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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.
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.
Exome-sequencing analysis in a Chinese cohort of 1,578 children with cerebral palsy established a genetic etiology in 387 of the patients (24.5%). Children with cerebral palsy for whom perinatal asphyxia had been recorded at birth were found to be more likely to carry pathogenic or potentially pathogenic variants.
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.
Most suspected cholera cases are not tested for Vibrio cholerae. Integrating systematic testing into cholera surveillance systems, even with imperfect rapid diagnostic tests, could yield large gains in efficiency and cost savings in the geographic targeting of mass oral cholera vaccination campaigns.
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.
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.
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.
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.
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.
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.
Longitudinal analysis of stool samples reveals new insights into how the gut microbiome changes during immunotherapy. These findings could inform the application of microbiome-targeted interventions to maximize the outcomes of immune checkpoint blockade.
This study seeks to highlight the scientific, regulatory and operational issues around the use of polygenic risk scores in a diverse population. The work presented here provides a framework for laboratories, providers and researchers wishing to advance the field of preventative medicine.
In a prospective study involving 1,090 high-risk pregnancies, a comprehensive screening test of fetal cell-free DNA successfully detected pathogenic aneuploidies, microdeletions and monogenic variants linked to fetal anomalies. The inclusion of monogenic conditions alongside chromosomal abnormalities in this test resulted in a 60.7% increase in the detection rate for suspected fetal structural abnormalities.
In a large-scale digital experiment on dermatology diagnosis, we found that specialists and generalists achieved diagnostic accuracy of 38% and 19%, respectively. With decision support from a fair deep learning system, the diagnostic accuracy of physicians improved by more than 33%, but the gap in accuracy of generalists widened across skin tones.
In one person with Parkinson’s disease, freezing of gait was averted through the use of a soft robotic apparel that provided a moderate level of hip-flexion assistance during the swing phase of walking. This approach delivered instantaneous effects and consistently improved walking quality and function across a range of conditions.
We deeply characterized the early-life gut virome, which consists mainly of bacteriophages (phages) and the diversity of which greatly exceeds bacterial diversity. The virome was associated with later asthma development, independently of the bacterial hosts of the phages; we further uncovered intriguing interactions with immune genetics.
We profiled human central nervous system (CNS)-associated macrophages (CAMs) in anatomically dissected CNS interface tissue from typical, fetal and glioblastoma-affected brains using single-cell multi-omics and spatially resolved transcriptomic techniques. Analyses of CAM (and microglia) turnover rates in stem-cell-transplanted glioblastoma and prenatal tissues highlighted the developmental phenotypes of these cells in patients, which lays the groundwork for potential replacement therapies.
Semaglutide, also known as Ozempic for treating type 2 diabetes and as Wegovy for treating obesity, compared with other weight management or diabetic medications, is not associated with higher risk of suicidal ideations in patients with obesity (or who are overweight) or patients with type 2 diabetes.
We developed and validated a deep learning system (termed DeepDR Plus) in a diverse, multiethnic, multi-country dataset to predict personalized risk and time to progression of diabetic retinopathy. We show that DeepDR Plus can be integrated into the clinical workflow to promote individualized intervention strategies for the management of diabetic retinopathy.