Pregnancy-associated cardiac complications

Thordsen and Arany review changes in maternal physiology that occur during pregnancy and highlight how these changes contribute to or exacerbate various common cardiovascular pathologies. They discuss modern management of cardio-obstetric conditions and highlight the importance of multidisciplinary care for optimal outcomes.

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Mucoadhesive recombinant human catalase for dry eye disease: From protein engineering to first-in-human study

Shao et al. report a carrier-free enzyme-engineering strategy by thiolation of recombinant human catalase for treating dry eye disease. Such thiolated enzyme with sustained ocular retention shows potent efficacies in treating various preclinical dry eye disease animal models and preliminarily demonstrates safety and therapeutic performance in a first-in-human study.

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Deep learning-enabled screening of chronic kidney disease from echocardiography

Chronic kidney disease (CKD) has an underdiagnosis rate of over 60%, and high-risk populations are not routinely screened. Here, Yuan et al. develop and externally validate a deep learning model to detect CKD from echocardiography, offering a promising avenue to enable earlier screening and close diagnostic gaps.

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An adult proteomic signature associated with very low birth weight and chronic disease risk

Huang et al. identify an adult plasma proteomic signature associated with recalled very low birth weight (VLBW). The index is associated with adult disease burden and subsequent disease risk, but is not VLBW specific, supporting hypothesis-generating links between birth history, adult molecular state, and later-life disease.

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N-of-1 investigational study of a novel antisense oligonucleotide drug in CHCHD10-related ALS shows early signs of efficacy

Cousin et al. report an individualized antisense oligonucleotide for CHCHD10-related ALS. In one participant, six intrathecal doses were well tolerated, plasma neurofilament light decreased to the reference range, and functional and respiratory measures were stable or modestly improved, supporting further evaluation of CHCHD10-directed therapy.

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Prenatal exposure to the plasticizer DEHP increases the likelihood of early-life autism and ADHD symptoms through epigenetic programming

Tanner et al. show that prenatal DEHP exposure increases autism and ADHD symptoms via epigenetic programming. Using a systems-biology framework, they identified cord blood DNA methylation signatures that mediate these neurotoxic effects. These signatures involve key neurodevelopmental gene networks and replicate across independent blood and postmortem brain datasets.

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Cardiovascular-kidney-metabolic syndrome and the risk of liver-related and cardiovascular events across the steatotic liver disease spectrum

Fan et al. show that higher cardiovascular-kidney-metabolic stage is associated with graded increases in both cardiovascular and liver-related events across the steatotic liver disease spectrum. Obesity and hypertension are the leading modifiable contributors, whereas diabetes contributes disproportionately to liver-related outcomes.

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

Xiao et al. report results of a randomized phase II trial showing that pomalidomide plus bortezomib-dexamethasone (PVd) significantly improves hematologic and renal responses compared with bortezomib-dexamethasone in newly diagnosed multiple myeloma patients with renal impairment, supporting PVd as a feasible induction option for this underserved population.

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Restoring locomotion in motor-complete spinal cord injury via trunk-mediated control using a commercial epidural spinal cord stimulator

Agnesi et al. show that trunk movements can modulate epidural spinal cord stimulation in people with motor-complete spinal cord injury. Trunk extension switches stimulation-induced lower-limb activity from extension to triple flexion, enabling participants to control stepping through their residual trunk movements.

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Adoptive MAIT cell therapy for liver cancer enhanced by multimodal modulation of immune receptors and checkpoints

Li et al. developed an optimized ex vivo expansion platform and evaluated cancer-patient-derived MAIT cells for adoptive liver cancer therapy. Antigen stimulation, IL-15, and dual PD-1/TIGIT blockade enhanced antitumor activity, persistence, and therapeutic efficacy, supporting MAIT cells as a promising next-generation immunotherapy for liver cancer.

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The human oral and airway viral genome catalog from metagenomes enables virome characterization informing respiratory health

Compared with the extensively studied gut virome, viruses inhabiting the upper aerodigestive tract remain poorly characterized. Zou et al. establish a comprehensive viral genome catalog that expands knowledge of oral and airway viruses and reveals their associations with respiratory health.

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Melanoma to rhabdomyosarcoma plasticity in the setting of immunotherapy

Knight et al. present the first molecularly validated case of metastatic melanoma that divergently evolved into rhabdomyosarcoma under treatment with immune checkpoint inhibitor. Longitudinal multiomic profiling revealed that this divergence was characterized by transcriptional changes rather than genetic mutations, providing insights into the mechanisms of lineage plasticity.

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Multiomics profiling of plasma reveals lipid-immune dysregulation and exosome remodeling in mpox and mpox-HIV co-infection

Yong et al. integrate plasma lipidomics, metabolomics, exosome proteomics, and exosome-treated cell transcriptomics to characterize immunometabolic alterations in MPXV-monoinfected and MPXV-HIV-coinfected patients. They identify reproducible lipid and metabolite signatures, with HIV co-infection associated with greater inflammatory, metabolic, and vesicle trafficking disruptions.

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A bimodal large language model reduces misalignment in patient education: A double-blinded randomized trial

Wan et al. develop Dolphin, a bimodal large language model that integrates audio and text to improve emotional-semantic alignment in patient education. In a double-blinded randomized trial, Dolphin improved patient experience, increased disclosure of clinically relevant concerns, and reduced 7-day unplanned recontact compared with a matched text-based LLM comparator.

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Concomitant lipid-lowering and anticoagulation therapy for recurrent venous thromboembolism prevention: A Bayesian meta-analysis

A Bayesian meta-analysis of 28 randomized and observational studies suggests that concomitant use of anticoagulant and lipid-lowering therapy may reduce recurrent venous thromboembolism risk beyond anticoagulants alone, without increasing bleeding risk. The evidence is consistent across study types and may be mediated, at least in part, by reducing inflammation.

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Adjuvant oxaliplatin with S-1 (SOX) versus S-1 for stage II–III gastric cancer (CAPITAL): A randomized, open-label, phase 3 trial

The phase 3 CAPITAL trial demonstrates that adjuvant oxaliplatin plus S-1 (SOX) significantly improves OS and DFS relative to S-1 monotherapy in patients with resected stage II–III gastric or GEJ adenocarcinoma. With a manageable safety profile, these findings support SOX as a superior adjuvant standard-of-care for high-risk patients.

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

Goel et al. report a mixed-methods randomized pilot trial evaluating ketamine, psychotherapy, and combined ketamine plus psychotherapy for chronic neuropathic pain. The combined intervention was feasible to deliver and acceptably safe, supporting a larger efficacy-powered trial, while exploratory clinical outcomes remain hypothesis-generating.

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Engineered mesenchymal stem cells regulate integrated stress response for fibrosis therapy

Yu et al. develop an engineered mesenchymal stem cell-liposome conjugate that homes to fibrotic lesions and releases ISRIB and NMN in response to reactive oxygen species. This platform regulates pathological integrated stress response activation, restores epithelial stress homeostasis, promotes tissue repair, and ameliorates pulmonary and liver fibrosis.

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Plasma proteomics linking primary and secondary diseases: Insights into molecular mediation from UK Biobank data

This study maps plasma-protein mediators linking diabetes, hypertension, and dyslipidemia to cardiovascular, neurological, renal, and pulmonary complications using longitudinal UK Biobank proteomics. Through mediation analysis, Mendelian randomization, and machine learning, the authors identify clinically accessible protein biomarkers that improve downstream disease risk prediction and nominate candidate therapeutic targets.

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Gene therapy for hypertrophic cardiomyopathy: From feasibility to a fieldwide framework

With the emergence of gene-based therapies for hypertrophic cardiomyopathy, it is imperative to have a developmental framework encompassing evaluation, safety, endpoint definition, long-term surveillance, and considerations of equity and scalability. Harmonization across these domains is essential to ensure that early clinical signals are interpretable, comparable, and translatable into durable patient benefit.

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Immunologic determinants of infusion products and the tumor microenvironment govern response to TIL therapy in advanced melanoma

Karapetyan et al. identify immunologic features of TIL infusion products and tumor microenvironments associated with clinical benefit in metastatic melanoma. Stem-like and LAG-3+CD8+ T cells, enhanced TIL persistence, and tertiary lymphoid structure-rich tumors predict response, providing a framework for optimizing TIL therapy and patient selection.

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Rewriting the sarcomere: Gene therapy approaches for hypertrophic cardiomyopathy from bench to bedside

The authors review recent advances in gene-based approaches for hypertrophic cardiomyopathy, including adeno-associated virus-mediated gene replacement, and emerging gene editing strategies and highlight the first demonstrations of in vivo target engagement and early clinical translation. They highlight both the promise and complexity of translating genetic insight into durable clinical benefit.

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Burden of 10 mental disorders in low- and middle-income countries, 1990–2023, with forecasts to 2050: a Global Burden of Disease Study

Without proactive policies and interventions in LMICs and LICs, the age-standardized prevalence of mental disorders is projected to continue increasing through 2050. These findings highlight the critical need for proactive strategies to address the growing burden of mental disorders, particularly in resource-limited settings.

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Tissue-reactive zonation of mesenchymal-like phenotypes in human glioblastoma

Mossi Albiach, Janusauskas, Jacobsen et al. use single-cell RNA sequencing and spatial transcriptomics across glioblastoma core-to-periphery biopsies to show that mesenchymal-like cell states represent a tissue-wide wound response to hypoxia and vascular leakage, spatially confined to the tumor bulk, inducible and reversible in organoids, and organized by perivascular hypoxia gradients.

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Safety and efficacy of low-dose, cord blood-derived CD19 CAR-NK cells with 4-1BB co-stimulation in refractory systemic lupus erythematosus

Zeng et al. show that low-dose allogeneic cord blood-derived CD19-BBz CAR-NK cells are well tolerated in five patients with refractory SLE, inducing profound B cell depletion, naive-dominant B cell reconstitution, and durable clinical responses.

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Ethics of gene therapy

This review argues that heritable gene editing should be assessed by target, distinguishing catastrophic monogenic disorders, polygenic risk reduction, and non-disease enhancement. Within a welfare-centric framework, the authors hold that editing is permissible—and perhaps obligatory—for catastrophic monogenic conditions, premature for polygenic traits, and least justified at present for enhancement.

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Immune-stromal interactions at the crossroads of tissue injury, repair, and tumor progression

Ning et al. review the origins, phenotypes, and crosstalk of macrophages and fibroblasts across fibrosis and cancer, highlighting how tissue context and developmental lineage shape their distinct subpopulations. Using an engineered tissue lens, the authors identify and suggest future directions for parsing these complex stromal relationships within pathological microenvironments.

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A unified multi-task framework enables interpretable chest radiograph analysis

Xu et al. present a unified multi-task transformer for chest radiograph analysis that integrates classification, localization, segmentation, and report generation. The framework enables interpretable diagnosis through evidence-linked reasoning and demonstrates strong performance across benchmarks, with radiologist evaluation confirming clinical relevance and report quality.

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Spatially defined microenvironmental niches are associated with clinical outcome and tumor ecosystem diversity in head and neck cancer

Using single-cell spatial multi-omics profiling of 44 HNSCC tumors, An et al. identify recurrent tumor ecosystem states associated with HPV status, tumor cell programs, and clinical outcome. Fibroblast-rich, immune-poor ecosystems are associated with adverse features and characterize a high-risk subset of HPV-positive tumors, highlighting clinically relevant heterogeneity beyond HPV status.

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AI-driven therapeutic antisense oligonucleotide for processing-deficient progeroid laminopathies

Lv et al. developed a deep-learning framework, ASOMAR, to design a genotype-inclusive antisense oligonucleotide targeting processing-deficient progeroid laminopathies with transcript-level specificity. This therapeutic candidate safely reversed cardiovascular pathology in patient-derived 3D cardiac organoids and dramatically improved the lifespan and healthspan of progeria mouse models.

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