WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Can artificial intelligence (AI) be used to accurately detect tuberculosis (TB) from chest X-rays? An evaluation of five AI products for TB screening and triaging in a high TB burden setting

Artificial intelligence (AI) products can be trained to recognizetuberculosis (TB)-related abnormalities on chest radiographs. Various AIproducts are available commercially, yet there is lack of evidence on how theirperformance compared with each other and with radiologists. We evaluated fiveAI software products for screening and triaging TB using a large dataset thathad not been used to train any commercial AI products. Individuals (>=15 yearsold) presenting to three TB screening centers in Dhaka, Bangladesh, wererecruited consecutively. All CXR were read independently by a group of threeBangladeshi registered radiologists and five commercial AI products: CAD4TB(v7), InferReadDR (v2), Lunit INSIGHT CXR (v4.9.0), JF CXR-1 (v2), and qXR(v3). All five AI products significantly outperformed the Bangladeshiradiologists. The areas under the receiver operating characteristic curve areqXR: 90.81% (95% CI:90.33-91.29%), CAD4TB: 90.34% (95% CI:89.81-90.87), LunitINSIGHT CXR: 88.61% (95% CI:88.03%-89.20%), InferReadDR: 84.90% (95% CI:84.27-85.54%) and JF CXR-1: 84.89% (95% CI:84.26-85.53%). Only qXR met the TPPwith 74.3% specificity at 90% sensitivity. Five AI algorithms can reduce thenumber of Xpert tests required by 50%, while maintaining a sensitivity above90%. All AI algorithms performed worse among the older age and people withprior TB history. AI products can be highly accurate and useful screening andtriage tools for TB detection in high burden regions and outperform humanreaders

Analysis of therapy monitoring in the International Congenital Adrenal Hyperplasia Registry.

Funder: European Society for Paediatric Endocrinology Research UnitOBJECTIVE: Congenital adrenal hyperplasia (CAH) requires exogenous steroid replacement. Treatment is commonly monitored by measuring 17-OH progesterone (17OHP) and androstenedione (D4). DESIGN: Retrospective cohort study using real-world data to evaluate 17OHP and D4 in relation to hydrocortisone (HC) dose in CAH patients treated in 14 countries. PATIENTS: Pseudonymized data from children with 21-hydroxylase deficiency (21OHD) recorded in the International CAH Registry. MEASUREMENTS: Assessments between January 2000 and October 2020 in patients prescribed HC were reviewed to summarise biomarkers 17OHP and D4 and HC dose. Longitudinal assessment of measures was carried out using linear mixed-effects models (LMEM). RESULTS: Cohort of 345 patients, 52.2% female, median age 4.3 years (interquartile range: 3.1-9.2) were taking a median 11.3 mg/m2 /day (8.6-14.4) of HC. Median 17OHP was 35.7 nmol/l (3.0-104.0). Median D4 under 12 years was 0 nmol/L (0-2.0) and above 12 years was 10.5 nmol/L (3.9-21.0). There were significant differences in biomarker values between centres (p  0.05). Multivariate LMEM showed HC dose decreasing by 1.0 mg/m2 /day for every 1 point increase in weight standard deviation score. DISCUSSION: Registry data show large variability in 17OHP and D4 between centres. 17OHP correlates with D4 well when accounting for age. Prescribed HC dose per body surface area decreased with weight gain