PubMed Trending Research Digest — October 15, 2026
A curated digest of 95 trending PubMed articles, automatically categorised and summarised across 15 research areas.
Jump to category
PubMed Trending Research Digest — October 15, 2026
Automated digest · 95 articles · 15 research areas · October 15, 2026
Overview
This week’s digest is dominated by two converging trends: (1) precision stratification using biomarkers and mechanistic vulnerabilities, and (2) translational delivery/targeting innovations that make therapies safer and more specific. Across multiple cancers, studies emphasize tailoring treatment to the right subgroup—whether through MRD and drug–drug interaction management in AML, ctDNA dynamics in urothelial and leptomeningeal breast cancer, variant-aware prediction for ESR1-mutant breast cancer, or recurrence-risk modeling in stage IIIA melanoma. In parallel, mechanistic work continues to uncover actionable nodes (e.g., Hippo–YAP/TEAD activation via LATS1 loss in posterior fossa ependymoma; kynurenine–AhR pathway rewiring downstream of ARID2 loss in CTNNB1-mutant HCC; and epigenetic/immune coupling such as KAT5 inhibition triggering cGAS–STING activation). Together, these papers reinforce a shift from one-size-fits-all regimens toward biomarker- and pathway-guided decision-making.
On the therapeutic delivery and systems side, several studies highlight how route, targeting, and monitoring can change outcomes. Intrathecal SMA gene therapy guidance stresses route-specific surveillance, while multiple platform papers (microglia-specific AAV targeting, nonviral CAR NK manufacturing with ligand-directed LNPs, and closed-loop AI for epilepsy) show the field’s push toward better specificity and real-time clinical integration. In critical care and renal medicine, randomized and observational work focuses on practical implementation questions—dialysis modality in AKI, vasopressor escalation thresholds, and real-world ICU fluid practice—underscoring that “how” care is delivered matters as much as “what” is delivered. Finally, neurovascular and neuroinflammatory studies (cSVD microvascular states, Huntington’s barrier segment vulnerability, and NAD+-mitochondrial/cGAS–STING modulation after stroke) broaden the mechanistic landscape for brain aging and disease, suggesting increasingly targetable, compartment-specific biology.
Endocrinology across the lifespan (sex steroids)
GLP-1 receptor agonist initiation and risk of psychiatric hospitalisation and emergency department presentation in adults with schizophrenia and type 2 diabetes in the USA: an observational cohort study using electronic health records data.
This observational cohort study used US electronic health records to examine whether initiating GLP-1 receptor agonists is associated with psychiatric hospitalisation or emergency department presentations in adults with schizophrenia and type 2 diabetes, compared with DPP-4 inhibitor initiation, SGLT2 inhibitor initiation, and non-initiation. The study’s central finding was the association between GLP-1 receptor agonist initiation and subsequent psychiatric acute-care outcomes relative to comparator medication initiation strategies. If confirmed, the results would clarify whether GLP-1 receptor agonists provide psychiatric safety/benefit alongside metabolic effects in a high-risk comorbidity population.
Davoodian N, Williams LJ, Berk M et al. · The lancet. Psychiatry · (2026) · View on PubMed ↗
Early detection of gastric cancer using DNA features in red blood cells, with multicenter validation.
This multicenter study investigated early gastric cancer detection using DNA features from red blood cells (RBCs), profiling genome-wide DNA remnants retained in RBCs (rbcDNA). In 865 participants (434 treatment-naive gastric cancer patients and 431 controls with benign gastric conditions), shallow whole-genome sequencing of rbcDNA from 1–2 mL peripheral blood enabled identification of reproducible rbcDNA features for GC detection and validation across centers. The approach is clinically significant because it offers a non-invasive blood-based strategy that could improve early gastric cancer diagnosis beyond endoscopy and conventional biomarkers.
Yao X, Sun H, Fang C et al. · Med (New York, N.Y.) · (2026) · View on PubMed ↗
Beyond libido: the multifaceted role of testosterone in women.
This narrative review examined testosterone physiology in women across the lifespan, synthesizing evidence from studies published between 1974 and 2025. It concludes that testosterone is the most abundant biologically active sex steroid in women and has multifaceted roles beyond libido across multiple physiological systems. Clinically, the review supports improved recognition and more nuanced evaluation of testosterone’s functions in women rather than treating it as primarily a male hormone.
Hernandez BS, Covarrubias A, Perez-Grego PG et al. · Sexual medicine reviews · (2026) · View on PubMed ↗
Neurodevelopmental genetics & ER/secretory pathway disorders
Biallelic variants in PIKFYVE cause a hypomyelinating leukodystrophy with endolysosomal dysfunction.
This genetic study investigated the cause of hypomyelinating leukodystrophy with endolysosomal dysfunction in five affected individuals from three families using exome/genome sequencing, MRI phenotyping, and patient-derived fibroblast assays. It identified biallelic variants in PIKFYVE as the underlying gene defect and linked them to altered vacuole size/number/acidity and reduced PI(3,5)P2 levels measured with high-performance assays. The findings are clinically important because they establish a molecular diagnosis for a rare inherited leukodystrophy and clarify endolysosomal lipid-pathway mechanisms that could guide future therapies.
Averdunk L, Groß M, Hamacher AB et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗
Bi-allelic variants in the secretory pathway gene SEC16A are associated with a neurodevelopmental disorder.
This study investigated bi-allelic variants in the secretory pathway scaffold gene SEC16A in six individuals with early-onset neurodevelopmental symptoms, and used Drosophila and neuron-specific Sec16 knockdown models to probe mechanism. The authors found that SEC16A loss causes developmental failure in flies and produces neurological phenotypes including locomotor defects and seizures when knocked down in neurons. These findings identify SEC16A as a human neurodevelopmental disorder gene and implicate disrupted ER exit/secretory pathway function in disease pathogenesis.
Ma M, Lei X, Li J et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗
Hematologic oncology: AML real-world therapy, MRD & drug interactions
TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.
The study examined how loss of the DNA demethylase TET2 (compared with DNMT3A loss) affects DNA replication fork progression and DNA damage in cells treated with the PARP inhibitor olaparib (PARPi). TET2 loss caused longer replication tracts, increased DNA breaks, and accumulation of PRIMPOL-dependent single-stranded DNA (ssDNA) gaps, which mechanistically linked abnormal fork elongation to heightened PARPi sensitivity. These findings suggest that TET2-deficient clonal hematopoiesis/hematologic malignancies may be particularly vulnerable to PARP inhibition and provide a replication-fork/ssDNA-gap biomarker rationale for PARPi use.
Agashe S, Athreya N, Jacobs W et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Single-cell CRISPR screen maps epigenetic regulators of lineage specification and malignancies in human HSPCs.
This study developed a massively parallel single-cell CRISPR screening platform (scCRISPR) in primary human hematopoietic stem and progenitor cells (HSPCs) to map epigenetic regulators of lineage specification and malignancy. Across 172,382 single-perturbed cells targeting 322 regulators, the authors generated a multi-layer regulatory atlas showing that regulators act within perturbation clusters to control distinct gene programs shaping cell fate, including malignancy-relevant phenotypes. The work provides a high-resolution functional map of epigenetic control in human HSPCs that can prioritize regulators for developmental biology and cancer mechanisms.
Yuan S, Yang S, Huang Y et al. · Cell stem cell · (2026) · View on PubMed ↗ · Free PDF ↗
A feedback mechanism of m6A via PARP1-mediated ADP ribosylation of METTL3/METTL14.
This study investigated m6A homeostasis regulation in human cell lines by examining how the m6A reader IGF2BPs and the m6A writer complex METTL3/METTL14 are connected through PARP1-mediated ADP ribosylation. IGF2BPs recruited PARP1 to m6A-modified RNAs, leading to ADP ribosylation of METTL3/METTL14 that impaired its RNA-binding capability and reduced m6A deposition, establishing a negative feedback loop. The findings link PARP1 signaling to m6A writer activity and suggest that PARP inhibitor (PARPi) therapy could modulate m6A levels through this read-orchestrate-write mechanism.
Bai Y, Zhou Z, Yan X et al. · Molecular cell · (2026) · View on PubMed ↗
VERIFY: A Phase III Trial of Rusfertide Versus Placebo in Phlebotomy-Dependent Patients With Polycythemia Vera Receiving Standard-of-Care Therapy.
The phase III VERIFY trial studied rusfertide, a subcutaneous hepcidin mimetic peptide, versus placebo in phlebotomy-dependent patients with polycythemia vera (PV) receiving standard-of-care therapy, with or without cytoreductive treatment. The trial’s primary endpoint was clinical response defined by absence of phlebotomy eligibility during weeks 20–32, with additional hematologic and safety outcomes assessed through week 32. If positive, rusfertide would provide a targeted alternative to repeated phlebotomy for controlling erythrocytosis in PV.
Kuykendall AT, Bankar A, Pettit KM et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗
Pharmacologically targeting CDK12 induces BRCAness and synergizes with merestinib to exacerbate DNA damage in high-risk neuroblastoma.
This preclinical study tested whether pharmacologically targeting CDK12 induces BRCAness and synergizes with the DNA damage–exacerbating agent merestinib in high-risk neuroblastoma models driven by MYCN amplification. Using CDK12 inhibition/degradation (including the selective CDK12/13 inhibitor OKI-1546), the authors found induction of BRCAness and apoptosis, with synergy observed across multiple pathways when combined with merestinib. These findings provide a rationale for combination strategies that exploit transcriptional vulnerabilities to intensify DNA damage in MYCN-driven neuroblastoma.
Goulding JR, Couwenbergh ST, Bekaert SL et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗
Real-World Survival Outcomes of Venetoclax Combination Therapies in Acute Myeloid Leukemia: Impact of Minimal Residual Disease Status and Antifungal Prophylaxis.
This real-world study evaluated survival outcomes and safety of venetoclax-based combination therapies in first-line and subsequent treatment settings for acute myeloid leukemia, focusing on how minimal residual disease (MRD) status and antifungal prophylaxis affect results. It reports that venetoclax efficacy and tolerability in practice are influenced by MRD status and by the need to adjust venetoclax dosing when co-administered with mold-active antifungals such as posaconazole (a CYP3A4 inhibitor), given venetoclax’s CYP3A4 metabolism and P-glycoprotein substrate status. The clinical significance is that MRD stratification and careful management of venetoclax–antifungal drug interactions (including dose reduction) are key to optimizing outcomes in AML patients.
Sciumè M, Bosi A, Marchetti A et al. · Hematological oncology · (2026) · View on PubMed ↗ · Free PDF ↗
Cerebrovascular & small vessel disease (microvasculature, BBB/cSVD)
NAD+ Attenuates Neuroinflammation in Ischemic Stroke by Suppressing the cGAS- STING Pathway via Mitochondrial Homeostasis Restoration.
This preclinical study tested whether nicotinamide adenine dinucleotide (NAD+) attenuates neuroinflammation after ischemic stroke by suppressing the cGAS–STING pathway through restoration of mitochondrial homeostasis. NAD+ reduced post-ischemic neuroinflammatory signaling and inhibited cGAS–STING activation linked to mitochondrial DNA stress. Targeting NAD+-mitochondrial homeostasis to dampen cGAS–STING–driven innate immune responses may represent a therapeutic strategy for limiting stroke-associated neuroinflammation.
Jiang S, Liao B, Wang G et al. · Molecular neurobiology · (2026) · View on PubMed ↗
Huntington’s disease vasculopathy is barrier-type-selective and arteriolar-dominant with spatially-coupled astrogliosis and reversible by S1pr1 stimulation.
The study used in vivo two-photon microscopy in R6/2 Huntington’s disease model mice to determine which brain vascular barriers fail and which vessel segments are most affected. It found barrier-type-selective pathology: blood–cerebrospinal fluid barrier (BCSFB) surface vessels showed paracellular leakage, whereas blood–brain barrier (BBB) parenchymal vessels showed increased vesicular transport and adsorptive-mediated transcytosis, with arterioles as the most critically impacted segment. The spatially coupled astrogliosis and the reversibility by S1pr1 stimulation indicate a segment-specific, therapeutically targetable vasculopathy mechanism in Huntington’s disease.
Kucharz K, Soylu-Kucharz R, Saint-Pierre M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Oral Fluid Inflammatory Biomarker Profile in Long COVID: Evaluation of Oral Active and Total MMP-8, MMP-9, and TIMP-1 in Relation to BMI and Disease Status.
In a cross-sectional study of 115 long COVID (LC) patients and 103 matched controls, oral rinse samples were assessed for inflammatory biomarkers including active and total matrix metalloproteinase-8 (aMMP-8, total MMP-8), MMP-9, and TIMP-1, with periodontal inflammation screened using a chair-side active MMP-8 point-of-care test (POCT). The key finding was that oral inflammatory biomarker profiles—particularly MMP-8/MMP-9 axis activity and related regulators such as TIMP-1—were associated with LC status and varied with disease status and body mass index (BMI). This supports the use of oral MMP-8/MMP-9-related biomarkers as potential noninvasive indicators of systemic inflammation in long COVID and informs stratified clinical assessment.
Seno Aji NRA, Thomas JT, Tervahartiala T et al. · International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · (2026) · View on PubMed ↗ · Free PDF ↗
Pericyte loss and endothelial activation define distinct vascular states in cerebral small vessel disease.
This post-mortem human study examined how pericyte loss and endothelial activation relate to cerebral small vessel disease (cSVD) severity and aging by performing quantitative single-vessel analysis of cortical microvasculature. Using multiplex immunohistochemistry with spectral unmixing and automated image analysis, the authors identified distinct vascular states defined by pericyte alterations versus endothelial activation across increasing cSVD severity. Scientifically, the work links specific microvascular cellular dysfunction patterns to cSVD progression and supports more targeted mechanistic models of blood–brain barrier breakdown.
Chagnot A, Jaime Garcia D, McQuaid C et al. · Acta neuropathologica · (2026) · View on PubMed ↗ · Free PDF ↗
Brain tumor genetics & targeted signaling vulnerabilities
Chromosome 6q mediated loss of LATS1 tumour suppression as a targetable mechanism of ultra-high-risk posterior fossa A ependymoma.
This study investigated chromosome 6q loss in ultra-high-risk posterior fossa A (PFA) ependymoma and tested whether it drives tumor suppression loss via LATS1. The authors found that 6q- loss leads to deletion of LATS1, causing dysregulation of the Hippo signaling pathway with increased YAP/TEAD activity, and they propose this as a targetable mechanism in primary and recurrent PFA ependymomas. The clinical significance is that LATS1/Hippo–YAP/TEAD pathway activation provides a rational therapeutic vulnerability for a subgroup with poor outcomes.
Donson AM, Griesinger AM, Chapman RJ et al. · Acta neuropathologica · (2026) · View on PubMed ↗ · Free PDF ↗
Diet, caloric restriction & brain aging/neuroprotection
An NAD+-responsive adipose signal coordinates inter-organ defense against muscle atrophy.
This study examined how NAD+ supplementation protects against skeletal muscle atrophy by identifying an adipose-derived signaling pathway, focusing on Serpina3n and STAT1-dependent transcription in models of aging, disuse, and cancer cachexia. It found that increased NAD+ in adipose tissue activates STAT1 to induce Serpina3n, which is released systemically and preserves muscle metabolic function by maintaining pyruvate carboxylase protein levels and promoting anaplerosis and oxidative metabolism. The findings support NAD+-adipose–Serpina3n signaling as a therapeutic axis to prevent or treat muscle wasting.
Liang N, He J, Guo X et al. · Cell metabolism · (2026) · View on PubMed ↗
Metabolomic aging and mortality clocks based on ensemble learning identify systemic aging risk across the human life span in 18,476 individuals.
This study profiled plasma metabolomes across 18,476 individuals aged 1–96 years to build metabolomic aging and mortality clocks using ensemble learning. Using nano-assisted laser desorption/ionization mass spectrometry (nano-assisted LDI-MS), it derived 56 age-associated metabolites and showed that metabolomic age acceleration (mAA) predicted health deterioration and mortality risk during follow-up (2019–2025). Clinically, the resulting metabolomic clocks quantify systemic aging risk beyond chronological age and could support risk stratification across the human lifespan.
Cao L, Chen Y, Zhang W et al. · Science translational medicine · (2026) · View on PubMed ↗
TIME FOR COFFEE coordinates phase separation and chromatin regulation for salt tolerance.
This study examined how the plant circadian clock component TIME FOR COFFEE (TIC) coordinates chromatin regulation with phase separation to improve salt tolerance. It found that TIC forms biomolecular condensates in response to salt stress (not osmotic stress alone), that tic mutants are hypersensitive to salt under constant conditions, and that they show enhanced salt tolerance under 21-hour light–dark cycles matching their shortened circadian period, alongside salt-stress–linked increases in H3K9ac at responsive genes. Scientifically, it connects circadian timing, condensate formation, and histone acetylation to salt-tolerance gene regulation.
Tian W, Lyu X, Qian GR et al. · Science advances · (2026) · View on PubMed ↗
The mechanism of dietary intervention in delaying brain aging and neurodegenerative diseases.
This review examined how dietary interventions—particularly caloric restriction (CR) and dietary restriction (DR)—affect brain aging and neurodegenerative/cerebrovascular disease risk in preclinical and mechanistic studies. It reports that CR/DR delay brain aging through coordinated modulation of gene expression and epigenetic modifications, alongside multiple converging protective pathways. These findings support dietary restriction as a scientifically grounded, potentially gene/epigenetic-targetable strategy to reduce neurodegeneration risk and preserve brain function with aging.
Luo B, Liu S, Zheng L et al. · Ageing research reviews · (2026) · View on PubMed ↗
Gene therapy delivery & neuromuscular disease (SMA intrathecal)
Consensus on the use of intrathecal gene therapy for spinal muscular atrophy.
This consensus article evaluated the clinical use of intrathecal (IT) gene therapy for spinal muscular atrophy (SMA), focusing on the newer administration route of onasemnogene abeparvovec and its monitoring needs in pediatric and adult care. It concludes that IT delivery requires structured, route-specific surveillance beyond existing intravenous guidelines, including monitoring for dorsal root ganglia toxicity and standardized long-term multidisciplinary follow-up with transition protocols. The guidance is significant for improving safety and consistency of care as SMA gene therapy expands beyond intravenous administration.
Blaschek A, Schara-Schmidt U, Petri S et al. · Neuropediatrics · (2026) · View on PubMed ↗ · Free PDF ↗
Solid tumor immunotherapy & checkpoint inhibitor strategies
Emerging Therapeutic targets and Early-phase drug Development in Gynecological Malignancies.
This review summarized emerging therapeutic targets and early-phase drug development strategies for gynecological malignancies, focusing on DNA damage response vulnerabilities (including WEE1, PKMYT1, and WRN), CCNE1 amplification, and actionable alterations such as TP53 Y220C. It reported encouraging early clinical activity for targeted approaches against these pathways and highlighted antibody-drug conjugates and immunotherapies as major expanding classes. The synthesis supports biomarker-driven trial design and prioritization of next-generation targets in recurrent or treatment-resistant gynecologic cancers.
Ouali K, Tan D, Lheureux S et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗
Phase 2 Trial of Icotrokinra for Patients with Ulcerative Colitis.
This phase 2b, double-blind, randomized trial evaluated oral icotrokinra, a peptide that blocks the interleukin-23 receptor, in adults with moderately to severely active ulcerative colitis. Participants received once-daily icotrokinra (400 mg, 200 mg, or 100 mg) or placebo, and the primary endpoint was clinical response at week 12 with secondary endpoints including clinical remission and endoscopic improvement. The study tests whether oral IL-23R blockade can achieve efficacy comparable to injectable IL-23–pathway therapies, potentially improving treatment convenience and adherence.
Abreu MT, Siegmund B, Surace L et al. · The New England journal of medicine · (2026) · View on PubMed ↗
Ponatinib-Blinatumomab or Imatinib-Chemotherapy for Adult Ph-Positive ALL.
This randomized clinical trial compared frontline ponatinib plus blinatumomab versus imatinib plus chemotherapy in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), with crossover allowed for measurable residual disease persistence or reappearance. The key reported outcome was event-free survival, assessing whether the targeted TKI plus immunotherapy strategy improves outcomes compared with standard chemotherapy-based treatment. If ponatinib–blinatumomab improves event-free survival, it would support a new frontline regimen for Ph+ ALL by combining kinase inhibition with CD19-directed immunotherapy.
Chiaretti S, Piciocchi A, Skert C et al. · The New England journal of medicine · (2026) · View on PubMed ↗
Restoration of PP2A AαB56αC trimer formation by RPT04402 molecular glue in high-grade uterine cancer.
This study examined whether the molecular glue RPT04402 can restore PP2A AαB56αC trimer formation in high-grade uterine cancers driven by PPP2R1A hotspot mutations. It identified small-molecule molecular glues that correct PP2A trimer assembly specifically in the P179R (Pro179→Arg) and S256F (Ser256→Phe) mutant contexts where B56/B55 binding is disrupted. Therapeutically, restoring PP2A tumor-suppressor complex formation provides a targeted strategy for aggressive uterine cancers with PPP2R1A mutations.
Peris I, Haanen TJ, Day A et al. · Science translational medicine · (2026) · View on PubMed ↗
Integrative multi-omics reveals CUL4B as a modulator of macrophage pyroptosis and innate defense against Staphylococcus aureus.
This multi-omics study identified host factors modulating macrophage pyroptosis and innate defense during Staphylococcus aureus infection, focusing on CUL4B. It used CRISPR-mediated deletion of CUL4B in human THP-1 macrophages to show enhanced intracellular bacterial killing with reduced cell death, decreased caspase-1 activation, and lower IL-1β production, consistent with altered inflammatory signaling programs. Clinically, it positions CUL4B as a regulator of macrophage pyroptosis that could be leveraged to improve innate immune control of S. aureus.
Askarian F, Sun D, Tat J et al. · Science advances · (2026) · View on PubMed ↗
ARID2 Loss Reprograms the Kynurenine-AhR Pathway to Restore Antitumor Immunity in CTNNB1-Mutant Hepatocellular Carcinoma.
This study investigated how ARID2 loss reprograms the kynurenine–AhR metabolic pathway to restore antitumor immunity in CTNNB1-mutant hepatocellular carcinoma (HCC). Integrative analyses of patient cohorts and a de novo MYC/CTNNB1GOF mouse model showed that concurrent CTNNB1 and ARID2 alterations drive a metabolic-immune network that modulates immune exclusion and sensitivity to immune checkpoint blockade. The work suggests that targeting the kynurenine–AhR axis downstream of ARID2 loss could overcome immunosuppression in CTNNB1GOF HCC and improve ICB responses.
Li Q, Yuan Y, Liu N et al. · Cancer research · (2026) · View on PubMed ↗
Radiation therapy for persistent or progressive mediastinal lymphoma after chemotherapy in FeLV-positive cats: a retrospective case series of four cats.
This retrospective case series evaluated radiation therapy outcomes in four FeLV-positive cats with persistent or progressive mediastinal lymphoma after chemotherapy. Using CT-based response assessment with RECIST criteria (truncated results), the study described treatment response and feasibility in a population with limited options and poor prognosis. The clinical significance is that it provides preliminary evidence for radiation as a salvage approach when chemotherapy fails in FeLV-associated mediastinal lymphoma.
Uno A, Hasegawa T, Mori T · Australian veterinary journal · (2026) · View on PubMed ↗ · Free PDF ↗
Pharmacotherapy for MASLD/MASH: approved therapies, drug repurposing, and emerging mechanism-based candidates.
This structured narrative review summarized pharmacotherapy options for MASLD/MASH, focusing on approved drugs, repurposed agents, and emerging mechanism-based candidates. It highlights that management is evolving after approvals of resmetirom and semaglutide for selected adults with noncirrhotic MASH and F2–F3 fibrosis, while also addressing comorbid obesity, type 2 diabetes, dyslipidemia, cardiovascular risk, and kidney disease (detailed comparative findings are not provided in the truncated abstract). The significance is practical: it consolidates evidence strength, safety, interactions, and implementation considerations to guide clinicians treating MASLD/MASH patients with metabolic and renal comorbidities.
Syed-Abdul MM · Expert opinion on pharmacotherapy · (2026) · View on PubMed ↗ · Free PDF ↗
Oncostatin M deficiency: A newly recognized inherited bone marrow failure syndrome with potential predisposition to myeloid malignancy.
This report described Oncostatin M (OSM) deficiency as a newly recognized autosomal recessive inherited bone marrow failure syndrome with potential predisposition to myeloid malignancy. The key finding is that OSM deficiency is associated with early-onset bone marrow failure and possible increased risk of myelodysplastic syndrome (MDS), based on genomic diagnostic advances (full case details truncated). Scientifically, it expands the IBMFS gene spectrum and clinically supports considering OSM deficiency in patients with early BMF and subsequent myeloid risk.
Haroon A, Fakih RE, Alfalah AH et al. · Hematology/oncology and stem cell therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Enlicitide: The First Oral PCSK9i for Lowering Low-Density Lipoprotein Cholesterol.
This article reviewed the pharmacology, pharmacokinetics, safety, and efficacy evidence for enlicitide, the first FDA-approved oral PCSK9 inhibitor (PCSK9i). It reports that phase 2 and 3 trials showed an LDL-cholesterol reduction of 57.1% to 64.6% (with additional safety/efficacy details truncated). The significance is that enlicitide offers a new oral mechanism for lowering LDL-C, potentially improving adherence and expanding treatment options for patients needing PCSK9 inhibition.
Lucas RC, Lussier ME, Nasuhidehnavi A et al. · The Annals of pharmacotherapy · (2026) · View on PubMed ↗
Eczema-Psoriasis Overlap: An eDelphi Consensus on Clinical Presentation and Therapeutic Management Among Italian Experts.
This Italian eDelphi consensus study surveyed 131 dermatologists to define clinical presentation and therapeutic management for eczema–psoriasis overlap, following statements developed by an eight-dermatologist steering committee. The panel produced 43 consensus statements specifying how to clinically define overlap and guide treatment decisions. Standardizing diagnosis and management for this Th2/Th1–Th17 mixed phenotype could improve care consistency for patients with combined eczematous and psoriatic lesions.
De Luca E, Campanati A, Galluzzo M et al. · Dermatology and therapy · (2026) · View on PubMed ↗ · Free PDF ↗
In vivo engineering of CAR natural killer cells for immunotherapy using ligand-directed lipid nanoparticles.
This study engineered natural killer (NK) cells in vivo using ligand-directed lipid nanoparticles (NtLNPs) that deliver CAR mRNA via engineered biparatopic NK cell ligands in mouse models. NtLNPs achieved high NK-cell transfection (~80%) with minimal off-target effects and generated functional CAR NK cells that depleted CD19+ B cells or eliminated autoreactive T cells in an autoimmune hepatitis model. The work supports a nonviral, targeted LNP platform for programmable CAR NK immunotherapy with potential translational advantages.
Chen Y, Monkovic J, Mughal H et al. · Nature biotechnology · (2026) · View on PubMed ↗
A selective NVL inhibitor suppresses tumor growth by targeting ribosome biogenesis.
This study identified and characterized a selective inhibitor of nuclear valosin-containing protein-like (NVL) as a way to suppress tumor growth by targeting ribosome biogenesis, using forward genetics and biochemical/structural validation. The dibenzothiazepinone MM17 inhibited NVL (an AAA+ ATPase required for 60S large subunit assembly), and resistance mutations in cells conferred reduced sensitivity to enzymatic inhibition, with cryo-EM used to support target engagement. Selective NVL inhibition offers a new, genetically validated druggable route to block ribosome biogenesis in cancer.
Guo HH, Tao Y, Cruz VE et al. · Nature chemical biology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
Targeting an IL-17/IL-36 pathogenic hub in hidradenitis suppurativa with a bispecific antibody.
The study investigated the inflammatory circuitry driving hidradenitis suppurativa (HS) tunnel disease and tested a cytokine-targeting bispecific antibody, HB0043, in relation to IL-17/IL-36γ signaling. Integrated multiomics supported self-amplifying HS tunnel circuits in a keratinocyte subset synergistically activated by IL-17 and IL-36γ, and HB0043 (IL-36R-binding to locally dual-block IL-17A and IL-36R/IL-36γ signaling) outperformed IL-17A/IL-17F bispecific and parental antibodies in vitro. This provides a mechanistically grounded therapeutic approach for treatment-resistant HS tunnels by targeting a pathogenic IL-17/IL-36 hub.
Sun Y, Mi Z, Yu Y et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Camrelizumab plus chemotherapy as induction therapy followed by concurrent chemoradiotherapy and camrelizumab consolidation in limited-stage small cell lung cancer: a randomized phase II trial.
The randomized phase II trial evaluated whether a camrelizumab-based induction–consolidation strategy improves outcomes versus standard induction chemotherapy followed by concurrent chemoradiotherapy (CRT) alone in previously untreated limited-stage small cell lung cancer (LS-SCLC). Patients receiving induction camrelizumab plus etoposide–platinum followed by concurrent CRT and camrelizumab consolidation (camrelizumab group) were compared with a control CRT-only consolidation approach, with 1-year progression-free survival (PFS) as the primary endpoint. If effective, this regimen could refine immunotherapy integration for LS-SCLC by improving PFS through camrelizumab induction and consolidation.
Liu D, Yang L, Hu M et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Affinity-optimized bispecific CAR-T cells targeting HLA-G and CD70 for the treatment of clear cell renal cell carcinoma.
The study engineered affinity-optimized bispecific CAR-T cells targeting HLA-G and CD70 for clear cell renal cell carcinoma (ccRCC) and assessed antigen expression to address immune escape from heterogeneous target expression. It analyzed HLA-G and CD70 in normal and tumor tissues using public RNA-seq databases and patient immunohistochemistry, and designed an HLA-G CAR using the natural inhibitory receptor ILT4 (with a bispecific strategy to co-target both antigens). This supports a rational CAR-T design to improve efficacy in ccRCC by reducing antigen-driven escape mechanisms.
Su L, Ma X, Chen D et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗
Myofibroblast Derived Transglutaminase 2 Activity is Upregulated in Stricturing Crohn’s Disease and its Inhibition Exerts Anti-Fibrotic Properties.
In human intestinal tissue and human intestinal myofibroblasts (HIMF) derived from stricturing Crohn’s disease (CD) and controls, investigators measured extracellular matrix–bound transglutaminase 2 (TG2) expression and activity and tested TG2 inhibition for anti-fibrotic effects. The key finding was that myofibroblast-derived TG2 activity was upregulated in stricturing CD and that inhibiting TG2 reduced pro-fibrotic ECM accumulation and related fibrotic phenotypes. This positions TG2 as a mechanistic driver and a potential therapeutic target for intestinal fibrosis in Crohn’s disease.
Chandra J, Czarnecki D, Mukherjee PK et al. · Gastroenterology · (2026) · View on PubMed ↗ · Free PDF ↗
HtpG-High-Expressing Escherichia coli Promotes Fibrosis in Chronic Pancreatitis.
Using multi-omics analyses in chronic pancreatitis (CP) patients and mice, investigators identified and functionally tested specific pathogenic Escherichia coli strains, including HtpG-high–expressing E. coli, in vitro and in vivo with macrophage-specific knockout mice and adenoviral/pharmacologic tools. The key finding was that HtpG-high–expressing E. coli promoted fibrosis in chronic pancreatitis, implicating microbial HtpG as a pro-fibrotic factor. This advances a causal gut-microbe mechanism for CP progression and suggests HtpG or related pathways as potential targets for antifibrotic interventions.
Pan LL, Liang W, Ren Z et al. · Gastroenterology · (2026) · View on PubMed ↗
IL-31 targets the hair follicle bulge across species and delays plucking-induced anagen in mice.
Through reanalysis of public single-cell RNA-seq datasets plus in situ hybridization, and then functional experiments in mice, the study examined IL-31 signaling in hair follicles, focusing on Il31ra expression in the bulge and secondary hair germ and the effects of recombinant IL-31 (rIL-31). The key finding was that IL-31 acted on keratinocyte Il31ra to activate JAK-STAT (STAT3/STAT5) and ERK1/2 signaling in the bulge/sHG and delayed plucking-induced anagen, with these responses abolished in keratinocyte-specific Il31ra-deficient mice. Scientifically, this defines IL-31/IL-31RA as a regulator of hair follicle cycling and provides mechanistic targets for disorders involving hair growth or shedding.
Katsuo K, Nakamizo S, Egawa G et al. · The Journal of investigative dermatology · (2026) · View on PubMed ↗
Vitiligo Biomarker CXCL10 Correlates With Clinical Response to Ruxolitinib Cream in the Phase 2 Randomized TRuE-V Mechanism-of-Action Study.
In the phase 2 randomized, double-blind, vehicle-controlled TRuE mechanism-of-action study, adults with vitiligo were treated with 1.5% ruxolitinib cream twice daily (n=41) or vehicle (n=19) for 24 weeks, with biomarker analyses extending through Week 52. The key finding was that serum CXCL10—a vitiligo biomarker linked to IFN-γ signaling—was significantly downregulated at multiple post-treatment time points with ruxolitinib, correlating with clinical response. This supports CXCL10 as a pharmacodynamic biomarker for JAK inhibition in vitiligo and strengthens the mechanistic rationale for ruxolitinib cream efficacy.
Passeron T, Lebwohl M, Lynde C et al. · The Journal of investigative dermatology · (2026) · View on PubMed ↗
SPP1+ TAMs drive colorectal tumorigenesis through an ARG2-orchestrated metabolic-immune crosstalk.
This study investigated how SPP1+ tumor-associated macrophages (TAMs), identified via single-cell transcriptomics, drive colorectal tumorigenesis through ARG2-orchestrated metabolic–immune crosstalk, and whether the gut microbiota regulates the process, using clinical specimens, murine models, and colorectal cancer cell lines. The key finding was that SPP1+ TAMs promote colorectal cancer progression via an ARG2-centered metabolic-immune signaling program. These results identify a macrophage–ARG2 axis as a potential therapeutic target and suggest microbiota-linked modulation of the tumor microenvironment in colorectal cancer.
Song L, Yan T, Lu SY et al. · Cancer letters · (2026) · View on PubMed ↗
Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation: A Multicenter Retrospective Study.
This multicenter retrospective study assessed real-world outcomes in patients with metastatic sarcomatoid renal cell carcinoma (msRCC) treated with immune checkpoint inhibitors (ICIs) versus those who did not, across 6 US academic centers. Patients receiving ICIs (ICI+; n=155) had different overall survival outcomes compared with those not receiving ICIs (ICI-; n=48), addressing whether ICI use improves prognosis in this aggressive subtype. Clinically, the study helps inform treatment selection for msRCC where VEGF-targeted therapy outcomes are typically poor.
Gopalakrishnan D, Fujiwara Y, Collier KA et al. · Journal of the National Comprehensive Cancer Network : JNCCN · (2026) · View on PubMed ↗
Rapid CAR-T manufacturing with low-intensity priming enhances CAR-T cell fitness and limits inflammatory programming in a phase 1 study.
This phase 1 study evaluated PrimeCAR, a 2-day CAR-T manufacturing strategy using low-intensity anti-CD3 priming plus IL-7 and IL-21, in comparison with conventional CAR-T manufacturing. PrimeCAR products showed a transcriptional state enriched for a primed naive T cell (Tn)-like program with preserved stemness, preferentially engaging proliferative programs after antigen stimulation while limiting exhaustion- and inflammation-associated regulators. Clinically, this suggests a manufacturing approach that improves CAR-T fitness and reduces inflammatory programming, potentially enhancing efficacy and tolerability.
Yang Z, Li S, Wang L et al. · Cell stem cell · (2026) · View on PubMed ↗
Transposable element splicing reveals a tumor-enriched class of gene-independent transcripts.
This study mapped transposable element (TE)-derived splicing across pan-cancer datasets and defined a tumor-enriched, gene-independent TE-derived transcript class called TEtrans. TEtrans initiate within TE loci, are spliced within or between TE loci, are predominantly composed of TE sequences, and their expression correlated with stemness and inflammation regulators in a context-dependent manner, including functional evidence for an endogenous retrovirus-derived TEtrans promoting colorectal cancer growth. These results show that TE splicing generates regulatory, tumor-associated transcripts that can drive cancer phenotypes independently of canonical gene expression.
Li Z, Bao Y, Yu H et al. · Molecular cell · (2026) · View on PubMed ↗
A potential biomarker for the efficacy of complement inhibitors in myasthenia gravis.
This study sought a biomarker for complement inhibitor efficacy in acetylcholine receptor (AChR) antibody-positive myasthenia gravis by incubating patient sera with AChR-expressing HEK293 cells and measuring AChR binding IgG and membrane attack complex (MAC) deposition by flow cytometry. The authors analyzed correlations between these complement-activation readouts and clinical manifestations in 14 MG patients versus 10 healthy controls to identify predictors of response. If validated, the identified serum/complement assay metrics could enable patient stratification for complement inhibitor therapy in AChR+ MG.
Ogaya E, Uzawa A, Akamine H et al. · Journal of the neurological sciences · (2026) · View on PubMed ↗ · Free PDF ↗
A second chance? Outcomes of immunotherapy retreatment after prior checkpoint inhibitor exposure in endometrial and cervical cancer.
This retrospective single-institution cohort study evaluated outcomes of immunotherapy retreatment after prior checkpoint inhibitor exposure in recurrent endometrial cancer (EC) and cervical cancer (CC). Among patients receiving at least one dose of subsequent immunotherapy after prior immunotherapy (2017–2025), the study assessed treatment patterns, toxicity (including immune-related adverse events), and survival outcomes. The results address an evidence gap for sequencing checkpoint inhibitors in EC/CC and can guide clinical decision-making on whether and how to retreat with immunotherapy after prior exposure.
Chalif J, Morton M, O’Connor R et al. · Gynecologic oncology · (2026) · View on PubMed ↗ · Free PDF ↗
Molecular Consequences and Targeting of PPM1D Overexpression in Myeloproliferative Neoplasms.
This study identified the histone acetyltransferase KAT5 as a dual-function therapeutic target in endometrial cancer (EC) and examined its effects on tumor growth and immune activation. KAT5 silencing inhibited EC proliferation and tumor growth, increased DNA damage and micronuclei formation, and triggered cGAS–STING–mediated proinflammatory immune responses via micronuclear DNA release. The work supports KAT5 as a druggable epigenetic regulator that can directly suppress cancer while simultaneously enhancing antitumor immunity.
Mia MB, Schaniel C, Clementelli C et al. · Blood · (2026) · View on PubMed ↗ · Free PDF ↗
Autoimmune hepatitis and primary biliary cholangitis are among a subset of autoimmune diseases defined by profound co-prevalence and genetic risk association with the IL12 pathway.
This genetic association study assessed IL12-pathway risk across 27 autoimmune diseases to determine whether autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) share a common genetic etiology. It identified a rare upstream IL12A variant with large per-allele odds ratios for AIH (OR=2.98) and PBC (OR=2.80), along with associations across several other autoimmune diseases. The results implicate IL12 signaling as a shared molecular driver for a subset of autoimmune disorders, informing pathway-focused risk biology.
Nakka P, Hobbs BD, Sidore C et al. · Hepatology (Baltimore, Md.) · (2026) · View on PubMed ↗ · Free PDF ↗
Cancer risk prediction & prognostic modeling
Clonal heterogeneity in human pancreatic ductal adenocarcinoma and its impact on tumor progression.
This study analyzed clonal heterogeneity in human pancreatic ductal adenocarcinoma by profiling 62 primary tumors with single-cell RNA sequencing (443,451 cells) and a subset of 11 tumors with matched spatial transcriptomics (53,236 spots), including pre- and post-chemotherapy samples from six tumors. The authors mapped clonal, transcriptional, and spatial diversity and linked heterogeneity patterns to tumor progression and treatment-associated changes. Understanding how clonal structure evolves in PDAC could inform prognostic stratification and therapeutic targeting strategies.
Kalfakakou D, Cameron DC, Kawaler EA et al. · Nature genetics · (2026) · View on PubMed ↗
Pulmonary nodules: classification, biomarkers, signaling pathways, diseases, early diagnosis and management.
This review summarized current knowledge on pulmonary nodules, including how to classify nodules, identify biomarkers and signaling pathways, and manage patients detected via thoracic imaging and low-dose CT lung cancer screening. It emphasizes risk stratification to distinguish nodules needing timely cancer-directed evaluation from those suitable for safe observation, integrating imaging phenotypes with disease spectrum and translational models. Clinically, the synthesis aims to improve early diagnosis and management decisions for the growing population undergoing lung cancer screening.
Ye Z, Li L, Zhang M et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
IHPBA 2026 global guideline for the management of hepatocellular carcinoma in resource-constrained healthcare settings.
The IHPBA 2026 global guideline group developed resource-constrained healthcare–sensitive recommendations for the diagnosis and management of hepatocellular carcinoma (HCC). The guideline process supported initial diagnosis with ultrasound and then used cross-sectional imaging and biomarker assessment (including alpha-fetoprotein) to guide care pathways tailored to limited resources. This provides an actionable global framework to standardize HCC management where access to advanced diagnostics and therapies is constrained.
Siriwardena AK, Jonas E, Bonney G et al. · HPB : the official journal of the International Hepato Pancreato Biliary Association · (2026) · 1 citations · View on PubMed ↗
Development and Validation of a Model to Predict Recurrence in Patients With Stage IIIA Melanoma.
This study developed and validated a recurrence prediction model for adults (≥18 years) with stage IIIA cutaneous melanoma diagnosed between 2001 and 2016 across 36 centers, using development (n=1,386) and validation (n=448) cohorts. Using a random forest approach, the model aimed to stratify patients by recurrence risk to identify those most likely to benefit from systemic adjuvant therapy. The work is significant because it could reduce unnecessary adjuvant toxicity by targeting treatment to higher-risk stage IIIA patients.
Maurichi A, Bartlett EK, Barretta F et al. · Journal of the National Comprehensive Cancer Network : JNCCN · (2026) · View on PubMed ↗
Neuroendocrine prostate cancer converges on a fetal pulmonary neuroendocrine-like program.
This study integrated single-cell, bulk, cistrome, and spatial datasets with fetal human atlases to determine the developmental program underlying neuroendocrine prostate cancer (NEPC). In a discovery cohort (35,696 tumor cells from 20 patients), NEPC shared copy-number architecture with adenocarcinoma but most strongly matched a fetal, lineage-restricted neuroendocrine program, best supported as pulmonary neuroendocrine-like among tested alternatives. The work clarifies NEPC’s developmental identity and may inform subtype-specific therapeutic strategies for this treatment-resistant, AR-independent state.
Yue W, Kyprianou N, Tewari AK et al. · Cancer genetics · (2026) · View on PubMed ↗ · Free PDF ↗
Differential impact of tumor-derived ESR1 mutations on elacestrant benefit in metastatic breast cancer.
This study analyzed tumor sequencing data from 3,344 metastatic breast cancer patients with ESR1 mutations (with whole-transcriptome sequencing in 1,663) to determine how specific ESR1 variants influence benefit from the oral SERD elacestrant using time-on-treatment (TOT) from insurance claims. The key finding was that elacestrant benefit varied by ESR1 mutation subtype and clinical context rather than being uniform across all ESR1-mutant tumors. Clinically, this supports more precise, variant-aware biomarker stratification to predict which ESR1-mutant patients are most likely to benefit from elacestrant.
Sledge GW, Xiu J, Fuqua S et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗ · Free PDF ↗
Hearing loss & mortality/public health outcomes
Hearing loss, hearing-aid use, and mortality risk: individual participant data meta-analysis of population-based studies from Australia, Iceland, and the USA and a replication study from Norway.
This individual-participant-data meta-analysis pooled population-based cohorts from Australia, Iceland, and the USA and included a replication study from Norway to evaluate associations between hearing loss, hearing-aid use, and mortality risk. It found that hearing loss is associated with increased mortality risk and assessed whether current hearing-aid use modifies that association. The results are important for public health and clinical counseling on hearing rehabilitation as a potential lever to reduce premature mortality.
Li CM, Hoffman HJ, Engdahl B et al. · The lancet. Healthy longevity · (2027) · View on PubMed ↗ · Free PDF ↗
Spine/neurology: degenerative cervical myelopathy screening
Adult Attention Deficit-Hyperactivity Disorder.
This narrative review summarized the clinical features, comorbidities, and diagnostic challenges of adult attention-deficit/hyperactivity disorder (ADHD) across the lifespan. It emphasized that adults with ADHD frequently have psychiatric comorbidities (e.g., anxiety, mood, sleep, substance use) and increased risk of somatic conditions such as obesity, cardiovascular disease, diabetes, and immune/inflammatory disorders. The review’s significance is to guide clinicians toward earlier recognition and more comprehensive management of adult ADHD in real-world care settings.
Buitelaar JK, Newcorn JH · The New England journal of medicine · (2026) · View on PubMed ↗
Evaluating the Effect of Positive Childhood Experiences on the Risk of Psychiatric Disorders in Early Adulthood.
This study evaluated whether positive childhood experiences (PCEs) measured in 3,499 children from the Avon Longitudinal Study of Parents and Children (ages 0–17) predict psychiatric disorder risk in early adulthood, using inverse probability weighting to address differential exposure. Higher PCE scores were associated with a lower risk of later psychiatric disorders. These findings suggest that strengthening positive childhood experiences may be a clinically relevant, modifiable upstream factor for reducing early-adulthood mental health burden.
Murphy J, Healy C, Mongan D et al. · The American journal of psychiatry · (2026) · View on PubMed ↗
Degenerative cervical myelopathy: early detection and the potential for preventing disability.
This narrative review focused on degenerative cervical myelopathy (DCM) and evaluated strategies for early detection to prevent disability, emphasizing the limitations of current reactive diagnosis. It highlights that earlier multimodal diagnosis and timely intervention could prevent progression to irreversible neurological injury (including tetraplegia) that often occurs when treatment is delayed. Scientifically and clinically, the article supports shifting DCM management toward proactive screening and earlier treatment to improve long-term outcomes.
Zipser CM, Hupp M, David G et al. · The Lancet. Neurology · (2026) · View on PubMed ↗ · Free PDF ↗
Vaccines & immunogenicity (RSV, allergy risk, shedding)
Orthogonal Fc engineering enables multiplexed delivery of mRNA-encoded bispecific antibodies that constrain viral escape.
This work studied mRNA-encoded bispecific antibodies engineered with orthogonal Fc designs for multiplexed delivery in human FcRn-expressing mice challenged with SARS-CoV-2. The authors reported that intravenous lipid nanoparticle delivery produced high serum concentrations, extended half-life, and serum neutralizing titers >1:10,000, while the bispecific/orthogonal Fc strategy constrained viral escape. The findings support a durable, escape-resilient antibody approach using mRNA technology to improve breadth against evolving SARS-CoV-2.
Wec AZ, Cho A, Pecetta S et al. · Science translational medicine · (2026) · View on PubMed ↗
Systemic Allergic Reactions to mRNA COVID-19 Vaccines: A Randomized Placebo-controlled Trial.
This multicenter randomized, double-blind, placebo-controlled trial measured systemic allergic reaction rates after Pfizer-BioNTech mRNA COVID-19 vaccination in adults and adolescents with prior severe allergic reactions and/or mast cell disorders (PSAR/MCD group) versus a non-PSAR/non-MCD comparison group. The study found that systemic allergic reactions occurred at quantifiable proportions in the PSAR/MCD group and were compared directly against the comparison group to determine whether risk was higher. Clinically, these results refine risk estimates for mRNA vaccination in people with mast-cell disorders or severe prior allergy histories and can guide counseling and monitoring strategies.
Wheatley LM, Baker JR, Adkinson NF et al. · The Journal of allergy and clinical immunology · (2026) · View on PubMed ↗
Immunogenicity and shedding of live-attenuated intranasal respiratory syncytial virus vaccine in children aged 6-18 months by baseline serostatus: a multicentre, randomised, placebo-controlled, phase 1/2 trial.
This phase 1/2 multicentre randomized placebo-controlled trial studied immunogenicity and live-attenuated intranasal RSV vaccine shedding in children aged 6–18 months stratified by baseline RSV serostatus. Using the RSV/ΔNS2/Δ1313/I1314L (RSVt) vaccine, it evaluated how pre-existing immunity influences vaccine immune responses and viral shedding after vaccination. The findings are significant for optimizing RSVt use in young children by clarifying how baseline serostatus affects both efficacy-related immunogenicity and transmissibility/safety considerations.
Idoko OT, Vargas SL, Bueso A et al. · The Lancet. Microbe · (2026) · View on PubMed ↗ · Free PDF ↗
Neurobiology tools & targeted delivery (AAV/microglia, toxins, imaging/AI)
Structural basis of ligand recognition and gating in mosquito IRs.
The study investigated how the mosquito ionotropic receptor complex IR8a–IR75k from Anopheles stephensi recognizes carboxylic-acid ligands and gates ion-channel opening, using cryo-electron microscopy and functional validation across multiple receptor states. Cryo-EM structures captured ligand-free closed (apo) and ligand-induced open conformations, and showed nonanoic acid and octanoic acid–dependent activation mechanisms in the full-length receptor complex. These structural insights define the ligand-recognition and gating logic of mosquito IRs, informing rational strategies to disrupt malaria-vector host seeking.
Xu L, Wang X, Quan X et al. · Nature · (2026) · View on PubMed ↗
Safety and efficacy of delpacibart zotadirsen in Duchenne muscular dystrophy mutations amenable to exon 44 skipping in the USA (EXPLORE44): a randomised, placebo-controlled, double-blind, phase 1/2 trial.
This phase 1/2 randomized, placebo-controlled, double-blind trial evaluated delpacibart zotadirsen (del-zota; AOC 1044), an antibody–oligonucleotide conjugate delivering an exon-44-skipping phosphorodiamidate morpholino oligomer, in healthy adult men and in Duchenne muscular dystrophy patients with DMD variants amenable to exon 44 skipping (DMD44). The key findings reported in the abstract indicate the trial assessed safety, tolerability, pharmacokinetics/pharmacodynamics, and dystrophin-related efficacy endpoints for this first-in-class therapy. Clinically, the results are intended to support whether del-zota can safely restore dystrophin expression via exon 44 skipping in DMD44 patients.
Veerapandiyan A, Eskuri J, Laverty CG et al. · The Lancet. Neurology · (2026) · View on PubMed ↗
Multi-omic profiling of 85 iPSC lines from familial dementia reveals cellular diversity and regulators of organoid development.
This study profiled 85 human induced pluripotent stem cell (iPSC) lines from familial dementia, focusing on MAPT mutation carriers and isogenic controls, using whole-genome sequencing, long-read sequencing of the MAPT locus, bulk and single-cell RNA sequencing, and DNA methylation arrays. It identified four reproducible iPSC cellular states and candidate surface markers, while also detecting unintended editing events that could confound disease modeling. Scientifically, the work provides a multi-omic framework to distinguish mutation-driven biology from iPSC state variation and genome-editing artifacts in organoid-based dementia research.
Qi L, Bertucci T, Borden S et al. · Neuron · (2026) · View on PubMed ↗
A pseudoenzyme sensor of trehalose-6-phosphate directly represses the metabolic integrator SnRK1 in plants.
This research investigated how the noncatalytic Class-II trehalose-6-phosphate synthase (TPS-II) acts as a pseudoenzyme sensor of trehalose-6-phosphate (T6P) to regulate the plant metabolic integrator SnRK1 in Arabidopsis. It found that in the apo state TPS-II dimerizes via an autoinhibitory inter-subunit interaction, while T6P binding triggers a conformational change that releases the C-terminal domain to enable TPS-II–SnRK1 interaction and repress SnRK1 kinase activity. These mechanistic insights connect T6P sensing to direct control of SnRK1, advancing understanding of how plants coordinate carbon availability with growth and metabolism.
Sun T, Li W, Liu X et al. · Cell · (2026) · View on PubMed ↗
Microtubules and nuclear pores position centromeres and genes in neural stem cells.
The study investigated how centromeres are positioned in Drosophila neural stem cells and how this spatial organization changes during differentiation. It found that centromeres cluster near the nuclear envelope adjacent to the apical centrosome during interphase, and that this asymmetric positioning is regulated by microtubules connected to nuclear pore complexes (NPCs) and is lost in differentiated progeny. Scientifically, it links microtubule–NPC architecture to centromere positioning, providing a mechanism for how chromatin organization is developmentally controlled.
Taylor JA, Cabernard C · The Journal of cell biology · (2026) · View on PubMed ↗
Preclinical and first-in-human evaluation of VG-3927/SAR448851, an oral small-molecule TREM2 agonist for Alzheimer’s disease.
This preclinical and first-in-human translational study evaluated VG-3927/SAR448851, an oral CNS-penetrant small-molecule TREM2 agonist, for Alzheimer’s disease. It reported that VG-3927 engages TREM2 and its adaptor DAP12 to promote higher-order receptor complex formation, restores signaling in disease-associated TREM2 variants, and reduces inflammatory cytokine responses in human iPSC-derived neuron–microglia–astrocyte co-cultures. Scientifically and clinically, it supports TREM2 agonism as a therapeutic strategy for late-onset AD risk driven by TREM2 loss-of-function.
Dejanovic B, Figley MD, Weisman E et al. · Science translational medicine · (2026) · View on PubMed ↗
Effectiveness of rTMS vs. Pharmacotherapy in Late-Life Treatment-Resistant Depression: An Observational Study of Individual Participant Data From Two Randomized Clinical Trials.
This observational individual-participant-data study compared repetitive transcranial magnetic stimulation (rTMS) versus pharmacotherapy augmentation or switching strategies in older adults with late-life treatment-resistant depression (LL-TRD). Using data from 758 participants age 60+ drawn from two randomized trials (rTMS once-daily bilateral for 4–6 weeks; pharmacotherapy arms including aripiprazole augmentation, bupropion augmentation, and switch to bupropion), the abstract excerpt does not provide the comparative effectiveness results (truncated). Clinically, the analysis aims to inform real-world decision-making about whether rTMS or medication strategies provide better outcomes and tolerability in LL-TRD.
Adler E, Blumberger DM, Lenze EJ et al. · The American journal of psychiatry · (2026) · View on PubMed ↗
Atomic, structural and molecular insights into GPCR ligand binding and signalling.
This Nature Reviews article synthesized recent atomic-, structural-, and molecular-level advances on how G-protein-coupled receptors (GPCRs) bind ligands and propagate signaling, integrating findings across multiple experimental and computational approaches. It highlights context-dependent mechanisms by which ligand binding reshapes GPCR conformational dynamics and downstream G-protein signaling. The review provides a mechanistic framework that can guide rational GPCR drug discovery and interpretation of ligand efficacy.
Nemec K, Mészáros B, Skiniotis G et al. · Nature reviews. Molecular cell biology · (2026) · View on PubMed ↗
Ligand-dependent G protein dynamics underlying opioid efficacy.
This study used single-molecule Förster resonance energy transfer (smFRET) imaging to measure ligand-dependent G-protein dynamics in Gi proteins coupled to the μ-opioid receptor across different ligand- and nucleotide-bound states. It found that opioid ligands differentially modulate Gα α-helical domain motions over distances >70 Å, with higher-efficacy agonists accelerating transitions required for GDP–GTP exchange. These mechanistic insights connect ligand efficacy to long-range conformational dynamics that govern opioid signaling.
Deutsch JC, Hilger D, Janetzko J et al. · Nature structural & molecular biology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
Human-artificial intelligence collaboration for comanaging epilepsy in real time.
This study developed and tested an inpatient prototype platform for human–artificial intelligence collaboration to comanage epilepsy in real time, linking scalp and intracranial EEG to a secure large language model-based AI. The system was designed to communicate with patients to support seizure management behaviors and to learn from clinical events. Such closed-loop, patient-facing AI could improve outcomes for medication-uncontrolled epilepsy by translating device-detected signals into actionable guidance.
Goldblum Z, Shi H, Xu Z et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Repurposing adult AI radiograph models for neonatal care through continual learning: an international multicentre study.
This international multicentre retrospective study evaluated continual learning to repurpose an adult AI radiograph model for neonatal care without data sharing, using neonatal chest radiographs from 30 NICUs across 20 countries/territories. The approach adapted a deep learning model for endotracheal tube assessment from adult to neonatal settings via privacy-preserving continual learning. This supports a scalable pathway to extend regulatory-grade AI tools to neonates where pediatric-labeled data are limited.
Rao VM, Chen E, Saenz A et al. · Nature biomedical engineering · (2026) · View on PubMed ↗ · Free PDF ↗
Multiple Argonaute complexes orchestrate epigenetic silencing in the Arabidopsis germline.
The study characterized which Argonaute (AGO) effector complexes associate with male reproductive small RNAs (sRNAs) in Arabidopsis germline cells and how they mediate epigenetic silencing. Arabidopsis male reproductive sRNAs associated with AGO4, AGO5, AGO6, and AGO9 (enriched in meiocytes with RNA polymerase V), enabling methylation of loci with imperfect sequence homology. This reveals a coordinated multi-AGO mechanism for germline epigenetic silencing in plants and clarifies how sRNAs can target non-perfectly matched genomic regions.
Long J, Yang C, Xu S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Reporting completeness of clinical trials evaluating large language model interventions in medicine: systematic review.
This systematic review and meta-research analysis evaluated the reporting completeness of clinical trials of large language model (LLM) interventions in medicine by screening trial reports, protocols, and registrations from 2017–2025 across Embase, MEDLINE, CENTRAL, ClinicalTrials.gov, and WHO ICTRP. The study found substantial gaps and inconsistent adherence to established reporting guidelines across LLM trial documentation. These findings highlight the need for improved, guideline-consistent reporting to enable reproducibility, risk-of-bias assessment, and evidence synthesis for LLM-based medical interventions.
Chen D, Blayne A, Ning T et al. · BMJ (Clinical research ed.) · (2026) · View on PubMed ↗ · Free PDF ↗
A protease-resistant D-amino acid αA-crystallin mini-chaperone with enhanced chaperone and antioxidant activities protects against amyloid-β proteotoxicity.
Researchers synthesized a protease-resistant, all–D-amino acid αA-crystallin mini-chaperone analog (D-MC-αA) and compared it with the parent peptide (MC-αA) using biochemical assays and cellular/biological models of amyloid-β proteotoxicity. The key finding was that D-MC-αA retained enhanced chaperone and antioxidant activities while improving proteolytic stability, leading to stronger protection against amyloid-β–driven toxicity. This supports D-amino-acid mini-chaperones as more durable therapeutic candidates for Alzheimer’s disease–related protein misfolding and oxidative stress.
Srivastava S, Santhoshkumar P, Tender T et al. · Free radical biology & medicine · (2026) · View on PubMed ↗ · Free PDF ↗
A cross-species AAV platform for precise microglial interrogation.
This Neuron study developed a cross-species AAV platform to precisely interrogate microglia using a Cre-independent design. The authors engineered an AAV2/9.m vector combining a 446-bp microglia-specific regulatory element (MSRE), microRNA-mediated neuronal de-targeting, and microglia-tailored codon optimization, achieving >90% microglial specificity and robust long-lasting expression across mouse brain regions including an Alzheimer’s disease model. This platform is significant because it improves targeting specificity and payload performance for microglial functional studies while reducing off-target expression.
Yu F, Wang R, Di R et al. · Neuron · (2026) · View on PubMed ↗
PTPRS mediates invasion of tetanus neurotoxin into the central nervous system.
This Cell study examined how tetanus neurotoxin (TeNT) enters the central nervous system (CNS) during retrograde transport through motoneurons in mouse models. It identifies receptor protein tyrosine phosphatase sigma (PTPRS; PTPσ) as the retrograde transport receptor for TeNT, showing that global or motoneuron-specific PTPRS knockout abolishes CNS entry and that PTPRS–TeNT interactions occur in endosomes to prevent translocation and direct trafficking. These findings are significant for understanding TeNT neuroinvasion mechanisms and could inform therapeutic strategies to block toxin trafficking.
Chen P, Wang H, Manion J et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗
Mechanisms of transcription control by distal enhancers from single-gene nanoscopy.
This study used real-time single-gene nanoscopy with targeted perturbations to define enhancer–promoter communication mechanisms in single cells. Productive enhancer–promoter interactions were dynamic, occurred at ≲100 nm proximity, were coordinated with transcriptional bursts, and were often driven by cohesin-mediated loop extrusion that determined burst frequency. These findings provide a physical and mechanistic framework for how distal enhancers control transcription, linking cohesin loop extrusion to burst kinetics at the single-gene level.
Cheng L, De C, Li J et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗
Rare k-mers reveal centromere haplogroups underlying human diversity and cancer translocations.
This study analyzed centromere variation in humans by using rare k-mers from centromeric regions and a new computational method (ascairn) applied to short-read whole-genome sequencing from thousands of genomes. The approach defined discrete centromere haplogroups with distinct structural features and revealed extensive global diversity and population-history signatures, and it was also applied to oligodendroglioma cases with 1p/19q co-deletion to assess relevance to cancer translocations. These results establish a practical sequencing-based way to genotype centromere haplogroups and may help explain centromere-driven mechanisms underlying genomic instability in cancer.
Shiraishi Y, Ochi Y, Sugawa M et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗
Reverse transcribed ssDNA derepresses translation of a retron antiviral protein.
This study characterized a non-canonical type VI retron antiviral mechanism by focusing on Retron-Vpa2 from Vibrio parahaemolyticus and testing system triggers when expressed in E. coli. Unlike canonical retrons, Retron-Vpa2 provides broad phage defense without detectable multicopy msDNA in the absence of phage, and the authors identified a highly enriched structured hybrid RNA within the retron operon that mediates the response. Scientifically, it reveals how reverse-transcribed ssDNA can derepress translation of a retron antiviral protein, expanding understanding of bacterial immune strategies beyond msDNA antitoxin models.
Zhang K, Rojas-Montero M, Poola D et al. · Molecular cell · (2026) · View on PubMed ↗
Endosome-associated Rab GTPases control distinct aspects of neural circuit assembly.
This in vivo study dissected how endosome-associated Rab GTPases regulate neural circuit assembly by using clonal analyses with null alleles to perturb Rab-mediated trafficking to early, late, and recycling endosomes across multiple stages of circuit formation. The key finding was that distinct Rab functions (notably Rab5 and Rab11) control different aspects of receptor routing and thereby different steps of neural circuit assembly. These mechanistic insights clarify how endocytic trafficking programs shape synaptic and circuit connectivity.
Dong KX, Zhang Y, Ji H et al. · eLife · (2026) · View on PubMed ↗ · Free PDF ↗
Cancer diagnostics via liquid biopsy & ctDNA/biomarkers
Treatment of Advanced Biliary Tract Cancer: ASCO Living Guideline, Version 2026.1.0.
This ASCO living guideline systematically reviewed evidence to make recommendations on liquid biopsy and systemic therapy for patients with advanced biliary tract cancer. It synthesized concordance data between liquid biopsy and tissue biopsy (six studies) and incorporated randomized trial evidence for first-line systemic therapy (nine RCTs) and second-line chemotherapy (one phase III and four phase II RCTs). Clinically, it provides an up-to-date framework for using liquid biopsy and selecting chemotherapy/targeted strategies in advanced biliary tract cancer as new biomarker and trial data emerge.
Shroff RT, Kennedy EB, Alarcon Rozas AE et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗
Real-World Tumor-Informed Circulating Tumor DNA Dynamics and Survival Associations in Advanced Urothelial Cancer Treated With First-Line Enfortumab Vedotin and Pembrolizumab.
This retrospective real-world study evaluated tumor-informed circulating tumor DNA (ctDNA) dynamics measured by the Signatera assay in patients with locally advanced or metastatic urothelial cancer (la/mUC) receiving first-line enfortumab vedotin plus pembrolizumab (EVP). Key findings showed that ctDNA clearance/dynamics after treatment initiation were associated with overall survival (OS) and progression-free survival (PFS). These results support tumor-informed ctDNA as a clinically actionable response biomarker for EVP in advanced urothelial cancer.
Nimgaonkar V, Arbuiso A, Vlachou E et al. · JCO precision oncology · (2026) · View on PubMed ↗
Cerebrospinal fluid and plasma circulating tumor DNA dynamics as a biomarker of response during trastuzumab deruxtecan treatment in patients with breast cancer with leptomeningeal disease.
This prospective DEBBRAH trial cohort analysis evaluated cerebrospinal fluid (CSF) and plasma ctDNA dynamics as a response biomarker in seven patients with cytology-confirmed breast cancer leptomeningeal disease treated with trastuzumab deruxtecan (T-DXd). Using ultra-low-pass whole-genome sequencing with targeted unique molecular identifiers (UMIs) to quantify ctDNA tumor fraction (TF), the study found that CSF and plasma ctDNA dynamics tracked with treatment response during T-DXd therapy. These findings suggest CSF ctDNA TF may enable quantitative, minimally invasive monitoring of therapeutic efficacy in leptomeningeal disease.
Fitzpatrick A, Shanmugalingam T, Haider S et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗
Renal/critical care: dialysis modality, fluids, shock vasopressors/dobutamine
Quinolinic acid contributes to maladaptive kidney injury and acute kidney injury-to-chronic kidney disease transition.
This study investigated whether quinolinic acid (QA) drives maladaptive kidney injury and the AKI-to-CKD transition using folic acid and cisplatin AKI models, genetic/exogenous QA manipulation, and clinical observations. It found that QA contributes to kidney injury and promotes the AKI-to-CKD transition, implicating the QA pathway via quinolinate phosphoribosyltransferase (QPRT) in renal pathophysiology. The results identify QA metabolism as a mechanistic target to prevent progression from acute kidney injury to chronic kidney disease.
Saade MC, Saliba A, Clark AJ et al. · Science translational medicine · (2026) · View on PubMed ↗
Intermittent or Continuous Renal-Replacement Therapy in Acute Kidney Injury.
This multicenter, open-label noninferiority trial studied whether intermittent hemodialysis versus continuous renal-replacement therapy (CRRT) as initial renal-replacement therapy improves outcomes in critically ill adults with acute kidney injury who had indications for dialysis. The trial was stopped early after interim analyses (results truncated in the abstract), evaluating a primary endpoint of major adverse kidney events by day 90 (death, dialysis dependence, or >25% creatinine rise from baseline). Clinically, the study directly informs which renal-replacement modality to start in ICU patients with AKI, potentially changing standard practice and resource allocation.
Gaudry S, Boubaya M, Louis G et al. · The New England journal of medicine · (2026) · View on PubMed ↗
Effect of Vasopressin Initiation Threshold on Septic Shock Mortality: The VASSPR Cluster Crossover Randomized Strategy Trial.
This cluster-randomized, cluster-crossover pragmatic strategy trial compared hospital-level protocols that initiate vasopressin infusion at a lower versus higher vasopressor threshold in adult patients with septic shock receiving vasopressors. The key finding is not included in the provided abstract text (truncated), but the study’s purpose was to determine whether earlier vasopressin initiation reduces septic shock mortality. If effective, the results would support a specific, implementable vasopressor escalation threshold to improve survival in septic shock.
Peltan ID, Groat D, Jacobs JR et al. · JAMA · (2026) · View on PubMed ↗
Intraoperative Dobutamine Plus Norepinephrine to Prevent Postoperative Acute Kidney Injury in Septic Shock: A Randomized Clinical Trial.
This randomized, open-label clinical trial studied whether intraoperative dobutamine combined with norepinephrine reduces postoperative acute kidney injury (AKI within 7 days) in adults with septic shock undergoing surgical source control. The key outcome results are not present in the provided abstract excerpt (truncated), but the intervention targets persistent hypoperfusion using guideline-recommended dobutamine added to norepinephrine. Scientifically and clinically, the trial tests whether adding dobutamine during surgery can prevent AKI beyond norepinephrine alone.
Chu L, Xie G, Shi R et al. · JAMA · (2026) · View on PubMed ↗
Fluid Therapy in Mechanically Ventilated Critically Ill Adult Patients.
This international prospective observational cohort study characterized ICU fluid therapy practices in mechanically ventilated critically ill adults across 206 ICUs in 41 countries. The abstract excerpt does not include the specific findings (truncated), but the study quantified real-world variation in fluid type, dose, and indications among adults ventilated for at least 24 hours. The results are significant for improving evidence-based fluid management and identifying targets for future interventional trials in mechanically ventilated patients.
Blok SG, de Grooth HJ, Pisani L et al. · JAMA · (2026) · View on PubMed ↗
PKM2 AP: a micropeptide inhibits vascular calcification via molecular glue-mediated ubiquitination of PKM2.
The study investigated a newly identified 40-amino-acid micropeptide, PKM2 AP, encoded by an ORF2-containing intron-retaining transcript from the LINC01139 locus, and its role in vascular calcification in the context of chronic kidney disease. PKM2 AP localized to mitochondria and cytoplasm, bound pyruvate kinase M2 (PKM2), and promoted ubiquitination-dependent degradation of PKM2, thereby inhibiting vascular calcification. This mechanistic “molecular glue”-like strategy highlights PKM2 AP as a potential therapeutic target to prevent CKD-associated vascular calcification.
Wang M, Cheng J, Ma L et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Rhein-induced free fatty acid generation cooperates with silver ions for biofilm-infected diabetic wound healing.
The study examined how rhein-induced free fatty acid (FFA) generation cooperates with silver ions to improve healing of biofilm-infected diabetic wounds, focusing on MRSA and carbapenem-resistant E. coli (CREC) biofilms. Proteomics/metabolomics of patient ulcer tissues suggested that healed tissue shows activation of LDLR-mediated LDL-C endocytosis and increased free fatty acid production, supporting a countermeasure concept against biofilms, and the work tested the combined rhein/Ag strategy to address oxidative instability and biofilm infection. This supports a translational antimicrobial–metabolic therapeutic concept for diabetic foot infections where biofilms drive treatment failure.
Du T, Cui M, Shan J et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
How do I manage candiduria: practical algorithms and remaining conundrums in 2026.
This 2026 clinical review synthesized evidence and proposed practical diagnostic and management algorithms for candiduria across common clinical scenarios in hospitalized patients, including asymptomatic colonization/contamination, true urinary tract infection, and rarer invasive candidiasis. The key finding was the identification of remaining diagnostic and therapeutic conundrums—especially how to distinguish colonization from infection and when to escalate beyond supportive care. Scientifically and clinically, the article provides an evidence-informed framework to standardize candiduria evaluation and reduce inconsistent management.
Blez D, Pana ZD, Lampros A et al. · Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · (2026) · View on PubMed ↗
Generated automatically on October 15, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.