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Research

Characteristics of TCR Repertoire Associated With Successful Immune Checkpoint Therapy Responses

Immunotherapies have revolutionized cancer treatment. In particular, immune checkpoint therapy (ICT) leads to durable responses in some patients with some cancers. However, the majority of treated patients do not respond. Understanding immune mechanisms that underlie responsiveness to ICT will help identify predictive biomarkers of response and develop treatments to convert non-responding patients to responding ones. ICT primarily acts at the level of adaptive immunity. The specificity of adaptive immune cells, such as T and B cells, is determined by antigen-specific receptors.

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Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows

Systematic comparison of recovered cell types and their transcriptional profiles across the workflows has highlighted protocol-specific biase

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COPD-related modification to the airway epithelium permits intracellular residence of nontypeable haemophilus influenzae

Our findings indicate that COPD, cigarette smoke and macrolide antibiotics potentiate the susceptibility to persistent intracellular NTHi

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Methylome-wide association study of central adiposity implicates genes involved in immune and endocrine systems

We conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist-to-hip ratio and waist-to-height ratio adjusted for body mass index, in 2684 African-American adults in the Atherosclerosis Risk in Communities study.

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Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in

There is a strong unmet need to improve systemic therapy in mesothelioma. Chemotherapy with cisplatin and pemetrexed improves survival in malignant pleural mesothelioma, and immune checkpoint inhibitors are an emerging treatment in this disease. We aimed to evaluate the activity of durvalumab, an anti-PD-L1 antibody, given during and after first-line chemotherapy with cisplatin and pemetrexed in patients with advanced malignant pleural mesothelioma.

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Validation of the Dutch version of the Multidimensional Adolescent Functioning Scale (MAFS)

The Multidimensional Adolescent Functioning Scale (MAFS) is a 23-item, self-report questionnaire assessing psychosocial functioning in adolescents aged 12-17 years. It captures three domains of functioning: 'general functioning', 'family-related functioning', and 'peer-related functioning'. The original English version has good psychometric properties. The aim of the current paper was to translate the MAFS to Dutch and to investigate the psychometric properties of this translation.

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A Meta-analysis on the Role of Children in Severe Acute Respiratory Syndrome Coronavirus 2 in Household Transmission Clusters

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n = 213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a pediatric index case.

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Parent and therapist perspectives on "uptime" activities and participation in Rett syndrome

People with a disability may spend more time sitting and lying (“downtime”) and less time standing and walking (“uptime”). Caregivers and therapists supporting individuals with Rett syndrome were surveyed, aiming to gather insights on how to support participation in “uptime” activities.

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Targeting host-microbial interactions to develop otitis media therapies

Otitis media (OM; middle ear infection) is the most common reason for pre-school children to visit a doctor, be prescribed antimicrobials, or undergo surgery. Recent Cochrane reviews of clinical trials have identified that antibiotics and grommet surgery are only moderately effective in treating OM, with recurrent or persistent infection observed in one-third of children. Research efforts are focusing on developing improved therapies to treat OM and prevent disease recurrence.

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Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced lifespan

Changes in the rate and fidelity of mitochondrial protein synthesis impact the metabolic and physiological roles of mitochondria. Here we explored how environmental stress in the form of a high-fat diet modulates mitochondrial translation and affects lifespan in mutant mice with error-prone or hyper-accurate mitochondrial ribosomes. Intriguingly, although both mutations are metabolically beneficial in reducing body weight, decreasing circulating insulin and increasing glucose tolerance during a high-fat diet, they manifest divergent (either deleterious or beneficial) outcomes in a tissue-specific manner.