Primordial germ cell DNA demethylation and development require DNA translesion synthesis.

Mutations in DNA damage response (DDR) factors are associated with human infertility, which affects up to 15% of the population. The DDR is required during germ cell development and meiosis. One pathway implicated in human fertility is DNA translesion synthesis (TLS), which allows replication impediments to be bypassed.

Propagating variational model uncertainty for bioacoustic call label smoothing.

Along with propagating the input toward making a prediction, Bayesian neural networks also propagate uncertainty. This has the potential to guide the training process by rejecting predictions of low confidence, and recent variational Bayesian methods can do so without Monte Carlo sampling of weights. Here, we apply sample-free methods for wildlife call detection on recordings made via passive acoustic monitoring equipment in the animals' natural habitats.

First report on genome wide association study in western Indian population reveals host genetic factors for COVID-19 severity and outcome.

Different human races across the globe responded in a different way to the SARS-CoV-2 infection leading to different disease severity. Therefore, it is anticipated that host genetic factors have a straight association with the COVID-19. We identified a total 6, 7, and 6 genomic loci for deceased-recovered, asymptomatic-recovered, and deceased-asymptomatic group comparison, respectively.

Laparoscopic management of moderate: Severe endometriosis.

Objectives: To assess the feasibility of laparoscopic surgery in cases of moderate-severe endometriosis.

Materials And Methods: A prospective study was carried out in a tertiary centre over a period of 2 years. Moderate to severe endometriosis was defined by revised American fertility society (rAFS) classification (41 patients).

Lead optimization of isocytosine-derived xanthine oxidase inhibitors.

We report our attempts at improving the oral efficacy of low-nanomolar inhibitors of xanthine oxidase from isocytosine series through chemical modifications. Our lead compound had earlier shown good in vivo efficacy when administered intraperitoneally but not orally. Several modifications are reported here which achieved more than twofold improvement in exposure.

Isocytosine-based inhibitors of xanthine oxidase: design, synthesis, SAR, PK and in vivo efficacy in rat model of hyperuricemia.

Structure-activity relationship studies were carried out for lead generation following structure-guided design approach from an isocytosine scaffold identified earlier for xanthine oxidase inhibition. A 470-fold improvement in in vitro IC(50) was obtained in the process. Five most potent compounds with nanomolar IC(50) values were selected for pharmacokinetics and in vivo experiments.

Peripartum cardiomyopathy in an elderly patient with in-vitro fertilization pregnancy.

Peripartum cardiomyopathy as a diagnosis needs to be considered in antenatal and immediate postpartum women with clinical features of cardiac failure. As more and more women at increasing age go for assisted reproduction, screening for risk factors needs to be done. Treatment involves coordination between cardiologist and obstetrician as both the patient's cardiac status and well being of the baby needs to be considered.

Identification of novel isocytosine derivatives as xanthine oxidase inhibitors from a set of virtual screening hits.

In recent years, xanthine oxidase has emerged as an important target not only for gout but also for cardiovascular and metabolic disorders involving hyperuricemia. Contrary to popular belief, recent clinical trials with uricosurics have demonstrated that enhanced excretion of uric acid is, by itself, not adequate to treat hyperuricemia; simultaneous inhibition of production of uric acid by inhibition of xanthine oxidase is also important. Virtual screening of in-house synthetic library followed by in vitro and in vivo testing led to the identification of a novel scaffold for xanthine oxidase inhibition.

Usefulness of cell counter-based parameters and formulas in detection of beta-thalassemia trait in areas of high prevalence.

The present study aimed to retrospectively evaluate the usefulness of cell counter-based parameters and formulas in beta-thalassemia trait (BTT) detection. The study included 170 BTT cases (hemoglobin [Hb]A(2) >4.0% [0.