistic Effects, and Nutritional Interventions.

This 2026 review evaluated the anti-androgenic potential of plant extracts (including dietary polyphenols, alkaloids, and flavonoids) by synthesizing molecular mechanisms and evidence for synergistic effects with nutritional interventions across androgen-dependent and androgen-independent signaling relevant to prostate and other androgen-related disorders. It concludes that multi-target plant-derived compounds can modulate androgen signaling pathways and may overcome limitations of conventional antiandrogen drugs such as resistance and off-target toxicity. Scientifically, the review highlights plant extracts as promising candidates for safer, combination-based anti-androgen strategies, while emphasizing the need for rigorous mechanistic and clinical validation.

Yang Y, Pang Y, Zhang J et al. · Molecules (Basel, Switzerland) · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular therapeutics (heart failure, cardiomyopathy, valvular disease)

LDL Cholesterol Lowering With Evolocumab Before Percutaneous Coronary Intervention for Acute Myocardial Infarction: The AMUNDSEN Randomized Clinical Trial.

This phase 4 randomized clinical trial studied whether in-catheterization laboratory initiation of the PCSK9 inhibitor evolocumab (before mechanical reperfusion) improves LDL-C control and 1-year outcomes in high-risk acute myocardial infarction patients undergoing percutaneous coronary intervention (PCI). Evolocumab given as first-line therapy before PCI was evaluated against standard care to determine whether earlier LDL-C lowering reduces prolonged periods of inadequate LDL-C control and improves clinical endpoints. If effective, this strategy would support earlier, procedure-timed PCSK9 inhibition as a practical escalation of lipid-lowering in acute MI patients undergoing PCI.

Montalescot G, Ferrari E, Souteyrand G et al. · JAMA · (2026) · View on PubMed ↗

Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy.

This phase 3 multinational double-blind trial evaluated aficamten, a cardiac myosin inhibitor, versus placebo in adults with symptomatic nonobstructive hypertrophic cardiomyopathy (HCM) over up to 72 weeks. Aficamten improved the dual primary endpoints—change in peak oxygen uptake and change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at week 36—compared with placebo. The results support aficamten as an evidence-based medical therapy for symptomatic nonobstructive HCM, addressing a major unmet need.

Masri A, Maron MS, Bhatia A et al. · The New England journal of medicine · (2026) · 1 citations · View on PubMed ↗

Individual Participant Data Meta-Analysis (IPDMA) of long-term COVID-19 outcomes in a systematic review-informed, international, multidisciplinary database.

This individual participant data meta-analysis (IPDMA) created an international, systematic review-informed database to synthesize long-term COVID-19 outcomes, predictors, and costs using contributed datasets from clinical, community, and research settings. By pooling individual-level data and including interventions from original studies as covariates, the study enabled more granular estimation of long-term effects and risk factors across populations. Scientifically, this IPDMA approach strengthens evidence for long-term COVID-19 prognosis and informs health and societal planning.

Ali M, Brady MC, Campbell P et al. · Health and social care delivery research · (2026) · View on PubMed ↗ · Free PDF ↗

Anticoagulation for Atrial Fibrillation with Intermediate Stroke Risk.

This multicenter, open-label, adjudicator-masked superiority trial in South Korea studied whether oral anticoagulation with a direct oral anticoagulant (DOAC) versus no anticoagulation improves outcomes in patients with atrial fibrillation and intermediate stroke risk (CHA2DS2-VASc score 1 in men or 2 in women). The trial tested whether DOAC therapy reduces the primary endpoint compared with withholding anticoagulation in this intermediate-risk group. If positive, it would provide randomized evidence to support guideline recommendations for anticoagulation in intermediate stroke risk atrial fibrillation.

Kim D, Lee YS, Shim J et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Eplontersen for Transthyretin Amyloid Cardiomyopathy.

This phase 3 international double-blind trial studied the antisense oligonucleotide eplontersen (45 mg subcutaneous every 4 weeks) versus placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), on top of standard treatment for up to 140 weeks. Eplontersen reduced hepatic production of transthyretin and was evaluated for its effect on a composite of cardiovascular death and recurrent cardiovascular clinical events through week 140. Clinically, a favorable result would establish eplontersen as a disease-modifying therapy targeting TTR biology in ATTR-CM.

Fontana M, Masri A, Solomon SD et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Global Efficacy of Aficamten in Nonobstructive Hypertrophic Cardiomyopathy: Results From ACACIA-HCM.

The ACACIA-HCM trial assessed the cardiac myosin inhibitor aficamten in adults with nonobstructive hypertrophic cardiomyopathy (nHCM) to determine clinical responder effects versus placebo. Aficamten produced significantly improved outcomes and a favorable responder profile compared with placebo in this nHCM population. These findings support aficamten as a mechanism-targeted therapy for excess contractility/diastolic dysfunction in nHCM and provide clinically interpretable effect estimates for future use and study.

Maron MS, Masri A, Bhatia A et al. · Circulation · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Delphi consensus on gene therapy of spinal muscular atrophy with onasemnogene abeparvovec in Germany, Austria and Switzerland - part II - expert based recommendations for surveillance and management of side-effects.

This Delphi consensus article studied how to implement long-term surveillance and side-effect management for children with spinal muscular atrophy treated with onasemnogene abeparvovec across Germany, Austria, and Switzerland. It provides structured, expert-based recommendations for safety monitoring protocols and clinical management of safety alerts, addressing the lack of systematic long-term gene-therapy surveillance guidance. The consensus aims to standardize care and improve patient safety and clinician confidence during ongoing follow-up after AAV-based SMN gene therapy.

Ziegler A, Weiß C, Vill K et al. · Journal of neuromuscular diseases · (2026) · View on PubMed ↗ · Free PDF ↗

Cardiovascular-Related Mortality and Hospitalizations in Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis: A Post Hoc Analysis of the Phase 3 ATTR-ACT and Long-Term Extension.

This post hoc analysis evaluated cardiovascular-related mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy treated with tafamidis 80 mg versus placebo in the phase 3 ATTR-ACT trial and then tafamidis in the long-term extension. The abstract truncation does not provide the quantitative hazard estimates for CV-related events and mortality. The analysis is significant because it extends evidence on how tafamidis modifies clinically meaningful cardiovascular outcomes over longer follow-up.

Damy T, Witteles R, Cappelli F et al. · Cardiology and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Real-world data for effectiveness and safety of palopegteriparatide in patients with chronic hypoparathyroidism: the PaTH REAL study.

This multicenter prospective real-world cohort study evaluated long-term efficacy and safety of palopegteriparatide, a long-acting prodrug of PTH(1-34), in patients with chronic hypoparathyroidism. The abstract indicates the study design and rationale but truncates before reporting quantitative outcomes. If confirmed in full, these real-world data would be clinically significant for guiding long-term management of chronic hypoparathyroidism beyond randomized trial evidence.

Yavropoulou MP, Tournis S, Chondrogianni ME et al. · European journal of endocrinology · (2026) · View on PubMed ↗

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Cardiovascular risk biomarkers and omics (proteomics/genomics/cell atlases)

Macrophage TREM2 is a triglyceride-rich lipoprotein receptor that undergoes shedding in prediabetic hepatic steatosis.

The study examined how macrophage TREM2 shedding relates to triglyceride-rich lipoprotein (TRL) metabolism in prediabetic hepatic steatosis by analyzing human prediabetes/steatosis cohorts and preclinical models. Soluble TREM2 (sTREM2) levels correlated positively with apolipoprotein C3 (APOC3), and prediabetes/steatosis patients had higher circulating sTREM2 and TRL-associated risk markers. This mechanistic link implicates TREM2 shedding as a contributor to elevated APOC3 and TRL burden, potentially informing cardiovascular risk stratification in metabolic disease.

Tang J, Kanter J, Shao B et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

Single-Nucleus and Multiomics Profiling of Epicardial Adipose Tissue in Atrial Fibrillation Reveals Novel Mechanisms and Translational Biomarkers.

This study profiled epicardial adipose tissue (EAT) in atrial fibrillation (AF) using single-nucleus RNA sequencing and multiomics approaches, integrating population genetics and Mendelian randomization with biomarker validation. The key finding was that EAT cellular and molecular/immune features differed in AF and yielded translational biomarkers supported by genetic evidence and validation experiments. This is significant because it identifies mechanistic EAT pathways and candidate biomarkers that could improve AF risk prediction and guide targeted interventions.

Huang S, Yang Z, Zhong X et al. · Journal of the American Heart Association · (2026) · View on PubMed ↗ · Free PDF ↗

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Diabetes, kidney disease, and cardiometabolic pharmacology (SGLT2/GLP-1/RAASi)

Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial.

This randomized clinical trial tested how diet macronutrient composition affects cardiometabolic responses to ~10% weight loss in people with metabolically unhealthy obesity (prediabetes and hepatic steatosis), comparing a very-low-carbohydrate ketogenic diet, a Mediterranean diet, and a very-low-fat plant-forward diet. All diets improved muscle insulin sensitivity by ~50%, but the very-low-carbohydrate ketogenic diet produced a 2–3-fold greater increase in hepatic insulin sensitivity than the other diets. The findings are significant because they suggest macronutrient composition can differentially modulate liver insulin sensitivity during weight loss in high-risk metabolic disease.

Petersen MC, Smith GI, Farabi SS et al. · Cell metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

SGLT2 inhibitors activate pantothenate kinase in the human heart.

This study examined how sodium-glucose cotransporter 2 inhibitors (SGLT2i) act in human cardiac tissue, focusing on the coenzyme A (CoA) synthesis enzyme pantothenate kinase 1 (PANK1). The authors found that SGLT2i directly bind and activate PANK1 at physiological concentrations, increasing PANK1 enzymatic activity and stimulating CoA synthesis and broad fuel use, supported by stable isotope infusions, conformational assays, in silico binding-site modeling, and amino-acid mutagenesis. These findings identify PANK1 as a mechanistic pharmacological target that could help explain SGLT2i cardioprotective effects beyond glucose transport.

Forelli N, Thome T, Eaton DM et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Early Sodium-Glucose Cotransporter-2 Inhibitor Use After Acute Kidney Injury in Type 2 Diabetes.

This cohort study used target trial emulation with TriNetX electronic health records to compare outcomes after acute kidney injury requiring dialysis (AKI-D) in adults with type 2 diabetes who initiated an SGLT-2 inhibitor within 30 days versus 31–90 days after discharge. The abstract truncation does not report the specific comparative outcomes. The study is clinically important because it informs optimal timing of SGLT-2 inhibitor initiation to improve kidney and cardiovascular outcomes after AKI-D.

Chou YT, Chen JY, Jiang ZH et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative Effectiveness of Combination Therapy in Patients with Chronic Kidney Disease and Diabetes mellitus Type 2 using Real World Data.

Using US Collaborative Network data from TriNetX, this study emulated target trials in adults with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) with eGFR 20–60 mL/min to compare renin-angiotensin-aldosterone system inhibitor (RAASi)–based strategies with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA), including potential additive effects of combination therapy. The key finding was the comparative effectiveness of different drug combinations on kidney-related outcomes in real-world practice after propensity score matching. Clinically, it informs which RAASi plus SGLT2i and/or GLP1-RA regimens may provide the best renal benefit for T2DM-CKD patients.

Casper J, Doricic J, Tian Z et al. · Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · (2026) · View on PubMed ↗

Treatment effects of dapagliflozin in patients with aortic stenosis undergoing transcatheter aortic valve implantation across left ventricular ejection fraction.

This pragmatic multicenter randomized open-label trial with blinded endpoint adjudication assessed the efficacy and safety of dapagliflozin 10 mg daily in elderly patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) across the full baseline left ventricular ejection fraction (LVEF) range. The abstract truncates before providing the trial’s effect estimates, but the key question was whether SGLT2 inhibition benefits TAVI patients regardless of LVEF. Clinically, results would extend SGLT2 inhibitor evidence into a previously excluded valvular population and inform post-TAVI risk management across LVEF strata.

Raposeiras Roubín S, Gonzalez-Manzanares R, Amat-Santos I et al. · European journal of heart failure · (2026) · View on PubMed ↗

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Oncology systemic therapy and treatment decision-making (breast/colorectal/gastric/solid tumors)

Perioperative Durvalumab for Resectable Non-Small Cell Lung Cancer: Updated Outcomes From the Phase III AEGEAN Trial.

The AEGEAN phase III double-blind, placebo-controlled trial studied perioperative durvalumab plus neoadjuvant platinum-based chemotherapy versus neoadjuvant chemotherapy alone in treatment-naïve resectable non-small cell lung cancer (R-NSCLC) patients (stage II–IIIB [N2]). Updated outcomes reported event-free survival (EFS) from a second interim analysis, interim disease-free survival (DFS) and overall survival (OS), along with safety after completion/discontinuation of therapy. If benefits persist with longer follow-up, perioperative durvalumab would further establish immunotherapy as a standard perioperative regimen to improve survival in resectable NSCLC.

Heymach JV, He J, Harpole D et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Prehabilitation models in patients undergoing radical prostatectomy: A scoping review.

This scoping review mapped evidence on prehabilitation models for patients undergoing radical prostatectomy, focusing on delivery formats, intervention components, and outcomes. It concluded that prehabilitation for radical prostatectomy is an emerging area with heterogeneous models and limited characterization of what is currently used and measured. The review is significant for guiding standardization and identifying gaps to support future trials and implementation planning in prostate cancer surgery.

Li Y, Chen Q, Chen H et al. · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗

Long-Term Survival Outcomes of Modified-FOLFOXIRI Plus Cetuximab Versus Bevacizumab in RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Final Analysis of the DEEPER Trial.

In the randomized phase II DEEPER trial, investigators compared modified FOLFOXIRI plus cetuximab versus modified FOLFOXIRI plus bevacizumab in RAS/BRAF wild-type metastatic colorectal cancer, with final overall survival (OS) and progression-free survival (PFS) analyzed in the per-protocol set using extended follow-up and exploratory subgroup analyses (including liver-limited disease and sex). The final analysis reported no differences in PFS and OS between the cetuximab and bevacizumab strategies in the reported RAS/BRAF wild-type population and subgroups. This is significant because it refines the expected long-term benefit of adding cetuximab versus bevacizumab to m-FOLFOXIRI in biomarker-defined metastatic colorectal cancer.

Sunakawa Y, Shiozawa M, Watanabe T et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Systemic Therapy Considerations in Older Adults With Early-Stage Breast Cancer: A Review.

This review synthesized evidence on systemic therapy decision-making for older adults with early-stage breast cancer, including how treatment benefits and harms vary by tumor subtype and patient factors. It highlights emerging strategies such as adjuvant cyclin-dependent kinase 4/6 inhibitors for hormone receptor–positive disease and neoadjuvant pembrolizumab for triple-negative breast cancer, while noting underrepresentation of older adults in trials. The review’s significance is to guide individualized systemic treatment selection that balances recurrence risk against toxicity in an aging population.

Smith CE, Sammons SL, Minami CA et al. · JAMA oncology · (2026) · View on PubMed ↗

Phase II study of mFOLFOX6 in advanced gastric cancer patients with severe peritoneal metastases (WJOG10517G), including an individual patient data comparison with JCOG1108/WJOG7312G.

This phase II trial tested mFOLFOX6 in HER2-negative, chemotherapy-naive advanced gastric cancer patients with severe peritoneal metastases (massive ascites and/or inadequate oral intake requiring IV support), with overall survival as the primary endpoint. The abstract truncation does not include the reported survival or response results. The study is important because it evaluates a regimen for a population excluded from pivotal trials and includes an individual patient data comparison with JCOG1108/WJOG7312G.

Masuishi T, Hara H, Ando T et al. · Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · (2026) · View on PubMed ↗ · Free PDF ↗

A Phase 2 Basket Trial of Ado-Trastuzumab Emtansine for Patients with HER2 Amplified Cancers: A Non-Randomized Clinical Trial.

This single-center, non-randomized phase 2 basket trial studied ado-trastuzumab emtansine (T-DM1) in 95 patients with advanced/metastatic HER2-amplified solid tumors, with HER2 status determined by next-generation sequencing or in-situ hybridization. The key finding was that the trial evaluated overall response rate (ORR) as the primary endpoint and reported efficacy and safety outcomes across five HER2-amplified cohorts treated with intravenous T-DM1 3.6 mg/kg every 21 days. Scientifically and clinically, it tests whether T-DM1 provides meaningful antitumor activity across diverse HER2-amplified cancers, supporting potential expansion of HER2-targeted therapy beyond breast cancer.

Ross JS, Wong W, Schoech L et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

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Immunotherapy and cellular therapies (CAR-T, CAR-Treg, ICI, immunoradiotherapy)

CD19 CAR T cell therapy for treatment-refractory seropositive rheumatoid arthritis: a phase 1 trial.

In the nonrandomized phase 1 portion of the COMPARE trial, six patients with severe, treatment-refractory, ACPA-positive seropositive rheumatoid arthritis received a single infusion of the autologous fully human CD19 CAR T cell therapy mivocabtagene autoleucel (miv-cel) after stopping DMARDs and undergoing standard lymphodepletion. The study reported clinical and molecular safety/efficacy data following miv-cel infusion in this small RA cohort. Clinically, it provides early translational evidence that CD19 CAR T cell therapy may be a feasible B-cell depletion strategy for refractory ACPA-positive RA.

Albach FN, Rehm MC, Hütter-Krönke ML et al. · Nature medicine · (2026) · View on PubMed ↗

Parkinsonism-like delayed neurotoxicity after idecabtagene vicleucel therapy for multiple myeloma: clinicopathological, cerebrospinal fluid, and autopsy analyses.

This clinicopathological study investigated Parkinsonism-like delayed neurotoxicity after idecabtagene vicleucel (ide-cel) therapy in multiple myeloma, using cerebrospinal fluid analyses and autopsy findings. The key finding was that ide-cel–associated delayed neurotoxicity manifested with Parkinsonism-like features and corresponding neuropathological changes detectable across clinical, CSF, and postmortem examinations. These results are significant because they highlight a rare but serious late neurologic adverse effect of CAR T-cell therapy and support CSF/autopsy-informed mechanistic surveillance for similar toxicities.

Yoshino H, Imi T, Nukii Y et al. · Haematologica · (2026) · View on PubMed ↗ · Free PDF ↗

CAR-T cells and CAR-Treg cells for treatment of inflammatory bowel diseases.

This review studied the therapeutic rationale and evidence for CAR-T cells and CAR-Treg cells in inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis. It highlights that CAR-based cellular therapies can be engineered to recognize defined antigens (e.g., CD19) and may enable immune recalibration for patients who fail biologics or small molecules. The significance is that CAR-T/CAR-Treg strategies represent a potential next-generation approach for durable control of intestinal inflammation.

Neurath MF · EULAR rheumatology open · (2026) · View on PubMed ↗ · Free PDF ↗

Immunotherapy in urological cancers: new paradigms and a systematic review of clinical trials and real-world evidence.

This systematic review studied immunotherapy strategies in urological cancers by synthesizing clinical trials and real-world evidence from 2010–2026. It identified 53 included studies spanning bladder, kidney, and prostate cancers, covering immune checkpoint inhibitors (ICIs) and other modalities such as immunoradiotherapy, antibody-drug conjugates (ADCs), vaccines, and cellular therapies. The significance is a consolidated view of emerging paradigms and effectiveness/safety signals that can guide clinical decision-making and future trial design.

Ismaili N, El Majjaoui S · Frontiers in oncology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer mechanisms and targeted drug design (PROTACs, DNA repair, resistance)

A Dual-Halogen Labeling Strategy to Detect and Quantify Double-Stranded RNAs Using NanoSIMS: A Proof-of-Concept Study.

This proof-of-concept study evaluated a dual-halogen labeling strategy (5-bromo- and 5-iodo-modified uracil) combined with NanoSIMS to detect and quantify double-stranded RNAs, including GalNAc-conjugated siRNA, in biological samples. The approach enabled discrimination and quantification of both RNA strands without bulky fluorescent tags. Scientifically, it provides a new nanoscale imaging framework to track siRNA uptake/trafficking/fate strand-specifically, which is important for improving oligonucleotide drug development.

Vicentini Q, Kurczy M, Estupiñán HY et al. · ACS omega · (2026) · View on PubMed ↗ · Free PDF ↗

De novo design of RNA pseudoknots with deep learning.

This experimental study in autism spectrum disorder (ASD) used affinity purification–mass spectrometry to map protein-protein interaction (PPI) networks for 100 high-confidence ASD genes and then assessed how pathogenic missense mutations rewire these networks. The authors found convergence onto shared protein complexes in the wild-type state and convergent PPI rewiring driven by independent mutations, with key findings supported by AlphaFold predictions and validation in human-derived model systems. This is significant because it links specific ASD mutations to network-level mechanisms, offering a route to identify common therapeutic targets across genetically diverse ASD cases.

Townley J, Kladwang W, Baker D et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Autism mutations rewire protein interaction networks to drive neurodevelopmental pathology.

This study reports de novo design of RNA pseudoknots using deep learning generative AI, aiming to overcome limitations in 3D structure prediction accuracy for RNA design. In an Eterna competition of 57 pseudoknots, AI-generated designs matched experienced human performance on most blind challenges and were validated using single-nucleotide-resolution chemical mapping, compensatory mutagenesis, and cryo-electron microscopy. The significance is that current deep learning can reliably generate complex RNA secondary structures that fold into well-ordered 3D conformations, enabling more effective RNA engineering.

Wang B, Vartak R, Hennick KM et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Assessment of generative de novo peptide design methods for G protein-coupled receptors.

This paper assessed the performance of generative de novo peptide design methods for G protein-coupled receptors (GPCRs), focusing on how computational confidence metrics relate to experimental outcomes. The key finding is that commonly used confidence measures for peptide/protein generation do not reliably predict experimental success for GPCR-targeting peptides, highlighting a gap between in silico scoring and real-world binding/function. Scientifically, it provides evidence to recalibrate evaluation strategies for peptide therapeutics design pipelines targeting GPCRs.

Junker H, Schoeder CT · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗

DIXDC1 Promotes Lymphatic Metastasis and Resistance to Cuproptosis in Bladder Cancer Through Mediating DLAT.

The study investigated the role of DIXDC1 in bladder cancer lymphatic metastasis and resistance to cuproptosis, using patient tissue analyses and in vivo functional assays. DIXDC1 promoted migration, invasion, proliferation, and lymph node dissemination and mechanistically bound DLAT (dihydrolipoamide S-acetyltransferase) to impede DLAT ubiquitination and thereby reduce cuproptosis sensitivity. These results identify a DIXDC1–DLAT axis that could be targeted to limit lymphatic spread and overcome cuproptosis resistance in bladder cancer.

Li H, Cheng L, Lu X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Allele-Specific Mechanisms Guide Salvage Therapy to Overcome Daraxonrasib Resistance in Pancreatic Cancer.

This study examined allele-specific resistance mechanisms to daraxonrasib (RMC-6236), a multi-selective RAS(ON) inhibitor, in pancreatic ductal adenocarcinoma (PDAC) models harboring KRASG12D versus KRASG12R mutations. The key finding was that daraxonrasib inhibited KRASMUT mainly through steric occlusion of effector binding, while KRASG12R resistance relied on EGFR/RASWT-GTP signaling and KRASG12D resistance used a different adaptive route. Clinically and scientifically, it suggests that KRAS allele identity can determine the dominant resistance pathway and therefore guide salvage therapy selection after RAS inhibitor failure.

Dorbin D, Herrera J, Davidson R et al. · Cancer research · (2026) · View on PubMed ↗ · Free PDF ↗

PCNA-RECQL5-RPRD1B recruit repair components to stressed replication forks to promote survival of BRCA1-deficient cancer cells.

This study investigated how PCNA-RECQL5-RPRD1B recruits DNA repair components to stressed replication forks to promote survival of BRCA1-deficient cancer cells. It found that microRNA miR-4485-3p suppresses RPRD1B, and that RPRD1B depletion selectively kills BRCA1-deficient cells by reducing POLQ microhomology-mediated end joining (MMEJ) and replication fork repair under replication stress. The significance is the identification of a potential synthetic-lethal vulnerability in BRCA1-deficient tumors that could be exploited therapeutically by targeting the miR-4485-3p/RPRD1B axis or the associated repair recruitment pathway.

Tran MT, Williamson EA, Jaiswal AS et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

Harnessing the E3 Ligase KLHL12 for Tumor-Selective Protein Degradation.

The study investigated whether the E3 ubiquitin ligase KLHL12 could be harnessed for tumor-selective proteolysis using KLHL12-recruiting PROTACs in cell models. Structure-guided macrocyclization produced a KLHL12-binding cyclic peptide (cp4) and an optimized PROTAC (k12bp-1) that selectively degraded BRD4(L) in A549 lung cancer cells, inhibiting proliferation and inducing apoptosis while sparing non-target proteins. This provides a first-in-class strategy to improve PROTAC tumor selectivity by recruiting a less ubiquitously expressed E3 ligase (KLHL12) to drive targeted degradation of oncogenic BRD4 and potentially EGFR.

Xu S, Zhang X, Hu S et al. · Angewandte Chemie (International ed. in English) · (2026) · View on PubMed ↗ · Free PDF ↗

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Hematologic malignancies (MDS/CLL/myelofibrosis/RA)

Integrated bioinformatic evaluation unveils a cellular senescence gene signature as a poor prognostic factor in hepatocellular carcinoma.

This study performed integrated bioinformatic analyses of cellular senescence (CS)-related genes in hepatocellular carcinoma (HCC), clustering CS genes into subtypes and building/validating a CS risk score across three independent cohorts. High CS risk (especially CS subtype 1) was associated with worse prognosis and correlated with tumor immune microenvironment features, mutation status, heterogeneity, and treatment efficacy, supported by single-cell distribution analyses and machine-learning/nominogram prognostic modeling. Scientifically, it identifies a CS gene signature that may stratify HCC patients by outcome and potentially inform prognosis and treatment-response prediction.

Lu S, Ma J, Wang X et al. · Clinical and experimental medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Refined Continuous Risk Index for Accurately Predicting Outcomes of Patients With Chronic Lymphocytic Leukemia After Limited-Duration Therapy.

This study developed and evaluated a refined continuous individualized risk index (CIRI2) for chronic lymphocytic leukemia (CLL) patients treated with fixed-duration targeted therapy, incorporating measurable residual disease (MRD) status at interim, end-of-treatment (EoT), and 12 months post-EoT. The key finding is that CIRI2 improves prognostic accuracy for survival outcomes compared with indices relying only on pretreatment features (e.g., CLL-IPI), leveraging dynamic MRD trajectories. Scientifically and clinically, this supports MRD-informed, time-updated risk modeling to better predict outcomes after limited-duration CLL therapy.

Al-Sawaf O, Zhang C, Esfahani MS et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Final results of a phase II study of the combination of azacitidine and ruxolitinib in patients with myelofibrosis.

This phase 2 clinical trial studied the combination of azacitidine (AZA) and ruxolitinib (RUX) in 61 patients with myelofibrosis, with the primary endpoint being objective response rate (IWG-MRT criteria). The key finding was that the final analysis reported an objective response rate of 72% (with interim results from 46 patients and median follow-up of 28 months). Clinically, it supports AZA+RUX as an effective regimen for reducing splenomegaly and symptom burden while potentially improving disease control compared with JAK inhibitor monotherapy.

Arora S, Senapati J, Chu V et al. · Haematologica · (2026) · View on PubMed ↗ · Free PDF ↗

Impact of Response to Hypomethylating Agent-Based Therapy on Survival Outcomes in the Context of Baseline Clinical-Molecular Risk and Transplant Status in Patients With Higher-Risk Myelodysplastic Syndromes/Neoplasms: An analysis From the International Consortium for MDS (icMDS).

Using the International Consortium for MDS (icMDS) VALIDATE database, this analysis studied 715 higher-risk myelodysplastic syndromes/neoplasms patients treated with hypomethylating agent (HMA) therapy to determine how IWG 2023 best response affects overall survival (OS) after accounting for baseline IPSS-M risk and whether patients received subsequent allogeneic stem cell transplant (allo-HCT). The key finding was that response to HMA-based therapy had prognostic impact on OS that remained relevant when stratified by baseline clinical-molecular risk and transplant strategy. The clinical significance is that it refines survival prediction and can help guide decisions about escalation to allo-HCT versus continued medical therapy in higher-risk MDS.

Rolles B, Bewersdorf JP, Kewan T et al. · American journal of hematology · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurology and neurorehabilitation (stroke/TBI/neurodegeneration)

Sex differences in blood pressure variability during critical illness: a retrospective cohort study.

This retrospective cohort study examined sex differences in blood pressure variability (BPV) during ICU critical illness and whether sex modifies the association between BPV and clinical outcomes in adult ICU patients admitted between 2013 and 2023. The study assessed BPV patterns by sex and tested whether BPV is differentially linked to outcomes such as mortality across females versus males. Clinically, identifying sex-specific BPV risk relationships could refine hemodynamic monitoring and individualized critical care targets.

Ng PY, Hui HYY, Ip A et al. · Open heart · (2026) · View on PubMed ↗

Robot-assisted integrated cognitive-motor rehabilitation in patients with chronic stroke: a randomized controlled trial.

In a single-center randomized controlled trial, 30 patients with chronic stroke were assigned to an end-effector robot-assisted integrated cognitive-motor rehabilitation program versus control to test effects on global cognition and upper-limb motor outcomes. The robot-assisted integrated cognitive-motor intervention improved global cognitive function and upper limb motor outcomes compared with control. Clinically, this supports integrated cognitive-motor robotic rehabilitation as a strategy to enhance functional recovery beyond motor training alone in chronic stroke.

Cha S, Lee J, Jeon H et al. · Frontiers in neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Genetic frontotemporal degeneration across the lifespan? A critical appraisal of the neurodevelopmental hypothesis.

This critical review appraised evidence for a neurodevelopmental hypothesis of genetic frontotemporal degeneration (FTD), focusing on whether FTD-associated variants show effects in youth and across the lifespan. The authors conclude that while presymptomatic and developmental signals have been suggested, direct human evidence in young populations remains limited and the current literature requires careful interpretation and stronger longitudinal studies. The significance is that clarifying whether FTD genetics act through neurodevelopment versus later-life mechanisms could reshape how early risk is studied and potentially how prevention strategies are conceptualized.

So I, Birkle TJY, Duff KE et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Digital Defocus Vision Training Using Virtual Reality for Myopia Control: A Randomized Clinical Trial.

This randomized clinical trial evaluated head-mounted virtual reality-based digital defocus vision training (DDVT) plus single-vision spectacles versus single-vision spectacles alone in children aged 6–12 years with myopia in Guangzhou, China. The abstract truncation does not provide the trial’s efficacy or safety outcomes. Clinically, the study directly tests whether home-based VR DDVT can slow myopia progression in pediatric patients.

Zhong J, Liu Y, Peng T et al. · JAMA ophthalmology · (2026) · View on PubMed ↗

Cognitive Behavior vs Bright Light Therapy for Insomnia in Women Undergoing Chemotherapy for Breast Cancer: A Randomized Clinical Trial.

This randomized clinical trial compared cognitive behavior therapy for insomnia (CBT-I) and bright light therapy (BLT), alone and in combination, in women undergoing chemotherapy for breast cancer. The abstract truncation does not include the main results for insomnia and fatigue outcomes. If effective, these nonpharmacologic interventions could improve sleep-related quality of life during chemotherapy and reduce symptom burden.

Do TT, Maccora J, Wallace R et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Balancing lung and brain: physiological strategies for ARDS management in acute brain injury.

This narrative review examined how acute respiratory distress syndrome (ARDS) pathophysiology interacts with acute brain injury (ABI) in critically ill patients, focusing on competing effects of ventilatory variables on lung and cerebral physiology. It highlights that lung-protective ventilation strategies (e.g., limiting tidal volume/pressures) can worsen cerebral parameters, while neuroprotective targets may compromise respiratory management. The review’s clinical significance is to frame an evidence-based “balancing” approach for ventilator settings in ABI patients to reduce mortality and neurological harm while still preventing ventilator-associated lung injury.

Robba C, Romero-García N, Taran S et al. · Intensive care medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Sex and Gender Differences in Physical Activity, Sedentary Behavior, and Sleep During Traumatic Brain Injury Recovery: A Narrative Review.

This narrative review synthesized evidence on sex and gender differences in physical activity, sedentary behavior, and sleep during traumatic brain injury (TBI) recovery in humans. The key finding was that recovery-related activity and sleep patterns appear to differ by sex/gender, but the determinants and mechanisms remain insufficiently characterized. Clinically, it underscores the need for sex- and gender-informed rehabilitation and monitoring of lifestyle factors to improve long-term outcomes after TBI.

España-Irla G, Perko M, Tinney EM et al. · European journal of sport science · (2026) · View on PubMed ↗ · Free PDF ↗

The non-canonical CDK2 activator SPY1 uses separable mechanisms to activate phosphorylated and unphosphorylated CDK2.

This biochemical study investigated how the non-canonical CDK2 activator SPY1 activates phosphorylated versus unphosphorylated CDK2 using separable mechanisms, focusing on the role of a specific SPY1 residue (D136) that mimics activation-loop phosphorylation. The key finding was that SPY1 can promote CDK2 activation without requiring CDK2 activation-loop phosphorylation on T160, with D136 stabilizing the active SPY1–CDK2 conformation via salt-bridge interactions. Scientifically, it clarifies a phosphorylation-independent activation mechanism for CDK2 that can inform broader models of cell-cycle control and meiosis regulation.

Fawcett LP, Levinson NM · The Biochemical journal · (2026) · View on PubMed ↗ · Free PDF ↗

Disruption of sphingolipid metabolism promotes tau seeding through endolysosomal membrane rigidification and rupture.

This study tested whether disrupting sphingolipid metabolism alters tau aggregation and toxicity by changing endolysosomal membrane properties in Caenorhabditis elegans and human cell culture models. The key finding was that silencing sphingolipid metabolism genes reduced endolysosomal membrane fluidity, increased vesicle rupture, and promoted seeded tau aggregation that further worsened endomembrane damage. This is significant because it links lipid metabolism to endolysosomal integrity as a mechanistic driver of tau seeding, suggesting potential therapeutic targets in tauopathies.

Tittelmeier J, Sandhof CA, Martin N et al. · eLife · (2026) · View on PubMed ↗ · Free PDF ↗

Neuroimaging Abnormalities and Genotype-Phenotype Correlations in Noonan Syndrome: A Multicenter Cohort Study.

This multicenter retrospective cohort study evaluated brain MRI abnormalities and their genotype–phenotype correlations in 130 children with genetically confirmed Noonan syndrome. The key finding was that neuroimaging abnormalities were common and showed associations with specific clinical features and underlying genetic variants. This is significant because it provides a more precise neuroimaging phenotype map for Noonan syndrome, supporting risk stratification and targeted clinical follow-up.

Patti G, Maiorano NG, Piccoli F et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

High-dose methylcobalamin in amyotrophic lateral sclerosis: mechanistic rationale, translational evidence, and clinical implications.

This article provided a mechanistic rationale and translational/clinical implications for high-dose methylcobalamin in amyotrophic lateral sclerosis (ALS) based on a structured literature review of studies published from 2017–2025. The key finding was that methylcobalamin has pleiotropic neurobiological effects—summarized from preclinical and translational evidence—that could plausibly address multiple ALS pathogenic pathways. This is significant because it consolidates the evidence base supporting methylcobalamin as a candidate intervention and helps frame future clinical trial design and mechanistic hypotheses.

da Silva AA, Pupe CCB, Dos Santos JCC · Neurodegenerative disease management · (2026) · View on PubMed ↗

2026 Guideline for Adult Stroke Rehabilitation and Recovery: A Guideline From the American Heart Association and American Stroke Association.

This guideline paper synthesized evidence to update adult stroke rehabilitation and recovery recommendations for clinical practice, replacing the 2016 American Heart Association/American Stroke Association guideline. The key finding was the establishment of an updated, evidence-based set of recommendations derived from literature searches conducted in 2025 across human-participant studies. This is significant because it standardizes contemporary rehabilitation care pathways and informs clinicians and caregivers on best practices for improving stroke recovery outcomes.

Richards LG, Ifejika NL, Stein J et al. · Stroke · (2026) · 4 citations · View on PubMed ↗

Toward autonomous artificial intelligence agents in sports science: a modular framework for development, validation, and implementation.

This review studied how to design, validate, and implement autonomous artificial intelligence (AI) agent systems for sports science, contrasting them with existing passive analytics and human-in-the-loop tools. It proposes a modular framework intended to enable 24/7 monitoring, independent reasoning, and proactive intervention execution by AI agents. Scientifically, it provides a development pathway for moving sports-science AI from reactive tools to continuously operating systems that can be tested and deployed more rigorously.

Dergaa I, Barbaria S, Dhahbi W et al. · Biology of sport · (2026) · 4 citations · View on PubMed ↗ · Free PDF ↗

Clinical Reasoning: A 28-Year-Old Man with Subacute-Onset Ataxic Gait.

This case report studied the diagnostic reasoning for a 28-year-old man presenting with subacute-onset ataxic gait and systemic features including intermittent fever and unintentional weight loss. The key clinical finding was a neurologic pattern with marked limb weakness, absent lower-extremity deep tendon reflexes, stocking-glove sensory loss, and positive Romberg sign, prompting a complex differential diagnosis. The significance is educational: it illustrates how to approach subacute progressive polyneuropathy/ataxia with systemic signs to avoid diagnostic delays.

Benetti M, Caiza-Zambrano F, Reisin R et al. · The Neurohospitalist · (2026) · View on PubMed ↗ · Free PDF ↗

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Neuroimaging and brain aging/vascular contributions

Lesion-Level Subtypes of White Matter Hyperintensity Evolution Beyond Spatial Location.

This longitudinal observational MRI study analyzed 3224 scans from 403 participants across cognitively normal aging, mild cognitive impairment, and dementia to identify lesion-level white matter hyperintensity (WMH) subtypes beyond spatial location and test links to neurodegeneration and vascular risk. The authors report that WMH evolution contains biologically distinct lesion-level subtypes that associate differentially with neurodegenerative outcomes and vascular risk factors rather than behaving as a single homogeneous process. These findings support more biologically informed WMH phenotyping for improving risk stratification and mechanistic understanding of cerebrovascular contributions to cognitive decline.

Gonzalez-Gomez R, Tagliazuchi E, Campo CG et al. · Neurology · (2026) · View on PubMed ↗ · Free PDF ↗

The Joint Effects of Life’s Essential 8 and Genetics on Mild Cognitive Impairment and Dementia Risk in People With Diabetes: Findings From the UK Biobank and All of Us.

This cohort analysis studied 41,374 participants from UK Biobank and 9,766 from All of Us without dementia to test joint associations of cardiovascular health (Life’s Essential 8; LE8) and genetic risk (APOE ε4 and Alzheimer disease polygenic risk scores) with mild cognitive impairment (MCI) and dementia risk in people with diabetes. The key finding was that LE8 and genetic risk jointly predicted cognitive outcomes, indicating that cardiovascular health modifies the impact of genetic susceptibility. The scientific significance is that it supports risk stratification and prevention strategies in diabetes by targeting modifiable cardiovascular components to reduce dementia risk even among those with higher genetic risk.

Wu X, Zu Y, Lu Y et al. · Diabetes care · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious disease, host-pathogen interactions, and diagnostics

Response-Tailored or Standard-Duration Antibiotic Treatment for Infective Endocarditis.

This international open-label randomized trial studied whether a response-tailored antibiotic strategy can safely shorten total treatment duration compared with standard-duration antibiotics in adults with left-sided infective endocarditis caused by Staphylococcus aureus, Enterococcus faecalis, or streptococcal species. The key finding was the comparative effectiveness and safety of tailoring therapy duration to clinical response versus giving up to 6 weeks per conventional recommendations. If noninferior, response-tailored management would reduce unnecessary antibiotic exposure while maintaining safety in left-sided infective endocarditis.

Bundgaard H, Pries-Heje M, Hjulmand J et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Beat- and Side-family cell-surface molecules are expressed combinatorially in the partner neurons of the olfactory circuit in Drosophila.

This Drosophila study used newly generated gene trap transgenic driver lines to map combinatorial expression of Beat- and Side-family IgSF cell-surface molecules in olfactory receptor neurons (ORNs) and their synaptic target projection neurons (PNs). It found that beat/side genes are expressed combinatorially in partner neurons, consistent with a combinatorial “recognition tag” model for olfactory circuit assembly. Scientifically, it clarifies how IgSF gene families contribute to wiring specificity in the olfactory circuit.

Duan Q, Okuwa S, Estrella R et al. · PLoS biology · (2026) · View on PubMed ↗ · Free PDF ↗

Pregnancy Outcomes in Individuals With Long COVID.

This multicenter prospective cohort analysis of RECOVER-Adult evaluated whether maternal Long COVID status (Long COVID Research Index [LCRI] ≥11) is associated with adverse pregnancy outcomes in pregnant adults with prior SARS-CoV-2 infection. The study found an association between likely Long COVID classification and worse pregnancy outcomes compared with those without likely Long COVID, based on symptom-survey–based Long COVID categorization recorded before or during pregnancy. Clinically, this suggests Long COVID may be a relevant maternal risk factor during pregnancy and motivates closer monitoring and risk-tailored obstetric care.

Metz TD, Sandoval GJ, Allshouse AA et al. · Obstetrics and gynecology · (2026) · View on PubMed ↗

Genomic predisposition is associated with the direction of sex chromosome evolution.

Using chromosome-level genomes from 19 gecko species, this study investigated how genomic predisposition relates to the direction of sex chromosome evolution (XY versus ZW). The authors found that sex chromosome origins are nonrandom in both timing and direction, with ancestral gene content predicting outcomes—testis-enriched regions tending toward ZW and testis-depleted regions toward XY—consistent across multiple amniote sex chromosome origins. This provides a mechanistic genomic framework for predicting sex chromosome evolutionary trajectories across lineages.

Zhou Y, Jin J, Jiang C et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

A tripartite genetic conflict system controls hybrid sterility in rice.

In hybrid rice, this study identified RHS3 as a major quantitative trait locus controlling hybrid sterility in interspecific Asian–African crosses and characterized its underlying gene system. RHS3 encodes a tripartite toxin–antidote module (MAO, DUN, and JIA) where MAO disrupts mitochondrial function to abort gametes, while DUN and JIA act as antidotes via selective autophagy through formation of a JIA–DUN–MAO complex, giving the African allele a transmission advantage. The significance is that it reveals a concrete molecular mechanism for hybrid sterility and demonstrates de novo origin of the RHS3 system in the AA-genome rice lineage, informing both evolutionary biology and crop breeding strategies.

He X, Zhao Z, Shao K et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

DDI-4 induces a temperature-sensitive exocytotic remodeling during C. elegans spermiogenesis via nsun-2-dependent sphingosine signaling.

This study examined how the small molecule DDI-4 induces temperature-sensitive exocytotic remodeling during Caenorhabditis elegans spermiogenesis, with emphasis on nsun-2-dependent sphingosine signaling. The authors identified DDI-4 as a benzylamine analog that triggers membranous organelle fusion (MOF) in spermatids and found that MOF is selectively impaired in males raised at elevated temperatures, implicating nsun-2-dependent sphingosine signaling in the process. These findings connect a chemical inducer of conserved exocytotic events to temperature-dependent regulation of fertilization competence.

Shimada Y, Shiraki R, Ogawa C et al. · PLoS genetics · (2026) · View on PubMed ↗ · Free PDF ↗

RNF213-dependent lytic destruction of Chlamydia-containing vacuoles activates host cell death pathways.

This study examined how the host ubiquitin E3 ligase RNF213 controls cell-autonomous immunity against the intracellular pathogen Chlamydia trachomatis. It found that in the absence of the Chlamydia effector GarD, RNF213 is recruited to Chlamydia-containing vacuoles (inclusions), where it ubiquitylates inclusion-associated substrates and triggers host cell death pathways via a lytic mechanism. The results clarify a host defense strategy that can be subverted by bacterial effectors and may inform antimicrobial immune-targeting approaches.

Dickinson MS, Walsh SC, Bastidas RJ et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Structural biology of retron-mediated immunity against phage.

This review studied the structural biology of retron-mediated immunity against phage, focusing on how retron components coordinate defense. It reports that cryo-EM and biochemical structures across retron types support a unifying mechanism in which the reverse transcriptase (RT) bound to multicopy msDNA keeps effector domains inactive until phage-triggered perturbation activates them. The synthesis provides a structural framework for understanding and potentially engineering retron-based anti-phage systems.

Jasnauskaitė M, Pausch P · Biological chemistry · (2026) · View on PubMed ↗ · Free PDF ↗

Complete genome-derived metabolic interactions reveal the impact of gut ecology on human health.

This study used 1,150 complete microbial genomes to reconstruct genome-scale metabolic models and infer metabolic interactions that shape gut ecology and human health. The key finding is that draft assemblies introduce systematic artifacts and miss critical transport functions, and that niche specialization and genomic traits—rather than random association—govern microbial metabolic competition and complementarity, with interaction asymmetry partitioning strains into four ecological groups (e.g., resource predators/utilizers/contributors). Scientifically, it provides a more accurate, genome-informed map of metabolite exchange rules that can link gut community structure to host health outcomes.

Gu Y, Wang H, Yang J et al. · Cell reports · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

HSV-1 LAT promotes ocular diseases in the absence of type I IFN responses in sensory neurons.

This mouse study examined how the herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) promotes ocular disease when type I interferon (IFN) responses are absent in sensory neurons, building on prior IFNα subtype deletion work (e.g., IFNα2A knockout). The key finding was that HSV-1 LAT can drive ocular pathology even without type I IFN signaling, indicating a functional crosstalk between LAT-mediated latency programs and innate antiviral defense pathways. This is significant because it reframes LAT as an active determinant of disease severity under IFN-compromised conditions, informing strategies to prevent HSV-1–associated ocular complications.

Wang S, Jaggi U, Oh JJ et al. · Journal of virology · (2026) · View on PubMed ↗ · Free PDF ↗

Chelonid alphaherpesvirus 5 qPCR of archived blood and skin samples underpredicts infections in juvenile green turtles Chelonia mydas.

This study evaluated how quantitative PCR (qPCR) detection of Chelonid alphaherpesvirus 5 (ChHV5) in archived blood and skin samples performs in juvenile green turtles (Chelonia mydas). Archived samples (>1 year old) can under-detect ChHV5, so negative qPCR results may reflect loss of viable viral DNA rather than absence of infection. The findings caution against interpreting negative ChHV5 qPCR from stored specimens as evidence of true infection-free status, which is important for fibropapillomatosis surveillance and retrospective studies.

Kelley JR, Lee T, Martin KR et al. · Diseases of aquatic organisms · (2026) · View on PubMed ↗

Epstein-Barr Virus and Multiple Sclerosis: Mechanistic Insights into Virus-Driven Autoimmunity.

This article provided mechanistic insights into how Epstein-Barr virus (EBV) may drive autoimmunity relevant to multiple sclerosis (MS). It highlights that nearly all people with MS are EBV-seropositive and that longitudinal studies show EBV infection precedes MS onset, consistent with a causal role, with EBV latency in B cells shaping immune responses. Understanding EBV-driven mechanisms is scientifically significant because it supports EBV as a modifiable environmental factor and informs potential prevention or immunotherapy strategies for MS.

Bashiardes S, Krashias G, Englezou E et al. · Microorganisms · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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Pulmonary and airway disease (asthma, fungal disease, eosinophilic disorders)

Asian consensus on diagnostic algorithm for invasive pulmonary fungal diseases in high-burden settings.

This work developed an Asian expert consensus diagnostic algorithm for invasive pulmonary fungal diseases (IPFD) in high-burden clinical settings with immunocompromised patients. The key output is a structured, region-tailored diagnostic approach designed to address challenges such as high rates of diabetes, tuberculosis, and HIV, pathogen heterogeneity, and limited diagnostic resources. Clinically, it aims to standardize IPFD diagnosis and improve diagnostic accuracy and timeliness across diverse Asian healthcare systems.

Fang W, Liu X, Bilal H et al. · Journal of translational internal medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative efficacy and safety of IL-23 p19 monoclonal antibodies for plaque psoriasis: a bayesian network meta-analysis of randomized controlled trials.

This Bayesian network meta-analysis studied the comparative efficacy and safety of IL-23 p19 monoclonal antibodies for moderate-to-severe plaque psoriasis using randomized controlled trials. It compared guselkumab, risankizumab, tildrakizumab, and mirikizumab across endpoints such as PASI75/90/100 and IGA/PGA/sPGA 0/1, and safety outcomes including overall and serious adverse events. The significance is that it provides relative odds and ranking (e.g., SUCRA) to support evidence-based selection among IL-23 p19 inhibitors.

Xin T, Sun S, Liu Y · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Mepolizumab Modifies Blood Eosinophil Proteome and Transcriptome in Severe Eosinophilic Asthma.

This study examined how mepolizumab, an anti-IL-5 monoclonal antibody, alters the blood eosinophil proteome and transcriptome in severe eosinophilic asthma (SEA) patients compared with healthy individuals. Using LC-MS/MS proteomics and Nanostring targeted transcriptomics on isolated eosinophils at baseline and after treatment, it aimed to define molecular signatures that persist despite eosinophil count reduction. These findings are significant for identifying residual disease mechanisms and potential biomarkers or therapeutic targets in SEA beyond eosinophil depletion.

Miguéns-Suárez P, Vázquez-Mera S, Martelo-Vidal L et al. · Allergy · (2026) · View on PubMed ↗ · Free PDF ↗

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Gastrointestinal and liver disease (IBD, MASLD/steatosis, endoscopy-relevant)

Nonviral delivery of chemically modified tRNA rescues nonsense mutations in cystic fibrosis.

This study investigated whether nonviral delivery of chemically modified suppressor transfer RNAs (sup-tRNAs) can rescue cystic fibrosis caused by nonsense mutations in vivo. By incorporating N1-methyladenosine into sup-tRNAs and packaging them in cargo-tailored pulmonary lipid nanoparticles (LNPs), the authors improved premature termination codon (PTC) readthrough, enhanced tRNA aminoacylation, prolonged functional persistence, and reduced innate immune activation, with formulation optimization guided by high-throughput ionizable lipid screening. The work supports a nonviral, lung-targeted gene-suppression strategy for nonsense-cystic fibrosis with improved efficacy and tolerability.

Chen J, Zhou M, Dong S et al. · Science (New York, N.Y.) · (2026) · 1 citations · View on PubMed ↗

A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease.

This study analyzed epithelial cell death pathways in inflammatory bowel disease (IBD) patients, including those in remission and on advanced therapy, to determine mechanisms that persist despite treatment. It found that nascent inflammation drives epithelial cells into an M1-macrophage-like transcriptional state that promotes RIPK1-independent necroptotic signaling, which then triggers inducible nitric oxide–linked downstream inflammatory damage (as described in the truncated abstract). The results suggest a persistent epithelial necroptotic-to-apoptotic signaling axis as a mechanistic target for preventing relapse in IBD.

Pang J, Al-Ani AH, Patel KM et al. · Science (New York, N.Y.) · (2026) · 6 citations · View on PubMed ↗

Effects of Semaglutide versus Bariatric Surgery on Noninvasive Markers of Hepatic Steatosis and Fibrosis in Obesity with MASLD.

This single-center prospective observational cohort study compared lifestyle therapy, lifestyle plus semaglutide (1.0±0.4 mg/week), and lifestyle plus bariatric surgery in 92 adults with obesity and metabolic dysfunction–associated steatotic liver disease (MASLD), focusing on noninvasive markers of hepatic steatosis and fibrosis over 72 weeks. The key finding was that semaglutide and bariatric surgery produced measurable improvements in noninvasive hepatic steatosis/fibrosis markers compared with lifestyle alone. This is significant because it supports semaglutide as a pharmacologic option with liver-benefit signals comparable to surgical approaches, using clinically scalable noninvasive endpoints.

Lünswilken P, Worobiec K, Braun LS et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Pathways of Epithelial Barrier Breakdown and Remodeling in Esophageal Organoids by Commonly Used Surfactants.

This experimental study used esophageal organoids to determine how commonly used surfactants—sodium dodecyl sulfate (SDS) and cocamidopropyl betaine (CAPB)—disrupt epithelial barrier integrity and trigger molecular remodeling relevant to eosinophilic esophagitis (EoE). The key finding was that exposure to these surfactants impaired epithelial barrier function and induced associated molecular responses consistent with barrier breakdown and remodeling. This is significant because it provides direct mechanistic evidence linking environmental surfactants to EoE pathogenesis via epithelial barrier weakening.

Ardicli O, Yazici D, Babayev H et al. · Allergy · (2026) · View on PubMed ↗ · Free PDF ↗

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Dermatology, fibrosis, and musculoskeletal disease (fibrosis, OA, myopathy, back pain)

Adipose-cartilage communication via EV-Mito-mtDNA signaling promotes osteoarthritis progression.

This study investigated how obesity-driven adipocyte extracellular vesicles enriched in mitochondrial components (EV-Mito) promote osteoarthritis progression by transferring mitochondrial DNA (mtDNA) to chondrocytes in murine and human models. EV-Mito internalization activated the cGAS–STING cytosolic DNA-sensing pathway, triggering inflammatory signaling, metabolic dysfunction, senescence, and cartilage degeneration, and genetic or pharmacologic cGAS–STING inhibition attenuated cartilage damage and pain-related outcomes. These findings identify EV-Mito–mtDNA–cGAS–STING signaling as a mechanistic therapeutic target to slow osteoarthritis progression in obesity-associated disease.

Gu C, Liao F, Kong G et al. · Science advances · (2026) · View on PubMed ↗

Cancer in systemic sclerosis: clinical associations and prognostic impact from the EUSTAR registry.

This nested case-control study within the EUSTAR registry assessed clinical associations and prognostic impact of cancer in systemic sclerosis (SSc), comparing SSc patients who developed cancer (n=454) with cancer-free matched controls. It evaluated how cancer timing relative to SSc onset (synchronous within ±3 years, subsequent >3 years after, or previous >3 years before) and specific clinical/serologic/treatment factors related to survival. The findings refine risk stratification for malignancy in SSc and clarify which patient subsets have worse prognosis when cancer occurs.

Tonutti A, Motta F, Moschetti L et al. · Arthritis & rheumatology (Hoboken, N.J.) · (2026) · View on PubMed ↗

Myocardial Fibrosis in Pediatric Heart Disease: Mechanisms, Imaging Biomarkers, Clinical Consequences, and Emerging Antifibrotic Therapies.

This review synthesized current evidence on myocardial fibrosis in pediatric heart disease, focusing on mechanisms, imaging biomarkers, clinical consequences, and emerging antifibrotic therapies across congenital and acquired pediatric conditions. It highlights fibrosis as a dynamic process driven by inflammation, neurohormonal activation, oxidative stress, and fibroblast-to-myofibroblast transformation, with multiple imaging and therapeutic avenues under development. The work is significant because it frames pediatric myocardial fibrosis as a modifiable target and guides selection of biomarkers and future antifibrotic interventions.

Asghar U, Choudhry S, Jabeen M et al. · Cardiology in review · (2026) · View on PubMed ↗

The effect of integrating pain neuroscience education with stabilization exercises using a flexi-bar on functional disability, pain, and geometry of abdominal and multifidus muscles in patients with chronic non-specific low back pain.

In a randomized study of 48 participants with chronic non-specific low back pain, investigators tested whether adding pain neuroscience education to Flexi-Bar-based stabilization exercises improved functional disability, pain intensity, and abdominal/lumbar multifidus muscle geometry versus stabilization exercises alone. The integrated intervention produced additional benefits across pain and disability outcomes and altered multifidus-related measures compared with control. Clinically, it supports combining education targeting pain-related cognitions/fear with targeted stabilization training to improve outcomes in chronic low back pain.

Dehghani Z, Abolahrari-Shirazi S, Emami F et al. · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗

SNHG26 orchestrates pro-fibrotic fibroblast maintenance via PTBP1-mediated alternative polyadenylation of AKT3 in dermal fibrosis.

This study investigated the role of the long noncoding RNA SNHG26 in pro-fibrotic fibroblast maintenance in dermal fibrosis, focusing on PTBP1-mediated alternative polyadenylation of AKT3. It found that SNHG26 is enriched in human CD90+ fibroblasts from hypertrophic scars and keloids, and that deleting Snhg26 or silencing it with antisense oligonucleotides disrupts mesenchymal identity and suppresses extracellular matrix synthesis, with the mechanism involving PTBP1-dependent alternative polyadenylation of AKT3 (as described in the truncated abstract). The work identifies an SNHG26–PTBP1–AKT3 axis as a potential molecular target to destabilize the fibrotic fibroblast state.

Pan L, Ren X, Wang J et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Cutaneous lymphomas - an update.

This review updated the classification of primary cutaneous lymphomas (CL) and lymphoproliferative disorders (LPD), integrating the WHO 5th edition and the International Consensus Classification with recent clinicopathological and molecular advances. The key finding was that multiple previously provisional entities—such as primary cutaneous small/medium CD4+ T-cell LPD, primary cutaneous gamma/delta T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, and EBV-positive mucocutaneous ulcer—are now established. The clinical significance is improved diagnostic accuracy and more consistent categorization of cutaneous lymphoma subtypes, which directly affects prognosis and treatment selection.

Kempf W, Mitteldorf C · Histopathology · (2026) · View on PubMed ↗

Plasma proteome reflects tissue damage and clinical manifestations in patients with inflammatory myopathies.

This study analyzed whether plasma proteomics can reflect tissue damage and clinical manifestations across idiopathic inflammatory myopathy (IIM) subtypes in 201 patients, using Olink proximity extension assay to quantify >1000 proteins. The key finding was that plasma protein signatures tracked with disease activity and clinical manifestations, consistent with circulating markers derived from tissue injury. This is significant because it advances blood-based biomarker development for IIM, potentially enabling more precise monitoring and stratification of patients by tissue-relevant disease processes.

Luo YB, Kenrick J, Galindo-Feria AS et al. · Arthritis & rheumatology (Hoboken, N.J.) · (2026) · View on PubMed ↗ · Free PDF ↗

Micronutrition as a Therapeutic Strategy for Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Narrative Review.

This narrative review assessed micronutrition as a therapeutic strategy for mitochondrial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia. It summarizes evidence implicating oxidative/nitrosative stress, immune dysregulation, and altered redox and NAD+ metabolism, and discusses how micronutrients support mitochondrial bioenergetics, antioxidant defenses, and immune-metabolic regulation. The clinical significance is that it identifies mechanistic rationale and evidence gaps to inform future studies of targeted micronutrient interventions in these chronic multisystem disorders.

Abanades S, Fernández I, Capdevila N et al. · Nutrients · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on August 29, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.