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  • Mathews posted an update 7 months, 2 weeks ago

    Osteoarthritis (OA) seriously affects people’s quality of life due to joint pain, stiffness, disability, and dyskinesia worldwide. Long noncoding RNA zinc finger antisense 1 (ZFAS1) is downregulated and tightly associated with proliferation, migration, apoptosis, and matrix synthesis of chondrocyte in OA. However, the molecular mechanisms of ZFAS1 in OA remain unknown. The expression correlation between ZFAS1, miR-302d-3p, and SMAD2 in OA tissues was analyzed by Pearson correlation analysis. ZFAS1 was a lower expression, and expedited proliferation and repressed apoptosis of chondrocytes. MiR-302d-3p was a direct target of ZFAS1. MiR-302d-3p hindered proliferation and facilitated apoptosis of chondrocytes. MiR-302d-3p partially reversed the effect of ZFAS1 on proliferation and apoptosis of chondrocytes. SMAD2 was positively regulated by the ZFAS1/miR-302d-3p. MiR-302d-3p-mediated proliferation and apoptosis were partly abrogated by targeting SMAD2. ZFAS1 promoted chondrocytes proliferation and repressed apoptosis possibly by regulating miR-302d-3p/SMAD2 axis, providing a potential target for OA treatment.

    Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly.

    To develop a prediction model of therapeutic response of acromegaly to fg-SRL.

    Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP).

    A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P < .001), and more frequently harbored tumors that were densely granulated (P = .014) or highly expressed SST2 (P < .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%.

    We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

    We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

    Primary ovarian insufficiency (POI) is defined by menopause before 40 years of age. POI prevalence is higher among women with autoimmune Addison’s disease (AAD) than in the general population, but their clinical characteristics are insufficiently studied.

    To assess the prevalence of POI in a large cohort of women with AAD and describe clinical, immunological, and genetic characteristics.

    An observational population-based cohort study of the Norwegian National Addison Registry. The Norwegian Prescription Database was used to assess prescription of menopausal hormone replacement therapy (HRT). A total of 461 women with AAD were studied. The primary outcome measure was prevalence of POI. Secondary outcomes were clinical characteristics, autoantibodies, and genome-wide single nucleotide polymorphism variation.

    The prevalence of POI was 10.2% (47/461) and one-third developed POI before 30 years of age. POI preceded or coincided with AAD diagnosis in more than half of the women. The prevalence of concomitant autoimmune diseases was 72%, and AAD women with POI had more autoantibodies than AAD women without (≥2 autoantibodies in 78% vs 25%). Sapogenins Glycosides Autoantibodies against side-chain cleavage enzyme (SCC) had the highest accuracy with a negative predictive value for POI of 96%. HRT use was high compared to the age adjusted normal population (11.3 % vs 0.7%).

    One in 10 women with AAD have POI. Autoantibodies against SCC are the most specific marker for autoimmune POI. We recommend testing women with AAD <40 years with menstrual disturbances or fertility concerns for autoantibodies against SCC.

    One in 10 women with AAD have POI. Autoantibodies against SCC are the most specific marker for autoimmune POI. We recommend testing women with AAD less then 40 years with menstrual disturbances or fertility concerns for autoantibodies against SCC.Thermotolerant microorganisms are useful for high-temperature fermentation. Several thermally adapted strains were previously obtained from Acetobacter pasteurianus in a nutrient-rich culture medium, while these adapted strains could not grow well at high temperature in the nutrient-poor practical culture medium, “rice moromi.” In this study, A. pasteurianus K-1034 originally capable of performing acetic acid fermentation in rice moromi was thermally adapted by experimental evolution using a “pseudo” rice moromi culture. The adapted strains thus obtained were confirmed to grow well in such the nutrient-poor media in flask or jar-fermentor culture up to 40 or 39 °C; the mutation sites of the strains were also determined. The high-temperature fermentation ability was also shown to be comparable with a low-nutrient adapted strain previously obtained. Using the practical fermentation system, “Acetofermenter,” acetic acid production was compared in the moromi culture; the results showed that the adapted strains efficiently perform practical vinegar production under high-temperature conditions.

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