PubMed Trending Research Digest — July 12, 2026

Automated digest · 93 articles · 15 research areas · July 12, 2026

Overview

This week’s digest is dominated by precision targeting—both in therapy delivery and in biological stratification. Multiple studies advance engineered delivery platforms (e.g., transporter-targeted brain metastasis nanocarriers; lysosome self-sorting nanodegraders for extracellular protein degradation; VLP-enhanced base editing), reflecting a field-wide push to increase on-target exposure while reducing systemic side effects. In parallel, cancer research continues to move toward mechanism- and microenvironment-aware treatment: single-cell atlases and spatially informed cross-omics models are being used to map immune infiltration states, tumor evolution across metastatic sites, and biomarker relationships that can guide checkpoint selection and next-line strategies.

A second major theme is immune modulation through more specific “levers” than classic checkpoint blockade alone. Long-term and phase 1/2 studies explore checkpoint combinations (GDF-15 with PD-1; LAG-3 with PD-1) and identify humoral requirements for CTLA-4 efficacy in glioma models. Complementing this, mechanistic immunology papers highlight new suppressive axes (e.g., macrophage micropeptides encoded by lncRNA affecting cGAS–STING/type I interferon), and autoimmunity-focused work targets signaling nodes such as TYK2 phosphorylation in CNS CD4+ T cell pathology. Together, these findings suggest that future immunotherapy will increasingly be “circuit-based,” aiming at the specific pathways that sustain resistance or immune dysfunction.

Finally, several studies connect metabolism, epigenetics, and systemic physiology to disease trajectories across organs. Gut-derived metabolites and microbiome-driven epigenetic changes (e.g., PAA–histone phenylacetylation affecting aging-related erythropoiesis; gut–liver immune remodeling in MASLD→HCC; urolithin A–mitophagy pathways in HFpEF) reinforce the idea that therapeutic opportunities may lie in modulating upstream metabolic inputs. In neurodegeneration and brain health, tau-PET connectomics, choroid plexus imaging biomarkers, and glymphatic clearance reviews converge on network- and clearance-based frameworks for stratifying risk and identifying modifiable targets.

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Targeted Nanomedicine & Drug Delivery

Brain targeting and trafficking of extracellular vesicles in central nervous system diseases: a therapeutic roadmap.

This 2026 therapeutic roadmap review analyzed how extracellular vesicles (EVs) are targeted and trafficked in the central nervous system (CNS) to deliver therapeutic cargo. It concludes that effective brain delivery depends on a linked sequence—EV ligand/protein corona engagement of receptor modules, selection of endocytic routes, and determination of intracellular fate (lysosomal degradation, recycling, rare cytosolic delivery, or blood–brain barrier transport)—and that the same pathways can also spread proteopathic seeds and amplify neuroinflammation in disease. The scientific significance is that it provides a mechanistic framework to guide EV engineering for CNS therapies while accounting for disease-relevant dissemination routes.

Baker B, Emerson S, Tran T et al. · Nanomedicine (London, England) · (2026) · View on PubMed ↗

Efficient in vivo cytosine base editing using virus-like particles with uracil DNA glycosylase inhibition.

This work developed an in vivo cytosine base editing approach using virus-like particles (VLPs) that include uracil DNA glycosylase inhibition to improve editing efficiency of a transformer base editor (tBE). In mouse liver and retina, single-injection tBE-VLPs achieved robust C-to-T editing (e.g., ~46% at mPcsk9 and ~64% at mHpd in liver) by enhancing recruitment of uracil DNA glycosylase inhibitor proteins. The results advance VLP-delivered base editing as a more efficient in vivo genome editing platform for therapeutic gene correction.

Zhu J, Ding L, Liu KM et al. · Nature biotechnology · (2026) · View on PubMed ↗

Advancements in extracellular vesicle research.

This article reviews recent advances in extracellular vesicle (EV) research, focusing on EV biology across prokaryotic and eukaryotic cells and the field’s translational applications. It highlights EVs as nanoscale lipid-bound carriers of proteins, nucleic acids, and lipids that modulate immune responses, tissue regeneration, cancer progression, and metabolic regulation. The synthesis is significant for guiding future EV biomarker, mechanism, and therapeutic development efforts discussed by the AAEV community.

Li B, Kalluri VS, Weaver AM et al. · Extracellular vesicle · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Platelet-Derived Growth Factor Receptor α-Targeted Cell Membrane-Camouflaged Nanotherapy Disrupts Fibrosis-Inflammation Coupling in Intervertebral Disc Degeneration.

This study investigated an engineered platelet-derived growth factor receptor α (PDGFRα)-targeted cell membrane-camouflaged nanotherapy in models of intervertebral disc degeneration (IVDD), integrating clinical stratification, single-cell transcriptomics, and mechanical modeling. The key finding was that the nanotherapy disrupted the fibrosis–inflammation coupling that sustains the degenerative disc state by overcoming delivery barriers in the avascular, ECM-dense disc environment. The scientific significance is that it provides a targeted, mechanism-driven approach that may yield more durable anti-degenerative effects than conventional anti-inflammatory strategies.

Su M, Chen R, Chen Y et al. · ACS nano · (2026) · View on PubMed ↗

Lysosome self-sorting nanodegraders for hepatic clearance of pathogenic serum mediators.

This Nature Nanotechnology study developed stiffness-oriented lysosome self-sorting nanodegraders (SOLIDs) to degrade pathogenic immune mediators in the liver by promoting lysosomal accumulation after blood exposure. SOLIDs used a rigid semiconducting polymer core and surface bioconjugation to capture target serum immune mediators via controlled protein corona formation, resulting in predominant hepatic biodistribution and near-quantitative lysosomal degradation across diverse cell types. The approach provides a platform for extracellular targeted protein degradation of circulating mediators with potential for treating immune-driven diseases.

Wu J, Liu X, Hu Y et al. · Nature nanotechnology · (2026) · View on PubMed ↗

Engineered zwitterion-nanodelivery for precision targeting of brain metastases.

This preclinical study engineered a zwitterionic polycarboxybetaine (PCB) nanodelivery system to target brain metastases in models of CNS cancer, focusing on transporter-mediated accumulation at the blood-brain-tumor barrier (BBTB). The PCB selectively binds and targets the betaine-γ-aminobutyric acid transporter 1 (BGT1), enriching nanoparticles in tumor vasculature and enabling rapid therapeutic release without external stimulation. This transporter-specific, stimulus-independent delivery strategy could improve the precision of anti-metastatic drug delivery while minimizing systemic side effects.

Peng H, Zeng Y, Huang Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer Immunotherapy & Immune Checkpoints

Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial.

This phase 1 multicenter open-label trial evaluated the anti–LAG-3 antibody relatlimab alone or combined with the anti–PD-1 antibody nivolumab in 46 patients with recurrent glioblastoma. Relatlimab monotherapy reached a maximum tolerated dose of 800 mg and the combination reached 160 mg relatlimab/240 mg nivolumab, with the primary safety endpoint met. These results support further development of LAG-3/PD-1 checkpoint blockade for recurrent GBM and provide early dosing guidance for combination immunotherapy.

Lim M, Ye X, Piotrowski AF et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

FDA-approved fulvestrant-induced CAR phase separation enables precise control of CAR T antitumor function.

This study developed an inducible CAR phase-separation system (iPhase-CAR) that uses FDA-approved fulvestrant to control CAR clustering and tonic signaling in CAR T cells. By enabling drug-inducible phase separation, the approach aimed to calibrate CAR activity to improve antitumor function while reducing risks associated with constitutively high signaling such as cytokine storm and neuronal toxicity. The work provides a strategy for more precise, controllable CAR T signaling to mitigate relapse and toxicity driven by dysregulated CAR activation.

Huang Y, Zhang Q, Wang K et al. · Cell stem cell · (2026) · View on PubMed ↗

The efficacy of immunotherapy in glioma requires distal B cell responses in tumor-draining lymph nodes.

This study examined how distal B cell responses in tumor-draining deep cervical lymph nodes (dcLNs) affect antitumor efficacy of CTLA-4 immune checkpoint blockade in glioma-bearing mice. Anti-CTLA-4 therapy expanded T follicular helper (TFH) cells in dcLNs, driving germinal center B cell responses, IgG class switching, and generation of glioma-reactive antibodies, and B cell activation in dcLNs was required for therapeutic efficacy. The results support a humoral-immunity requirement for CTLA-4 blockade in glioma and point to lymph-node B cell pathways as potential precision immunotherapy targets.

Kim Y, Kang I, Kang BH et al. · Science immunology · (2026) · View on PubMed ↗

Real-World Use of Avelumab First-Line Maintenance for Locally Advanced or Metastatic Urothelial Carcinoma in Japan: Treatment Patterns, Effectiveness, and Safety.

This narrative review synthesized Japanese real-world evidence on first-line (1L) platinum-based chemotherapy followed by avelumab maintenance for locally advanced or metastatic urothelial carcinoma (la/mUC), drawing on post-marketing surveillance and studies including JAVEMACS. Across these real-world datasets, the review reports treatment patterns and effectiveness/safety outcomes for avelumab maintenance in contemporary practice. The findings help contextualize how avelumab maintenance performs outside clinical trials and support shared decision-making for la/mUC patients in Japan.

Kikuchi E, Kobayashi T, Shono M et al. · International journal of urology : official journal of the Japanese Urological Association · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative efficacy and toxicity of Axicabtagene Ciloleucel versus Tisagenlecleucel in European patients with large B-cell lymphoma: a systematic review and meta-analysis.

This systematic review and meta-analysis compared efficacy and toxicity of axicabtagene ciloleucel (Axi-cel) versus tisagenlecleucel (Tisa-cel) in European patients with large B-cell lymphoma (LBCL). The analysis pooled available evidence to estimate relative differences in treatment outcomes and adverse-event profiles between the two CAR-T products. The findings support evidence-based selection and risk counseling for CAR-T therapy choices in European clinical practice.

Li H, Liu Y, Wang T et al. · PeerJ · (2026) · View on PubMed ↗ · Free PDF ↗

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

This long-term follow-up analysis studied visugromab (neutralizing anti-GDF-15 antibody) combined with nivolumab (anti-PD-1) in heavily pretreated patients with anti–PD-1/PD-L1 relapsed/refractory locally advanced or metastatic non-squamous non-small-cell lung cancer, urothelial carcinoma, or hepatocellular carcinoma from the GDFATHER-01 phase 1/2a trial. The key finding was that the combination produced encouraging objective responses with durability assessed over extended follow-up. Clinically, these results are important because targeting the GDF-15 resistance pathway alongside PD-1 blockade may improve outcomes in tumors that have progressed on anti–PD-1/PD-L1 therapy.

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

Neoadjuvant intraprostatic immunotherapy for high-risk localized prostate cancer.

The review evaluated the emerging strategy of neoadjuvant intraprostatic immunotherapy for high-risk localized prostate cancer, contrasting it with systemic neoadjuvant androgen deprivation therapy. It reports that intraprostatic, viral-vector-based gene therapies can be safe and technically feasible while inducing antitumor immune responses by directly modulating the tumor microenvironment and overcoming local immune suppression. Clinically, this supports intraprostatic immunotherapy as a promising neoadjuvant approach to reduce recurrence risk without the long-term morbidity of systemic androgen deprivation.

Fletcher SA, Pickersgill NA, Osorio JC et al. · Nature reviews. Urology · (2026) · View on PubMed ↗

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

The study identified a tumor-associated macrophage micropeptide encoded by the lncRNA USP30-AS1 (UEIS) and tested its role in regulating cGAS–STING–type I interferon signaling. UEIS promoted tumor growth by attenuating type I IFN signaling in macrophages, driving a protumorigenic phenotype and suppressing antitumor T cell immunity, with UEIS induction occurring after tumoral DNA stimulation via cGAS–STING signaling. These results suggest USP30-AS1/UEIS as a mechanistic immune-suppression axis and a potential target to enhance immunotherapy efficacy.

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

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Cancer Genomics, Multi-omics & AI for Oncology

Optimal treatment strategies for unresectable stage III EGFR-mutated non-small cell lung cancer: a systematic review and Bayesian network meta-analysis.

This 2026 systematic review and Bayesian network meta-analysis evaluated optimal treatment strategies for unresectable stage III EGFR-mutated non-small cell lung cancer (NSCLC), focusing on regimens around consolidation durvalumab after chemoradiotherapy (PACIFIC) versus sequential targeted therapy with EGFR tyrosine kinase inhibitors (TKIs) after chemoradiotherapy, including evidence from the phase III LAURA trial and real-world data. The key finding is that the optimal combination regimen remains uncertain and requires comparative synthesis of randomized controlled trials and high-quality evidence to determine the best sequencing and regimen choice for EGFR-mutated patients. Clinically, the work aims to inform regimen selection for unresectable stage III EGFR-mutated NSCLC where toxicity and sequencing effects are increasingly recognized.

Yang Y, Sun J, Luo T et al. · Frontiers in oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Large-scale Genomic Landscape and Clinical Outcomes of De Novo and Treatment-emergent Neuroendocrine Prostate Cancer.

This 2026 retrospective nationwide genomic profiling study compared de novo neuroendocrine prostate cancer (NEPC) with treatment-emergent NEPC (t-NEPC) and assessed overall survival (OS) after initiation of NEPC treatment using large-scale comprehensive genomic data. The key finding (as framed by the study design) is that genomic landscape differences and survival outcomes can be contrasted between de novo and t-NEPC despite NEPC rarity, enabling exploratory outcome comparisons. The clinical significance is improved understanding of NEPC biology and prognosis, which can support risk stratification and therapeutic decision-making in patients developing NEPC during or after androgen-deprivation therapy.

Iida K, Tashiro K, Urabe F et al. · European urology open science · (2026) · View on PubMed ↗ · Free PDF ↗

A scalable deep-learning framework for cancer detection using cell-free DNA shallow whole-genome sequencing.

This study developed UNITE, a universal cfDNA feature ensemble framework for cancer detection using genomic bin–fragment length matrices derived from shallow whole-genome sequencing (sWGS) at 0.1× depth. Using sWGS-based fragmentomic features in a large dataset (reported as 2063 participants), it showed that tumor-naive, scalable fragmentomic modeling can improve cancer detection sensitivity compared with mutation-only tumor-informed approaches. Scientifically and clinically, it supports earlier, noninvasive cancer screening strategies that do not require known tumor mutations.

Wang H, Mennea PD, McAndrew G et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Single-cell sequencing profiling of intratumoral heterogeneity and immunosuppressive microenvironment in primary thyroid cancer and lymph node metastases.

This study profiled intratumoral heterogeneity and immunosuppressive microenvironments in paired primary thyroid cancers and lymph node metastases using single-cell RNA sequencing (55,005 cells) with CNV inference and consensus nonnegative matrix factorization (cNMF). It delineated malignant evolutionary heterogeneity across sites and characterized checkpoint-regulated immune infiltration patterns associated with metastasis. The resulting single-cell atlas provides a high-resolution map of tumor–immune interactions that could guide checkpoint-based stratification and targeted immunotherapy in thyroid cancer.

Xu S, Su Y, Zhang S et al. · Oncoimmunology · (2026) · View on PubMed ↗ · Free PDF ↗

Glycolysis‑driven immunosuppression in gastric cancer: Metabolic crosstalk between tumor cells and the immune microenvironment (Review).

This review examined how glycolysis-driven metabolic reprogramming in gastric cancer creates immunosuppression through metabolic crosstalk between tumor cells and the immune microenvironment. It highlights mechanisms involving lactate accumulation and signaling pathways such as HIF-1α and PI3K/AKT/mTOR that promote glycolytic enzymes and lactate transporters, contributing to resistance to immune checkpoint blockade (ICB). Scientifically, the synthesis supports targeting tumor metabolism (e.g., glycolysis/lactate pathways) as a strategy to improve antitumor immunity and ICB responsiveness in gastric cancer.

Zhang B, Shang L, Kuang Z et al. · International journal of oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Bioinformatics and multi-omics approaches in male infertility: implications for diagnosis and assisted reproduction.

This review summarized how bioinformatics and multi-omics approaches (genetic, epigenetic, transcriptomic, proteomic, and metabolic data) are being used to understand male infertility and address limitations of conventional diagnostics such as semen analysis and hormonal profiling. The key finding was that integrating high-throughput sequencing and multi-omics via computational methods can help classify previously idiopathic cases and improve diagnostic and assisted reproduction decision-making. The scientific significance is that it provides a roadmap for translating complex molecular signatures into more precise evaluation and treatment of male infertility.

Onemli D, Sati L · Journal of assisted reproduction and genetics · (2026) · View on PubMed ↗

NicheTrans: spatial-aware cross-omics translation.

This Nature Methods study introduced NicheTrans, a spatially aware cross-omics translation framework using a Transformer-based multimodal model that incorporates cellular microenvironment information. The key finding was that NicheTrans outperformed single-omics translation approaches and revealed spatial multi-omics domains not detectable when analyzing single-omics data alone, with interpretability highlighting key molecular relationships. This is significant because it expands the practical utility of spatial multi-omics by enabling cross-omics inference that can uncover microenvironment-driven biology.

Wang Z, Zou Q, Lin S et al. · Nature methods · (2026) · 6 citations · View on PubMed ↗ · Free PDF ↗

Paediatric therapeutic development workshop on medulloblastoma.

This article summarizes a pediatric medulloblastoma therapeutic development workshop focused on high-risk molecular subgroups (SHH-medulloblastoma, MYCN-amplified, TP53-mutated; Group 3 with c-MYC amplification) and lower-risk WNT-medulloblastoma. The workshop prioritized developing less-toxic strategies and highlighted targeting SRC using a degrader, alongside inhibition strategies for c-MYC/MYC. The synthesis is intended to guide future clinical and translational research toward vulnerability-driven, subtype-specific therapies for children with medulloblastoma.

Montiel Equihua C, Baxter JS, Molenaar JJ et al. · British journal of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

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

In a phase 1b/2 clinical trial, the study evaluated the KRAS-G12D inhibitor HRS-4642 (a high-affinity noncovalent inhibitor delivered as a liposomal nanoparticle for IV dosing) combined with chemotherapy (nab-paclitaxel and gemcitabine) in patients with advanced KRASG12D-mutant pancreatic ductal adenocarcinoma (PDAC). The trial assessed safety and preliminary efficacy of HRS-4642 plus AG, enrolling 31 patients as of 5 December 2025. This is significant because it tests a next-generation KRAS-G12D targeted therapy designed to improve tumor exposure while addressing limitations of earlier oral KRAS inhibitors.

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

A unified vision-language model for precision oncology and biomarker prediction in neuroblastoma.

This Nature Communications study developed NEVA (NEuroblastoma Vision-language AI), a multimodal foundation model for precision oncology and biomarker prediction in neuroblastoma, and evaluated it in a multi-institutional cohort of 1,238 patients. NEVA used an end-to-end, pathologist-inspired hierarchical workflow (rather than frozen encoders and multiple instance learning) and outperformed multiple foundation models for biomarker prediction tasks. The work suggests that vision-language AI can improve access to molecularly informed risk stratification in neuroblastoma where routine profiling is limited.

Zhu J, Hu R, Yang S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular Disease Prevention & Therapeutics

Trajectory of liver-related events following incident cardiovascular disease in MASLD: A 15-year population-based cohort study.

This 15-year population-based cohort study used UK Biobank data to evaluate whether incident cardiovascular disease (CHD, MI, HF, or AF) predicts subsequent liver-related events in individuals with metabolic dysfunction–associated steatotic liver disease (MASLD). Using semi-Markov multi-state models and time-dependent Cox regression, it assessed risks of cirrhosis, decompensation, hepatocellular carcinoma, and liver-related death following CVD onset. The findings aim to clarify long-term liver risk trajectories after cardiovascular events in MASLD, supporting improved surveillance and risk stratification.

Lian LY, Chen QF, Xia T et al. · Metabolism: clinical and experimental · (2026) · View on PubMed ↗

The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.

This preclinical study investigated cardiotoxicity mechanisms of the MEK inhibitor trametinib (Tram) in mouse heart using complementary in vitro and in vivo approaches. It found that trametinib induces mitochondrial dysfunction in cardiomyocytes, leading to rapid contractile dysfunction in vivo and triggering innate immune responses. This is clinically important because it clarifies a mechanistic basis for trametinib-associated cardiomyopathy/heart failure and may inform monitoring and mitigation strategies during therapy.

Fisher-Wellman KH, Lutze RD, Kirkland LG et al. · Science advances · (2026) · View on PubMed ↗

Gut Microbiota, Immunity, and Metabolism in the Progression From Chronic Liver Disease to Hepatocellular Carcinoma.

This study used UK Biobank data with sex-stratified survival analyses and multi-omics approaches, including sex-specific two-sample and one-sample Mendelian randomization (MR), to test whether depression affects coronary heart disease (CHD) risk differently by sex. Depression was associated with higher CHD risk in females (adjusted hazard ratio 1.30, 95% CI 1.24–1.37) compared with males, and the analysis integrated reproductive factors, Life’s Essential 8, and plasma proteomics to explore mechanisms. These findings highlight sex-specific pathways linking depression to CHD and support more tailored cardiovascular risk prevention strategies.

Hu Y, Lin C, Zhang L et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Diabetes Mellitus Type 2 and Coronary Artery Bypass Grafting: Elevated Risks of Mortality and Postoperative Complications.

This retrospective study compared perioperative characteristics, postoperative outcomes, and mortality between patients with type 2 diabetes mellitus (T2DM) and without diabetes undergoing coronary artery bypass grafting (CABG) in a sample of 425 patients. Diabetic patients had worse baseline metabolic status (e.g., higher BMI and poorer glycemic control such as elevated HbA1c) and experienced higher perioperative risk, including increased postoperative complications and mortality. Clinically, the results support tighter preoperative glycemic and metabolic optimization to reduce CABG complications in T2DM patients.

Al-Lahham S, Hawash AA, Taha B et al. · BioMed research international · (2026) · View on PubMed ↗ · Free PDF ↗

Piezo1 Impairs Endothelial Barrier and Drives Aortic Aneurysm and Dissection via STAT3-Dependent Activation of the CCL2-CCR2 Axis.

The study examined whether the mechanosensor Piezo1 in endothelial cells contributes to aortic aneurysm and dissection (AAD) using single-cell mRNA sequencing in AAD model mice, validation in human and mouse AAD tissues, and disturbed-flow models combining abdominal aortic constriction with angiotensin II. Piezo1 was upregulated in endothelial cells, and Piezo1 inhibition or endothelial-specific Piezo1 deficiency reduced AAD incidence via a STAT3-dependent activation of the CCL2–CCR2 inflammatory axis. This is clinically significant because it identifies Piezo1–STAT3–CCL2/CCR2 signaling as a potential therapeutic target to prevent AAD progression.

Yang K, Liu Y, Huang X et al. · Research (Washington, D.C.) · (2026) · View on PubMed ↗ · Free PDF ↗

Triple Antithrombotic Therapy vs Dual Antiplatelet for Prevention of Left Ventricular Thrombus After Anterior Myocardial Infarction: An Updated Meta-Analysis.

This updated meta-analysis compared triple antithrombotic therapy (DAPT plus anticoagulation) versus dual antiplatelet therapy (DAPT) for preventing left ventricular thrombus (LVT) after anterior myocardial infarction using pooled randomized and observational evidence. Triple therapy showed effects on LVT formation and evaluated safety endpoints including bleeding, stroke, systemic embolism, and net adverse clinical events (NACE). The clinical significance is that it informs post–anterior MI antithrombotic strategy by balancing thrombus prevention against hemorrhagic risk.

Abomohsen M, Elkhayat I, Mohamed AE et al. · Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · (2026) · View on PubMed ↗ · Free PDF ↗

Tirzepatide and risk of newly diagnosed aortic stenosis in patients with obesity: a multi-institutional real-world cohort study.

This multi-institutional real-world retrospective cohort study used the TriNetX federated database to evaluate adults with obesity and compared tirzepatide (dual GIP/GLP-1 receptor agonist) versus GLP-1 receptor agonists for risk of newly diagnosed aortic stenosis (AS) or aortic valve replacement (AVR). The key finding was the association between tirzepatide exposure and incident AS/AVR risk relative to GLP-1 receptor agonists. This is significant because it tests whether a specific incretin-based therapy can prevent degenerative AS onset, an unmet need in cardiovascular prevention.

Wu JY, Lee KW, Huang SC et al. · BMC cardiovascular disorders · (2026) · View on PubMed ↗ · Free PDF ↗

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

This disease-stratified network meta-analysis synthesized randomized controlled trials to compare SGLT2 inhibitors and GLP-1 receptor agonists for ventricular arrhythmias and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and/or heart failure (HF). The key finding was a comparative ranking/estimate of effects on ventricular arrhythmias and major cardiovascular endpoints across these drug classes and disease strata. This matters clinically because it helps clinicians choose glucose-lowering therapies with potentially different cardiovascular and arrhythmia risk profiles.

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

Cardiomyocyte-specific depletion of integrin α3 preserves cardiac function after myocardial infarction.

This study investigated the role of integrin alpha-3 (ITGA3) in vivo by generating mice with cardiomyocyte-specific ITGA3 depletion (ITGA3 KO) and assessing cardiac function at baseline and after myocardial infarction (MI). Cardiomyocyte ITGA3 loss preserved cardiac function following MI compared with controls. The findings suggest ITGA3 is a therapeutically relevant target for limiting post-MI cardiac dysfunction by modulating cardiomyocyte–extracellular matrix signaling.

Bogert NV, Kuhnle AA, Din S et al. · Basic research in cardiology · (2026) · View on PubMed ↗

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Neurodegeneration, Brain Biomarkers & Brain Networks

Glymphatic dysfunction in neurodegeneration: From impaired clearance to mechanism-driven therapeutic innovation.

This review examined how glymphatic system dysfunction—impaired cerebrospinal fluid–interstitial fluid (CSF-ISF) clearance—contributes to neurodegenerative diseases including Alzheimer’s disease (amyloid-β and tau), Parkinson’s disease (α-synuclein), and Huntington’s disease (mutant huntingtin). It highlights mechanistic drivers such as aging-related changes, astroglial aquaporin-4 (AQP4) depolarization, vascular impairment, and sleep abnormalities, and frames these as targets for mechanism-driven therapies. The synthesis is clinically significant because it links a modifiable clearance pathway to disease pathogenesis and therapeutic innovation across major neurodegenerative disorders.

Kalra P, Grewal AK · Current opinion in pharmacology · (2026) · View on PubMed ↗

Modeling Parkinson’s pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity.

This work created an isogenic human iPSC-derived dopaminergic neuron (iDA) model to study Parkinson’s disease (PD) Lewy body (LB) formation and heterogeneity driven by α-synuclein (aSyn) aggregation. The key finding was that the iDA model recapitulated diverse biochemical, morphological, and ultrastructural LB features and reproduced temporal relationships between neuritic and cell-body aSyn pathology, along with corresponding proteomic and posttranslational modification patterns. This is significant because it provides a human cellular platform to dissect mechanisms of LB heterogeneity and to test targeted interventions for PD.

Mahul-Mellier AL, van den Heuvel L, Teixeira M et al. · Science advances · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Remote network for cognitive symptoms derived from tau accumulation in progressive supranuclear palsy.

This study used tau-PET with a high-contrast probe and a normative connectome to map tau-derived functional networks in 37 patients with progressive supranuclear palsy (PSP) and 48 healthy controls. Tau deposition sites converged on a common cortical action-mode network that was not explained by atrophy. These findings suggest a connectome-based, tau-driven biomarker framework for PSP cognitive symptoms that could improve mechanistic stratification and targeting in clinical trials.

Hori Y, Endo H, Tagai K et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Genetically linked brain imaging markers of memory decline in aging and Alzheimer’s disease.

This genetic imaging study used GNOVA (GeNetic cOVariance Analyzer) to estimate genetic covariance between GWASs of memory performance and memory decline and 3,935 UK Biobank imaging-derived phenotypes, stratifying by cognitive status and APOE inclusion. It identified genetically linked brain imaging markers associated with memory decline in aging and Alzheimer’s disease contexts. The scientific significance is that it provides candidate early neuroimaging biomarkers for AD-related cognitive deterioration using genetically informed discovery.

Yang Y, Lorenz A, Sathe A et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

C9orf72-associated poly-GR in skeletal muscle leads to neuromuscular junction deficits and muscle atrophy.

This mouse gene-therapy/pathogenesis study examined whether C9orf72-associated poly-GR expressed in skeletal muscle causes neuromuscular junction (NMJ) deficits and muscle atrophy. Muscle-restricted poly-GR expression produced motor deficits, muscle atrophy, and NMJ structural and functional impairment by interacting with MuSK and promoting MuSK degradation. The significance is that it implicates poly-GR in skeletal muscle as a contributor to ALS-like pathology and supports MuSK-targeted strategies as potential therapeutic approaches.

Tan X, Sun S, Yan Y et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗

The choroid plexus, cognitive decline, and incident dementia: insights from the UK Biobank.

This prospective UK Biobank cohort study examined whether choroid plexus (CP) volume and signal intensity measured on 3.0T multiparametric MRI (quantified with FreeSurfer) predict cognitive decline and incident dementia, and whether CP relates to structural brain MRI biomarkers. Using 45,306 participants (mean age 64, 47.2% men), the study found longitudinal associations between CP measures and subsequent dementia risk alongside links to brain structural biomarkers. These findings suggest CP imaging biomarkers may help stratify dementia risk and illuminate mechanisms connecting brain homeostasis to neurodegeneration.

Yu T, Han X, Huang X et al. · Molecular psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

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Neuroimmunology & CNS Inflammation

Phosphorylated TYK2 orchestrates the pathogenic program of CD4 + T cells in the development of CNS autoimmunity.

This 2026 study investigated how phosphorylated TYK2 regulates the pathogenic program of CD4+ T cells during CNS autoimmunity and assessed the therapeutic potential of selective TYK2 inhibition. It examined TYK2 phosphorylation in CD4+ T cell subsets from autoimmune uveitis (AU) patients and from experimental models, linking subset-specific TYK2 activation to Th1/Th17 pathogenic differentiation versus regulatory T cell balance. The significance is that it identifies a mechanistic TYK2 phosphorylation axis in CD4+ T cell pathology and supports targeted TYK2 inhibition as a potential therapy for CNS autoimmune diseases.

Wu H, Xiao Z, Mai Z et al. · Journal of neuroinflammation · (2026) · View on PubMed ↗ · Free PDF ↗

G protein selectivity in group I metabotropic glutamate receptors.

This structural biology study used cryo-electron microscopy to determine how group I metabotropic glutamate receptors (mGlu1 and mGlu5) achieve preferential coupling to Gq/11 versus Gi/o. It reported active-state structures of mGlu1-Gq, mGlu1-Gi, mGlu5-Gq, and mGlu5-Gi complexes bound to l-glutamate and positive allosteric modulators (PAMs), plus additional activated-state structures of mGlu1. The mechanistic insight is significant for understanding synaptic signaling specificity and for guiding development of receptor modulators that bias G-protein coupling.

Lu Y, Wen T, Lu X et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting IL-33 in Precision Neuroimmunology: Cellular Mechanisms and Therapeutic Strategies for CNS Disorders.

This review synthesized evidence on IL-33 biology in neuroimmunology, focusing on IL-33/ST2 signaling effects on microglia, T cell differentiation, type 2 innate lymphoid cells (ILC2s), and mast cell–macrophage circuits across CNS disorders. It highlights that IL-33 can be protective or pathogenic depending on disease context and immune-cell state. The work frames IL-33 as a precision immunology target and outlines therapeutic strategies for epilepsy, stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, cerebral malaria, and glioma.

Li L, Wang S, Duan L et al. · Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · (2026) · View on PubMed ↗

Epicardial Fat Drives Macrophage Response in Atrial Cardiomyopathy.

The study investigated how epicardial fat shapes macrophage responses in atrial cardiomyopathy using spatial gene expression analysis in human atria and obesity/atrial cardiomyopathy mouse models with single-cell RNA sequencing. It found macrophage subpopulations concentrated in epicardial fat, including Lyve1+ resident macrophages and CCR2+ monocyte-derived macrophages, and showed that depleting Lyve1+ macrophages prevented early fat expansion and altered disease progression. This is significant because it links adipose–immune crosstalk to atrial fibrillation substrate development and identifies macrophage subsets as potential intervention points.

Crepin L, Dasari A, Mougenot N et al. · Circulation research · (2026) · View on PubMed ↗

Proliferative Effects of the Psychedelic N,N-Dimethyltryptamine (DMT) in Human Neural Stem Cells.

This in vitro study tested whether brief exposure to the psychedelic N,N-dimethyltryptamine (DMT) drives proliferative signaling in human neural stem cells (iPSC-derived NSCs). A 24-hour DMT treatment increased proliferation in a concentration-dependent manner (EC50 ~59.7 nM) and upregulated G1 cell-cycle regulators while shifting trophic gene expression (decreasing neurotrophin-3 and increasing nerve growth factor and brain-derived neurotrophic factor). The significance is that it provides mechanistic human-cell evidence supporting DMT’s potential to promote neuroplasticity via cell-cycle and trophic pathway modulation.

Salerno JA, Dominguez ER, Karmirian K et al. · ACS chemical neuroscience · (2026) · View on PubMed ↗ · Free PDF ↗

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Stem Cells, Regenerative Medicine & Cell Fate

Multiscale analysis and functional validation of the cellular and genetic determinants of skeletal disease.

This study used cross-species skeletal single-cell profiling and UK Biobank–based genetic prioritization to identify cellular and genetic determinants of skeletal disease, followed by functional testing in >1,000 genetically modified mouse models. It defined an endosteal compartment as a key regulator of bone turnover and prioritized disease-relevant cell types by enrichment for rare skeletal disorder genes and bone-mineral-density–associated genes. The work links human genetic risk to specific skeletal cell populations and provides experimentally validated targets for bone-active therapies.

Chai RC, Lundberg M, Freudenthal B et al. · Nature genetics · (2026) · View on PubMed ↗

Generation of spermatogonia from human and non-human primate pluripotent stem cells.

This study generated spermatogonia from human and non-human primate pluripotent stem cells by differentiating human iPSCs into primordial germ cell-like cells that self-organize with mouse fetal testicular cells in a xenogeneic reconstituted testis (xrTestis). After transplantation of xrTestes into immunodeficient mice, it produced male germ cells up to meiotic onset, including spermatogonia with evidence of prepachytene piRNA biogenesis. The platform provides a human-relevant model of spermatogenesis that could accelerate male infertility research and therapeutic development.

Whelan EC, Guo M, Yokomizo R et al. · Cell stem cell · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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

This phase 1/2 open-label multicenter trial studied STEM-PD, a cryopreserved off-the-shelf human pluripotent stem cell-derived dopaminergic progenitor product, in eight individuals with moderate Parkinson’s disease receiving bilateral intraputaminal transplants at two escalating doses. At 12 months, the study reported primary safety outcomes and interim efficacy signals consistent with tolerability of the intracerebral grafts. These results support the feasibility of standardized stem-cell dopaminergic progenitor transplantation as a potential disease-modifying strategy for PD and justify larger controlled trials.

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

Single-cell analysis reveals impaired Müller glia-mediated intercellular communication and photoreceptor pathology in USH1C retinal organoids.

This study used single-cell RNA sequencing to compare healthy versus USH1C patient-derived retinal organoids, generated from induced pluripotent stem cells, to define cellular communication defects and photoreceptor pathology in Usher syndrome type 1. In USH1C organoids, Müller glia-mediated intercellular communication was impaired and photoreceptor-related transcriptional programs showed pathology, alongside altered cell adhesion and canonical Wnt signaling. These findings identify candidate molecular pathways (including Wnt/adhesion changes) that may be targeted to prevent or slow retinal degeneration in USH1C-associated disease.

Wenck N, Zorin M, Wang Q et al. · Cellular and molecular life sciences : CMLS · (2026) · View on PubMed ↗ · Free PDF ↗

Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets.

This Nature Communications study investigated how human stem cell-derived endocrine progenitors allocate α versus β cell fate by testing the proposed cross-inhibition model involving ARX and PAX4. Using a newly generated ARXCFP/CFP; PAX4mCherry/mCherry knock-in induced pluripotent stem cell reporter line, the authors combined lineage labeling with single-cell multiomic analysis to resolve human α versus β specification dynamics. The results clarify transcriptional control of islet cell fate in humans, informing more reliable generation of stem cell-derived α and β cells for diabetes-relevant cell therapies.

Akgün Canan M, Cozzitorto C, Sterr M et al. · Nature communications · (2026) · 2 citations · View on PubMed ↗ · Free PDF ↗

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Epigenetics, Mitochondria & Metabolic Reprogramming

LSD1-based dual-target inhibitors as emerging anticancer agents: pharmacological perspectives and SAR exploration.

This 2026 review examined LSD1 (lysine-specific demethylase 1) as an epigenetic target and surveyed structure–activity relationship (SAR) and pharmacological strategies for LSD1-based dual-target anticancer inhibitors across multiple cancer types. It reports that dual inhibitors designed to co-target LSD1 with partners such as HDAC, EGFR, EZH2, tubulin, ERα, G9a, JmjC, DCN1, or SMOX are being pursued to address limitations of LSD1 monotherapy including low selectivity, high toxicity, and drug resistance. The significance is that it consolidates emerging dual-inhibition design rationales that may improve therapeutic efficacy and safety for cancers driven by aberrant LSD1 activity.

Ghosh P, Dhir R, Sharma D et al. · Future medicinal chemistry · (2026) · View on PubMed ↗

Immune regulation in mitochondrial transfer: knowledge structure and emerging trends from a bibliometric perspective.

This 2026 bibliometric study mapped the knowledge structure and emerging trends of mitochondrial transfer in immune regulation by analyzing publications from 2016–2025. Using PubMed, Embase, Cochrane Library, Scopus, and Web of Science and tools including bibliometrix (R) and CiteSpace, it identified publication trajectories and research hotspots in the intersection of mitochondrial transfer and immune/inflammatory processes relevant to tumor immunity and tissue repair. The scientific significance is that it characterizes where the field is growing and what themes are emerging, helping researchers target future mechanistic and translational work.

He Q, Tan Z, Xu J et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF.

This study tested whether urolithin A, a gut microbiome–derived mitophagy-activating compound, ameliorates cardiac remodeling in a mouse model of HFpEF and investigated mechanisms via the AMPK–mTOR axis and gut-ceramide signaling. In a two-hit HFpEF model (high-fat diet plus Nω-nitro-L-arginine methyl ester), multi-omics and in vitro/in vivo experiments showed UA activated mitophagy through AMPK–mTOR and modulated the gut-ceramide axis to improve cardiac remodeling. These findings suggest UA as a potential therapeutic strategy targeting mitochondrial quality control and gut-lipid signaling in HFpEF.

Song H, Yun C, Choi Y et al. · Experimental & molecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Gut Microbiota Drives Aging-related Erythropoiesis Impairment via Phenylacetic Acid-induced Histone Phenylacetylation.

This study investigated aging-related erythropoiesis impairment in humans and mice and tested a mechanism linking gut microbiota to epigenetic dysregulation via phenylacetic acid (PAA)-induced histone phenylacetylation. Aging increased phenylalanine metabolism and plasma PAA, and the gut symbiont Odoribacter splanchnicus was identified as a key driver of PAA-mediated histone phenylacetylation that impaired erythropoiesis. These findings connect microbiome metabolism to hematopoietic stem/progenitor epigenetic control and suggest microbiota/PAA–histone acetylation as a therapeutic avenue for anemia of aging.

Xie Y, Qiao X, Wu H et al. · Blood · (2026) · View on PubMed ↗

Sex-specific effects of depression on the incidence and risk factors for coronary heart disease: insights from multi-omics approaches.

This multi-omics review synthesized how gut microbiota, immune remodeling, and metabolic changes interact during progression from chronic liver disease to hepatocellular carcinoma (HCC), using the MASLD–MASH–fibrosis/cirrhosis–HCC sequence as a mechanistic scaffold. It emphasizes that progression is a heterogeneous continuum involving immune, metabolic, fibrotic, and microbial remodeling rather than a single linear pathway, with etiology-specific differences across ALD, HBV, HCV, and mixed causes. The review supports a gut–liver–immune framework for understanding and potentially stratifying HCC risk and mechanisms across liver disease etiologies.

Huang H, Chen M, Lu X et al. · European journal of preventive cardiology · (2026) · View on PubMed ↗

Autophagy in the liver.

This review article summarizes how autophagy functions in the liver and how it is regulated by nutrient/energy-sensing and transcriptional pathways in hepatocytes. It emphasizes that hepatic autophagy is controlled by AMPK and mTOR signaling and coordinated by insulin/glucagon and regulators including TFEB, FOXO proteins, PPAR isoforms, FXR, and NRF2, with additional modulation by epigenomic and microRNA mechanisms. The scientific significance is that it frames autophagy as a central homeostatic process that can be leveraged to understand and potentially treat liver disease.

Burks E, Copes J, Nguyen K et al. · Autophagy reports · (2026) · View on PubMed ↗ · Free PDF ↗

Cell-Type-Specific Calibration of Mitochondrial Ubiquitination in Stem Cell Fate Decisions.

This review examined how mitochondrial ubiquitination is calibrated in a cell-type-specific manner to influence stem cell fate decisions, focusing on the ubiquitin-proteasome and selective autophagy surveillance systems at the mitochondrial outer membrane. The key finding was that the canonical PINK1–Parkin pathway and non-Parkin E3 ligases (including MARCH5 and MUL1) plus the Cullin-RING component RBX2 coordinate outer-membrane protein degradation to shape lineage-determining transcriptional programs. The significance is that it links specific mitochondrial quality-control ubiquitination circuits to stem cell self-renewal, differentiation, and senescence, informing future regenerative and anti-aging strategies.

Liu HC, Chen SY, Yu NN et al. · Stem cell reviews and reports · (2026) · View on PubMed ↗

Inhibition of lagging strand replication by G-rich telomeric DNA and the shelterin subunit POT1.

The authors reconstituted human telomere replication in vitro with purified proteins to test how G-rich telomeric DNA and the shelterin subunit POT1 affect lagging-strand synthesis. They found that G-rich telomeric DNA directly and specifically blocks lagging strand replication, an effect counteracted by the BLM helicase, and that shelterin (via POT1) also inhibits lagging-strand replication. These mechanistic insights clarify how canonical replication is altered at telomeres and identify BLM and shelterin as key modulators of telomere-associated replication stress.

Leonard-Booker C, Mazzucco G, Fisher CEL et al. · The EMBO journal · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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

The authors investigated how spaceflight microgravity causes intervertebral disc degeneration by focusing on nucleus pulposus (NP) cells and AMPK-related signaling, identifying PIEZO1 as a key mediator. They reported that space microgravity induces NP degeneration via PIEZO1 and that targeting AMPK signaling in NP cells ameliorated microgravity-induced intervertebral disc degeneration. Scientifically, this links microgravity stress to PIEZO1-driven degeneration pathways and positions AMPK modulation as a potential countermeasure for disc degeneration.

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

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

This Nature Communications study examined how intracellular iron homeostasis regulates epigenetic reprogramming in -7/del(7q) acute myeloid leukemia, focusing on the mitochondrial iron transporter ABCB8. In hematopoietic stem and progenitor cells, a differentiation CRISPR screen identified ABCB8 as essential for differentiation; ABCB8 deficiency disrupted iron homeostasis, reduced cytoplasmic iron availability, impaired iron-dependent enzymes including the histone demethylase KDM6A, and accelerated leukemogenesis in vivo. These findings link a specific 7q-associated leukemia mechanism to iron–epigenetic coupling and suggest ABCB8/iron-pathway vulnerabilities as potential therapeutic targets.

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

CHAC2-mediated glutathione metabolic reprogramming drives N1 polarization of bone marrow neutrophils and exacerbates inflammatory comorbidities.

This study examined how CHAC2-mediated glutathione (GSH) metabolic reprogramming regulates N1 polarization of bone marrow neutrophils in the context of periodontitis-associated systemic inflammation. Integrated transcriptomic and metabolomic analyses showed that periodontitis reprograms GSH metabolism in bone marrow neutrophils to drive N1 polarization, with CHAC2 as a central mediator that exacerbates inflammatory comorbidities. These findings link CHAC2–GSH metabolic control to neutrophil inflammatory fate decisions, suggesting potential metabolic targets to prevent periodontitis-driven systemic inflammatory complications.

Niu Y, Li Y, Sun S et al. · International journal of oral science · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious Disease Mechanisms & Viral Dynamics

Age and Gender-Based Clinical and Laboratory Features in Dengue Infection: A Comparative Study.

This analytical cross-sectional study compared clinical and laboratory features of dengue fever (DF) and dengue hemorrhagic fever (DHF) across age and sex in 162 pediatric and adult patients diagnosed in Surabaya hospital in 2022. It assessed hemoglobin, hematocrit, leukocyte, and platelet levels across six age groups and found age- and gender-associated differences in these laboratory/clinical patterns. These findings support more tailored interpretation of WHO-style clinical/laboratory criteria for dengue triage and management, especially as dengue increasingly affects adults.

Sulistiawati, Dewanti L, Athiyyah AF et al. · Journal of infection in developing countries · (2026) · View on PubMed ↗ · Free PDF ↗

Cell cycle checkpoint activity in the malaria parasite Plasmodium falciparum.

This study examined DNA damage–induced cell cycle checkpoint activity in the malaria parasite Plasmodium falciparum, focusing on intra-S-phase checkpoint hallmarks and a putative damage-marker histone. The authors found acute reductions in DNA replication and phosphorylation of the putative damage-marker histone upon DNA damage, consistent with an intra-S-phase checkpoint response. These findings improve mechanistic understanding of how P. falciparum regulates replication under stress and may inform strategies to counter artemisinin action and resistance.

Johnson MK, Naldoni J, Lewis WH et al. · mSphere · (2026) · View on PubMed ↗ · Free PDF ↗

Intra-host viral population dynamics during acute hepatitis E virus infection.

This study investigated intra-host viral population dynamics and mutational signatures during acute, asymptomatic hepatitis E virus (HEV-3) infection in a cohort of over 80 blood donors using highly sensitive HEV amplicon sequencing. Overall intra-host diversity was constrained, but recurrent mutational patterns suggested selective pressures shaping viral populations within hosts. Understanding these dynamics in acute infection can clarify how HEV adapts during immune changes and may help predict or prevent progression to chronicity.

Janshoff S, Plümers R, Kohl A et al. · mBio · (2026) · View on PubMed ↗ · Free PDF ↗

Evaluation of targeted Massively Parallel Sequencing methods for forensic metagenomics.

The study evaluated three targeted DNA enrichment approaches for forensic metagenomics using whole metagenome sequencing (WMS) data from 134 soil samples collected across 46 locations in Poland. Using 200 extracted DNA markers, the authors assessed how targeted massively parallel sequencing (MPS) performs for species-level microbial profiling compared with whole-metagenome approaches. This work supports more accurate, geography-linked microbial signatures for forensic investigations by improving resolution beyond standard 16S rRNA methods.

Marszałek K, Kowalski MB, Jagiełło A et al. · Applied microbiology and biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Identification of the SARS-CoV-2 genome packaging signal in the nsp12-coding region.

This study investigated where SARS-CoV-2 cis-acting genome packaging signals reside and how they are recognized by the nucleocapsid (N) protein, using CLIP-seq and virus-like particle assays. The authors identified a conserved packaging signal within the nsp12 (RNA-dependent RNA polymerase) coding region, confirmed by an orthogonal defective-interfering RNA approach, and mapped two critical N-engaging subregions (α and β). Defining the nsp12-region packaging signal and its N-binding determinants advances mechanistic understanding of selective genome packaging and may inform antiviral strategies targeting this step.

Park Y, Lim J, Cho H et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Clinical Trials & Comparative Effectiveness (Non-oncology)

Cognitive Versus Software-based Fusion Targeted Biopsy for the Diagnosis of Clinically Significant Prostate Cancer: A Multicenter, Randomized, Noninferiority Trial (IMAGINATION).

This multicenter randomized blinded noninferiority trial (IMAGINATION) compared cognitive fusion (mental registration) versus software-based fusion targeted biopsy for detecting clinically significant prostate cancer in 648 predominantly biopsy-naive men in China. Cognitive fusion was tested as noninferior to software-based fusion targeted biopsy for csPCa detection using MRI-targeted biopsy workflows. If confirmed by the full results, this could expand access to effective MRI-targeted prostate biopsy in settings lacking costly fusion software platforms.

He BM, Zhang K, Zhou Z et al. · European urology · (2026) · View on PubMed ↗ · Free PDF ↗

Magnitude and Determinants of Placebo Response in Acute Migraine Trials: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis quantified placebo response magnitude and determinants in randomized, double-blind, parallel-group phase 2/3 acute migraine treatment trials. Across included RCTs, it identified patient-level, drug-level, and study-level factors that systematically influenced placebo response. Clinically, this helps refine trial design and interpretation for acute migraine therapies by accounting for context-driven effects that can mask or mimic drug efficacy.

Makita LM, Katsuyama E, Christensen RH et al. · Neurology · (2026) · View on PubMed ↗

Comparative effects of low-level laser acupuncture and dry needling on clinical and functional outcomes in patients with chronic cervical myofascial pain syndrome: a randomized controlled trial.

This randomized controlled trial compared low-level laser acupuncture versus dry needling, both combined with routine physical therapy, in 100 patients with chronic cervical myofascial pain syndrome. The trial was assessor-blinded and randomly allocated participants to two equal groups to evaluate clinical and functional outcomes over the study period (June 2023 to November 2024). The study’s design supports evidence-based selection of nonpharmacologic interventions for cervical myofascial pain, though the provided abstract truncation limits the specific effect estimates.

Zaidi F, Ahmed U, Ahmad A et al. · Lasers in medical science · (2026) · View on PubMed ↗ · Free PDF ↗

The hypermobility crisis: A review and call to action.

This narrative review examined hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) in clinical populations and evaluated how current diagnostic criteria capture (or fail to capture) their heterogeneity. It found that existing criteria inadequately reflect multi-organ involvement, leading to diagnostic delays and fragmented care that worsen comorbid chronic pain and psychological distress. The review’s call to action is significant because improving diagnostic frameworks and access barriers could enable earlier, more integrated management for a common but underrecognized connective-tissue disorder.

Motlak M, Lee E, Guilarte G et al. · Developmental dynamics : an official publication of the American Association of Anatomists · (2026) · View on PubMed ↗

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Musculoskeletal, Rehabilitation & Tissue Repair

A circuit linking dentate gyrus and retrosplenial granular cortex regulates fracture healing in male mice.

This study mapped and functionally tested a neural circuit linking the hippocampal dentate gyrus (DG) and retrosplenial granular cortex (RSGc) in male mice after skeletal injury. It found that inhibiting excitatory neurons in DG or RSGc—or suppressing DG–RSGc pathway–associated populations—accelerated fracture healing, whereas activating these excitatory neurons delayed repair. The results identify a DG–RSGc brain-bone communication pathway that could be targeted to modulate fracture healing after traumatic brain injury.

Zhang W, Zhang W, Guo Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Low-intensity stimulation drives macrophage efferocytosis via ACSL4 lipid remodeling and CCL9-CCR1 signaling for tendon-bone healing.

This mouse study tested whether low-intensity mechanical stimulation enhances tendon-bone healing by promoting macrophage efferocytosis through ACSL4-dependent lipid remodeling and CCL9-CCR1 signaling. It found that low-intensity stimulation increased macrophage M2 polarization, phagocytosis, and efferocytosis at the tendon-bone interface, and that Acsl4 silencing reduced fatty acid oxidation and efferocytosis, impairing healing; CCL9-CCR1 then supported bone marrow stromal cell homing after efferocytosis. The findings are clinically relevant for exercise-based rehabilitation strategies by identifying ACSL4 and CCL9-CCR1 as mechanistic targets to enhance tissue repair.

Yao J, Wu Y, Wang X et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Effectiveness of Manual Therapy Versus Strength Training for Iliotibial Band Syndrome on Pain and Functional Recovery in Runners: A Pilot Study.

This pilot randomized study compared manual therapy versus strength training for iliotibial band syndrome (ITBS) in 34 runners (n=17 per group) to assess pain reduction and functional recovery. The trial found differential improvements between the two rehabilitation approaches on pain and functional outcomes over the study period. These preliminary results can guide larger, definitive trials to determine which intervention is more effective for runner ITBS rehabilitation.

Khizar HF, Siva S, Ramaswami S et al. · International journal of therapeutic massage & bodywork · (2026) · View on PubMed ↗ · Free PDF ↗

The combined effects of whey protein and collagen supplementation on bone mineral density and muscle mass in resistance-trained men: a randomized controlled trial.

This double-blind, randomized, placebo-controlled trial studied 40 resistance-trained men comparing combined whey protein plus collagen peptides (30 g/day whey + 10 g/day collagen) versus whey alone, collagen alone, or placebo. The key finding was that the combined supplementation produced greater improvements in muscle mass, bone mineral density (BMD), strength, and bone turnover markers than either supplement alone or placebo. Scientifically and clinically, this supports a complementary nutrition strategy for enhancing musculoskeletal adaptations in resistance-trained adults.

Seyhan S, Jourkesh M, Salatin A et al. · BMC sports science, medicine & rehabilitation · (2026) · View on PubMed ↗ · Free PDF ↗

Biological aging clocks in health and disease.

This Nature Medicine review assessed how biological aging clocks—quantitative biomarkers derived from multi-omic and clinical data—track aging across individuals and organs and can be used to predict disease risk and evaluate interventions. The authors conclude that biological clocks are increasingly validated but require critical appraisal regarding assay standardization, causal interpretation, and clinical translation. Scientifically, the review frames clocks as tools for prevention/early detection and for testing whether interventions truly modulate aging trajectories.

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

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Autoimmunity, Inflammation & Immunomodulation (Non-checkpoint)

Mycophenolate and Azathioprine in Fibrotic Interstitial Lung Disease.

This 2026 multicenter retrospective comparative effectiveness study evaluated whether mycophenolate or azathioprine improves three-year transplant-free survival and lung function trajectory in fibrotic interstitial lung disease (ILD) populations including non-IPF idiopathic interstitial pneumonia, fibrotic hypersensitivity pneumonitis, and connective-tissue disease–associated ILD. Using a clone-censor-weighting framework to emulate a randomized controlled trial, it tested the impact of these immunosuppressants on long-term outcomes in fibrotic ILD. The clinical significance is that it aims to provide more trial-like evidence to guide immunosuppression choices in fibrotic ILD where randomized data are limited.

Pugashetti JV, Jee AS, Yu AR et al. · American journal of respiratory and critical care medicine · (2026) · View on PubMed ↗

Cancer risk of Janus kinase inhibitors and other advanced therapies in immune-mediated inflammatory diseases: a systematic review and Bayesian network meta-analysis of RCTs.

This systematic review and Bayesian network meta-analysis of randomized controlled trials estimated cancer risk associated with Janus kinase inhibitors (JAKis) versus other advanced therapies across immune-mediated inflammatory diseases. It specifically addressed the class-wide concern raised by the Oral Rheumatoid Arthritis Trial Surveillance trial (tofacitinib vs TNF inhibitors) by comparing relative and absolute malignancy risk across multiple IMIDs and treatment comparators. The analysis informs comparative safety decision-making for JAKi use in inflammatory diseases by quantifying cancer risk relative to alternative therapies.

Gibson M, Allen V, Adas M et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗ · Free PDF ↗

Antibodies against interleukin-10 receptor reduce IL-6 and TNF-α levels and increase TGF-β levels in patients with severe fever with thrombocytopenia syndrome virus and SARS-CoV-2 infection.

This clinical study analyzed patients with severe fever with thrombocytopenia syndrome virus (SFTSV) and SARS-CoV-2 infection to test the impact of antibodies against the interleukin-10 receptor (IL-10R) on cytokine profiles and macrophage phenotypes. IL-10R blockade reduced IL-6 and TNF-α levels while increasing TGF-β, alongside shifts in macrophage populations including changes in HLA-DR+CD86+ and CD163+CD206+ subsets. The findings are significant because they suggest IL-10R-targeted immunomodulation may dampen cytokine-storm inflammation in severe viral disease.

Kang SY, Yoo JR, Bae E et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

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Imaging, Biomarkers & Risk Prediction

Implementing a Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease in a Diverse Cohort.

This prospective phase IV eMERGE Network cohort study (NCT05277116) implemented a multi-ancestry coronary heart disease polygenic risk score (PRSCHD; PGS004696) and evaluated outcomes after return of results in a diverse population. Participants with high PRSCHD (top 5th percentile) and those with familial hypercholesterolemia (FH) received results from study personnel, while those with family history of CHD (FamHxCHD) were informed by mail/email, with the PRS integrated into a Genome Informed Risk Assessment (GIRA) alongside monogenic FH risk and clinical risk factors. The study’s significance is that it tests real-world feasibility and impact of multi-ancestry PRS-based genomic risk reporting for CHD in routine clinical workflows.

Hamed M, Naderian M, Bangash H et al. · Genetics in medicine : official journal of the American College of Medical Genetics · (2026) · View on PubMed ↗

Polysomnography in otorhinolaryngology (1995-2025): Bibliometric analysis and database comparison.

This 2026 bibliometric analysis studied polysomnography (PSG) research in otorhinolaryngology over 1995–2025 and compared database coverage and citation behavior between Web of Science and PubMed. It reports trends in publication output and characterizes contributions by authors, journals, institutions, and evolving keywords, while also evaluating cross-database citation comparability. The significance is that it clarifies how PSG research is distributed and measured in different indexing systems, which affects interpretation of impact metrics in this clinical specialty.

Zengin ÖF, Salihoglu Zengin G · Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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

This prospective cohort study used UK Biobank participants with intrapancreatic fat deposition (IPFD) quantified by MRI to test whether IPFD predicts mortality, and it incorporated genetic risk profiling using GWAS and Mendelian randomization. The key finding was that higher IPFD was associated with increased mortality risk, with genetic analyses supporting a causal relationship rather than only confounding. This is significant because it positions MRI-measured pancreatic fat as a prognostic biomarker and potential causal factor in exocrine pancreatic disease risk.

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

Performance of DeepSeek-R1 and ChatGPT-5 in the Generation of North American Spine Society Clinical Guidelines for Adult Vertebral Compression Fractures: Comparative Study.

This comparative study evaluated large language models—DeepSeek-R1 and ChatGPT-5—on their ability to generate answers consistent with the 2024 North American Spine Society clinical guidelines for adult vertebral compression fractures (VCFs). Using 34 open-ended and 87 closed-ended guideline questions as the reference standard, it found differences in guideline-consistent performance between the two LLMs. The results are important for safely deploying LLMs in clinical guideline support, indicating which model performs better for VCF-related decision support tasks.

Chen R, Pan Y, Liang M et al. · Journal of medical Internet research · (2026) · View on PubMed ↗ · Free PDF ↗

From measurement to biomarker trajectories: platform-agnostic Z score analysis of serum NfL and GFAP in ocrelizumab-treated multiple sclerosis.

This pooled multicentre analysis assessed whether platform-agnostic Z score normalization of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) enables monitoring of biomarker trajectories in people with multiple sclerosis (pwMS) treated with ocrelizumab for at least 12 months. Using harmonized Elecsys® and Simoa® assays via covariate-adjusted Z scores, the study evaluated 24-month biomarker trajectories and identified early timepoints that stratify subsequent trajectories. These results aim to reduce inter-assay variability and improve real-world biomarker tracking for ocrelizumab-treated MS.

Inojosa H, Masanneck L, Akgün K et al. · Journal of neurology · (2026) · View on PubMed ↗ · Free PDF ↗

The pharmacokinetics and its covariates of rituximab in different clinical populations: a systematic review and narrative synthesis.

This systematic review and narrative synthesis analyzed pharmacokinetics (PK) of rituximab across different clinical populations and identified covariates that explain PK variability. The key finding was that rituximab shows substantial PK differences between populations, implying that exposure may vary in ways that could affect response. This is significant for clinical practice because better understanding of rituximab PK covariates can support more individualized dosing and improved therapeutic consistency.

Zhenyan B, Huang L, Lu J et al. · European journal of clinical pharmacology · (2026) · View on PubMed ↗ · Free PDF ↗

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

This multicenter retrospective validation study developed automated venous thromboembolism (VTE) risk scoring using large language models (LLMs) with expert knowledge-augmented prompting, evaluated against Padua and Caprini risk scores. Across anonymized EHRs from 30 hospitals (development: 50 cases from 10 hospitals; testing: 200 cases from 20 hospitals), the approach compared expert-augmented prompts versus basic and complex prompting strategies across six open-source LLMs. The clinical significance is improved, scalable VTE risk stratification from unstructured EHR text, potentially enabling earlier prevention in hospitalized patients.

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

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Genetic Diagnostics & Rare Disease Modeling

Uncovering Phenotypic Expansion in AXIN2-Related Disorders through Precision Animal Modeling.

This study characterized AXIN2-related disorders by combining structural modeling and precision animal modeling to test the pathogenicity of specific de novo heterozygous AXIN2 variants (including p.Glu66Lys) identified in individuals with oligodontia-colorectal cancer syndrome (ODCRCS). Using a prime editing N1 screen in mouse embryos (and additional Drosophila models), the authors assessed whether the p.Glu66Lys variant recapitulates disease phenotypes. These results refine genotype–phenotype understanding for AXIN2 and strengthen causal evidence for variant-driven developmental and ectodermal manifestations.

Aceves-Ewing NM, Lanza DG, Marcogliese PC et al. · Genetics in medicine : official journal of the American College of Medical Genetics · (2026) · View on PubMed ↗

Integrative and systematic genomic approaches to improve diagnosis in rare and undiagnosed diseases: results from the RareBoost project.

The RareBoost project study evaluated an integrative stepwise genomic diagnostic pipeline in 134 patients from 120 families with rare and previously undiagnosed diseases. By combining systematic exome sequencing with genome sequencing when indicated, followed by targeted RNA-sequencing plus comprehensive phenotyping and segregation analysis, the project achieved definitive molecular diagnoses in 25.0% of families and additional diagnoses in a further 25.8% (per the reported partial abstract). Clinically, this demonstrates that layered DNA/RNA strategies can substantially increase diagnostic yield beyond conventional testing for genetically heterogeneous rare disorders.

Yigit A, Pekerbas M, Salman B et al. · European journal of human genetics : EJHG · (2026) · View on PubMed ↗

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Public Health, Lifestyle & Health Outcomes

Integrative oncology in colorectal cancer: evidence-based strategies from prevention through survivorship.

This 2026 narrative review synthesized evidence for integrative oncology in colorectal cancer (CRC) across the care continuum from prevention through survivorship. It reports that multiple lifestyle and supplement interventions—high-fiber diets, Mediterranean dietary patterns, calcium supplementation, regular physical activity, healthy weight maintenance, and berberine—show reproducible CRC risk reduction in large prospective cohorts and multicenter randomized trials, with additional trial evidence (including the CHALLENGE trial) discussed for broader care implications. The significance is that it consolidates actionable, evidence-based integrative strategies that could be incorporated into routine CRC prevention and survivorship care.

Shen C, Lou R, Bai F et al. · Frontiers in oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Concussion Clinical Subtypes and Modifiers: A Framework for Longitudinal Study of Low-Level Blast Exposure.

This paper proposed a framework for longitudinal study of concussion clinical subtypes and modifiers in relation to low-level blast overpressure (BOP) exposure in U.S. Armed Forces. It focuses on special operations forces (SOF) as a high-risk group for repeated sub-concussive BOP events while noting that conventional forces and other occupational groups may also face meaningful cumulative exposure. The framework is intended to improve blast safety oversight, surveillance, and research by enabling subtype- and modifier-aware longitudinal risk assessment.

Hoppes CW, Scherer MR, Stout KC et al. · Military medicine · (2026) · View on PubMed ↗

Endocrine‑metabolic imbalance drives osteoarthritis: From whole‑joint pathobiology to precision therapy (Review).

This review summarized evidence that endocrine–metabolic imbalance drives osteoarthritis (OA) as a whole-joint disorder, integrating findings from joint pathobiology to precision therapy concepts. It links systemic endocrine factors (e.g., sex hormones, thyroid hormone, melatonin, parathyroid hormone, vitamin D) and metabolic disturbances (e.g., obesity, insulin resistance, dysregulated glucose/lipid metabolism) to cartilage degeneration, synovial inflammation, subchondral bone remodeling, and pain. The work supports a precision-therapy framework that targets both local joint pathology and systemic metabolic/endocrine contributors to OA progression.

Yang R, Zeng H, Xiao Q et al. · International journal of molecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Sugar sweetened and artificially sweetened beverages, fruit and vegetable juices and cancer risk: a World Cancer Research Fund International Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

This World Cancer Research Fund International CUP Global systematic review and meta-analysis evaluated associations between sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and fruit/vegetable juices and cancer risk using cohort studies identified in PubMed and Embase through September 2024. The authors calculated relative risks per standardized serving/day (355 mL for SSBs/ASBs and 177 mL for juices) and graded evidence using the CUP Global Expert Panel. The results inform global cancer-prevention recommendations regarding beverage consumption patterns.

Jayedi A, Markozannes G, Kazmi SZ et al. · medRxiv : the preprint server for health sciences · (2026) · View on PubMed ↗ · Free PDF ↗

The Clinical Outcomes of Preclinical and Clinical Obesity Across Multiple Cohorts.

This cohort study assessed the clinical outcomes of “clinical obesity” defined by the Lancet Diabetes & Endocrinology Commission criteria across multiple populations including CHARLS, ELSA, and NHANES. It reported varying prevalence of clinical obesity by cohort and used Cox proportional hazards models to estimate associations with subsequent clinical outcomes. The significance is that it evaluates whether the new clinical obesity definition improves prognostic stratification across diverse aging cohorts.

Li S, Huang Q, Liu Y et al. · Obesity (Silver Spring, Md.) · (2026) · View on PubMed ↗

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

Using large-scale electronic health records from the Shanghai Hospital Link Database, the cohort study compared incident depressive and anxiety disorders during and after discontinuation of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes versus dipeptidyl peptidase-4 inhibitors (DPP4is) or sodium-glucose cotransporter-2 inhibitors (SGLT2is). The key finding was that GLP-1RA discontinuation was associated with an increased risk of psychiatric events after stopping. This has clinical significance for monitoring mental health around GLP-1RA cessation and for informing safer discontinuation practices.

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

Thalassaemia.

This Nature Reviews Disease Primers article reviewed the thalassaemia syndromes, focusing on α- and β-thalassaemia, their global epidemiology, and current management strategies. It highlights that while transfusion and iron chelation have improved survival and quality of life, major forms still cause chronic morbidity and remain a significant global health burden. The review synthesizes how prevention and evolving treatments could further reduce disease impact worldwide.

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

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Generated automatically on July 12, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.