Normal view
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Molecular Therapy Advances
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Transduction Efficiency in Clinical CAR T-Cell Products: A Retrospective Study at a Single Center
Transduction efficiency is a critical determinant of CAR T-cell manufacturing quality. Analysis of 204 clinical CAR T-cell products revealed that transduction efficiency is shaped primarily by manufacturing workflows and protocol-dependent starting material composition. Higher transduction efficiency was associated with early memory-like cellular states, providing insights into optimizing CAR T-cell.
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Molecular Therapy
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Advanced iPSC-based modelling of LMNA-related congenital muscular dystrophy enables development of genetic therapies for muscle laminopathies
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.
Advanced iPSC-based modelling of LMNA-related congenital muscular dystrophy enables development of genetic therapies for muscle laminopathies
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Molecular Therapy
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Leveraging host-cell modulators of adeno-associated vector transduction to tailor viral biodistribution
AAV gene therapies are powerful but often limited by inefficient or unwanted tissue delivery. This study maps host genes that help or hinder AAV transduction, revealing that transiently tuning these factors can reshape vector biodistribution, offering a new strategy to improve gene therapy precision.
Leveraging host-cell modulators of adeno-associated vector transduction to tailor viral biodistribution
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Molecular Therapy
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In vivo engineering of T cells with a synthetic cytokine receptor enables selective enrichment and expansion of anti-CD22 CAR T cells
In preclinical studies, UB-VV400, an off-the-shelf, investigational lentiviral drug product, generates fully human anti-CD22 CAR T cells in vivo without the need for lymphodepletion. Activation of the synthetic rapamycin-activated cytokine receptor drives selective CAR T cell expansion and enrichment, resulting in complete tumor clearance and B cell depletion.
In vivo engineering of T cells with a synthetic cytokine receptor enables selective enrichment and expansion of anti-CD22 CAR T cells
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Molecular Therapy
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A combinatorial EV-miRNA signature mediates the anti-tumoral activity of NFAT3-regulated extracellular vesicles in aggressive cancers
NFAT3-regulated extracellular vesicles deliver a combinatorial miRNA signature that suppresses proliferation and invasion in aggressive breast and pancreatic cancer models. This study identifies the underlying molecular programs targeted by the miRNA combination and supports extracellular vesicles as a promising platform for multi-target RNA-based cancer therapy.
A combinatorial EV-miRNA signature mediates the anti-tumoral activity of NFAT3-regulated extracellular vesicles in aggressive cancers
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Molecular Therapy
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Tissue-specific silencing of synthetic mRNAs by de-targeting elements maps vaccination-competent tissues and allows Cas9 de-immunization
Sasso and colleagues leveraged organ-specific miRNAs by engineering synthetic mRNA vaccines containing miR target sites to generate a functional map of immunologically competent organs. This work lays the foundation for novel vaccines designed to target the most immunologically proficient organs. They subsequently applied this approach to de-immunize Cas9, rendering it immunologically masked.
Tissue-specific silencing of synthetic mRNAs by de-targeting elements maps vaccination-competent tissues and allows Cas9 de-immunization
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Molecular Therapy
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Triple-AAV intein-mediated gene therapy ameliorates dystrophic phenotype in MDC1A mice
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.
Triple-AAV intein-mediated gene therapy ameliorates dystrophic phenotype in MDC1A mice
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Molecular Therapy
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Repurposing base editors for targeted knockin and simultaneous multiplex knockouts to generate allo-CAR T cells with minimal translocations
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.
Repurposing base editors for targeted knockin and simultaneous multiplex knockouts to generate allo-CAR T cells with minimal translocations
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Molecular Therapy
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Repurposing triamterene as chloride intracellular channel 1 inhibitor via ligand-based approach for glioblastoma
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.
Repurposing triamterene as chloride intracellular channel 1 inhibitor via ligand-based approach for glioblastoma
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cs.AI, q-bio.NC updates on arXiv.org
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Teacher Geometry Shapes Learnability in Teacher-Student Networks
arXiv:2609.09595v1 Announce Type: cross Abstract: Teacher-student systems, in which a teacher neural network generates training labels so that a student neural network can learn to implement the same function, are widely used as an abstract setting to study learning. However, the structure of the teachers is often overlooked by assuming randomly-generated, normally-distributed parameters. This hides substantial variation in how learnable different teachers are. We formalize learnability as the
Teacher Geometry Shapes Learnability in Teacher-Student Networks
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cs.AI, q-bio.NC updates on arXiv.org
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HiRAD: A Flexible Large-Scale AGV Routing System
arXiv:2609.09752v1 Announce Type: cross Abstract: Automatic Guided Vehicles (AGVs) substantially boost warehouse throughput, but routing large-scale AGV fleets remains challenging. Classical Multi-Agent Pathfinding solvers suffer from exploding combinatorial complexity and super-quadratic runtime, while relying on idealized grid or piecewise-linear motion models that mismatch real-world kinematics. Recent Reinforcement Learning (RL) solutions improve flexibility via decentralized agent policies
HiRAD: A Flexible Large-Scale AGV Routing System
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cs.AI, q-bio.NC updates on arXiv.org
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Zero-shot World Models Are Developmentally Efficient Learners
arXiv:2604.10333v2 Announce Type: replace Abstract: Young children demonstrate early abilities to understand their physical world, estimating depth, motion, object coherence, interactions, and many other aspects of physical scene understanding. Children are both data-efficient and flexible cognitive systems, creating competence despite extremely limited training data, while generalizing to myriad untrained tasks -- a major challenge even for today's best AI systems. Here we introduce a novel co
Zero-shot World Models Are Developmentally Efficient Learners
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cs.AI, q-bio.NC updates on arXiv.org
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PRIME-SVR: Physics-infoRmed Implicit Multi-Echo Slice-to-Volume Reconstruction for Fetal T2 mapping
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 bra
PRIME-SVR: Physics-infoRmed Implicit Multi-Echo Slice-to-Volume Reconstruction for Fetal T2 mapping
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cs.AI, q-bio.NC updates on arXiv.org
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Investigating Hyperparameter Optimization and Transferability for ES-HyperNEAT: A TPE Approach
arXiv:2609.00449v2 Announce Type: replace-cross Abstract: Neuroevolution of Augmenting Topologies (NEAT) and its advanced version, Evolvable-Substrate HyperNEAT (ES-HyperNEAT), have shown great potential in developing neural networks. However, their effectiveness heavily depends on the selection of hyperparameters. This study investigates the optimization of ES-HyperNEAT hyperparameters using the Tree-structured Parzen Estimator (TPE) on the MNIST classification task, exploring a search space o
Investigating Hyperparameter Optimization and Transferability for ES-HyperNEAT: A TPE Approach
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cs.AI, q-bio.NC updates on arXiv.org
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When Does a Laugh Begin? Structured Annotator Disagreement in Temporal Laughter Localization
arXiv:2609.06646v2 Announce Type: replace-cross Abstract: Annotators routinely disagree on laughter boundaries and subtle chuckles, yet temporal laughter localization typically evaluates against a single reference annotation. We show that this disagreement is structured rather than random noise. Re-annotating the SMILE-Temporal benchmark (672 videos, 1,683 events) with 3-5 annotators per video (alpha = 0.757), we find systematic patterns: disagreement is 1.73 times larger at offsets than onsets
When Does a Laugh Begin? Structured Annotator Disagreement in Temporal Laughter Localization
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cs.AI, q-bio.NC updates on arXiv.org
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Omni Interaction Agent Technical Report
arXiv:2609.08977v2 Announce Type: replace-cross Abstract: In this work, we present Gander, an end-to-end model that unifies omni perception, realtime interaction, and agentic capabilities within a single framework. In contrast to turn-based conventional paradigms, Gander continuously receives streaming inputs across multiple modalities, including video, speech, and text, enabling natural full-duplex interaction in both everyday conversations and complex workflow-oriented agent scenarios. Users
Omni Interaction Agent Technical Report
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Journal of Medical Internet Research
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“Small” Large Language Models in the Hospital: Evaluation Study on Real-World Data in a Resource-Constrained Setting
Background: Large language models (LLMs) are increasingly being deployed in health care, but their use and deployment in many real-world hospital environments pose significant challenges and concerns. In particular, state-of-the-art commercial models store or process data externally, which is often in conflict with ensuring patient data protection. At the same time, using LLMs locally is limited by the lack of available computing infrastructure. Small open-source LLMs that do not require substan
“Small” Large Language Models in the Hospital: Evaluation Study on Real-World Data in a Resource-Constrained Setting
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Omics in Gastric
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Innovative pathological and therapeutic approaches for poorly cohesive gastric cancer
Front Oncol. 2026 Aug 25;16:1842715. doi: 10.3389/fonc.2026.1842715. eCollection 2026.ABSTRACTPoorly cohesive gastric cancer (PCGC) represents a biologically distinct subtype of gastric cancer, characterized by diffuse growth, marked intratumoral heterogeneity, and a consistently worse prognosis compared with other histological subtypes. Despite advances in pathological classification and molecular profiling, treatment strategies remain largely independent of histological subtype, and no specifi
Innovative pathological and therapeutic approaches for poorly cohesive gastric cancer
Front Oncol. 2026 Aug 25;16:1842715. doi: 10.3389/fonc.2026.1842715. eCollection 2026.
ABSTRACT
Poorly cohesive gastric cancer (PCGC) represents a biologically distinct subtype of gastric cancer, characterized by diffuse growth, marked intratumoral heterogeneity, and a consistently worse prognosis compared with other histological subtypes. Despite advances in pathological classification and molecular profiling, treatment strategies remain largely independent of histological subtype, and no specific therapeutic approaches have been established for PCGC. In this review, we summarize current evidence on the biological features, diagnostic challenges, and emerging therapeutic strategies, with a focus on novel targeted agents and innovative treatment platforms. Recent years have witnessed the development of therapies directed against specific molecular targets, including HER2, PD-L1, CLDN18.2, FGFR2b, and TROP2, as well as the introduction of antibody-drug conjugates and bispecific antibodies, progressively expanding the therapeutic landscape of gastric cancer. However, their clinical impact in poorly cohesive tumors remains to be fully defined. In parallel, advances in digital pathology, artificial intelligence, and multi-omics approaches are providing new opportunities to improve diagnostic reproducibility, refine prognostic stratification, and support personalized treatment strategies by integrating histomorphological and molecular tumor features. Overall, the convergence of novel therapeutic strategies and advanced diagnostic technologies may pave the way toward a more precise and biologically informed management of PCGC, although further validation and integration into clinical practice are required.
PMID:42713041 | PMC:PMC13550965 | DOI:10.3389/fonc.2026.1842715
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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Innovative pathological and therapeutic approaches for poorly cohesive gastric cancer
Front Oncol. 2026 Aug 25;16:1842715. doi: 10.3389/fonc.2026.1842715. eCollection 2026.ABSTRACTPoorly cohesive gastric cancer (PCGC) represents a biologically distinct subtype of gastric cancer, characterized by diffuse growth, marked intratumoral heterogeneity, and a consistently worse prognosis compared with other histological subtypes. Despite advances in pathological classification and molecular profiling, treatment strategies remain largely independent of histological subtype, and no specifi
Innovative pathological and therapeutic approaches for poorly cohesive gastric cancer
Front Oncol. 2026 Aug 25;16:1842715. doi: 10.3389/fonc.2026.1842715. eCollection 2026.
ABSTRACT
Poorly cohesive gastric cancer (PCGC) represents a biologically distinct subtype of gastric cancer, characterized by diffuse growth, marked intratumoral heterogeneity, and a consistently worse prognosis compared with other histological subtypes. Despite advances in pathological classification and molecular profiling, treatment strategies remain largely independent of histological subtype, and no specific therapeutic approaches have been established for PCGC. In this review, we summarize current evidence on the biological features, diagnostic challenges, and emerging therapeutic strategies, with a focus on novel targeted agents and innovative treatment platforms. Recent years have witnessed the development of therapies directed against specific molecular targets, including HER2, PD-L1, CLDN18.2, FGFR2b, and TROP2, as well as the introduction of antibody-drug conjugates and bispecific antibodies, progressively expanding the therapeutic landscape of gastric cancer. However, their clinical impact in poorly cohesive tumors remains to be fully defined. In parallel, advances in digital pathology, artificial intelligence, and multi-omics approaches are providing new opportunities to improve diagnostic reproducibility, refine prognostic stratification, and support personalized treatment strategies by integrating histomorphological and molecular tumor features. Overall, the convergence of novel therapeutic strategies and advanced diagnostic technologies may pave the way toward a more precise and biologically informed management of PCGC, although further validation and integration into clinical practice are required.
PMID:42713041 | PMC:PMC13550965 | DOI:10.3389/fonc.2026.1842715
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Nature - Issue - nature.com science feeds
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Breaking timescales with generative sampling of conformational transitions
Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-11025-1A generative committor-guided path-sampling framework reconstructs rare biomolecular transition pathways and reveals the underlying thermodynamics and kinetics without using predefined collective variables or brute-force sampling, at an acceptable computational cost.
Breaking timescales with generative sampling of conformational transitions
Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-11025-1
A generative committor-guided path-sampling framework reconstructs rare biomolecular transition pathways and reveals the underlying thermodynamics and kinetics without using predefined collective variables or brute-force sampling, at an acceptable computational cost.