PubMed Trending Research Digest — July 11, 2026

Automated digest · 96 articles · 15 research areas · July 11, 2026

Overview

Across this week’s PubMed highlights, a clear through-line is the move from single-biomarker thinking toward mechanism-linked, risk-stratified care. Several studies connect measurable physiology or imaging surrogates to downstream outcomes—such as intramuscular fat infiltration and intrapancreatic fat deposition for thromboembolism and mortality risk, CT-defined emphysema phenotypes for AECOPD prognosis, and perfusion metrics for EVT selection in posterior circulation stroke. In parallel, multiple papers emphasize that “who benefits” depends on context: drug class and patient subgroup for arrhythmia risk with diabetes/HF therapies, phenotype and duration for severe asthma biomarkers and biologic responsiveness, and gene/phenotype-informed selection for hereditary ATTR amyloidosis.

A second dominant theme is translational biology using modern systems tools—multi-omics, spatial mapping, and computational modeling—to uncover hidden drivers and therapeutic leverage points. Examples include spatial multi-omics to reveal metastatic dormancy programs in colorectal cancer, transformer-based approaches for spatial cross-omics translation and long-horizon cardiovascular risk prediction, and multi-omic aging clocks that aim to quantify intervention effects. On the therapeutic frontier, the digest also features targeted immune and molecular strategies (e.g., dual-checkpoint NK-cell engineering, GDF-15 axis targeting beyond PD-1, and complement inhibition frameworks), alongside gene- and cell-based interventions such as AAV9-GBA1 delivery for lysosomal disease and stem cell–derived dopaminergic progenitors for Parkinson’s disease.

Finally, several articles underscore how environment and physiology shape disease trajectories through inflammation, microbiome, and metabolic/epigenetic pathways. Dietary sugar and EDC exposure link to biological aging and metabolic liver disease; tissue-resident microbiota shifts may help explain obesity-associated breast cancer risk; and multiple studies tie immune activation to specific signaling axes (IL-13 in cDC2-mediated anaphylaxis, IL-23R hypomorphic variants in tuberculosis susceptibility, and complement-mediated synapse loss in neurodegeneration). Together, these findings reinforce a broader message: modifiable exposures and pathway-specific interventions are increasingly measurable, targetable, and ready for more personalized clinical translation.

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Cardiomyopathy, Arrhythmia, and Cardiac Remodeling

Efficacy and Safety of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Ventricular Arrhythmias and Cardiovascular Events: A Disease-Stratified Network Meta-Analysis.

This disease-stratified network meta-analysis synthesized randomized controlled trials to compare sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for ventricular arrhythmias and cardiovascular outcomes in patients with type 2 diabetes mellitus and/or heart failure. The key finding was differential effects by drug class and patient subgroup on ventricular arrhythmia risk and downstream cardiovascular events. These results help clinicians choose glucose-lowering therapies with consideration of arrhythmia and cardiovascular risk profiles in T2DM/HF populations.

Sun WT, Liu RX, Jiang YH et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

Human embryonic stem cell-derived dopaminergic cells for Parkinson’s disease: a phase 1/2 open-label trial.

This phase 1/2 open-label multicenter trial studied STEM-PD, a cryopreserved off-the-shelf human pluripotent stem cell–derived dopaminergic progenitor product, in eight individuals with moderate Parkinson’s disease receiving bilateral intraputaminal transplantation at two escalating doses. At 12 months, the study reported primary safety outcomes and interim efficacy signals following transplantation of the dopaminergic progenitors. These results are clinically significant as they provide early evidence for feasibility and potential disease-modifying activity of stem cell–derived dopaminergic cell replacement in human Parkinson’s disease.

Paul G, Bjartmarz H, Kirkeby A et al. · Nature medicine · (2026) · View on PubMed ↗

Transformer-based models for predicting cardiovascular risk in Chinese adults: development and validation.

This study developed and validated sex-specific transformer-based deep learning models (China-AIHeart) to predict 10-year cardiovascular disease (CVD) risk in Chinese adults using data from the China Cardiometabolic Disease and Cancer Cohort and external validation cohorts in Xinjiang and CHARLS. The key finding was that transformer-based models improved CVD risk prediction performance compared with traditional Cox proportional hazards approaches in this population. Clinically, this supports deploying sex-specific transformer models for more accurate long-term CVD risk stratification in Chinese adults.

Cao Q, Xu X, Lin H et al. · European heart journal · (2026) · View on PubMed ↗

Standardized endpoint definitions for trials of transcatheter left atrial appendage closure: a consensus from the Left Atrial Appendage Academic Research Consortium†.

This consensus article from the Left Atrial Appendage Academic Research Consortium (LAARC) studied how to standardize endpoint definitions, data collection, analysis, and reporting for trials of transcatheter left atrial appendage closure (LAAC) across academic, regulatory, and clinical stakeholders. The key finding is the establishment of harmonized, trial-ready endpoint definitions intended to improve comparability and quality of LAAC studies. Scientifically and clinically, this framework should reduce heterogeneity across LAAC trials and facilitate evidence synthesis and regulatory evaluation.

Garot P, Mehran R, de Backer O et al. · European heart journal · (2026) · View on PubMed ↗

Left ventricular recovery and outcomes in patients with a durable left ventricular assist device: the EUROMACS registry.

This EUROMACS registry analysis studied left ventricular recovery after durable left ventricular assist device (LVAD) implantation by classifying changes in left ventricular ejection fraction (LVEF) from baseline to post-implant measurements and assessing predictors and clinical impact. The key finding was that the degree of LVEF recovery after LVAD support was associated with subsequent clinical outcomes, with recovery categories (no/mild/intermediate/greater) carrying prognostic differences. These results support using serial LVEF response to predict prognosis and guide management decisions in LVAD patients.

Sener YZ, Jahangiri P, Veen K et al. · European heart journal · (2026) · View on PubMed ↗ · Free PDF ↗

Resistant Hypertension Variants Link to Hyperaldosteronism and Potassium Levels.

This genome-wide association study characterized the genetic architecture of resistant hypertension (rHTN) and linked variants to hyperaldosteronism and potassium levels using 23,508 rHTN cases and 24,393 controlled hypertension (cHTN) controls defined by antihypertensive use and blood pressure response. The analysis identified genetic associations that connect rHTN susceptibility with pathways relevant to aldosterone biology and potassium homeostasis. These findings improve mechanistic understanding of rHTN and may support more targeted risk stratification for patients with hyperaldosteronism-related phenotypes.

Tragante V, Sulem P, Thorleifsson G et al. · Hypertension (Dallas, Tex. : 1979) · (2026) · View on PubMed ↗

Role of Perfusion Parameters on Outcomes and Safety of Endovascular Therapy in Posterior Cerebral Artery Stroke.

This prespecified secondary analysis of the international, multicenter PLATO registry assessed whether baseline perfusion imaging parameters predict outcomes and modify the effect of endovascular therapy (EVT) in isolated posterior cerebral artery occlusion (iPCAO). Using CT or MR perfusion imaging with reconstructed perfusion parameters, the study tested associations with 90-day outcomes and safety and whether perfusion metrics change the EVT–outcome relationship. The results aim to refine patient selection and procedural decision-making for EVT in iPCAO based on baseline cerebral perfusion physiology.

Diel NJ, Strambo D, Abdalkader M et al. · Stroke · (2026) · View on PubMed ↗

Hypoxia-Inducible Factor Prolyl Hydroxylase EGLN3 Stabilizes Atherosclerotic Plaques in ApoE-/- Mice Independently of Its Catalytic Activity.

This preclinical study tested whether the hypoxia-inducible factor prolyl hydroxylase EGLN3 (gene egl-9 in C. elegans) stabilizes atherosclerotic plaques in ApoE-/- mice independently of its catalytic hydroxylase activity. Using ApoE-/- mice with global EGLN3 deficiency, macrophage-specific EGLN3 deficiency, or EGLN3 hydroxylase-activity disruption, the researchers evaluated effects on NLRP3 inflammasome activation, vascular inflammation, and atherosclerosis development. The findings implicate EGLN3 as a regulator of plaque biology via inflammatory pathways beyond its enzymatic activity, informing potential targets for atherosclerosis modulation.

Jin Y, Xu L, Xiong Y et al. · Arteriosclerosis, thrombosis, and vascular biology · (2026) · View on PubMed ↗

AMPKγ2 Regulates Cardiac Hypertrophy and Arrhythmias via Interacting With Myosin.

The study investigated how PRKAG2 (AMPKγ2) variants drive cardiomyocyte hypertrophy and arrhythmias during early cardiac development using myocardium-specific transgenic zebrafish expressing wild-type Prkag2 or the pathogenic variant Prkag2 T299Q (TgR299Q). TgR299Q zebrafish developed hypertrophic cardiomyopathy phenotypes with electrical abnormalities consistent with disrupted AMPKγ2–myosin interactions. These findings mechanistically link PRKAG2 mutations to myosin-dependent cardiac remodeling, supporting PRKAG2/AMPKγ2 as a potential therapeutic target for hypertrophic cardiomyopathy with conduction disturbances.

Ge Q, Saha K, Burch ML et al. · Circulation research · (2026) · View on PubMed ↗ · Free PDF ↗

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Exercise, Rehabilitation, and Cardiovascular Risk Management

Comprehensive Care Goals in Myasthenia Gravis: Expert Consensus Recommendations Using the RAND/UCLA Appropriateness Method.

This work produced international expert consensus recommendations for comprehensive care goals in myasthenia gravis (MG) using the RAND/UCLA Appropriateness Method. The key finding is that structured, consensus-based guidance was developed to operationalize comprehensive care across MG management domains despite variable disease severity and presentation. This is significant because it provides a standardized framework to improve implementation of patient-centered care goals globally.

Narayanaswami P, Mantegazza R, Barnett-Tapia C et al. · Neurology. Clinical practice · (2026) · View on PubMed ↗

Exercise Training in High-Risk Populations: A Scientific Statement From the American Heart Association.

This American Heart Association scientific statement reviewed evidence for aerobic exercise training in high-risk cardiovascular populations, including frailty, stroke, spinal cord injury, rheumatologic disease, genetic cardiomyopathies, advanced heart failure recipients, and patients with cardiac implantable electronic devices. The key conclusion was that exercise training generally improves cardiorespiratory fitness and reduces adverse cardiovascular events, but requires population-specific screening, monitoring, and program modifications. Clinically, it provides guidance to safely extend exercise benefits to groups traditionally excluded from standard exercise recommendations.

Fleg JL, Golbus JR, Afilalo J et al. · Circulation · (2026) · View on PubMed ↗

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Thromboembolism and Venous Thrombosis Risk

Automated risk scoring for venous thromboembolism using large language models with expert knowledge-augmented prompting: a multicenter validation study.

This multicenter retrospective validation study developed automated venous thromboembolism (VTE) risk scoring using large language models (LLMs) with expert knowledge-augmented prompting for the Padua and Caprini scores. Using anonymized EHRs from 30 hospitals, the approach was evaluated across multiple open-source LLMs with stratified sampling for development and testing. The clinical significance is that LLM-based, prompt-engineered risk scoring could standardize VTE prevention workflows when structured data are incomplete.

Ma J, Wang D, Zhang Y et al. · NPJ digital medicine · (2026) · View on PubMed ↗

Aspirin for cancer prevention in individuals with Lynch syndrome: first results from the CaPP3 multicentre, randomised, double-blind, non-inferiority trial.

This randomized, double-blind, non-inferiority CaPP3 trial studied whether lower-dose aspirin (100 mg or 300 mg daily) is non-inferior to 600 mg daily for cancer prevention in Lynch syndrome carriers aged over 18 years across UK, Australia, Finland, Israel, and Spain. The key finding reported in the first results is the comparative efficacy/safety signal of the lower aspirin doses versus the 600 mg standard. If confirmed, this could directly inform dose selection for aspirin chemoprevention in Lynch syndrome to maintain benefit while potentially reducing dose-related toxicity.

Burn J, Borthwick GM, Elliott F et al. · The lancet. Gastroenterology & hepatology · (2026) · View on PubMed ↗

Colchicine as an Adjunctive Therapy to Improve Ischemic Stroke Reperfusion Outcomes in Mice.

This study tested colchicine, an FDA-approved microtubule inhibitor, as an adjunct to mechanical thrombectomy in a mouse model of acute ischemic stroke reperfusion. Colchicine improved ischemic stroke reperfusion outcomes by suppressing neutrophil-driven thrombo-inflammation, particularly neutrophil extracellular trap (NET)-mediated microvascular obstruction and subsequent neurovascular injury. The findings are significant because they support a repurposed, clinically actionable adjunct strategy to improve microvascular reperfusion and BBB-related damage after thrombectomy.

Wang D, Xiu Y, Shi M et al. · CNS neuroscience & therapeutics · (2026) · View on PubMed ↗

P2Y12 Inhibitors and Mortality in Patients Hospitalized With Intracerebral Hemorrhage.

This nationwide cohort study used the Get With The Guidelines-Stroke registry to compare stroke severity, in-hospital mortality, and functional outcomes in intracerebral hemorrhage (ICH) among patients receiving P2Y12 inhibitor monotherapy, P2Y12-based dual antiplatelet therapy (P2Y12 inhibitor plus aspirin), aspirin alone, or no antiplatelet therapy prior to ICH. The study’s central aim was to determine whether P2Y12 inhibitor exposure is associated with worse ICH outcomes relative to other antiplatelet strategies or none. Clinically, the results address a key decision point for antiplatelet management in patients at risk of ICH.

Jin C, Song Y, Mac Grory B et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Association of Intramuscular Fat Infiltration With Incident Venous Thromboembolism: A Population-Based Cohort Study.

This population-based cohort study examined whether thigh intramuscular fat infiltration (IMFI), a modifiable marker linked to inflammation and muscle weakness, is associated with incident venous thromboembolism (VTE) outcomes (pulmonary embolism and deep vein thrombosis) in 24,529 UK Biobank participants. Higher thigh IMFI was associated with increased risk of incident VTE, including both PE and DVT. The results identify IMFI as a potentially modifiable risk factor that could inform future VTE prevention strategies.

Wang N, Zhang Y, Zhang W et al. · Journal of cachexia, sarcopenia and muscle · (2026) · View on PubMed ↗ · Free PDF ↗

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Inflammatory Bowel Disease and Biologic Comparative Effectiveness

Real-World Efficacy of Ustekinumab versus Vedolizumab for Ulcerative Colitis: Differences between Short- and Long-Term Outcomes Based on Endoscopic Remission.

This retrospective real-world study compared ustekinumab (UST) versus vedolizumab (VED) for ulcerative colitis in patients treated at two tertiary centers, focusing on endoscopic remission defined by the Mayo Endoscopic Subscore (MES 0–1 and MES 0 alone) at 1 and 2 years. After inverse probability of treatment weighting to address baseline imbalances, the study found differences in endoscopic remission and related outcomes between UST and VED that varied by short- versus long-term follow-up. These findings help clinicians interpret comparative effectiveness of biologics in routine care, particularly for achieving and sustaining endoscopic remission.

Furuya M, Kato J, Takeuchi K et al. · Inflammatory intestinal diseases · (2026) · View on PubMed ↗ · Free PDF ↗

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COPD Phenotyping and Acute Exacerbation Prognosis

Celastrol alleviates airway remodeling in severe steroid-resistant asthma via AMOTL1-dependent restoration of Hippo/YAP signaling.

This study tested whether celastrol (CEL) can reverse airway remodeling in severe steroid-resistant asthma (SSRA) and whether the effect depends on AMOTL1-mediated restoration of Hippo/YAP signaling. In SSRA mice generated by OVA/CFA/LPS sensitization and challenge, CEL alleviated airway remodeling via AMOTL1-dependent reactivation of the Hippo/YAP (and downstream YAP/TAZ) pathway. These findings are clinically relevant because they suggest a mechanistically defined, non-steroid therapeutic route for irreversible remodeling in SSRA.

Sun J, Liu Z, Zhang Y et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Systemic Autoimmune Rheumatic Disease-Associated Interstitial Lung Disease: A Pulmonary Perspective on Recent Guidelines.

This guideline-focused review provided a pulmonary perspective on recent recommendations for systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD). The key finding was that disease course and progression risk vary by underlying rheumatic disease, radiologic phenotype, extent of involvement, and progression risk, making early recognition critical to prevent irreversible fibrosis. Scientifically and clinically, it emphasizes guideline-based evaluation and risk stratification to improve outcomes across heterogeneous SARD-ILD conditions.

Ozduygu G, Kaenmuang P, Guedes ABF et al. · Advances in therapy · (2026) · View on PubMed ↗

Longer Asthma Duration Is Associated With Elevated Non-T2 Sputum Biomarkers and Reduced T2 Inflammation in Severe Asthma.

In cross-sectional analyses of adults with severe asthma from U-BIOPRED and a validation cohort (PRISM), this study tested whether longer asthma duration correlates with sputum inflammatory biomarkers, including non-T2 and T2 markers. Longer duration was associated with elevated non-T2 sputum biomarkers and reduced T2 inflammation, even after adjusting for age, sex, ethnicity, BMI, smoking, and oral corticosteroid dose. This is clinically significant because it may help predict differential biologic responsiveness in severe asthma based on disease duration and inflammatory phenotype.

Yang F, Seo S, Hasegawa T et al. · Allergy · (2026) · View on PubMed ↗ · Free PDF ↗

Real-Life Effectiveness and Safety of Lebrikizumab in Elderly Patients with Atopic Dermatitis: A Multicenter Study.

This retrospective multicenter real-life study assessed the effectiveness and safety of lebrikizumab (an IL-13 monoclonal antibody) in 90 elderly patients (≥60 years) with moderate-to-severe atopic dermatitis across 23 Italian dermatology centers. EASI scores decreased substantially through weeks 16, 24, and 52, with EASI75 achieved in 58.4%, 82.0%, and 87.0% of patients, respectively. The findings support lebrikizumab’s clinical benefit and tolerability in an elderly AD population where evidence has been limited.

Napolitano M, Lauletta G, Cimmino M et al. · Clinical and experimental dermatology · (2026) · View on PubMed ↗ · Free PDF ↗

Clinical and prognostic differences in mild to moderate AECOPD with and without emphysema: a 3-year multicenter prospective study.

This 3-year multicenter prospective cohort study from the MAGNET AECOPD Registry evaluated whether CT-defined emphysema phenotype modifies clinical course and prognosis in hospitalized patients with mild-to-moderate acute exacerbation of chronic obstructive pulmonary disease (AECOPD) meeting Rome criteria. Patients with emphysema on early CT had worse long-term outcomes, including higher 3-year all-cause mortality and adverse rehospitalization patterns compared with those without emphysema. Scientifically and clinically, it supports using CT emphysema phenotyping at admission to risk-stratify mild-to-moderate AECOPD and tailor follow-up intensity.

Pu J, Yu M, Wei H et al. · Frontiers in medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Gene Therapy and Viral Vector Delivery (AAV/Enzyme Replacement)

Intra-CNS AAV9-GBA1 delivery yields species and route of administration differences in safety and transgene expression.

The study assessed safety, biodistribution, and transgene expression after intra-CNS AAV9 delivery of GBA1 (AAV9-GBA1 encoding glucocerebrosidase) in mice and non-human primates, comparing effects by species and route of administration. AAV9-GBA1 produced measurable CNS transgene expression and increased GCase activity, with safety and expression patterns differing by administration route and species. These data are significant for optimizing AAV9-based lysosomal enzyme delivery strategies for Gaucher’s disease and for related neurodegenerative indications involving GBA1 loss-of-function.

Amaral AC, Grubor B, Gianni D et al. · Molecular therapy. Advances · (2026) · View on PubMed ↗

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Surgical Risk Stratification and Perioperative Outcomes

Aberrant and Ectopic Cell Populations in Restrictive Allograft Syndrome after Lung Transplantation.

This study characterized restrictive allograft syndrome (RAS) after lung transplantation by profiling human lung tissue using single-nucleus RNA sequencing (snRNA-seq) in 15 RAS patients undergoing lung re-transplantation and 9 healthy controls. The key finding was the presence of aberrant and ectopic cell populations in RAS lungs, supported by validation/extension using histologic methods including immunofluorescence and RNA in situ hybridization. Clinically, this is significant because it identifies cellular programs associated with post-transplant fibrosis, potentially informing future therapeutic targets for RAS.

Leiber LM, Christian L, Neubert L et al. · The European respiratory journal · (2026) · View on PubMed ↗

Conversion to open surgery during robotic pancreatoduodenectomy in surgical high-risk groups: patterns, risk factors, and outcomes in elderly and/or obese patients.

This retrospective multi-institutional study evaluated conversion from robotic pancreatoduodenectomy (RPD) to open surgery in surgically high-risk patients defined as age ≥80 years and/or BMI ≥30 kg/m2. The study identified preoperative predictors of conversion and assessed how conversion affected postoperative outcomes specifically in elderly and/or obese groups. These findings are clinically significant for risk stratification and perioperative planning when attempting RPD in older and/or obese patients.

Marchese T, Valle V, Ielpo B et al. · Surgical endoscopy · (2026) · View on PubMed ↗

Long-Term Incidence of Peri-Implant Conditions: 25-Year Results of The Bernese Prospective Cohort Study.

This 25-year Bernese prospective cohort study evaluated implant survival, success, peri-implant mucositis (PM), peri-implantitis (PI), and loss of osseointegration in partially edentulous patients rehabilitated with tissue-level implant-supported prostheses. Implant failure was 1.2% at 10 years and 6.0% at 25 years, with implant survival rates of 98.8% and 94.0%, respectively, and the study assessed clinical/radiographic predictors of PM and PI at final follow-up. These long-term data inform risk estimation and long-horizon maintenance planning for peri-implant disease in real-world implant dentistry.

Couso-Queiruga E, Roccuzzo A, Raabe C et al. · Clinical implant dentistry and related research · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular Safety of Drugs (Real-world/Comparative)

Association of GLP-1RA discontinuation and risk of depressive and anxiety disorders in people with type 2 diabetes: a cohort study.

This large-scale cohort study using electronic health records from the Shanghai Hospital Link Database examined whether discontinuation of GLP-1 receptor agonists (GLP-1RAs) increases incident depressive and anxiety disorders in people with type 2 diabetes, compared with DPP-4 inhibitors and SGLT2 inhibitors. The key finding was that stopping GLP-1RAs was associated with a higher risk of subsequent depressive and anxiety disorders relative to comparator therapies. Clinically, it highlights a post-discontinuation psychiatric safety signal that may warrant monitoring and risk mitigation when de-escalating GLP-1RA treatment.

Zhang T, He P, Ji Y et al. · Nature metabolism · (2026) · View on PubMed ↗

Special Considerations When Using GLP-1 Receptor Agonists in the Treatment of Obesity and Diabetes Mellitus Type 2 in Older Adults.

This review article discussed special considerations for using GLP-1 receptor agonists in older adults with obesity and type 2 diabetes mellitus, focusing on age-related risks and comorbidity burden. The key message was that GLP-1 RAs (including agents such as tirzepatide and liraglutide) require tailored monitoring and risk mitigation in older patients due to adverse-effect susceptibility. Clinically, it supports safer prescribing and individualized benefit–risk assessment of GLP-1–based therapies in geriatric populations.

Pendrey AG, Rivera Sierra JA, Alvarez Lobo FA et al. · Advances in therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond Single-Class Therapy: Real-World Combined Use of GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes and Atherosclerotic Cardiovascular Disease.

This retrospective observational real-world study assessed factors associated with combined GLP-1 receptor agonist (GLP-1RA) and SGLT2 inhibitor use in 202 adults with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD). The key finding was identification of clinical characteristics linked to dual therapy adoption in routine practice. This informs how clinicians select and implement complementary cardiometabolic therapies outside randomized trials.

Vournas G, Sarvani A, Mavridou M et al. · Advances in therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Cardiovascular Safety of Romosozumab Versus Other Anti-Osteoporosis Medications in Patients with Osteoporosis: A Nationwide Health Insurance Claims Database Study in Japan.

Using Japan’s nationwide health insurance claims database, this study compared cardiovascular outcomes after initiation of romosozumab (Rmab) versus other anti-osteoporosis medications (parathyroid hormone analogues, denosumab, and bisphosphonates) in adults aged ≥50 years. The key result was the relative incidence of acute myocardial infarction, ischemic heart disease, and cerebrovascular disease within 570 days of treatment initiation across drug classes. This is important for evidence-based cardiovascular safety counseling when selecting osteoporosis therapies in real-world Japanese populations.

Fujita Y, Kouda K, Fujimori K et al. · Calcified tissue international · (2026) · View on PubMed ↗

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Diet, Metabolic Health, and Biological Aging

Association of Intrapancreatic Fat Deposition with Mortality: A Prospective Cohort Study with Genetic Risk Profiling.

This prospective cohort study in UK Biobank participants quantified intrapancreatic fat deposition (IPFD) by MRI and assessed its association with all-cause mortality using Kaplan–Meier and multivariable Cox models, alongside genetic risk profiling via GWAS and Mendelian randomization. Higher IPFD was associated with increased mortality risk after adjustment for clinical covariates. These findings support the PANDORA hypothesis that excessive IPFD is a clinically relevant risk marker for fatal outcomes in exocrine pancreatic disease pathways.

Dong X, Zhu Q, Huang Z et al. · The American journal of gastroenterology · (2026) · View on PubMed ↗

Biological aging clocks in health and disease.

This Nature Medicine review assessed how biological aging clocks—quantitative biomarkers derived from multi-omic and other data—track aging across individuals, organs, tissues, and cells, and how they can be used to evaluate interventions such as epigenetic reprogramming, thymus rejuvenation, and senolytics. The key finding is that biological clocks can stratify disease risk and serve as measurable endpoints for prevention/early detection and for testing whether interventions modulate the aging process. Scientifically, this frames aging clocks as translational tools for quantifying biological aging and accelerating evaluation of anti-aging strategies.

Wyss-Coray T, Topol EJ · Nature medicine · (2026) · View on PubMed ↗

Thalassaemia.

This study investigated how human stem cell–derived endocrine progenitors allocate α- versus β-cell fate, testing a model derived from mouse work involving cross-inhibition between ARX and PAX4. Using a newly generated human induced pluripotent stem cell reporter line (ARXCFP/CFP; PAX4mCherry/mCherry) combined with lineage labeling and single-cell multi-omics, the authors aimed to resolve whether ARX and PAX4 behave as the key fate determinants in humans. The significance is that clarifying ARX/PAX4-driven fate specification will improve the rational generation of functional, stem cell–derived islets for diabetes cell therapy.

Piel FB, de Montalembert M, Das R et al. · Nature reviews. Disease primers · (2026) · View on PubMed ↗

Cross-definition GWAS of IBS in 2.8 million individuals reveals cardiometabolic and triglyceride-linked mechanisms.

This cross-definition GWAS meta-analysis studied irritable bowel syndrome (IBS) using genetic data from 2,775,539 individuals across 22 biobanks, evaluating multiple ancestries, case definitions, and symptom-related subtypes. The key finding was that IBS genetic risk implicates cardiometabolic and triglyceride-linked mechanisms, supported by heritability/genetic correlation analyses and Mendelian randomization for causal inference. This is significant because it moves IBS toward actionable biological pathways that could enable biomarker development and mechanism-driven prevention or treatment.

Di Lorenzo B, Camargo Tavares L, Díaz-Muñoz C et al. · Gut · (2026) · View on PubMed ↗

Bridging omics and physiology to build multimodal clocks of human aging.

This article describes an approach to build multimodal clocks of human aging by integrating clinical data, multi-omics measurements, and organ-associated signatures to quantify biological aging across molecular, tissue, and physiological scales. The key finding is that a multi-layer framework can bridge omics and physiology to produce more comprehensive measures of aging heterogeneity. This is significant because it supports more precise, cross-scale biomarkers for aging and for evaluating interventions in human studies.

Koyuncu S, Petrovic D, Vilchez D · Cell · (2026) · View on PubMed ↗

Adaptation across an extreme elevational gradient in Andean leaf-eared mice, the world’s highest-dwelling mammal.

This study analyzed adaptation across an extreme elevational gradient in Andean leaf-eared mice (Phyllotis vaccarum), the world’s highest-dwelling mammal, integrating population genomics with physiological context. Population genomic analyses identified mechanisms of hypoxia adaptation and suggested an additional, unanticipated dimension of adaptation: selection on biotransformation pathways consistent with evolved capacity to metabolize plant-derived diet. These findings broaden understanding of how mammals adapt to combined hypoxia and dietary/biochemical challenges across very high elevations.

Liphardt S, Bautista NM, Quiroga-Carmona M et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Neuromuscular junction failure in sarcopenia is linked to NaV1.4 loss and reversed by ClC-1 inhibition.

This study examined neuromuscular junction (NMJ) failure in sarcopenia in weak older humans and aged rodent models, linking the phenotype to sodium channel NaV1.4 loss and testing whether it can be reversed by inhibiting the chloride channel ClC-1. The authors found that NMJ transmission failure correlated with muscle weakness severity in older individuals and that aged rodents showed similar NMJ excitability defects associated with localized NaV1.4 loss, which were reversed by ClC-1 inhibition. These results suggest a mechanistic and therapeutic pathway for sarcopenia-related NMJ dysfunction centered on NaV1.4 excitability and ClC-1–targeted rescue.

Arnold WD, Jeppesen Morgen J, Thomasen PB et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗

New-Onset Type 2 Diabetes Mellitus and Cancer Risk: A Matched Cohort Study in China Kadoorie Biobank.

This matched cohort study in the China Kadoorie Biobank evaluated the causal effect of new-onset type 2 diabetes mellitus (T2DM) on cancer risk using bias-minimizing design choices (including sequential longitudinal matching and pre-diagnosis BMI) and triangulation with two-sample Mendelian randomization in East Asians. The key finding was an association consistent with a causal increase in cancer risk after T2DM onset, supported by both time-split Cox modeling and Mendelian randomization analyses. Scientifically, it strengthens causal inference about T2DM as a driver of cancer risk and supports risk stratification for patients developing T2DM.

Wang M, Tipping O, Liu B et al. · International journal of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Frequent Sweetened Beverage Consumption Is Associated With Accelerated Biological Aging: Evidence From a Population-Based Study and Gut Microbiota Analysis.

In 9104 adults (18–80 years) from the WELL-China cohort, this population-based study assessed whether frequent sweetened beverage consumption is linked to accelerated biological aging and explored gut microbiota-related mechanisms. Frequent sweetened beverage intake was associated with increased Klemera and Doubal method (KDM)-derived biological age acceleration (BAacc) compared with non-consumption. This supports a mechanistic link between dietary sugar exposure, gut microbiome changes, and accelerated aging risk.

Shi Y, Li X, Hao Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Environmental Exposures and Metabolic Liver Disease

SLC22A3 regulates ferroptosis in the mesenchymal subtype of triple-negative breast cancer by modulating histone H3K4 serotonylation.

This study examined how SLC22A3 regulates ferroptosis in the mesenchymal subtype of triple-negative breast cancer (TNBC) by modulating histone H3K4 serotonylation. The key finding is that SLC22A3 influences ferroptosis sensitivity specifically in the MES TNBC context through an epigenetic mechanism involving H3K4 serotonylation. This is significant because it identifies a subtype-specific iron-dependent cell death control axis that could be exploited to improve ferroptosis-based therapies in aggressive TNBC.

Zhai D, Li W, Chen G et al. · Cell death & disease · (2026) · View on PubMed ↗

Dietary Guidelines 2025-2030 For Americans Are Concerning For Liver Health.

This analysis evaluated whether dietary components aligned with the 2025–2030 Dietary Guidelines for Americans (DGA-2025) are associated with steatotic liver disease (SLD), fibrosis, and cirrhosis risk in U.S. adults using NHANES 2017–2023 data (n=10,944) and vibration-controlled transient elastography (VCTE). The key finding is that the updated dietary guideline framework (including increased emphasis on total protein and omission of prior alcohol guidance) was concerning for liver health based on associations between guideline-aligned dietary exposures and liver outcomes. Scientifically and clinically, it suggests that the DGA-2025 changes may have unintended implications for liver disease risk and warrants refinement or targeted guidance.

Dunn N, Patel S, Díaz LA et al. · The American journal of gastroenterology · (2026) · View on PubMed ↗

Sex Differences in Long-Term Overall and Cause-Specific Mortality in Patients With Cirrhosis.

This population-based retrospective cohort study compared long-term all-cause and cause-specific mortality between male and female hospitalized adults with cirrhosis in the California Department of Healthcare Access and Information database (2005–2019), using propensity score matching to balance baseline characteristics. Female sex was associated with different long-term and cause-specific mortality patterns than male sex over follow-up. These findings help refine prognostic counseling and risk stratification for cirrhosis by sex in real-world clinical populations.

Su X, Xia L, Huang R et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Environmental Endocrine-Disrupting Chemicals and Metabolic Dysfunction-Associated Steatotic Liver Disease.

This systematic review and meta-analysis synthesized quantitative evidence on endocrine-disrupting chemical (EDC) exposure—phthalates, bisphenols, PFAS, POPs, and heavy metals—and its association with metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence. The key finding was an overall relationship between higher EDC exposure and greater MASLD prevalence across included studies. Clinically, this strengthens the rationale for considering environmental exposures as modifiable contributors to MASLD risk.

Zhao Y, He H, Zeng J et al. · Liver international : official journal of the International Association for the Study of the Liver · (2026) · View on PubMed ↗

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Microgravity, Spaceflight, and Osteoarticular Degeneration

Targeting AMPK signaling in nucleus pulposus cells ameliorates spaceflight microgravity-induced intervertebral disc degeneration.

This experimental study investigated how spaceflight microgravity induces intervertebral disc degeneration by focusing on nucleus pulposus (NP) cells and AMPK signaling, identifying PIEZO1 as a key upstream mediator. The authors found that space microgravity drives NP degeneration through PIEZO1 and that targeting AMPK signaling ameliorated microgravity-induced intervertebral disc degeneration. Scientifically, it links mechanosensing (PIEZO1) to metabolic signaling (AMPK) in microgravity-related disc pathology and suggests a potential therapeutic pathway for preventing IVDD.

Xie Z, Jiang B, Wang G et al. · Cell death and differentiation · (2026) · View on PubMed ↗

Characterisation of the thermal and non-thermal stress conditions that activate the Plasmodium falciparum AP2-HS-dependent heat-shock response.

This study characterized thermal and non-thermal stress conditions that activate the Plasmodium falciparum heat-shock response regulated by the transcription factor AP2-HS, using parasite exposure experiments under controlled stress regimes. The authors found that AP2-HS-dependent heat-shock gene induction can be triggered by mild heat-stress conditions that do not compromise parasite viability, defining specific activation thresholds and stress parameters. Scientifically, this maps how P. falciparum senses host fever–like temperatures to engage protective transcriptional programs, which may be relevant for targeting stress-response pathways in malaria.

Ràfols N, Nyarko PB, Chillarón-Adán M et al. · PLoS pathogens · (2026) · View on PubMed ↗

Kaempferol Attenuates Spaceflight-Associated Knee Cartilage Degradation by Targeting NOX4-Mediated Mitochondrial Dysfunction.

This study tested whether kaempferol protects against spaceflight-associated knee cartilage degradation by targeting NOX4-mediated mitochondrial dysfunction in mouse models and in human chondrocytes. Simulated microgravity and spaceflight increased inflammatory/senescence-related cartilage changes, while kaempferol attenuated degradation by interfering with NOX4-driven mitochondrial dysfunction. These results are scientifically significant for developing countermeasures to microgravity-induced osteoarticular damage.

Yin Y, Xu R, Makarczyk MJ et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Microbiome and Cancer Risk (Tissue-Resident/Mechanistic)

Human gut flagellome profiling using FlaPro reveals TLR5-related phenotype-specific alterations in IBD.

This study developed FlaPro, a computational pipeline to profile human gut flagellomes from metagenomic data and to functionally annotate flagellins based on predicted Toll-like receptor 5 (TLR5) binding and stimulatory activity. Applying FlaPro to individuals with inflammatory bowel disease (IBD) revealed TLR5-related, phenotype-specific alterations in the gut flagellin repertoire. The work provides a technique to connect individual flagellin composition to host innate immune activation, supporting mechanistic links between TLR5 signaling and IBD subtypes.

Bogdanova AA, Borbón-García A, Ley RE et al. · Gut microbes · (2026) · View on PubMed ↗

Obesity and Age Elevate Tissue-Resident Microbiota Akkermansia muciniphila to Induce Oxidative Stress and Promote Breast Cancer Risk.

Using non-cancerous breast tissue from postmenopausal women, this study examined how obesity and aging alter tissue-resident microbiota—focusing on Akkermansia muciniphila—and thereby relate to breast cancer risk. Obesity and aging interacted to shift breast tissue microbiome composition, with higher Akkermansia muciniphila abundance in obese postmenopausal patients and associated oxidative stress signals. This is important for identifying microbiome-linked pathways that may help explain obesity-associated breast cancer risk.

Clear KY, Arnone AA, Tsai YT et al. · Cancer research · (2026) · View on PubMed ↗ · Free PDF ↗

Immune regulatory mechanisms and potential microbiota-associated targets in Kawasaki disease: an integrative multi-omics and network pharmacology study.

This integrative multi-omics and network pharmacology study examined immune regulatory mechanisms and potential microbiota-associated targets in Kawasaki disease using gut microbiota–metabolite interaction analyses. It identified key molecular targets via network analyses and machine learning, used Mendelian randomization for causal validation, and applied single-cell transcriptomics plus molecular docking to map immune cell–metabolite and metabolite–protein interactions. The study proposes microbiota-linked regulatory pathways and candidate targets that could guide future mechanistic research and therapeutic development for Kawasaki disease.

Mei Z, Xiong X · Artificial cells, nanomedicine, and biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

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Hereditary Amyloidosis and Disease-Modifying Therapy Guidelines

Guidelines for the management of hereditary ATTR amyloidosis 2026.

This 2026 guideline document for hereditary ATTR amyloidosis (ATTRv) reviewed evidence and provided recommendations for disease-modifying therapy selection. It specifically states that TTR tetramer stabilizers (e.g., tafamidis) and TTR gene silencers (e.g., vutrisiran, patisiran, eplontersen, acoramidis, and others) should be used according to whether patients have ATTRv polyneuropathy (ATTRv-PN) and/or ATTRv cardiomyopathy (ATTR-CM). The clinical significance is standardized, gene- and phenotype-informed treatment guidance for hereditary ATTR amyloidosis worldwide.

Sekijima Y, Ueda M, Berk JL et al. · Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis · (2026) · View on PubMed ↗

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Brain Metastases and Neuro-Oncology Therapeutic Strategies

Long-term follow-up of a phase 1/2 trial of anti-GDF-15 antibody visugromab plus anti-PD-1 antibody nivolumab in anti-PD-1/-L1 relapsed/refractory solid tumors.

This long-term follow-up analysis of the phase 1/2a GDFATHER-01 trial studied visugromab (neutralizing anti-GDF-15 antibody) combined with nivolumab (anti-PD-1) in patients with anti-PD-1/PD-L1 relapsed/refractory solid tumors, including non-squamous non-small-cell lung cancer, urothelial carcinoma, and hepatocellular carcinoma. The study reports durable clinical activity and continued safety signals over extended follow-up for the V+N regimen in heavily pretreated populations. Clinically, it strengthens the rationale for targeting the GDF-15 resistance axis to improve outcomes beyond PD-1 blockade in refractory solid tumors.

Melero I, de Miguel M, Cabanas EG et al. · Journal of hematology & oncology · (2026) · View on PubMed ↗

Neuron-tumor communication in solid tumors: from bona fide synapses to pseudo-synaptic neural interfaces.

This Trends in Cancer review synthesized evidence on neuron–tumor communication in solid tumors, ranging from bona fide synapses in the brain to extracranial “pseudo-synaptic” neural interfaces and autonomic neuroimmune pathways. The key finding is that malignant cells can sense neuronal activity and convert neural signals into growth-promoting programs, with tumor–nerve interactions mediated by neurochemical niches, receptor-enriched contacts, and injury-associated neuroimmune signaling. Scientifically, this reframes tumor progression as partly driven by neural circuitry and highlights new mechanistic targets for future anti-cancer strategies.

Ren L, Liu C, Chen W et al. · Trends in cancer · (2026) · View on PubMed ↗

Plasma proteomics predicts pathological complete response and reveals LIF as a potential mediator of resistance to neoadjuvant immunochemotherapy in resectable NSCLC.

This study profiled pretreatment plasma proteomes using the Olink proximity extension assay in 86 patients with resectable non-small cell lung cancer (NSCLC) receiving neoadjuvant immunochemotherapy to identify biomarkers of pathological complete response (pCR) and resistance mechanisms. Differentially abundant proteins predictive of pCR were identified, and LIF (leukemia inhibitory factor) emerged as a potential mediator of resistance to neoadjuvant immunochemotherapy. These findings suggest a minimally invasive plasma proteomics approach and implicate LIF as a candidate target to improve response rates to neoadjuvant immunochemotherapy in resectable NSCLC.

Feng S, Feng Z, Xie S et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

GABA promotes resistance to immunotherapy in patients with TLS-positive tumors.

This study examined how GABA signaling affects immunotherapy response in tertiary lymphoid structure (TLS)-positive tumors using multi-omic profiling of clear cell renal cell carcinoma (ccRCC) and soft tissue sarcomas (STSs) and mechanistic experiments with human B cells. The key finding was that GABA-related signatures were enriched in non-responders, and GABA exposure impaired B cell maturation and function (including reduced HLA-DR expression and proliferation), contributing to resistance to immune checkpoint inhibitors (ICIs). These results suggest that targeting the GABA axis could help overcome TLS-associated resistance to immunotherapy.

Hernández-Verdin I, Calvez A, Sun CM et al. · Cancer cell · (2026) · View on PubMed ↗

Recent advances in Alzheimer’s disease: From molecular mechanisms to therapeutic strategies.

This review synthesized recent advances in Alzheimer’s disease (AD) research, emphasizing molecular mechanisms and therapeutic strategies, with particular focus on apolipoprotein E (APOE) biology and neuroimmunology. It highlights that disease-modifying therapies can slow cognitive decline by removing amyloid plaques, while preventing or stopping cognitive impairment remains unresolved. Scientifically, it integrates evolving multi-pathology concepts (amyloid plaques and neurofibrillary tangles alongside neurodegeneration drivers) to guide next-generation therapeutic development.

Rudman MD, Ulrich JD, Holtzman DM · Cell · (2026) · View on PubMed ↗

Triplet therapy with darolutamide and docetaxel for metastatic castration-sensitive prostate cancer: a multicenter real-world study.

This multicenter real-world retrospective study evaluated triplet therapy with darolutamide plus docetaxel in 112 patients with metastatic castration-sensitive prostate cancer (mCSPC). The study reported deep PSA responses (PSA <0.2 ng/mL or ≥90% decline) and analyzed castration-resistant prostate cancer (CRPC)-free survival, identifying clinicopathological factors associated with CRPC-free survival using Cox proportional hazards modeling. These findings provide clinically relevant real-world estimates of efficacy and toxicity signals for darolutamide–docetaxel triplet treatment in mCSPC beyond trial settings.

Tsuru I, Taguchi S, Tanaka R et al. · Japanese journal of clinical oncology · (2026) · View on PubMed ↗

C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain.

This work studied how complement component C1q and immunoglobulins contribute to activity-dependent synapse loss in the adult brain, using in vivo chemogenetic manipulation in mouse models. Neuronal hyperactivity induced region-specific, C1q-dependent synapse loss in the adult hippocampus, and suppressing perforant pathway hyperactivity in an Alzheimer’s disease model reduced amyloid-β, C1q deposition, and partially rescued synapse loss. The results support a causal role for C1q-mediated complement deposition in adult synaptic pruning triggered by neural activity, with implications for complement-targeted therapies in neurodegeneration.

Crowley G, Kim M, O’Neill N et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Neural circuits for valence updating in social memory.

This study examined neural circuits that update social valence during social memory by experimentally transforming a neutral conspecific into an aggressive one and tracking circuit changes. Valence updating required enhanced synaptic connectivity and physiological changes within a hippocampal ventral CA1 (vCA1)–basolateral amygdala (BLA)–nucleus accumbens (NAc) circuit, where vCA1 social memory engram neurons strengthened connections with BLA neurons carrying negative valence after defeat. These findings identify a circuit mechanism for dynamically revising social threat/affiliation memories, informing how brain networks encode changing social relationships.

Suto N, Wang MY, Morikawa S et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Neurofilament Light Chain as a Biomarker in Neurology.

This review synthesized evidence on neurofilament light chain (NfL) as a biomarker in neurology, including its diagnostic, prognostic, and therapeutic-monitoring performance across diseases such as multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis. The key finding is that NfL rises with neuroaxonal injury and correlates with inflammatory activity, lesion burden, and disability progression in multiple sclerosis, while also predicting severity and survival in ALS and reflecting neurodegeneration in Alzheimer’s disease. Clinically, the review emphasizes NfL’s broad sensitivity while outlining limitations and the complementary role of glial fibrillary acidic protein (GFAP) for interpreting CNS pathology.

Szyłak E, Czarnowska A, Kulczyńska-Przybik A et al. · European neurology · (2026) · View on PubMed ↗

Global Consensus on the Management of Primary Localized Chordoma.

This international multidisciplinary consensus update synthesized current evidence to guide diagnosis, treatment, and follow-up for pediatric and adult patients with primary localized chordoma. The key outcome was an expanded, updated set of recommendations reflecting advances in pathology, imaging, surgery, radiotherapy, and supportive care since the 2015 guidelines. Clinically, this provides a standardized framework to improve management decisions for a rare tumor with high local recurrence and substantial metastatic risk.

Radaelli S, Frezza AM, Fossati P et al. · JAMA oncology · (2026) · View on PubMed ↗

Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer: A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial.

This post hoc analysis of the global, double-blind, placebo-controlled phase 3 TOPAZ-1 randomized clinical trial evaluated 4-year overall survival and safety of durvalumab plus gemcitabine/cisplatin (GemCis) in adults with advanced biliary tract cancer. Durvalumab plus GemCis maintained an overall survival benefit versus placebo plus GemCis with comparable safety through longer follow-up. The results support durvalumab-based first-line chemoimmunotherapy as a durable treatment option for advanced biliary tract cancer.

Oh DY, He AR, Qin S et al. · JAMA oncology · (2026) · View on PubMed ↗

Neutrophils as chameleons of tissue inflammation and host-pathogen interactions.

This narrative review examined how neutrophils function as dynamic regulators of tissue inflammation and host-pathogen interactions, with emphasis on their roles in cancer and chronic inflammatory disease. The key finding is that neutrophils can drive immunomodulation through cytokine/chemokine production, reactive oxygen species, granule secretory proteins, and regulated inflammatory cell death pathways including neutrophil extracellular trap formation. Scientifically, it highlights neutrophil “chameleon” behavior as a mechanistic bridge between infection biology and therapeutic opportunities in cancer and chronic inflammation.

Zhu YP, Catz SD, Croker BA · Blood · (2026) · View on PubMed ↗

Consolidative Thoracic Radiotherapy With Atezolizumab Maintenance in Extensive-Stage Small Cell Lung Cancer: The Phase 2 TREASURE Randomized Clinical Trial (AIO-TRK-0320).

This multicenter open-label phase 2 randomized clinical trial tested whether adding consolidative thoracic radiotherapy (TRT) to immunotherapy maintenance improves outcomes and safety in extensive-stage small cell lung cancer (ES-SCLC) in Germany and Austria (2020–2022). The study evaluated overall survival and progression-free survival for patients receiving consolidative TRT alongside atezolizumab maintenance compared with the trial control strategy. If beneficial, this approach could refine first-line treatment sequencing by integrating radiotherapy with maintenance immunotherapy in ES-SCLC.

Bozorgmehr F, Chung I, Behnisch R et al. · JAMA oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Neurotropism and Therapeutic Targeting of Brain Metastases in Small Cell Lung Cancer.

This Cancer Research review summarized mechanisms of neurotropism and therapeutic targeting of brain metastases (BM) in small cell lung cancer (SCLC), including tumor–astrocyte/microglia interactions and neuronal mimicry. It highlights emerging intracranial-active targets such as DLL3 and B7H3 while emphasizing ongoing challenges like treatment resistance and limited brain drug penetration. The significance is to guide future therapeutic development and trial design for SCLC patients at high risk of BM.

Sen T, Gobbini E, Mustafayev K et al. · Cancer research · (2026) · View on PubMed ↗

The European Association for Neuro-oncology (EANO) Consensus Statement on Radiation Necrosis.

This study developed a European Association for Neuro-Oncology (EANO) consensus statement on radiation necrosis (RN) in neuro-oncology using a three-round Delphi process among 20 European experts. The panel reached consensus (≥80% agreement) on 53 statements covering RN diagnosis and management, including how to distinguish RN from tumor recurrence. This provides a standardized, evidence-informed framework to guide clinical decision-making for RN in patients with brain tumors receiving radiotherapy.

Duerinck J, Van Den Bent M, Brandal P et al. · Neuro-oncology · (2026) · View on PubMed ↗

NAD+ modulates REST isoform expression and its downstream mitophagy in Alzheimer’s disease.

This experimental study investigated how NAD+ modulates REST (repressor element 1-silencing transcription factor) isoform expression and downstream mitophagy in models of Alzheimer’s disease. Activation of the NAD+-SIRT1 axis increased REST nuclear activity, restored REST-linked mitochondrial/neuroprotective gene programs, and reduced pathological and cognitive decline in experimental AD models. The work identifies the NAD+-SIRT1–REST pathway as a potential therapeutic target to preserve mitochondrial quality control and neuronal function in Alzheimer’s disease.

Lagartos-Donate MJ, Escobar-Doncel B, Zhang CS et al. · Autophagy · (2026) · View on PubMed ↗

Complement System Inhibitors in Nephrology: A Comprehensive Review.

This comprehensive review synthesized evidence on complement system inhibitors in nephrology, focusing on how complement dysregulation drives kidney injury and how targeted inhibition is being translated into therapy. It highlights established terminal complement inhibitors (eculizumab and ravulizumab) and discusses emerging agents across complement pathways for kidney diseases associated with poor outcomes. Clinically, the review frames complement inhibition as a therapeutic paradigm shift and summarizes current and future options for nephrology practice.

Mathew GG, Lakshmikanthan RR, Jenishbabu A et al. · Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia · (2026) · View on PubMed ↗

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DNA Repair, Genomic Stability, and Genome Defense

Advancements in extracellular vesicle research.

This article reviews recent advances presented at the 2026 AAEV (American Association of Extracellular Vesicles) Annual Meeting on extracellular vesicle (EV) biology and translational applications across immune modulation, tissue regeneration, cancer progression, and metabolic regulation. The key message is that EVs—nanoscale lipid-bound particles carrying proteins, nucleic acids, and lipids—are increasingly recognized as actionable mediators of intercellular communication with expanding experimental and clinical research momentum. Scientifically, it consolidates current EV methodologies and highlights how improved EV characterization and engineering could accelerate biomarker and therapeutic development.

Li B, Kalluri VS, Weaver AM et al. · Extracellular vesicle · (2026) · View on PubMed ↗

NicheTrans: spatial-aware cross-omics translation.

This study introduced NicheTrans, a spatially aware cross-omics translation method using a Transformer-based multimodal framework, to integrate spatial microenvironment information with multi-omics data. NicheTrans improved translation performance over single-omics approaches and enabled discovery of spatial multiomics domains not detectable when analyzing single modalities alone. Scientifically, it provides an interpretable computational tool to map spatially structured molecular programs across omics layers.

Wang Z, Zou Q, Lin S et al. · Nature methods · (2026) · View on PubMed ↗

A micropeptide encoded by the lncRNA USP30-AS1 promotes tumor growth by attenuating cGAS-STING-type I IFN signaling in macrophages.

This mechanistic cancer study identified a micropeptide encoded by the lncRNA USP30-AS1 (UEIS) and tested its role in tumor-associated macrophages and antitumor immunity. UEIS promoted tumor growth by attenuating cGAS–STING–type I interferon signaling in macrophages, including via a negative feedback mechanism on type I IFN pathways. These findings suggest USP30-AS1–UEIS as a targetable immunosuppressive axis that could potentially enhance the efficacy of immune checkpoint blockade.

Wang X, Zhang Y, Ma J et al. · Nature cancer · (2026) · View on PubMed ↗

KRAS-G12D inhibitor HRS-4642 plus chemotherapy in advanced KRASG12D-mutant pancreatic cancer: a phase 1b/2 trial.

This phase 1b/2 clinical trial evaluated the KRAS-G12D inhibitor HRS-4642, formulated as a liposomal nanoparticle for intravenous delivery, in combination with chemotherapy (nab-paclitaxel and gemcitabine) in patients with advanced KRASG12D-mutant pancreatic ductal adenocarcinoma. The study assessed safety and preliminary efficacy of the HRS-4642 plus chemotherapy regimen, aiming to improve tumor exposure and target inhibition compared with prior oral KRAS-G12D inhibitors. Clinically, it tests a next-generation KRAS-G12D targeting strategy for a high-need molecular subset of PDAC.

Cui J, Jiang K, Li W et al. · Nature medicine · (2026) · View on PubMed ↗

Intracellular iron homeostasis-regulated epigenetic reprogramming contributes to -7/del(7q) leukemia.

This work studied how intracellular iron homeostasis–regulated epigenetic reprogramming contributes to -7/del(7q) acute myeloid leukemia, focusing on the mitochondrial iron transporter ABCB8 and the histone demethylase KDM6A. In hematopoietic stem and progenitor cells, a differentiation CRISPR screen identified ABCB8 as essential for differentiation, and ABCB8 deficiency disrupted iron homeostasis, reduced cytoplasmic iron availability, impaired iron-dependent KDM6A activity, and accelerated leukemogenesis in vivo. These findings are significant because they link a specific iron-transport gene (ABCB8) to epigenetic control and tumor suppression in -7/del(7q) leukemia, suggesting iron/epigenetic pathways as therapeutic targets.

Zheng J, Peng Y, Deng X et al. · Nature communications · (2026) · View on PubMed ↗

Multifunctional-engineered NK cells overcome tumor immunosuppression by combining PD-L1 and HLA-E targeting and endogenous IL15 production.

This study engineered next-generation NK cells using a tri-cistronic retroviral vector to overcome tumor immunosuppression by simultaneously targeting PD-L1 and HLA-E and producing endogenous IL-15. The key finding was that pan-cancer transcriptomic analyses showed consistent co-expression of PD-L1 and HLA-E across tumors associated with immune infiltration and strong immunosuppression, motivating the dual-target design. Clinically, this is significant because it provides a rationale and platform for NK-cell immunotherapy that attacks redundant checkpoint escape mechanisms while enhancing NK survival and function via IL-15.

Fiore PF, Forcelloni S, Moretta L et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

Temocillin versus carbapenems for bacteraemia due to third-generation cephalosporin-resistant Enterobacterales in Spain (ASTARTÉ): a multicentre, phase 3, open-label, non-inferiority, randomised clinical trial.

This multicentre phase 3 open-label non-inferiority randomized clinical trial (ASTARTÉ) studied intravenous temocillin versus carbapenems (meropenem) for bacteraemia due to third-generation cephalosporin-resistant Enterobacterales in 29 Spanish hospitals. The key finding was that temocillin was evaluated as non-inferior to carbapenems for targeted treatment of these infections. Clinically, this supports an evidence-based carbapenem-sparing strategy to reduce selection pressure in 3GCR-E bacteraemia.

Dezza FC, Pulido LB, Borreguero IB et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Fixed-duration pirtobrutinib plus venetoclax-rituximab versus venetoclax-rituximab for patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (BRUIN CLL-322): an open-label, multicentre, randomised, controlled, phase 3 trial.

This open-label, multicentre phase 3 randomized controlled trial (BRUIN CLL-322) studied whether adding pirtobrutinib, a non-covalent BTK inhibitor, to fixed-duration venetoclax-rituximab improves outcomes versus venetoclax-rituximab alone in previously treated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL). The key finding is the efficacy/safety comparison of the fixed-duration pirtobrutinib plus VR regimen against VR alone after prior covalent BTK inhibitor exposure. If the combination improves response depth or durability, it could change fixed-duration treatment strategies for relapsed/refractory CLL/SLL.

Davids MS, Eyre TA, Woyach JA et al. · Lancet (London, England) · (2026) · View on PubMed ↗

CRISPR-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice.

This study developed a CRISPR-guided method for precise large fragment insertion in mouse zygotes by deleting the murine 2.4-Mb IgH variable (VH) locus and inserting a 155-kb human VH fragment via BAC integration. The key finding was that full-length, single-copy BAC integration produced stable, heritable humanized immunoglobulin heavy-chain expression with normal B cell development and functional recombination after immunization. Scientifically, this enables rapid generation of humanized IgH mouse models for studying human antibody repertoires and immune responses.

Nair U, Akauliya M, Warner JE et al. · Immunity · (2026) · View on PubMed ↗

A conserved mechanism of membrane fusion in nuclear pore complex assembly.

This study investigated how the ER-anchored UFSP2-ODR4 complex regulates UFM1 deconjugation in neurons by spatially confining the deUFMylation module. The key finding was that ODR4 recruits UFSP2 to the ER to efficiently deUFMylate UFMylated RPL26, and disrupting UFSP2–ODR4 interaction led to accumulation of UFMylated RPL26 and defective ER-associated ribosome quality control (ER-RQC) with impaired neuronal proteostasis. Clinically/scientifically, it identifies a mechanism safeguarding neuronal proteostasis through controlled UFM1 pathway turnover.

Fischer JS, Wojtynek M, Kumar A et al. · Molecular cell · (2026) · View on PubMed ↗

Menin-dependent megakaryocyte proliferation and fibrosis in myeloproliferative neoplasms.

This study investigated how menin inhibition affects megakaryocyte progenitors and fibrosis in human CD34+ cultures and in mouse models of myeloproliferative neoplasms (MPNs), focusing on the menin inhibitor revumenib and its interaction with ruxolitinib. Revumenib reduced megakaryocyte progenitors and showed potent anti-tumor activity with synergy with ruxolitinib while producing only subtle effects in healthy mice. These findings mechanistically link menin to MPN megakaryopoiesis/fibrosis and support revumenib (alone or with ruxolitinib) as a strategy to improve MPN disease biology and potentially mitigate thrombocytopenia-related liabilities.

Wen J, Cotton A, Mehmood R et al. · Cancer cell · (2026) · View on PubMed ↗

Spatial multi-omics landscape of colorectal cancer macro- and micrometastases.

This study used spatial multi-omics—including spot-level and high-resolution spatial transcriptomics, multi-regional whole-genome sequencing after laser-capture microdissection, and high-plex protein imaging—to map clonal evolution and microenvironmental states across paired primary colorectal tumors and matched liver and lung macro- and micrometastases from 19 patients. Liver micrometastases arose from early clonal divergences and contained a stem-like, quiescent state consistent with metastatic dormancy, revealed by phylogenetic reconstruction and spatially resolved molecular programs. Clinically, this provides a spatially grounded framework for understanding minimal residual disease and dormancy in CRC metastasis, potentially informing targeted strategies to prevent relapse.

Liu Y, Jadhav AS, Pan Y et al. · Cancer cell · (2026) · View on PubMed ↗

Shashen Maidong decoction alleviates influenza A virus-induced lung injury by modulating ZBP1-mediated PANoptosome assembly.

This study evaluated Shashen Maidong decoction (SMD) in an influenza A virus (IAV)-induced lung injury model and tested its mechanism through the ZBP1-dependent PANoptosis pathway. SMD alleviated IAV lung injury by modulating ZBP1-mediated PANoptosome assembly, thereby reducing PANoptosis-driven inflammatory damage. The results are significant because they identify a specific ZBP1-PANoptosis target pathway through which a traditional medicine formulation may confer antiviral lung protection.

Xu M, Gong K, Zhu J et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Dark tea-derived exosome-like nanovesicles suppress hepatocellular carcinoma via inhibiting Akt pathway and modulating immune profiles.

This study developed dark tea-derived exosome-like nanovesicles (DTELNs) and assessed their anti-hepatocellular carcinoma (HCC) effects and mechanisms, using techniques including tangential flow filtration for isolation, TEM/NTA for characterization, and LC-MS/MS plus nucleic acid/protein analyses for composition. DTELNs suppressed HCC by inhibiting the Akt pathway and by modulating immune profiles. The significance is that plant-derived exosome-like delivery may improve bioavailability while targeting Akt signaling and tumor immunity to enhance HCC therapy.

Zheng Y, Wang S, Ying J et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Roots navigate around decay regions by sensing local pH gradients.

This study investigated how plant roots navigate decaying plant-derived material in soil, focusing on a newly defined “saprotropism” response in the context of fungal-driven decomposition. The authors found that fungal decomposition releases organic acids that form stable local pH gradients, which roots detect to bend away from decay via a root epidermal meristem growth factor peptide–receptor module. This mechanistic insight links microbial decomposition chemistry to directional root behavior, advancing understanding of nutrient cycling and plant survival in hostile soil microenvironments.

Bao Z, Wang H, Zhang A et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Degron-independent recruitment of KAT2A expands the target space of CRBN molecular glues.

This study investigated CRBN-based molecular glues that degrade lysine acetyltransferase KAT2A, aiming to expand beyond canonical degron-dependent recruitment. Using cryo-electron microscopy, the authors showed that CRBN recruits KAT2A independently of a degron by engaging a surface-exposed tyrosine, and that selective KAT2A degradation produced potent anti-tumor effects (as reported in the truncated abstract). The work provides a degron-independent strategy to widen the target space of CRBN molecular glues, potentially improving selectivity for KAT family members in cancer therapeutics.

Ojeda S, Wang M, Baek K et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

The CARM1 epigenetic enzyme inhibits cross-presenting dendritic cell function in cancer immunity.

This study investigated whether the epigenetic enzyme CARM1 (CARM1/Carm1) regulates cancer antigen presentation by dendritic cell subsets in cancer immunity. The authors found that CARM1 selectively inhibited cross-presenting cDC1 function, and that Carm1 gene inactivation promoted cDC1 antigen cross-presentation and tumor accumulation/activation, while a CARM1 inhibitor enhanced cDC1-mediated T cell priming when combined with a cancer neoantigen vaccine. These results position CARM1 inhibition as a strategy to boost the cancer-immunity cycle by improving intratumoral cDC1 cross-presentation.

Zhang X, Xirenayi S, Zhao Y et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Bacteria sense virus-induced genome degradation via methylated mononucleotides.

This study characterized a bacterial defense system, Metis, that senses phage-induced host genome degradation by detecting methylated mononucleotides. The authors reported that Metis aborts phage infection upon sensing m6dAMP, where accumulation of this modified deoxyadenosine signals host genome degradation, and that type I Metis triggers NAD+ diphosphatase activity leading to NAD+ depletion while type II Metis uses a membrane-spanning effector whose toxicity is activated by m6dAMP. This mechanism reveals how bacteria directly couple chemical signatures of genome damage to aborting viral infection, expanding understanding of innate antiviral immunity.

Osterman I, Hurieva B, Moses S et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Virome-wide ubiquitin ligase discovery reveals diverse mechanisms of immune evasion.

This study used a virome-wide discovery approach to identify viral ubiquitin ligases and determine their immune-evasion mechanisms. By screening ~10,000 viral open reading frames with targeted CRISPR screens and proteomics, the authors classified viral ligases into canonical ligases, hijackers that redirect host E3s, and non-canonical ligases that rewire Cullin-RING machinery, with convergence on immune-related substrates such as JAK1 and CUL1β-TrCP. The findings map diverse viral degradation strategies that target host immune signaling pathways, informing antiviral and immune-modulating therapeutic development.

Glassman CR, Baek K, Hou G et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Autonomous biomedical research with an artificial intelligence agent.

This study developed and evaluated Biomni, an artificial intelligence agent designed to autonomously execute biomedical research workflows. Biomni used an action-discovery component to mine tools, databases, and protocols across thousands of publications in 25 domains, then combined large language model reasoning with retrieval-augmented planning and code-based execution to dynamically compose workflows without predefined templates. The reported benchmarking indicates strong generalization across heterogeneous biomedical tasks, suggesting a scalable path toward reducing repetitive bottlenecks in biomedical discovery.

Huang K, Zhang S, Wang H et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

A DNA break-5mC cycle activates transposable elements in Arabidopsis.

This study examined how defective single-strand break (SSB) repair and DNA methylation (5mC) regulate transposable element (TE) activity in Arabidopsis, focusing on mutations in the 3’-end repair enzymes ZDP/APE2. The authors found that impaired repair of 3’-blocked SSBs (generated from base excision repair) triggers genome-wide TE derepression alongside extensive de novo 5mC deposition, with concurrent activation of the ATR–SOG1 DNA damage response. These findings link specific SSB repair defects to an epigenetic TE-activation cycle, highlighting a mechanistic route by which DNA damage can destabilize plant genomes.

Liang W, Cao H, Zou C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

IL-13 signaling in cDC2 is required for systemic anaphylactic responses.

This study investigated the role of interleukin-13 (IL-13) signaling in conventional dendritic cells type 2 (cDC2) using a murine cutaneous allergen sensitization model of systemic anaphylaxis and cell-specific deletion of the IL-13 receptor alpha1 subunit (Il13ra1). IL-13 receptor signaling in cDCs—not T or B cells—was identified as required to orchestrate systemic anaphylactic responses. The results pinpoint cDC2 as a critical cellular target of IL-13 in systemic allergy, informing potential immune-cell–directed strategies to prevent anaphylaxis.

Harada Y, Sasaki T, Obata-Ninomiya K et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Humans homozygous for rare or common hypomorphic IL23R variants are prone to tuberculosis.

This study analyzed human tuberculosis susceptibility in individuals homozygous for rare or common hypomorphic IL23R variants, using genetic enrichment and functional immunology to assess IL-23–dependent IFN-γ production. The authors reported selective enrichment of four hypomorphic IL23R alleles (G300V, G149R, L372F, and the relatively common R381Q) among tuberculosis patients, and showed that homozygosity abolishes IL-23-dependent IFN-γ responses by lymphocytes including NK and innate-like T cells. Clinically, the work establishes IL23R hypomorphic variants as a genetic risk factor for tuberculosis and clarifies how impaired IL-23/IFN-γ immunity predisposes to disease.

Olguín Calderón D, Kilpatrick LE, Conil C et al. · The Journal of experimental medicine · (2026) · View on PubMed ↗

ADAR1 loss-of-function variants altering RNA editing define a new interferon-dependent psoriasis subtype.

This study investigated early-onset plaque psoriasis families for genetic causes of interferon-dependent disease by identifying ADAR1 variants and assessing type I interferon signatures using whole-exome sequencing and single-cell transcriptomic analyses. It found four rare heterozygous ADAR1 loss-of-function mutations that cosegregated with disease and elevated interferon-stimulated gene expression, defining a new interferon-dependent psoriasis subtype. The findings establish ADAR1 RNA-editing deficiency as a monogenic driver of an IFN-high psoriasis phenotype, with implications for targeted interferon-pathway therapies.

Assan F, Tragin M, Marella S et al. · The Journal of experimental medicine · (2026) · View on PubMed ↗

An Integrative RNA Spliceosomic Landscape of Pancreatic Neuroendocrine Tumors Identifies Clinically Relevant Molecular Subgroups.

This integrative RNA spliceosomic study analyzed RNA-seq data from 174 pancreatic neuroendocrine tumor (PanNET) samples to define clinically relevant molecular subgroups based on alternative splicing patterns. It identified three robust spliceosomic groups (SPN1, SPN2, SPN3) with distinct clinical and molecular characteristics. The work provides a splicing-based stratification framework that may improve diagnosis and enable subgroup-specific therapeutic hypotheses in a highly heterogeneous rare cancer.

Blázquez-Encinas R, García-Vioque V, Mafficini A et al. · Endocrine pathology · (2026) · View on PubMed ↗ · Free PDF ↗

Ku70-SAP domain has an overlapping function with DNA-PKcs in limiting the lateral movement of the Ku ring along DNA.

In murine models of non-homologous end joining (NHEJ), this study investigated the Ku70 SAP domain’s role in restricting Ku ring movement along DNA and its relationship to DNA-PKcs. The SAP domain was dispensable for Ku70 stability and recruitment to DNA breaks, and Ku70ΔSAP/ΔSAP mice showed normal lymphocyte development with only mild radiation sensitivity. This advances mechanistic understanding of NHEJ regulation and could inform strategies to modulate DNA repair.

Zhu Y, Jonchhe S, Zhang H et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

Reattempt of tyrosine kinase inhibitor discontinuation after maintenance therapy with ponatinib in patients with chronic myeloid leukaemia in the chronic phase: Result of the Japan Adult Leukemia Study Group RE-STOP219 study.

The RE-STOP219 study evaluated whether patients with chronic myeloid leukemia in chronic phase (CML-CP) who previously failed tyrosine kinase inhibitor (TKI) discontinuation could achieve treatment-free remission (TFR) after maintenance therapy with ponatinib. The trial enrolled patients who relapsed after prior TKI discontinuation and then regained a deep molecular response defined as MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale). This addresses a key clinical question for TFR reattempt strategies in CML patients who do not succeed on first TKI discontinuation.

Iriyama N, Takahashi N, Fujimaki K et al. · British journal of haematology · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on July 11, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.