PubMed Trending Research Digest — August 16, 2026

A curated digest of 97 trending PubMed articles, automatically categorised and summarised across 15 research areas.

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Post-viral and Long COVID Cardiovascular Sequelae Inflammation, Innate Immunity, and Inflammasome Signaling ARDS and Critical Care Pharmacotherapy Clinical Trial Evidence, Heterogeneity, and Trial Design Gastrointestinal Diagnostics and IBS-D Mimics Tumor Immunology and Myeloid Cell Reprogramming Cancer Genomics, Molecular Stratification, and Biomarkers Viral Immunology, Vaccines, and Host-Pathogen Interactions Chromatin, Epigenetics, and Nuclear Architecture Neurodegeneration: Tau, TDP-43, and Proteostasis Neuroinflammation and Glial Biology Neurodevelopmental Risk and Early-Life Biomarkers Metabolic Disease, Endocrine Risk, and Drug Adverse Effects Cardiovascular Risk Prediction and Lipid Therapies Therapeutic Delivery, Gene Editing, and Drug Design/Mechanisms

Automated digest · 97 articles · 15 research areas · August 16, 2026

Overview

Across this week’s set of papers, a dominant theme is precision and stratification—moving beyond one-size-fits-all approaches in both infectious/inflammatory disease and oncology. Reviews and clinical studies emphasize that treatment effects depend on biological context (e.g., ARDS phenotypes for corticosteroids; spatiotemporal macrophage programs for TREM2; myeloid heterogeneity shaped by targets like CD1d or IL-17D–CD93 in tumors). In cancer, multiple studies focus on actionable biomarkers and molecular subgrouping, including exposure-driven mutational patterns in head and neck cancer, SPEN-linked resistance to androgen receptor pathway inhibitors, and DNA hypomethylation signatures predicting benefit from durvalumab plus olaparib in extensive-stage small-cell lung cancer. Even in diagnostics and monitoring, blood-based Alzheimer biomarker panels and ctDNA assay strategies reflect a shift toward decision-support tools that can be deployed in real-world workflows.

A second major thread is immune–metabolism and inflammation–tissue damage coupling. Mechanistic work links innate immune signaling to disease progression across organ systems: GPR84 amplifies neuroinflammation via inflammasome pathways; ATX/LPA drives macrophage osteoclastogenesis and inflammation in periodontitis; type I interferon signaling can selectively blunt IFNγ responses in tuberculosis; and hypoxia-driven metabolic reprogramming promotes ferroptosis resistance and immunosuppression in hepatocellular carcinoma. Cardiovascular papers similarly connect immune programs to risk and injury (single-cell immune signatures for atherosclerotic risk; conserved hypertension-associated renal injury gene programs), while lipid-focused reviews (including Lp(a)) highlight why new targeted therapies are needed.

Finally, several studies underscore advances in therapeutic technology and delivery—ranging from next-generation drug modalities (molecular glues, ADCs, targeted protein degradation, and nucleic-acid therapeutics) to improved delivery/engineering for gene editing and cell-based therapies. In parallel, neurobiology continues to progress from circuit- and cell-type mechanisms (astrocyte NFIX control of oscillations and memory; perivascular macrophage cMAF→IGF1 effects on vascular function) to molecular proteostasis mapping in tau/TDP-43 disorders. Together, these findings point toward increasingly mechanistic, biomarker-guided interventions that target not just disease markers, but the upstream cellular programs that generate pathology.

Post-viral and Long COVID Cardiovascular Sequelae

Exercise intensity modulates interorgan communication and is associated with cardiometabolic health outcomes in humans.

This multi-cohort human exercise intervention study compared sprint-interval exercise (SIE) and moderate-intensity exercise (MIE) to determine how exercise intensity modulates interorgan communication and relates to cardiometabolic health outcomes. The key finding was that exercise intensity distinctly altered the plasma proteome and metabolome in both untrained and trained participants, and that integrated multi-organ gene/protein expression analyses linked these changes to health outcomes. Scientifically, it identifies intensity-dependent circulating molecular signals that may mediate exercise benefits and guide personalized exercise prescriptions.

Olsen L, Botella J, Barrows D et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Ketamine assisted psychotherapy to reduce chronic neuropathic pain: A mixed-methods randomized pilot trial.

This randomized, outcome-assessor-blinded single-center pilot trial studied whether combining intravenous ketamine infusions with cognitive behavioral psychotherapy improves feasibility and outcomes in adults with moderate-to-severe chronic neuropathic pain. Participants were assigned to ketamine alone, psychotherapy alone, or ketamine plus psychotherapy, with ketamine delivered as three IV infusions over 16 weeks and psychotherapy delivered as 16 weekly CBT sessions. The trial’s design tests a clinically relevant multimodal approach to extend beyond ketamine’s short-term analgesic effects and informs future efficacy trials.

Goel A, Diep C, Zahin A et al. · Med (New York, N.Y.) · (2026) · View on PubMed ↗

Digital Health Technology for Improving Physical Function in Adults With Chronic Heart Failure: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis studied the effects of digital health technologies (DHTs) on physical function and physical activity outcomes in adults with chronic heart failure (CHF) using randomized controlled trials. The authors found that DHTs can improve health-related outcomes and/or functional capacity, while the impact on daily physical behavior versus functional capacity varied across interventions and study designs. Scientifically and clinically, the synthesis helps define which DHT characteristics may be most effective for CHF rehabilitation and highlights where evidence remains inconsistent.

Meng Z, Li J, Yang J et al. · Journal of medical Internet research · (2026) · View on PubMed ↗ · Free PDF ↗

Exercise and Cardiovascular Risk Modulation in Post-COVID Syndrome.

This review examined cardiovascular pathophysiology in people with post-COVID syndrome (PASC) and evaluated evidence for exercise training as a countermeasure. It reports that PASC is associated with persistent low-grade inflammation, endothelial dysfunction, arterial stiffness, metabolic and autonomic disturbances, and increased atherosclerotic risk, with exercise training showing potential to mitigate vascular dysfunction and cardiovascular risk. These findings support exercise-based rehabilitation as a plausible strategy to reduce long-term cardiovascular complications in PASC, though the evidence base is still evolving.

Goulart CDL, Franzoni LT, Ferrari F et al. · Current atherosclerosis reports · (2026) · View on PubMed ↗ · Free PDF ↗

Inflammation, Innate Immunity, and Inflammasome Signaling

Gut microbiota and gut-kidney axis in kidney diseases: therapeutic potential and perspectives of natural products.

This review examined how gut microbiota dysbiosis and the gut–kidney axis contribute to chronic kidney disease (CKD) progression and how natural products might therapeutically target these pathways. It found CKD-associated shifts toward opportunistic pathogens and loss of beneficial commensals drive accumulation of uremic toxins (indoxyl sulfate, p-cresyl sulfate, and TMAO) while reducing protective intestinal metabolites such as short-chain fatty acids (SCFAs) and indole-3-aldehyde. These mechanistic links support natural-product strategies aimed at restoring microbiome balance and metabolite profiles to mitigate CKD-related systemic toxicity and inflammation.

Wang Q, Zhang J, Chen R et al. · Frontiers in pharmacology · (2026) · View on PubMed ↗ · Free PDF ↗

Strong, sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility.

This work investigated how type I interferon (IFN) signaling affects Mycobacterium tuberculosis (Mtb) immunity in infected macrophages, focusing on cell-intrinsic impairment of IFNγ responses. The authors found that IFNγ signaling is selectively impaired in the subset of infected macrophages experiencing high and sustained type I IFN signaling, and genetic elimination of RESIST (regulated stimulator of interferon via stabilization of transcript) altered this susceptibility pathway. These findings clarify a mechanism by which type I IFNs promote tuberculosis susceptibility and suggest RESIST as a potential target to restore IFNγ-driven antimicrobial immunity.

Fattinger SA, Parisi B, Chavez RA et al. · Cell host & microbe · (2026) · View on PubMed ↗

Polyamines buffer labile iron to suppress ferroptosis.

This study examined how polyamines regulate ferroptosis by buffering labile redox-active iron, using a genome-wide CRISPR screen to uncover genetic interactions. Polyamine depletion showed synthetic lethality with the ferroptosis suppressor GPX4, and mechanistic experiments indicated that polyamines control iron redistribution that suppresses ferroptotic execution. The work connects polyamine metabolism to ferroptosis control and suggests that targeting polyamine–iron homeostasis could modulate ferroptosis therapeutically.

Sharma P, Keys HR, Mansell RP et al. · Cell · (2026) · View on PubMed ↗

Mechanism and plasticity of primitive pyroptosis.

This study investigated the mechanism and plasticity of “primitive” pyroptosis by functionally characterizing two gasdermin (GSDM) variants with cytotoxicity: a bacterial homolog (bGSDM) from Runella zeae and a fungal homolog (fGSDM/HET-Q1) from Podospora anserina. The authors compared how these non-canonical GSDM proteins execute cell death, contrasting them with the well-studied modern proteolytic activation pathway. Understanding primitive GSDM pore formation can reveal evolutionary principles of pyroptosis and inform how different GSDM proteins might be targeted or engineered.

Su Z, Huang M, Gan J et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Autotaxin/Lysophosphatidic Acid Axis Promotes Periodontitis by Modulating Macrophage Osteoclastogenesis and Inflammation.

This mechanistic study investigated the autotaxin/lysophosphatidic acid (ATX/LPA) axis in periodontitis by analyzing ATX/LPA expression in human gingival and gingival crevicular fluid samples from periodontitis patients and healthy controls. Using macrophage Atx knockout (CKO) mice, bone marrow-derived macrophages, and the ATX inhibitor PF8380, the authors showed that ATX/LPA promotes periodontitis by modulating macrophage osteoclastogenesis and inflammation. These results identify the ATX/LPA pathway as a potential therapeutic target to reduce bone destruction and inflammatory drive in periodontitis.

Liu E, Ding J, Jiang Y et al. · Journal of clinical periodontology · (2026) · View on PubMed ↗ · Free PDF ↗

Methicillin-resistant Staphylococcus aureus.

This article is a disease primer summarizing what is known about methicillin-resistant Staphylococcus aureus (MRSA) across colonization and infection. It highlights that MRSA transitions from asymptomatic skin/mucosal commensal colonization to invasive disease (e.g., bacteremia, pneumonia, osteomyelitis, endocarditis) when host barriers or immune defenses fail, driven by virulence factors for adhesion, immune evasion, invasion, and persistence. Clinically, the review frames MRSA as a major antimicrobial-resistance threat and underscores virulence and host-transition mechanisms as key targets for prevention and treatment strategies.

Parsons JB, Westgeest AC, Conlon BP et al. · Nature reviews. Disease primers · (2026) · View on PubMed ↗

TREM2 signaling in cardiovascular disease: macrophage heterogeneity, timing, and therapeutic opportunity.

This review summarized evidence on TREM2 signaling in cardiovascular disease, emphasizing macrophage heterogeneity and the timing of TREM2+ macrophage programs across atherosclerosis, myocardial infarction, heart failure, and sepsis-induced cardiopulmonary dysfunction. It concludes that TREM2 acts as a pivotal molecular hub within a dynamic, spatiotemporal macrophage landscape rather than a static M1/M2 classification. The therapeutic significance is that timing- and context-specific modulation of TREM2+ macrophage states may improve outcomes in cardiovascular inflammation and injury.

Yang K, Ma X, Wang B et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

Hypoxia drives ferroptosis resistance and immunosuppression in hepatocellular carcinoma by inducing UBASH3B-mediated glutamine metabolism reprogramming and CXCL8 expression.

This study examined how hypoxia regulates ferroptosis resistance and immunosuppression in hepatocellular carcinoma (HCC) through HIF-1α–driven UBASH3B-mediated glutamine metabolism reprogramming and CXCL8 expression. The authors found that HIF-1α promotes UBASH3B, which dephosphorylates MYBL2 at Y15 to stabilize MYBL2, thereby reprogramming glutamine metabolism to confer ferroptosis resistance and increasing CXCL8-associated immunosuppressive signaling. These findings link hypoxia, transcriptional control (MYBL2), and ferroptosis escape in HCC, suggesting UBASH3B/MYBL2/CXCL8 as potential therapeutic targets to overcome treatment resistance.

Pan GQ, Zhang SP, Wang X et al. · Redox biology · (2026) · View on PubMed ↗ · Free PDF ↗

GPR84 and Neuroinflammation: A Receptor Worth Targeting, or A Target Worth Reconsidering?

This review analyzed the role of the medium-chain fatty acid–sensing receptor GPR84 in neuroinflammation, focusing on innate immune cells including microglia and its signaling pathways. It finds that GPR84 activation engages Gi/o, MAPK/ERK, NF-κB, and the NLRP3 inflammasome to amplify pro-inflammatory cytokine programs (e.g., TNF-α and IL-1β) in models of neurodegeneration, traumatic CNS injury, and neuropathic pain, while also noting context-dependent protective effects. The work suggests GPR84 is a potential therapeutic target in neuroinflammatory disease but cautions that target validity may depend on disease context and microglial state.

Jarco J, Malek N · Molecular neurobiology · (2026) · View on PubMed ↗ · Free PDF ↗

ARDS and Critical Care Pharmacotherapy

Navigating Asparaginase Treatment for Patients With Acute Lymphoblastic Leukemia: US Consensus Panel Recommendations on the Role of Multidisciplinary Care.

This article provided US consensus panel recommendations on multidisciplinary care to improve safe, timely, and complete delivery of asparaginase-based therapy in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL). It highlighted operational and clinical barriers—such as complex administration, distinct toxicity, prolonged treatment duration, and variability in institutional infrastructure—that can compromise asparaginase delivery across care settings. The guidance is clinically significant because it aims to standardize coordination and supportive services to reduce treatment delays and toxicity-related failures in ALL/LBL care.

Ali A, Elsey G, Fulginiti K et al. · American journal of hematology · (2026) · View on PubMed ↗

This multicentre, randomised, double-blind, placebo-controlled phase 3 trial studied the safety and efficacy of erythrocyte encapsulated dexamethasone sodium phosphate (eDSP) in children aged 6–9 years with ataxia telangiectasia (NEAT). eDSP was evaluated against placebo for effects on neurological outcomes in a population with progressive cerebellar neurodegeneration and no approved therapies. If effective and safe, eDSP would provide the first randomised-trial evidence to support corticosteroid-based disease modification in paediatric ataxia telangiectasia.

Russo S, Zielen S, Pietrucha B et al. · The Lancet. Child & adolescent health · (2026) · View on PubMed ↗

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

This review studied the evidence for corticosteroid therapy in acute respiratory distress syndrome (ARDS), emphasizing timing, inflammatory burden, and host response across etiologies including COVID-19 ARDS and severe community-acquired pneumonia. It concludes that clinical data support corticosteroids in moderate-to-severe ARDS with reductions in mortality and duration of mechanical ventilation, but that treatment effects vary by ARDS phenotype (hyperinflammatory vs hypoinflammatory) and biological subgroups. These insights indicate that future ARDS management should move toward phenotype- and timing-informed corticosteroid use rather than one-size-fits-all treatment.

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

Clinical Trial Evidence, Heterogeneity, and Trial Design

Decades of intensive care medicine trials: what randomised evidence has changed, corrected, and still questions to resolve.

This interpretive historical review examined landmark randomized controlled trials (RCTs) in adult intensive care medicine (ICM) from the early 1990s onward to determine what evidence changed practice, corrected errors, or left unresolved questions. It finds that many interventions with strong physiological rationale failed to improve patient-centered outcomes, while durable gains often came from optimizing supportive care, avoiding iatrogenic harm, and re-evaluating established practices. The review highlights the need for better trial designs and biologically informed stratification to address heterogeneity in acute organ failure and recovery trajectories.

Martin-Loeches I, Leone M, Coopersmith CM et al. · Intensive care medicine · (2026) · View on PubMed ↗

Gastrointestinal Diagnostics and IBS-D Mimics

Mistakes in the management of irritable bowel syndrome-diarrhoeal subtype and mimics: a narrative review.

This narrative review studied diagnostic pitfalls in irritable bowel syndrome with diarrhoea (IBS-D) by focusing on management mistakes and common mimics in clinical practice. It reports that conditions such as microscopic colitis, bile acid diarrhoea, small intestinal bacterial overgrowth, coeliac disease, exocrine pancreatic insufficiency, endocrine disorders, lactase deficiency, sucrase-isomaltase deficiency, early inflammatory bowel disease, and functional diarrhoea can present with overlapping symptoms, leading to misdiagnosis and inappropriate symptom-based treatment. The clinical significance is that careful evaluation for these mimics is essential to avoid delayed or incorrect therapy in patients labeled as IBS-D.

Senadheera P, Silva B, Jayasena H et al. · Current medical research and opinion · (2026) · View on PubMed ↗

Tumor Immunology and Myeloid Cell Reprogramming

CD1d remodels the tumor-infiltrating myeloid populations controlling antitumor immunity.

This study investigated how the lipid-presenting molecule CD1d regulates tumor-infiltrating myeloid populations and antitumor immunity in mouse models of breast cancer. It found that genetic deletion or antibody-mediated targeting of CD1d reduced tumor growth, reshaped immune infiltration, and improved the efficacy of anti–PD-1 immunotherapy, consistent with CD1d-driven control of myeloid heterogeneity in the tumor microenvironment. These results support CD1d as a mechanistic immunotherapy target that could enhance responses to PD-1 blockade by reprogramming tumor myeloid cells.

Evans L, Conde Poole M, Celik C et al. · The Journal of experimental medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer Genomics, Molecular Stratification, and Biomarkers

DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy.

This multi-omics analysis of a phase II trial studied whether DNA hypomethylation can identify a clinical benefit subgroup among patients with extensive-stage small-cell lung cancer (ES-SCLC) receiving durvalumab plus olaparib as maintenance therapy. In 60 enrolled patients (NCT05245994), the analysis linked specific DNA hypomethylation patterns to differential clinical benefit during maintenance, suggesting a biomarker-defined responder subgroup. This is significant because it could enable stratification of ES-SCLC patients likely to benefit from combined PARP inhibition (olaparib) and PD-L1 blockade (durvalumab).

Zhao Y, Wang Q, Xiao B et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Prognostic Significance of Spread Through Airspaces (STAS) in Stage Ia/bN0 Non-small Cell Lung Cancer - An Evaluation in the JCOG0802/WJOG4607L Clinical Trial Patients.

This study evaluated the prognostic impact of spread through airspaces (STAS) and tumor grade on relapse-free survival (RFS) and overall survival (OS) in stage IA pT1a/bN0 non-small cell lung cancer (NSCLC) patients from the JCOG0802/WJOG4607L trial. STAS and grade were assessed in 593 tumors by 32 expert pulmonary pathologists, and the analysis compared outcomes in lobectomy versus segmentectomy to determine how surgical extent interacts with STAS risk. The findings are clinically important for refining surgical decision-making in early-stage NSCLC by clarifying whether STAS should influence the choice between segmentectomy and lobectomy.

Yatabe Y, Beasley MB, Borczuk A et al. · Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · (2026) · View on PubMed ↗

Identifying independent causal cell types for human diseases and risk variants.

This study developed cell-type fine-mapping methods (CT-FM and CT-FM-SNP) to identify independent causal cell-type sets and candidate causal variants for complex traits using 63 GWAS datasets and 924 candidate regulatory element (cRE) annotations. Applying CT-FM explained 39.0% ± 1.8% of trait SNP heritability and identified 14 traits (including height, schizophrenia, and autoimmune diseases) with multiple independent cellular mechanisms. The approach improves mechanistic interpretation of GWAS signals by pinpointing which cell types independently drive disease risk.

Kim A, Zhang ZE, Legros C et al. · Cell genomics · (2026) · View on PubMed ↗ · Free PDF ↗

Mosunetuzumab With Response-Adapted Polatuzumab Vedotin and Obinutuzumab in Untreated Indolent B-Cell Non-Hodgkin Lymphoma.

This clinical study evaluated a chemotherapy-free strategy in untreated indolent B-cell non-Hodgkin lymphoma by combining the CD3/CD20 bispecific antibody mosunetuzumab with response-adapted polatuzumab vedotin and obinutuzumab. Patients received eight cycles of mosunetuzumab, and those without complete response by PET-CT could receive six cycles of polatuzumab vedotin plus obinutuzumab. If successful, this regimen could reduce chemotherapy exposure while maintaining efficacy in follicular lymphoma and marginal zone lymphoma.

Lynch RC, Poh C, Shadman M et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Efficacy of Olaparib Plus Abiraterone for Patients with Metastatic Castration-resistant Prostate Cancer and Single Homologous Recombination Repair Gene Mutations in PROpel.

This analysis evaluated efficacy of olaparib plus abiraterone in PROpel (phase 3, randomized double-blind trial) for metastatic castration-resistant prostate cancer (mCRPC) patients with single homologous recombination repair gene mutations (HRRm). The trial previously met its primary endpoint with improved investigator-assessed radiographic progression-free survival (rPFS) versus placebo plus abiraterone, and this report extends the efficacy characterization to the HRRm subgroup. Clinically, it supports using olaparib plus abiraterone as a targeted first-line option for mCRPC patients harboring specific single HRR gene defects.

Shore N, Clarke NW, Armstrong AJ et al. · European urology oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Spatial proteogenomic profiling uncovers sensitization strategies for antibody-drug conjugate in HER2-positive breast cancer.

The study used imaging mass cytometry and spatial proteogenomic profiling of 912,360 single cells from 47 HER2-positive/hormone receptor-negative breast cancer patients in the FASCINATE-N trial treated with the HER2-targeting antibody-drug conjugate SHR-A1811. Elevated tumor-cell H3K27ac predicted improved ADC efficacy, while collagen-positive fibroblasts mediated resistance; combining SHR-A1811 with the histone deacetylase inhibitor chidamide or the collagen-modulating agent losartan produced synergistic antitumor effects. These spatial biomarkers and combination strategies could guide patient selection and rational ADC combination therapy to overcome stromal-mediated resistance in HER2+ breast cancer.

Cai YW, Jia SH, Wang H et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Platelet Reactivity and Sex Differences: Clinical Implications for Women.

This study investigated whether SPEN inactivation drives resistance to androgen receptor pathway inhibitors (ARPIs) in metastatic prostate cancer using preclinical models and clinical datasets. The key finding was that SPEN loss/mutation is associated with ARPI resistance, supported by analyses in LNCaP and VCaP cell lines and by clinico-genomic database correlations with time to next treatment, with SPEN immunohistochemistry on metastatic tissue. Clinically, SPEN could serve as a biomarker to predict ARPI resistance and guide treatment selection in metastatic prostate cancer.

Aggarwal A, Barrett TJ, Mehta PK et al. · Circulation research · (2026) · View on PubMed ↗

Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial.

In the phase 3 NRG-GU005 randomized clinical trial, the investigators compared stereotactic body radiotherapy (SBRT) versus moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) for localized intermediate-risk prostate cancer, focusing on patient-reported urinary/bowel quality of life and disease-free survival (DFS). SBRT was evaluated for superiority relative to MH-IMRT in both symptom outcomes and DFS. The trial informs how to optimize radiotherapy delivery speed while maintaining or improving oncologic and quality-of-life outcomes for intermediate-risk patients.

Ellis RJ, Pugh SL, Yu JB et al. · JAMA · (2026) · 1 citations · View on PubMed ↗

Tissue-Free vs Tumor-Informed ctDNA Assays for Molecular Residual Disease Detection in Early Triple Negative Breast Cancer.

This prognostic/exploratory analysis compared tissue-free versus tumor-informed circulating tumor DNA (ctDNA) assays for molecular residual disease (MRD) detection in early triple-negative breast cancer (TNBC) patients at moderate to high recurrence risk. The study evaluated whether the tissue-free ctDNA approach—without sequencing the primary tumor—matches the accuracy of tumor-informed assays for MRD detection and prognostic performance. If comparable, tissue-free MRD testing could simplify adjuvant therapy selection workflows for TNBC by reducing dependence on tumor tissue sequencing.

Cunningham N, Cutts RJ, Swift C et al. · JAMA oncology · (2026) · View on PubMed ↗ · Free PDF ↗

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

This study analyzed exposure-driven somatic alterations in TP53, PIK3CA, and CCND1 across oral cavity (OC) and oropharyngeal (OPC) tumors, including HPV-positive and HPV-negative disease, using a 1,109-gene panel in 1,086 tumors. It found that PIK3CA alterations were widespread but context-specific—HPV+ OPC showed APOBEC-driven mutations and co-occurring FGFR3 mutations in a subset, whereas HPV− OPC and OC were characterized by 3q26/28 amplifications involving PIK3CA/TP63/SOX2—and that TP53 was the most frequently mutated gene in HPV− tumors. The significance is that these gene-exposure patterns can refine molecular stratification of head and neck cancers and potentially guide more tailored prevention and treatment strategies.

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

Viral Immunology, Vaccines, and Host-Pathogen Interactions

Canonical Antibodies Adopt Distinct Binding Modes to Recognize Viral Glycan Shields.

This study examined how canonical Y-shaped human antibodies (VRC35 and VRC36) isolated from an HIV-1-infected donor recognize viral glycan shields on diverse viral entry glycoproteins. Cryo-electron microscopy structures showed that these antibodies adopt distinct binding modes to engage N-linked glycan-rich surfaces across targets including HIV-1 envelope, influenza hemagglutinin, SARS-CoV-2 spike, and the Lassa virus glycoprotein complex. The results clarify structural principles for antibody recognition of glycosylated epitopes, informing vaccine and therapeutic antibody design against glycan-shielded viruses.

Cheng J, Cale EM, Maghsoudi A et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Functional atlas of vertebrate viral RNA elements that stabilize RNA and enhance translation.

The study used massively parallel reporter assays across ~200,000 genomic segments from 297 vertebrate-infecting viral genera to map viral RNA elements that stabilize RNA and enhance translation. It identified many elements that act via TENT4-mediated mixed tailing across 19 genera in six subclasses, plus additional TENT4-independent elements using alternative pathways, including a Potamipivirus element (Pt1) that stabilizes linear mRNA to circular-RNA-like levels. These functional maps clarify convergent viral strategies for post-transcriptional gene expression and provide candidate RNA elements for engineering translation/stability in biotechnology.

Seo JJ, Lee C, Lim D et al. · Cell · (2026) · View on PubMed ↗

Recent advances in cryoelectron tomography and applications to parasitology.

This review summarizes recent advances in cryo-electron tomography (cryo-ET) and how improvements in sample preparation, data collection, and computational analysis expand what can be resolved in eukaryotic parasites. It highlights applications to medically important pathogens such as Toxoplasma gondii, Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi, Cryptosporidium parvum, and Microsporidia, covering accessible resolutions and cellular structures. The article underscores cryo-ET’s growing role in revealing native parasite ultrastructure and structural cell biology relevant to parasitology and drug target discovery.

Coudray N, Ekiert DC, Bhabha G · Current opinion in structural biology · (2026) · View on PubMed ↗

A tonsil organoid model reveals Epstein-Barr virus-infected germinal center B cell states during primary infection.

This work developed an EBV human tonsil organoid model to study Epstein-Barr virus infection dynamics in B cells during primary infection, focusing on germinal center-like states and antiviral responses. The key finding was that EBV drove B-cell differentiation toward germinal center-like phenotypes, with transcriptomic programs and B-cell receptor repertoire changes characteristic of EBV-infected cells. The model’s significance is that it enables mechanistic study of EBV-infected B-cell states in a lymphoid microenvironment that better reflects in vivo infection.

Mitul MT, Sun Y, Yates TB et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

A boost for chemical vaccination against malaria.

This Science article discussed the concept of chemical vaccination against malaria by inhibiting Plasmodium plasmepsin proteins as a drug-based vaccine strategy. The key point was that targeting plasmepsins can induce protective immune effects, positioning plasmepsin inhibition as a feasible platform for vaccination-like interventions. The significance is that it reframes malaria prevention toward pharmacologically driven “chemical vaccination,” potentially complementing or accelerating traditional vaccine development.

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

‘Mismatched’ Ebola vaccine may soon be rolled out widely.

This commentary reviewed emerging evidence on whether an Ebola Zaire vaccine could also protect against Bundibugyo virus in the context of potential widespread rollout. The key finding was that new data suggest cross-protection between Ebola Zaire and Bundibugyo, supporting broader use of the Zaire vaccine. Clinically, this could accelerate and simplify Ebola outbreak preparedness by enabling “mismatched” vaccine deployment when Bundibugyo-specific vaccines are unavailable.

Kupferschmidt K · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Chromatin, Epigenetics, and Nuclear Architecture

The SF3b complex in cancer: structural basis, molecular mechanisms, and therapeutic opportunities.

This review summarized the structural basis and molecular mechanisms of the splicing factor 3b (SF3b) complex in cancer, emphasizing how cryo-EM has revealed its conformational dynamics during spliceosome assembly. It highlighted how genetic and functional perturbations of SF3b—particularly recurrent mutations in core subunits—can drive aberrant alternative splicing and cancer phenotypes. The review also outlines therapeutic opportunities, including strategies to target SF3b-dependent splicing vulnerabilities.

Li S, Shang L, Yang J et al. · Blood advances · (2026) · View on PubMed ↗ · Free PDF ↗

Alternative splicing dysregulation in CAG repeat expansion diseases.

This review examined how alternative splicing dysregulation (“spliceopathy”) contributes to CAG repeat expansion diseases, drawing on evidence from murine and patient-derived models of Huntington’s disease and multiple spinocerebellar ataxias. It highlights that splicing changes are widespread across these disorders and parallels the well-characterized CTG repeat expansion disease myotonic dystrophy type 1, where mis-splicing drives core symptoms. The synthesis supports alternative splicing as a shared mechanistic vulnerability and a potential therapeutic target across CAG repeat neurodegeneration.

Aliyeva A, Cleary JD, Shorrock HK et al. · Trends in neurosciences · (2026) · View on PubMed ↗ · Free PDF ↗

A regulatory adaptor for RAD51’s AAA+ unfoldase promotes homologous recombination-mediated DNA repair and genome stability.

This study investigated how the adaptor MACIR/C5orf30 regulates the FIGNL1–FIRRM AAA+ unfoldase to promote homologous recombination (HR)–mediated DNA repair and genome stability. The key finding was that MACIR directly binds FIRRM, enabling FIRRM-mediated RAD51 nucleoprotein filament disassembly via an ATPase-driven unfolding mechanism distinct from other anti-recombinase pathways. This is significant because it identifies a new regulatory component controlling RAD51 turnover during HR, offering potential targets for improving genome stability or sensitizing tumors to DNA-damage therapies.

Zhou T, Pang M, Liang X et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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

This study investigated how eukaryotic chromosomes condense during metaphase, focusing on a two-state condensed/decondensed model controlled by histone acetylation dynamics. The key finding was that chromosomes behave like ionic hydrogels undergoing a volume phase transition analogous to a liquid–gas transition, with ionic contacts between histone tails and DNA regulated by histone acetylation/deacetylation. Scientifically, it links chromatin condensation to a physical phase-change mechanism rather than loop extrusion alone, refining models of condensin-driven chromosome architecture.

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

Neurodegeneration: Tau, TDP-43, and Proteostasis

PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures.

This study investigated Alzheimer’s disease (AD) genetic risk mechanisms by downregulating PLCG2 in rat primary neuronal cultures and human neuronal cultures (hNCs), including analysis of rare PLCG2 loss-of-function (LoF) variants. PLCG2 downregulation impaired synaptic function and dendritic morphology and increased amyloid-β (Aβ) levels and Tau phosphorylation in hNCs, while PLCG2 LoF (including the R953* mutation) was linked to a ~10-fold increased AD risk and reduced PLCG2/PLCγ2 mRNA/protein. The results identify PLCG2 as a synaptic-protective gene whose loss promotes AD hallmark pathology, supporting PLCG2 pathway targeting as a potential therapeutic direction.

Coulon A, Rabiller F, Takalo M et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

The UNC13A cryptic exon associates with cognitive impairment in Alzheimer’s disease.

This study investigated whether a cryptic exon (CE) in the UNC13A gene is associated with cognitive impairment in Alzheimer’s disease. It builds on prior evidence that the UNC13A CE SNP rs12973192 (C>G) weakens TDP-43 binding and promotes CE inclusion, which is linked to higher risk and reduced survival in ALS/FTD. The work aims to connect TDP-43 splicing dysfunction at the UNC13A cryptic exon to AD-related cognitive decline, potentially identifying a splicing-based genetic risk factor.

Reeves MM, Aviles Carpintero S, Zanovello M et al. · Alzheimer’s research & therapy · (2026) · View on PubMed ↗ · Free PDF ↗

UV irradiation drives lineage-specific MITF-mediated transcription of PD-L1 to confer immune tolerance to UV-mutated melanocytes.

This work examined how UV irradiation alters melanocyte-intrinsic gene regulation in primary human melanocytes, focusing on the MITF transcription factor and PD-L1 (CD274). MITF directly bound a conserved upstream enhancer with functional E-box elements to drive lineage-specific PD-L1 transcription after UV exposure, enabling immune tolerance to UV-mutated melanocytes. The findings identify a MITF→PD-L1 pathway as a mechanistic driver of immune evasion after UV damage, informing strategies to prevent or treat UV-associated melanoma immune tolerance.

Lo JA, Rachmin I, Flesher JL et al. · Immunity · (2026) · View on PubMed ↗

Tau can wreak havoc in brain cells’ energy factories.

This news-style report summarized research on how tau pathology disrupts mitochondrial “energy factories” in brain cells, with implications for Alzheimer’s disease and related neurodegenerative disorders. The key finding was that mitochondrial dysfunction is a central downstream consequence of tau-related cellular stress, pointing to energy/mitochondria-targeted therapeutic strategies. Clinically, it supports developing treatments that address tau-driven bioenergetic failure rather than only targeting tau aggregation.

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

Artificial hibernation reveals synaptic engram architecture associated with memory retention.

This mouse study examined how artificial hibernation affects the synaptic structural trace of memory retention, focusing on dendritic spine and synapse architecture in hippocampal neurons. The key finding was that during hibernation there was extensive elimination of dendritic spines and synapses and reduced neuronal activity, yet memory and associated hippocampal neuronal representations remained intact. Scientifically, it suggests that stable memory retention can persist despite large synaptic turnover, implicating a specific “synaptic engram” subset or architecture rather than overall spine size/number.

Lin YJ, Takahashi-Nakazato A, Tsutsumi K et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗ · Free PDF ↗

Dietary vitamin A restricts intestinal tuft cell differentiation.

The study examined how dietary vitamin A/retinoic acid signaling regulates intestinal tuft cell differentiation in mice and in stem cell–derived intestinal organoids. Epithelial-intrinsic retinoic acid receptor signaling controlled tuft cell numbers, and retinoic acid administration reduced tuft cell abundance while dietary vitamin A dynamically altered tuft cells in vivo and impacted tuft cell–dependent anti-helminth immunity. These findings identify retinoic acid as a differentiation regulator of tuft cells, linking nutrient sensing to mucosal immune defense and suggesting a mechanistic basis for vitamin A–driven helminth susceptibility/resistance.

Didriksen BJ, Eshleman EM, Rice T et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

Selective Brain-Penetrant TTBK1 Inhibitors Modulate TDP-43 Pathology and Rescue Cognitive Deficits in a Mouse Model of TDP-43 Proteinopathy.

The research used a structure-guided medicinal chemistry program to discover selective, brain-penetrant tau tubulin kinase 1 (TTBK1) inhibitors and tested their effects on TDP-43 pathology in a mouse model of TDP-43 proteinopathy. Lead compounds potently and selectively inhibited TTBK1 without affecting ciliogenesis (TTBK2 selectivity) and improved central nervous system outcomes, including rescue of cognitive deficits. This supports TTBK1 as a druggable target for TDP-43–related neurodegeneration and provides candidate brain-penetrant inhibitors with reduced on-target ciliogenesis risk.

Sanchez-Santos C, Jimenez-Amor A, Martinez-Gonzalez L et al. · Journal of medicinal chemistry · (2026) · View on PubMed ↗ · Free PDF ↗

Plasma Alzheimer Biomarkers and Diagnostic Decision-Making in Memory Clinics.

This prospective diagnostic study evaluated how a tailored plasma biomarker panel—pTau181, GFAP, and NfL—presented during multidisciplinary memory clinic meetings related to final syndrome diagnosis, suspected etiology, and clinician confidence. The plasma biomarker panel was associated with diagnostic decision-making in memory clinics, influencing both suspected causes and clinician confidence levels. The work supports the clinical validity of blood-based Alzheimer-related biomarkers as decision aids in real-world diagnostic workflows.

Vigneswaran S, Verberk IMW, Boonkamp L et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Neuroinflammation and Glial Biology

Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human.

This study used single-cell multi-omics and in vivo functional experiments to define transcriptional regulators of brain perivascular macrophages in both mouse and human, identifying cMAF as a key factor. Conditional deletion of cMAF disrupted the perivascular macrophage phenotype, drove reduced IGF1 expression, and altered cerebral artery transcription and vascular function. The results link a specific macrophage transcriptional program (cMAF→IGF1) to endothelial regulation, informing how perivascular macrophages may contribute to vascular disease.

Brioschi S, Belk JA, Storck SE et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in Drosophila.

This Drosophila study mapped a neural circuit controlling aggressive escalation by using neurotransmitter-specific manipulations of an octopamine-glutamate cotransmitting VPM4 neuron and its downstream GABAergic target MBON-11. The authors found that octopamine and glutamate release from VPM4 are independently regulated by presynaptic OAα2R and mGluR receptors, respectively, gating escalation through layered inhibition. The work provides a mechanistic framework for how transmitter-specific presynaptic feedback can precisely constrain complex social behaviors.

Prunier A, Sherer LM, Da Silva M et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

IL-17D reprograms CD93+ antigen-presenting cells in the glioblastoma microenvironment.

This study examined how interleukin-17D (IL-17D) affects CD93+ antigen-presenting cells in the glioblastoma (GBM) microenvironment using orthotopic GBM models. Restoring IL-17D extended survival by selectively reprogramming the myeloid compartment through IL-17D signaling via the receptor CD93. These findings suggest a CNS-intrinsic IL-17D–CD93 axis that could be therapeutically exploited to reverse GBM immune suppression.

Tang W, Zhang S, Qi Y et al. · Cellular & molecular immunology · (2026) · View on PubMed ↗

Spatially distinct macrophage subsets drive myofibroblast heterogeneity and maladaptive fibrosis in lupus nephritis.

This study investigated how spatially distinct macrophage subsets interact with fibroblast subsets to drive myofibroblast heterogeneity and maladaptive fibrosis in human lupus nephritis (LN), validated in mouse models. Using single-cell RNA sequencing of 156 LN biopsies and 30 healthy controls (AMP-SLE cohort) and spatial transcriptomics, it mapped macrophage–fibroblast interaction programs linked to fibrotic remodeling. These results support macrophage subset–targeted approaches to modulate stromal heterogeneity and slow progression of LN fibrosis.

Raparia C, Hoover P, Ai J et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗

Decoding TREM2: A microglial receptor governing the fate of myelin.

This article reviewed and mechanistically “decoded” the role of the microglial receptor TREM2 in governing myelin fate across CNS diseases, focusing on TREM2 expression in central resident microglia versus border-associated macrophages and lesion-infiltrating monocyte-derived macrophages. It reports that TREM2 signaling regulates microglial immune balance, lipid transport, lysosomal degradation, and cell polarization—processes tightly linked to myelin integrity and regeneration. Scientifically, it positions TREM2 as a key regulator of myelin maintenance and a potential therapeutic lever for demyelinating and white-matter injury conditions.

Zhang Z, Zhang W, Jin L et al. · Cellular signalling · (2026) · View on PubMed ↗

Astrocytic NFIX regulates thalamocortical circuits through GABA and purinergic signaling.

This study investigated how the astrocytic transcription factor NFIX regulates thalamocortical circuits by using TRN (thalamic reticular nucleus) astrocyte-specific perturbations in a neural circuit context. NFIX was required to maintain TRN astrocyte function, and its deletion caused aberrant thalamocortical oscillations and impaired memory formation; NFIX directly regulated MAOB and the purinergic receptor P2RX7, and disrupting Maob or P2rx7 in TRN astrocytes reduced astrocytic GABA release. The work links an NFIX→MAOB/P2RX7→GABA signaling axis to circuit oscillations and cognition, highlighting astrocyte transcriptional control as a therapeutic target for neurocognitive dysfunction.

Murali S, Silva-Pérez M, Woo J et al. · Neuron · (2026) · View on PubMed ↗

Histone H3K27M variants determine myeloid subset dependencies and immune reprogramming in diffuse midline glioma.

This study examined how histone H3K27M variants shape myeloid subset dependencies and immune reprogramming in diffuse midline glioma (DMG). Using CRISPR/Cas9-based genome editing in a mouse model deficient for CCR1/CCR2/CCR3/CCR5 (Δ1235), the authors found that in H3.1K27M DMGs, loss of monocyte recruitment reduces monocyte-derived macrophages while increasing microglia and neutrophils, indicating compensatory myeloid remodeling. The significance is that H3K27M subtype-specific biology governs immune cell recruitment and reprogramming, informing immunomodulatory strategies tailored to DMG epigenetic drivers.

Puigdelloses Vallcorba M, Rawat K, Soni N et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Insulin resistance is associated with mammary mitochondrial dysfunction at the onset of human lactation.

This study characterized mammary gland transcriptomes and insulin resistance–related hormones in 75 postpartum women (days 1–5) to determine whether insulin resistance is linked to delayed secretory activation (SA) and mammary mitochondrial dysfunction. Women in the highest insulin resistance tertile (based on plasma leptin-to-adiponectin ratio) showed later SA onset and greater neonatal weight loss, consistent with impaired mammary mitochondrial function at the onset of human lactation. Clinically, the results suggest that insulin resistance may mechanistically contribute to lactation insufficiency via mitochondrial pathways, identifying potential biomarkers and targets to improve breastfeeding outcomes.

Meng X, Elajnaf T, Rostom H et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

A Multidimensional Engineering Strategy Reprograms Microglia via Targeted and Sustained-Release Extracellular Vesicles for Spinal Cord Injury Repair.

The study developed a multidimensional engineering approach using extracellular vesicles (EVs) derived from umbilical cord mesenchymal stem cells (UCMSCs) for spinal cord injury (SCI) repair, including tetramethylpyrazine (TMP) pretreatment and targeted, sustained-release design. Engineered EVs were enriched with anti-inflammatory and pro-regenerative cargo and were delivered with improved targeting and controlled release to reprogram microglia toward a repair-supportive state. This provides a translational strategy to overcome EV limitations (bioactivity, targeting specificity, and release kinetics) for modulating neuroinflammation after SCI.

Xiong W, Liu M, Zheng M et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Neurodevelopmental Risk and Early-Life Biomarkers

This study assessed whether prenatal targeted maternal urinary metabolomic profiles across early, mid, and late pregnancy in the NYU Children’s Health and Environment Study (NYU CHES) cohort predict preschool emotional/behavioral problems and autism-related traits at a mean age of 2.3 years. The abstract indicates associations between specific maternal metabolite patterns and later child outcomes measured with the Child Behavior Checklist (CBCL), including DSM-5-oriented autism-related domains. If confirmed, metabolomic biomarkers could improve early identification of children at risk for neurodevelopmental and autism-related outcomes.

Cavalier H, Volk H, Afanasyeva Y et al. · Molecular psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

Metabolic Disease, Endocrine Risk, and Drug Adverse Effects

SGLT2 inhibition improves sarcomere contractile dysfunction in human models of dilated cardiomyopathy.

This study tested the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMP) in patient-specific human models of dilated cardiomyopathy (DCM) to determine whether SGLT2 inhibition can improve cardiomyocyte (CM) sarcomere contractile dysfunction. EMP improved sarcomere contractile function in the human DCM model, implicating a molecular mechanism for SGLT2i benefit in heart failure with reduced ejection fraction (HFrEF) beyond glycemic effects. The findings strengthen the scientific rationale for SGLT2 inhibitors as direct modulators of cardiomyocyte contractile biology in inherited DCM/HFrEF.

Plota D, Saleem HN, Lin KH et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

This study assessed whether physical activity (PA) delays ovarian aging in humans and explored mechanisms in mice, focusing on adiponectin-related signaling pathways. In UK Biobank (n=152,435) and NHANES (n=12,418), lower PA was associated with postmenopausal status compared with premenopausal status, and mouse experiments supported a causal role for PA in delaying ovarian aging via adiponectin-linked signaling. The findings suggest adiponectin-related pathways as mechanistic mediators and potential targets for interventions to preserve ovarian function.

Li B, Zheng N, Luo T et al. · Nature aging · (2026) · View on PubMed ↗

Efficacy and safety of oral treatments for allergic rhinitis in children: A network meta-analysis.

This network meta-analysis synthesized randomized controlled trials in children under 12 years with seasonal or perennial allergic rhinitis to compare oral antihistamines (OAH) and leukotriene receptor antagonists (LTRA). It evaluated efficacy outcomes such as Total Nasal Symptom Score (TNSS) and Total Ocular Symptom Score (TOSS), alongside safety endpoints across oral treatment options. The findings provide comparative evidence to guide selection of oral therapies for pediatric allergic rhinitis based on symptom control and tolerability.

Thomander T, Gil-Mata S, Riera-Serra P et al. · Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · (2026) · View on PubMed ↗

Dendritic translation and neuroproteasome-mediated degradation of endogenous tau revealed by STARFISH.

This Nature Neuroscience study developed STARFISH to visualize dendritic translation and neuroproteasome-mediated degradation of endogenous tau with single-molecule sensitivity and near-codon resolution in primary neurons and in vivo. Using STARFISH, the authors mapped where tau mRNA is translated and how tau is degraded by the neuroproteasome, revealing spatial dynamics of tau synthesis–degradation balance. These findings advance mechanistic understanding of tau aggregation risk in Alzheimer’s disease by showing how local proteostasis controls endogenous tau turnover.

Konrad-Vicario KD, Paradise V, Demir LY et al. · Nature neuroscience · (2026) · View on PubMed ↗

This retrospective multinational cohort study evaluated whether gabapentin exposure is associated with cognitive impairment after traumatic brain injury (TBI) using the TriNetX Research Network. Among 49,925 adults with a first TBI (excluding those with baseline cognitive impairment or gabapentin exposure), the analysis stratified by Glasgow Coma Scale severity (mild, moderate, severe) to estimate the risk of subsequent cognitive impairment. If an association is observed, it would have immediate implications for medication selection and cognitive risk management in TBI survivors.

Ji L, Gao L, Li B et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Gabapentin and cognitive impairment after traumatic brain injury: A multinational cohort of 49,925 patients.

This retrospective cohort study examined whether gabapentin use is associated with cognitive impairment after traumatic brain injury (TBI) in a multinational TriNetX dataset. Using 49,925 adults with a first TBI and excluding those with known cognitive impairment or gabapentin exposure, it stratified patients by Glasgow Coma Scale severity (mild, moderate, severe) to estimate cognitive impairment risk. The findings are relevant for clinical decision-making about gabapentin in TBI care and for understanding medication-related cognitive outcomes after brain injury.

Thorman IB, Sacknovitz A, Goyal A et al. · Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · (2026) · View on PubMed ↗ · Free PDF ↗

Associations of self-reported and objectively measured physical activity and amyotrophic lateral sclerosis risk.

This UK Biobank cohort study analyzed whether self-reported and device-measured physical activity is associated with incident amyotrophic lateral sclerosis (ALS) risk, including subgroup analyses for people with high genetic risk defined by C9ORF72 expansion carriage or UNC13A rs12608932 C-allele homozygosity. The key finding was the presence/shape of an association between physical activity and ALS risk, with differences evaluated across genetic-risk strata using Cox regression with cubic splines. Clinically, it informs whether lifestyle factors may modify ALS risk and whether genetic background (C9ORF72/UNC13A) alters that relationship.

Gao J, Chalitsios CV, Bennett D et al. · Journal of neurology, neurosurgery, and psychiatry · (2026) · View on PubMed ↗

Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.

This open-label, multicentre, treat-to-target randomized phase 3b trial (COMBINE 4) studied once-weekly IcoSema—combining basal insulin icodec and semaglutide—in adults with type 2 diabetes on oral glucose-lowering medications, compared with once-daily insulin glargine U100. The key finding was the relative efficacy and safety of IcoSema versus glargine U100 over 40 weeks under a treat-to-target design. Clinically, it informs whether weekly insulin/GLP-1 combination therapy can improve glycaemic control while managing hypoglycaemia and weight outcomes versus standard basal insulin.

Ji L, Benamar M, Mohan V et al. · The lancet. Diabetes & endocrinology · (2026) · 1 citations · View on PubMed ↗

Efficacy and safety of upadacitinib in adults and adolescents for treatment of non-segmental vitiligo (Viti-Up): results of two phase 3 randomised controlled studies.

This report presented results from two phase 3, global, multicentre, randomized, double-blind, placebo-controlled trials (Viti-Up) evaluating upadacitinib, a selective once-daily Janus kinase inhibitor, in adults and adolescents (≥12 years) with non-segmental vitiligo. The key finding was that upadacitinib improved clinical outcomes compared with placebo, with efficacy and safety assessed across the two studies. The significance is that systemic JAK inhibition may provide an effective treatment option for non-segmental vitiligo where no systemic therapies were previously approved.

Passeron T, Prajapati VH, Sivamani RK et al. · Lancet (London, England) · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Symptoms and treatment response to florensocatib and inhaled tobramycin in bronchiectasis: Post hoc analysis of two randomized trials.

This post hoc analysis of two randomized bronchiectasis trials (SAVE-BE, n=224; TORNASOL, n=357) tested whether baseline symptom burden measured by the QoL-Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) predicts differential response to florensocatib versus placebo and to inhaled tobramycin. It found that florensocatib reduced exacerbation rates versus placebo and that the relative risk estimates were observed in both high and low symptom-burden groups. Clinically, it suggests that baseline symptom burden may not preclude benefit from florensocatib and helps refine expectations for treatment response in bronchiectasis.

Gao YH, Li XS, Sun XL et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Unraveling the association between triclosan and breast cancer: A multidimensional research strategy integrating machine learning, mendelian randomization, and molecular dynamics simulations.

This multidimensional study integrated computational toxicology, network toxicology, machine learning, Mendelian randomization, and molecular dynamics simulations to evaluate whether triclosan is associated with breast cancer risk and to infer mechanisms. It used ProTox3 carcinogenicity prediction, intersected predicted triclosan targets with breast cancer differentially expressed genes to build a PPI network, and then performed in vitro experiments to determine directionality and core molecular mechanisms. By combining causal inference (Mendelian randomization) with mechanistic modeling and experiments, it aims to resolve conflicting evidence on triclosan’s role in breast cancer.

Wu D, Yuan J, Xu H et al. · Environment international · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of Zinc Supplementation on Glycemic Control, Insulin Resistance, Inflammation and Oxidative Stress in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis assessed randomized controlled trials of zinc supplementation in people with diabetes, gestational diabetes, or prediabetes to determine effects on glycemic control, insulin resistance, inflammation, and oxidative stress. The key finding was that across 18 RCTs (1023 participants), zinc supplementation showed clinically relevant but variable effects on metabolic and inflammatory/oxidative biomarkers depending on the outcome measured. The study’s significance lies in clarifying whether zinc can be a consistent adjunct intervention in diabetes care and identifying where heterogeneity limits firm conclusions.

Loaiza-Giraldo JP, Amigo-Fierro F, Cancino-Castro CI et al. · Endocrinology, diabetes & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

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

This review article examined sex-related differences in platelet reactivity and how these differences affect clinical outcomes and antiplatelet therapy decisions. The key finding was that platelet signaling and thrombotic/bleeding risk vary by sex and hormonal and biological context, meaning standard antiplatelet paradigms may not fully capture this heterogeneity. Clinically, it supports more personalized antiplatelet strategies for women to balance ischemic protection against bleeding risk.

Steel RWJ, Chua YC, Abdalla WAI et al. · Science (New York, N.Y.) · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Association between diabetes mellitus and the risk of temporomandibular disorder: A nationwide population-based study.

This nationwide Taiwanese cohort study investigated whether diabetes mellitus (DM) increases the risk of temporomandibular disorder (TMD) using longitudinal registry data. The key finding was that DM patients had a higher incidence of TMD than matched non-DM controls, with Cox proportional hazards modeling used to quantify risk. Clinically, it identifies DM as a potential risk factor for TMD, supporting earlier screening and risk-informed management in diabetic populations.

Chang TF, Kung LY, Chung CH et al. · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗

Gastroparesis induced by glucagon-like peptide-1 receptor agonists: A systematic review of clinical features, diagnosis, management, and outcomes.

This systematic review evaluated clinical features, diagnosis, management, and outcomes of gastroparesis associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in real-world practice. The key finding was that symptomatic gastroparesis is an under-recognized but clinically important adverse effect of GLP-1RA therapy, with the review synthesizing patterns in presentation and management across reported cases. Scientifically and clinically, it helps clinicians better identify and treat GLP-1RA–associated gastroparesis and informs risk–benefit discussions for diabetes and obesity treatment.

Olubodun T, Osundina MA, Soyoye DO et al. · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative Risk of Hyponatremia Among Patients Treated With Second-Generation Antipsychotics.

This retrospective cohort and disproportionality analysis compared the risk of hyponatremia among patients treated with individual second-generation antipsychotics using the FDA Adverse Event Reporting System (FAERS, 1997–2023), a Japanese dataset, and a Japanese claims database (Medical Data Vision, 2008–2024). The study found differential hyponatremia risk across specific second-generation antipsychotics rather than a uniform risk profile. The results have clinical significance for selecting and monitoring antipsychotics to reduce hyponatremia risk.

Hatano M, Koseki T, Saito T et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Metabolic Dysfunction After Initiation of Androgen Receptor Pathway Inhibitors in Prostate Cancer.

This retrospective cohort study characterized the occurrence and timing of metabolic syndrome (MetS) after initiation of androgen deprivation therapy combined with androgen receptor pathway inhibitors (ADT–ARPI) in men with prostate cancer, and assessed associations with age and ARPI type. Metabolic dysfunction/MetS emerged during the first year after starting ADT–ARPI, with patterns varying by age and ARPI type and with measurable changes in MetS components. These findings are clinically important for early metabolic monitoring and risk mitigation when initiating ARPI-based prostate cancer therapy.

Shaver AL, Zarrabi KK, Nikita N et al. · JAMA oncology · (2026) · View on PubMed ↗

Cardiovascular Risk Prediction and Lipid Therapies

Histological aging signatures for monitoring tissue-specific aging and disease.

This work studied whether deep-learning analysis of human whole-slide histopathology can quantify tissue-specific biological aging using 25,712 images spanning 40 tissue types from 983 individuals in the Genotype-Tissue Expression (GTEx) cohort. The authors developed “tissue clocks” that predict biological age and correlate with established aging measures including telomere attrition, subclinical pathologies, and comorbidities. These histology-based aging signatures could enable scalable monitoring of tissue aging and earlier detection of age-associated disease risk.

Abila E, Buljan I, Zheng Y et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Development and External Validation of an Echocardiography-Based AI Model for Predicting Aortic Stenosis Progression.

This retrospective study developed and externally validated an echocardiography-based AI model to predict fixed-horizon progression of aortic stenosis (AS) from mild or moderate to severe disease. Using structured echocardiographic report data from two independent tertiary centers (derivation cohort reported as 9,247 patients), the model was designed to address limitations of fixed surveillance intervals. Clinically, an accurate progression predictor could enable more personalized monitoring and earlier intervention for patients at high risk of rapid AS deterioration.

Itelman E, Faierstein K, Caller T et al. · JACC. Advances · (2026) · View on PubMed ↗ · Free PDF ↗

Immunological risk identified by single-cell multi-omics and cardiovascular outcomes.

This exploratory proof-of-concept nested case-control study within the LURIC cohort (3316 participants) used single-cell multi-omics to identify immunological signals associated with increased cardiovascular risk and related outcomes. It linked immunological risk signatures to cardiovascular outcomes beyond established inflammatory markers such as hsCRP and IL-6. The work suggests that single-cell immune profiling may improve risk stratification for atherosclerotic cardiovascular disease by capturing determinants not reflected in standard blood biomarkers.

Horstmann H, Anto Michel N, Losert C et al. · European heart journal · (2026) · View on PubMed ↗ · Free PDF ↗

Polydatin in combination with hawthorn flavonoids alleviates atherosclerosis by inhibiting mitochondrial division through the YTHDF2-DRP1 axis.

This preclinical study tested whether polydatin combined with hawthorn flavonoids (PH) reduces atherosclerosis in ApoE-/- mice on a high-fat diet and whether it protects ox-LDL–injured human umbilical vein endothelial cells (HUVECs). The key finding was that the combination alleviated atherosclerotic pathology by inhibiting mitochondrial division through the YTHDF2–DRP1 axis. This supports a targeted mechanism linking RNA-binding protein YTHDF2 to DRP1-mediated mitochondrial fission as a potential anti-atherosclerosis strategy.

Li Y, Zhang X, Yang S et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗

Real-World Experience With TRBC1 Immunohistochemistry Across Cutaneous T-Cell Lymphoma Subtypes:A Large Cohort Study.

This large real-world cohort study evaluated TRBC1 immunohistochemistry (IHC) performance for identifying clonal αβ T-cell populations across cutaneous T-cell lymphoma (CTCL) subtypes using 665 biopsies from 566 patients with paired T-cell receptor (TCR) clonality testing. It found that at the primary <15%/>85% positivity threshold, TRBC1 IHC achieved 85.8% sensitivity (with performance assessed across MF variants, MF/Sézary syndrome, and related cutaneous lymphoproliferative disorders). The clinical significance is improved diagnostic confidence and practical interpretation of TRBC1 IHC in routine CTCL pathology workflows.

Erem AS, Pepin N, Sacknovitz Y et al. · Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · (2026) · View on PubMed ↗

A cross-organ single-cell analysis of hypertension.

This study used cross-organ single-cell RNA-seq analysis to map hypertension-associated end-organ damage in angiotensin II–treated mice, Dahl salt-sensitive rats, and spontaneously hypertensive rats, and then integrated findings with human genomic data. The key finding was identification of conserved blood pressure and renal injury gene programs, including a vascular smooth muscle cell program and coordinated cross-cell-type renal tubular endothelial adaptations, with model-specific and shared cell type–trait links. Scientifically and clinically, it prioritized a noncoding variant (rs28451064) for further investigation as a potential genetic driver connecting hypertension to specific cellular injury pathways.

Qiu Q, Liu Y, Xue H et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

Novel Lipoprotein (a) Therapies: A Comprehensive Review.

This comprehensive review synthesized evidence on lipoprotein(a) [Lp(a)] biology and the development of novel Lp(a)-lowering therapies, emphasizing RNA-based approaches and their clinical trial pipeline through mid-2026. It highlights that Lp(a) is largely genetically determined and poorly controlled by standard lipid-lowering drugs, while emerging therapies can substantially lower Lp(a) and are being tested in cardiovascular outcomes trials (CVOTs). The review is significant for guiding clinicians and researchers toward the most promising mechanistic strategies and upcoming evidence for reducing atherosclerotic cardiovascular disease and calcific aortic valve stenosis risk.

Ebubechukwu U, Ugoala O, Shahid R et al. · Current atherosclerosis reports · (2026) · View on PubMed ↗ · Free PDF ↗

Therapeutic Delivery, Gene Editing, and Drug Design/Mechanisms

Comparative evaluation of precision, morphology, and structural stability in AI-based dental crown design software programs.

This study compared the precision, morphology, and structural stability of dental crowns designed using AI-based computer-aided design (CAD) software versus a conventional CAD program (3Shape Dental Designer). Using a digital cast of a maxillary first molar and designing crowns with three CAD programs (one conventional and two AI-based), it evaluated how AI-generated designs perform relative to conventional design outputs. The results are relevant for clinical adoption of AI dental design tools by establishing whether AI CAD can match or improve crown accuracy and mechanical reliability.

Sim JH, Noh MJ, Kim HR et al. · The Journal of prosthetic dentistry · (2026) · View on PubMed ↗

Comparative effectiveness of ofatumumab and ocrelizumab in relapsing multiple sclerosis: a target trial emulation using multinational registry data.

This target trial emulation used multinational registry data to compare real-world effectiveness of anti-CD20 therapies ofatumumab versus ocrelizumab in adults with relapsing-remitting multiple sclerosis (RRMS). Patients initiating either drug were propensity-score matched 1:1, and the primary outcomes were annualised relapse rate (ARR) and time to first relapse. The study provides comparative effectiveness evidence to inform treatment selection between two high-efficacy anti-CD20 agents in routine RRMS practice.

Zhu C, Vukusic S, Kalincik T et al. · Journal of neurology, neurosurgery, and psychiatry · (2026) · View on PubMed ↗

Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria-A Subgroup Analysis from the FORTRESS Study.

This real-world subgroup analysis of the prospective, multicenter, multinational FORTRESS observational study evaluated intravenous fosfomycin (FOS)-containing regimens in patients with infections due to carbapenem-resistant (CR) Gram-negative bacteria. The study assessed clinical and microbiological outcomes, treatment patterns, and safety in the interim cohort of FOS-treated patients. These findings support the clinical use and risk–benefit profile of IV fosfomycin for difficult-to-treat CR Gram-negative infections outside randomized trials.

Bodmann KF, Mularoni A, Russelli G et al. · Infectious diseases and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

EZH2 Inhibition and Myeloid Risk: A Feature of On-Target Biology.

This article discusses the hematologic risk associated with EZH2 inhibition, focusing on the withdrawn EZH2 inhibitor tazemetostat (Tazverik) after confirmatory Phase Ib/III SYMPHONY-1 results. It highlights that hematologic second primary malignancies (notably myelodysplastic syndrome and acute myeloid leukemia) occurred in 5.7% of tazemetostat-treated patients versus none in controls. The work argues that EZH2’s context-dependent biology may imply broader, on-target myeloid risk beyond a single-agent idiosyncrasy.

Alumkal JJ, Ellis L · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

KRASG12V Degraders Provide a Potential Therapeutic Opportunity in Lung Adenocarcinoma.

This Cancer Research commentary highlights preclinical work using a dTAG-KRASG12V syngeneic mouse model to study targeted degradation of the KRASG12V oncoprotein in lung adenocarcinoma. The key finding is that degrading KRASG12V leads to regression of lung adenocarcinoma tumors in vivo. The study supports targeted protein degradation (e.g., dTAG/PROTAC-like strategies) as a promising approach to overcome resistance mechanisms that limit conventional mutant KRAS inhibition.

Garcia Borrego S, Misale S · Cancer research · (2026) · View on PubMed ↗

Anti-CD20 Discontinuation Versus Continuation in People Aged Over 50 With Non-Active Multiple Sclerosis.

This observational, multicenter retrospective cohort study compared anti-CD20 discontinuation versus continuation in people aged over 50 with non-active relapsing-onset multiple sclerosis using the French MS registry. In 2283 matched patients (1:1 propensity score matching), discontinuation was assessed for time to first relapse, inflammatory MRI activity, confirmed disability accrual, and serious infection. The study addresses whether stopping anti-CD20 therapy in older, stable patients increases clinical or infectious risk compared with ongoing treatment.

Moukhine A, Rollot F, Casey R et al. · Annals of clinical and translational neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Proteome-wide identification of the druggable CRBN interactome.

This study mapped the druggable cereblon (CRBN) interactome for molecular glue degraders (MGDs) by testing latent CRBN interactors using a highly parallel protein complementation assay (GluePCA) with CRBN–pomalidomide. They identified ~210 zinc fingers that bind CRBN–pomalidomide, with top binders overlapping proteins already known to be degraded by dedicated MGDs. The results expand the CRBN–MGD substrate interaction network, supporting more rational design of next-generation molecular glue degraders.

Galli P, Xiao S, Meng Y et al. · Nature biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Genome-wide CRISPR screening identifies cellular factors controlling nonviral genome editing efficiency.

This study used a genome-wide CRISPR screening platform linking perturbation of 19,114 genes to nonviral genome editing efficiency outcomes in human cells. It identified six negative regulators of delivery whose depletion increased editing efficiency up to six-fold across diverse payloads, loci, and cell types, and validated GJB2 and BET1L in models correcting a pathogenic adenine base mutation in KCNJ13 and introducing a cytosine base mutation in the GABAA receptor gene. These findings provide actionable host targets to improve nonviral base editing performance for therapeutic genome editing.

Saxena S, Kabra M, Abdeen AA et al. · Nature communications · (2026) · View on PubMed ↗

Low-dose blinatumomab in multidrug-resistant rheumatoid arthritis-a case series.

This case series studied low-dose blinatumomab, a T-cell engager, in 15 patients with multidrug-resistant rheumatoid arthritis (MDR-RA) to assess safety and efficacy as an alternative to high-dose depletion strategies. The study monitored cytokine release syndrome (CRS), immune effector cell-related neurotoxicity syndrome (ICANS), clinical disease activity scores (including CDAI and CRP), and tissue inflammation by ultrasound. The findings could inform dosing strategies for blinatumomab in refractory autoimmune disease by balancing efficacy with reduced toxicity risk.

Bucci L, Hagen M, Böltz S et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗ · Free PDF ↗

EGFR-targeting ADCs: From oncogene addiction to antigen-guided drug delivery.

This article discusses evidence from a first-in-human phase 1 study of the EGFR-targeting antibody-drug conjugate SYS6010 in advanced solid tumors, emphasizing implications for non-small cell lung cancer. The key concept highlighted is that EGFR-directed therapy can shift from kinase inhibition to antigen-guided cytotoxic delivery, leveraging EGFR as an ADC antigen to improve targeting. Clinically, this reframes how oncogene addiction and antigen expression can be exploited for next-generation EGFR ADC development in NSCLC.

Liu L, Fei K, Wang J · Cancer cell · (2026) · View on PubMed ↗

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

In a phase 1 trial (ChiCTR2300072141), 236 patients with advanced non-small cell lung cancer received the EGFR-targeting antibody-drug conjugate SYS6010 to evaluate safety and preliminary efficacy. SYS6010 showed a dose-limiting toxicity at 6.4 mg/kg with 4.2, 4.5, and 4.8 mg/kg selected for expansion, and treatment-related adverse events occurred in 99.6% of patients (57.2% grade ≥3), with common grade ≥3 events including neutropenia, leukopenia, and thrombocytopenia; objective response rate was reported as 34.7% in EGFR-mutant NSCLC after prior EGFR TKI and platinum chemotherapy. These results support SYS6010’s clinical tolerability and antitumor activity in heavily treated EGFR-mutant NSCLC, informing dose selection and further development.

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

AAV-DJ enables efficient, function-preserving neuronal transduction for circuit interrogation in human cortical and thalamic organoids.

The study compared seven AAV capsids (AAV-2, -6, -9, -DJ, -2-retro, -PHP.eB, and -Cap-Mac) for gene delivery performance in human cortical and thalamic organoids, assessing transduction efficiency, neuronal tropism, cytotoxicity, and functional integrity. AAV-Cap-Mac achieved the highest transduction efficiency but caused cytotoxicity and reduced neuronal activity, whereas AAV-DJ provided efficient neuronal transduction with better preservation of neuronal function. This identifies AAV-DJ as a function-preserving vector for circuit interrogation in human brain organoid models.

Adachi S, Nishimura M, Yamaguchi K et al. · Cell reports methods · (2026) · View on PubMed ↗ · Free PDF ↗

A Prospective, Multi-Site Study of Performance of Cell-Free DNA Testing for Recessive Conditions in a Large, General-Risk Pregnancy Population.

This prospective multi-site study evaluated the clinical performance of cell-free DNA (cfDNA) screening as a primary test for autosomal recessive conditions in a large general-risk pregnant population undergoing carrier screening with reflex cfDNA fetal risk assessment at nine U.S. institutions. The key finding was the test’s stratification into high-risk (≥1-in-4 predicted fetal risk) versus low-risk results with performance metrics calculated against the studied recessive conditions (cystic fibrosis, spinal muscular atrophy, and alpha/beta hemoglobinopathies). Clinically, the results support evidence-based use of cfDNA as a primary screening approach for recessive disorders in routine obstetric populations.

McElwee ER, Wynn J, Rego S et al. · Obstetrics and gynecology · (2026) · View on PubMed ↗

A First-in-Human study of AHB-137, an unconjugated antisense oligonucleotide, in healthy subjects and patients with chronic hepatitis B.

This first-in-human phase 1 study investigated AHB-137, an unconjugated antisense oligonucleotide targeting a conserved region near the 3′ end of all HBV mRNA, in healthy subjects and in patients with chronic hepatitis B (CHB) who were HBeAg-negative and virally suppressed on stable nucleos(t)ide analogue therapy. The key findings reported were the safety/tolerability and pharmacokinetics of single-ascending and multiple-dose subcutaneous AHB-137 regimens, along with antiviral efficacy signals in the CHB cohort. These results are significant for advancing AHB-137 as a potential next-generation HBV mRNA-targeting therapy beyond nucleos(t)ide analogues.

Gane EJ, Hsu YC, Chen CY et al. · Hepatology (Baltimore, Md.) · (2026) · View on PubMed ↗

Codon optimization depletes stop codons in alternative reading frames of protein-coding nucleic acid therapeutics.

This study examined how codon optimization affects stop codons in alternative reading frames of protein-coding nucleic acid therapeutics using quantitative dual-fluorescence reporters across multiple organisms. The key finding was that codon optimization can deplete stop codons in alternative frames, reducing the “checkpoint” density that normally terminates out-of-frame translation and thereby increasing permissiveness for extended out-of-frame products. Scientifically, this highlights a design risk for nucleic acid therapeutics: optimizing codons for the intended frame may inadvertently increase off-target translation in alternative frames.

Liu Z, Ying Z, Shen L et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Generated automatically on August 16, 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 — August 16, 2026

PubMed Trending Research Digest — August 16, 2026

Overview

Post-viral and Long COVID Cardiovascular Sequelae

Exercise intensity modulates interorgan communication and is associated with cardiometabolic health outcomes in humans.

Ketamine assisted psychotherapy to reduce chronic neuropathic pain: A mixed-methods randomized pilot trial.

Digital Health Technology for Improving Physical Function in Adults With Chronic Heart Failure: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Exercise and Cardiovascular Risk Modulation in Post-COVID Syndrome.

Inflammation, Innate Immunity, and Inflammasome Signaling

Gut microbiota and gut-kidney axis in kidney diseases: therapeutic potential and perspectives of natural products.

Strong, sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility.

Polyamines buffer labile iron to suppress ferroptosis.

Mechanism and plasticity of primitive pyroptosis.

Autotaxin/Lysophosphatidic Acid Axis Promotes Periodontitis by Modulating Macrophage Osteoclastogenesis and Inflammation.

Methicillin-resistant Staphylococcus aureus.

TREM2 signaling in cardiovascular disease: macrophage heterogeneity, timing, and therapeutic opportunity.

Hypoxia drives ferroptosis resistance and immunosuppression in hepatocellular carcinoma by inducing UBASH3B-mediated glutamine metabolism reprogramming and CXCL8 expression.

GPR84 and Neuroinflammation: A Receptor Worth Targeting, or A Target Worth Reconsidering?

ARDS and Critical Care Pharmacotherapy

Navigating Asparaginase Treatment for Patients With Acute Lymphoblastic Leukemia: US Consensus Panel Recommendations on the Role of Multidisciplinary Care.

Neurological effects of encapsulated dexamethasone sodium phosphate in children aged 6-9 years with ataxia telangiectasia (NEAT): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

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

Clinical Trial Evidence, Heterogeneity, and Trial Design

Decades of intensive care medicine trials: what randomised evidence has changed, corrected, and still questions to resolve.

Gastrointestinal Diagnostics and IBS-D Mimics

Mistakes in the management of irritable bowel syndrome-diarrhoeal subtype and mimics: a narrative review.

Tumor Immunology and Myeloid Cell Reprogramming

CD1d remodels the tumor-infiltrating myeloid populations controlling antitumor immunity.

Cancer Genomics, Molecular Stratification, and Biomarkers

DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy.

Prognostic Significance of Spread Through Airspaces (STAS) in Stage Ia/bN0 Non-small Cell Lung Cancer - An Evaluation in the JCOG0802/WJOG4607L Clinical Trial Patients.

Identifying independent causal cell types for human diseases and risk variants.

Mosunetuzumab With Response-Adapted Polatuzumab Vedotin and Obinutuzumab in Untreated Indolent B-Cell Non-Hodgkin Lymphoma.

Efficacy of Olaparib Plus Abiraterone for Patients with Metastatic Castration-resistant Prostate Cancer and Single Homologous Recombination Repair Gene Mutations in PROpel.

Spatial proteogenomic profiling uncovers sensitization strategies for antibody-drug conjugate in HER2-positive breast cancer.

Platelet Reactivity and Sex Differences: Clinical Implications for Women.

Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial.

Tissue-Free vs Tumor-Informed ctDNA Assays for Molecular Residual Disease Detection in Early Triple Negative Breast Cancer.

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

Viral Immunology, Vaccines, and Host-Pathogen Interactions

Canonical Antibodies Adopt Distinct Binding Modes to Recognize Viral Glycan Shields.

Functional atlas of vertebrate viral RNA elements that stabilize RNA and enhance translation.

Recent advances in cryoelectron tomography and applications to parasitology.

A tonsil organoid model reveals Epstein-Barr virus-infected germinal center B cell states during primary infection.

A boost for chemical vaccination against malaria.

‘Mismatched’ Ebola vaccine may soon be rolled out widely.

Chromatin, Epigenetics, and Nuclear Architecture

The SF3b complex in cancer: structural basis, molecular mechanisms, and therapeutic opportunities.

Alternative splicing dysregulation in CAG repeat expansion diseases.

A regulatory adaptor for RAD51’s AAA+ unfoldase promotes homologous recombination-mediated DNA repair and genome stability.

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

Neurodegeneration: Tau, TDP-43, and Proteostasis

PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures.

The UNC13A cryptic exon associates with cognitive impairment in Alzheimer’s disease.

UV irradiation drives lineage-specific MITF-mediated transcription of PD-L1 to confer immune tolerance to UV-mutated melanocytes.

Tau can wreak havoc in brain cells’ energy factories.

Artificial hibernation reveals synaptic engram architecture associated with memory retention.

Dietary vitamin A restricts intestinal tuft cell differentiation.

Selective Brain-Penetrant TTBK1 Inhibitors Modulate TDP-43 Pathology and Rescue Cognitive Deficits in a Mouse Model of TDP-43 Proteinopathy.

Plasma Alzheimer Biomarkers and Diagnostic Decision-Making in Memory Clinics.

Neuroinflammation and Glial Biology

Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human.

An octopamine-glutamate cotransmitting neuron gates aggressive escalation through layered inhibition in Drosophila.

IL-17D reprograms CD93+ antigen-presenting cells in the glioblastoma microenvironment.

Spatially distinct macrophage subsets drive myofibroblast heterogeneity and maladaptive fibrosis in lupus nephritis.

Decoding TREM2: A microglial receptor governing the fate of myelin.

Astrocytic NFIX regulates thalamocortical circuits through GABA and purinergic signaling.

Histone H3K27M variants determine myeloid subset dependencies and immune reprogramming in diffuse midline glioma.

Insulin resistance is associated with mammary mitochondrial dysfunction at the onset of human lactation.

A Multidimensional Engineering Strategy Reprograms Microglia via Targeted and Sustained-Release Extracellular Vesicles for Spinal Cord Injury Repair.

Neurodevelopmental Risk and Early-Life Biomarkers

Prenatal targeted maternal pregnancy metabolomic profiles, child emotional and behavioral problems, and autism related traits in the NYU CHES cohort.

Metabolic Disease, Endocrine Risk, and Drug Adverse Effects

SGLT2 inhibition improves sarcomere contractile dysfunction in human models of dilated cardiomyopathy.

Physical activity delays ovarian aging in part through adiponectin-related signaling pathways.

Efficacy and safety of oral treatments for allergic rhinitis in children: A network meta-analysis.

Dendritic translation and neuroproteasome-mediated degradation of endogenous tau revealed by STARFISH.

Oral nonpeptide GLP-1 receptor agonist VCT220 for obesity treatment: a randomized, double-blind, phase II trial.

Gabapentin and cognitive impairment after traumatic brain injury: A multinational cohort of 49,925 patients.

Associations of self-reported and objectively measured physical activity and amyotrophic lateral sclerosis risk.