A monocyte-centered framework for predicting immunochemotherapy efficacy in lung squamous cell carcinoma patients

By: Jiangnan Zhao · Zijin Wang · Manyu Xiao · Yeyuan Zhang · Boxin Liu · Silin Chen · Yiping Tian · Dongqing Lv · Pingli Wang · Hai Song · Yuefeng Wu · Jian Liu · Kai Wang

30 March 2026 at 18:00

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

A monocyte-centered framework for predicting immunochemotherapy efficacy in lung squamous cell carcinoma patients

(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)

By: Jiangnan Zhao · Zijin Wang · Manyu Xiao · Yeyuan Zhang · Boxin Liu · Silin Chen · Yiping Tian · Dongqing Lv · Pingli Wang · Hai Song · Yuefeng Wu · Jian Liu · Kai Wang

30 March 2026 at 18:00

EMBO Mol Med. 2026 Mar 30. doi: 10.1038/s44321-026-00410-y. Online ahead of print.

ABSTRACT

Lung cancer is the leading cause of cancer-related mortality worldwide, with lung squamous cell carcinoma (LUSC) comprising 20-30% of cases. Immunochemotherapy (IC) is the standard first-line treatment for advanced LUSC, yet reliable predictors of therapeutic response remain unavailable. Using single-cell multi-omics profiling of paired pre- and post-treatment tumor and blood samples, we observed that patients responding to IC exhibited significantly higher baseline levels of peripheral blood monocytes, tumor-infiltrating classical monocytes, and APOBEC3A+ monocytes across both compartments compared with non-responders. These associations were independently validated in additional cohorts using routine complete blood count testing and multiplex immunofluorescence analysis of native tumor tissues. Our findings reveal monocyte-related parameters as clinically accessible indicators that link systemic immunity with the tumor microenvironment and hold promise for predicting IC responsiveness in patients with LUSC.

PMID:41912871 | DOI:10.1038/s44321-026-00410-y

MetaKE: Meta-learning Aligned Knowledge Editing via Bi-level Optimization

cs.AI, q-bio.NC updates on arXiv.org

By: Shuxin Liu · Ou Wu

16 March 2026 at 12:00

arXiv:2603.12677v1 Announce Type: cross Abstract: Knowledge editing (KE) aims to precisely rectify specific knowledge in Large Language Models (LLMs) without disrupting general capabilities. State-of-the-art methods suffer from an open-loop control mismatch. We identify a critical "Semantic-Execution Disconnect": the semantic target is derived independently without feedback from the downstream's feasible region. This misalignment often causes valid semantic targets to fall within the prohibited space, resulting in gradient truncation and editing failure. To bridge this gap, we propose MetaKE (Meta-learning Aligned Knowledge Editing), a new framework that reframes KE as a bi-level optimization problem. Departing from static calculation, MetaKE treats the edit target as a learnable meta-parameter: the upper-level optimizer seeks a feasible target to maximize post-edit performance, while the lower-level solver executes the editing. To address the challenge of differentiating through complex solvers, we derive a Structural Gradient Proxy, which explicitly backpropagates editability constraints to the target learning phase. Theoretical analysis demonstrates that MetaKE automatically aligns the edit direction with the model's feasible manifold. Extensive experiments confirm that MetaKE significantly outperforms strong baselines, offering a new perspective on knowledge editing.

Insulin resistance prediction from wearables and routine blood biomarkers

Nature - Issue - nature.com science feeds

By: Ahmed A. Metwally · A. Ali Heydari · Daniel McDuff · Alexandru Solot · Zeinab Esmaeilpour · Anthony Z. Faranesh · Menglian Zhou · Girish Narayanswamy · Maxwell A. Xu · Xin Liu · Yuzhe Yang · David B. Savage · Mark Malhotra · Conor Heneghan · Shwetak Patel · Cathy Speed · Javier L. Prieto

16 March 2026 at 08:00

Nature, Published online: 16 March 2026; doi:10.1038/s41586-026-10179-2

A machine-learning model that integrates data from wearable devices (such as smartwatches) with blood biomarkers and demographic data can predict whether someone has insulin resistance, enabling timely lifestyle interventions to prevent progression to type 2 diabetes.

Property-driven Protein Inverse Folding With Multi-Objective Preference Alignment

cs.AI, q-bio.NC updates on arXiv.org

By: Xiaoyang Hou · Junqi Liu · Chence Shi · Xin Liu · Zhi Yang · Jian Tang

10 March 2026 at 12:00

arXiv:2603.06748v1 Announce Type: cross Abstract: Protein sequence design must balance designability, defined as the ability to recover a target backbone, with multiple, often competing, developability properties such as solubility, thermostability, and expression. Existing approaches address these properties through post hoc mutation, inference-time biasing, or retraining on property-specific subsets, yet they are target dependent and demand substantial domain expertise or careful hyperparameter tuning. In this paper, we introduce ProtAlign, a multi-objective preference alignment framework that fine-tunes pretrained inverse folding models to satisfy diverse developability objectives while preserving structural fidelity. ProtAlign employs a semi-online Direct Preference Optimization strategy with a flexible preference margin to mitigate conflicts among competing objectives and constructs preference pairs using in silico property predictors. Applied to the widely used ProteinMPNN backbone, the resulting model MoMPNN enhances developability without compromising designability across tasks including sequence design for CATH 4.3 crystal structures, de novo generated backbones, and real-world binder design scenarios, making it an appealing framework for practical protein sequence design.

How Well Do Multimodal Models Reason on ECG Signals?

cs.AI, q-bio.NC updates on arXiv.org

By: Maxwell A. Xu · Harish Haresamudram · Catherine W. Liu · Patrick Langer · Jathurshan Pradeepkumar · Wanting Mao · Sunita J. Ferns · Aradhana Verma · Jimeng Sun · Paul Schmiedmayer · Xin Liu · Daniel McDuff · Emily B. Fox · James M. Rehg

10 March 2026 at 12:00

arXiv:2603.00312v2 Announce Type: replace Abstract: While multimodal large language models offer a promising solution to the "black box" nature of health AI by generating interpretable reasoning traces, verifying the validity of these traces remains a critical challenge. Existing evaluation methods are either unscalable, relying on manual clinician review, or superficial, utilizing proxy metrics (e.g. QA) that fail to capture the semantic correctness of clinical logic. In this work, we introduce a reproducible framework for evaluating reasoning in ECG signals. We propose decomposing reasoning into two distinct, components: (i) Perception, the accurate identification of patterns within the raw signal, and (ii) Deduction, the logical application of domain knowledge to those patterns. To evaluate Perception, we employ an agentic framework that generates code to empirically verify the temporal structures described in the reasoning trace. To evaluate Deduction, we measure the alignment of the model's logic against a structured database of established clinical criteria in a retrieval-based approach. This dual-verification method enables the scalable assessment of "true" reasoning capabilities.

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