Background In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown. Methods We did an individual participant data meta-analysis of large randomised controlled

Background A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT

Background Patients with relapsed or refractory B-cell non-Hodgkin lymphoma have few treatment options. We aimed to establish the safety and recommended phase 2 dose of epcoritamab, a novel bispecific antibody that targets CD3 and CD20 and induces T-cell-mediated cytotoxic activity against CD20+ malignant B cells. Methods For the dose-escalation part of this phase 1/2 study, we enrolled adults (aged

Progress has been made in the prevention and treatment of community-acquired bacterial meningitis during the past three decades but the burden of the disease remains high globally. Conjugate vaccines against the three most common causative pathogens (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae) have reduced the incidence of disease, but with the replacement by non-vaccine

Hypertrophic cardiomyopathy (HCM) is often caused by pathogenic variants in sarcomeric genes and characterized by left ventricular (LV) hypertrophy, myocardial fibrosis and increased risk of heart failure and arrhythmias. There are no existing therapies to modify disease progression. In this study, we conducted a multi-center, double-blind, placebo-controlled phase 2 clinical trial to assess the safety

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Our study suggests that the global CO2 fertilization effect (CFE) on vegetation photosynthesis has declined during the past four decades. The Comments suggest that the temporal inconsistency in AVHRR data and the attribution method undermine the results’ robustness. Here, we provide additional evidence that these arguments did not affect our finding and that the global decline in CFE is robust.

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Science, Volume 373, Issue 6562, Page 1452-1452, September 2021.

Wang et al. (Research Articles, 11 December 2020, p. 1295) reported a large decline in the CO2 fertilization effect (CFE) on global photosynthesis, on the basis of changing regression coefficients of CO2 (β) for satellite proxies/products of photosynthesis. We show that their methods cannot robustly estimate CFE, leading to incorrect attribution, and largely neglect CO2 effects on the photosynthetic

Wang et al. (Research Articles, 11 December 2020, p. 1295) reported a large decrease in CO2 fertilization effect (CFE) across the globe during the period 1982–2015 and suggested that ecosystem models underestimate the rate of CFE decline. We find that their claims are artifacts of incorrect processing of satellite data and problematic methods for deriving and comparing CFE between satellite data and

Wang et al. (Research Articles, 11 December 2020, p. 1295), using photosynthesis proxies from long-term satellite records, report a significant decline in CO2 fertilization effects. We find that small systematic biases in Advanced Very High Resolution Radiometer (AVHRR) data affect their analysis to the degree that the key finding is not robust. Caution is recommended when using AVHRR to detect changes

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The sequencing of the human genome has allowed the study of the genetic architecture of common diseases: the number of genomic variants that contribute to risk of disease and their joint frequency and effect size distribution. Common diseases are polygenic, with many loci contributing to phenotype, and the cumulative burden of risk alleles determines individual risk in conjunction with environmental

Recent advancements in DNA sequencing technologies and laboratory preparation protocols have rapidly expanded the scope of ancient DNA research over the past decade, both temporally and geographically. Discoveries include interactions between archaic and modern humans as well as modern human population dynamics, including those coinciding with the Last Glacial Maximum and the settlement history of

Cancer is a major cause of global mortality underpinned by genomic and epigenomic derangements. Here, we highlight the importance of multimodal data integration in understanding the molecular evolution of malignant cell states across the cancer life cycle. The widespread presence of driver mutations and epigenetic alterations in normal-appearing tissues is prompting a reassessment of how cancer initiation

Over the next decade, the primary challenge in human genetics will be to understand the biological mechanisms by which genetic variants influence phenotypes, including disease risk. Although the scale of this challenge is daunting, better methods for functional variant interpretation will have transformative consequences for disease diagnosis, risk prediction, and the development of new therapies.

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Defects may display high reactivity because the specific arrangement of atoms differs from crystalline surfaces. We demonstrate that high-temperature steam pretreatment of palladium catalysts provides a 12-fold increase in the mass-specific reaction rate for carbon-hydrogen (C–H) activation in methane oxidation compared with conventional pretreatments. Through a combination of experimental and theoretical

Starches, a storage form of carbohydrates, are a major source of calories in the human diet and a primary feedstock for bioindustry. We report a chemical-biochemical hybrid pathway for starch synthesis from carbon dioxide (CO2) and hydrogen in a cell-free system. The artificial starch anabolic pathway (ASAP), consisting of 11 core reactions, was drafted by computational pathway design, established

Many human proteins contain domains that vary in size or copy number because of variable numbers of tandem repeats (VNTRs) in protein-coding exons. However, the relationships of VNTRs to most phenotypes are unknown because of difficulties in measuring such repetitive elements. We developed methods to estimate VNTR lengths from whole-exome sequencing data and impute VNTR alleles into single-nucleotide

The normal state of optimally doped cuprates is dominated by the “strange metal” phase that shows a linear temperature (T) dependence of the resistivity persisting down to the lowest T. For underdoped cuprates, this behavior is lost below the pseudogap temperature T*, where charge density waves (CDWs), together with other intertwined local orders, characterize the ground state. We found that the T-linear

Archaeologists and researchers in allied fields have long sought to understand human colonization of North America. Questions remain about when and how people migrated, where they originated, and how their arrival affected the established fauna and landscape. Here, we present evidence from excavated surfaces in White Sands National Park (New Mexico, United States), where multiple in situ human footprints

Topological insulator lasers are arrays of semiconductor lasers that exploit fundamental features of topology to force all emitters to act as a single coherent laser. In this study, we demonstrate a topological insulator vertical-cavity surface-emitting laser (VCSEL) array. Each VCSEL emits vertically, but the in-plane coupling between emitters in the topological-crystalline platform facilitates coherent

The development of silicon anodes for lithium-ion batteries has been largely impeded by poor interfacial stability against liquid electrolytes. Here, we enabled the stable operation of a 99.9 weight % microsilicon anode by using the interface passivating properties of sulfide solid electrolytes. Bulk and surface characterization, and quantification of interfacial components, showed that such an approach

Cardiomyocyte (CM) replacement is very slow in adult mammalian hearts, preventing regeneration of damaged myocardium. By contrast, fetal hearts display considerable regenerative potential owing to the presence of less mature CMs that still have the ability to proliferate. In this study, we demonstrate that heart-specific expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) induces adult CMs to dedifferentiate

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Science, Volume 373, Issue 6562, Page 1449-1449, September 2021.

Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover/spillback events between humans and animals. To develop prevention and therapeutic strategies, we

ATP-binding cassette (ABC) transporters couple ATP hydrolysis to substrate transport across biological membranes. Although many are promising drug targets, their mechanisms of modulation by small molecule inhibitors remain largely unknown. Intriguingly, two first-generation inhibitors of the MsbA transporter, TBT1 and G247, induce opposite effects on ATP hydrolysis. Using single-particle cryo-electron

Most multicomponent high-entropy alloys (HEAs) lose ductility with increasing strength, similar to conventional materials. We controllably introduced novel gradient nano-scaled dislocation-cell structures in one stable single-phase face-centered-cubic HEA, which result in enhanced strength without apparently losing ductility. The sample-level structural-gradient induces the progressive formation of

Collaboration between coastal communities and sprawling metropolises helps the drive to meet UN targets.

Nature highlights three key infographics from the week in science and research.

Cluster of tiny tube-shaped devices creates an intense, focused light source.

Catalyst based on nickel and iron allows electrical current to be harvested from the breakdown of urea.

Local challenges help to explain why some goals are prioritized over others.

A slippery slope.