Reviews & Analysis

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  • The commonly indolent chronic lymphocytic leukemia may evolve into Richter transformation (RT), a very aggressive large B cell lymphoma. We identified early seeding of RT cells decades before its final expansion, mapped the underlying (epi)genomic alterations driving this process, and validated in vitro potential actionable therapeutic pathways.

    Research Briefing
  • Cellular senescence has emerged as a promising therapeutic target for disorders across the lifespan; this Review highlights the most promising strategies for translating senescence-targeting interventions into clinical use in the near future.

    • Selim Chaib
    • Tamar Tchkonia
    • James L. Kirkland
    Review Article
  • Incorporating genetic factors into risk models improves the prediction of severe obesity for survivors of childhood cancer, which could promote early interventions and better long-term care.

    • Lynda M. Vrooman
    • Lisa R. Diller
    News & Views
  • Infrequently dosed, longer-acting antiretroviral agents are making adherence to medication easier, leading to better outcomes for those living with HIV or at risk of infection.

    • Linda-Gail Bekker
    News & Views
  • Historically, hypertension control has been neglected in global and national health policies. We demonstrate how achieving an ‘80-80-80’ target for hypertension worldwide could considerably improve population-wide cardiovascular health and lessen inequalities across countries, forming a pillar of a renewed global non-communicable diseases agenda in the post-COVID-19 era.

    Research Briefing
  • A real-time early warning system for sepsis detection shows promising adoption by healthcare providers and important improvements in patient outcomes.

    • David W. Bates
    • Ania Syrowatka
    News & Views
  • A study evaluating serial injections of oncolytic virus therapy shows promising outcomes in patients with glioblastoma, and opens the door to longitudinal study designs with the potential to yield rich molecular insights.

    • John D. Christie
    • E. Antonio Chiocca
    News & Views
  • This Perspective delivers an introduction to syndemic thinking, and provides insights into how epidemics interact and what scientists, clinicians and policymakers can do with this information.

    • Emily Mendenhall
    • Brandon A. Kohrt
    • Alexander C. Tsai
    Perspective
  • In the phase 3 SPR1NT trial, pre-symptomatic gene therapy demonstrated impressive clinical outcomes in infants with a genetic diagnosis of spinal muscular atrophy (SMA); long-term safety follow-up of these patients must now be a key priority.

    • Charlotte J. Sumner
    • Thomas O. Crawford
    News & Views
  • Findings from a nationwide cohort study in Sweden, polygenic risk score analyses in a general population-based cohort in the United Kingdom, Mendelian randomization analyses and genetic correlation (linkage disequilibrium) analyses suggest a link between parental diagnosis of and genetic liability to inflammatory bowel disease and autism in children.

    Research Briefing
  • Analysis of SARS-CoV-2 evolution during chronic infection reveals that in this setting, the virus evolves to bear mutations similar to those seen in variants of concern, and that many of these mutations are associated with antibody evasion. However, as mutations associated with high SARS-CoV-2 transmissibility are not observed, the emergence of variants of concern during chronic infection might be rare.

    Research Briefing
  • The concentrations of two key blood biomarkers for Alzheimer’s disease are affected by some medical conditions, which could potentially lead to misdiagnosis.

    • Suzanne E. Schindler
    • Thomas K. Karikari
    News & Views
  • Precision medicine for rheumatic diseases is still in its infancy, but recent advances are enabling comprehensive profiling and mechanistic insights. This Review outlines the progress, promises, and challenges of translating these findings into the clinic.

    • Joel M. Guthridge
    • Catriona A. Wagner
    • Judith A. James
    Review Article
  • Climate change is projected to increase the frequency and intensity of extreme ambient temperatures, particularly in the Global South. By analyzing temperature and mortality data from over 300 cities in Latin America, we found that sub-optimal ambient temperatures are associated with increases in age- and cause-specific mortality.

    Research Briefing
  • A new genome-wide polygenic risk score for chronic kidney disease (CKD) that combines APOL1 risk genotypes with polygenic effects was validated in 15 diverse cohorts. The top 2% of the score reproducibly conveyed a threefold higher risk of CKD across all ancestries, a degree of risk that is equivalent to a positive family history of kidney disease.

    Research Briefing
  • The authors propose a new conceptual model of critical illness that moves away from the current syndrome-based framework in favor of more precise biological descriptors—spurred by mounting translational evidence and insights from Coronavirus Disease 2019 (COVID-19) research.

    • David M. Maslove
    • Benjamin Tang
    • John C. Marshall
    Perspective
  • Restoration of visual function in degenerative retinal disease may be an attainable goal, thanks to advances in cell-based therapy, gene therapy, and prosthetics. This Review discusses the most promising strategies that will probably reach clinical use in the next decade.

    • Russell N. Van Gelder
    • Michael F. Chiang
    • Clive N. Svendsen
    Review Article