PubMed Trending Research Digest — September 11, 2026

A curated digest of 98 trending PubMed articles, automatically categorised and summarised across 15 research areas.

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Clinical trials & therapeutics (non-oncology) Cancer genetics & mutational mechanisms Infectious disease & host-pathogen mechanisms Cancer cell biology & tumor vulnerabilities Immunotherapy & tumor microenvironment Autoimmunity & immune-related adverse events Clinical trials & therapeutics (oncology) Biomarkers & risk prediction (imaging/omics/fluids) Neuroscience & brain circuits/neuromodulation Targeted protein degradation & molecular glue therapies Cardiometabolic disease & liver (MASLD/MASH/CKM) Respiratory disease & airway inflammation Microbiome & host-microbe axes Neurodegeneration & dementia biomarkers Sleep & circadian/physiology interventions

Automated digest · 98 articles · 15 research areas · September 11, 2026

Overview

Across this week’s papers, a dominant thread is the move from “what disease is” to “what mechanism is running,” enabling more precise targeting. In oncology, multiple studies identify actionable vulnerabilities tied to transcriptional programs (e.g., PAX3::FOXO1–driven FANCM dependency), chromatin regulation (short AR polyglutamine tracts shaping an AR–LSD1 axis), and mitochondrial/iron or stress pathways (MAVS–HIF signaling under hypoxia; USP7 lactylation controlling mitophagy; adipocyte oxylipins inducing ferroptosis). Parallel work in tumor microenvironments highlights how immune niches and suppressive cell states can be mapped and potentially disrupted—such as PLA2G2D+ myeloid neighborhoods in tumor-draining lymph nodes, serpin-driven immune suppression in PDAC spatially organized niches, NET-driven liver metastasis and NK-cell impairment, and PRKX-dependent PD-L1 stabilization in gastric cancer.

A second major theme is biomarker and risk stratification—often using advanced, scalable measurement technologies—to guide therapy selection and monitoring. Several studies leverage imaging/omics and computational models: ctDNA tracking in localized sarcoma, inflammatory blood indices predicting response/toxicity for an antibody-drug conjugate, radiomic signatures linking spleen biology to coronary risk, and whole-body or whole-organism live-imaging approaches that aim to capture system-level dynamics. In neurodegeneration and neuroimaging, consensus and review pieces emphasize how blood and fluid biomarkers (e.g., p-tau217, NfL) and imaging (MRI, amyloid PET) are increasingly used to define biologically grounded disease stages and eligibility for disease-modifying therapies.

Finally, the digest also reflects rapid translational momentum beyond cancer: new clinical trial results for thalassemia (mitapivat), stroke (loberamisal), ALS (RIPK1 inhibition), and inhaled siRNA targeting RAGE in pulmonary inflammation. Across autoimmune and immune-related safety, studies address early detection strategies (islet autoantibodies for type 1 diabetes), medication-associated risks (IBD after IL-17 inhibitors; celiac disease after immune checkpoint inhibitors; TB signals with JAK inhibitors), and practical guidance for managing treatment toxicities. Together, these findings underscore a broader shift toward mechanism-linked, biomarker-guided, and safety-aware medicine.

Clinical trials & therapeutics (non-oncology)

This phase 3, double-blind, randomized, placebo-controlled ENERGIZE-T trial studied the oral allosteric pyruvate kinase activator mitapivat in adults (≥18 years) with transfusion-dependent α-thalassaemia or β-thalassaemia across 19 countries. Mitapivat improved disease-related outcomes compared with placebo while demonstrating an acceptable safety profile in this transfusion-dependent population. These results support mitapivat as a potential disease-modifying oral therapy for both α- and β-thalassaemia patients who rely on regular transfusions.

Cappellini MD, Sheth S, Taher A et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Loberamisal for Acute Ischemic Stroke: The LAIS Randomized Clinical Trial.

This multicenter, double-blind, randomized, placebo-controlled phase 3 trial evaluated intravenous loberamisal in adults with acute ischemic stroke across 32 hospitals in China. Loberamisal, which targets the PSD-95 pathway and α2γ-aminobutyric acid type α (α2-GABAA) receptor, improved functional outcomes compared with placebo while maintaining an acceptable safety profile. The trial supports loberamisal as a candidate neuroprotective/neuroreparative therapy for acute ischemic stroke.

Li S, Feng B, He D et al. · JAMA · (2026) · View on PubMed ↗

Dual orexin receptor antagonist-assisted dose reduction of benzodiazepines and benzodiazepine receptor agonists: a mirror-image analysis of insurance claims data.

This mirror-image self-controlled analysis of Japanese health insurance claims evaluated whether initiating the dual orexin receptor antagonists (DORAs) suvorexant or lemborexant enables dose reduction of benzodiazepines or benzodiazepine receptor agonists (BZ/BZRAs) in long-term users with chronic insomnia. Compared with the pre-initiation period, the study assessed changes in bedtime BZ/BZRA dose (diazepam-equivalent units) after DORA treatment. The clinical significance is that DORAs may facilitate safer tapering strategies for chronic insomnia patients dependent on BZ/BZRAs.

Matsui K, Sugiura K, Shimura A et al. · Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · (2026) · View on PubMed ↗

Anesthetic Safety and Perioperative Outcomes in GLP-1 Receptor Agonist-Treated Patients Undergoing Lipoabdominoplasty.

The study retrospectively compared anesthetic safety and perioperative outcomes in patients undergoing high-definition lipoabdominoplasty under general anesthesia who were treated with GLP-1 receptor agonists versus those not receiving them. It assessed whether GLP-1–associated effects on gastric emptying, metabolism, and nutritional status translate into measurable differences in perioperative safety outcomes. The results are intended to inform perioperative risk management for patients on GLP-1 receptor agonists undergoing body-contouring surgery.

Albanese R, Tomaselli F, Berkane Y et al. · Aesthetic plastic surgery · (2026) · View on PubMed ↗

Effect of exercise on bone health in middle aged and older adults: hierarchical network meta-analysis of randomised trials.

This hierarchical network meta-analysis studied which types and doses of structured exercise best preserve bone mineral density (BMD) and reduce fracture risk in adults aged ≥40 years using randomized controlled trials. Across middle-aged and older populations, the analysis synthesized dose-response effects on lumbar spine and femoral BMD to identify exercise regimens associated with better bone outcomes. Clinically, it helps guide evidence-based exercise prescriptions for osteoporosis prevention and fracture risk reduction in aging adults.

Lu C, Li L, Zhang L et al. · BMJ (Clinical research ed.) · (2026) · View on PubMed ↗

Comorbidities in clinical cohorts of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

This systematic review and meta-analysis studied comorbidities in clinical cohorts of patients with idiopathic pulmonary fibrosis (IPF) by pooling observational studies (≥100 adults) and assessing prevalence and associations with health outcomes. It included 251 studies (606,398 participants) and summarized common comorbidities and their impact on outcomes, highlighting how comorbidity burden may shape prognosis and management. These results are significant for risk stratification and for tailoring IPF care to patients’ comorbidity profiles.

Leong MCH, Green S, Guan M et al. · European respiratory review : an official journal of the European Respiratory Society · (2026) · View on PubMed ↗ · Free PDF ↗

Reducing Inequities in Restraint Use in the Pediatric Emergency Department.

This quality-improvement study in a pediatric emergency department examined drivers of racial/ethnic inequities in physical and chemical restraint use and aimed to reduce disparities to <1% within 12 months. After identifying contributing factors such as staffing and standardized agitation-management protocols, the intervention targeted lower restraint rates among non-Hispanic Black and Hispanic patients, where baseline physical restraint (2.7% and 2.7%) and higher intramuscular chemical restraint (6.0% in non-Hispanic Black vs 2.6% in non-Hispanic White) were observed. The clinical significance is improved safety and equity in pediatric acute agitation management by reducing harmful and disproportionate restraint practices.

Adu MR, Rolison M, Powers E et al. · Pediatrics · (2026) · View on PubMed ↗

RECREA: Registry of Cardiac Rehabilitation Centers in Latin America of the Council of Cardiac Rehabilitation and Sports Cardiology of the Inter-American Society of Cardiology.

This registry-based study (RECREA) characterized cardiac rehabilitation (CR) centers in Latin America by examining their geographic distribution and operational characteristics. The work aimed to document how CR programs are structured and how they function across the region, addressing a lack of regional data on CR evolution and outcomes. Its significance lies in informing health-system planning and identifying gaps to improve access and delivery of CR services in Latin America.

Lara-Vargas J, Anchique C, Noriega J et al. · Current problems in cardiology · (2026) · View on PubMed ↗

Comparative effectiveness of mood stabiliser monotherapy versus second-generation antipsychotic monotherapy versus combination therapy for continuation and maintenance treatment after a first episode of psychotic mania in North America, Chile, and Spain: a target trial emulation using data from the BD-CAUSAL Collaboration.

This target trial emulation using BD-CAUSAL Collaboration data compared mood stabiliser monotherapy versus second-generation antipsychotic monotherapy versus combination therapy for continuation and maintenance after a first episode of psychotic mania in individuals aged 16 years or older across North America, Chile, and Spain. The key finding was that comparative effectiveness differed by treatment strategy, informing which regimen is more favorable for longer-term outcomes after initial psychotic mania. Clinically, these results help guide maintenance treatment selection early in bipolar I disorder when evidence is limited.

Szmulewicz AG, Liang YH, Martínez-Alés G et al. · The lancet. Psychiatry · (2026) · View on PubMed ↗

This multicentre, randomized, double-blind, placebo-controlled phase 2 trial (HIMALAYA) evaluated the RIPK1 inhibitor SAR443820 in adults with amyotrophic lateral sclerosis (ALS) to assess safety, tolerability, and efficacy. The key finding was that SAR443820’s safety and tolerability profile was characterized and its efficacy signals were tested against placebo in ALS patients across multiple countries and clinical sites. If efficacy is supported, targeting RIPK1-mediated inflammatory signaling with a CNS-penetrant oral inhibitor could represent a new therapeutic approach for ALS.

Cudkowicz ME, Shefner J, van den Berg LH et al. · The Lancet. Neurology · (2026) · 1 citations · View on PubMed ↗

Longitudinal Outcomes of Total Hip Arthroplasty in Developmental Dysplasia of the Hip: A National Database Propensity-Matched Analysis.

This national database propensity-matched cohort study examined long-term outcomes of total hip arthroplasty (THA) in patients with developmental dysplasia of the hip (DDH) using TriNetX data from 104 healthcare organizations. The key finding was that DDH patients undergoing THA had measurable differences in early medical complications (90-day) and 2-year mechanical outcomes/revision risk compared with matched controls, addressing gaps in long-term implant performance evidence. Clinically, the results help refine risk counseling and postoperative surveillance strategies for DDH patients receiving THA.

Al-Jamal M, Abdalla O, Hasan A et al. · Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · (2026) · View on PubMed ↗

Intravenous gene therapy improves life span and clinical outcomes in a feline model of Sandhoff disease.

This preclinical study tested an intravenous, bicistronic adeno-associated virus (AAV) gene therapy in a feline model of Sandhoff disease (SD), administered presymptomatically at 1 month of age. The key finding was that systemic AAV delivery improved survival and clinical outcomes compared with untreated SD cats, addressing the lack of prior clinical-trial testing for this delivery route in SD. Clinically and translationally, it supports intravenous AAV as a potentially practical route for lysosomal enzyme replacement strategies targeting GM2 ganglioside accumulation.

Maguire AS, Ta NL, Gross AL et al. · Science translational medicine · (2026) · View on PubMed ↗

Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice.

The study developed selective, proteolytically stable monoclonal antibodies (mAbs) that inhibit matrix metalloproteinase-9 (MMP-9) activity and tested them in mouse models of diabetic peripheral neuropathy (DPN). The MMP-9–inhibiting mAbs alleviated peripheral neuropathy phenotypes in diabetic mice by suppressing neuroinflammation driven by MMP-9. These target-specific biologics suggest a disease-modifying therapeutic strategy for DPN that may overcome limitations of less selective small-molecule MMP-9 inhibitors.

Lee KB, He W, Matsuoka Y et al. · Science translational medicine · (2026) · View on PubMed ↗

Engineering suppressor tRNAs for effective treatment of Duchenne muscular dystrophy.

The study engineered suppressor transfer RNAs (sup-tRNAs) to treat Duchenne muscular dystrophy (DMD) caused by nonsense mutations, and tested systemic delivery in mouse models using optimized AAV expression vectors and RNA polymerase III promoters. The evolved UAA sup-tRNAs restored full-length dystrophin and improved muscle strength and motor function in mice at lower doses than prior AAV microdystrophin approaches. These findings support a potentially scalable gene-agnostic therapy for the ~15% of DMD patients with nonsense mutations by enabling translational readthrough of premature stop codons.

Oury J, Chen YH, McFarland S et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Drug Survival of Omalizumab and Factors Associated With Discontinuation in Chronic Urticaria: A Meta-Analysis.

This meta-analysis studied long-term drug survival and discontinuation factors for omalizumab in patients with chronic urticaria using observational studies. Across included datasets, the analysis evaluated time-to-discontinuation/drug survival outcomes and synthesized determinants associated with stopping omalizumab. The findings are intended to improve clinical decision-making by helping clinicians predict persistence on omalizumab therapy and identify patients at higher risk of discontinuation.

Altayf A, Kolkhir P, Alwefati M et al. · JAMA dermatology · (2026) · View on PubMed ↗

Cancer genetics & mutational mechanisms

Noncoding transcription controls the developmental dynamics of long-range gene regulation.

This study investigated how noncoding transcription regulates long-range gene activation during Drosophila embryonic development using live imaging and single-allele co-visualization of enhancer activity and ncRNA transcription. Sequential transcription of enhancer-associated noncoding RNAs controlled the timing of gene activation, with optimal activation occurring at moderate enhancer activity and disruption of these ncRNAs causing precocious gene expression. The findings establish a mechanistic role for enhancer ncRNAs in developmental gene-regulatory dynamics, informing how timing—not just expression level—is encoded by regulatory transcription.

Batut PJ, Levine MS · Science (New York, N.Y.) · (2026) · View on PubMed ↗

The complete telomere-to-telomere sequence of a mouse Y chromosome.

This study generated and analyzed a telomere-to-telomere assembly of a mouse Y chromosome (mT2T Y) from a C57BL/6 mouse to resolve gaps in the GRCm39 reference, using long-read genome assembly and comprehensive annotation. The new assembly filled all prior gaps, corrected structural errors, added >8.70 Mb of previously unassembled sequence, and enabled identification of Y-specific satellite arrays, 142 previously unidentified genes, and Y-linked dosage compensation patterns. The improved mY reference and gene mapping provide a high-resolution genomic resource for studying male reproduction, Y-chromosome evolution, and X–Y regulatory compensation.

Li Q, Liu J, Chen S et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

International consensus guidance for general population screening for islet autoantibodies to diagnose early-stage type 1 diabetes: a nominal group technique process.

This genomic meta-analysis studied binge-eating behavior and anorexia nervosa using genome-wide association and polygenic risk score approaches across large case-control datasets (including 39,279 binge-eating cases and 1,227,436 controls, and 24,223 anorexia nervosa cases and 1,243,971 controls). The authors identified six binge-eating-associated loci and eight anorexia nervosa loci (with validation of six), and polygenic risk scores supported shared and distinct genetic biology across eating disorder phenotypes. These results improve understanding of the unique and overlapping genetic architecture of eating disorder subtypes and may inform future risk prediction and mechanistic studies.

Ziegler AG, Rewers MJ, Achenbach P et al. · Diabetologia · (2026) · View on PubMed ↗

Integrated signatures define mutational processes in prostate cancer.

This study integrated mutational signatures across 959 prostate cancer donors from the Pan Prostate Cancer Group to define mutational processes and their clinical relevance. By combining single-base substitution, insertion-deletion, copy-number signatures, and six complex structural variant signatures, the authors derived eight integrated mutational footprints (IMFs) explaining 85% of primary prostate cancer genomes, with strong influences from regional genomic biases including androgen receptor-mediated mutagenesis and replication-associated processes. The results provide a unified framework for interpreting prostate cancer genome evolution and potentially linking mutational mechanisms to clinical phenotypes.

Gruber AJ, Olsen AV, Hernando B et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Predicting genome-wide functional constraints with GPN-Star.

The study developed GPN-Star, a phylogeny-aware genomic language model that uses whole-genome alignments and species trees to predict genome-wide functional constraints. GPN-Star outperformed standard NLP-style genomic language models and classical evolutionary approaches by explicitly incorporating evolutionary relationships through a species-tree architecture. Scientifically, it provides a more biologically grounded framework for learning functional constraint landscapes from comparative genomics.

Ye C, Benegas G, Albors C et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Recurrent mechanisms of biallelic epigenetic inactivation reveal new putative tumour suppressor genes in prostate cancer.

The authors developed Epi2Hit, an integrative computational method combining whole-genome sequencing, epigenomic profiling, and gene expression to identify tumor suppressor genes with biallelic epigenetic inactivation in prostate cancer. Applying Epi2Hit to 2,021 prostate cancers revealed recurrent mechanisms where one allele is silenced by promoter/enhancer DNA methylation while the other allele is lost, enabling discovery of new putative tumor suppressors in hemizygously deleted regions. This provides a framework to uncover clinically relevant prostate cancer drivers that would be missed by analyses focused only on homozygous genomic loss.

Kiriy D, Favero F, Gerhäuser C et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Caloric restriction modulates genome-wide somatic mutation in mice.

This study investigated how caloric restriction (CR) affects genome-wide somatic mutation accumulation in mice across multiple tissues and cell types. Using high-fidelity duplex DNA sequencing of bulk liver, bulk kidney, hepatocytes, and cerebellar neurons, the authors found that CR reduced overall somatic mutation burdens, including both substitutions and insertion/deletion events, and decreased activity of the single-base substitution mutational process SBS5. These data support CR as a modulator of aging-associated genomic instability and suggest SBS5 as a mechanistic biomarker of mutational processes influenced by diet.

Grońska-Pęski M, Acosta-Rodríguez V, Srinivasa A et al. · Cell · (2026) · View on PubMed ↗

The CENP-A chaperone complex spatially organizes centromeres.

This work examined how the CENP-A chaperone machinery organizes centromeres during interphase, focusing on CENP-A and the constitutive centromere-associated network (CCAN) in cells. The authors found that in interphase, CENP-A and CCAN assemble conserved shell-like structures that enclose a chromatin-poor central cavity, which is occupied by the interphase-specific CENP-A chaperone complex that promotes CENP-A deposition/maintenance. The results reveal a structural role for the CENP-A chaperone complex in interphase centromere architecture, advancing mechanistic understanding of chromosome segregation fidelity.

Gupta H, Haase J, Wu Y et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

A direct protein bridge connects the ds and ds-ss junction telomeric DNA segments in C. elegans.

The authors studied telomere end protection in Caenorhabditis elegans by dissecting how the TEBP-1/2 (DTN-1/2) and POT-1 proteins connect double-stranded (ds) and double-strand–single-strand (ds–ss) junction telomeric DNA segments. Using protein crystallography plus in vivo functional analyses, they identified a direct protein interface in which the POT-1 OB domain is repurposed to engage TEBP-1/2, forming a physical bridge between ds and ds–ss junction telomeric DNA. This clarifies the molecular architecture of telomere connectivity in a simplified shelterin-like system, informing broader principles of chromosome end protection.

Tesmer VM, Lambacher NJ, Yamamoto I et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Infectious disease & host-pathogen mechanisms

Mechanism of membrane perforation in rotavirus cell entry.

This work examined the mechanism of membrane perforation during rhesus rotavirus cell entry using cryogenic electron tomography with subtomogram averaging and time-resolved live-cell fluorescence. The authors visualized the full entry pathway from attachment and uptake through release of the subviral particle, linking high-resolution virion structures to the sequential steps of entry. By defining structural intermediates that enable membrane translocation, the study clarifies how nonenveloped dsRNA viruses breach cellular membranes and may guide antiviral targeting of entry steps.

de Sautu M, Leistner C, Kirchhausen T et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Bacterial co-detection in individuals with acute respiratory infections through a direct-to-consumer platform in China: a retrospective cross-sectional study.

This retrospective cross-sectional study used a direct-to-consumer multiplex respiratory pathogen testing platform in China to characterize bacterial co-detection among community individuals with acute respiratory infections attributed to viral causes. The key finding was the epidemiological profile of bacterial co-detection rates and patterns in this broad, self-referred population, quantifying how often bacteria were detected alongside viral infection. This has public-health significance by informing interpretation of multiplex test results and guiding stewardship decisions about when bacterial-directed treatment is or is not warranted.

Xiang C, Li J, Yan M et al. · The Lancet. Microbe · (2026) · View on PubMed ↗ · Free PDF ↗

Oligoclonal nanobody-based recombinant antivenom protects mice challenged with venom from cobras and king cobras from India.

This preclinical study developed an oligoclonal recombinant antivenom composed of five nanobodies (VHHs) against major cobra and king cobra toxin families and evaluated it in murine models of envenoming. The key finding was that the nanobody cocktail provided protective efficacy in preincubation and rescue experiments against venom challenge from Indian cobras and king cobras, addressing limitations of variable efficacy and cross-neutralization of plasma-derived antivenoms. Scientifically and clinically, it advances a rational, potentially more consistent antivenom platform for snakebite treatment in India.

Samanta A, Rudresha GV, Ahmadi S et al. · Science translational medicine · (2026) · View on PubMed ↗

FERONIA phosphorylates the amino-terminal extension of phytochrome B to modulate plant light and temperature responses.

This study investigated the plant receptor kinase FERONIA (FER) and whether it phosphorylates the amino-terminal extension (NTE) of phytochrome B (phyB) to regulate light and temperature responses. FERONIA was shown to phosphorylate phyB NTE (aa1–90), and NTE phosphorylation at multiple sites reduced Pfr stability, thereby modulating the light-dependent and temperature-dependent phyB signaling outputs. These results identify a specific post-translational control mechanism connecting FER kinase activity to phyB conformational stability and plant environmental response regulation.

Wang P, Du J, He J et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer cell biology & tumor vulnerabilities

Lean adipocyte oxylipin signaling restrains breast cancer through ferroptosis.

This study tested whether lean adipocyte oxylipin signaling restrains breast cancer by inducing ferroptosis, using mammary adipocyte and breast cancer models plus human correlation analyses. Mammary adipocytes secreted 9S-hydroxyoctadecadienoic acid (9S-HODE), which induced ferroptosis in breast cancer cells by disrupting iron homeostasis, and obese conditions reduced 9S-HODE and ferroptosis with corresponding effects on tumor growth. These results identify a potentially actionable lipid–ferroptosis axis that could explain obesity-associated breast cancer aggressiveness and suggest therapeutic strategies to restore 9S-HODE–mediated ferroptosis.

Curtin MC, Jackson AE, Lee MD et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Targeting USP7 lactylation suppresses NSCLC tumorigenesis by promoting PINK1 ubiquitination and degradation.

This study examined USP7 lactylation in non-small cell lung cancer (NSCLC) using integrated proteomics/lactylomics of clinical NSCLC specimens and matched adjacent normal tissues, and functional assays in NSCLC models. USP7 was upregulated and USP7 K1084 lactylation increased in NSCLC, and USP7 knockout or inhibition of USP7 lactylation impaired mitophagy, causing mitochondrial damage and suppressing NSCLC tumorigenicity via promoting PINK1 ubiquitination and degradation. These findings identify USP7 K1084 lactylation as a mechanistic vulnerability that links lactylation control to mitophagy regulation and NSCLC progression.

Wang Z, Li C, Zhu R et al. · Autophagy · (2026) · View on PubMed ↗

TM184C is a GPCR-like regulator of intercellular exchange and autophagy.

The study characterized TM184C, a human “superdark” seven-transmembrane protein with GPCR-like structural similarity, and tested its role in intercellular exchange and autophagy using AlphaFold2-derived structural mining and cellular assays. TM184C localized to highly dynamic intracellular vesicles (rather than the plasma membrane) and exhibited GPCR-like signaling features including β-arrestin recruitment and GRK-dependent phosphorylation, linking it to vesicle-mediated trafficking processes. This suggests TM184C/PRRT-family proteins are a previously underappreciated regulator of vesicle biology that may couple intercellular exchange to autophagy.

Lee KD, Taylor S, Arcuri J et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

KRAS/ERK2-driven stabilization of AARS1 reprograms tumor metabolism and confers Sorafenib resistance in lung adenocarcinoma.

The research investigated how KRAS/ERK2 signaling stabilizes alanyl-tRNA synthetase 1 (AARS1) to reprogram metabolism and drive sorafenib resistance in lung adenocarcinoma (LUAD). It found that AARS1 protein (not mRNA) is upregulated due to impaired selective autophagic degradation mediated by the E3 ligase TRIM21, and that KRAS G12C activates ERK2-dependent phosphorylation of AARS1 at Ser882 to disrupt the AARS1–TRIM21 interaction. This identifies the KRAS/ERK2–AARS1–TRIM21 pathway as a metabolic resistance mechanism and a potential therapeutic vulnerability to overcome sorafenib resistance in KRAS-mutant LUAD.

Hu W, Chen Z, Yang J et al. · Cell death and differentiation · (2026) · View on PubMed ↗

Alveolar epithelial depletion of βPAK-interacting exchange factor drives spontaneous pulmonary fibrosis by impairing stemness.

The study used conditional βPAK-interacting exchange factor (βPIX) knockout mice to test whether alveolar epithelial βPIX depletion drives pulmonary fibrosis by impairing stemness. Selective loss of βPIX in alveolar type 2 (AT2) cells caused progressive pulmonary fibrosis with features resembling human idiopathic pulmonary fibrosis, and single-nucleus RNA sequencing showed emergence of progenitor-like/transitional cell states consistent with disrupted AT2 stemness. These results establish βPIX as a key regulator of AT2 regenerative capacity and a potential target for preventing or treating pulmonary fibrosis.

Kim HB, Song W, Kim SO et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Inflammatory neuropathy in mouse and primate models of colorectal cancer.

This work investigated whether colorectal cancer induces peripheral inflammatory neuropathy in mouse and primate models and characterized associated molecular changes in peripheral nerves. Tumor-bearing mice developed peripheral neuropathy with subtle locomotor deficits and widespread alterations in pro-inflammatory cytokines and lipid metabolites, alongside macrophage accumulation, myelin decompaction, and ryanodine receptor oxidation. The results strengthen the preclinical link between colorectal cancer and chronic neuropathy risk, supporting mechanistic targets for preventing cancer-associated nerve damage.

Gaffney CM, Casaril AM, Mahmud I et al. · Nature communications · (2026) · View on PubMed ↗

The stress-sensing MARCH5 axis governs blood cancer apoptotic resilience via tractable protein-protein interactions.

This mechanistic study investigated how the mitochondrial E3 ligase MARCH5 regulates apoptotic resilience in blood cancers, using cell models and perturbation of MARCH5 and its partners UBE2J2 and MFN2. The key finding was that MARCH5 forms a stress-sensing complex at mitochondria–ER contact sites (MERCS) that restrains apoptosis in response to organellar damage signals, and that MARCH5 loss sensitizes blood cancer cells to BCL-2/BCL-XL inhibition with tissue-selective synergy with venetoclax (BCL-2) and an additional BCL-XL–targeting strategy. Scientifically, it identifies a tractable protein–protein interaction axis that can be exploited to improve targeted apoptosis-based therapies in acute myeloid leukemia and myeloma.

Lew TE, van Delft MF, Heitink L et al. · Blood · (2026) · View on PubMed ↗ · Free PDF ↗

Peroxiredoxin 1 safeguards the nucleolar genome from oxidative damage.

The authors investigated how peroxiredoxin 1 (PRDX1) protects the nucleolar genome from oxidative damage by studying PRDX1-null mice and nucleolar function. They found that PRDX1 deficiency alters nucleolar morphology, impairs RNA polymerase I (POL-I)–dependent transcription of pre-ribosomal RNAs, and triggers nucleolar genomic instability. This mechanistic link between redox control, nucleolar transcription, and genome stability explains how PRDX1 loss promotes tumorigenesis and genomic instability.

Gujar V, Furusawa T, Sharma S et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Rare Hematopoietic Stem Cells resilient to infection-induced stress sense yet withstand inflammation.

This study analyzed heterogeneity in hematopoietic stem cell (HSC) responses to infection-induced stress at the single-cell level using a natural murine malaria model and an NHS-ester biotin dilution assay. It found rare HSC subpopulations that are resilient to infection-induced stress, can sense inflammatory/infection cues, yet still withstand inflammation without losing function. These results refine how HSCs maintain lifelong hematopoiesis under infectious pressure and identify resilient states that could inform strategies to protect stem cells during infection or inflammatory disease.

Georgiou C, Liu Q, Bruno F et al. · Blood · (2026) · View on PubMed ↗ · Free PDF ↗

FANCM is required for the PAX3::FOXO1-driven oncogenic program in rhabdomyosarcoma.

This study investigated the DNA translocase FANCM in alveolar rhabdomyosarcoma (ARMS) driven by the PAX3::FOXO1 fusion transcription factor. Sequential CRISPR-Cas9 functional genomic screens identified FANCM as a selective dependency in PAX3::FOXO1+ ARMS, where FANCM loss reduced fusion protein levels and disrupted the oncogenic program while promoting myogenic differentiation. These findings suggest FANCM as a potential therapeutic vulnerability to target PAX3::FOXO1-driven oncogenic transcription in ARMS.

Delaney CD, Lu M, Zimmerman SP et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

MAVS undergoes aggregation under hypoxia to enhance the hypoxia signaling pathway by promoting the generation of mitochondrial ROS.

This study examined how hypoxia affects the mitochondrial antiviral signaling protein MAVS and how this impacts hypoxia signaling in mammalian and zebrafish models. Hypoxia induced MAVS aggregation, which stabilized HIF1/2α proteins and enhanced hypoxia response signaling via a MAVS–TRAF6–ECSIT axis that promoted mitochondrial ROS generation and likely inhibited PHD2-mediated HIF degradation. Disrupting MAVS reduced hypoxia-response gene expression in mice and zebrafish, indicating MAVS as a mechanistic regulator linking hypoxic stress to HIF signaling.

Sun X, Zhu C, Liu W et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Minimal-length CAG repeats in AR define a hyperactive AR-LSD1 axis driving metabolic reprogramming in prostate cancer.

This study analyzed how minimal-length CAG repeats (≤17) in the androgen receptor (AR) gene shape an AR–LSD1 transcriptional axis and metabolic reprogramming in prostate cancer. The authors report that shorter AR polyglutamine tracts define a hyperactive AR-LSD1 program that drives metabolic changes associated with prostate cancer risk and worse outcomes, particularly in men of African ancestry where these alleles are enriched. Clinically, this links a specific AR genetic polymorphism to a druggable chromatin/transcription vulnerability involving LSD1.

Zhang S, Li M, Liu M et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Immunotherapy & tumor microenvironment

Chronic type II interferon promotes tumor growth through mitochondrial RNA-induced type I interferon and prostaglandin synthesis.

This study investigated how chronic type II interferon (IFN-II) promotes tumor growth by using mechanistic experiments to connect IFN-II signaling to mitochondrial RNA sensing and downstream interferon pathways. Chronic IFN-II induced tumor growth by triggering a type I interferon (IFN-I) response mediated by cytoplasmic release of double-stranded mitochondrial RNA (ds-mtRNA), and the IFN-I and IFN-II signals synergized to enhance tumor growth. These findings reveal a specific ds-mtRNA–dependent pathway that converts chronic IFN signaling from antitumor to protumor, highlighting a potential target for modulating interferon-driven cancer progression.

Johnson MA, Varanasi SK, Mangalhara KC et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.

This review analyzed mechanistic roles of E3 ubiquitin ligases in regulating tumor radiosensitivity and immunoresponsiveness relevant to tumor radioimmunotherapy. It concludes that E3 ubiquitin ligases control protein stability across DNA repair, immune signaling, and stress-response pathways, thereby shaping response to combined radiation and immunotherapy. The synthesis highlights actionable mechanistic targets and translational pathways for improving durable efficacy of radioimmunotherapy.

Yang Q, Xing X, Wang Y et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

PLA2G2D in tumour-draining lymph nodes regulates anti-tumour immunity.

The study investigated how tumor-draining lymph nodes (TDLNs) regulate anti-tumor T cell priming in melanoma patients, using imaging mass cytometry and targeted spatial transcriptomics to map immune neighborhoods. It identified a paracortex spatial neighborhood where activated CD8+ T cells engage myeloid cells expressing high levels of the immunosuppressive enzyme PLA2G2D, and PLA2G2D+ myeloid cells were associated with metastatic outcomes. This supports a specific PLA2G2D-driven myeloid immunosuppressive niche in human TDLNs as a potential target to improve systemic anti-tumor immunity.

van Krimpen A, Huang J, Eterman M et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

A serpin-myeloid axis in pancreatic cancer heterogeneity and immune evasion.

The study used Perturb-map spatial functional genomics to determine how specific genes shape pancreatic ductal adenocarcinoma (PDAC) clone growth, immune neighborhood composition, and immune evasion across space and time. It found early gene-driven remodeling of local immune microenvironments that precedes later spatial clonal dominance, identifying SERPINE1 (PAI1) and SERPINB2 as key components of a serpin-myeloid axis associated with immune suppression. These findings connect defined serpin genes to spatially organized immune escape in PDAC, highlighting potential targets for niche-directed immunomodulation.

Falcomatà C, Schaefer MM, Singh B et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Neutrophil extracellular traps promote liver metastasis by impairing NK cell-dependent tumor surveillance via CCDC25.

The study examined how neutrophil extracellular traps (NETs) promote liver metastasis and impair NK-cell–dependent tumor surveillance, focusing on the CCDC25 axis, using longitudinal single-cell RNA sequencing in a 4T1 orthotopic breast cancer model. It found progressive neutrophil infiltration, robust NETosis, and an immunosuppressive liver niche during metastatic progression, and multiple in vivo models showed that macrophage-dependent NET formation drives liver metastasis. These findings implicate NETs and CCDC25-linked immune evasion as actionable mechanisms to improve control of metastatic disease in the liver.

Zhang Y, Zeng J, Li H et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Cutaneous Toxicities of T-Cell-Redirecting Therapies in Multiple Myeloma: An EADV Task Force Position Paper and Practical Recommendations.

This EADV Task Force position paper summarized and provided practical recommendations on cutaneous toxicities caused by T-cell–redirecting therapies in multiple myeloma, including GPRC5D-targeting agents and BCMA-targeted bispecific antibodies and anti-BCMA CAR T cells. It concluded that GPRC5D-targeting therapies show prominent on-target, off-tumor skin effects related to hard-keratinizing tissues, whereas BCMA-targeted therapies produce milder and less phenotypically distinct cutaneous adverse events. Clinically, the recommendations aim to improve recognition, reporting, and management of dermatologic toxicities to support safer use of these immunotherapies.

Nikolaou V, Koumaki D, Perrot A et al. · Clinical lymphoma, myeloma & leukemia · (2026) · View on PubMed ↗

PRKX-mediated stabilization of PD-L1 characterizes an immunosuppressive gastric cancer subtype.

This study investigated gastric cancer immune microenvironment heterogeneity by integrating single-cell transcriptomic data and then testing mechanisms using in vitro assays and in vivo mouse models, focusing on PRKX-mediated stabilization of PD-L1. The authors identified an immunosuppressive gastric cancer subtype characterized by PRKX-dependent PD-L1 stabilization, linking PRKX activity to a more immune-evasive tumor state. Scientifically, this provides a potential biomarker/therapeutic axis (PRKX–PD-L1) to improve immune stratification and treatment targeting in gastric cancer.

Wang Q, Chen Y, Huang D et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.

This clinical translational study treated seven patients with immune checkpoint inhibitor (ICI)-refractory metastatic Merkel cell carcinoma (MCC) who were HLA-A*02:01 positive with TCR^MCC1-transduced autologous T cells (TTCR-MCC1) targeting MCPyV large-T antigen 15–23 after lymphodepletion and HLA-enhancing interventions. The key finding was that TTCR-MCC1 cells trafficked to tumor sites, showed a gene expression profile consistent with T cell activation, and produced tumor regression in the treated patients. Clinically, it demonstrates a strategy to overcome ICI resistance in MCPyV+ MCC by engineering high-avidity, virus-specific T cells.

Asano Y, Veatch JR, Sung CJ et al. · Science translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

TCR-JANUS engager proteins enable bispecific targeting to overcome tumor heterogeneity in TCR-T cell therapy.

The study engineered TCR-JANUS engager proteins to enable bispecific targeting that works with TCR-engineered T cells (TCR-T) against heterogeneous tumors, using a model targeting a humanized KRAS-G12V-specific TCR and the tumor antigen Trop2. TCR-JANUS redirected TCR-T cells to lyse Trop2-expressing tumor cells while preserving intrinsic specificity toward the cognate pHLA target, thereby addressing antigen heterogeneity–driven relapse. This provides a strategy to improve the robustness of TCR-T therapies by combining dual antigen engagement with maintained TCR specificity.

Cheng C, Liang T, Yao P et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Spatiotemporal mapping of tertiary lymphoid structure heterogeneity shapes immune niches and clinical outcomes in intrahepatic cholangiocarcinoma.

This study mapped the spatiotemporal heterogeneity of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA) using a multimodal spatial atlas and linked TLS features to clinical outcomes. It identified intratumoral TLSs (iTLSs) as independent prognostic markers and defined a four-tier TLS-based tumor microenvironment classification supported by bulk proteomics and a TLS-predictive random forest classifier, with imaging mass cytometry showing structured immune niches in iTLS+ tumors. The work suggests that TLS architecture can stratify iCCA patients and may guide immune-targeted prognostic and therapeutic strategies.

Gao L, Mei J, Hong L et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Rheumatoid Arthritis in Adults: A Review.

This article provides international consensus guidance for general-population screening for islet autoantibodies (IAbs) to diagnose early-stage type 1 diabetes, using a nominal group technique process to synthesize evidence and recommendations. It outlines how IAb screening can identify individuals before clinical diagnosis and emphasizes monitoring and education to prevent severe presentations such as diabetic ketoacidosis (DKA). The guidance is clinically significant because it standardizes an approach for earlier detection and risk management in a rising global type 1 diabetes population.

Smolen JS, Kerschbaumer A, Aletaha D et al. · JAMA · (2026) · View on PubMed ↗

Genomic meta-analyses of binge-eating behavior and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes.

This review summarized epidemiology, clinical features, and diagnostic considerations for rheumatoid arthritis in adults, including prevalence, sex differences, age of onset, and autoantibody status. It consolidates current knowledge on disease manifestations and the role of biomarkers such as rheumatoid factor and anticitrullinated peptide antibodies in diagnosis and characterization. The review is significant for clinicians because it provides an up-to-date framework for recognizing and managing adult rheumatoid arthritis across diverse presentations.

Termorshuizen JD, Davies HL, Lee SH et al. · Nature. Mental health · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Risk of Coeliac Disease After Immune Checkpoint Inhibitor Exposure in Patients With Cancer.

This study used the TriNetX US Collaborative Network to assess the risk of developing celiac disease (CeD) after immune checkpoint inhibitor (ICI) exposure in adults with malignancies, excluding those with pre-existing CeD. Patients were stratified by ICI exposure to drugs including nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, tremelimumab, and avelumab, and the analysis estimated CeD incidence risk after exposure. Scientifically and clinically, it informs immune-related adverse event surveillance and risk counseling for CeD in ICI-treated cancer patients.

Aburumman R, Alsakarneh S, Choung RS et al. · Alimentary pharmacology & therapeutics · (2026) · View on PubMed ↗

Tuberculosis during JAK inhibitor or TNF-α inhibitors therapy: a disproportionality analysis from WHO pharmacovigilance database.

This pharmacovigilance study used the WHO VigiBase database to quantify disproportionality of tuberculosis (TB) reports during treatment with JAK inhibitors versus TNF-α inhibitors. It performed a drug-related TB infection disproportionality analysis, using an information component threshold (IC0.25 > 0) to define statistical significance, and characterized patient and respiratory infection features under each drug class. The findings aim to clarify comparative TB risk signals for JAK inhibitors relative to TNF-α inhibitors, informing safer monitoring strategies in patients receiving these immunomodulators.

Maitre T, Bihan K, Veziris N et al. · Thorax · (2026) · View on PubMed ↗

Efgartigimod and Steroid Pulse Therapy as an Early Fast-acting Treatment Strategy for Anti-MUSK Myasthenic Crisis.

This case report studied an 83-year-old Japanese woman with anti-MUSK myasthenia gravis who developed anti-MUSK myasthenic crisis and was treated acutely with the neonatal Fc receptor (FcRn) antagonist efgartigimod plus steroid pulse therapy. The combination enabled rapid clinical improvement with prompt extubation and remission without plasma exchange or intravenous immunoglobulin, and she was maintained on tacrolimus without oral corticosteroids. These findings suggest efgartigimod may be a fast-acting option for acute anti-MUSK MG crisis, potentially reducing reliance on standard rescue therapies.

Senda J, Kato H, Kamiya-Goto R et al. · Internal medicine (Tokyo, Japan) · (2026) · View on PubMed ↗ · Free PDF ↗

Inflammatory Bowel Disease and Interleukin-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated whether IL-17 inhibitors increase inflammatory bowel disease (IBD) incidence in patients with hidradenitis suppurativa (HS). The study compared IBD event rates between HS patients treated with IL-17 inhibitors and placebo groups (and assessed incidence across included trials/records). The results address a key safety concern—whether IL-17 blockade unmasks underlying IBD risk or truly increases IBD risk in the HS population.

Cutrona M, Jolkovsky EL, Romanelli S et al. · JAMA dermatology · (2026) · View on PubMed ↗

Clinical trials & therapeutics (oncology)

Severity and management of hypercortisolism in patients with adrenocortical carcinoma and overt Cushing´s syndrome.

This retrospective international cohort study evaluated how baseline hypercortisolism severity relates to progression-free survival, disease-free survival, and overall survival in patients with adrenocortical carcinoma (ACC) presenting with overt Cushing’s syndrome. Patients had markedly elevated urinary free cortisol (UFC) at diagnosis (median 6.4× ULN), and the study assessed whether the degree of hypercortisolism predicted subsequent survival outcomes. Clinically, the results aim to refine prognostication in ACC-associated Cushing’s syndrome by tying cortisol burden to long-term outcomes.

Araujo-Castro M, Bancos I, Detomas M et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗

Actual Five-year Survival After Neoadjuvant Therapy and Resection for Localized Pancreatic Ductal Adenocarcinoma.

This retrospective cohort study evaluated actual 5-year survival after neoadjuvant therapy followed by curative-intent pancreatectomy in patients with localized pancreatic ductal adenocarcinoma (PDAC) treated at two high-volume centers. Among 660 patients with complete follow-up, the study measured actual (not actuarial) 5-year survival from surgery as the primary endpoint. The findings provide more realistic long-term outcome estimates to guide expectations and decision-making for localized PDAC treated with neoadjuvant strategies.

De Stefano F, Belfiori G, Wu NF et al. · Annals of surgery · (2026) · View on PubMed ↗

This phase 3, global, randomized, double-blind, placebo-controlled MATTERHORN trial evaluated whether perioperative durvalumab plus FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) improves overall survival in adults with resectable stage II–IVa gastric or gastro-oesophageal junction adenocarcinoma. The key finding was that overall survival and event-free survival benefits were assessed according to pathological response, extending the previously observed improvements in event-free survival and pathological complete response. If confirmed, these results strengthen the clinical rationale for adding the anti–PD-L1 antibody durvalumab to perioperative FLOT to improve long-term outcomes after curative-intent surgery.

Janjigian YY, Al-Batran SE, Wainberg ZA et al. · Lancet (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗

Pomalidomide plus bortezomib and dexamethasone for newly diagnosed multiple myeloma with renal impairment: Randomized phase II study (POM-MM-003).

This randomized phase II trial studied pomalidomide plus bortezomib and dexamethasone (PVd) versus bortezomib and dexamethasone (Vd) in newly diagnosed multiple myeloma (NDMM) patients with renal impairment (creatinine clearance 15 to <60 mL/min). The primary endpoint was very good partial response or better (≥VGPR) after 4 cycles of induction, and patients were assigned 2:1 to PVd (n=58) versus Vd (n=24) (full results truncated in the abstract). If PVd improves response in this renal-impairment population, it could refine induction regimens for NDMM patients who are often excluded from standard trials.

Xiao F, Wang L, Li F et al. · Med (New York, N.Y.) · (2026) · View on PubMed ↗ · Free PDF ↗

Treatment Decisions in Multiple Myeloma.

This article reviewed how treatment decisions in multiple myeloma should be individualized in the era of transplantation, targeted therapy, and immune therapies. It proposes a practical framework that integrates cytogenetic/genomic risk stratification, functional fitness, and measurable residual disease (MRD) status to guide therapy selection across the disease spectrum, including newly diagnosed disease where quadruplet induction is standard (truncated). The synthesis helps clinicians translate trial evidence and emerging biology into more precise, patient-specific treatment strategies.

Mouhieddine TH, Anderson KC · The New England journal of medicine · (2026) · View on PubMed ↗

Risk-Adapted Optimization of Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer.

This review studied risk-adapted de-escalation strategies for neoadjuvant therapy in women with stage II–III HER2-positive early-stage breast cancer, focusing on regimens built around docetaxel or paclitaxel plus trastuzumab and pertuzumab and the evidence for omitting carboplatin in selected patients. The key finding is that randomized trial data support safely omitting carboplatin for most stage II patients while maintaining comparable pathological complete response rates and reducing toxicity, enabling more individualized treatment intensity. Clinically, this supports biomarker- and risk-guided optimization of HER2-directed neoadjuvant therapy to improve tolerability without sacrificing efficacy.

Kleeman SO, Stearns V · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Biomarkers & risk prediction (imaging/omics/fluids)

Chronic conditions and aortic disease risk: a prospective cohort study with predictive and etiological analyses.

This prospective cohort study assessed associations between 42 chronic conditions/multimorbidity and incident aortic disease in UK Biobank (UKB), with external validation in the China Kadoorie Biobank (CKB). After multiple-testing correction in UKB, 21 chronic conditions—including coronary heart disease, hypertension, atrial fibrillation, peripheral vascular disease, heart failure, and COPD—were associated with overall aortic disease, with similar patterns in CKB. The results broaden etiologic understanding of aortic disease beyond traditional cardiovascular risk factors and support improved risk stratification using multimorbidity profiles.

Yu L, Lu P, Yang M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

An operational perturbation proteomics-based virtual cell model.

This work developed an operational perturbation proteomics-based virtual cell model by generating large-scale, time-resolved perturbation proteomics data from systematically perturbed breast cancer cell lines. Using more than 38 million temporal protein-abundance measurements, the authors built ProteinTalks, an interpretable virtual cell framework with a pretraining approach that learns transferable dynamical latent representations to predict therapeutic responses. Scientifically, it advances AI-enabled, mechanism-linked in silico modeling for drug discovery using dynamic proteome trajectories.

Sun R, Qian L, Li Y et al. · Nature · (2026) · 1 citations · View on PubMed ↗

Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2.

The study developed Tracking-seq2, an ultra-sensitive method to profile CRISPR-Cas off-target effects in primary human cells by combining exogenous 5’→3’ exonuclease treatment with NHEJ pathway inhibitors on top of Tracking-seq. Tracking-seq2 improved sensitivity across multiple editors—including Cas9, Cas12a, cytosine base editors (CBEs), adenine base editors (ABEs), and prime editors (PEs)—and was positioned as directly applicable to clinically relevant primary human cell types. This advances the safety assessment of genome-editing therapies by enabling detection of low-frequency off-target events that may be missed by existing assays.

Cong T, Xu R, Chen X et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Development and external validation of a new prognostic model for metastatic clear cell renal cell carcinoma: a preregistered analysis using data from randomised clinical trials in the checkpoint inhibitor era.

This preregistered study developed and externally validated prognostic models for metastatic clear cell renal cell carcinoma (mccRCC) using individual patient data from randomized checkpoint inhibitor trials. The key finding was that the newly developed Clinical Prognostic Index in the Checkpoint Inhibitor era (CPI2), derived from CheckMate-214 and externally validated using CheckMate-9ER, provided prognostic stratification in the checkpoint inhibitor era, with performance compared against the IMDC model. Clinically, improved prognostic indexing can better inform risk-adapted trial design and treatment decisions for patients with mccRCC receiving immune checkpoint inhibitors.

Richters A, Bond MJG, Westgeest HM et al. · The Lancet. Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

This study introduced UniCure, a multi-modal model designed to predict personalized cancer therapy response by forecasting drug-induced transcriptomic changes across diverse cell and tissue contexts. Trained on 1.9 million transcriptomic perturbation profiles covering >22,000 compounds, 166 cell types, and 24 tissues, UniCure accurately predicted dose-dependent and combination responses and enabled individualized drug ranking. This approach aims to bridge the gap between cell-line-trained models and patient-relevant biology for more reliable precision oncology decision support.

Chen Z, Tian S, Pei J et al. · Cancer cell · (2026) · View on PubMed ↗

Nighttime light exposure and cardiac structure and function.

This population-based cohort study examined whether nighttime light exposure is associated with cardiac structure and function in humans. Using 11,071 UK Biobank participants who wore wrist accelerometers with integrated light sensors for 7 days (2013–2015) and underwent cardiovascular magnetic resonance (CMR) imaging 3 years later, the authors assessed dose-response relationships for nighttime light exposure (>3 lux) with CMR phenotypes and subsequent cardiovascular outcomes (truncated). If confirmed, nighttime light exposure could represent a modifiable environmental risk factor relevant to cardiac remodeling and future cardiovascular disease prevention.

Dai J, Dai W, Heianza Y et al. · European heart journal · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

LymphGen-Sig: Integrating Genetic and Transcriptional States to Predict Therapeutic Response in Diffuse Large B-Cell Lymphoma.

This study developed LymphGen-Sig (LGsig), a gene expression-based platform that integrates genetic and transcriptional states to predict therapeutic response in diffuse large B-cell lymphoma (DLBCL). Built from subtype-specific gene expression signatures of each LymphGen (LG) class using paired genomic and transcriptomic data (N=764), LGsig was designed to classify all DLBCLs and harmonize genetic and non-genetic dimensions of disease biology (truncated). By improving comprehensive classification beyond existing LymphGen tools, LGsig could enhance precision treatment selection and response prediction in DLBCL.

Tumuluru S, Cooper A, Jiang Y et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Personalized Circulating Tumor DNA Analysis for Predicting Outcomes and Tracking Response to Radiotherapy and Pembrolizumab in Localized Sarcomas: Analysis of the SU2C-SARC032 Trial.

This study investigated personalized circulating tumor DNA (ctDNA) analysis in 106 patients with high-risk, localized soft tissue sarcoma enrolled in the SU2C-SARC032 phase II trial receiving preoperative radiotherapy with or without perioperative pembrolizumab. The key finding was that personalized ctDNA profiling from serial plasma samples (pre-treatment, post-radiotherapy/presurgery, and post-surgery) could predict outcomes and track treatment response despite the technical challenges of low mutational burden and tumor heterogeneity. Scientifically and clinically, it supports ctDNA as a feasible, patient-specific biomarker platform for monitoring radiotherapy and pembrolizumab response in localized sarcoma.

Subramanian A, Nouth SCL, Nemat-Gorgani N et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Machine learning-driven spleen imaging and genomics uncover a splenic connection to coronary artery disease.

This study used machine learning to connect spleen imaging features with coronary artery disease (CAD) risk by extracting 107 splenic radiomic features from abdominal MRI in 42,059 UK Biobank participants and validating in 2,745 participants from the Mass General Brigham Biobank. The key finding was that specific deep-learning-derived splenic radiomic signatures were associated with CAD and helped uncover a mechanistic “splenic connection” beyond traditional risk factors. Scientifically, it positions spleen radiomics as a scalable, imaging-based proxy for hematopoietic biology relevant to CAD risk stratification.

Kamineni M, Raghu V, Hua Z et al. · Science translational medicine · (2026) · View on PubMed ↗

Proteomics identify disease-associated variants in patients with rare diseases undiagnosed after genome sequencing.

This study evaluated whether serum proteomics can improve diagnostic yield in rare disease patients who remained genetically undiagnosed after genome sequencing, analyzing 424 patients from the 100,000 Genomes Project. The key finding was that Olink Explore 1536 serum proteomic profiling (1,463 proteins) identified significant protein “outliers” in 13 patients, enabling resolution of variants of uncertain significance or prioritization for targeted reanalysis, and extended diagnostic insights in an additional 23 patients. Scientifically and clinically, it supports integrating proteomics with genome sequencing to increase diagnostic rates in rare diseases when genetic testing alone is inconclusive.

Carrasco-Zanini J, Andrade J, Pietzner M et al. · Science translational medicine · (2026) · View on PubMed ↗

Changes in Characteristics Associated With ADHD and ASD Diagnoses Over Time.

This population-based matched case-control study used nationwide Danish registry data to examine how prediagnostic characteristics associated with ADHD and ASD diagnoses have changed over time. The authors assessed temporal trends in associations between well-defined risk factors and subsequent ADHD/ASD diagnoses among individuals followed from birth cohorts through age 18. Understanding these shifting associations is clinically important for interpreting changing diagnostic patterns and for refining early risk identification strategies.

Tarp ME, Lousdal ML, Rask CU et al. · JAMA psychiatry · (2026) · View on PubMed ↗

Associations of Baseline Neutrophil-to-Lymphocyte Ratio with Efficacy and Toxicity of the B7H3 ADC YL201, Linked to Interleukin-6: Analysis of the Phase 1/1b Trial.

This analysis studied whether baseline and on-treatment inflammation markers predict efficacy and toxicity of the B7H3-targeting antibody-drug conjugate YL201 in a phase 1/1b trial. In peripheral blood, baseline and cycle-specific systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were associated with progression-free survival and toxicity outcomes using Cox and logistic regression models. These findings support using readily measurable inflammatory biomarkers to stratify patients likely to benefit from YL201 and to anticipate adverse events.

Hu J, Zhong X, Ma Y et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗ · Free PDF ↗

Neuroscience & brain circuits/neuromodulation

Imaging cellular activity across all organs reveals body-wide circuits.

This study introduced WHOLISTIC (WHole-Organism Live-Imaging System for recording Tissue and IntraCellular activity) to image second-timescale cellular activity across the entire vertebrate body at cellular resolution. Using this whole-body live-imaging approach, the authors revealed body-wide circuits by capturing coordinated cellular activity patterns across organs and cell types. The technique and findings enable system-level mapping of physiological interactions that underlie behavior and disease responses.

Ruetten VMS, Zheng W, Siwanowicz I et al. · Nature · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Neocortical long-range inhibition promotes cortical synchrony and sleep.

The study examined how a sparse class of neocortical GABAergic inhibitory neurons that co-express somatostatin (Sst) and chondrolectin (Chodl) coordinates long-range cortical inhibition in mice during sleep and wake. The authors found that Sst/Chodl inhibitory cells are selectively active during low-arousal states and that their long-range inhibition promotes cortical synchrony and slow-wave-like rhythmic activity across widespread neocortex. This identifies a genetically defined inhibitory circuit mechanism that can causally link specific interneuron populations to global cortical state regulation during sleep.

Ratliff JM, Terral G, Vazquez A et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Cryoprotectants-assisted plunge freezing of thick brain tissue specimens for targeted physiologically relevant cryo-imaging in situ.

This work studied how cryoprotectants-assisted plunge freezing can vitrify thick mouse brain tissue specimens for targeted in situ cryo-imaging using cryo-electron tomography (cryoET) and cryo-FIB/SEM volume electron microscopy (volume-EM). The authors benchmarked plunge freezing conditions enabling vitrification of ~100 μm thick tissue and used a knock-in mouse with fluorescent astrocytes to target regions for cryo-FIB/SEM and cryoET imaging. The method improves feasibility and throughput of near-native structural imaging in thick brain samples, supporting more physiologically relevant connectomics and ultrastructural studies.

Weier A, Gao F, Morgan ET et al. · Cell reports methods · (2026) · View on PubMed ↗ · Free PDF ↗

Mapping cell-type- and age-dependent neuronal vulnerability through genome-wide in vivo CRISPRi screens in the mouse brain.

This study developed a scalable, cell-type-resolved in vivo CRISPR interference (CRISPRi) platform to map genome-wide neuronal vulnerability across four neuronal populations and three ages (youth to aging) in the mouse brain. Genome-wide screens identified neuronal essential genes missed in vitro and produced a consensus set of 269 neuronal core essential genes, revealing cell-type-specific genetic dependencies that were validated for targets including Exosome component 9 (Exosc9) and osteopetrosis-associated gene osteopetro (truncated in abstract). The results provide a functional, age-aware genetic vulnerability atlas that can guide mechanism-focused therapeutic target discovery for neurodegeneration.

Lin R, Ke Z, Wang J et al. · Neuron · (2026) · View on PubMed ↗

Targeted protein degradation & molecular glue therapies

TRI-611, a selective, brain-penetrant molecular glue degrader of ALK.

The study evaluated TRI-611, a brain-penetrant molecular glue degrader designed to target ALK fusion proteins, and tested how it engages the ALK kinase domain and the CRL4 substrate adaptor CRBN in relevant models of ALK-positive non-small-cell lung cancer (NSCLC). TRI-611 promotes proximity between the ALK kinase domain and CRBN via a unique degron interface distal to the kinase active site, producing selective ALK fusion protein degradation with proteome-wide selectivity. Clinically, this provides an orthogonal therapeutic strategy to overcome resistance to conventional ALK tyrosine kinase inhibitors (TKIs) in ALK-positive NSCLC.

Conery AR, La DS, Alekseyenko AA et al. · Nature · (2026) · View on PubMed ↗

Cardiometabolic disease & liver (MASLD/MASH/CKM)

Heart-liver co-management in MASLD: expert perspectives and recommendations from a multidisciplinary cardiometabolic framework.

This article synthesized expert perspectives and recommendations on coordinated cardiometabolic management of metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on cardiovascular risk and clinical pathways. It emphasizes that MASLD is frequently under-recognized in cardiology and outlines how to integrate non-invasive fibrosis assessment (e.g., FIB-4, vibration-controlled transient elastography) with emerging therapies that may benefit both liver and cardiovascular outcomes, such as resmetirom and GLP-1 receptor agonists or SGLT2 inhibitors. Clinically, it aims to reduce care gaps by providing a multidisciplinary framework for screening, risk stratification, and treatment coordination.

Zhou XD, Jeong S, Chen QF et al. · Nature reviews. Gastroenterology & hepatology · (2026) · View on PubMed ↗

A Bisubstrate Inhibitor of NNMT Suppresses Myofibroblast Reprogramming to Mitigate Skin Fibrosis.

This preclinical study investigated how inhibiting nicotinamide N-methyltransferase (NNMT) with the bisubstrate-like inhibitor II559 affects myofibroblast reprogramming and skin fibrosis. In TGF-β-stimulated fibroblasts and in bleomycin-induced mouse skin fibrosis, II559 suppressed fibrotic gene expression and extracellular matrix (ECM) pro-fibrotic programs, indicating reduced profibrotic fibroblast activation. Scientifically, it positions the NNMT–methylation/NAD+ metabolic axis as a therapeutic target to mitigate systemic sclerosis–associated skin fibrosis.

Saba K, Kataria S, Shi B et al. · The Journal of investigative dermatology · (2026) · View on PubMed ↗

Global Proteomic Profiling of Cerebral Malaria-Infected Erythrocytes Reveals a specific PfEMP1 Expression Pattern.

This proteomics study analyzed cerebral malaria–infected erythrocytes from the NeuroCM cohort (10 uncomplicated malaria and 9 cerebral malaria children from Benin) to define PfEMP1 expression patterns associated with cerebral malaria. Using global proteomic profiling, the authors found a specific PfEMP1 expression pattern that distinguished cerebral malaria cases and linked it to domain cassette features known to be associated with cerebral disease. The significance is improved mechanistic understanding of cerebral malaria pathogenesis and potential biomarker targets within PfEMP1 for future diagnostics or interventions.

Fraering J, Salnot V, Joste V et al. · Molecular & cellular proteomics : MCP · (2026) · View on PubMed ↗ · Free PDF ↗

This study evaluated whether cardiovascular-kidney-metabolic (CKM) syndrome stage stratifies risk for major adverse cardiovascular events (MACEs) and liver-related events (LREs) across the steatotic liver disease (SLD) spectrum. In UK Biobank participants with SLD classified as MASLD, MetALD, or ALD, the authors used Cox models and Kaplan–Meier analyses to assess associations of CKM stage with incident MACEs and LREs overall and by subtype (details truncated). The work supports CKM staging as a cross-disease risk stratification framework linking cardiometabolic dysfunction to both cardiovascular and liver outcomes in SLD.

Fan QY, Lian LY, Xia TY et al. · Med (New York, N.Y.) · (2026) · View on PubMed ↗

Dysregulated m6A via compensatory arginine methylation primes premalignancy in metabolic dysfunction-associated steatotic liver disease.

The authors investigated how dysregulated N6-methyladenosine (m6A) regulation, driven by compensatory arginine methylation, primes premalignancy during metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH) progression, using PRMT1 liver-specific knockout (Prmt1 LKO) mice and related models. They found that loss of PRMT1 reprograms mRNA stability via m6A-mediated changes through paralog compensation, with increased PRMT6 activating m6A methyltransferases and accelerating premalignant progression toward hepatocellular carcinoma (HCC). This links PRMT1–PRMT6–m6A regulatory circuitry to MASLD/MASH-associated carcinogenesis, identifying potential molecular targets for preventing HCC in metabolic liver disease.

Kim GD, Choi D, Kim SY et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Semaglutide and Tirzepatide for the treatment of MASH: What Works, What’s Coming, and What’s Missing.

This article reviewed evidence for incretin-based pharmacotherapies—specifically semaglutide (GLP-1 receptor agonist) and tirzepatide (dual GLP-1/GIP agonist)—for treating metabolic dysfunction-associated steatohepatitis (MASH). It summarizes what is known to work, what is emerging, and what gaps remain in clinical outcomes and translational understanding for these drugs in MASH. The review helps clinicians and researchers prioritize next steps for improving histologic and clinical endpoints in MASH beyond lifestyle interventions.

Chirapongsathorn S, Tacke F · Digestion · (2026) · View on PubMed ↗

Respiratory disease & airway inflammation

Inhaled siRNA therapy targeting RAGE for pulmonary inflammation: a first-in-human randomized trial.

The study conducted a first-in-human randomized trial of ARO-RAGE, an inhaled, lung-epithelium-targeted siRNA designed to silence pulmonary RAGE mRNA in participants with pulmonary inflammation. ARO-RAGE produced dose-dependent reductions in RAGE expression with deep and durable target silencing observed from preclinical models and reported early clinical effects consistent with reduced inflammatory signaling. This supports inhaled siRNA against RAGE as a translational approach to dampen innate immune amplification in lung disease.

O’Carroll M, Kasahara D, Huetsch J et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and Predictors of Response to Biologic Therapy and Endoscopic Sinus Surgery in Patients With Nasal Polyps: A Systematic Review.

This systematic review studied efficacy and predictors of response to biologic therapy versus endoscopic sinus surgery (ESS) in adults with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) by extracting SNOT-22 and nasal polyp score (NPS) outcomes from randomized trials. Across 13 trials (including 10 phase-3 placebo-controlled biologic RCTs, ESS trials, and a head-to-head biologic trial), the authors synthesized overall effect sizes and subgroup interactions to identify which patient subgroups may respond better. Scientifically and clinically, it supports more personalized selection between biologics and ESS for CRSwNP.

Chakravorty A, Lin ME, Lubner R et al. · International forum of allergy & rhinology · (2026) · View on PubMed ↗ · Free PDF ↗

Assessing the impact of earlier initiation of biologics on clinical remission and other outcomes in a global real-life severe asthma cohort from CHRONICLE, ISAR and OPCRD.

This global cohort study assessed whether earlier initiation of biologics improves clinical remission and other outcomes in severe asthma by analyzing real-life data from the International Severe Asthma Registry, CHRONICLE, and the UK Optimum Patient Care Research Database across 26 countries. The key finding was that timing of biologic initiation (using proxies such as duration of asthma) was associated with differences in remission and outcomes, addressing the gap between RCT efficacy and optimal treatment timing. Clinically, it informs when to escalate to biologics in severe asthma to maximize remission chances.

Canonica GW, Christoff GC, Tsai MJ et al. · Chest · (2026) · View on PubMed ↗ · Free PDF ↗

Microbiome & host-microbe axes

Commensal Nakaseomyces glabratus migrates into prostate tumors to accelerate cancer progression.

The study examined whether the commensal fungus Nakaseomyces glabratus contributes to prostate cancer progression by migrating into tumors, using patient sample correlations and mouse models of castration-resistant prostate cancer. Oral N. glabratus administration in castrated mice accelerated cancer progression by promoting infiltration and activation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and mechanistically androgen deprivation therapy increased intestinal permeability leading to fungal leakage into circulation. This identifies a gut-fungus–myeloid axis that may worsen outcomes under androgen deprivation therapy and suggests microbiome-targeted interventions as potential adjuncts in prostate cancer.

Lai P, Liu L, Pernigoni N et al. · Nature cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Novel insight into the effects of the metabolites from gut microbiota in both unmedicated depressive adolescents and mice: key roles of indole derivatives-aryl hydrocarbon receptor signaling in neurogenesis and microglial homeostasis.

The study examined gut microbiota tryptophan/indole metabolite alterations in unmedicated adolescents with depression and in mice, focusing on indole derivative–aryl hydrocarbon receptor (AhR) signaling in neurogenesis and microglial homeostasis. 16S rRNA gene sequencing showed reduced Bacteroidetes abundance in depressed adolescents, and the indole/AhR axis was implicated in impaired neurogenesis and disrupted microglial homeostasis. These findings support targeting microbiota-derived indole–AhR signaling as a potential mechanism-based strategy for adolescent depression and its neuroimmune dysregulation.

Wang X, Hu M, Wu W et al. · Molecular psychiatry · (2026) · View on PubMed ↗

Chronic psychological stress impairs sperm quality via a gut-endotoxin-testis axis.

This study examined how chronic unpredictable mild stress in male C57BL/6 mice alters the gut microbiota and metabolites and thereby impairs sperm quality through a gut–endotoxin–testis axis. Using 16S rRNA gene sequencing, shotgun metagenomics, and metabolomics alongside assessments of gut barrier integrity, systemic inflammation, and testicular phenotypes, the authors found that stress-driven gut dysbiosis and endotoxin-related changes were associated with worsened testicular outcomes and reduced sperm quality. These findings support a mechanistic gut–testis pathway linking psychological stress to male infertility and suggest that targeting gut barrier function or microbiome/endotoxin signaling could be a therapeutic strategy.

Pan Y, Wang S, Li B et al. · Brain, behavior, and immunity · (2026) · View on PubMed ↗

Microbial indole-3-acetamide alleviates polycystic ovary syndrome through HIF-2α-ceramide signaling.

This study examined whether the gut bacterium Collinsella aerofaciens and its metabolite indole-3-acetamide (IAM) modulate polycystic ovary syndrome (PCOS) in women and through what adipose signaling pathway. The authors found that C. aerofaciens and IAM were reduced in PCOS patients and that IAM activates adipose hypoxia-inducible factor 2α (HIF-2α) signaling to promote adipose ceramide degradation, thereby ameliorating PCOS phenotypes. These findings link gut microbial metabolism to HIF-2α–ceramide regulation as a potential therapeutic axis for PCOS.

Chen W, Zhao M, Yan S et al. · Cell host & microbe · (2026) · View on PubMed ↗

Neurodegeneration & dementia biomarkers

Brain-gut crosstalk associated with brain ageing in young and mid-life adults: a multicohort cross-sectional study.

The multicohort cross-sectional study assessed whether a functional-connectivity-derived brain ageing index (BAI) reflects early brain ageing and relates to cognitive-affective function and gut-derived biological signatures in young and mid-life adults. Using resting-state fMRI with discovery (n=674), replication (n=444), and independent validation (n=344), the study tested reproducible variability in early brain ageing and its association with gut-brain crosstalk markers. If confirmed by the reported analyses, these results would support BAI as an early biomarker and link brain ageing to gut-derived biological pathways relevant to preventive interventions.

Zhao K, Vignolle GA, Labus JS et al. · EBioMedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Plasma phosphorylated tau 217 concentrations, APOE genotype, and timing of cognitive impairment in individuals across diverse racial and ethnic groups: a pooled analysis of prospective cohort studies.

This pooled analysis of seven multi-ethnic prospective cohorts studied whether APOE genotype adds prognostic information beyond baseline plasma phosphorylated tau at threonine 217 (p-tau217) for predicting the risk and timing of cognitive impairment in older adults. The key finding was that individuals’ APOE genotype meaningfully modified the relationship between plasma p-tau217 levels and subsequent cognitive decline timing, indicating genotype-dependent differences in risk trajectories despite similar biomarker concentrations. Scientifically and clinically, combining APOE genotype with plasma p-tau217 could improve individualized prediction of cognitive impairment onset in diverse populations.

Xu Y, Gunasekaran TI, Gu Y et al. · The Lancet. Neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Clinical pathways for cognitively unimpaired individuals with Alzheimer’s disease neuropathological change.

This article reviewed clinical pathways for cognitively unimpaired individuals who have Alzheimer’s disease neuropathological change (ADNC), focusing on how biomarker-defined disease status intersects with emerging disease-modifying therapies. The key finding was that anti-amyloid monoclonal antibodies may offer greatest benefit in subgroups with lower baseline AD pathology, and that prevention trials are testing treatment in cognitively unimpaired people with biomarker evidence of ADNC. The significance is that it frames how to operationalize biomarker testing and treatment eligibility in real-world care for preclinical/early AD.

Graff-Radford J, Karliner L, Barnes DE et al. · The Lancet. Neurology · (2026) · 2 citations · View on PubMed ↗

Neuroimaging in the era of biologically defined Alzheimer’s disease and disease-modifying therapy.

This narrative review discussed how neuroimaging is used in the era of biologically defined Alzheimer’s disease and disease-modifying therapy. The key finding was that imaging—especially MRI and amyloid PET—has become central for visualizing cumulative pathology, determining treatment eligibility, and monitoring patients as diagnosis shifts from clinical symptoms to biological evidence. Scientifically and clinically, it highlights how imaging biomarkers can support more precise management in patients receiving amyloid-targeting therapies.

Benzinger TLS, Cogswell PM, Arani A et al. · The Lancet. Neurology · (2026) · 3 citations · View on PubMed ↗

This review summarized the role of fluid biomarkers in the evolving care landscape for Alzheimer’s disease and related disorders, emphasizing advances in ultrasensitive multiplexing and high-specificity antibodies. The key finding was that blood-based biomarkers such as neurofilament light (for FTD/ALS) and plasma p-tau217 (for Alzheimer’s disease diagnosis) are increasingly being implemented clinically, and that multiple fluid biomarkers are needed to capture disease complexity. The significance is that fluid biomarker panels can enable earlier, more accurate diagnosis and better selection/monitoring for amyloid-targeting treatments.

Teunissen CE, Vermunt L, Barthélemy NR et al. · The Lancet. Neurology · (2026) · 2 citations · View on PubMed ↗

Sleep & circadian/physiology interventions

Closed-loop auditory stimulation in phase with slow waves during sleep enhances cerebrospinal fluid flow in humans.

This human study examined whether closed-loop auditory stimulation timed to NREM sleep slow waves can causally enhance cerebrospinal fluid (CSF) flow, using real-time EEG-guided targeting during simultaneous MRI. The key finding was that phase-locked auditory stimulation increased CSF flow waves associated with slow-wave activity compared with control conditions. Clinically and scientifically, it provides evidence that modulating sleep slow waves can drive CSF dynamics, supporting a potential noninvasive approach to influence brain fluid homeostasis.

Levitt J, Zeng X, Yang Z et al. · Science translational medicine · (2026) · View on PubMed ↗

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

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PubMed Trending Research Digest — September 11, 2026

PubMed Trending Research Digest — September 11, 2026

Overview

Clinical trials & therapeutics (non-oncology)

Efficacy and safety of mitapivat in adults with transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE-T): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.

Loberamisal for Acute Ischemic Stroke: The LAIS Randomized Clinical Trial.

Dual orexin receptor antagonist-assisted dose reduction of benzodiazepines and benzodiazepine receptor agonists: a mirror-image analysis of insurance claims data.

Anesthetic Safety and Perioperative Outcomes in GLP-1 Receptor Agonist-Treated Patients Undergoing Lipoabdominoplasty.

Effect of exercise on bone health in middle aged and older adults: hierarchical network meta-analysis of randomised trials.

Comorbidities in clinical cohorts of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

Reducing Inequities in Restraint Use in the Pediatric Emergency Department.

RECREA: Registry of Cardiac Rehabilitation Centers in Latin America of the Council of Cardiac Rehabilitation and Sports Cardiology of the Inter-American Society of Cardiology.

Safety, tolerability, and efficacy of RIPK1 inhibitor, SAR443820, in amyotrophic lateral sclerosis (HIMALAYA): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Longitudinal Outcomes of Total Hip Arthroplasty in Developmental Dysplasia of the Hip: A National Database Propensity-Matched Analysis.

Intravenous gene therapy improves life span and clinical outcomes in a feline model of Sandhoff disease.

Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice.

Engineering suppressor tRNAs for effective treatment of Duchenne muscular dystrophy.

Drug Survival of Omalizumab and Factors Associated With Discontinuation in Chronic Urticaria: A Meta-Analysis.

Cancer genetics & mutational mechanisms

Noncoding transcription controls the developmental dynamics of long-range gene regulation.

The complete telomere-to-telomere sequence of a mouse Y chromosome.

International consensus guidance for general population screening for islet autoantibodies to diagnose early-stage type 1 diabetes: a nominal group technique process.

Integrated signatures define mutational processes in prostate cancer.

Predicting genome-wide functional constraints with GPN-Star.

Recurrent mechanisms of biallelic epigenetic inactivation reveal new putative tumour suppressor genes in prostate cancer.

Caloric restriction modulates genome-wide somatic mutation in mice.

The CENP-A chaperone complex spatially organizes centromeres.

A direct protein bridge connects the ds and ds-ss junction telomeric DNA segments in C. elegans.

Infectious disease & host-pathogen mechanisms

Mechanism of membrane perforation in rotavirus cell entry.

Bacterial co-detection in individuals with acute respiratory infections through a direct-to-consumer platform in China: a retrospective cross-sectional study.

Oligoclonal nanobody-based recombinant antivenom protects mice challenged with venom from cobras and king cobras from India.

FERONIA phosphorylates the amino-terminal extension of phytochrome B to modulate plant light and temperature responses.

Cancer cell biology & tumor vulnerabilities

Lean adipocyte oxylipin signaling restrains breast cancer through ferroptosis.

Targeting USP7 lactylation suppresses NSCLC tumorigenesis by promoting PINK1 ubiquitination and degradation.

TM184C is a GPCR-like regulator of intercellular exchange and autophagy.

KRAS/ERK2-driven stabilization of AARS1 reprograms tumor metabolism and confers Sorafenib resistance in lung adenocarcinoma.

Alveolar epithelial depletion of βPAK-interacting exchange factor drives spontaneous pulmonary fibrosis by impairing stemness.

Inflammatory neuropathy in mouse and primate models of colorectal cancer.

The stress-sensing MARCH5 axis governs blood cancer apoptotic resilience via tractable protein-protein interactions.

Peroxiredoxin 1 safeguards the nucleolar genome from oxidative damage.

Rare Hematopoietic Stem Cells resilient to infection-induced stress sense yet withstand inflammation.

FANCM is required for the PAX3::FOXO1-driven oncogenic program in rhabdomyosarcoma.

MAVS undergoes aggregation under hypoxia to enhance the hypoxia signaling pathway by promoting the generation of mitochondrial ROS.

Minimal-length CAG repeats in AR define a hyperactive AR-LSD1 axis driving metabolic reprogramming in prostate cancer.

Immunotherapy & tumor microenvironment

Chronic type II interferon promotes tumor growth through mitochondrial RNA-induced type I interferon and prostaglandin synthesis.

Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.

PLA2G2D in tumour-draining lymph nodes regulates anti-tumour immunity.

A serpin-myeloid axis in pancreatic cancer heterogeneity and immune evasion.

Neutrophil extracellular traps promote liver metastasis by impairing NK cell-dependent tumor surveillance via CCDC25.

Cutaneous Toxicities of T-Cell-Redirecting Therapies in Multiple Myeloma: An EADV Task Force Position Paper and Practical Recommendations.

PRKX-mediated stabilization of PD-L1 characterizes an immunosuppressive gastric cancer subtype.

Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.

TCR-JANUS engager proteins enable bispecific targeting to overcome tumor heterogeneity in TCR-T cell therapy.

Spatiotemporal mapping of tertiary lymphoid structure heterogeneity shapes immune niches and clinical outcomes in intrahepatic cholangiocarcinoma.

Autoimmunity & immune-related adverse events

Rheumatoid Arthritis in Adults: A Review.

Genomic meta-analyses of binge-eating behavior and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes.

Risk of Coeliac Disease After Immune Checkpoint Inhibitor Exposure in Patients With Cancer.

Tuberculosis during JAK inhibitor or TNF-α inhibitors therapy: a disproportionality analysis from WHO pharmacovigilance database.

Efgartigimod and Steroid Pulse Therapy as an Early Fast-acting Treatment Strategy for Anti-MUSK Myasthenic Crisis.

Inflammatory Bowel Disease and Interleukin-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis.

Clinical trials & therapeutics (oncology)

Severity and management of hypercortisolism in patients with adrenocortical carcinoma and overt Cushing´s syndrome.

Actual Five-year Survival After Neoadjuvant Therapy and Resection for Localized Pancreatic Ductal Adenocarcinoma.

Pomalidomide plus bortezomib and dexamethasone for newly diagnosed multiple myeloma with renal impairment: Randomized phase II study (POM-MM-003).

Treatment Decisions in Multiple Myeloma.

Risk-Adapted Optimization of Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer.

Biomarkers & risk prediction (imaging/omics/fluids)

Chronic conditions and aortic disease risk: a prospective cohort study with predictive and etiological analyses.

An operational perturbation proteomics-based virtual cell model.

Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2.

Development and external validation of a new prognostic model for metastatic clear cell renal cell carcinoma: a preregistered analysis using data from randomised clinical trials in the checkpoint inhibitor era.

UniCure: A multi-modal model for predicting personalized cancer therapy response.

Nighttime light exposure and cardiac structure and function.

LymphGen-Sig: Integrating Genetic and Transcriptional States to Predict Therapeutic Response in Diffuse Large B-Cell Lymphoma.

Personalized Circulating Tumor DNA Analysis for Predicting Outcomes and Tracking Response to Radiotherapy and Pembrolizumab in Localized Sarcomas: Analysis of the SU2C-SARC032 Trial.

Machine learning-driven spleen imaging and genomics uncover a splenic connection to coronary artery disease.