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Here the authors use drug susceptibility data from Plasmodium falciparum field isolates in a pharmacometric model to evaluate cabamiquine and pyronaridine efficacy, both individually and in combination. The combined treatment shows over 90% parasite reduction in most simulated cases, providing valuable guidance for clinical dose selection in real-world settings.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Climate change adaptation policies could influence public decarbonization behaviours positively or negatively, impacting further mitigation and adaptation efforts. This study examines public responses to planned power outages in California and finds that the outages shaped some energy behavioural intentions but did not alter climate or energy policy preferences.

Antimicrobial peptides are identified from metagenomics data using deep learning.

Microbial communities, exposed to early Earth-like conditions in a modern microbialite reef, change cyclically due to seasonal environmental variations, implying evolved metabolic processes in microbialites over time, based on multiple chemical, physical, and biological analyses.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

Tirofiban is an inhibitor of platelet αIIbβ3 which may contribute to venous thrombosis. Here the authors developed a non-agonizing modified tirofiban, defined by its cryo-EM structure bound to platelet αIIbβ3 and elucidated the pathogenic role of αIIbβ3 in venous thrombogenesis.

Michaelson et al. report that human SYNGAP1 variation alters touch-related sensory processing. Studies in Syngap1 mice revealed circuit-specific impairments in the somatosensory cortex that underlie reduced cortical activation in response to touch.

Intravascularly infused extracellular matrix from ventricular myocardium binds to leaky vasculature and induces the regeneration of inflamed heart tissue, as shown in rats and pigs.

The equilibrium response of global temperatures to an increase in atmospheric carbon dioxide concentrations is difficult to quantify. Simulations and proxy data of the mid-Pliocene warm climate suggest that the response is 30 to 50% higher than traditionally calculated when slowly adjusting components of the Earth system, such as ice sheets and vegetation, are included in the estimate.

The neural mechanisms underlying how the brain generates internal models of the environment is not fully understood. Here authors show that mouse perirhinal cortex is involved in forming stable stimulus-outcome associations, possibly via cholinergic signaling.

Epilepsy is a brain network disorder with associated genetic risk factors. Here, the authors show that spatial patterns of transcriptomic vulnerability co-vary with structural brain network alterations in focal and generalized epilepsy.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

An inhibitor of NAPE-PLD involved in lipid biosynthesis lowers levels of the endocannabinoid anandamide and other N-acylethanolamines in cells and mouse brain and activates the hypothalamus–pituitary–adrenal axis and impaired fear extinction.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Tailored to provide diabetes management recommendations from large training and validation datasets, an artificial intelligence system integrating language and computer vision capabilities is shown to improve self-management of patients in a prospective implementation study.

Mucosal Associated Invariant T cells have been implicated in response to bacterial pathogens. Here the authors show that in human viral infections, these cells are activated by IL-18 in cooperation with other pro-inflammatory cytokines, producing interferon gamma and granzyme B.

A significant proportion of individuals with inherited neuromuscular disease do not receive a genetic diagnosis. Here, the authors establish CCG expansions in the 5’ untranslated region of ABCD3 as a cause of oculopharyngodistal myopathy (OPDM) in individuals of European ancestry and identify increased expression of expansion-containing ABCD3 transcripts as a possible disease mechanism underlying muscle degeneration.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Many SARS-CoV-2 infections may go undetected through conventional PCR or lateral flow tests. Here, the authors analyse the utility of analysing longitudinal nucleocapsid antibody trajectories to improve identification of prior SARS-CoV-2 infections using surveillance data from the UK.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Accounting for near-surface temperature gradients leads to estimates for annual CO₂ uptake in the North Atlantic that are 7% higher, based on a comparison of eddy covariance and bulk CO₂ measurements, which is consistent with theory, laboratory assessments and model analysis.

The molecular mechanisms underlying the Bezold–Jarisch reflex and syncope (fainting) involve vagal sensory neurons that express neuropeptide Y receptor Y2, the deletion of which in animal models abolishes the Bezold–Jarisch reflex.

Taxonomy classification of amplicon sequences is an important step in investigating microbial communities in microbiome analysis. Here, the authors show incorporating environment-specific taxonomic abundance information can lead to improved species-level classification accuracy across common sample types.

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 SMC5/6 complex is critical for genome stability. Here, the authors identify mutations in SLF2 and SMC5 as cause of Atelís Syndrome characterized by microcephaly, short stature, anemia, segmented chromosomes and mosaic variegated hyperploidy.

A study reports the development of an algorithm, BISCUT, that detects genomic loci under selective pressure by relying on the distribution of breakpoints across chromosome arms, and uses it to explore how aneuploidies affect tumorigenesis.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Influenza A H1N1/2009 virus emerged from swine and rapidly replaced the seasonal H1N1 virus. Here, the authors show that natural selection acting on H1N1/2009 after introduction into humans was driven by adaptation to the new host but later selection has been driven by immunological escape.

The authors report on a temperate Earth-sized planet orbiting the cool M6 dwarf LP 791-18 with a radius of 1.03 ± 0.04 R_⊕ and an equilibrium temperature of 300–400 K, with the permanent night side plausibly allowing for water condensation.

T cell receptor (TCR) gene therapy is a promising immunotherapy for cancer and infectious disease. But introducing exogenous TCR α and β chains into T cells may have unintended consequences. In this issue, Bendle et al. show that the transfer of TCR-transduced T cells into mice triggered a lethal pathology that resembles graft-versus-host disease and is caused by the pairing of endogenous and exogenous TCR chains resulting in autoreactive T cells (pages 520–521).

A strong association has been found between three regions of the Plasmodium falciparum genome and sickle haemoglobin in children with severe malaria, suggesting parasites have adapted to overcome natural host immunity.