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Human papillomavirus (HPV)-associated oropharyngeal cancer is increasing but the natural history of oral HPV infection is not well understood. Here, the authors investigate clearance of oncogenic oral HPV infection in a cohort of men from the US, Brazil, and Mexico.

The JAK inhibitor ruxolitinib has been used for treatment of myeloproliferative neoplasms (MPN) and its association with clonal evolution requires further investigation. Here the authors report accumulation of RAS pathway mutations in ruxolitinib-treated myelofibrosis patients, stemming from RAS clonal selection induced by JAK2 inhibition.

The authors examine the impact of monthly unconditional cash transfers starting at childbirth on families with low incomes. Transfers had minimal effects on family processes and maternal wellbeing, but improved family incomes and time mothers spent doing enriching activities with their child.

Tan and colleagues conducted a single-cell multiomic analysis of T cell acute lymphoblastic leukemia and identified a treatment-resistant subpopulation of bone marrow progenitor-like blasts associated with poor outcomes.

Peptide-based cancer vaccines require epitopes for both CD8+ and CD4+ T cells. Here the authors report the long-term outcomes of a randomized phase II trial (NCT00118274) in patients with melanoma designed to evaluate a class I MHC-restricted peptide vaccine plus one of two “helper” peptide preparations to stimulate CD4+ T cells, either non-specific help or melanoma-specific help.

Reducing levels of mitochondrial iron by diet or pharmacological chelation ameliorates symptoms of cigarette smoke–induced chronic obstructive pulmonary disease in mice.

Intranasal inoculation of BALB/c and C57BL/6J mice with the bovine H5N1 clade 2.3.4.4b virus  results in rapid fatal disease characterized with high viral titers in lung and brain. Interestingly, only the C57BL/6J mice develop neurologic disease.

Proteins usually expressed solely in the testes are often found over-expressed in cancer and are termed cancer testis antigens. Here, the authors use a comprehensive screening strategy to identify 26 cancer-testis antigens that promote tumorigenic behaviour.

Li et al. uncover a lysosomal surveillance response whereby intestinal lumen deacidification induces a transcriptional programme that boosts lysosomal activity and improves protein aggregate clearance in multiple worm disease models, extending healthspan.

In the phase 3 EVER-132-002 trial, patients with HR⁺HER2⁻ metastatic breast cancer from Asia were treated with the Trop-2-directed antibody–drug conjugate sacituzumab govitecan or chemotherapy, and those receiving sacituzumab govitecan experienced prolonged progression-free survival compared with patients treated with chemotherapy.

Comprehensive genomic and transcriptomics analyses of more than 1,300 cases of childhood T-lineage acute lymphoblastic leukaemia identify 15 distinct subtypes that are associated with specific outcomes.

Authors perform an analysis of the patient data and risk factors to evaluate unfavorable outcomes and adverse events in adults with pulmonary tuberculosis treated with a 4-month rifapentine based regimen. Low rifapentine exposure was the most clinically significant risk factor for treatment failure and tuberculosis relapse.

Cage change of mice with persistent murine astrovirus infection triggers stress responses marked by corticosterone fluctuation, which is followed by CD8 T cell activation and induction of epithelial antiviral responses leading to viral clearance.

Analysis of a large cohort of EGFR-mutant lung cancer cell-free DNA samples along with longitudinal samples from a patient with EGFR-mutant lung cancer identifies pathways that inhibit EGFR-inhibitor response. Co-occurring genetic alterations influence clinical outcomes and underscore the need for combination therapies.

In an analysis of adult patients with hematologic malignancies who received anti-CD19 chimeric antigen receptor T cell therapy, baseline gut microbiome composition was correlated with clinical response and treatment with broad-spectrum antibiotics in the four weeks prior to infusion was associated with worse survival and increased neurotoxicity.

In cancer, the impact on cellular fitness of copy-number gains affecting collaterally-amplified genes remains poorly understood compared to oncogenes. Here, the authors integrate genomic data from tumours and cell lines and identify a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes, with potential therapeutic applications.

Multinational analysis of oral human papillomavirus infection incidence and associated factors in 3,137 men reveals infection risk is maintained throughout lifetime, with implications for vaccination strategies.

Pancreatic cancer patients have previously been noted to have a change in medication history prior to diagnosis. Here, the authors utilise two large population cohorts to show associations between recent medication changes and risk of a subsequent pancreatic cancer diagnosis.

A genomic and transcriptomic analysis of 2,754 childhood acute lymphoblastic leukemias identifies 376 putative driver genes, and associations between disease subtypes and prognosis.

Transcriptomic and metabolic profiling reveals that the creatine kinase pathway is essential for growth of acute myeloid leukemias expressing the transcription factor EVI1.

Elevated levels of interleukin-33 have been associated with poor prognosis in patients with glioma. Here the authors show that glioma-derived IL-33 modulates a pro-tumorigenic immune microenvironment by activating resident and recruiting peripheral innate immune cells.

In this randomized controlled trial, Gennetian et al. evaluated the impacts of cash transfers on family investments. Families with low income were randomized to receive monthly unconditional cash starting at childbirth. Households spent more money and time on child-specific goods and learning activities.

The majority of cancer patients do not respond to single agent immune checkpoint blockade and several combinatorial approaches have now been tested. Here the authors report the results of a phase I dose escalation trial of nivolumab (anti-PD1) in combination with IFN-γ in patients with advanced solid tumors.

The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

Pancreatic cancer cells may develop resistance to KRAS inhibitors due to activation of compensatory pathways. In this study, the authors demonstrate that KRAS is dispensable in a subset of pancreatic cancer and that PI3K signalling may have an important role in mediating tumor growth following KRAS inhibition.

Mishra et al. have generated mice with a single amino acid substitution in BRCA2, which disrupts its interaction with DSS1 resulting in a severe HR defect. They show the interaction to be dispensable for HR at replication induced and meiotic DSBs.

Armstrong and colleagues discover that combined targeting of IKAROS and MENIN is a therapeutic strategy for acute myeloid leukemia through disruption of essential leukemogenic transcriptional programs.

Longitudinal genomic and transcriptomic profiling of 1,143 patients with multiple myeloma by the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study yields an improved copy number and gene expression subtype scheme, most notably a high-risk proliferative subtype associated with complete loss of RB1 or MAX.

Yang and colleagues perform a network system–pharmacology approach and clinical data integration, and identify LCK and BCL2 signaling as the molecular determinants of dasatinib response in pediatric and adult patients with T-ALL.

Despite its great potential, immune checkpoint blockade has shown efficacy in only a restricted number of patients. In this Article, the authors present a nano-based platform for the co-delivery of chemo- and immunotherapeutics that shows efficient synergic antitumour activity in large, hard-to-treat tumour models.

BET-bromodomain inhibitors could be used to treat medulloblastoma tumors with Myc amplifications. Here, the authors show that both the response and resistance to BET inhibitors in mice is mediated by bHLH/homeobox transcription factors.

CDK4/6 inhibitors are standard-of-care treatment of breast cancer, however resistance is common. Here, the authors analyse real world multi-omics data from 400 breast cancer patients and identify bifurcated evolutionary trajectories associated with ER independent resistance.

In a study of children with high genetic risk aged 2 years or older, a risk score integrating pancreatic islet autoantibodies, genetic factors and family history is highly predictive of type 1 diabetes in the subsequent 8 years.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

Patient-derived xenografts provide a resource for basic and translational cancer research. Here, the authors generate multiple pediatric high-grade glioma xenografts, use omics technologies to show that they are representative of primary tumours and use them to assess therapeutic response.

p53 inactivation is nearly universal in small-cell lung cancer (SCLC), but its tumor suppressive role in this cancer type is poorly understood. Here the authors show that intertumoral heterogeneity in SCLC influences the biological mechanisms of p53-mediated tumor suppression and identify a role for cyclophilins in p53-dependent necrotic cell death.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Cross-talk between innate immune cells helps to enhance the antitumor T cell response during checkpoint blockade therapy.

Parkinson’s disease (PD) is linked to environmental factors. Through quantitative epidemiology, this study ties 53 pesticides to PD. An innovative human stem cell platform revealed that 10 of these were directly toxic to human dopamine neurons.

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.

While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2. Here, Rosenke et al. provide evidence that orally delivered MK-4482, a nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model.

The overexpression of Esyt1 presynaptic organiser in V1 spinal interneurons restores connectivity, increases motor neuron survival, and ameliorates motor phenotypes in ALS mice. So, inhibitory interneurons are a target to attenuate ALS symptoms.

The mechanisms through which gut microbiota affect extramucosal tumors are poorly understood. Here the authors show that the gut microbiota promotes multiple myeloma by inducing differentiation and migration of Th17 cells in the bone marrow resulting also in increased recruitment of pro-tumorigenic eosinophils.