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COPD-related modification to the airway epithelium permits intracellular residence of nontypeable haemophilus influenzaeOur findings indicate that COPD, cigarette smoke and macrolide antibiotics potentiate the susceptibility to persistent intracellular NTHi
Research
Methylome-wide association study of central adiposity implicates genes involved in immune and endocrine systemsWe 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-inThere 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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Decreased Physical Working Capacity in Adolescents With Nonalcoholic Fatty Liver Disease Associates With Reduced Iron AvailabilityIn a well-defined cohort of adolescents, we found non-alcoholic fatty liver disease to be associated with decreased cardiorespiratory fitness, independent of BMI
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Comparing Web-Based Mindfulness With Loving-Kindness and Compassion Training for Promoting Well-Being in Pregnancy: Protocol for a Three-Arm Pilot Randomized Controlled TrialPromoting psychological well-being and preventing distress among pregnant women is an important public health goal. In addition to adversely impacting the mother's health and well-being, psychological distress in pregnancy increases the risk of poor pregnancy outcomes, compromises infant socioemotional development and bonding, and heightens maternal and child vulnerability in the postpartum period. Mindfulness and compassion-based interventions show potential for prevention and early intervention for perinatal distress.
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Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastomaMedulloblastoma (MB) consists of four core molecular subgroups with distinct clinical features and prognoses. Treatment consists of surgery, followed by radiotherapy and cytotoxic chemotherapy. Despite this intensive approach, outcome remains dismal for patients with certain subtypes of MB, namely, MYC-amplified Group 3 and TP53-mutated SHH. Using high-throughput assays, six human MB cell lines were screened against a library of 3208 unique compounds. We identified 45 effective compounds from the screen and found that cell cycle checkpoint kinase (CHK1/2) inhibition synergistically enhanced the cytotoxic activity of clinically used chemotherapeutics cyclophosphamide, cisplatin, and gemcitabine.
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Prevalence and predictors of vitamin D deficiency in a nationally representative sample of Australian Aboriginal and Torres Strait Islander adultsVitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration <50 nmol/l) is recognised as a public health problem globally. The present study details the prevalence and predictors of vitamin D deficiency in a nationally representative sample (n 3250) of Australian Aboriginal and Torres Strait Islander adults aged ≥18 years. We used data from the 2012-2013 Australian Aboriginal and Torres Strait Islander Health Survey (AATSIHS). Serum 25(OH)D concentrations were measured by liquid chromatography-tandem MS.
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Characteristics of TCR Repertoire Associated With Successful Immune Checkpoint Therapy ResponsesImmunotherapies 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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Aural toilet (ear cleaning) for chronic suppurative otitis mediaChronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane.
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RAD51-Mediated DNA Homologous Recombination Is Independent of PTEN Mutational StatusPTEN mutation occurs in a variety of aggressive cancers and is associated with poor patient outcomes. Recent studies have linked mutational loss of PTEN to reduced RAD51 expression and function, a key factor involved in the homologous recombination (HR) pathway. However, these studies remain controversial, as they fail to establish a definitive causal link to RAD51 expression that is PTEN-dependent, while other studies have not been able to recapitulate the relationship between the PTEN expression and the RAD51/HR function.