Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles.

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms

Predicting drug-target interactions through integrative analysis of chemogenetic assays in yeast

Peer reviewe

Neutrino masses and mixings in the baryon triality constrained minimal supersymmetric standard model

We discuss how the experimental neutrino oscillation data can be realized in the framework of the baryon triality ($B_3$) constrained supersymmetric Standard Model (cSSM). We show how to obtain phenomenologically viable solutions, which are compatible with the recent WMAP observations. We present results for the hierarchical, inverted and degenerate cases which illustrate the possible size and structure of the lepton number violating couplings. We work with a new, as yet unpublished version of SOFTSUSY, where we implemented full one--loop neutrino masses. Finally, we shortly discuss some phenomenological implications at the LHC.Comment: 25 pages, 17 figure

Процедура внесення змін до конституції: порівняльно-правовий аспект

Розглядається процедура внесення змін до Конституції, проводиться її порівняльно правовий аналіз, досліджуються особливості цієї процедури в різних країнах. Ключові слова: Конституція, зміни до Конституції, суб’єкт законодавчої ініціативиРассматривается процедура внесения изменений в Конституцию, проводится е сравнительно правовой анализ, исследуются особенности этой процедуры в различных странах. Ключевые слова: Конституция, изменения в Конституции, субъект законодательной инициативы.In article procedure of modification of the Constitution is considered, its ratherlegal analysis is carried out, features of this procedure in the various countries are investigated. Key words: Constitution, modification of the Constitution

Contemporary Ritual Landscapes. Preface to the Special Issue

This special issue of the Journal of Ethnology and Folkloristics is composed on the basis of papers presented at the Ethnography of Contemporary Ritual Landscapes panel organised at the Conference of the Finnish Anthropological Society at the University of Helsinki, October 21–22, 2015

Daytime along-valley winds in the Himalayas as simulated by the Weather Research and Forecasting (WRF) model

Peer reviewe

IN-CAM Outcomes Database: Its Relevance and Application in Massage Therapy Research and Practice

One of the most commonly used complementary and alternative medicine (CAM) modalities in North America is massage therapy (MT). Research to date indicates many potential health benefits of MT, suggesting that ongoing research efforts to further elucidate and substantiate preliminary findings within the massage profession should be given high priority. Central to the development of a sound evidence base for MT are the use of valid, reliable, and relevant outcome measures in research, and practice in assessing the effectiveness of MT. The purpose of the present article is to introduce MT researchers and massage therapists interested in using outcome measures in research and clinical practice to the IN-CAM Outcomes Database website by describing the Outcomes Database and identifying its utility in MT research and practice. The IN-CAM Outcomes Database is a centralized location where information on outcome measures is collected and made accessible to users. Outcome measures are organized in the database within the Framework of Outcome Domains. The Framework includes health domains relevant to conventional medicine and CAM alike, and health domains that have been identified as important to CAM interventions. Users of the website may search for information on a specific outcome measure, plan research projects, and engage in discussions related to outcomes assessment in the CAM field with other users and with members of the CAM research community. As the MT profession continues to evolve and move toward evidence-informed practice, the IN-CAM Outcomes Database website can be a valuable resource for MT researchers and massage therapists

Association between moderate to severe atopic dermatitis and lifestyle factors in the Dutch general population

Background Studies on the association between severity of atopic dermatitis (AD) and lifestyle factors in adults have not been conducted in the Netherlands to date. Aim To explore the association between moderate to severe AD and lifestyle factors in adults in the Dutch general population. Methods We conducted this cross-sectional study within the Lifelines Cohort Study by sending a digital AD questionnaire to 135 950 adults in 2020. We extracted data on lifestyle factors from baseline, collected between 2006 and 2013. We analysed the association between lifestyle factors and presence of AD of any severity and of moderate to severe AD, using binary logistic regression and linear regression models. Results We enrolled 56 896 participants (mean age 55.8 years, 39.7% males). The lifetime prevalence of self-reported physician-diagnosed AD was 9.1%, and the point prevalence of any AD and of moderate to severe AD was 3.3% and 2.3%, respectively. We found that moderate to severe AD was associated with smoking habit of > 15 pack-years, alcohol consumption of > 2 drinks per day, chronic stress, Class I obesity, and both shorter and longer sleep duration. Moreover, we found dose-response associations with increases in smoking pack-years and level of chronic stress. We observed no associations with abdominal obesity, physical activity, diet quality or a vegetarian/vegan diet. Conclusion We found associations between moderate to severe AD and some modifiable lifestyle factors. Our findings indicate that more screening and counselling for lifestyle factors, particularly smoking, alcohol use, stress, obesity and sleep disturbances, appears warranted in patients with moderate to severe AD. Further longitudinal studies are required to better characterize the direction of these associations and to develop strategies for prevention

Novel Ex Vivo DOAC Removal Methods Reduce Interference in Lupus Anticoagulant Testing

Direct oral anticoagulants (DOAC) interfere in laboratory coagulation testing. The aim here was to study how commercial DOAC removal methods, DOAC Filter® and DOAC-Stop™, perform to eliminate DOAC concentrations and false positive results in lupus anticoagulant (LAC) testing. We acquired 50 patient samples with high concentrations of DOACs: apixaban (n = 18, range 68–572 ng/mL), dabigatran (n = 8, range 47–154 ng/mL), edoxaban (n = 8, range 35–580 ng/mL) and rivaroxaban (n = 16, range 69–285 ng/mL). DOACs were removed ex vivo with either DOAC Filter® (n = 28) or DOAC-Stop™ (n = 22). Additionally, commercial control and calibrator samples were studied (n = 13 for DOAC Filter®, n = 14 for DOAC-Stop™). LAC screening was performed before and after DOAC removal. Both DOAC Filter® and DOAC-Stop™ were effective in removing DOAC concentrations in samples: DOAC concentrations decreased to median of 0 ng/mL (range 0–48 ng/mL). Only one sample had more than residual 25 ng/mL of DOAC (apixaban). Before DOAC removal, 96% (48/50) of patient samples and over 90% (12/13 DOAC Filter®, 13/14 DOAC-Stop™) of control/calibrator samples were positive in the LAC screening. In patient samples, LAC screening turned negative in 61% (17/28) after DOAC Filter® and 45% (10/22) after DOAC-Stop™ treatment. All control samples became negative after DOAC removal. In conclusion, DOAC removal ex vivo reduces false positives in LAC screening. DOAC removal halved the need for confirmation or mixing tests- Although a subset of patients would require further testing, DOAC removal reduces unnecessary repeated LAC testing