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Analysis of the spread of the 20E (EU1) variant of SARS-CoV-2 through Europe suggests that international travel and insufficient containment, rather than increased transmissibility, led to a resurgence of infections.

Sjögren’s syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.

New treatments are essential for methicillin-susceptible Staphylococcus aureus bacteremia, but progress is slow. In this phase III–IV trial, cloxacillin plus fosfomycin failed to show superiority over cloxacillin alone, underscoring the challenges to improving patient outcomes.

Immune checkpoint inhibitors have been incorporated as the standard of care for some high-grade neuroendocrine neoplasms (NEN), but their efficacy in digestive NEN is still unclear. Here the authors report the results of a phase II trial of nivolumab (anti-PD1) in combination with platinum-doublet chemotherapy (carboplatin-etoposide) as first-line treatment in patients with unresectable or metastatic advanced grade 3 NENs of gastro-enteropancreatic or unknown origin.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Substrate reduction therapies (SRT) are a promising therapeutic approach for monogenic inherited metabolic diseases. Here the authors evaluate the therapeutic potential of an in vivo CRISPR/Cas9-mediated SRT to treat primary hyperoxaluria type I and demonstrate its safety and efficacy.

The discovery of a human lower jaw associated with stone tools and animal bones from the Sima del Elefante in northern Spain is reported. The finds have been dated to between 1.1 and 1.2 million years using a variety of dating techniques, making the site the oldest and most accurately dated record of human occupation in Europe.

Targeting solid tumours by chimeric antigen receptor (CAR) T cells require strategies that improve trafficking and effector function of these cells in the immunologically hostile cancer microenvironment. Here, authors show that CAR T cells engineered with incorporation of the CD28 transmembrane domain to the 4-1BB costimulatory domain and a membrane-bound form of IL-12 can achieve efficient anti-tumour activity and promote systemic disease targeting via regional T cell delivery in multi-metastatic disease models.

Observations of a 3-million-year-old pre-main-sequence star with a misaligned disk reveal a giant orbiting planet; the system is ideal for studying the early formation and migration of planets.

Drug induced liver injury (DILI) is an important cause acute liver failure. Here the authors report that serum Mg2+ serum levels decrease in patients with DILI as well as in preclinical animal models treated with acetaminophen overdose, and that early intervention targeting the Mg2+ transporter Cyclin M4 may be beneficial for acetaminophen overdose in preclinical models.

The molecular mechanisms underlying metastasis in pheochromocytoma/paraganglioma (mPPGL) remain to be explored. Here, the authors perform genomic and immunogenomic profiling of mPPGL tumors and suggest potential biomarkers for risk of metastasis and immunotherapy response.

Studies of species interactions tend to focus on single ecological functions. Here, the authors show that plant species tend to participate across different ecological functions in a non-random, nested structure, and some species and functions emerge as unexpected keystone actors of the multifunctional ecosystem.

Analysis of data from California prisons shows that both COVID-19 vaccination and prior SARS-CoV-2 infection reduces the risk of virus transmission to close contacts.

An analysis of 52 million births in 26 countries shows small reductions in preterm birth during the first to third months of lockdown. Further research is needed to examine causal pathways.

The palaeoenvironmental context for early hominins in northern Africa during the Plio-Pleistocene transition is poorly documented. Here, the authors present multiproxy palaeoecological evidence for heterogeneous open grasslands, forested areas, wetlands, and seasonal aridity from Guefaït-4.2 in Morocco.

Huntington's disease is a neurodegenerative disorder associated with glutamate receptor dysfunction. Now Isabel Pérez-Otaño and colleagues report that the HTT protein that aggregates in the brains of individuals with the disease disrupts the ability of the adaptor protein PACSIN1 to keep the glutamate receptor subunit GluN3A away from the surface of neurons.

A general approach to address the 'phase problem' in protein crystallography is described, allowing protein structures to be directly solved from 2 Å resolution diffraction data without using heavy atom doping or relying on a preexisting structure model for molecular replacement.

Targeted inhibition of the ERK-MAPK pathway is challenged by the development of resistance and toxicity. Here, the authors show that SHOC2 genetic inhibition impairs lung tumour development and improves MEK inhibitor efficacy in RAS- and EGFR-mutant cells.

VVD-133214, a clinical-stage, covalent allosteric inhibitor of the helicase WRN, was well tolerated in mice and led to robust tumour regression in multiple microsatellite-instability-high colorectal cancer cell lines and patient-derived xenograft models.

This study presents the first annual update of the indicator framework developed by the Food Systems Countdown Initiative, published in Nature Food in 2023. Almost half of all indicators show some desirable trends. Governance and resilience indicators were revealed as the most connected across themes, constituting entry points for transformative change.

The function of macrophages in myeloid leukaemia can be difficult to assess because of lack of differentiation between transformed and non-transformed cells. Here the authors use a chimeric mouse model to characterise the effect of myeloid leukaemia on bystander macrophages noting altered functional properties of these cells.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

In vivo partial reprogramming by expression of Oct4, Sox2, Klf4 and c-Myc has been shown to have rejuvenating effects in a mouse model of premature aging. Here, the authors report that longer-term partial reprogramming regimens are safe and effective in delaying age-related changes in physiologically aged mice.

Valik et al. incorporate genomic biomarkers from Pseudomonas aeruginosa isolates and clinical data into machine-learning models to predict the severity of bloodstream infection. Bacterial virulence markers identified through whole genome sequencing offer prognostic insights that could inform treatment strategies in sepsis management.

Bhattacharjee and Schaeffer et al. map exclusive breastfeeding (EBF) in 94 low- and middle-income countries (LMICs), finding increased EBF practice and reduced subnational variation across the majority of LMICs from 2000 to 2018. However, only six LMICs will meet WHO’s target of ≥70% EBF by 2030 nationally, and only three will achieve this in all districts.

Antibody mediated immunity to SARS-CoV-2 will affect future transmission and disease severity. This systematic review on antibody response to coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and endemic coronaviruses provides insights into kinetics, correlates of protection, and association with disease severity.

Multiyear analysis of antibody responses in recipients of the dengue vaccine Dengvaxia in the Philippines supports their utility as a predictor of protection against disease, and reveals that Dengvaxia efficacy declines 3 years after complete vaccination.

Short term systemic expression of the reprogramming factors Oct-3/4, Sox2, Klf4, c-Myc (OSKM) rejuvenates aging cells and promotes tissue regeneration. Here the authors show that myofiber-specific expression of OSKM accelerates muscle regeneration by reducing secretion of muscle stem cell quiescence promoting Wnt4.

Herd immunity to dengue acts at the household level according to a longitudinal, multigenerational cohort study.

Indoor residual spraying (IRS) of insecticide is one of the primary malaria vector control initiatives, but implementation is limited. Here, the authors show that discontinuation of IRS in Uganda was associated with increased malaria incidence, and introduction of IRS was associated with decreased incidence.

Newly emerged pathogens are inherently difficult to forecast, due to many unknowns about their biology early in an epidemic. Here, the authors assess forecasts of a suite of models during the Zika epidemic in Colombia, finding that the models that performed best changed over the course of the epidemic.

Population-based surveys are the gold standard for estimating seroprevalence but are expensive and often only capture a small geographic area or window of time. This study describes a new platform, SCALE-IT, for serosurveillance based on algorithmic sampling of electronic health records, and uses it to estimate the seroprevalence of SARS-CoV-2 in San Francisco.

Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology. Here, the authors investigated whether plasma ptau181 could be a potential biomarker of AD in individuals with Down syndrome (DS) and find plasma p-tau181 can detect AD in DS adults.

An algorithm and software tool, Borges, utilizes nonspecific tertiary-structure fragment information available in the Protein Data Bank to phase protein X-ray diffraction data.