Search

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Activity recognition in live-cell imaging is laborious. Here, authors present, IVEA, a fully automated AI ImageJ plugin, that efficiently detects and classifies exocytosis events, from synaptic transmission to single-vesicle fusion, across cell types and imaging setups.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

Multisystem inflammatory syndrome following SARS-CoV-2 infection results from increased serum levels of TGFβ, which impairs the reactivation of virus-specific T cells.

While fluid restriction is typically recommended for patients with chronic heart failure, this randomized clinical trial showed no difference in health status, as assessed by patient-reported outcomes, between patients recommended to a liberal versus a restrictive fluid regimen over the course of 3 months in an outpatient setting.

Some brain lesions recover in multiple sclerosis, while others do not; however, the underlying mechanisms are unclear. Here, the authors show that microglia-derived TGFα orchestrates immune control and tissue repair, and that intranasal delivery of TGFα in the autoimmune encephalomyelitis model promotes lesion resolution.

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.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

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.

We illustrate that including data from Greenlandic Inuit can greatly reduce inequity in genomic-based healthcare in Greenland and other indigenous Arctic populations.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

Our understanding on the humoral immunity induced by SARS-CoV-2 is still lacking. Here the authors analyze B cell responses at the single cell level to find that, in severe COVID-19 patients, plasmablasts shift from IFN to TGFβ instruction to produce IgA antibodies that are not specific to dominant SARS-CoV-2 antigens.

Cancer is often associated with mutant transcription factors (TFs) but their functional characterization is challenging. Here, the authors describe a recurrent mutation within TF IRF4 in human lymphomas and they show how it causes a complex switch in TF specificity and functionality.

Approximately half of the people currently with multiple sclerosis (MS) are ≥50 years of age, yet guidelines for management of MS in older age are lacking. This Consensus statement presents the outcomes of an International Advisory Committee on Clinical Trials (IACCT) in MS workshop on ageing and MS, including recommendations for advancing research, care and awareness.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

It is challenging to approach protein structures in living cells. Here the authors investigate Interleukin-4 receptor alpha, which has a noncanonical amino acid incorporated at different locations, and see that evaluating click efficiency with calibrated imaging gives information on structure-related properties.

Establishing the relative transmissibility of emerging variants of SARS-CoV-2 is key for pandemic management. Here, the authors use full-population administrative data from Denmark linked to PCR test results and estimate that the Alpha variant was ~60% higher than other strains circulating in early 2021.

Traumatic brain injury is associated with changes to the metabolome. Here the authors show that acute traumatic brain injury has distinctive serum metabolic patterns which may suggest protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Linnerbauer and colleagues find that HB-EGF produced by reactive astrocytes is protective during autoimmune neuroinflammation, but epigenetically suppressed during late stages.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Peter Campbell, Mel Greaves and colleagues use exome and whole-genome sequencing to characterize somatic mutations in childhood acute lymphoblastic leukemias with the ETV6-RUNX1 fusion gene. They find that RAG-mediated deletions are the dominant mutational process.

After infection with SARS-CoV-2, individuals show a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and a greater reduction in global brain size.

Tan et al. reveal that a class of lipids, 3-sulfogalactosyl diacylglycerols, decrease in the central nervous system with aging. 3-sulfogalactosyl diacylglycerols are present in the human brain and suppress inflammation suggesting these lipids may play a role in age-related diseases and inflammation.

In the non-randomized phase 3b/4 DESTINY-Breast12 study, trastuzumab deruxtecan (T-DXd) treatment of patients with HER2⁺ advanced breast cancer and active or stable brain metastases showed consistent intracranial activity and systemic efficacy of T-DXd.

Yeast and cancer cells both favor sugar fermentation in aerobic conditions. Here the authors describe a conserved mechanism from yeast to mammals where the glycolysis intermediate fructose-1,6-bisphosphate binds Cdc25/Sos1 and couples increased glycolytic flux to increased Ras proto-oncoprotein activity.

Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.

Douglas Easton and colleagues report a genome-wide association analyses for breast cancer in ~70,000 cases and ~68,000 controls. They identify three new breast cancer susceptibility loci, two of which show association only with estrogen receptor–positive disease.

In many solution systems, nanometre-sized structural units are present before nucleation, but little is known about these pre-nucleation clusters. Habraken et al.show that, for the crystallization of calcium phosphate, these nanometre-sized units are calcium triphosphate complexes.

Radiotherapy can induce fibrosis in cancer patients, limiting its use in clinical settings. Here, the authors identify a differentially methylated enhancer of the lipid kinase DGKA in fibroblasts from breast cancer patients developing fibrosis after radiotherapy and they show that DGKA inhibition affects lipid homeostasis and reduces pro-fibrotic fibroblast activation.

Activation of telomere maintenance mechanisms—caused by novel somatic rearrangements of TERT, by MYCN amplification, or ATRX mutations—is a hallmark of high-risk neuroblastomas.

Advanced ecological modelling reveals how Sahul (Australia and New Guinea) was first peopled, suggesting the most probable routes and surprisingly rapid early settlement of this continent by anatomically modern humans starting 50,000 to 75,000 years ago.

Typically, microbial methane production occurs under oxygen-free conditions and abiotic methane production occurs under harsh conditions. Here, the authors show methane production from organosulphur compounds under ambient conditions, suggesting a role for these compounds in methane formation in the environment.

Alexander Schramm, Johannes Schulte and colleagues characterize 16 paired samples from patients with neuroblastoma at diagnosis and relapse using whole-exome sequencing, mRNA expression profiling, array CGH and DNA methylation analysis. Their data show the frequency, identity and evolution of genetic alterations in neuroblastoma.

Here, using an integrative experimental and computational approach, Imle et al. show how cell motility and density affect HIV cell-associated transmission in a three-dimensional tissue-like culture system of CD4⁺ T cells and collagen, and how different collagen matrices restrict infection by cell-free virions.

The surface-directed mineralization of calcium phosphate from simulated body fluid is studied by cryogenic transmission electron microscopy. Prenucleation clusters aggregate close to the surface, then amorphous calcium phosphate forms in this region, leading to the nucleation of oriented apatite crystals at the surface.

On 22 December 2018, the western flank of Anak Krakatau collapsed into the sea of the Sunda Strait triggering a tsunami which killed approximately 430 people and displaced 33,000. Here, the authors show that Anak Krakatau exhibited an elevated state of activity several months prior to the collapse, including precursory thermal anomalies, an increase in the island’s surface area, and a gradual seaward motion of the southwestern flank.

Dewald et al. combine a non-invasive sampling approach (Lolli-Test) with an RT qPCR-pool testing strategy to screen for SARS-CoV-2 infections in children and use the method for surveillance and infection control in > 4000 school and daycare settings.