Reviews & Analysis

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  • This Review explores how research coproduction with Indigenous peoples is evolving; it discusses the challenges and complexities and makes recommendations for researchers wishing to pursue coproduction with Indigenous peoples in responsive and effective ways.

    • Chris Cunningham
    • Monica Mercury
    Review Article
  • Epidural electrical stimulation of the spinal cord alleviated freezing-of-gait and other postural impairments in a patient with Parkinson’s disease, potentially addressing an unmet need and offering an exciting new avenue for therapy.

    • Aviv Mizrahi-Kliger
    • Karunesh Ganguly
    News & Views
  • A new approach that combines CAR T cells with serial mRNA vaccine injections facilitates robust anti-neoplastic activity in patients with genitourinary cancers, which will pave the way for a promising new targeted treatment strategy.

    • Alex Chehrazi-Raffle
    • Lihua E. Budde
    • Sumanta K. Pal
    News & Views
  • By analyzing human samples and multiple mouse models of Huntington’s disease, we found that complement proteins and microglia mediate early and selective loss of corticostriatal synapses. Strategies that block this process can reduce synaptic loss, increase excitatory input to the striatum and prevent the development of cognitive deficits in mice.

    Research Briefing
  • Aberrant immune responses to the intestinal microbiome have emerged as major contributors to chronic intestinal inflammation, but the microbial species involved in inflammatory bowel diseases remain unknown. Our study identified dietary and commensal yeasts of the gut that drive the expansion of some cross-reactive CD4+ type 1 helper T cells with cytotoxic effector functions, which potentially contributes to immunopathology in patients with Crohn’s disease.

    Research Briefing
  • A novel AI-based decision support system for insulin titration in type 2 diabetes reveals important considerations surrounding the feasibility of clinical implementation.

    • Georgia M. Davis
    • Hui Shao
    • Francisco J. Pasquel
    News & Views
  • A spatially coupled, individual-based simulation of malaria in Rwanda was used to evaluate changes in drug policy in response to artemisinin-resistant Plasmodium falciparum. Our findings suggest that the deployment of multiple first-line therapies has the potential to reduce treatment failures and slow the fixation of resistant alleles in populations.

    Research Briefing
  • Recent years have seen major advances in heart failure treatment, but gaps in implementation and disparities in care remain; this Review outlines the current state of the field.

    • Carolyn S. P. Lam
    • Kieran F. Docherty
    • Torbjørn Omland
    Review Article
  • Researchers have developed a screening tool for autism that uses computer vision and machine learning to analyze autism-related behaviors — but greater reliability and robust validation will be needed if such tools are to be used in primary care settings.

    • Catherine Lord
    • Rujuta B. Wilson
    News & Views
  • The response to neoadjuvant treatment can be used to stratify individuals with muscle-invasive bladder cancer according to their risk of progression, enabling bladder-sparing approaches for some — and heralding a shift from the existing one-size-fits-all approach.

    • Roger Li
    News & Views
  • Clinical and population-based cohorts revealed an interaction between the inherited PNPLA3 p.I148M variant and female sex in determining liver disease. Transcriptomic and functional studies showed that the mechanism encompasses ERα-dependent upregulation of PNPLA3 in hepatocytes, highlighting a target for precision medicine therapeutics in cisgender women.

    Research Briefing
  • As the search for new and better treatments for Alzheimer’s disease continues, a phase 1 proof-of-concept study evaluating senolytic therapy breaks new ground.

    • Frank M. Longo
    • Stephen M. Massa
    News & Views
  • Mounting evidence, including the recent (and unprecedented) phase 2 data on retatrutide, supports a role for incretin hormone agonists in treating obesity. But with great power comes great responsibility.

    • Ildiko Lingvay
    • Shubham Agarwal
    News & Views
  • Using pathology data from Twitter, researchers have built a visual-language model for classifying and retrieving histopathology images — representing a milestone in the development of multifunctional foundational artificial intelligence models in computational pathology.

    • Ming Y. Lu
    • Bowen Chen
    • Faisal Mahmood
    News & Views
  • At a time when global mental health is in crisis, new data support the promotion of hobby engagement at the policy level in all countries.

    • Sophie Wickham
    News & Views
  • By integrating genomic and in vitro functional analysis, this study uncovers tumor-intrinsic mechanisms of resistance to immunotherapies that target B cell maturation antigen (BCMA) or the orphan G-protein-coupled-receptor GPRC5D in multiple myeloma (MM), highlighting a pivotal role for mutations in the genes encoding BCMA and GPRC5D in driving clinical relapse. These insights provide crucial guidance for the selection of therapeutic strategies and the development of next-generation targeted immunotherapies in MM.

    Research Briefing
  • Our study exposes the determinants of healthy aging in Latin America, underscoring the importance of the effects of social and health disparities compared with traditional factors such as age and sex. Our findings highlight an urgent need for more targeted detection of health risks, interventions and policies, particularly in low-income regions.

    Research Briefing
  • Despite an urgent need, approved and clinically usable biomarkers for non-alcoholic steatohepatitis (NASH) remain elusive — but a new study moves the field closer to this goal.

    • Aleksander Krag
    • Mary E. Rinella
    News & Views