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Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

Research in the tropics is unevenly distributed across regions and biomes. Here, the authors find that moist broadleaf forests account for 73% of all tropical citations but cover 29% of the land area, while drier, climate-vulnerable areas with fewer trees remain under-sampled and under-cited.

Improved understanding of the tumor ecosystem in glioblastoma is critical for developing new treatment strategies for the disease. Here, the authors identify pericytes as an active paracrine signaling hub within the tumor parenchyma that orchestrates a tumor-suppressive microenvironment, suggesting pericyte preservation as a key feature of future therapeutic regimens for glioblastoma.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

A rare gene variant has been found that decreases the peptide deposition seen in the brains of people with Alzheimer's disease. The mutation may also slow the normal cognitive decline that occurs with age. See Letter p.96

BRCA-deficient breast cancer is characterised by homologous recombination deficiency. Here, the authors show that hypermethylated BRCA1 phenotypically copies mutated BRCA1 in triple negative breast cancers.

Intense electromagnetic impulses induced by Jupiter’s lightning can produce both low-frequency dispersed whistler emissions and non-dispersed radio pulses. Here, the authors show Jupiter dispersed pulses associated with Jovian lightning that are evidence of low density holes in Jupiter’s ionosphere.

Historical interbreeding between Neanderthals and humans should leave signatures of historical demographics in modern human genomes. Analysing the size distribution of Neanderthal fragments in non-African genomes suggests consistent differences in the generation interval across Eurasia, and that this could explain mutational spectrum variation.

The availability of translated consent documents improves recruitment of patients with limited English proficiency to clinical trials, indicating a potentially modifiable barrier to the inclusion of patients with limited English proficiency.

Mass extinctions have repeatedly restructured communities through geological time, but biotic interactions are rarely considered in investigations of extinction dynamics and ecosystem recovery. Here the authors present evidence that secondary extinction cascades were important during a Jurassic hyperthermal extinction event and that it took over 7 million years for community structure to fully recover.

In this genomic analysis of peripheral blood samples of the phase 3 CheckMate-067 trial of ipilimumab (IPI) versus nivolumab (NIVO) versus ipilimumab and nivolumab (IPI-NIVO) in melanoma, the status of certain mitochondrial haplogroups in patients was associated therapeutic resistance to NIVO or IPI-NIVO, a finding validated in an independent cohort.

Lateral root development is dependent on precise control of the distribution of the plant hormone auxin. Here Chen et al. propose the transcription factors ARF7 and FLP participate in a feed forward motif to mediate expression of the auxin transporter PIN3and consequently regulate lateral root development.

Methylmercury in aquatic biota constitutes a severe environmental issue globally, but models struggle to provide accurate quantification. Here, the authors combine experimental approaches to assess contributions from different pools and use the data to interpret the mercury cycle in an estuarine setting.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The ferroptosis suppressor protein FSP1 has a critical role in ferroptosis protection of tumours across multiple in vivo models and is linked to worse prognosis in human lung adenocarcinoma, suggesting its potential as a therapeutic target in lung cancer.

The opening of a Dirac point gap in topologically non-trivial materials is key to potential applications. Here, the authors use photoelectron spectroscopy to study gap formation and carrier mass acquisition in a topological crystalline insulator as a function of composition and temperature.

To measure selection on variants, whole-genome sequencing of approximately 150,000 individuals from the UK Biobank is used to rank sequence variants by their level of depletion.

Removing fossil fuel subsidy could reduce the CO₂ emissions and improve the use of government budget, while the feasibility is in doubt. This research demonstrates the public attitudes in developing countries are not worse than that for carbon tax, and better use of the public fund is preferred.

The joint analysis of datasets from NOvA and T2K, the two currently operating long-baseline neutrino oscillation experiments, provides new constraints related to neutrino masses and fundamental symmetries.

A large fraction of patients with melanoma still does not benefit from immune checkpoint blockade, associated with both primary and acquired resistance. Here the authors report genetic and immunological patterns of resistance in patients with melanoma after progression on anti-CTLA4 or anti-PD1 monotherapy.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

Therapeutic T cells engineered to recognize tumour antigens are frequently short-lived and acquire unfavourable phenotypes in tumours. Here authors show that a tandem approach using autologous T cells targeted against the tumour antigen NY-ESO-1, followed by transfer of hematopoietic stem cells with the same specificity in the clinical trial NCT03240861, provides a safe and promising therapeutic option.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The largest dense-water plume feeding the lower limb of the Atlantic meridional overturning circulation from the Nordic seas comes from Denmark Strait overflow water. Measurements of hydrography and water velocity north of Iceland and ocean model simulations indicate that a significant part of this water is supplied by the North Icelandic Jet.

The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

In cohort B of the phase 2 SWOG S1512 trial, pembrolizumab monotherapy in patients with unresectable desmoplastic melanoma elicited a complete response rate of 37% and an objective response rate of 89%, supporting a new treatment option for this tumor type.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

Stacy Steinberg, Hreinn Stefansson, Thorlakur Jonsson and colleagues found that rare variants predicted to alter the function of ABCA7 are associated with risk of Alzheimer's disease. The association was found in Iceland and replicated in northern Europe and the United States.