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Wastewater surveillance for disease outbreaks currently requires lab testing which causes delays. Here, authors develop ultra-sensitive quantum sensors enabling 2-hour near-source pathogen detection from raw wastewater with high sensitivity and specificity, creating a portable “lab-in-a-suitcase” system.

APOBEC mutational signatures are commonly found in multiple cancer types. Here, the authors utilize multi-omics analyses to reveal that the cooccurrence of APOBEC associated mutagenesis and tobacco-smoking-related mutations affects lung tumor evolution and age at onset of lung cancer from smokers.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

The heterogeneity of tumor evolution from AR-positive, adenocarcinoma to AR-negative, neuroendocrine prostate cancer (NEPC) is not fully characterized. Here the authors generate a mouse model to show that Rb1 loss and MYCN overexpression accelerates the progression to AR-negative NEPC and identify emergence of distinct subpopulations of NEPC cells.

Vaccination efficiency in HIV infection is hampered by the low immunogenicity of HIV-1 Env glycoprotein (Env). Here authors optimise the neutralising antibody response to Env by stabilizing the Env trimers in the context of expressing them in a Newcastle Disease Virus-like particle and providing conditions that mimics replicating virus infection.

Lipidomics revealed that neurons of patients with ALS/FTD have reduced levels of polyunsaturated fatty acid (PUFA)-containing phospholipids. Increasing neuronal PUFA levels increased survival of Drosophila models of ALS/FTD and patient neurons, suggesting that interventions that increase neuronal PUFA levels in patients with ALS/FTD may also be beneficial.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

The molecular mechanisms underlying malignant transformation of the Schwann lineage in Schwann cell tumours remain to be explored. Here, the authors suggest that NF2 inactivation leads to PAK activation leading to NF1-mutant Schwann cell tumour de-differentiation and resistance to selumetinib.

Patients with mild COVID-19 show a pattern of interferon-stimulated gene (ISG) expression across all major cell types, but in patients with severe disease, antibodies block the production of these ISG-expressing cells.

Early-career researchers have been particularly impacted by the COVID-19 pandemic. To re-assemble the supramolecular research community, the inaugural Women in Supramolecular Chemistry workshop promoted a community-led approach to skills development, as Ruhee Dawood and Alyssa-Jennifer Avestro recount.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Characterization of medulloblastoma tissues using single-cell transcriptomics shows that the different molecular subtypes consist of distinct developmental phenotypes.

C9orf72 ALS/FTD polyGR and polyPR knock-in mice show cortical hyperexcitability and motor neuron loss accompanied by an increase in extracellular matrix proteins in the spinal cord that is conserved in patient iPS cell-derived neurons and is neuroprotective.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

p53 is shown to have a pivotal role in the differentiation of alveolar type 1 cells in cancer and alveolar repair after injury, and loss of this governance can promote diseases such as lung adenocarcinoma.

CRISPR-CasRx effectively reduces ALS- and FTD-causing C9orf72 sense and antisense repeat derived RNAs and proteins in cell lines, patient iPSC-neurons and two independent mouse models of C9orf72 repeat expansion.

Gut microbes influence our health and may contribute to human adaptation to different lifestyles. Here, the authors describe the gut microbiome of a community of hunter-gatherers and identify unique features that could be linked to a foraging lifestyle.

Compound MMV006833 inhibits ring-stage development of Plasmodium falciparum. Here, the authors show that it targets lipid transfer enzyme PfSTART1 and prevents PfSTART1 from expanding the vacuole membrane encasing the parasite after red blood cell invasion, thereby blocking parasite growth.

Specific actions to develop equitable partnerships in microbiome research are proposed.

In this work, authors assess airway microbiome dynamics to show bacterial pneumonia in critically ill COVID-19 patients is significantly associated with death, corticosteroid treatment, disruption of the lung microbiome and a distinct pulmonary host response.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Using a global interaction dataset, the authors quantify the distribution of trophic interactions among marine fish, finding a high degree of geographic connectivity but low spatial modularity.

Dexamethasone has been used in the treatment of critically ill COVID-19 patients. Here the authors apply transcriptomics to investigate the effects of dexamethasone treatment in COVID-19 patients, and show both systemic and compartment-specific effects.

Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.

Development of a single-molecule photobleaching method, SiMPull-POP, allowed to discover that the lipid cholesterol inhibits assembly of the receptor tyrosine kinase EphA2, which prevents oncogenic signalling by the receptor.

A diagnostic tool based on blood RNA-seq is shown to identify causal genes and variants linked to clinical phenotypes in individuals with rare diseases for which whole-exome genetic sequencing was uninformative.