Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification.

Endometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes.

Molecular and clinical predictors of improvement in progression-free survival with maintenance PARP inhibitor therapy in women with platinum-sensitive, recurrent ovarian cancer: A meta-analysis.

Background: The authors performed a meta-analysis to better quantify the benefit of maintenance poly(ADP-ribose) polymerase inhibitor (PARPi) therapy to inform practice in platinum-sensitive, recurrent, high-grade ovarian cancer for patient subsets with the following characteristics: germline BRCA mutation (gBRCAm), somatic BRCA mutation (sBRCAm), wild-type BRCA but homologous recombinant-deficient (HRD), homologous recombinant-proficient (HRP), and baseline clinical prognostic characteristics.

Methods: Randomized trials comparing a PARPi versus placebo as maintenance treatment were identified from electronic databases. Treatment estimates of progression-free survival were pooled across trials using the inverse variance weighted method.

The impact of the first COVID-19 surge on severe asthma patients in the UK. Which is worse: the virus or the lockdown?

https://bit.ly/3jImUsG.

The diagnostic and prognostic significance of liver histology in alcoholic hepatitis.

Background: Liver biopsy may be of diagnostic and prognostic value but its role in alcoholic hepatitis (AH) has been controversial.

Aim: To assess the utility of liver biopsy in the assessment of clinically severe AH METHODS: The histological features of alcoholic steatohepatitis (ASH) were recorded and scored in patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial who underwent liver biopsy. These features were then assessed relative to outcome and established clinical prognostic scores.

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

Using prednisolone and cortisol assays to assess adherence in oral corticosteroid dependant asthma: An analysis of test-retest repeatability.

Background And Objective: Non-adherence is an important issue within severe asthma. Prednisolone and cortisol assays have been proposed as an inexpensive, objective measure of adherence for oral corticosteroid (OCS)-dependent asthmatics, however, little is known about the reliability of these tests.

Methods: 41 severe OCS-dependent asthmatics had their prednisolone and cortisol measured during six study visits over a three month time period.

Composite type-2 biomarker strategy versus a symptom-risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial.

Background: Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom-risk-based algorithm (control).

Tracheal intubation in traumatic brain injury: a multicentre prospective observational study.

Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity.

Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters.

MicroRNA-17-5p Reduces Inflammation and Bone Erosions in Mice With Collagen-Induced Arthritis and Directly Targets the JAK/STAT Pathway in Rheumatoid Arthritis Fibroblast-like Synoviocytes.

Objective: We undertook this study to examine microRNA (miRNA) expression across rheumatoid arthritis (RA) phenotypes, along with the effects and mechanisms of action of miRNA-17-5p (miR-17).

Methods: A miRNA array was performed in synovial tissue biopsied from patients with naive erosive RA (n = 3) and patients with nonerosive RA (n = 3). MicroRNA-17 lipoplex was delivered intraarticularly in the murine collagen-induced arthritis model.

Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors.

Purpose: To support future dosing recommendations, the effect of food on the pharmacokinetics of adavosertib, a first-in-class, small-molecule reversible inhibitor of WEE1 kinase, was assessed in patients with advanced solid tumors.

Methods: In this Phase I, open-label, randomized, two-period, two-sequence crossover study, the pharmacokinetics of a single 300 mg adavosertib dose were investigated in fed versus fasted states.

Results: Compared with the fasted state, a high-fat, high-calorie meal (fed state) decreased adavosertib maximum plasma concentration (C) by 16% and systemic exposure (area under the plasma concentration-time curve [AUC]) by 6%; AUC decreased by 7% and time to maximum plasma concentration was delayed by 1.

Distinct temporal trends in breast cancer incidence from 1997 to 2016 by molecular subtypes: a population-based study of Scottish cancer registry data.

Background: We describe temporal trends in breast cancer incidence by molecular subtypes in Scotland because public health prevention programmes, diagnostic and therapeutic services are shaped by differences in tumour biology.

Methods: Population-based cancer registry data on 72,217 women diagnosed with incident primary breast cancer from 1997 to 2016 were analysed. Age-standardised rates (ASR) and age-specific incidence were estimated by tumour subtype after imputing the 8% of missing oestrogen receptor (ER) status.

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.

Prognostic gene expression signature for high-grade serous ovarian cancer.

Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.

Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial.

Background: State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin-paclitaxel or carboplatin-gemcitabine) or the most active non-bevacizumab regimen: carboplatin-pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin-pegylated liposomal doxorubicin combined with bevacizumab.

Methods: This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK.

Terms and nomenclature used for plant-derived components in nutrition and related research: efforts toward harmonization.

Many terms for plant-derived food components are commonly used in the literature, but there is a notable lack of standardization and definition of nomenclature. The use of terms is often field-specific, leading to misunderstanding and problems with literature searches and systematic reviews, and results in isolated and divided research; this impacts not only publication quality but also innovation, regulatory compliance, and enforcement. To begin to address this issue, this narrative review describes the current use and definition of terms.

DNA methylation aging clocks: challenges and recommendations.

Epigenetic clocks comprise a set of CpG sites whose DNA methylation levels measure subject age. These clocks are acknowledged as a highly accurate molecular correlate of chronological age in humans and other vertebrates. Also, extensive research is aimed at their potential to quantify biological aging rates and test longevity or rejuvenating interventions.

Opportunities and challenges of incorporating clinical outcome assessments in brain tumor clinical trials.

Regulatory agencies have progressively emphasized the importance of assessing broader aspects of patient well-being to better define therapeutic gain. As a result, clinical outcome assessments (COAs) are increasingly used to evaluate the impact, both positive and negative, of cancer treatments and in some instances have played a major factor in the regulatory approval of drugs. Challenges remain, however, in the routine incorporation of these measures in cancer clinical trials, particularly in brain tumor studies.

Use of mobile apps and technologies in child and adolescent mental health: a systematic review.

Question: This review will aim to critically evaluate the currently available literature concerning the use of online mobile-based applications and interventions in the detection, management and maintenance of children and young people's mental health and well-being.

Study Selection And Analysis: A systematic literature search of six electronic databases was conducted for relevant publications until May 2019, with keywords pertaining to mental health, well-being and problems, mobile or internet apps or interventions and age of the study population. The resulting titles were screened and the remaining 92 articles were assessed against the inclusion and exclusion criteria with a total of 4 studies included in the final review.

Stacked in-plane histology for quantitative validation of non-invasive imaging biomarkers: Application to an infiltrative brain tumour model.

Background: While it is generally agreed that histopathology is the gold standard for assessing non-invasive imaging biomarkers, most validation has been by qualitative visual comparison. To date, the difficulties involved in accurately co-registering histology sections with imaging slices have prevented a voxel-by-voxel assessment of imaging modalities. By contrast with previous studies, which focus on improving the registration algorithms, we have taken the approach of improving the quality of the histological processing and analysis.