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Extreme heterogeneity exists in the hypersensitive stress response exhibited by the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy. Because stress hypersensitivity can impact dystrophic phenotypes, this research aimed to understand the peripheral pathways driving this inter-individual variability. Male and female mdx mice were phenotypically stratified into "stress-resistant" or "stress-sensitive" groups based on their response to two laboratory stressors. Quantitative proteomics of striated muscle revealed that stress-resistant females were most dissimilar from all other groups, with over 250 proteins differentially regulated with stress hypersensitivity. Males showed less proteomic variation with stress hypersensitivity; however, these changes were associated with pathway enrichment. In the heart, stress-sensitive males had significant enrichment of pathways related to mitochondrial ATP synthesis, suggesting that increased cardio-metabolic capacity is associated with stress hypersensitivity in male mdx mice. In both sexes, stress hypersensitivity was associated with greater expression of beta-actin-like protein 2, indicative of altered cytoskeletal organisation. Despite identifying proteomic signatures associated with stress hypersensitivity, these did not correlate with differences in the serum metabolome acutely after a stressor. These data suggest that the heterogeneity in stress hypersensitivity in mdx mice is partially driven by cytoskeletal organisation, but that sex-specific cardio-metabolic reprogramming may also underpin this phenotype. SIGNIFICANCE: Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease which is associated with a premature loss of ambulation and neurocognitive dysfunction. The hypersensitive stress response in DMD is a heterogeneous phenotype which is poorly understood. This study provided the first investigation of the peripheral mechanisms regulating the hypersensitive stress response by undertaking multi-omics analysis of phenotypically stratified mdx mice. Variations in behaviour and the striated muscle proteomic profiles suggest that cardio-metabolic remodelling and cytoskeletal organisation may contribute to this phenotype. This research offers significant insights into understanding how peripheral dystrophin deficiency relates to the cognitive abnormalities seen in patients with DMD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Machine learning algorithms have proven to be effective for essential quantum computation tasks such as quantum error correction and quantum control. Efficient hardware implementation of these algorithms at cryogenic temperatures is essential. Here we utilize magnetic topological insulators as memristors (termed magnetic topological memristors) and introduce a cryogenic in-memory computing scheme based on the coexistence of a chiral edge state and a topological surface state. The memristive switching and reading of the giant anomalous Hall effect exhibit high energy efficiency, high stability and low stochasticity. We achieve high accuracy in a proof-of-concept classification task using four magnetic topological memristors. Furthermore, our algorithm-level and circuit-level simulations of large-scale neural networks demonstrate software-level accuracy and lower energy consumption for image recognition and quantum state preparation compared with existing magnetic memristor and complementary metal-oxide-semiconductor technologies. Our results not only showcase a new application of chiral edge states but also may inspire further topological quantum-physics-based novel computing schemes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Clinical uncertainty is associated with increased resource utilization, worsened health-related quality of life for patients, and provider burnout, particularly during critical illness. Existing data are limited, because determining uncertainty from notes typically requires manual, qualitative review. We sought to develop a consensus list of descriptors of clinical uncertainty and then, using a thematic analysis approach, describe how respondents consider their use in intensive care unit (ICU) notes, such that future work can extract uncertainty data at scale., Design: We conducted a Delphi consensus study with physicians across multiple institutions nationally who care for critically ill patients or patients with advanced illnesses. Participants were given a definition for clinical uncertainty and collaborated through multiple rounds to determine which words represent uncertainty in clinician notes. We also administered surveys that included open-ended questions to participants about clinical uncertainty. Following derivation of a consensus list, we analyzed participant responses using thematic analysis to understand the role of uncertainty in clinical documentation., Results: Nineteen physicians participated in at least 2 of the Delphi rounds. Consensus was achieved for 44 words or phrases over 5 rounds of the Delphi process. Clinicians described comfort with using uncertainty terms and used them in a variety of ways: documenting and processing the diagnostic thinking process, enlisting help, identifying incomplete information, and practicing transparency to reflect uncertainty that was present., Conclusions: Using a consensus process, we created an uncertainty lexicon that can be used for uncertainty data extraction from the medical record. We demonstrate that physicians, particularly in the ICU, are comfortable with uncertainty and document uncertainty terms frequently to convey the complexity and ambiguity that is pervasive in critical illness., Highlights: Question: What words do physicians caring for critically ill patients use to document clinical uncertainty, and why?Findings: A consensus list of 44 words or phrases was identified by a group of experts. Physicians expressed comfort with using these words in the electronic health record.Meaning: Physicians are comfortable with uncertainty words and document them frequently to convey the complexity and ambiguity that is pervasive in critical illness., Competing Interests: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided in part by grants from the NIH (P0546214), UCSF (UCSF Noyce Initiative for Digital Transformation in Computational Biology & Health, the Hellman Fellows Foundation, UCSF Anesthesia Department Seed Grant) and the NIA (P30 AG044281, R01AG057751 and K24AG068312). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.