Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnosis and Management of Interstitial Cystitis/ Painful Bladder Syndrome.

Much has changed in our understanding of the interstitial cystitis/painful bladder syndrome (IC/PBS) over time. The International Continence Society (ICS) prefers the term Painful Bladder Syndrome (PBS) defined as "the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased daytime and night-time frequency, in the absence of proven urinary infection or other obvious pathology". Interstitial cystitis is a clinical diagnosis primarily based on symptoms of urgency/frequency and pain in the bladder and or pelvis. The pathogenesis of IC is still not completely understood, but it is likely multifactorial. The major etiologic theories include abnormality of the bladder urothelium, bladder mast cell activation, bladder inflammation, and altered bladder innervation. The sensitivity and specificity of urinary markers and the potassium sensitivity test have not been prospectively studied. Antiproliferative factor and Tamm-Horsfall protein are novel tests that may prove to be worthwhile pending future studies. Management includes patient education, dietary and lifestyle counseling, oral therapy, intravesical therapy, and surgery. Recently, the European Society for the Study of Interstitial Cystitis (ESSIC) proposed a new nomenclature and classification system. This article discusses recent data and outlines current concepts of IC/PBS. (J Korean Continence Soc 2008;12:99-113)
Genetic Changes in Experimental Populations of a Hybrid in the Cryptococcus neoformans Species Complex

Hybrids between Cryptococcus neoformans and Cryptococcus deneoformans are commonly found in patients and the environment. However, the genetic stability of these hybrids remains largely unknown. Here, we established mutation accumulation lines of a diploid C. neoformans × C. deneoformans laboratory hybrid and analyzed the genotypes at 33 markers distributed across all 14 chromosomes. Our analyses found that under standard culture conditions, heterozygosity at most loci was maintained over 800 mitotic generations, with an estimated 6.44 × 10−5 loss-of-heterozygosity (LoH) event per mitotic division. However, under fluconazole stress, the observed LoH frequency increased by > 50 folds for the two markers on Chromosome 1, all due to the loss of the fluconazole susceptible allele on this chromosome. Flow cytometry analyses showed that after the 40th transfer (120 days), 19 of the 20 lines maintained the original ploidy level (2N), while one line was between 2N and 3N. The combined flow cytometry, genotyping at 33 markers, and quantitative PCR analyses showed the allelic loss was compensated for by amplification of the resistant ERG11 allele in eight of the ten fluconazole-stress lines. Our results suggest that hybrids in C. neoformans species complex are generally stable but that they can undergo rapid adaptation to environmental stresses through LoH and gene duplication.
Meta-analysis of influences of Biejiajian Pill combined with entecavir on serum liver fibrosis markers of compensatory period of hepatitis b cirrhosis

Abstract Background: Chronic viral hepatitis b and its related complications have caused serious harm to human health and become a worldwide public health problem. Hepatitis b cirrhosis is one of the most common complications in Asia. Traditional Chinese medicine combined with antiviral therapy has become the first choice for clinical treatment of hepatitis b Cirrhosis. Biejia Pill is an effective prescription of traditional Chinese medicine in treating Compensatory period of cirrhosis, and there are more and more clinical reports about its validity in treating Compensatory period of cirrhosis. Therefore, we designed this study protocol to evaluate the adjuvant role of Biejia Pill in the treatment of Compensatory period of cirrhosis. Method: Electronic Databases, PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc, (CBM), will be systematically searched from inception to July 2019. Randomized controlled trials (RCTs) on Biejiajian Pill combined with Entecavir and Entecavir alone against Compensatory period of hepatitis b cirrhosis will be included; inclusion and exclusion criteria will be used to screen the trials. liver fibrosis biomarkers including ECM or its metabolites (serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), and type IV collagen (IV-C)) will be measured as primary outcomes. Liver function, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms will be measured as secondary outcomes. RevMan5 software will be used for literature quality evaluation and data synthesis and analysis. Result: To evaluate the efficacy and safety of Biejiajian Pill in combination therapy by observing the outcomes of serum liver fibrosis markers, adverse reactions and liver function. Conclusion: This study protocol will be used to evaluate the efficacy and safety of Biejia Pill in combination with entecavir in the treatment of Compensatory period of hepatitis b cirrhosis, as well as the adjuvant treatment of Biejia Pill in combination. PROSPERO registration number: CRD42019135402
Mood and behavioral problems are important predictors of quality of life of nursing home residents with moderate to severe dementia: A cross-sectional study

Objectives To examine the predictors associated with quality of life of nursing home residents with dementia, in order to identify which predictors are most important and hold most promise for future intervention studies. Methods/Design This cross-sectional analysis of data collected in two intervention trials included 143 participants with moderate to severe dementia who resided in 40 psychogeriatric wards in 13 nursing homes. The outcome measure quality of life was assessed with the Qualidem. Predictors examined were demographic factors, cognition, mood, behavioral problems, and comorbid conditions. Results Linear mixed regression analyses showed that all nine domains of quality of life showed independent (negative) associations with either depression, agitation, apathy, or a combination of these predictors. Agitation, apathy, depression, and the presence of neurological disease explained 50% of the variance in total quality of life. Male gender, psychiatric/mood disorders, and having one or more comorbid conditions was associated with worse social relations, while the presence of comorbid neurological diseases was associated with more social isolation and a worse care relationship. The presence of endocrine/metabolic disorders and pulmonary disorders was associated with less restless tense behavior. Conclusions Different domains of quality of life showed different associations, confirming the multidimensionality of quality of life in nursing home residents with dementia. Quality of life is independently associated with mood and behavioral problems, comorbid conditions, and gender. This knowledge may help to identify older persons at risk of a lower quality of life, and to offer targeted interventions to improve quality of life. Trial registration Dutch Trial registration NTR5641
Impact of Bovine Diet on Metabolomic Profile of Skim Milk and Whey Protein Ingredients

The influence of bovine diet on the metabolome of reconstituted skim milk powder (SMP) and protein ingredients produced from the milk of cows fed on pasture or concentrate-based diets was investigated. Cows were randomly assigned to diets consisting of perennial ryegrass only (GRS), perennial ryegrass/white clover sward (CLV), or indoor total mixed ration (TMR) for an entire lactation. Raw milk obtained from each group was processed at pilot scale, to produce SMP and sweet whey, and SMP was further processed at laboratory scale, to yield ideal whey and acid whey. The total amino acid composition and metabolome of each sample were analyzed, using high-performance cation exchange and a targeted combination of direct-injection mass spectrometry and reverse-phase liquid chromatography–tandem mass spectrometry (LC–MS/MS), respectively. The nitrogen composition of the products from each of the diets was similar, with one exception being the significantly higher nonprotein nitrogen content in TMR-derived skim milk powder than that from the GRS system. Total amino acid analysis showed significantly higher concentrations of glycine in GRS- and CLV-derived sweet whey and acid whey than in those from TMR. The cysteine contents of CLV-derived ideal whey and acid whey were significantly higher than for TMR, while the valine content of GRS-derived acid whey was significantly higher than TMR. The phenylalanine content of GRS-derived ideal whey was significantly higher than that from CLV. Metabolomic analysis showed significantly higher concentrations of the metabolites glutamine, valine, and phosphocreatine in each ingredient type derived from TMR than those from GRS or CLV, while the serine content of each GRS-derived ingredient type was significantly higher than that in TMR-derived ingredients. These results demonstrate that the type of bovine feeding system used can have a significant effect on the amino acid composition and metabolome of skim milk and whey powders and may aid in the selection of raw materials for product manufacture, while the clear separation between the samples gives further evidence for distinguishing milk products produced from different feeding systems based on LC–MS/MS.
Redox Biology of Human Cumulus Cells: Basic Concepts, Impact on Oocyte Quality and Potential Clinical Use.

Significance Four decades have passed since the first successful human embryo conceived from a fertilization in vitro. Despite all advances, success rates in assisted reproduction techniques still remain unsatisfactory and it is well established that oxidative stress can be one of the major factors causing failure in in vitro fertilization techniques. Critical Issues There are many sources of Reactive Oxygen Species (ROS) in the female reproductive tract in vivo, that can be exacerbated (or aggravated) by pathological features. While an imbalance between ROS and antioxidants can result in oxidative damage, physiological levels of ROS are essential for oocyte maturation, ovulation and early embryonic growth where they act as signaling molecules. At the event of an assisted reproduction procedure, the Cumulus-Oophorus Complex (COC) is exposed to additional sources of oxidative stress in vitro. The cumulus cells (CCs) play essential roles in protecting the oocytes from oxidative damage. Recent Advances In the past years, researchers have been shown details of the supportive role cumulus cells play along oocyte maturation, development and fertilization processes. Regarding redox metabolism, it is now evident that the synergism between gamete and somatic cumulus cells is fundamental to further support a healthy embryo, since the oocyte lacks several defense mechanisms that are provided by the cumulus cells. Future Directions More studies are needed in order to elucidate redox biology in human CCs and oocyte. Also, randomized controlled trials will identify possible benefits of in vivo or in vitro administration of antioxidants for patients seeking IVF procedure.
Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients

Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays.
A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP’s discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.
Physical Activity-Related Health Competence, Physical Activity, and Physical Fitness: Analysis of Control Competence for the Self-Directed Exercise of Adolescents

(1) Background: Individuals have to effectively manage their physical activity in order to optimize the associated physical and psychological health benefits. Control competence allows the individual to structure and pace physical activity in a health-enhancing way. The concept was developed within a model of physical activity-related health competence, and is related to the concepts of health literacy and physical literacy. Therefore, the study firstly aimed to validate a self-report scale to measure the physical and psychological facets of control competence in adolescents. Secondly, relationships between control competence and its basic elements, knowledge and motivation, as well as between control competence, sport activity, and fitness, were investigated. (2) Methods: In two cross-sectional studies, ninth grade adolescents (study A: n = 794, 51% female; study B: n = 860, 52% female) were tested using self-report scales (study A and B), a test for health-related fitness knowledge (study B), and cardiovascular and muscular fitness tests (study B). (3) Results: Confirmatory factor analyses confirmed the two-factor structure of the self-report scale for control competence in studies A and B. In addition, the results of structural equation modeling in study B showed a relationship between motivation (via control competence) and sport activity, and a relationship between control competence and fitness. (4) Conclusion: The questionnaire extends the ability to assess control competence in adolescents. Moreover the findings support the importance of control competence in order to achieve health benefits through physical activity.
The Nature of Reality: Human Stress Recovery during Exposure to Biodiverse, Multisensory Virtual Environments

Immersive virtual environments (IVEs) were used to test the effects of biodiversity on recovery from induced stress. Three natural environments and one urban environment were used to represent ordinal levels of biodiversity (none, low, moderate, and high). The four IVEs comprised visual, auditory, and olfactory stimuli. An additional high biodiversity IVE without auditory or olfactory stimuli was also included to study the effects of multisensory stimulation per se on recovery from stress and perceptions of biodiversity. Following stress induction via a novel IVE Trier Social Stress Test (TSST-IVE), heart rate and five self-reported well-being measures were used to assess participants’ recovery after immersion in one of the five IVEs. The results showed consistent well-being responses across both self-reported and physiological measures, suggesting biodiversity does directly affect human well-being. However, the relationship was not linear. For most measures of well-being, stress recovery was least effective in the urban IVE, consistent with past research. The low biodiversity IVE elicited the greatest improvement in all well-being measures except self-reported calmness. One could speculate that the landscape features of the least biodiverse IVE may elicit subconscious preferences toward savanna-like landscapes, as suggested by previous studies. The IVE depicting a moderate level of biodiversity was the least restorative of the natural environments. A multisensory experience was associated with better recovery in all measures of well-being than a visual-only experience, and perceptions of landscape components significantly differed between two identical nature scenes when auditory and olfactory stimuli were removed. Nuances in the data and implications of the findings are discussed. The results signal a need for caution and question the assumption that cultural ecosystem services align with positive outcomes for biodiversity conservation.
Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

The objectives of this document are to provide guidance in the diagnosis and management of autoimmune hepatitis (AIH) based on current evidence and expert opinion, and to present guidelines to clinically relevant questions based on systematic reviews of the literature and the quality of evidence (1). This practice guideline/guidance constitutes an update of the guidelines on AIH published in 2010 by the American Association for the Study of Liver Diseases (AASLD) (2). It updates the epidemiology, diagnosis, management, and outcomes of AIH in adults and children.
The mutual effect of hyperlipidemia and proinflammatory cytokine related to periodontal infection

Hyperlipidemia is a highly prevalent worldwide disease. Moreover, it is a known risk factor for cardiovascular diseases. In contrast, periodontitis is an inflammatory disease in which Gram-negative microorganisms and their products are the principal etiologic agents. They produce endotoxins in the form of lipopolysaccharides, which are instrumental in generating a host-mediated tissue destructive immune response and have been connected to several systemic health changes, including an altered lipid metabolism. The aim of this study was to evaluate the bidirectional effect of hyperlipidemia and pharmacological treatment of hyperlipidemia on proinflammatory cytokines related to the severity of periodontal disease. Twenty-four individuals aged above 20 years seen at the clinics of Ain Shams University (Cairo, Egypt), were recruited into this study and were divided into three groups. All of them suffered from chronic periodontitis, and two individuals suffered from hyperlipidemia. Only one group received lipid-lowering treatment and was paired according to sex and age. Their levels of total cholesterol, low-density cholesterol and high-density cholesterol, and triglycerides, as well as serum level of interleukin-1&bgr; and tumor necrosis factor &agr;, were determined at baseline, after 3 weeks, and after 6 months of mechanical and chemical periodontal treatments. Variables related to high-cholesterol levels, including age and sex, were evaluated. The values recommended by the World Health Organization were considered to classify hyperlipidemia. The results showed that the change between baseline and week 3 showed no significant change except in mean levels of total cholesterol, with a significance of 0.022 or less, and low-density lipoprotein, with a significance of 0.022 or less, in individuals who received lipid-lowering treatment with periodontitis treatment. However, the group with hyperlipidemia that did not receive lipid-lowering drugs showed a decrease in triglyceride levels, but it was a nonsignificant change, which may show a trend. None of the other lipid and cytokine profiles showed a significant change. Therefore, in this studied population, although a relationship was found between periodontal disease treatment and blood lipid levels it was not significant.
Unification of Opposites between Two Antioxidant Transcription Factors Nrf1 and Nrf2 in Mediating Distinct Cellular Responses to the Endoplasmic Reticulum Stressor Tunicamycin

The water-soluble Nrf2 (nuclear factor, erythroid 2-like 2, also called Nfe2l2) is accepted as a master regulator of antioxidant responses to cellular stress, and it was also identified as a direct target of the endoplasmic reticulum (ER)-anchored PERK (protein kinase RNA-like endoplasmic reticulum kinase). However, the membrane-bound Nrf1 (nuclear factor, erythroid 2-like 1, also called Nfe2l1) response to ER stress remains elusive. Herein, we report a unity of opposites between these two antioxidant transcription factors, Nrf1 and Nrf2, in coordinating distinct cellular responses to the ER stressor tunicamycin (TU). The TU-inducible transcription of Nrf1 and Nrf2, as well as GCLM (glutamate cysteine ligase modifier subunit) and HO-1 (heme oxygenase 1), was accompanied by activation of ER stress signaling networks. Notably, the unfolded protein response (UPR) mediated by ATF6 (activating transcription factor 6), IRE1 (inositol requiring enzyme 1) and PERK was significantly suppressed by Nrf1α-specific knockout, but hyper-expression of Nrf2 and its target genes GCLM and HO-1 has retained in Nrf1α−/− cells. By contrast, Nrf2−/−ΔTA cells with genomic deletion of its transactivation (TA) domain resulted in significant decreases of GCLM, HO-1 and Nrf1; this was accompanied by partial decreases of IRE1 and ATF6, rather than PERK, but with an increase of ATF4 (activating transcription factor 4). Interestingly, Nrf1 glycosylation and its trans-activity to mediate the transcriptional expression of the 26S proteasomal subunits, were repressed by TU. This inhibitory effect was enhanced by Nrf1α−/− and Nrf2−/−ΔTA, but not by a constitutive activator caNrf2ΔN (that increased abundances of the non-glycosylated and processed Nrf1). Furthermore, caNrf2ΔN also enhanced induction of PERK and IRE1 by TU, but reduced expression of ATF4 and HO-1. Thus, it is inferred that such distinct roles of Nrf1 and Nrf2 are unified to maintain cell homeostasis by a series of coordinated ER-to-nuclear signaling responses to TU. Nrf1α (i.e., a full-length form) acts in a cell-autonomous manner to determine the transcription of most of UPR-target genes, albeit Nrf2 is also partially involved in this process. Consistently, transactivation of ARE (antioxidant response element)-driven BIP (binding immunoglobulin protein)-, PERK- and XBP1 (X-box binding protein 1)-Luc reporter genes was mediated directly by Nrf1 and/or Nrf2. Interestingly, Nrf1α is more potent than Nrf2 at mediating the cytoprotective responses against the cytotoxicity of TU alone or plus tBHQ (tert-butylhydroquinone). This is also further supported by the evidence that the intracellular reactive oxygen species (ROS) levels are increased in Nrf1α−/− cells, but rather are, to our surprise, decreased in Nrf2−/−ΔTA cells.