Nature Medicine, Published online: 13 September 2026; doi:10.1038/s41591-026-04488-2

In a large international real-world study of non-small cell lung cancer, a multimodal explainable AI model outperformed established biomarkers for immunotherapy outcome prediction and improved physician decision-making.

Science, Ahead of Print.

Science, Ahead of Print.

Recombinant AAV gene therapies deliver durable clinical benefit but face immune-mediated challenges that vary by vector, dose, route, and patient. Gulve and colleagues synthesize the clinical manifestations, temporal patterns, and mechanisms of rAAV immunogenicity, highlighting risk assessment and emerging mitigation strategies to support safer, more effective gene therapy development.

This study identifies the interleukin-2-inducible T cell Kinase (ITK)-mediated phosphorylation of Y218 in the CD28 cytoplasmic domain as key for CAR-T cell function and demonstrates that engineering a synthetic ITK-binding motif into the CAR enhances IL-2 production and antitumor efficacy in vivo.

The efficacy of vaccines remains suboptimal in many settings, underscoring the need for new strategies. Baydemir and colleagues show that modulation of acetyl-CoA metabolism reshapes metabolic and epigenetic programs underlying Bacille Calmette-Guérin-induced trained immunity, enhancing cellular innate immune responses and identifying immunometabolic targeting as a promising approach to improve vaccine efficacy.

LMNA-related congenital muscular dystrophy (L-CMD) is a devastating early-onset muscle disease caused by dysfunctional nuclear lamina. Current models fail to capture the complexity of human muscle pathology, limiting translational progress. This study overcomes this limitation by establishing a robust, human iPSC-based platform for modelling L-CMD and testing gene editing strategies.

Obesity expands a pathogenic ITGA7high adipose stromal cell population that promotes fibrosis. We engineered ITGA7-targeted lipid-coated mesoporous silica nanoparticles to selectively deliver plasminogen activator inhibitor-1 small interfering RNA, suppress profibrotic signaling, and restore a healthier adipose microenvironment.

To overcome the strict packaging limits of AAV vectors, this study utilizes a triple-AAV system paired with orthogonal split inteins to reconstitute the exceptionally large LAMA2 protein. This scarless, multi-vector approach successfully rescues the dystrophic phenotype in vivo, offering a scalable platform for large-gene therapies.

Wagner and colleagues develop BEKI (Base Editor-mediated Knock-In), a non-viral platform that combines targeted transgene insertion with simultaneous gene knockouts in a single step. BEKI-engineered CAR T cells show markedly reduced chromosomal rearrangements compared with conventional nuclease-based approaches, advancing safer manufacturing of multiplex-edited cell therapies for cancer and autoimmune diseases.

Currently no effective therapies are available for glioblastoma. Florio and colleagues identified, via computational screening, triamterene as a CLIC1 blocker that suppresses human glioblastoma stem cell proliferation, invasiveness, and tumor growth. Triamterene also enhances temozolomide and radio-chemotherapy efficacy, making it a repurposed therapeutic candidate for glioblastoma treatment in future clinical applications.

Stanek and colleagues uncover a novel PRPF31 intronic mutation that disrupts splicing and lowers protein levels. Targeted antisense oligonucleotides restore normal splicing and boost PRPF31 expression in patient-derived RPE, highlighting a potential therapeutic strategy for retinitis pigmentosa.

arXiv:2609.09884v1 Announce Type: cross Abstract: Recent advances in Intrinsic Image Decomposition (IID) have increasingly relied on generative models. However, progress remains limited by three key challenges: (a) insufficient physical consistency, (b) high computational cost at inference time, and (c) limited generalization capabilities. In this work, we show that latent bridge matching (LBM) effectively addresses these limitations for albedo estimation. We introduce a novel LBM-based architecture that enforces physical consistency through a pixel reconstruction loss, benefits from the inherent efficiency of LBM low-cost inference, and improves generalization across diverse datasets by incorporating a shading conditioning. In this extended version, we additionally show that conditioning the shading estimator itself on the predicted albedo further improves reconstruction fidelity, and we benchmark our best model against stateof-the-art IID methods across five real and synthetic datasets.

arXiv:2609.10132v1 Announce Type: cross Abstract: The development of generative artificial intelligence resources enables opportunities of speeding up systems and engineering design work. This contribution introduces a framework of formal operations for assembling context in LLM-based engineering design. This framework involves the assembly of modular context units, including policy prompts, reference units with persistence, and user questions with prompt vectoring. This approach enables the systematic structuring of interactions with generative models. A formal method for evaluating modelling-as-code LLM outputs is also presented, which enables the evaluation of compliance to intent from LLM answers and thereby asses the support from LLMs for systems architecture modelling.

arXiv:2605.13841v3 Announce Type: replace-cross Abstract: Voice agents are increasingly deployed across enterprise applications. However, no existing benchmark jointly addresses realistic conversation simulation and comprehensive voice-specific evaluation. We present EVA-Bench, an end-to-end evaluation framework that addresses both. On the simulation side, EVA-Bench orchestrates dynamic bot-to-bot audio conversations with automatic simulation validation that detects user simulator error and appropriately regenerates conversations before scoring. On the measurement side, EVA-Bench introduces two composite metrics: EVA-A (Accuracy) and EVA-X (Experience). EVA-Bench includes 213 scenarios across three enterprise domains, a controlled perturbation suite for accent and noise robustness, and multi-trial measurements that distinguish peak from reliable capability. Across 12 systems spanning all three architectures, we find: (1) no system simultaneously exceeds 0.5 on both EVA-A pass@1 and EVA-X pass@1; (2) peak and reliable performance diverge substantially (median pass@k--pass^k gap of 0.44 on EVA-A); and (3) accent and noise perturbations expose substantial robustness gaps, with effects varying across architectures, systems, and metrics (mean $\Delta$ up to 0.314). We release EVA-Bench under an open-source license.

arXiv:2607.20136v2 Announce Type: replace-cross Abstract: Slice-to-volume reconstruction (SVR) is the standard method for obtaining high-resolution (HR) 3D fetal brain volumes from motion-corrupted 2D MRI slice stacks acquired in multiple orientations. Existing SVR methods are optimized and validated only for clinical-range echo times (TEs), limiting their use at non-clinical TEs and making them incompatible with quantitative T2 mapping, a protocol- and center-independent biomarker of fetal brain maturation requiring HR reconstructions across multiple TEs. We present PRIME-SVR, the first implicit neural representation (INR) framework for joint HR reconstruction from multi-echo MRI. A single fully connected network models a continuous function from spatial coordinates to signal intensities across TEs, while a second network estimates slice-specific acquisition degradations. Cross-TE coherence is enforced via a Bloch equation-derived regularization penalizing deviations from expected T2 decay, with adaptive weighting that strengthens coupling for degraded stacks. The method is fully self-supervised. We validate PRIME-SVR on 39 in vivo fetal acquisitions (13 subjects x 3 TEs) from two centers, two vendors, and two field strengths (1.5 T and 0.55 T). Compared to state-of-the-art SVR, PRIME-SVR improves reconstruction sharpness by 47%, anatomical accuracy by 30%, and cross-TE structural consistency by 14%. It enables reconstruction at late TEs previously inaccessible to SVR, yielding the first 0.8 mm isotropic T2 maps at 0.55 T and the first T2 maps derived from INR-based SVR. PRIME-SVR also accelerates quantitative imaging by reducing the data needed for multi-TE reconstruction, cutting acquisition from 15 to 10 minutes while keeping T2 accuracy within 1.7% in white and deep gray matter, or to 5 minutes with a mean T2 error of 2.3% for high-quality acquisitions.

Listen Labs walked away from a signed Series C term sheet from Menlo Ventures, sources say.

Background: Postoperative outcome assessment is often based on discrete follow-up visits, limiting characterization of individual recovery trajectories, and the timely identification of adverse events (AEs). Longitudinal smartphone-based monitoring may overcome these limitations by enabling frequent, resource-efficient collection of patient-reported outcomes and complications throughout recovery. Such data may provide a more patient-centered understanding of the postoperative course and complement conventional clinical surveillance. Objective: This study aimed to evaluate the feasibility of smartphone-based longitudinal monitoring of quality of life, subjective well-being, and AEs after elective neurosurgery and compare postoperative recovery trajectories and agreement between patient- and clinician-reported AEs. Methods: This interim analysis of a prospective cohort study included adult patients undergoing elective lumbar decompression, lumbar fusion, supratentorial craniotomy, or infratentorial craniotomy at a Swiss tertiary referral center between June 2023 and January 2025. Participants used a smartphone app to longitudinally report subjective well-being (Subjective Well-Being Index; 0‐10), quality of life (EQ-5D-5L), and AEs for up to 1 year postoperatively. Complications were self-reported using the Therapy-Disability-Neurology (TDN) classification and retrospectively adjudicated by physicians. Descriptive analyses assessed data density, engagement, and concordance between patient- and clinician-reported events. Mixed-effects models were used to evaluate factors associated with postoperative well-being. Results: Of the 100 enrolled patients (median age 64.0, IQR 52.95‐71.6 years; n=45, 45% women), 86 (86%) provided postoperative data. During a median follow-up of 3.2 (IQR 0.2‐11.3) months, participants submitted 4354 longitudinal well-being entries. Patients reported 22 unique AEs, whereas physicians identified 44 AEs, with overlap for 9 (20.5%) events. Most physician-reported AEs were mild (30/44, 68.2%; TDN grade 1‐2), and no grade 4 or 5 events occurred. Patient-reported AEs primarily reflected symptomatic and functional impairments, whereas physician-reported events more often included clinically detected or subclinical findings. In mixed-effects models, time since surgery was associated with improved well-being, and no other factors were statistically significant. Conclusions: Smartphone-based postoperative monitoring was feasible in this elective neurosurgical cohort and generated dense longitudinal patient-reported data beyond routine follow-up. Patient and clinician AE reporting captured partly distinct aspects of postoperative recovery, suggesting that smartphone-based self-reporting may complement rather than replace clinical surveillance. Trial Registration: ClinicalTrials.gov NCT06352710; https://clinicaltrials.gov/study/NCT06352710

ARPA-H, the government agency that funds cutting-edge health research, plans to commit $62.7 million to develop artificial intelligence bots that direct treatment of heart failure. Among the goals of the program, called ADVOCATE, is to produce partially autonomous AI devices authorized by the Food and Drug Administration to help treat patients, including assessing symptom severity, prescribing drugs, and ordering lab tests. 

ARPA-H on Wednesday announced the first batch of awards to health tech companies Atman Health, UpDoc, Tempus AI, and teams from Stanford University, Duke University, and the Kaiser Permanente health system. ARPA-H may still fund additional teams. The amount committed for the first year is $33.7 million, and the remainder may be renegotiated up or down. 

Many of the 6.7 million Americans with heart failure don’t get optimal treatment because of difficulty accessing specialists, and the hope is that AI agents developed with ARPA-H funding can help address the gap, especially in rural and other underserved settings.

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