The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 20221-6. Here, shotgun metagenomics allowed the rapid reconstruction and phylogenomic characterization of the first MPXV outbreak genome sequences, showing that this MPXV belongs to clade 3 and that the outbreak most likely has a single origin. Although 2022 MPXV (lineage B.1) clustered with

Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence—supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—suggests that

Most children with biallelic SMN1 deletions and three SMN2 copies develop spinal muscular atrophy (SMA) type 2. SPR1NT (NCT03505099), a Phase III, multicenter, single-arm trial, investigated the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated within six postnatal weeks. Of 15 children with three SMN2 copies treated before symptom onset

Causes of blindness differ across the globe; in higher-income countries, most blindness results from the degeneration of specific classes of cells in the retina, including retinal pigment epithelium (RPE), photoreceptors, and retinal ganglion cells. Advances over the past decade in retinal regenerative medicine have allowed each of these cell types to be produced ex vivo from progenitor stem cells

Abstract SPR1NT (NCT03505099) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric

New technologies allow the noninvasive detection and staging of asymptomatic alcohol-associated liver disease; further refinement of this approach could transform clinical management and improve patient outcomes.

Online access during the pandemic widened participation in scientific conferences for women, young scientists and those from low- and middle-income countries, and should be continued

Patients with HER2-low metastatic breast cancer are a historically overlooked group, but a phase 3 trial reveals trastuzumab deruxtecan as a new treatment option that prolongs survival.

A phase 3 trial suggest that upadacitinib, a JAK inhibitor, may help patients with moderately to severely active ulcerative colitis obtain long-term control of the condition.

Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide

Timely evaluation of the protective effects of Coronavirus Disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is urgently needed to inform pandemic control planning. Based on 78 vaccine efficacy or effectiveness (VE) data from 49 studies and 1,984,241 SARS-CoV-2 sequences collected from 31 regions, we analyzed the relationship between

Substance addiction is a major public health crisis. Neuromodulation treatments show promise, but the therapeutic targets remain unclear. Studying human brain lesions that led to addiction remission with the lesion-network-mapping approach resulted in the identification of a brain circuit shared across addiction disorders that may have therapeutic potential.

Leading researchers explain how the COVID-19 pandemic has spurred research on wearables, genomic surveillance, behavioral interventions and drug discovery.

Drug addiction is a public health crisis for which new treatments are urgently needed. In rare cases, regional brain damage can lead to addiction remission. These cases may be used to identify therapeutic targets for neuromodulation. We analyzed two cohorts of patients addicted to smoking at the time of focal brain damage (cohort 1 n = 67; cohort 2 n = 62). Lesion locations were mapped to a brain atlas

In a first-in-human study, intranasal transplantation of mesenchymal stromal cells was safe and well-tolerated in newborns who had suffered a stroke — laying the foundation for large-scale clinical trials.

Biopsies from synovial joints — and the abundance of B cells and macrophages therein — may instruct more effective treatment decisions for individuals with rheumatoid arthritis.

Preventing atherosclerotic cardiovascular disease in adults will require innovative public health approaches focused on children and families, to improve risk factor trajectories across the lifespan and prioritize children at highest risk of future disease.

In a brief but pivotal study, pig kidneys were transplanted into two brain-dead humans for 54 hours, where they functioned well and avoided rejection.

Epidemiologic surveillance has revealed decoupling of COVID-19 hospitalizations and deaths from case counts following emergence of the Omicron (B.1.1.529) SARS-CoV-2 variant globally. However, assessment of the relative severity of Omicron variant infections presents challenges because of differential acquired immune protection against Omicron and prior variants, and because longer-term changes have

A phase 3 trial highlights the importance of problem-led design, multidisciplinary commitment and patient-reported outcomes — with skilled oncology nurses having a crucial role.

Designing a new drug is not enough; it has to be delivered to its target, which can be achieved via a cornucopia of vehicles, from nanoparticles and microneedles to red blood cells and microalgae.

RNA-guided RNA-targeting nucleases, such as CRISPR–Cas13 proteins, have therapeutic potential for gene editing. Among Cas13d enzymes, Cas13d from the bacteria Ruminococcus flavefaciens (RfxCas13d) is of particular interest owing to its small size and high specificity. However, the existence of pre-existing immunity against RfxCas13d is unclear. In this study, we evaluated antibody and T cell responses

Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial (NCT02977052) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic

The poor transferability of genetic risk scores (GRSs) derived from European ancestry data in diverse populations is a cause of concern. We set out to evaluate whether GRSs derived from data of African American individuals and multiancestry data perform better in sub-Saharan Africa (SSA) compared to European ancestry-derived scores. Using summary statistics from the Million Veteran Program (MVP), we

Evidence linking parental inflammatory bowel disease (IBD) with autism in children is inconclusive. We conducted four complementary studies to investigate associations between parental IBD and autism in children, and elucidated their underlying etiology. Conducting a nationwide population-based cohort study using Swedish registers, we found evidence of associations between parental diagnoses of IBD

Alcohol-related liver disease (ALD) is a major cause of liver-related death worldwide, yet understanding of the three key pathological features of the disease—fibrosis, inflammation and steatosis—remains incomplete. Here, we present a paired liver–plasma proteomics approach to infer molecular pathophysiology and to explore the diagnostic and prognostic capability of plasma proteomics in 596 individuals

The elimination of malaria from China relied on local decision-makers who tested and implemented interventions, combined with a centralized drug discovery program. This holds lessons for other malaria-endemic countries.

Ethnicity information is often missing from health data, impeding action on inequalities. Recording and using ethnicity data will require training, efforts at standardization, and policy changes, while engaging with patients and the public.

Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic.

The latency between acquisition of an initiating somatic driver mutation by a single-cell and clinical presentation with cancer is largely unknown. We describe a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) (aged 37 and 38 years), with a clinical phenotype of primary myelofibrosis. The CALR mutation was absent in T cells and dermal

Plasma phosphorylated tau 181 (P-tau181) and 217 (P-tau217) are indicators of both amyloid and tau pathology in clinical settings, but their performance in heterogeneous community-based populations is unclear. We examined P-tau181 and P-tau217 (n = 1,329, aged 30–98 years), in the population-based Mayo Clinic Study of Aging. Continuous, unadjusted plasma P-tau181 and P-tau217 predicted abnormal amyloid

The treatment landscape of acute myeloid leukemia (AML) is evolving, with promising therapies entering clinical translation, yet patient responses remain heterogeneous, and biomarkers for tailoring treatment are lacking. To understand how disease heterogeneity links with therapy response, we determined the leukemia cell hierarchy makeup from bulk transcriptomes of more than 1,000 patients through deconvolution

Immune checkpoint inhibitors (ICIs) show limited clinical activity in patients with advanced soft-tissue sarcomas (STSs). Retrospective analysis suggests that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in these patients. PEMBROSARC is a multicohort phase 2 study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS (NCT02406781)

People with less-severe Ebola virus disease may go undiagnosed, but they can still suffer long-term sequelae; this highlights the public health value of testing close contacts to identify and adequately treat all infections.

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with

A prospective clinical study evaluating patients 28–60 days after hospitalization for COVID-19 reveals increased cardio-renal inflammation, reduced lung function and poorer self-reported clinical outcomes in patients relative to that in control participants.

The outbreak of the B.1.1.529 lineage of SARS-CoV-2 (Omicron) has caused an unprecedented number of COVID-19 cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but to date, the evidence is sparse. Leveraging a population-based cohort in Chile of 490,694 children aged 3-5

Abstract The pathophysiology and trajectory of post-Coronavirus Disease 2019 (COVID-19) syndrome is uncertain. To clarify multisystem involvement, we undertook a prospective cohort study including patients who had been hospitalized with COVID-19 (ClinicalTrials.gov ID NCT04403607). Serial blood biomarkers, digital electrocardiography and patient-reported outcome measures were obtained in-hospital and

Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the diseased tissue. Approximately 40% of patients do not respond to individual biologic therapies and 5–20% are refractory to all. In a biopsy-based, precision-medicine, randomized clinical trial in RA (R4RA; n = 164), patients with low/absent synovial B cell

Nanoparticle vaccines show promise in preclinical models; clinical evaluation is warranted to assess whether they could help reduce the burden of disease associated with EBV in humans.

To maximize the benefits of patient-reported outcomes data while protecting patient welfare, a panel of experts set out ethical guidelines for the incorporation of these into clinical research.

We are raising the standards on reporting on sex and gender in research. Starting this June, authors will be prompted to provide details on how sex and gender were considered in study design.

With the increase in genomic data available and the advent of new technology for mining it, balancing the needs for data sharing and data protection becomes more challenging. Different disciplines must come together to find new solutions.

Experiencing a mental health crisis has a detrimental impact on a patient’s life. A machine learning algorithm trained retrospectively with electronic health records can predict almost 60% of mental health crises 4 weeks in advance. Prospective evaluation of the algorithm in clinical practice reveals its potential to enable preemptive interventions.

A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system’s actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use

SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine

Nicotine replacement therapy, in the form of nicotine patches, is commonly offered to pregnant women who smoke to help them to stop smoking, but this approach has limited efficacy in this population. Electronic cigarettes (e-cigarettes) are also used by pregnant women who smoke but their safety and efficacy in pregnancy are unknown. Here, we report the results of a randomized controlled trial in 1

Electronic cigarettes might be superior to nicotine replacement therapy as a quitting aid for pregnant women — but enthusiasm is hampered by low rates of smoking cessation and unknown long-term harm.

An online program developed in collaboration with the English National Opera could help with rehabilitation, by improving mental health and symptoms of breathlessness.