PubMed Trending Research Digest — August 14, 2026

Automated digest · 98 articles · 15 research areas · August 14, 2026

Overview

This week’s digest is dominated by translational and mechanistic work that links upstream biology to measurable clinical outcomes—spanning neurodegeneration, cancer immunotherapy, and systemic disease. In Alzheimer’s disease, BBB leakage signals (CSF fibrinogen) tracked with subsequent tau accumulation in cognitively unimpaired older adults, while estrogen-only menopausal hormone therapy was evaluated for associations with Alzheimer’s biomarkers and outcomes. In parallel, multiple studies in cancer emphasized how microenvironmental and molecular context shapes therapy response: for example, ctDNA patterns may help stratify benefit from perioperative nivolumab, and tumor-stroma features (including N-glycans on TME cells) can impair CAR-T function in solid tumors. Several mechanistic cancer papers also highlighted actionable vulnerabilities—such as RNA exosome control of C9orf72 repeat translation to limit DPR toxicity, TDP-43–regulated ferroptosis evasion in lung adenocarcinoma, and succinate–GPR91 context dependence in rheumatoid arthritis inflammation.

A second major theme is improved risk stratification and precision implementation of care using modern data and trial designs. Central adiposity metrics (waist circumference/waist-to-hip ratio) reclassified cardiovascular risk beyond BMI across multiple outcomes, while guideline simulations (dyslipidemia) and large-scale prognostic models (e.g., cholangiocarcinoma ML risk prediction, geriatric Hodgkin lymphoma risk scoring) aim to better target prevention and surveillance. In cerebrovascular care, individualized blood pressure control during mechanical thrombectomy and intensive BP lowering after spontaneous intracerebral hemorrhage were tested/emulated to refine practical secondary prevention strategies. Across infectious disease and immunology, the microbiome and host-defense angle remained strong: maternal microbiomes shaped infant colonization trajectories, and multiple Plasmodium-focused studies explored plasmepsin inhibition as a route to more scalable malaria vaccination strategies.

Finally, several papers showcase emerging therapeutic modalities and platforms. These include living, glucose-sensing probiotics for diabetes; in vivo mRNA delivery systems to generate CAR T cells directly in the body; engineered Treg approaches using receptor-tethered orthogonal IL-2; and targeted immunomodulation strategies for neuroinflammation (e.g., nitrated α-synuclein CAR-Tregs for Parkinson’s). Together, the set reflects a broader shift toward mechanism-guided interventions—paired with better biomarkers, computational tools, and single-cell/multi-omics technologies—to increase the probability of durable clinical benefit.

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Neurodegeneration & Dementia Biomarkers

Efficacy and safety of filgotinib in patients with active radiographic and nonradiographic axial spondyloarthritis: results from OLINGUITO, a phase 3 trial consisting of 2 randomised, placebo-controlled, double-blind, parallel-group studies.

This phase 3 OLINGUITO program studied filgotinib, a JAK1 preferential inhibitor, for efficacy and safety in patients with axial spondyloarthritis (axSpA), including both radiographic (r) and nonradiographic (nr) disease, who had inadequate response or intolerance to at least two NSAIDs. Across two international randomized, double-blind, placebo-controlled parallel-group studies, patients were randomized 1:1 to filgotinib 200 mg once daily or placebo through week 16, stratified by hs-CRP level and prior biologic DMARD use. If filgotinib improves clinical outcomes with acceptable safety, it would strengthen evidence for JAK1 inhibition as a treatment strategy across the axSpA spectrum.

Baraliakos X, Maksymowych WP, Navarro-Compán V et al. · Annals of the rheumatic diseases · (2027) · View on PubMed ↗

Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology.

This cohort study tested associations between menopausal hormone therapy (MHT)—specifically estrogen-only use—and Alzheimer disease outcomes using two large datasets: National Alzheimer’s Coordinating Center (NACC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). The analysis evaluated relationships between MHT exposure and dementia outcomes as well as neuropathologic and imaging/fluid biomarker measures. The results help clarify whether estrogen-only MHT use is linked to Alzheimer disease neuropathology and related biomarkers.

Bruno J, Shaw JS, Hosseini SMH · Neurology · (2026) · View on PubMed ↗

CSF fibrinogen predicts longitudinal Tau accumulation in cognitively unimpaired older adults.

This cohort study tested whether cerebrospinal fluid (CSF) fibrinogen, a marker of blood–brain barrier (BBB) leakage, predicts longitudinal tau accumulation in cognitively unimpaired (CU) older adults. Baseline CSF fibrinogen was associated with subsequent increases in phosphorylated tau (pTau181) over time, indicating that BBB dysfunction may drive or accelerate tau pathology before cognitive impairment. Scientifically, it links vascular/BBB injury signals to early Alzheimer’s disease biomarker progression and supports fibrinogen as a prognostic CSF marker.

Lisgaras CP, Jacobs T, Figueredo L et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodevelopmental Disorders & Circuit Plasticity

Procognitive restoration of PV neuron plasticity in neurodevelopmental disorders.

This work investigated how restoring experience-dependent plasticity of hippocampal parvalbumin-expressing (PV) inhibitory neurons in neurodevelopmental disorder models can normalize downstream pyramidal neuron (PN) activity. The authors report that a procognitive intervention reinstated PV neuron plasticity, improving circuit-level control of PN firing and reducing hyperexcitability phenotypes. Clinically, targeting PV interneuron plasticity may offer a mechanism-based strategy to treat seizure-prone, cognition-impairing neurodevelopmental disorders.

Shih YT, Alipio JB, Klaft ZJ et al. · Nature · (2026) · View on PubMed ↗

Safety and efficacy of guanabenz in early-childhood onset vanishing white matter: primary analysis of a single-arm, phase 1/2 trial.

This single-arm phase 1/2 trial evaluated the safety, tolerability, and efficacy of the α2-adrenergic agonist guanabenz in young children (early-childhood onset) with vanishing white matter, a disease caused by defects in eukaryotic initiation factor 2B (eIF2B) and characterized by an integrated stress response. The key finding was the observed clinical safety/tolerability profile and preliminary efficacy signals of guanabenz in this pediatric population, consistent with its ability to inhibit the stress response. If efficacy is supported, guanabenz could represent a disease-modifying therapeutic approach for children with eIF2B-related vanishing white matter.

van der Knaap MS, Verbeek RJ, van Voorst RJ et al. · The Lancet. Neurology · (2026) · View on PubMed ↗

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Neuroimmunology & Autoimmune Neurology

Myasthenia thymus reprograms class-switched B cells into BAFF-dependent survivors.

This study investigated how the myasthenia gravis (MG) thymus alters B-cell fate and survival mechanisms using single-cell RNA sequencing, V(D)J repertoire analysis, and spatial transcriptomics in a large MG atlas (237,661 cells). It found a “tolerance checkpoint swap” in which pathological class-switched B cells in thymic germinal centers show reduced antigen presentation (CD74/CD1C) and diminished CD40 costimulation, enabling BAFF-dependent survivor persistence independent of canonical tolerance checkpoints. These findings explain why autoantibody titers can poorly predict severity and suggest thymic BAFF-dependent survival pathways as potential therapeutic targets.

Yan Y, Patino DA, Zhao Y et al. · Science advances · (2026) · View on PubMed ↗

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Neuroinflammation, Itch & Stress Circuits

Status-dependent competition engagement via mesocortical pathway.

This study used a win-maze behavioral task in mice to examine how prior outcomes shape the decision to re-engage in competition, focusing on neural dynamics in the mesocortical pathway. Dominant males showed a stronger preference to re-engage than subordinate males, and dorsomedial prefrontal cortex (dmPFC) population activity exhibited rotational dynamics with competition producing an enlarged loop trajectory within a competition-related latent space. These results clarify circuit-level mechanisms for status-dependent, outcome-dependent competition engagement and may inform models of adaptive decision-making.

Jin S, Liu Y, Wang T et al. · Neuron · (2026) · View on PubMed ↗

A prefrontal peptidergic circuit for psychogenic itch.

This study examined how psychological stress produces itch without peripheral stimuli in mice by mapping a peptidergic circuit in the medial prefrontal cortex (mPFC). Chronic restraint stress increased gastrin-releasing peptide (GRP) release and activated GRP receptor (GRPR)-expressing mPFC neurons, and GRP microinjection into the mPFC reproduced itch while GRPR neuron ablation abolished it. The results define a specific mPFC GRP–GRPR pathway for psychogenic itch, offering a mechanistic target for treating stress-related itch.

Zhang S, Qi Z, Luo H et al. · Science advances · (2026) · View on PubMed ↗

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Stroke & Cerebrovascular Trials

Advances in chronic subdural haematoma management: beyond the burr hole.

This review studied advances in chronic subdural haematoma management beyond traditional burr-hole drainage, synthesizing evidence from trials since 2020 on operative strategies and medical approaches. It found that routine steroid use is not supported by robust trial evidence and that minimally invasive middle meningeal artery embolisation is an important alternative for selected patients. Scientifically and clinically, the review emphasizes patient stratification and expanding treatment options to improve outcomes in an aging population with increasing incidence.

Edlmann E, Davies BM, Stubbs DJ et al. · The Lancet. Neurology · (2026) · View on PubMed ↗

Intensive blood pressure lowering after spontaneous intracerebral haemorrhage for secondary stroke prevention (RECAP-ICH): a systematic review and individual participant data meta-analysis.

This systematic review and individual participant data meta-analysis studied the effects of intensive blood pressure lowering after spontaneous intracerebral haemorrhage for secondary stroke prevention across subgroups and over time. The key finding was the pooled estimate of benefit (and heterogeneity/timing) of blood pressure-lowering treatment on major cardiovascular endpoints in patients with prior intracerebral haemorrhage. This is important for refining post-ICH blood pressure targets and optimizing secondary prevention strategies.

Wang X, Gao Y, Velasco MJ et al. · The Lancet. Neurology · (2026) · View on PubMed ↗

Individualized vs Standard Blood Pressure Control During Thrombectomy for Ischemic Stroke: The DETERMINE Randomized Clinical Trial.

This randomized clinical trial (DETERMINE) evaluated whether individualized blood pressure (BP) control during mechanical thrombectomy (MT) for acute ischemic stroke improves functional outcome at 90 days compared with a standard one-size-fits-all BP target. In an open-label, blinded-endpoint multicenter trial in France, adult patients with anterior large vessel occlusion undergoing MT were assigned to individualized versus standard BP management. The study directly tests a practical intra-procedural strategy to optimize safety and outcomes during thrombectomy.

Maïer B, Gory B, Chabanne R et al. · Neurology · (2026) · View on PubMed ↗

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Cardiovascular Risk, Lipids & Imaging

Intravenous Nicorandil in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: The CLEAN Randomized Clinical Trial.

This study quantified how the 2026 versus 2018 ACC/AHA multisociety dyslipidemia guidelines would change lipid-lowering therapy eligibility and treatment recommendations for U.S. adults using NHANES survey data (2011–2020). The key finding was the proportion and number of adults aged ≥20 years who would be eligible for initiation of lipid-lowering therapy under the newer guideline thresholds and risk calculators. These population-level estimates can help anticipate downstream impacts on prescribing, preventive care, and health system burden.

Huang D, Wu H, Lu Y et al. · Journal of the American College of Cardiology · (2026) · View on PubMed ↗

Hormone levels of female patients with SLE after anti-CD19 CAR T-cell treatment do not indicate a signal of impaired ovarian reserve.

This study examined whether central adiposity measures—waist circumference (WC) and waist-to-hip ratio (WHR)—reclassify cardiovascular risk beyond BMI across multiple cardiovascular outcomes in the Cross-Cohort Collaboration (CCC). WC and WHR improved risk reclassification compared with BMI-based categories, reducing misclassification of normal weight/overweight/obesity status for cardiovascular outcomes. Scientifically and clinically, it supports using central adiposity metrics to better stratify CVD risk, especially when BMI fails to capture body-composition heterogeneity.

Pecher AC, Henes J, Henes M et al. · Rheumatology (Oxford, England) · (2026) · View on PubMed ↗

Risk Reclassification Beyond BMI by Waist Circumference and Waist-to-Hip Ratio Across 9 Cardiovascular Outcomes: Results From the Cross-Cohort Collaboration.

This cross-cohort collaboration study quantified how waist circumference (WC) and waist-to-hip ratio (WHR) reclassify cardiovascular risk beyond BMI across nine cardiovascular outcomes. Central adiposity measures provided additional prognostic information and improved risk classification compared with BMI alone, which can misclassify individuals due to limited representation of body composition. The results support incorporating WC/WHR into cardiovascular risk assessment to better identify people at higher risk despite “normal” BMI.

Dardari ZA, Yao Z, Zhang J et al. · Journal of the American College of Cardiology · (2026) · 1 citations · View on PubMed ↗

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Cardiovascular Therapeutics & Devices

Conduction system vs. biventricular pacing in heart failure with reduced ejection fraction: a meta-analysis of randomized controlled trials.

This meta-analysis of randomized controlled trials compared conduction system pacing (CSP) versus biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) undergoing cardiac resynchronization therapy (CRT). Thirteen RCTs (1320 participants; 657 CSP, 663 BiVP) were synthesized using random-effects meta-analysis, and CSP was associated with a lower risk of the composite outcome reported in the abstract. If consistent across endpoints, CSP could be favored over BiVP as a physiologic CRT alternative for improving clinical outcomes in HFrEF.

Karakasis P, Vlachos K, Siontis KC et al. · Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · (2026) · View on PubMed ↗

Vutrisiran Treatment and Changes in Cardiac Parameters and Amyloid Burden Assessed by Cardiovascular MRI.

This analysis evaluated how vutrisiran treatment, an RNA interference therapeutic that suppresses hepatic TTR production, affects cardiac parameters and amyloid burden measured by multiparametric cardiovascular MRI in patients with transthyretin amyloid cardiomyopathy. Using CMR tissue characterization metrics such as extracellular volume (ECV) mapping, the study assessed associations between vutrisiran and changes in cardiac structure/function and amyloid-related measures. The findings extend HELIOS-B by linking TTR-lowering therapy to measurable cardiac remodeling and amyloid burden changes on high-fidelity imaging.

Razvi Y, Sheikh A, Patel RK et al. · JAMA cardiology · (2026) · View on PubMed ↗

Livestock Multi-Omics Integration: A Systematic Framework From Statistical Association to Causal Interpretation.

The CLEAN randomized clinical trial studied adjunctive intravenous nicorandil versus placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The key finding was the effect of nicorandil on 12-month clinical outcomes compared with placebo in this large multicenter, double-blind setting. If beneficial, nicorandil could become an evidence-based strategy to reduce reperfusion injury and microvascular obstruction after STEMI.

Wen J, Wang Z, Huang J et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Rethinking Disease Progression in Transthyretin Amyloid Cardiomyopathy: Toward Mechanism-Specific Monitoring and Therapeutic Response Assessment.

This JACC perspective/review discussed transthyretin amyloid cardiomyopathy and argued that current disease progression monitoring relies on downstream clinical/biomarker/functional measures rather than mechanism-specific processes targeted by therapies. The key finding is a conceptual framework calling for mechanism-specific monitoring and therapeutic response assessment as treatment classes (transthyretin stabilizers, gene-silencing therapies, and amyloid-depleting approaches) diversify. Clinically, this could improve how trials and practice evaluate progression and response, enabling more precise treatment decisions aligned to underlying biology.

Fontana M, Solomon SD, Hawkins PN et al. · Journal of the American College of Cardiology · (2026) · View on PubMed ↗

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Renal Disease & Kidney Outcomes

Comparative Effectiveness and Cardiovascular Safety of Romosozumab versus Teriparatide in Osteoporosis Patients with CKD: Target Trial Emulation Study.

This target trial emulation study compared cardiovascular safety and effectiveness of romosozumab versus teriparatide in osteoporosis patients with chronic kidney disease stages 3–5 using the TriNetX U.S. research network. After 1:1 propensity score matching, outcomes were analyzed with Cox proportional hazards models, showing comparative effectiveness and cardiovascular safety profiles between the two osteoporosis therapies in an eGFR <60 mL/min/1.73 m2 population. The study helps inform treatment selection for CKD patients where evidence for fracture prevention and cardiovascular risk is limited.

Hung CH, Yang FY, Huang HE et al. · Clinical journal of the American Society of Nephrology : CJASN · (2026) · View on PubMed ↗

The Impact of Renin-Angiotensin Aldosterone System Inhibitors in IgA Nephropathy: A Meta-Analysis of Randomized Controlled Trials.

This meta-analysis of randomized controlled trials evaluated the impact of renin-angiotensin-aldosterone system inhibitors (RAASi) on disease progression in IgA nephropathy. Across included RCTs, RAASi were assessed for their ability to slow kidney function decline and related clinical outcomes in IgAN patients. The synthesis supports evidence-based use (or refinement) of RAASi in IgAN to reduce long-term risk of end-stage kidney disease.

Rastogi A, Sarkar M, Kawai K et al. · Clinical journal of the American Society of Nephrology : CJASN · (2026) · View on PubMed ↗

Hepatic fibrosis severity assessed by FIB-4 index is independently associated with reduced kidney function in patients with metabolic dysfunction-associated steatotic liver disease: a nationwide multicenter study from Türkiye.

In a nationwide multicenter cross-sectional analysis of the Turkish DAHUDER MASLD Study, investigators assessed whether hepatic fibrosis severity estimated by the FIB-4 index is independently associated with reduced kidney function in metabolic dysfunction-associated steatotic liver disease (MASLD). The key finding was that higher FIB-4–defined fibrosis severity correlated with lower estimated glomerular filtration rate (eGFR) independent of other factors. This supports using FIB-4 as a noninvasive marker to identify MASLD patients at increased risk for chronic kidney disease.

Sumbul HE, Kirik A, Yaylaci S et al. · Hepatology international · (2026) · View on PubMed ↗

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Metabolic Health, Obesity & Diabetes Therapies

The Metabolic Revolution in Dermatology: Obesity, Insulin Resistance, and Ultra-Processed Diets as Drivers of Skin Inflammation.

This narrative review examined how systemic metabolic drivers—obesity, insulin resistance, and ultra-processed diets—contribute to skin inflammation across inflammatory dermatoses. The key finding is that metabolic dysregulation promotes a pro-inflammatory, Th1/Th17-skewed milieu via adipokines/cytokines and hyperinsulinemia/IGF-1 effects on keratinocytes, sebum production, and autoinflammation, linking these mechanisms to diseases such as hidradenitis suppurativa, psoriasis, atopic dermatitis, and others. This frames metabolic intervention as a potential adjunct strategy for managing inflammatory skin disease by targeting upstream systemic inflammation.

Khalaf R, Chow W, Lazarowitz R et al. · Journal of cutaneous medicine and surgery · (2026) · View on PubMed ↗

Changes in Muscle Mass and Quality Mediate the Effect of High-Calorie Intake on Clinical Outcomes.

This translational study examined whether early high-calorie full enteral nutrition alters skeletal muscle mass and quality to mediate clinical outcomes in critically ill patients, supported by a 72-hour ventilated piglet model with serial limb muscle ultrasounds and biopsies. The key finding was that changes in muscle mass and muscle quality mediated the effect of early high-calorie intake on downstream clinical outcomes, with associated molecular pathway changes identified in muscle tissue. Scientifically, it links early nutrition strategy to acquired muscle dysfunction via measurable structural and molecular mechanisms, informing interventions to improve outcomes in critical illness.

Aarab Y, Raynaud F, Capdevila M et al. · Journal of cachexia, sarcopenia and muscle · (2026) · View on PubMed ↗

Anti-Obesity Medications in Longevity and Aesthetic Medicine.

This narrative review evaluated anti-obesity medications, emphasizing GLP-1 receptor agonists (semaglutide, liraglutide) and the dual GIP/GLP-1 receptor agonist tirzepatide, in the context of longevity and aesthetic medicine. The key finding was that beyond weight loss, accumulating cardiovascular/renal outcome trial data and mechanistic/biomarker evidence suggest benefits that may intersect with aging biology. Clinically, it frames how current AOMs could influence long-term healthspan and appearance-related outcomes, guiding future research and patient counseling.

Bijoch J · Journal of clinical medicine · (2026) · View on PubMed ↗

Glucose-responsive probiotics for glycaemic modulation in mice and monkeys.

This study engineered an oral-deliverable, glucose-sensing probiotic living drug using a synthetic gene circuit with the glucose-responsive transcriptional regulator HexR to control glucose-lowering output in diabetic mice and monkeys. The engineered probiotic produced glucose-responsive functional responses that modulated blood glucose in a sense-and-respond manner without requiring external control or transplantation of mammalian gene circuits. These results advance a potentially safer, scalable “living drug” approach for diabetes therapy based on bacterial synthetic biology.

Guan N, Kong D, Gao X et al. · Nature · (2026) · View on PubMed ↗

Preoperative Glucagon-Like Peptide-1 Receptor Agonists and Postoperative Outcomes: An Observational Analysis.

This observational study assessed whether preoperative glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with postoperative outcomes in adult patients with type 2 diabetes undergoing anesthesia, using TriNetX electronic health record data from June 1, 2013 to June 1, 2023. Patients were propensity-score matched 1:1 by surgery type and patient characteristics to compare outcomes between those exposed to GLP-1 RAs preoperatively and those not exposed. The findings aim to inform perioperative risk management for patients on GLP-1 RAs in real-world practice.

Choi UE, Nicholson RC, Messinger C et al. · Anesthesiology · (2026) · View on PubMed ↗

Comparative risk of hepatocellular carcinoma and mortality among initiators of GLP-1 receptor agonists versus other glucose-lowering therapies: a target trial emulation.

Using a target trial emulation with PCORnet-UT Southwestern data (2010–2025), this study compared hepatocellular carcinoma (HCC) incidence and mortality among adults with type 2 diabetes initiating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus other glucose-lowering therapies. The key finding was the estimated association of GLP-1 RA initiation with HCC risk and subsequent all-cause mortality after HCC diagnosis in an active-comparator new-user design. If GLP-1 RAs alter HCC or mortality risk, these findings could refine diabetes medication selection for patients at risk of liver cancer.

Hernández-Pérez JG, Abdelgadir O, Jang S et al. · Hepatology international · (2026) · View on PubMed ↗

FDA Approval Summary: Erdafitinib for FGFR3-Altered Locally Advanced or Metastatic Urothelial Carcinoma.

This longitudinal study assessed reproductive endocrine markers in women with severe, treatment-refractory systemic lupus erythematosus (SLE) receiving autologous anti-CD19 CAR T-cell therapy (Miltenyi Biomedicine) to evaluate ovarian reserve and hypothalamic-pituitary-ovarian (HPO) axis function. The hormone trajectories after anti-CD19 CAR T did not indicate impaired ovarian reserve, suggesting preserved ovarian function despite prior concerns about gonadotoxicity. Clinically, this supports the reproductive safety profile of anti-CD19 CAR T in refractory SLE and informs counseling and fertility planning.

Maguire WF, Chang E, Mulkey F et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

Mechanisms and Predisposing Conditions for Statin-Induced New-Onset Type 2 Diabetes Mellitus: A Paradox Relative to Their Pleiotropic Metabolic Effects.

This review analyzed mechanisms and predisposing conditions for statin-induced new-onset type 2 diabetes mellitus (T2DM) despite statins’ pleiotropic metabolic effects. It synthesizes evidence that statin-associated T2DM risk reflects a paradoxical shift toward impaired glucose homeostasis under certain biological contexts (e.g., insulin sensitivity and insulin secretion pathways) rather than the expected antidiabetic benefits. The work is significant for clinicians and researchers because it frames when and why statins may increase T2DM risk, informing risk–benefit decisions and mechanistic research.

Andevari AN, Koolivand M · Endocrinology, diabetes & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer Immunotherapy & Cellular Therapies

Bacterial Outer Membrane Vesicle-Based Versatile In Situ Nanovaccine Enhancer Synergized With Radiofrequency Ablation Against Hepatocellular Carcinoma.

This preclinical study developed an outer membrane vesicle-based in situ nanovaccine enhancer, OMVbsAb-MAL, for local post–radiofrequency ablation (RFA) treatment of hepatocellular carcinoma (HCC). The key finding was that OMVbsAb-MAL—engineered with DEC205/PD-L1 bispecific antibodies and maleimide (MAL) to form thioether bonds with tumor proteins—captured tumor-associated antigens in situ and synergized with RFA to enhance antitumor immunity and reduce residual tumor immunosuppression. This is significant because it offers a strategy to improve the immunologic completeness of RFA and potentially overcome resistance to immune checkpoint inhibitors in early HCC.

Li Y, Liu K, Guo J et al. · Advanced healthcare materials · (2026) · View on PubMed ↗

The Great Debate: CAR-T-Cell Therapy Versus Bispecific Antibodies in B-Cell Lymphoma.

This narrative synthesis compared CAR-T-cell therapy versus CD20×CD3 bispecific antibodies (BsAbs) for relapsed/refractory large B-cell lymphoma using phase 2/3 trial data, real-world evidence, and meta-analyses. The key finding was that in the second-line setting, CAR-T therapy shows superior event-free survival and progression-related outcomes compared with BsAbs, while acknowledging differences in trial designs and patient selection. The clinical significance is that it helps clarify current equipoise and supports more informed treatment selection for R/R LBCL as randomized head-to-head data remain limited.

Martino M, Marafioti V, Pitea M et al. · Cancers · (2026) · View on PubMed ↗

TIM3-targeted delivery of venetoclax overcomes drug resistance and reinvigorates NK cell activity in acute myeloid leukemia.

This preclinical study developed VINCENT (VEN-integrated natural killer cell engager targeting TIM3), a nanoformulated venetoclax (VEN) platform combined with anti-CD16 and anti-TIM3 antibodies, to overcome VEN resistance in acute myeloid leukemia (AML). The key finding was that VINCENT overcame VEN resistance in VEN-resistant AML cell lines and patient-derived xenograft models by enhancing VEN delivery, eliminating TIM3+ blasts and dysfunctional T cells, and reactivating NK cell activity. This is clinically significant because it provides a targeted strategy to improve outcomes for older or unfit AML patients who fail or resist VEN-based regimens.

Wang Q, Li J, Zeng X et al. · Nature cancer · (2026) · View on PubMed ↗

In vivo genome-wide CRISPR screens of human T cells in solid tumours.

This study developed an in vivo model to efficiently recover human tumor-infiltrating T cells from solid tumors in mice, enabling genome-wide CRISPR knockout screening with few animals. The key finding was that T cells recovered from tumors show hallmarks of dysfunction distinct from splenic T cells, providing a physiologically relevant context for identifying genetic regulators of T cell performance in solid tumors. Scientifically, it establishes a scalable platform for in vivo CRISPR screens that can accelerate discovery of actionable targets to enhance cellular immunotherapy.

Liu Q, Chen PA, Urs E et al. · Nature · (2026) · View on PubMed ↗

Biomarkers of nivolumab benefit in resectable non-small cell lung cancer.

This analysis evaluated perioperative biomarker correlates of benefit from nivolumab versus placebo in resectable non-small cell lung cancer in the CheckMate 77T trial (NCT04025879), focusing on circulating tumor DNA (ctDNA) detection before neoadjuvant therapy and at completion. Among evaluable patients, ctDNA was detectable at both timepoints in most nivolumab- and placebo-treated participants, and the study identifies biomarker patterns associated with nivolumab benefit in event-free survival. Scientifically and clinically, ctDNA-based stratification could help select patients most likely to benefit from perioperative immune checkpoint blockade.

Cascone T, Awad MM, Spicer JD et al. · Nature · (2026) · View on PubMed ↗

An inherent T cell-activating mRNA delivery carrier for in vivo CAR T generation.

This study developed an inherent T cell-activating polymer–lipid nanoparticle carrier (ERTLNPs) using RT-modified oligoethylenimine-based lipid nanoparticles for ligand-free in vivo mRNA transfection and CAR T generation. The carrier enabled efficient mRNA delivery and T cell activation in vivo, with preferential transfection in the spleen after systemic administration, overcoming limitations of antibody-conjugated lipid nanoparticles. This supports a scalable, non-invasive route to generate CAR T cells directly in the body using mRNA delivery.

Cao Q, Yao Y, Zheng W et al. · Nature materials · (2026) · View on PubMed ↗

Molecular co-accessibility identifies coordinated regulation between distant cis-regulatory elements.

This preclinical study developed and tested nitrated α-synuclein-specific CAR-Treg therapy for Parkinson’s disease, generating regulatory T cells using CAR technology targeting nitrated α-synuclein (NαSyn) and using a human α-synuclein antibody recognizing three nitrated tyrosines (3NY-hαSyn). The key finding was that NαSyn-targeted CAR-Tregs can be generated with antigen specificity relevant to PD-associated nitrated α-synuclein and evaluated in preclinical models for therapeutic potential. This is significant because it supports a targeted immunomodulatory strategy aimed at T cell-mediated neuroinflammation in Parkinson’s disease.

Boulanger M, Chatsirisupachai K, Badayeva Y et al. · Molecular cell · (2026) · View on PubMed ↗

Cofilin1-driven cytoskeletal remodeling modulates pan-cancer CD8+ T cell immunotherapy responses.

This study integrated pan-cancer single-cell RNA sequencing data to identify cofilin 1 (CFL1) as a determinant of CD8+ T cell immunotherapy responses across tumor types. CFL1 overexpression synergized with CD8+ T cell-targeted immunotherapy by expanding intratumoral CD8+ T cells and physically sensitizing tumors, mechanistically via CFL1 hyperactivation that increased F-actin bundling/actin rod accumulation and cytoskeletal tension. These findings suggest CFL1-driven cytoskeletal remodeling could be leveraged to broaden and potentiate immunotherapy efficacy in otherwise “cold” tumors.

Li L, Chao Z, Li J et al. · Cell reports. Medicine · (2026) · View on PubMed ↗

Receptor-tethered orthogonal IL-2 enhances regulatory T cell therapy.

This preclinical study examined regulatory T cell (Treg) therapy using receptor-tethered orthogonal interleukin-2 (ortho IL-2) in a mouse model of autoimmune diabetes. The key finding was that infusing orthogonal IL-2 alone did not boost corresponding orthoIL-2 receptor–expressing Tregs, whereas engineering Tregs with an IL-2 tether to its receptor enabled selective autocrine signaling, increased CD25/CTLA-4/Foxp3, and improved Treg persistence without exogenous IL-2. This provides a mechanism-specific approach to deliver IL-2 preferentially to therapeutic Tregs while minimizing off-target IL-2 effects on other immune cells.

Indart AC, Lyu H, Nguyen VQ et al. · The Journal of experimental medicine · (2026) · View on PubMed ↗

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Cancer Targeted Therapy & Precision Oncology

SYS6010, epidermal growth factor receptor-targeting antibody-drug conjugate for advanced non-small cell lung cancer: A phase 1 trial.

This phase 1 clinical trial studied SYS6010, an epidermal growth factor receptor (EGFR)-targeting antibody-drug conjugate, in 236 patients with advanced non-small cell lung cancer (NSCLC) (ChiCTR2300072141). SYS6010 showed a dose-limiting toxicity at 6.4 mg/kg with subsequent cohort-expansion doses of 4.2, 4.5, and 4.8 mg/kg, and high treatment-related adverse events (TRAEs) with an objective response rate of 34.7% specifically in EGFR-mutant NSCLC previously treated with EGFR tyrosine kinase inhibitors (TKIs) and platinum chemotherapy. These results support further development of EGFR-targeted ADC therapy for EGFR-mutant, TKI- and platinum-exposed NSCLC while characterizing safety and response in this high-need population.

Li ZM, Zhou Z, He ZY et al. · Cancer cell · (2026) · View on PubMed ↗

Somatic alterations in TP53, PIK3CA, and CCND1 reveal exposure-driven patterns in oral and oropharyngeal tumors.

This study profiled 1,086 oral cavity (OC) and oropharyngeal (OPC) tumors (including 287 HPV-positive OPC) using a 1,109-gene panel to determine how somatic alterations in TP53, PIK3CA, and CCND1 reflect tobacco, alcohol, and HPV exposure patterns. The key finding is that PIK3CA alterations are widespread but context-specific—HPV-positive OPC shows APOBEC-driven mutations and a subset with FGFR3 co-occurrence, whereas HPV-negative OPC and OC show 3q26/28 amplifications (PIK3CA/TP63/SOX2)—and TP53 is most frequently mutated in HPV-negative tumors. These exposure-linked genomic signatures improve understanding of tumor etiology and may guide more tailored molecular risk stratification and therapy selection.

Cortez Cardoso Penha R, Virani S, Holt JR et al. · Journal of the National Cancer Institute · (2026) · View on PubMed ↗

Mechanistic and Clinical Differences Between Daratumumab and Isatuximab in Multiple Myeloma: Emerging Roles of 1q Gain and Immune Remodeling.

This review compared the mechanistic and clinical differences between daratumumab and isatuximab in multiple myeloma, despite both targeting CD38. The key finding was that differences in epitope recognition and immunomodulatory activity (including isatuximab’s near-catalytic-site binding leading to enzymatic inhibition and downstream effects such as FOXM1 suppression and reactive oxygen species–mediated cytotoxicity) suggest they are not fully interchangeable. This is significant because it supports more tailored selection of anti-CD38 antibodies based on tumor biology and immune remodeling factors such as 1q gain.

Kikuchi J, Yasui H · Cells · (2026) · View on PubMed ↗

First-line PD-1/VEGF bispecific antibody plus chemotherapy in triple-negative breast cancer: a phase 2 trial.

This open-label, multicenter, single-arm phase 2 trial studied first-line ivonescimab (PD-1/VEGF bispecific antibody) plus chemotherapy in female patients with locally advanced unresectable or metastatic triple-negative breast cancer (TNBC) who had not received prior systemic therapy. The study evaluated safety and efficacy using an ivonescimab 20 mg/kg IV every 2 weeks combined with paclitaxel or nab-paclitaxel on days 1, 8, and 15 of 28-day cycles. If effective, this regimen could provide a new first-line targeted immunotherapy approach for TNBC by simultaneously engaging PD-1 and VEGF signaling alongside standard taxane chemotherapy.

Shao X, Tian C, Chen Z et al. · Nature medicine · (2026) · View on PubMed ↗

Mefatinib versus gefitinib as a first-line treatment for EGFR-mutated non-small cell lung cancer: a randomized, double-blind, multicenter phase III study.

This randomized, double-blind, multicenter phase III trial compared the EGFR tyrosine kinase inhibitors mefatinib versus gefitinib as first-line therapy in 336 Chinese patients with advanced nonsquamous non-small cell lung cancer (NSCLC) harboring EGFR L858R or exon 19 deletion (ex19del). The primary endpoint was progression-free survival (PFS) assessed by an independent review committee, with patients assigned 2:1 to mefatinib 60 mg daily (n=223) or gefitinib 250 mg daily (n=113). Demonstrating superior PFS would support mefatinib as a more effective first-line EGFR-targeted option for this molecularly defined NSCLC population.

Yu J, Xiong A, Wang Q et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

Darolutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase 3 ARANOTE Trial.

This post hoc analysis of the phase 3 ARANOTE trial evaluated darolutamide plus androgen-deprivation therapy (ADT) versus placebo plus ADT by disease volume and risk subgroup in metastatic hormone-sensitive prostate cancer. Using CHAARTED-defined high-volume and LATITUDE-defined high-risk criteria, it assessed outcomes including radiologic progression-free survival (rPFS) and time to subsequent systemic therapy and progression to metastatic castration-resistant prostate cancer. Subgroup-specific benefit would refine how darolutamide is positioned for patients most likely to gain from intensified androgen-axis therapy.

Saad F, Shore N, Vjaters E et al. · European urology · (2026) · View on PubMed ↗

Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial.

This phase 3, open-label randomized trial studied belzutifan plus lenvatinib versus cabozantinib in adults with previously treated advanced clear-cell renal cell carcinoma after anti–PD-1/PD-L1 therapy. The key finding was the comparative efficacy and safety of the combination regimen versus cabozantinib as an active control in this post–immune checkpoint inhibitor population (primary endpoint results reported at week 48). Clinically, the trial informs whether belzutifan–lenvatinib can serve as a new standard option after prior checkpoint inhibitor treatment in advanced clear-cell RCC.

Motzer RJ, McDermott R, Park SH et al. · Lancet (London, England) · (2026) · View on PubMed ↗

COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib in BRAF V600-Mutant Advanced Melanoma.

This final extended follow-up analysis of the COMBI-I randomized trial evaluated long-term overall survival with spartalizumab plus dabrafenib and trametinib versus placebo plus dabrafenib and trametinib in BRAF V600-mutant advanced melanoma (NCT02967692; n=267 vs n=265). Although the primary endpoint of progression-free survival at 24 months was not met, the study reports overall survival over a median follow-up of 76.9 months, with median OS of 61.5 months in the spartalizumab arm versus 41.6 months in the placebo arm. The long-term OS results support continued assessment of spartalizumab-containing regimens for durable benefit in this molecularly defined melanoma population.

Ribas A, Robert C, Schadendorf D et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Proteogenomic characterization of pulmonary large-cell neuroendocrine carcinoma identifies molecular features and therapeutic strategy.

This study performed proteogenomic profiling of pulmonary large-cell neuroendocrine carcinoma (LCNEC) using tumor and paired adjacent normal tissues from 107 patients to define molecular features and therapeutic stratification. It identified APOBEC mutational signatures associated with tumor initiation and immune suppression, KEAP1 mutations linked to metabolic reprogramming (especially in combined LCNEC), and defined three LCNEC subtypes with distinct prognostic and microenvironment characteristics. The work provides a molecular framework for precision therapy selection in this aggressive NSCLC subtype.

Zhang L, Sun L, Duan S et al. · Science advances · (2026) · View on PubMed ↗

Upadacitinib for Severe Alopecia Areata in Adults and Adolescents: Two Phase 3 UP-AA Randomized Clinical Trials.

Two parallel phase 3 UP-AA randomized clinical trials evaluated upadacitinib, an oral selective Janus kinase (JAK) inhibitor, for severe alopecia areata in adults and adolescents. The key finding was the efficacy and safety profile of upadacitinib across the replicate trials (UP-AA1 and UP-AA2) for improving severe AA outcomes compared with placebo. These results support whether upadacitinib can expand systemic treatment options beyond existing therapies such as ritlecitinib for adolescent patients.

Mostaghimi A, Gooderham MJ, Lynde C et al. · JAMA dermatology · (2026) · View on PubMed ↗

Zolbetuximab plus pembrolizumab and chemotherapy in CLDN18.2-positive, HER2-negative, PD-L1-positive gastric or gastroesophageal junction adenocarcinoma: randomized, double-blind, phase III LUCERNA trial.

This randomized, double-blind phase III LUCERNA trial evaluated zolbetuximab plus pembrolizumab and chemotherapy in patients with CLDN18.2-positive, HER2-negative, PD-L1-positive locally advanced unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma. The study was designed to build on ILUSTRO’s phase 2 activity by testing whether adding the anti-CLDN18.2 antibody zolbetuximab to checkpoint inhibition and chemotherapy improves outcomes in this biomarker-defined population. If positive, the trial would expand targeted first-line options for CLDN18.2+/PD-L1+ gastric cancer and strengthen the clinical role of CLDN18.2-directed therapy.

Shitara K, Enzinger P, Lordick F et al. · ESMO gastrointestinal oncology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer Mechanisms, Resistance & Tumor Biology

Nucleoside-Modified mRNA Encoding Alpha-Galactosidase A Ameliorates Fabry Disease Phenotypes in Human IPSC-Derived Cardiomyocytes.

This preclinical study tested nucleoside-modified mRNA encoding alpha-galactosidase A (modGLA mRNA) in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as a model of Fabry disease. The key finding is that nucleoside-modified GLA mRNA delivery ameliorated Fabry disease phenotypes in these human cardiomyocytes, consistent with restoring lysosomal alpha-galactosidase A function to reduce globotriaosylceramide (Gb3) accumulation. This supports nucleoside-modified GLA mRNA as a potential therapeutic approach for Fabry disease, particularly for cardiac manifestations.

Juchem M, Oehlsen L, Ersoy S et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

RAN Translation-Coupled Decay of the C9orf72 GGGGCC Repeat Transcript by the RNA Exosome Suppresses Dipeptide Repeat Production.

This mechanistic study investigated how the RNA exosome regulates repeat-associated non-AUG (RAN) translation of the C9orf72 GGGGCC hexanucleotide repeat expansion (C9-HRE) transcript and suppresses dipeptide-repeat (DPR) production. The key finding was that RAN translation-coupled decay of the C9orf72 repeat transcript by the RNA exosome limits DPR generation, identifying a co-translational surveillance mechanism for toxic repeat RNAs. This is significant for C9-ALS/FTD biology because it reveals a potential therapeutic leverage point to reduce DPR toxicity by enhancing RNA exosome–mediated clearance.

Wu Y, Li L, Tian J et al. · International journal of molecular sciences · (2026) · View on PubMed ↗

Rb-driven transcription limits its tumour-suppressive effects in breast cancer.

This study examined how pharmacologically activated retinoblastoma protein (Rb) via CDK4/6 inhibition remodels chromatin and transcription in hormone receptor-positive (HR+) breast cancer cells. It found that CDK4/6 inhibition redistributes hypophosphorylated Rb to promoters and enhancers, where Rb not only represses canonical cell-cycle genes but also unexpectedly promotes expression of additional programs that limit Rb’s tumor-suppressive effects. The work suggests that combining CDK4/6 inhibitors with strategies to counteract Rb’s enhancer-associated transcriptional effects could improve therapeutic efficacy.

Watt AC, Ahn A, Blyth C et al. · Nature · (2026) · View on PubMed ↗

Epigenetic modulation of stromal cell states underpins pathological tissue niches in Crohn’s disease.

This study used single-cell spatial transcriptomics, RNA sequencing, and ATAC sequencing to map stromal cell states in human full-thickness Crohn’s disease (CD) bowel and determine how inflammatory niches arise. It identified 18 stromal states and showed that inflammatory fibroblasts are induced by combinatorial cytokines and stabilized by transcription factor activity involving GLI3, TWIST1, ETV4, PRDM1, and RELB without spontaneous reversion. These findings link specific epigenetic/transcriptional programs in stromal cells to pathological tissue niche formation, suggesting potential stromal-targeted strategies to modulate inflammation in CD.

Koplev S, Sharma O, Woelfel S et al. · Nature immunology · (2026) · View on PubMed ↗

N-glycans in non-malignant tumor microenvironment cells dampen CAR-T cell function in solid tumors.

This mechanistic study investigated how N-glycans on non-malignant tumor microenvironment (TME) cells impair CAR-T cell function in solid tumors, focusing on M2-like macrophages and hepatic stellate cells in liver metastases from colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). Using in vitro co-culture systems, transcriptomic analysis, and tumor-bearing humanized mouse models, it tested the contribution of TME N-glycans to CAR-T dysfunction. The results support targeting glycosylation pathways in the TME as a potential strategy to improve CAR-T efficacy in solid tumors.

Sirini C, Balestrieri C, Greco B et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

PGE2-mediated NK cell reprogramming drives acquired immunotherapy resistance in lung adenocarcinoma.

This study examined how PGE2 drives NK cell reprogramming to cause acquired immunotherapy resistance to PD-1 blockade in lung adenocarcinoma. In an orthotopic, bioluminescence-tracked Lewis lung carcinoma (LLC1) model in immunocompetent mice treated with anti-PD-1, tumor-intrinsic mediators of resistance were identified via an in vivo genome-wide CRISPR loss-of-function screen and validated with inducible tetracycline-off gene perturbation. Defining the PGE2–NK reprogramming axis provides actionable targets to overcome or prevent relapse after PD-1 therapy in lung adenocarcinoma.

Wang Y, Peng C, Feng S et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

Lactate promotes liver regeneration by increasing fatty acid oxidation through GCN5-mediated H3K9 lactylation.

This study examined how lactate and histone H3K9 lactylation regulate liver regeneration after 70% partial hepatectomy in mice, focusing on the lactyltransferase GCN5 and downstream gene programs using CUT&Tag and bulk RNA-seq, with validation in murine hepatocyte organoids and human liver tissue. Lactate promoted fatty acid oxidation and enhanced regenerative responses by increasing GCN5-mediated H3K9 lactylation (H3K9la), which coordinated expression of genes involved in metabolic remodeling. These findings identify a lactate–GCN5–H3K9 lactylation axis as a mechanistic target to potentially improve therapeutic strategies for liver repair.

Qiu X, Xu H, Meng L et al. · Cellular and molecular gastroenterology and hepatology · (2026) · View on PubMed ↗

TDP-43 drives ferroptosis evasion by modulating PCBP1/PCBP2 axis to promote lung adenocarcinoma growth.

This study investigated how TAR DNA-binding protein 43 (TDP-43) regulates ferroptosis to promote lung adenocarcinoma (LUAD) growth, focusing on the PCBP1/PCBP2 axis. TDP-43 was upregulated in LUAD and associated with worse prognosis, and TDP-43 knockdown impaired LUAD proliferation while promoting cell death, whereas TDP-43 overexpression promoted growth by modulating PCBP1/PCBP2-dependent ferroptosis evasion. These findings position TDP-43 and the PCBP1/PCBP2 pathway as potential therapeutic targets to restore ferroptosis sensitivity in LUAD.

Liu B, Chen X, Chen J et al. · Redox biology · (2026) · View on PubMed ↗

Mitochondrial stress activates ELT-2-dependent lysosomal proteostasis to extend lifespan in C. elegans.

This study tested how mild mitochondrial stress extends lifespan in Caenorhabditis elegans and identified the transcriptional and lysosomal mechanisms involved. Inhibition of mitochondrial respiration triggered an ELT-2–dependent program that increases lysosomal protease gene transcription and lysosomal proteolysis during aging, with the zinc-finger residue R249 required for ELT-2 activity. These results link mitochondrial stress to ELT-2–driven lysosomal proteostasis as a conserved longevity pathway and suggest ELT-2/lysosomal protease regulation as a potential target for lifespan extension strategies.

Yang R, Sun Y, Wang W et al. · Science advances · (2026) · View on PubMed ↗

Mito-TEMPO improves survival rates in npc1-knockout zebrafish by reducing oxidative stress and enhancing mitophagy via Sod2.

This study tested whether the mitochondria-targeted antioxidant Mito-TEMPO improves survival in npc1-knockout zebrafish and identified the downstream oxidative stress/mitophagy pathway. In NPC1-KO zebrafish, npc1 deficiency was associated with reduced Sod2 expression, excessive oxidative stress, mitochondrial dysfunction, and defective mitophagy, and Mito-TEMPO treatment improved survival by reducing oxidative stress and enhancing mitophagy via Sod2. The work supports Mito-TEMPO/Sod2 axis modulation as a candidate therapeutic strategy for Niemann-Pick type C disease.

Zhao W, Hu X, Wang R et al. · Science advances · (2026) · View on PubMed ↗

RNA terminal uridylyl transferases are druggable vulnerabilities in AML but are dispensable for normal hematopoiesis.

This study evaluated whether RNA terminal uridylyl transferases TUT4 and TUT7 are required for acute myeloid leukemia (AML) growth and whether they represent druggable vulnerabilities. Genetic deletion of TUT4/7 suppressed AML growth, induced apoptosis, and improved survival in leukemic mouse models, while a preclinical TUT4/7 inhibitor promoted cell death in patient AML samples and synergized with venetoclax. Mechanistically, TUT4/7 inactivation suppressed mevalonate pathway gene expression, linking RNA uridylation to metabolic control in AML.

Mapperley C, Georges E, Azar AA et al. · Science advances · (2026) · View on PubMed ↗

Succinate drives macrophage inflammation by promoting GPR91 mitochondrial signaling in rheumatoid arthritis.

This study examined how succinate drives macrophage inflammation in rheumatoid arthritis (RA) through GPR91 mitochondrial signaling and whether the receptor’s effects depend on succinate concentration. It found that at physiological succinate levels, membrane-localized GPR91 promotes M2 polarization via Gq-mediated phospholipase C and intracellular calcium signaling, whereas in RA elevated succinate induces GPR91 internalization and mitochondrial translocation to promote inflammatory programs. The results reconcile conflicting reports and support context-dependent targeting of the succinate–GPR91 axis in RA.

Zhang W, Wang L, Zhao Y et al. · Science translational medicine · (2026) · View on PubMed ↗

Blocking somatic repeat expansion and lowering huntingtin by RNAi synergize to attenuate Huntington’s disease pathogenesis in mice.

This study tested therapeutic divalent siRNAs targeting MSH3 (to block somatic repeat expansion), HTT (huntingtin) lowering, or both in Q111 Huntington’s disease mice (>110 CAGs). Combined MSH3 silencing plus HTT RNAi synergized to attenuate HD pathogenesis, including reduced mutant HTT burden and improved transcriptional dysregulation by 12 months. The results support a dual-mechanism RNAi strategy that simultaneously limits somatic expansion and toxic huntingtin species as a more effective preclinical therapeutic approach for Huntington’s disease.

Belgrad J, Summers A, Landles C et al. · Science translational medicine · (2026) · View on PubMed ↗

Mutant p53 reactivation and DNA demethylation in the treatment of AML/MDS.

This work examined whether arsenic trioxide (ATO) can reactivate mutant p53 in AML/MDS cells and whether this reactivation cooperates with the DNA hypomethylating agent decitabine. ATO-rescued mutant p53 strengthened interferon signaling by directly transactivating IRF7, and decitabine further enhanced ATO-rescued p53 activity via p53 serine-20 phosphorylation while blocking MDM2-mediated inhibition, leading to combined killing of p53-mutant AML cells and reduced tumor growth. Clinically, the study provides a mechanistic rationale for combining ATO with decitabine to restore p53-driven innate immune responses in p53-mutant AML/MDS.

Song H, Chen X, Xiao S et al. · Science translational medicine · (2026) · View on PubMed ↗

MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration.

This study investigated how microRNA-34a (miR-34a) regulates angiogenesis in an injury-induced murine model of choroidal neovascularization for age-related macular degeneration. miR-34a promoted pathological angiogenesis by suppressing KLF2 and activating the CXCR4/CXCL12 pathway, without changing Vegfa or Kdr expression. The findings identify a non-VEGF mechanism that could inform alternative therapeutic targets for neovascular AMD.

Colasanti JJ, Santeford A, Lin JB et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

New insights into the molecular regulation of bridge-like lipid transfer proteins revealed by the Atg2-Atg18 structure.

This mechanistic study investigated how the autophagy bridge-like lipid transfer protein (BLTP) Atg2 is regulated by Atg18 in the Atg2–Atg18 complex. Using structural analysis of the Atg2–Atg18 architecture, the authors showed that Atg18 stimulates Atg2 lipid-transfer activity to promote phagophore elongation at ER exit sites, enabling efficient autophagosome biogenesis. These findings clarify the molecular control of lipid transfer during autophagy and identify specific protein–lipid/protein interactions that could be targeted to modulate autophagy.

Chumpen Ramirez S, Shvarev D, Reggiori F et al. · Autophagy · (2026) · View on PubMed ↗

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Genomics, Epigenomics & Computational Biology

The eukaryote chromosome, a two-state system with interconversion by a volume phase transition.

This study investigated how eukaryotic metaphase chromosomes condense and decondense as a physical two-state system, using the concept of ionic hydrogels and volume phase transitions. The key finding is that chromosomal material behaves like a liquid–gas-like transition between condensed and decondensed states, with histone acetylation/deacetylation controlling ionic contacts between histone tails and DNA. This provides a mechanistic, physics-informed framework for chromosome condensation that links epigenetic histone modifications to large-scale genome organization.

Beel AJ, Matteï PJ, Kornberg RD · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Mechanistic machine learning for prediction of prime editing outcomes.

This paper developed OptiPrime, a mechanistic machine learning model to predict prime editing (PE) outcomes from pegRNA design, including PE3 nicking guide RNA and twin pegRNA (twinPE) configurations. OptiPrime achieved state-of-the-art PE efficiency prediction and learned determinants tied to mismatch repair (MMR), enabling nomination of MMR-evasive silent edits that improve PE efficiency. This provides a practical computational tool to reduce experimental optimization and increase the success rate of PE in mammalian genome editing.

Hsu A, Chen PJ, Li AH et al. · Nature biotechnology · (2026) · View on PubMed ↗

Simultaneous single-cell profiling of chromatin, transcriptome and surface markers with OneCell CUT&Tag captures epigenomic reprogramming.

This study introduced OneCell CUT&Tag to simultaneously profile chromatin, full transcriptomes, and surface markers from individual cells with input as low as one cell, without metacell aggregation. Using this approach, the authors uncovered epigenomic priming of mammary basal cells and captured basal-to-luminal transdifferentiation dynamics, linking epigenomic changes to transcriptional programs at single-cell resolution. The method enables mechanistic mapping of cell-state transitions in rare populations and should broaden single-cell multi-omic studies in development and disease.

Schwager A, Moutaux E, Durand A et al. · Nature biotechnology · (2026) · View on PubMed ↗

hnRNPK condensates facilitate enhancer-promoter looping and RNA polymerase II recruitment.

This study identified hnRNPK as an RNA-binding protein that facilitates enhancer–promoter looping and transcriptional activation by preferentially binding nascent RNAs from enhancer and promoter regions. It showed that hnRNPK forms phase-separated, cavity-containing condensates that encapsulate RNA polymerase II via the RPB3 subunit, promoting chromatin looping and potentially Pol II recruitment from enhancers to promoters. The work links a specific hnRNPK mutation to altered condensate function, providing mechanistic insight into how RNA-mediated nuclear organization controls gene expression.

Ye R, Zhao H, Chen J et al. · Nature genetics · (2026) · View on PubMed ↗

Preclinical evaluation of nitrated α-synuclein-specific CAR-Treg therapy in Parkinson’s disease.

This study investigated how distant cis-regulatory elements coordinate to regulate transcription in the Drosophila genome by using single-molecule footprinting together with long-read sequencing to measure co-accessibility and transcription factor binding across entire cis-regulatory landscapes. The key finding was that cis-regulatory elements form a coordinated network where chromatin accessibility and transcription factor binding co-occur in specific patterns, indicating coordinated regulation rather than independent enhancer activation. Scientifically, this provides a mechanistic framework for understanding how enhancer networks drive gene expression across large genomic distances.

Ugalde V, Elgueta D, Espinoza S et al. · Cell reports. Medicine · (2026) · View on PubMed ↗

A single-cell multi-omic atlas of the human pancreas reveals potential for cellular plasticity across development, health, and disease.

This work generated a single-cell multi-omics atlas of the human pancreas by profiling >4 million cells/nuclei from 57 donors spanning fetal development, adult homeostasis, and type 2 diabetes (T2D) using scRNA-seq/snRNA-seq, snATAC-seq, VASA-seq, Xenium spatial transcriptomics, and CODEX multiplexed proteomics. The authors identified transcriptionally plastic centroacinar-like cells (pCACs) and mapped gene expression, chromatin accessibility, and spatial organization changes associated with development and T2D. The atlas provides a high-resolution resource to study cellular plasticity mechanisms relevant to pancreatic disease and to guide future therapeutic targeting.

Mereu E, Balboa D, Liebig J et al. · Cell metabolism · (2026) · View on PubMed ↗

Mapping the architecture of protein complexes in Arabidopsis using cross-linking mass spectrometry.

This study mapped the architecture of protein complexes in Arabidopsis thaliana using an optimized cross-linking mass spectrometry workflow with the trifunctional PhoX cross-linker. Using pLink 3.2, the authors identified 52,944 unique cross-linked peptide pairs corresponding to 37,531 residue-level contacts across 5,064 proteins from whole-cell lysates, chloroplasts, and nuclei. The resulting large-scale structural proteomics resource enables improved mechanistic understanding of plant protein complex organization and gene function.

Trinh CS, Shrestha R, Mao P et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Biochemically Constrained Multi-Omics Integration Reveals Protein-Metabolite Dependencies Across Diseases.

This study introduced ProMetNet, a biochemically constrained multi-omics integration framework that combines proteomics and metabolomics by encoding protein–metabolite relationships using reaction topology from Reactome. By structuring cross-omics dependencies in neural network architecture rather than relying only on statistical associations, ProMetNet reduced spurious associations and improved stability in small clinical cohorts. The approach advances disease modeling by leveraging mechanistic biochemical constraints to better infer protein–metabolite dependencies across diseases.

Zhao M, Zhou N, Liu R et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

Lessons from a systematic review of family-based studies in ALS.

This systematic review evaluated family-based ALS gene-discovery studies across five pedigrees to identify unresolved linkage regions and causal genes. Reanalysis resolved two pedigrees by nominating FUS and SYNE1 as causal genes, while the remaining three pedigrees showed linkage to four unresolved regions with no convincing evidence for new ALS-causing variants using large-scale genetic datasets. These findings refine the genetic architecture of familial ALS and highlight that unresolved loci may stem from complex pedigrees (e.g., consanguinity or few affected individuals), guiding future gene-discovery strategies.

Wang BN, Van Der Spek RAA, Van Nispen Tot Sevenaer JDAM et al. · Amyotrophic lateral sclerosis & frontotemporal degeneration · (2026) · View on PubMed ↗ · Free PDF ↗

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Microbiome, Infection & Antiviral/Vaccine Strategies

A boost for chemical vaccination against malaria.

This Science commentary/article discusses chemical inhibition of Plasmodium plasmepsin proteins as a strategy to enable drug-based malaria vaccination. The key finding is that targeting plasmepsins can provide a “boost” to chemical vaccination approaches against malaria. This highlights plasmepsin inhibition as a promising platform for next-generation, potentially more scalable antimalarial vaccines.

Prudêncio M, Mota MM · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Chemovaccination with a late-liver-stage antimalarial induces durable immunity against malaria.

This preclinical study examined chemovaccination in mice using a single low-dose Plasmodium sporozoite exposure followed by treatment with plasmepsin IX and X (PMIX/X) inhibitors (WM382 or MK-7602) to induce chemo-attenuated liver merozoites (CALM). The key finding is that this regimen induced sterile, long-lasting immunity against malaria for up to 21 months, mediated by anti-circumsporozoite protein (CSP) antibodies and CD8+ T cells including liver-resident memory subsets recognizing diverse antigens (e.g., SERA1, RPL6, GAP50, RNT, PHIST, S20). This supports plasmepsin-targeted chemo-attenuation as a durable vaccination strategy that may reduce reliance on high-dose, complex sporozoite manufacturing.

Steel RWJ, Chua YC, Abdalla WAI et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Characterization of Sec14 Domain-Containing Proteins in the Malaria Parasite Plasmodium falciparum.

This study characterized Sec14 domain-containing proteins in the malaria parasite Plasmodium falciparum, focusing on Sec14-like phosphatidylinositol transfer proteins that regulate phosphoinositide-dependent membrane trafficking and signaling. The key finding is the identification and analysis of six P. falciparum Sec14 domain-containing proteins (including PfSec14-1, PF3D7_0626400, and others) to define their roles in parasite biology. This work identifies potential parasite vulnerabilities in phosphoinositide transport pathways that could be exploited for new antimalarial therapeutics, especially in the context of artemisinin resistance.

Lauruol F, Šťastný D, Fernandez-Murray JP et al. · Molecular microbiology · (2026) · View on PubMed ↗

Maternal influences on infant gut microbiome and health.

This study used metagenomic sequencing of 4,526 longitudinal fecal samples from 714 mother–infant pairs in the Dutch Lifelines NEXT birth cohort, integrating maternal diet, infections, and pre-pregnancy smoking with ultra-deep sequencing of breast milk and vaginal microbiomes. The maternal gut microbiome showed only subtle pregnancy/postpartum changes but acted as a major reservoir shaping the infant gut microbiome and early health trajectories. These findings support maternal microbiome modulation as a lever to influence infant colonization and downstream health risk.

Sinha T, Brushett S, Fernández-Pato A et al. · Nature · (2026) · View on PubMed ↗

Shared principles of human and bacterial antiviral immunity.

This Review synthesized evidence that antiviral immunity shares conserved principles across humans and bacteria, including pathogen recognition, signal amplification, and effector mechanisms. It argues that key components of human antiviral pathways are evolutionarily ancient and trace back to bacterial defenses against phage replication. The unifying framework helps explain host–virus interaction features and guides cross-kingdom discovery of antiviral strategies.

Kranzusch PJ · Nature · (2026) · View on PubMed ↗

PUF family RNA-binding proteins Puf1 and Puf2 promote transcript degradation in Toxoplasma gondii.

This study characterized the PUF family RNA-binding proteins TgPuf1 and TgPuf2 in the parasite Toxoplasma gondii and tested their roles in mRNA degradation. The authors identified conserved PUF members, assessed expression/localization and RNA-binding activity, and evaluated essentiality during asexual stages (with additional functional analyses described in the full text). Demonstrating that TgPuf1/TgPuf2 promote transcript degradation would advance understanding of post-transcriptional gene regulation mechanisms that support Toxoplasma life-cycle transitions.

Khandavalli CR, Gurupwar R, Deshmukh AS · The Journal of biological chemistry · (2026) · View on PubMed ↗

Direct bacterial transcript visualization illuminates spatiotemporal environmental adaptation of Mycobacterium tuberculosis in the lung.

This study developed and applied an HCR-FISH–based hybridization chain reaction fluorescence in situ hybridization method to visualize Mycobacterium tuberculosis (Mtb) mRNA in intact lung and lesion architecture. The technique enabled spatiotemporal mapping of bacterial transcript states within lesions, revealing how Mtb adapts to heterogeneous microenvironments during infection progression. This provides a powerful tool to connect in situ bacterial gene expression programs to lesion immune landscapes and potentially to treatment response.

Lawrence AE, Tan S · Science advances · (2026) · View on PubMed ↗

Full-length premembrane protein is not required for mature Zika virus particle assembly.

This study investigated whether full-length Zika virus (ZIKV) premembrane (prM) protein and furin-mediated proteolytic activation are required for flavivirus particle assembly. It showed that infectious virion biogenesis does not require an intact prM or proteolytic activation: expressing E protein with a truncated prM (M-E) was sufficient to form noninfectious ZIKV subviral particles and pseudo-infectious reporter virions. These findings refine understanding of flavivirus assembly requirements and could inform antiviral strategies targeting maturation steps.

Dowd KA, Schroeder M, Sanchez E et al. · Science translational medicine · (2026) · View on PubMed ↗

TBC1D23-AAVR interaction drives endosome-to-TGN trafficking required for rAAV transduction.

This study examined the intracellular trafficking mechanism of the adeno-associated virus receptor AAVR (KIAA0319L) during rAAV transduction, focusing on the interaction between AAVR’s cytosolic C-terminal domain (AAVR-C) and the trafficking adaptor TBC1D23. Using GST-fused AAVR-C pulldown to identify interacting host proteins, the authors found that TBC1D23-AAVR interaction drives endosome-to-trans-Golgi network (TGN) trafficking required for efficient rAAV transduction. Scientifically, the work clarifies a host trafficking step that can be targeted to modulate AAV delivery efficiency.

Zhang X, Habib A, McFarlin S et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

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Clinical Trial Methods, Risk Prediction & Health Services Research

Corticosteroids in ARDS: old controversies, new insights, and future directions.

This review article analyzed evidence on corticosteroid therapy in acute respiratory distress syndrome (ARDS), focusing on glucocorticoid receptor signaling and how timing and biological heterogeneity affect outcomes. The key finding is that clinical data support corticosteroids in moderate-to-severe ARDS—especially COVID-19 ARDS and severe community-acquired pneumonia—showing reductions in mortality and duration of mechanical ventilation, while effects vary by ARDS subphenotype (hyperinflammatory vs hypoinflammatory). This synthesis informs future trial design and patient stratification to optimize when and for whom corticosteroids are beneficial.

Daoud T, Villar J, Annane D · Intensive care medicine · (2026) · View on PubMed ↗

Effectiveness of the recombinant zoster vaccine in adult patients with multiple sclerosis: A claims-based retrospective cohort study in the United States.

This claims-based retrospective cohort study evaluated vaccine effectiveness (VE) of the recombinant zoster vaccine (RZV) in adults with multiple sclerosis (MS) in the United States using Medicare and commercial insurer data from 2018 to 2023. The key finding is that VE against incident herpes zoster (HZ) occurring at least 31 days after the second RZV dose was estimated using matched cohorts and Cox models with inverse probability of treatment weighting, providing real-world effectiveness evidence in an MS population. This supports evidence-based immunization decisions for adults with MS by quantifying RZV protection against HZ in routine clinical practice.

Kluberg SA, Mayer SE, Spence O et al. · Multiple sclerosis (Houndmills, Basingstoke, England) · (2026) · View on PubMed ↗

Development and Validation of a Novel Geriatric Risk Score for Prognostication in Older Patients With Hodgkin Lymphoma: A Multicenter Retrospective Study.

This multicenter retrospective study developed and validated a geriatric prognostic model in 306 Chinese patients aged ≥60 years with histologically confirmed Hodgkin lymphoma, using training/validation cohorts and integrating metabolic tumor burden with geriatric assessment. The key finding was that the novel geriatric risk score improved prognostic discrimination beyond commonly used tools such as the International Prognostic Score (IPS) and Comprehensive Geriatric Assessment (CGA). This supports more accurate risk stratification for older HL patients by combining disease burden with frailty-relevant geriatric factors to better guide clinical decision-making.

Zhao P, Wang Y, Bai M et al. · American journal of hematology · (2026) · View on PubMed ↗

Recent advances in the medical management of thyroid eye disease.

This narrative review summarized recent advances in the medical management of thyroid eye disease (TED), focusing on emerging targeted therapies and their clinical evidence. It found that intravenous methylprednisolone remains first-line for active moderate-to-severe TED but has limited efficacy for resolving proptosis and diplopia, motivating newer targeted approaches. The review is clinically significant because it frames how mechanism-driven therapies may improve outcomes beyond steroid-responsive soft-tissue inflammation.

Agarwal K, Rao-Waronski V, Thomas N et al. · Current opinion in endocrinology, diabetes, and obesity · (2026) · View on PubMed ↗

Faricimab for Polypoidal Choroidal Vasculopathy: 48-Week Results from the Phase 3b/4 SALWEEN Trial.

This phase 3b/4 SALWEEN trial evaluated faricimab for polypoidal choroidal vasculopathy (PCV) by reporting 48-week efficacy and safety outcomes in treatment-naïve Asian patients aged ≥50 years with symptomatic macular PCV. Participants received faricimab 6 mg every 4 weeks during a loading period to week 12, then a treat-and-extend regimen with Q8W–Q16W through week 48 and protocol-defined interval adjustments based on central subfield thickness and best-corrected visual acuity. If results show sustained anatomic and visual benefits with acceptable safety, faricimab could become an effective anti-VEGF pathway option for PCV using individualized dosing.

Cheung CMG, Lee WK, Chen SJ et al. · Ophthalmology. Retina · (2026) · View on PubMed ↗

Switch to once-weekly, single-tablet islatravir-lenacapavir from daily standard of care for HIV-1 (ISLEND-2): a multicentre, randomised, open-label, active-controlled, phase 3 non-inferiority trial.

This multicentre phase 3 non-inferiority trial evaluated switching virologically suppressed adults with HIV-1 from daily standard-of-care antiretroviral therapy to once-weekly single-tablet islatravir–lenacapavir (ISLEND-2). The primary week-48 results showed whether the once-weekly regimen maintained virologic suppression with acceptable safety compared with continued daily therapy. If non-inferiority was met, this would support a longer dosing interval strategy to improve treatment satisfaction while preserving efficacy in suppressed HIV-1 patients.

Colson AE, Kumar PN, Ruane PJ et al. · Lancet (London, England) · (2026) · View on PubMed ↗

The trajectory of inflammatory bowel disease in east and southeast Asia: transitioning from acceleration in incidence to compounding prevalence.

This epidemiologic analysis studied the population-level trajectory of inflammatory bowel disease (IBD) across east and southeast Asia, mapping transitions between emergence, incidence acceleration, prevalence compounding, and prevalence equilibrium. The key finding was that the region is transitioning from earlier acceleration in incidence toward increasing prevalence, with patterns reflecting differences in industrialization timing and healthcare/diagnostic expansion. This matters for public health planning because it predicts a growing IBD burden in newly industrialized settings and helps target prevention and resource allocation.

Okabayashi S, Hracs L, Windsor JW et al. · The lancet. Gastroenterology & hepatology · (2026) · View on PubMed ↗

Antiseizure medication use in pregnancy and the risk of poor fetal growth in the EURAP international registry: a prospective cohort study.

This prospective cohort study in the EURAP international registry examined whether antiseizure medication exposure during pregnancy is associated with poor fetal growth, comparing monotherapy versus polytherapy and specific antiseizure drugs and combinations. The key finding was the differential risk of poor fetal growth by antiseizure medication regimen type and by commonly used monotherapies/combination patterns. These results are clinically significant for counseling and selecting antiseizure therapy in pregnant people to reduce perinatal risk.

Perucca P, Malpas CB, Berry-Noronha A et al. · The Lancet. Neurology · (2026) · View on PubMed ↗

Machine learning for population-level risk prediction of future cholangiocarcinoma.

This study developed and validated machine learning models for population-level risk prediction of future cholangiocarcinoma using prospective multimodal data from 487,495 UK Biobank participants (649 incident cases), with development on England data and testing on withheld cohorts from Scotland, Wales, and Newcastle. Iterative ablation studies were used to identify which data modalities contributed most to prediction performance. If externally robust, the resulting ML risk stratification could enable earlier, cost-effective identification of individuals for CCA surveillance.

van Haag F, Clusmann J, Koop PH et al. · EBioMedicine · (2026) · View on PubMed ↗

Harmonizing Multi-Institutional Clinical Documentation Using Natural Language Processing in Neurofibromatosis Type 1.

This study examined whether physician-authored electronic health record (EHR) documentation of neurofibromatosis type 1 (NF1) features shows systematic lexical variation that could hinder computational phenotyping. Using natural language processing and machine learning approaches on multi-institutional clinical documentation, the authors characterized documentation variability relevant to harmonizing NF1 data for surveillance and trial readiness. The work supports improving NLP-based phenotyping pipelines for heterogeneous genetic disorders like NF1.

Morris SM, Kaster L, Amagai S et al. · Neurology. Clinical practice · (2026) · View on PubMed ↗

Prognostic and Predictive Effect of Age in Molecularly Defined Lower-Grade Gliomas.

This study analyzed whether age (18–39 vs ≥40 years) remains prognostic in molecularly defined lower-grade gliomas using the Prospective Gliomas Research (PROGRES) database of individual patient data from 11 prospective trials/registries. Across contemporary molecular definitions stratified by IDH1/2 status, age ≥40 was evaluated for associations with progression-free survival (PFS) and its prognostic/predictive relevance. The findings clarify how to apply guideline “high-risk by age” concepts in the molecular era for patients with IDH-mutant vs IDH-wildtype lower-grade glioma.

Kinslow CJ, Minniti G, Brown PD et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Predicting US Army Soldier Suicide-Related Behaviors at the Time of Periodic Health Assessments.

This study developed machine learning models to predict suicide-related behaviors among US Army soldiers at the time of periodic health assessments (PHAs) using administrative data from 2015–2019. The models were trained on 70% of PHA data for suicides and nonfatal suicide attempts to identify eligibility for a remote group dialectical behavior therapy-based skills training intervention. The work supports targeted, cost-effective deployment of preventive interventions by enabling risk stratification using routinely collected PHA information.

Edwards ER, Borowski S, Nock MK et al. · JAMA psychiatry · (2026) · View on PubMed ↗

Total Intravenous vs Volatile Inhalational Anesthesia for Major Noncardiac Surgery: A Randomized Clinical Trial.

This pragmatic multicenter randomized clinical trial studied whether total intravenous anesthesia (TIVA) versus volatile-based inhalational anesthesia improves recovery in older adults undergoing major noncardiac surgery in 49 UK National Health Service hospitals. The trial’s primary patient-centered outcome was days alive and at home at 30 days, with safety and recovery differences assessed between anesthesia strategies. If TIVA improves recovery without added risk, it could inform anesthesia selection to reduce postoperative morbidity and health care use in older surgical patients.

Jhanji S, Booth K, Hiller L et al. · JAMA · (2026) · View on PubMed ↗

Depression and SSRI Treatment During Pregnancy-Prioritizing Maternal Mental Health.

This JAMA Psychiatry article reviewed depression and selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy, focusing on maternal major depressive disorder (MDD) and perinatal-specific factors. It emphasizes that MDD is multifactorial and that perinatal pathophysiology and maternal stress/psychiatric illness can adversely affect outcomes, motivating careful treatment decisions. Clinically, the synthesis supports prioritizing maternal mental health while guiding evidence-based risk–benefit considerations for SSRI use in pregnancy.

Wisner KL, Oberlander TF, Osborne LM et al. · JAMA psychiatry · (2026) · View on PubMed ↗

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Generated automatically on August 14, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.