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Two years after the earthquake and thousands of deaths later, the debate about whether to use the cholera vaccine in Haiti continues.

An effective and scalable cure strategy is a top priority for the HIV research field; this Review discusses recent advances, knowledge gaps, and priority research areas for the next 5 years.

BRCA2 mutations are well known to increase cancer risk, however, the significance of many variants remains unknown. Here, the authors combine data from two saturation genome editing studies to classify a total of 5926 variants as pathogenic or benign.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Analysis of tuberculosis drug trials identifies features to stratify patients for longer or shorter treatment duration than the standard of care, in order to improve therapeutic outcomes.

A soft robotic probe enables continuous in utero monitoring of fetal physiological parameters, including heart rate, blood oxygen saturation, temperature and electrocardiogram data, during open or fetoscopic surgery to provide real-time information on fetal condition and distress.

Acetic acid efficiently depolymerizes aliphatic and aromatic epoxy-amine thermosets used in carbon fibre-reinforced polymers (CFRPs) to yield recoverable monomers and pristine carbon fibres, which, based on process modelling, techno-economic analysis and life cycle assessment, could enable industrial recycling of CFRPs.

Neonates and infants infected with HIV generally develop disease rapidly, with early antiretroviral therapy (ART) often failing to achieve a sustained state of ART-free virologic remission. Here, the authors study viral reservoirs in neonatal macaques with early initiation of ART and an integrase inhibitor.

The authors show that plasma AT(N) biomarkers can distinguish Alzheimer’s disease and frontotemporal lobar degeneration in diverse Latin American populations. Using machine learning and integrating neuroimaging, significant diagnostic accuracy was achieved, enhancing clinical assessments of these conditions in Latin America.

As presented at the ESMO Congress 2025: Results of the phase 2/3 AGITG DYNAMIC-III trial show that de-escalated chemotherapy based on ctDNA-negative status in patients with stage III colon cancer did not meet non-inferiority for 3-year recurrence-free survival when compared to standard of care, although it enables better informed treatment decisions.

The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid and non-lymphoid tissues and show that while the viral reservoir exhibits a wide anatomic heterogeneity, persistent viral transcription is mainly restricted to secondary lymphoid organs.

Quantifying the total-body virus burden in HIV-infected individuals is necessary to understand viral persistence and guide development of cure strategies. Here, Estes et al. find a high burden of residual virus in tissues of SIV-infected monkeys and HIV-infected humans, and evidence of low-level viral replication, even under antiretroviral therapy.

The susceptibility of mouse and human T cells to ferroptosis is determined by the balance of systemic polyunsaturated and monounsaturated fatty acids, highlighting a key role for lipid metabolism and dietary composition in regulating T cell function.

Clinical trials may soon test whether gene editing can cure a group of debilitating haemoglobin disorders.

Targeting incretins is emerging as an effective approach to treat cardiovascular–kidney–metabolic syndrome. Here, the authors examine the biological effects of incretins and other metabolic hormones, such as glucagon and amylin, as well as discussing current clinical data demonstrating the organ-protective effects of incretin drugs and their potential underlying mechanisms.

Application of multiancestry and ensemble-based approaches yields improved polygenic risk prediction models for breast cancer and its subtypes among women of African ancestry.

In monkeys infected with an AIDS-like virus, a combination of a broadly neutralizing antibody and an immune stimulator during antiretroviral therapy suppressed viral rebound after antiretroviral drug discontinuation.

An assay to measure the latent HIV-1 reservoir that separately quantifies intact and defective proviruses will facilitate evaluation of HIV-1 cure strategies by measuring the provirues that pose a barrier to cure.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

Majzner and colleagues show that engineering T cells with a membrane-tethered version of the signaling adaptor molecule SLP-76 alongside a chimeric antigen receptor (CAR) enhances CAR T cell activity against low-antigen-density tumors.

CCR5 is a co-receptor for many transmitted HIV strains. Here, the authors show that biweekly injection of the CCR5-specific antibody Leronlimab protects rhesus macaques against infection following repeated intrarectal challenges of a CCR5-tropic SHIV.

Here, the authors apply positron emission tomography (PET) imaging to visualize HIV tissue-wide burden in infected individuals using a radiolabeled broadly neutralizing antibody, ⁸⁹Zr-VRC01, and show that PET tracer lymph node uptake positively correlates with HIV protein levels measured directly from cells obtained from these tissues. This strategy may allow non-invasive characterization of residual HIV infection in the setting of therapeutic interventions.

Since publication of the first issue of Nature Reviews Nephrology 20 years ago, advances across various subspecialities of nephrology have provided insights into disease processes and led to the development of new therapeutics for people with kidney disease. However, despite this progress, many kidney diseases remain untreatable, the costs of kidney disease care are immense, and vast inequities persist in disease burden and access to care. In this Viewpoint, we ask experts from several key subspecialties of nephrology to reflect on progress made over the past 20 years, remaining challenges and the steps needed to move the field forward.

Triclosan (TCS), an antimicrobial agent commonly found in consumer products, has been reported to exacerbates colitis in animal models. Here, using in vitro and in vivo approaches, the authors show that gut bacterial enzymes can drive the metabolic activation and gut toxicity of TCS, highlighting an important role of intestinal microbial factors in the complex etiology of colitis.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Staphylococcus epidermidis induces a potent, durable and specific antibody response that is conserved in humans and non-human primates, and which could be redirected against pathogens as a new form of topical vaccination.

Multi-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.

This study uses spatial proteomic and spatial compartment-based whole-transcriptome profiling to develop predictive models for immunotherapy outcomes in non-small cell lung cancer.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Targeted protein degradation (TPD) is a promising strategy for drug development. In this proof-of-concept study, the authors use telaprevir, which binds hepatitis C virus (HCV) NS3/4A protease, to target the protease for protein degradation, and show inhibition of wildtype as well as drug resistant HCV.

Rhesus macaques are not ideal for studying response to allogeneic hematopoietic stem cell transplant (allo-HSCT) owing to complex MHC genetics that prevent full MHC-matching. Here the authors show that inbred Mauritian-origin cynomolgus macaques are a superior preclinical model of allogeneic stem cell transplantation that mimics diverse clinical outcomes of human allo-HSCT.

Glucocorticoid resistance is partly due to epigenetic alterations, but the regulatory mechanisms driving these remain poorly understood. Here, a link between the activity of a lineage-specific transcription factor PU.1 and epigenetic modulators mediating the response to glucocorticoids is described in acute lymphoblastic leukemia.

Diffuse Intrinsic Pontine Gliomas are diagnosed by sampling a small portion of the tumour. Here, using multiple samples from tumours, the authors analyse the spatial and temporal distribution of driver mutations revealing that H3K27M mutations arise first in tumorigenesis followed by a specific invariable sequence of driver mutations, which are homogeneously distributed across the tumour mass.

Empirically based models of disease progression in familial frontotemporal dementia reveal the relative ordering of clinical, neuroimaging, and fluid biomarker changes and facilitate novel clinical trial designs

Hundreds of mutations in the gene CFTR lead to cystic fibrosis and represent a challenge to developing therapeutics. Here, authors demonstrate the ability of airway cells derived from human iPSCs to model genotype-specific CFTR function as well as pharmacologic rescue of disease causing mutations.

The social exposome—lifelong social and economic adversity—can shape brain health and dementia risk. Here, the authors show that an adverse social exposome is linked to poorer clinical, cognitive, and brain changes in Latin American older adults.

The theme of World Kidney Day 2024 is “kidney health for all — advancing equitable access to care and optimal medication practice”. To mark this event, Nature Reviews Nephrology invited five researchers from different geographical regions worldwide to discuss the impact of new and emerging therapies for diabetic kidney disease on patient care as well as the barriers that must be overcome to ensure equitable access to these therapies.

Developing broad antiviral drugs against dengue is challenging due to genetic diversity. Here, the authors generate PROTACs targeting the dengue virus envelope protein demonstrating improved potency and broadened activity against other mosquito-borne flaviviruses as compared to the parental inhibitors.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.

In the fungal pathogen Cryptococcus neoformans, Bim1 is a copper-binding lytic polysaccharide monooxygenase-like protein that participates in copper uptake in concert with the Ctr1 importer to drive virulence mechanisms during fungal meningitis.

Hepatitis B virus (HBV) has a limited host range and current animal models can only recapitulate certain aspects of HBV replication. Here, the authors show that expression of the HBV receptor NTCP in macaques supports HBV replication in vivo, suggesting this as animal model for future HBV studies.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

This study demonstrates that brain functional network imbalance appears linked to progressive brain atrophy and cognitive decline across the dementia spectrum.

The authors describe a mechanism for the clearance of macromolecules from cerebrospinal fluid in which macromolecules traverse from periarterial to perivenous spaces, at sites where intersecting leptomeningeal perivascular (arteriovenous) spaces overlap.

Single-cell transcriptomic and proteomic data from synovial tissue from individuals with rheumatoid arthritis classify patients into groups based on abundance of cell states that can provide insights into pathology and predict individual treatment responses.

Alison Dunning, Stacey Edwards and colleagues analyze 3,872 common variants across the ESR1 locus in 118,816 women. They find five independent variants within regulatory regions that associate with different breast cancer–related phenotypes and regulate the expression of ESR1, RMND1 and CCDC170.