Articles

The primary report of the EMBARK phase 3 trial, testing the AAV-based gene therapy delandistrogene moxeparvovec in Duchenne muscular dystrophy, did not meet its primary endpoint of improvement in NSAA mobility scores compared to placebo. Secondary endpoints show that the therapy was safe and associated with improvements in micro-dystrophin expression and in individual mobility scores.

Using data from a cohort of patients (n = 346) with lung adenocarcinoma and from multiple independent cohorts, DNA methylation signatures were evaluated to build and validate an accurate model predicting the development of brain metastasis.

Individuals with Parkinson’s disease treated with prasinezumab demonstrated slower motor progression over 4 years compared with an external comparator cohort derived from the Parkinson’s Progression Markers Initiative observational study.

Using ethnically and geographically diverse metagenomic data, the authors identify microbiota alterations associated with inflammatory bowel disease (IBD). They discover universal IBD-associated bacteria, which serve as the basis for a multibacteria biomarker panel that could support a noninvasive tool for IBD diagnosis.

In participants from a randomized controlled trial, doxy-PEP use over 6 months minimally affected the gut microbiome’s taxonomic composition but increased the abundance and active expression of tetracycline antibiotic resistance genes.

In the phase 3 EVER-132-002 trial, patients with HR⁺HER2⁻ metastatic breast cancer from Asia were treated with the Trop-2-directed antibody–drug conjugate sacituzumab govitecan or chemotherapy, and those receiving sacituzumab govitecan experienced prolonged progression-free survival compared with patients treated with chemotherapy.

In a phase 1 trial, pediatric or adult patients with T-ALL who received CD5-targeted CAR-T cell therapy using cells from previous or newly matched donors showed an encouraging clinical response rate, with some severe adverse events that required attention and effective management.

Repeat expansion disorders are found in all major global populations, and their frequency is up to three times higher than typically quoted, suggesting underdiagnosis or incomplete penetrance.

In this biomarker cohort analysis of CheckMate 153, analyses of genomic alterations and neoepitope immunogenicity in tumor tissue samples from patients with non-small cell lung cancer treated with nivolumab show the evolution of neoantigens during nivolumab-induced selection pressure and how it associates with clinical response.

A randomized controlled trial involving patients with stage 3b chronic kidney disease from primary care reported that in contrast to reported cardiorenal protective effects of nonsteroidal mineralocorticoid receptor antagonists (MRA), the steroidal MRA spironolactone did not reduce mortality or cardiovascular disease hospitalization compared to usual care.

The rapid waning of SARS-CoV-2-specific serum antibodies observed after immunization with COVID-19 mRNA vaccines may be accounted for by the absence of long-lived plasma cells in the bone marrow specific for the virus.

In a phase 1 trial followed by translational analyses, patients with acute myeloid leukemia (AML) treated with chimeric antigen receptor (CAR) T cell therapy targeting CD123 experienced high levels of cytokine release syndrome and short-lived clinical responses, probably due to CAR T cell-derived cytokines increasing the viability of AML blasts and antigen persistence.

This study reports substantial economic value in annual income if mortality due to cardiovascular diseases, cancers and injuries is reduced.

Forming the recommendations of the World Bank’s Healthy Longevity Initiative, this analysis finds that the economic impact of avoidable mortality globally is equivalent to 23% of the annual income.

Trained on a medical knowledge graph, a foundation model is used to rank drugs as potential indications and contraindications across 17,080 diseases, identifying therapeutic candidates in a zero-shot framework even for diseases with limited treatment options or no existing drugs and outperforming existing models by a large margin.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at one-year, associated with elevated brain injury markers and reduced grey matter volume.

Prespecified exploratory genomic and transcriptomic profiling of tumor tissues and circulating tumor DNA from patients with BRAF-V600E-mutant metastatic colorectal cancer who participated in the phase 3 BEACON CRC trial identifies biomarkers of response and mechanisms of acquired resistance to treatment with the BRAF inhibitor encorafenib plus the anti-EGFR antibody cetuximab, with or without the MEK inhibitor binimetinib.

Identifying a complex panel of bias dimensions to be evaluated, a framework is proposed to assess how prone large language models are to biased reasoning, with possible consequences on equity-related harms, and is applied to a large-scale and diverse user survey on Med-PaLM 2.

A single-cell ex vivo screening of repurposable drugs in glioblastoma and machine learning of drug–target networks show that anti-tumor neuroactive drugs converge on the AP-1/BTG pathway, based on which prediction models and experimental in vivo and in silico validation identify the anti-depressant vortioxetine as a potential therapeutic agent.

A combination of cross-sectional study and lifestyle intervention program uncovered altered lipid profiles in children and adolescents with obesity and demonstrated that a personalized obesity management program can restore a healthy lipid profile.