Publications by authors named "Catherine John"

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  • The text indicates that there is a correction to a previously published article identified by the DOI 10.1016/j.lanepe.2021.100299.
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  • Readers interested in the original article should refer to this correction for accurate information.
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Objective: Interventions that combat obesity and its associated metabolic perturbations may decrease incidence and improve outcomes of endometrial cancer (EC). Potential options for weight loss include pharmacotherapeutic interventions such as tirzepatide, a dual-acting glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor agonist. Given this, we explored the anti-obesity and anti-tumorigenic effects of tirzepatide in our pre-clinical mouse model of endometrioid EC.

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  • Respiratory infections are a major global health issue, but the genetic factors influencing them are not well understood, leading to this study that aimed to investigate genetic determinants through genome-wide association studies (GWAS).
  • The research analyzed data from 19,459 patients with respiratory infections and 101,438 controls in Stage 1, discovering 56 significant genetic signals, including one strong signal related to a gene important for immune response, but the follow-up Stage 2 study did not replicate these findings.
  • Possible reasons for the lack of replication include variations in how the studies were conducted and differences in patient populations, but the research suggests a novel gene may be linked to susceptibility to respiratory infections, warranting further investigation.
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Purpose: Uterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells.

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Objective: Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells.

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Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and interstitial lung diseases are frequently occurring disorders with a polygenic basis that account for a large global burden of morbidity and mortality. Recent large-scale genetic epidemiology studies have identified associations between genetic variation and individual respiratory diseases and linked specific genetic variants to quantitative traits related to lung function. These associations have improved our understanding of the genetic basis and mechanisms underlying common lung diseases.

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Background: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV) <80% predicted and FEV/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities.

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Reprogramming of fatty acid metabolism promotes cell growth and metastasis through a variety of processes that stimulate signaling molecules, energy storage, and membrane biosynthesis in endometrial cancer. Oleic acid is one of the most important monounsaturated fatty acids in the human body, which appears to have both pro- and anti-tumorigenic activities in various pre-clinical models. In this study, we evaluated the potential anti-tumor effects of oleic acid in endometrial cancer cells and the mouse model of endometrial cancer.

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Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated.

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Endometrial cancer is the most common gynecologic cancer and one of the only cancers for which incidence and mortality is steadily increasing. Although curable with surgery in the early stages, endometrial cancer presents a significant clinical challenge in the metastatic and recurrent setting with few novel treatment strategies emerging in the past fifty years. Ipatasertib (IPAT) is an orally bioavailable pan‑AKT inhibitor, which targets all three AKT isoforms and has demonstrated anti‑tumor activity in pre‑clinical models, with clinical trials emerging for many cancer types.

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Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes.

Methods: Exome sequencing and genome comparisons were used to identify the likely causal variant.

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Article Synopsis
  • Chronic sputum production negatively affects quality of life and this study aims to identify genetic factors linked to this condition through a genome-wide association study (GWAS) involving over 9,700 cases.
  • The GWAS found six significant genetic signals related to chronic sputum production, particularly pinpointing associations with the human leukocyte antigen (HLA) locus and mucin loci, which are also connected to respiratory conditions like asthma.
  • Further analysis revealed that these genetic signals are linked to various health conditions and suggest that mucin fucosylation may play a key role in chronic sputum production.
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  • A major study involving 580,869 participants identified 1,020 genetic signals linked to lung function impairment, which is crucial in understanding chronic obstructive pulmonary disease (COPD) and predicting mortality.
  • * The research found 559 genes related to lung function that were connected to 29 different biological pathways and demonstrated variations across ancestry, age, and smoking habits.
  • * Findings suggest potential new targets for therapy by highlighting specific genetic variants and proteins, ultimately contributing to better understanding and treatment of COPD.
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  • Air pollution poses significant public health risks, particularly for adolescents, yet its impact on their respiratory health in high pollution areas like Secunda and eMbalenhle, South Africa, remains under-researched.
  • This study gathered air quality data from 2005 to 2019, compared it to national and WHO standards, and surveyed adolescents on health symptoms related to air pollution, revealing a high prevalence of respiratory issues.
  • Key findings showed that particulate matter and ozone frequently surpassed air quality standards, with reported respiratory symptoms ranging from 2% for bronchitis and pneumonia to 42% for allergies, indicating a notable public health concern among the youth in these areas.
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  • * A nationwide study found that 35.2% of HCWs reported having aPPE at all times during the first lockdown, which improved to 83.9% by early 2021, highlighting a significant increase over time.
  • * Factors influencing access to aPPE included age and work environment, with older HCWs and those in Intensive Care Units more likely to report consistent access, while Asian HCWs and those in non-medical roles were less likely to do so.
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Background: Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs.

Methods And Findings: We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021.

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  • Eosinophils are linked to airway inflammation and their regulation, particularly by interleukin-5, impacts conditions like asthma, but their role in chronic obstructive pulmonary disease (COPD) is unclear.
  • The study used Mendelian randomization to explore the relationship between eosinophils and various respiratory issues, analyzing genetic variants and lung function among participants from the UK Biobank.
  • Findings indicate that increased eosinophils may raise the risk of asthma-COPD overlap and moderate-severe asthma, while negatively affecting lung function, but caution is advised due to the complexity of the underlying mechanisms.
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Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory airway disease. The epithelial-derived IL-33 and its receptor ST2 have been implicated in airway inflammation and infection. We aimed to determine whether astegolimab, a selective ST2 IgG2 monoclonal antibody, reduces exacerbations in COPD.

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Background: Several countries now have mandatory SARS-CoV-2 vaccination for healthcare workers (HCWs) or the general population. HCWs' views on this are largely unknown. Using data from the nationwide UK-REACH study we aimed to understand UK HCW's views on improving SARS-CoV-2 vaccination coverage, including mandatory vaccination.

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  • Some individuals display characteristics of both asthma and COPD, leading to a condition known as asthma-COPD overlap, which yields worse health outcomes compared to having either condition alone.
  • The study aimed to explore the genetic factors behind asthma-COPD overlap and how these differ from those linked to asthma or COPD separately.
  • Researchers identified eight new genetic signals associated with asthma-COPD overlap, revealing a mix of genetic influences related to type 2 inflammation and potential long-term health impacts.
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New data collection in established longitudinal population studies provides an opportunity for studying the risk factors and sequelae of the novel coronavirus disease 2019 (COVID-19), plus the indirect impacts of the COVID-19 pandemic on wellbeing. The Extended Cohort for E-health, Environment and DNA (EXCEED) cohort is a population-based cohort (N>11,000), recruited from 2013 in Leicester, Leicestershire and Rutland. EXCEED includes consent for electronic healthcare record (EHR) linkage, spirometry, genomic data, and questionnaire data.

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Objectives: BRCA 1 or 2 mutation carriers have increased risk of developing breast cancer (BC) and serous epithelial ovarian cancer (EOC). The incidence of BC over time after EOC is unknown. Optimal BC surveillance for BRCA mutation carriers following EOC has not been defined.

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