Research Briefing

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  • Ventral striatal activity in individuals with OCD has strong circadian periodicity and high predictability in the severely symptomatic state. After deep brain stimulation, these features decrease substantially in clinical responders but remain raised in non-responders, thus providing a measurable predictor of clinical status.

    Research Briefing
  • In an observational cohort study of adults living with obesity and diabetes, we found that the primary incidence of congestive heart failure was lower in patients treated with bariatric metabolic surgery than in those on first-generation GLP-1 receptor agonists, an effect that was not explained by greater weight loss in the group that received bariatric metabolic surgery.

    Research Briefing
  • Using routinely collected multimodal clinical data, we developed an artificial intelligence (AI) model to identify dementia and determine factors causing it, including mixed dementias and Alzheimer’s disease. The model’s predictions were confirmed with biomarker evidence and neuropathological findings, and we show that the AI model, when used in conjunction with neurologist assessments, outperformed neurologist assessments alone.

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  • Although gut microorganisms have been associated with type 2 diabetes, the mechanisms involving specific microbial strains remain unidentified. Now, a comprehensive study has analyzed 8,117 shotgun metagenomes from the USA, Europe, Israel and China, providing cross-population microbial signatures in a strain-resolved manner and new mechanistic insights into type 2 diabetes.

    Research Briefing
  • A lack of biomarkers for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) hinders clinical trials of therapies for these disorders. We now show that blood extracellular vesicles contain proteins associated with ALS and FTD that can act as biomarkers to reliably detect the molecular pathology that underlies these disorders.

    Research Briefing
  • This study distinguished age- and metabolism-related gut microbiota signatures and constructed gut microbial age metric using data from a large, prospective cohort. Longitudinal analysis showed that younger microbial age seems to counteract the increased cardiovascular disease risk in metabolically unhealthy older people, indicating an interplay between gut microbiota and host age and metabolism.

    Research Briefing
  • We quantified liver, pancreas, heart and kidney fibrosis using MRI T1 mapping in over 40,000 individuals. Using genetic association analyses, we identified a total of 58 loci, 10 of which overlapped across organs. A high burden of fibrosis in three or more organs was associated with an increased risk of mortality.

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  • A longitudinal multiomic dataset was assembled to characterize the immune landscape in myocardial infarction and chronic coronary syndromes. Multiomics factor analysis (MOFA) revealed immune signatures that associate with disease stage or treatment outcomes. This work opens new directions for future mechanistic and clinical studies on coronary artery disease and myocardial infarction.

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  • Dapagliflozin improved a hierarchical composite outcome, including death, a worsening kidney disease event, and estimated glomerular filtration rate slope, compared with placebo, in patients with heart failure. This hierarchical outcome — analyzed with win statistics — might provide the statistical power to evaluate the effect of treatments on kidney function in heart failure trials.

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  • Using single-cell RNA and T cell receptor sequencing along with microscopy, we identified the cell types and genes associated with immune checkpoint inhibitor therapy-related colitis. Our study will help to identify targets for early diagnosis and lays the groundwork for the development of safer immunotherapy regimens.

    Research Briefing
  • QR4 is a new cardiovascular disease (CVD) risk score developed and evaluated in 16.9 million people that has better performance than other commonly used CVD risk scores. It includes nine new risk factors associated with increased risk of developing CVD (for example, a heart attack or stroke) over the next 10 years.

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  • The implementation of PCR tests of pooled saliva samples for universal screening of congenital cytomegalovirus infection was assessed in 15,805 neonates over 13 months. This extensive analysis revealed the high feasibility and empirical efficiency of the pooled testing approach, which had a clinically insignificant loss of sensitivity.

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  • Clinical disease trajectories that describe neuropsychiatric symptoms were identified using natural language processing for 3,042 brain donors diagnosed with various neurodegenerative disorders. Trajectories revealed distinct temporal patterns that result in the identification of new clinical subtypes, and a subset of misdiagnosed donors.

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  • Chronic pain is common, with more than one in five adult Americans reporting having pain daily or on most days. A multi-ancestry genomic analysis in 598,339 military veterans in the USA identifies 125 genetic variants associated with pain intensity, highlights shared genetic risk with substance use and psychiatric disorders, and reveals enrichment in GABAergic neurons as a key molecular contributor to experiencing pain.

    Research Briefing
  • Acute kidney injury affects one in five hospitalized patients and can lead to lasting kidney damage or death. We show that clonal hematopoiesis of indeterminate potential — a common age-related condition caused by blood cell mutations — increases the risk of acute kidney injury in multiple cohorts of human patients and in mouse models.

    Research Briefing
  • Primary fetal organoids are currently derived from tissue samples obtained at termination of pregnancy. We developed an approach that enables prenatal derivation of epithelial organoids from fetal fluids. Single-cell mapping of the human amniotic fluid content unveiled the presence of viable fetal epithelial progenitors of multiple tissues that can form fetal lung, kidney and intestinal organoids.

    Research Briefing
  • In a difference-in-differences analysis among Medicare beneficiaries in the USA, billion-dollar weather disasters were associated with higher rates of emergency department visits and deaths in the weeks after the disaster. Observed changes were more pronounced among counties that experienced the most loss and damage compared to all affected counties.

    Research Briefing