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The regulatory pathways involved in maintaining the pluripotency of embryonic stem cells are partially known, whereas the regulatory pathways governing adult stem cells and their "stem-ness" are characterized to an even lesser extent. We, therefore, screened the transcriptome profiles of 20 osteogenically induced adult human adipose-derived stem cell (ADSC) populations and investigated for putative transcription factors that could regulate the osteogenic differentiation of these ADSC. We studied a subgroup of donors' samples that had a disparate osteogenic response transcriptome from that of induced human fetal osteoblasts and the rest of the induced human ADSC samples. From our statistical analysis, we found activating transcription factor 5 (ATF5) to be significantly and consistently down-regulated in a randomized time-course study of osteogenically differentiated adipose-derived stem cells from human donor samples. Knockdown of ATF5 with siRNA showed an increased sensitivity to osteogenic induction. This evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose-derived stem cells. To our knowledge, this is the first report that indicates a novel role of transcription factors in regulating osteogenic differentiation in adult or tissue specific stem cells.

ObjectivesThere exists a wide gap in the availability of mechanical ventilator devices and their acute need in the context of the COVID-19 pandemic. An initial triaging method that accurately identifies the need for mechanical ventilation in hospitalised patients with COVID-19 is needed. We aimed to investigate if a potentially deteriorating clinical course in hospitalised patients with COVID-19 can be detected using all X-ray images taken during hospitalisation.MethodsWe exploited the well-established DenseNet121 deep learning architecture for this purpose on 663 X-ray images acquired from 528 hospitalised patients with COVID-19. Two Pulmonary and Critical Care experts blindly and independently evaluated the same X-ray images for the purpose of validation.ResultsWe found that our deep learning model predicted the need for mechanical ventilation with a high accuracy, sensitivity and specificity (90.06%, 86.34% and 84.38%, respectively). This prediction was done approximately 3 days ahead of the actual intubation event. Our model also outperformed two Pulmonary and Critical Care experts who evaluated the same X-ray images and provided an incremental accuracy of 7.24%–13.25%.ConclusionsOur deep learning model accurately predicted the need for mechanical ventilation early during hospitalisation of patients with COVID-19. Until effective preventive or treatment measures become widely available for patients with COVID-19, prognostic stratification as provided by our model is likely to be highly valuable.

The in vivo and in vitro effects of the insecticide deltamethrin (DM) on hepatic cytochrome P450 (Cyt P450) monooxygenase were examined in adult carp. The in vivo experiments were carried out with 0.2 microgram/l DM at 20 degrees C. The changes in the hepatic microsomal Cyt P450 content and the Cyt P450-dependent monooxygenase activities were studied in DM-treated fish. Although there were no changes in the Cyt P450 content during the exposure time, after treatment for 24 h all the investigated isoenzyme activities (para-nitrophenetole-O-deethylase, p-NPOD; aminopyrene-N-demethylase, APND; ethylmorphine-N-demethylase, EMND; 7-ethoxycoumarin-O-deethylase, ECOD; and ethoxyresorufin-O-deethylase, EROD) were significantly inhibited. After 72 h, all the activities were still lower than in the control animals. In vitro incubation of liver microsomes with DM led to a concentration-dependent decrease in total microsomal Cyt P450 content. A complete loss of Cyt P450 occurred after a 5-min incubation with 60 microM DM. The maximum in the difference spectra of microsomes was shifted to higher wavelength, showing the strong interaction of DM with Cyt P450. EROD and ECOD activities were inhibited by DM. The in vitro kinetic results on ECOD revealed that the inhibition was of non-competitive type, with K1 = 9.8 +/- 2.3 microM. This study indicates important biochemical effects of DM in fish liver, and suggests that exposure to DM may cause loss of the Cyt P450-dependent metabolism in fish.

Objective: Diabetes is a known risk factor for mortality in Coronavirus disease 2019 (COVID-19) patients. Our objective was to identify prevalence of hyperglycemia in COVID-19 patients with and without diabetes and quantify its association with COVID-19 disease course. Research Design and Methods: In this observational cohort study, all consecutive COVID-19 patients admitted to John H Stroger Jr. Hospital, Chicago, IL from March 15, 2020 to May 15, 2020 were included. The primary outcome was hospital mortality and the main predictor was hyperglycemia (any blood glucose ≥7.78 mmol/L during hospitalization). Results: Of 403 COVID-19 patients studied, 228 (57%) developed hyperglycemia. Of these, 83 (21%) had hyperglycemia without diabetes. A total of 51 (12.7%) patients died. Compared to the reference group no-diabetes/no-hyperglycemia patients the no-diabetes/hyperglycemia patients showed higher mortality (1.8% versus 20.5%, adjusted odds ratio 21.94 (95% confidence interval 4.04-119.0), p < 0.001); improved prediction of death (p=0.0162) and faster progression to death (p=0.0051). Hyperglycemia within the first 24 and 48 hours was also significantly associated with mortality (odds ratio 2.15 and 3.31, respectively). Further, compared to the same reference group, no-diabetes/hyperglycemia patients had higher risk of ICU admission (p<0.001), mechanical ventilation (p<0.001) and acute respiratory distress syndrome (p<0.001) and a longer hospital stay in survivors (p<0.001). Conclusions: Hyperglycemia in the absence of diabetes was common (21% of hospitalized COVID-19 patients) and was associated with an increased risk of and faster progression to death. Development of hyperglycemia in COVID-19 patients who do not have diabetes is an early indicator of poor prognosis.