Reviews & Analysis

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.

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.

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.

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.

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.

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.

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.

This Review summarizes recent advances in biomarkers and therapies for Alzheimer disease—the products of decades of research—and discusses the challenges, gaps and clinical implications.

A blood test done in early pregnancy that measures cell-free DNA methylation could represent a novel way to predict the risk of preterm pre-eclampsia.

The current definition of myocardial infarction is applied inconsistently, with implications for patients and research; here, the authors propose a new definition and call for further research and consensus.

We performed gene therapy to induce expression of GDNF in the ventral tegmental area of rhesus monkey brains. Our approach countered the hypodopaminergic state that is associated with chronic alcohol drinking and reduced alcohol intake to fewer than two drinks per day while other ingestive behaviors remained intact. These findings, along with results from our ongoing clinical trials of GDNF gene therapy in other diseases, support future application of this approach in humans with alcohol-use disorder.

OncoNPC, a machine learning classifier developed to predict the primary origin of tumors, made confident predictions for over 40% of cancers of unknown primary (CUP) cases analyzed. Patients with CUP who had received site-specific treatments that retrospectively matched the OncoNPC predictions had better outcomes than patients who had been treated with discordant site-specific therapies. OncoNPC predictions doubled the number of patients with CUP who would be eligible for genomically guided therapies.

We transplanted gene-edited porcine hearts into two brain-dead human recipients, then evaluated their cardiac function and immune response over the following 66 hours. Both hearts showed sustained cardiac function over the course of the study, without evidence of hyperacute rejection or zoonotic transmission.

Alzheimer’s disease is a complex and chronic disease that evolves over decades. Proteomic analysis of cerebrospinal fluid from people with dominantly inherited forms of the disease reveals the temporal progression of pathological changes in Alzheimer’s disease and identifies extracellular matrix proteins as some of the earliest biomarkers of the disease.

Cost-effective fluid biomarkers for tau aggregate pathology would improve the diagnostic and prognostic work-up of Alzheimer’s disease and facilitate the discovery of anti-tau therapies. We identified MTBR-tau243 as a specific marker for tau aggregate pathology that could be implemented in clinical practice and trials.

Innovative clinical trial designs with a patient-centered mission are crucial to advancing modern cancer care; the adaptive phase 2 umbrella study CTONG1702 provides one model for this new era of trial design.

In individuals with anorexia nervosa, psilocybin therapy comes with specific risks and concerns; but an encouraging phase 1 trial underscores the necessity for more research into classic psychedelics to address the urgent need for effective treatments.

The authors generate a checklist of key considerations to guide patient and public involvement and engagement in future research, informed by lessons from the TLC study, which evaluated therapies for long COVID.

This study reveals that the production of cobalamin and succinyl-CoA is increased in the anal microbiome of patients with precancerous anal lesions. Testing for these two metabolites significantly improves diagnostic accuracy over standard cytology screening, which suggests potential for enhanced screening strategies for anal cancer.

Escalating severity and frequency of heatwaves have outpaced the effectiveness of existing prevention and adaptation measures; there is urgency for reassessment, enhancement and implementation of strategies to mitigate health impacts in dealing with this global health challenge.