Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of a Multi-Dimensional Group Counseling Program Based on the GATHER Approach on the Quality of Life in Surgically Menopausal Women

Objectives Surgical menopause can influence women's quality of life in many aspects. This study was designed to assess the effectiveness of a multi-dimensional group counseling program based on the great clients, ask clients, tell clients, help clients, explain how to use, return for follow up (GATHER) approach, on quality of life in the surgically menopausal women. Methods This randomized clinical trial was conducted using two groups. The study comprised 78 women meeting inclusion criteria who had visited 4 healthcare centers in Tehran from December 2017 to September 2018. The participants were selected through simple random sampling (39 in each group). The intervention group underwent 6 consecutive weekly group counseling sessions based on GATHER approach, whereas the control group received no interventions. Data were collected using the Menopause-specific Quality of Life questionnaire at 4 time-points (i.e., baseline, immediately after the intervention, 1 month after the intervention, and 3 months after the intervention). Results The trend of changes at four time-points obtained on the basis of repeated measures test results showed significant betweengroup differences in vasomotor (P = 0.001), psychosocial (P = 0.025), and physical (P = 0.001) domains. Friedman test showed significant between-group differences in the mean score trend of changes at 4 time-points in sexual (P = 0.002) and overall quality of life (P = 0.004) domains. Conclusions On the basis of the study results, implementation of this approach with less expenditure in healthcare centers aimed at improving quality of life in surgically menopausal women is highly recommended.
Rheumatic Diseases in Lebanon: Continuing Medical Education in Rheumatology

Copyright: © 2012 Slim ZFN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Musculoskeletal (MSK) conditions are responsible for a high proportion of disability, reduced quality of life and a significant consumption of health and social resources [1]. They are the most common reason for visiting family physicians and constitute 18% of general practitioner’s perceived workload [2]. In response to this burden, the Bone and Joint Decade, renewed for another ten years, aims to highlight the huge impact of such conditions and to improve the quality of life of people suffering from rheumatic diseases through raising awareness, empowering patients to actively participate in their own care, and updating the knowledge of physicians [3].
Circulating gluten‐specific, but not CMV‐specific, CD39+ regulatory T cells have an oligoclonal TCR repertoire

Understanding the T cell receptor (TCR) repertoire of regulatory CD4+ T‐cell (Treg) populations is important for strategies aiming to re‐establish tolerance in autoimmune diseases. We studied circulating deamidated gluten‐epitope‐specific CD39+ Tregs in patients with coeliac disease following an oral gluten challenge, and we used cytomegalovirus (CMV)‐specific CD39+ Tregs from healthy controls as a comparator population.
The Perception of Coronary Artery Disease and Cardiac Catheterization in Saudi Arabia: “What the Public Know”

Objective Coronary artery disease (CAD) constitutes a significant health hazard in middle-aged individuals in Saudi Arabia. We sought to assess the level of knowledge of cardiovascular risk factors and describe the perception of coronary intervention among the general population in the city of Jeddah in the western part of Saudi Arabia. Methods A cross-sectional study was conducted in the city of Jeddah during the period from April 2019 to September 1, 2019, by using a structured online questionnaire to assess the participants’ awareness of risk factors for CAD and coronary intervention. The survey included questions about socio-demographic data, risk factors of cardiovascular diseases, symptoms of heart attack, knowledge of coronary catheterizations, as well as resources of knowledge about coronary heart disease. Results The study included 984 participants. The majority of the participants had university diplomas (78.1%). Only 38.5 % were healthcare workers. Dyslipidemia and smoking were identified by 70.5% and 66.7%, respectively, as a recognized risk factor for CAD. Diabetes was mentioned by 32.1%. Participants without CAD risk factors had a significantly lower level of knowledge regarding the strong association between diabetes mellitus (DM) II and CAD (p-value=0.02). Healthcare professionals had a significantly lower level of knowledge regarding cardiac catheterization as compared to non-healthcare professionals. A higher percentage of healthcare professionals would agree to have cardiac catheterization if indicated (p-value=0.003). Awareness campaigns were the most common source of information for the public. Conclusion The current level of knowledge of CAD in the western part of Saudi Arabia is fair. National awareness campaigns are required to improve the level of healthcare education.
Nicotinic-nAChR signaling mediates drug resistance in lung cancer

Lung cancer is the leading cause of cancer death worldwide. Cigarette smoking is the most common risk factor for lung carcinoma; other risks include genetic factors and exposure to radon gas, asbestos, secondhand smoke, and air pollution. Nicotine, the primary addictive constituent of cigarettes, contributes to cancer progression through activation of nicotinic acetylcholine receptors (nAChRs), which are membrane ligand-gated ion channels. Activation of nicotine/nAChR signaling is associated with lung cancer risk and drug resistance. We focused on nAChR pathways activated by nicotine and its downstream signaling involved in regulating apoptotic factors of mitochondria and drug resistance in lung cancer. Increasing evidence suggests that several sirtuins play a critical role in multiple aspects of cancer drug resistance. Thus, understanding the consequences of crosstalk between nicotine/nAChRs and sirtuin signaling pathways in the regulation of drug resistance could be a critical implication for cancer therapy.
Internal Labor Mobility and Transition in Central and Eastern Europe

In this paper we present a 2-country, 3-region New Economic Geography model with limited interregional and no international (East-West) labor mobility. Our aim is reproducing the most salient stylized facts experienced by transition economies during the 1990s, emphasizing trade openness and factor mobility as crucial driving forces. Liberalizing trade with a larger Western bloc leads to an initial deindustrialization and welfare loss for the East, followed by a nal recovery. Freedom to migrate within the East is also found to be key in both the nal international and interregional convergence processes. If permanent East-West migration is shut down, internal labor mobility within the East proves to be detrimental to overall e¢ ciency.
OCT Angiography Study of the Macula in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept

ABSTRACT Purpose: To compare foveal avascular zone density (FAZ) in the superficial (SCP) and deep (DCP) capillary plexus and vessel density (VD) in the macula in eyes with diabetic macular edema (DME) treated with intravitreal aflibercept. Methods: Patients with DME were imaged at baseline, and 30 days after the 1st, 2nd and 3rd intravitreal aflibercept injection. Images were analyzed for the FAZ area in the SCP and DCP in each visit and VD. Results: Twenty eyes were enrolled. FAZ was 0.304 ± 0.131 mm2 in the SCP and 0.738 ± 0.5836 mm2 in the DCP at baseline. SCP FAZ was not significantly different whereas, FAZ in the DCP decreased (p = .035) after treatment. VD in the center was 20.62 ± 4.31 at baseline and decreased by 8% (p = .002). Parafoveal VD remained unchanged with treatment. Conclusion: DCP ischemia may improve after aflibercept treatment. Central macular vessel density was found to decrease post-treatment, but the clinical relevance needs further investigation.
Phase I trial of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration resistant prostate cancer (mCRPC)

5004 Background: IPI is a fully human, anti-CTLA 4 monoclonal antibody capable of enhancing anti-tumor immunity. In preclinical models, XRT results in tumor antigen release and enhances anti-tumor activity of CTLA-4 blockade. Methods: Pts with mCRPC and ECOG PS of 0–1 were treated with escalating doses of IPI every 3 weeks X 4 doses in cohorts of 6 pts at dose levels of 3, 5, and 10 mg/kg. After the 10 mg/kg cohort was completed, a protocol amendment added single fraction XRT prior to IPI starting at the 3 mg/kg dose level. The primary endpoint was safety. Imaging was repeated every 3 months and serum PSA was monitored monthly. Results: Between 1/2006 and 12/2007, 8, 6, and 6 pts were treated at the 3, 5, and 10 mg/kg dose levels respectively; 6 pts were then treated in the first XRT cohort for a total of 26 pts. 19 pts experienced 29 immune-related adverse events (irAEs) including diarrhea/colitis (14), rash (9), hepatitis (4), endocrinopathy (2). irAEs were ≥ Grade 3 in 9 pts: GI (6), hepatitis (2), and.
Cervicovaginal Microbiome and Urine Metabolome Paired Analysis Reveals Niche Partitioning of the Microbiota in Patients with Human Papilloma Virus Infections

In this study, we evaluate the association between vaginal and cervical human papillomavirus infections high-risk types (HPV+H), negative controls (HPV−), the bacterial biota, and urinary metabolites via integration of metagenomics, metabolomics, and bioinformatics analysis. We recently proposed that testing urine as a biofluid could be a non-invasive method for the detection of cervical HPV+H infections by evaluating the association between cervical HPV types and a total of 24 urinary metabolites identified in the samples. As a follow-up study, we expanded the analysis by pairing the urine metabolome data with vaginal and cervical microbiota in selected samples from 19 Puerto Rican women diagnosed with HPV+H infections and HPV− controls, using a novel comprehensive framework, Model-based Integration of Metabolite Observations and Species Abundances 2 (MIMOSA2). This approach enabled us to estimate the functional activities of the cervicovaginal microbiome associated with HPV+H infections. Our results suggest that HPV+H infections could induce changes in physicochemical properties of the genital tract through which niche partitioning may occur. As a result, Lactobacillus sp. enrichment coincided with the depletion of L. iners and Shuttleworthia, which dominate under normal physiological conditions. Changes in the diversity of microbial species in HPV+H groups influence the capacity of new community members to produce or consume metabolites. In particular, the functionalities of four metabolic enzymes were predicted to be associated with the microbiota, including acylphosphatase, prolyl aminopeptidase, prolyl-tRNA synthetase, and threonyl-tRNA synthetase. Such metabolic changes may influence systemic health effects in women at risk of developing cervical cancer. Overall, even assuming the limitation of the power due to the small sample number, our study adds to current knowledge by suggesting how microbial taxonomic and metabolic shifts induced by HPV infections may influence the maintenance of microbial homeostasis and indicate that HPV+H infections may alter the ecological balance of the cervicovaginal microbiota, resulting in higher bacterial diversity.
An RNA thermometer dictates production of a secreted bacterial toxin

Frequent transitions of bacterial pathogens between their warm-blooded host and external reservoirs are accompanied by abrupt temperature shifts. A temperature of 37°C serves as reliable signal for ingestion by a mammalian host, which induces a major reprogramming of bacterial gene expression and metabolism. Enteric Yersiniae are Gram-negative pathogens accountable for self-limiting gastrointestinal infections. Among the temperature-regulated virulence genes of Yersinia pseudotuberculosis is cnfY coding for the cytotoxic necrotizing factor (CNFY), a multifunctional secreted toxin that modulates the host’s innate immune system and contributes to the decision between acute infection and persistence. We report that the major determinant of temperature-regulated cnfY expression is a thermo-labile RNA structure in the 5’-untranslated region (5’-UTR). Various translational gene fusions demonstrated that this region faithfully regulates translation initiation regardless of the transcription start site, promoter or reporter strain. RNA structure probing revealed a labile stem-loop structure, in which the ribosome binding site is partially occluded at 25°C but liberated at 37°C. Consistent with translational control in bacteria, toeprinting (primer extension inhibition) experiments in vitro showed increased ribosome binding at elevated temperature. Point mutations locking the 5’-UTR in its 25°C structure impaired opening of the stem loop, ribosome access and translation initiation at 37°C. To assess the in vivo relevance of temperature control, we used a mouse infection model. Y. pseudotuberculosis strains carrying stabilized RNA thermometer variants upstream of cnfY were avirulent and attenuated in their ability to disseminate into mesenteric lymph nodes and spleen. We conclude with a model, in which the RNA thermometer acts as translational roadblock in a two-layered regulatory cascade that tightly controls provision of the CNFY toxin during acute infection. Similar RNA structures upstream of various cnfY homologs suggest that RNA thermosensors dictate the production of secreted toxins in a wide range of pathogens.
The intuitive use of contextual information in decisions made with verbal and numerical quantifiers

Verbal and numerical formats (e.g., verbal: “low fat,” or numerical: “20% fat”) are used interchangeably to communicate nutritional information. However, prior research implies that verbal quantifiers are processed more intuitively than numerical ones. We tested this hypothesis in two pre-registered experiments measuring four indicators of processing style: (a) response time, (b) decision performance, (c) reliance on irrelevant contextual information, which we inferred from participants’ decision patterns, and (d) the level of interference from a concurrent memory task. Participants imagined they had consumed a given amount of a nutrient (represented in a pie chart) and decided whether a new quantity (either verbal or numerical) could be eaten within their guideline daily amount (GDA). The experiments used a mixed design varying format (verbal or numerical), concurrent memory load (no load, easy, and hard load in Experiment 1; no load and hard load in Experiment 2), nutrient (fat and minerals), quantity (low, medium, and high in Experiment 1; low and high in Experiment 2), and the assigned correct response for a trial (within and exceeding limits). Participants were faster and made fewer correct decisions with verbal quantifiers, and they relied more on contextual information (i.e., the identity of the nutrient involved). However, memory load did not impair decisions with verbal or numerical quantifiers. Altogether, these results suggest that verbal quantifiers are processed intuitively, slightly more so than numerical quantifiers, but that numerical quantifiers do not require much analytical processing to reach simple decisions.
A Model for Human Action Potential Dynamics In Vivo.

Computational modeling based on experimental data remain important components in cardiac electrophysiological research, especially because clinical data such as human action potential (AP) dynamics are scarce or limited by practical or ethical concerns. Such modeling has been used to develop and test a variety of mechanistic hypotheses, with the majority of these studies involving the rate dependence of action potential duration (APD) and conduction velocity (CV). However, there is very little information regarding the complex dynamics at the boundary of repolarization (or refractoriness) and re-excitability. Here, we developed a 'minimal' ionic model of the human action potential, based on in-vivo human AP recordings obtained during clinical programmed electrical stimulation (PES), to address the progressive decrease in AP take-off potential (TOP) and associated CV slowing seen during tightly spaced extra-stimuli. Recent voltage clamp data demonstrating the effect of intracellular calcium on sodium current availability was incorporated and was required to reproduce large (> 15 mV) elevations in TOP and progressive encroachment. Introducing clinically observed APD gradients into the model enabled us to replicate the dynamic response to PES in patients leading to conduction block and reentry formation for the positive, but not the negative, APD gradient. Finally, we modeled the dynamics of reentry and show that spiral waves follow a meandering trajectory with a period of ~180 ms. We conclude that our model reproduces a variety of electrophysiological behavior including the response to sequential premature stimuli and provides a basis for studies of the initiation of reentry in human ventricular tissue.
Androgen Receptor in Breast Cancer—Clinical and Preclinical Research Insights

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy among females worldwide. The concordance of more than 70% of AR expression in primary and metastatic breast tumors implies that AR may be a new marker and a potential therapeutic target among AR-positive breast cancer patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. AR exhibits different behavior depending on the breast cancer subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since the prognostic and predictive value of AR positivity remains uncertain, it is difficult to identify and stratify patients that would benefit from AR-targeted therapies. Herein, through a review of preclinical studies, clinical studies, and clinical trials, we summarize the biology of AR, its prognostic and predictive value, as well as its therapeutic implications by breast cancer molecular subtype.
Signs of Reduced Basal Progenitor Levels and Cortical Neurogenesis in Human Fetuses with Open Spina Bifida at 11–15 Weeks of Gestation

Open spina bifida (OSB) is one of the most prevalent congenital malformations of the CNS that often leads to severe disabilities. Previous studies reported the volume and thickness of the neocortex to be altered in children and adolescents diagnosed with OSB. Until now, the onset and the underlying cause of the atypical neocortex organization in OSB patients remain largely unknown. Open spina bifida (OSB) is one of the most prevalent congenital malformations of the CNS that often leads to severe disabilities. Previous studies reported the volume and thickness of the neocortex to be altered in children and adolescents diagnosed with OSB. Until now, the onset and the underlying cause of the atypical neocortex organization in OSB patients remain largely unknown. To examine the effects of OSB on fetal neocortex development, we analyzed human fetuses of both sexes diagnosed with OSB between 11 and 15 weeks of gestation by immunofluorescence for established neuronal and neural progenitor marker proteins and compared the results with healthy controls of the same, or very similar, gestational age. Our data indicate that neocortex development in OSB fetuses is altered as early as 11 weeks of gestation. We observed a marked reduction in the radial thickness of the OSB neocortex, which appears to be attributable to a massive decrease in the number of deep- and upper-layer neurons per field, and found a marked reduction in the number of basal progenitors (BPs) per field in the OSB neocortex, consistent with an impairment of cortical neurogenesis underlying the neuronal decrease in OSB fetuses. Moreover, our data suggest that the decrease in BP number in the OSB neocortex may be associated with BPs spending a lesser proportion of their cell cycle in M-phase. Together, our findings expand our understanding of the pathophysiology of OSB and support the need for an early fetal therapy (i.e., in the first trimester of pregnancy). SIGNIFICANCE STATEMENT Open spina bifida (OSB) is one of the most prevalent congenital malformations of the CNS. This study provides novel data on neocortex development of human OSB fetuses. Our data indicate that neocortex development in OSB fetuses is altered as early as 11 weeks of gestation. We observed a marked reduction in the radial thickness of the OSB neocortex, which appears to be attributable a decrease in the number of deep- and upper-layer neurons per field, and found a marked reduction in the number of basal progenitors per field, indicating that impaired neurogenesis underlies the neuronal decrease in OSB fetuses. Our findings support the need for an early fetal therapy and expand our understanding of the pathophysiology of OSB.
Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament

Heat shock protein 27 (HSP27) is commonly involved in cellular stress. Increased levels of HSP27 as well as autoantibodies against this protein were previously detected in glaucoma patients. Moreover, systemic immunization with HSP27 induced glaucoma-like damage in rodents. Now, for the first time, the direct effects of an intravitreal HSP27 application were investigated. For this reason, HSP27 or phosphate buffered saline (PBS, controls) was applied intravitreally in rats (n = 12/group). The intraocular pressure (IOP) as well as the electroretinogram recordings were comparable in HSP27 and control eyes 21 days after the injection. However, significantly fewer retinal ganglion cells (RGCs) and amacrine cells were observed in the HSP27 group via immunohistochemistry and western blot analysis. The number of bipolar cells, on the other hand, was similar in both groups. Interestingly, a stronger neurofilament degeneration was observed in HSP27 optic nerves, while no differences were noted regarding the myelination state. In summary, intravitreal HSP27 injection led to an IOP-independent glaucoma-like damage. A degeneration of RGCs as well as their axons and amacrine cells was noted. This suggests that high levels of extracellular HSP27 could have a direct damaging effect on RGCs.