Miracle-dz/UniFAR-FTUs huggingface dataset:
Skeletal Muscle Mass Reduction Velocity as a Simple Prognostic Indicator for Patients with Metastatic Urothelial Carcinoma Receiving Second-Line Chemotherapy

Background: Patients with metastatic urothelial carcinoma (mUC) have an uncertain prognosis. The aim of the current study was to evaluate the prognostic potential of a skeletal muscle mass reduction index measured by computed tomography (CT) for mUC patients undergoing second-line gemcitabine and docetaxel (GD) chemotherapy. Methods: We retrospectively reviewed 44 patients with mUC who received second-line GD chemotherapy between 2006 and 2015 in our hospital. Skeletal muscle area (SMA) at the third lumbar vertebra was measured using CT images obtained from medical records, and a skeletal muscle index (SMI) was calculated for each patient as: SMI = SMA / height2. Changes in SMI across timepoints (SMI inclination) were calculated as: SMI inclination = [( SMI/SMI)/duration of the interval between imaging visits]. Patients were then divided into two groups: a “steep” group (SMI inclination < -0.01) and a “gentle” group (SMI inclination ≥ -0.01). Kaplan-Meier curves and multivariate Cox proportional hazards regression models were used to evaluate the relationship between SMI inclination and overall survival (OS). Results: There were no differences in patient characteristics between the two groups with respect to median age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), disease control rate or first-line treatment regimen. OS from the start of second-line GD therapy group was significantly shorter in the “steep” group relative to the “gentle” group. The multivariate analysis revealed that “steep” SMI inclination and presence of anemia were strong predictors of poor prognosis. Conclusion: Higher values of SMI inclination, indicating a faster rate of skeletal muscle mass reduction, may serve as a useful predictive marker for OS in mUC patients undergoing second-line GD chemotherapy.
GATA1 mutations in red cell disorders

GATA1 is an essential regulator of erythroid cell gene expression and maturation. In its absence, erythroid progenitors are arrested in differentiation and undergo apoptosis. Much has been learned about GATA1 function through animal models, which include genetic knockouts as well as ones with decreased levels of expression. However, even greater insights have come from the finding that a number of rare red cell disorders, including Diamond–Blackfan anemia, are associated with GATA1 mutations. These mutations affect the amino‐terminal zinc finger (N‐ZF) and the amino‐terminus of the protein, and in both cases can alter the DNA‐binding activity, which is primarily conferred by the third functional domain, the carboxyl‐terminal zinc finger (C‐ZF). Here we discuss the role of GATA1 in erythropoiesis with an emphasis on the mutations found in human patients with red cell disorders.
The Pivotal Roles of the Epithelial Membrane Protein Family in Cancer Invasiveness and Metastasis

The members of the family of epithelial membrane proteins (EMPs), EMP1, EMP2, and EMP3, possess four putative transmembrane domain structures and are composed of approximately 160 amino acid residues. EMPs are encoded by the growth arrest-specific 3 (GAS3)/peripheral myelin protein 22 kDa (PMP22) gene family. The GAS3/PMP22 family members play roles in cell migration, growth, and differentiation. Evidence indicates an association of these molecules with cancer progression and metastasis. Each EMP has pro- and anti-metastatic functions that are likely involved in the complex mechanisms of cancer progression. We have recently demonstrated that the upregulation of EMP1 expression facilitates cancer cell migration and invasion through the activation of a small GTPase, Rac1. The inoculation of prostate cancer cells overexpressing EMP1 into nude mice leads to metastasis to the lymph nodes and lungs, indicating that EMP1 contributes to metastasis. Pro-metastatic properties of EMP2 and EMP3 have also been proposed. Thus, targeting EMPs may provide new insights into their clinical utility. Here, we highlight the important aspects of EMPs in cancer biology, particularly invasiveness and metastasis, and describe recent therapeutic approaches.
Ohmic Contacts on p-Type Al-Implanted 4H-SiC Layers after Different Post-Implantation Annealings

This paper reports on the electrical activation and Ohmic contact properties on p-type Al-implanted silicon carbide (4H-SiC). In particular, the contacts were formed on 4H-SiC-implanted layers, subjected to three different post-implantation annealing processes, at 1675 °C, 1175 °C, and 1825 °C. Under these post-implantation annealing conditions, the electrical activation of the Al dopant species increased from 39% to 56%. The Ti/Al/Ni contacts showed an Ohmic behavior after annealing at 950 °C. The specific contact resistance ρc could be lowered by a factor of 2.6 with the increase of the post-implantation annealing temperature. The result can be useful for application in device fabrication. Moreover, the dependence of ρc on the active acceptor concentration followed the thermionic field emission model, with a barrier height of 0.63 eV.
Association of Twelve Candidate Gene Polymorphisms with the Intramuscular Fat Content and Average Backfat Thickness of Chinese Suhuai Pigs

Simple Summary Appropriate intramuscular fat content (IFC) is the goal of consumers and the direction that breeders must pursue. However, it is difficult to improve the IFC but not average backfat thickness (ABT) by traditional breeding methods, and pigs must be slaughtered to accurately measure IFC. Marker-assisted selection (MAS) provides an economic and efficient method to improve the IFC in pigs. Our research indicated that the FABP3 (rs1110770079) single nucleotide polymorphism (SNP) could be a candidate gene associated with IFC (but not ABT), and IFC could be improved by selecting the individuals with a favorable genotype (GG) of FABP3 (rs1110770079) SNP for pig breeding. Abstract The present study aimed to identify the molecular markers for genes that influence intramuscular fat content (IFC), but not average backfat thickness (ABT). A total of 330 Suhuai pigs were slaughtered, and measurements of IFC and ABT were obtained. Phenotypic and genetic correlations between IFC and ABT were calculated. Thirteen single nucleotide polymorphisms (SNPs) among 12 candidate genes for IFC were analyzed, including FABP3, LIPE, IGF1, IGF2, LEP, LEPR, MC4R, PHKG1, RETN, RYR1, SCD, and UBE3C. Associations of the evaluated SNPs with IFCIFC and ABT were performed. Our results showed that the means of IFC and ABT were 1.99 ± 0.03 % and 26.68 ± 0.28 mm, respectively. The coefficients of variation (CVs) of IFC and ABT were 31.21% and 19.36%, respectively. The phenotypic and genetic correlations between IFC and ABT were moderate. Only the FABP3 (rs1110770079) was associated with IFC (p < 0.05) but not with ABT. Besides, there was a tendency for associations of RYR1 (rs344435545) and SCD (rs80912566) with IFC (p < 0.1). Our results indicated that the FABP3 (rs1110770079) SNP could be used as a marker to improve IFC without changing ABT in the Suhuai pig breeding system.
cAMP Response Element Modulator α Induces Dual Specificity Protein Phosphatase 4 to Promote Effector T Cells in Juvenile-Onset Lupus

Key Points CREMα induces DUSP4 phosphatase expression in CD4+ T cells. DUSP4 promotes IL-17A and reduces IL-2 production by effector T cells. The CREMα/DUSP4 axis is involved in the pathophysiology of SLE. Effector CD4+ T cells with increased IL-17A and reduced IL-2 production contribute to tissue inflammation and organ damage in systemic lupus erythematosus (SLE). Increased expression of the transcription factor cAMP response element modulator (CREM) α promotes altered cytokine expression in SLE. The aim of this study was to investigate CREMα-mediated events favoring effector CD4+ T cells in health and disease. Using CRISPR/Cas9 genome editing and lentiviral transduction, we generated CREMα-deficient and CREMα-overexpressing Jurkat T cells. Gene expression and regulatory events were assessed using luciferase reporter assays and chromatin immunoprecipitation. Interaction between CREMα and p300 was investigated using proximity ligation assays, coimmunoprecipitation, and knockdown of p300. Gene expression profiles of modified cells were compared with CD4+ T cells from patients with juvenile-onset SLE. We show that CREMα induces dual specificity protein phosphatase (DUSP) 4 in effector CD4+ T cells through corecruitment of p300. The transcriptional coactivator p300 mediates histone acetylation at DUSP4, prompting increased gene expression. Using DUSP4 transfection models and genetically modified CREM-deficient and CREMα-overexpressing T cells, we demonstrate the molecular underpinnings by which DUSP4 induces IL-17A while limiting IL-2 expression. We demonstrate that CD4+ T cells from patients with juvenile-onset SLE share phenotypical features with CREMα-overexpressing CD4+ T cells, including increased DUSP4 expression and imbalanced IL-17A and IL-2 production. Taken together, we describe CREMα-mediated mechanisms that involve the transcriptional upregulation of DUSP4, leading to imbalanced cytokine production by effector T cells. Our findings identify the CREMα/DUSP4 axis as a promising candidate in the search for biomarkers and therapeutic targets in SLE.
PINK1 overexpression protects against cerebral ischemia through Parkin regulation

Mitochondrial dynamics and function are important for cell survival regulation under stress. In this study, we report that cerebral ischemia/reperfusion (I/R) injury significantly reduced mitochondrial function through reduced PTEN‐induced kinase 1 (PINK1) expression, ATP (Adenosine triphosphate) levels, and increased oxidative stress compared to sham rats. PINK1 overexpression mice significantly improved mitochondrial function by increased mitochondrial complex I, II, and III activities and ATP levels with concomitant decline in reactive oxygen species levels. PINK1 overexpression mice after I/R injury significantly reduced apoptosis through downregulation of cytochrome c, p53 expressions compared to cerebral I/R injury rats. Furthermore, we showed from parkin siRNA studies that PINK1 regulated phosphorylation parkin is critical to the protection against cerebral I/R injury. Altogether, we show that PINK1 mediated parkin regulation is key to the protection against cerebral I/R injury through regulation of mitochondrial function and apoptosis.
Accelerometer-measured Physical Activity, Reproductive Hormones, and DNA Methylation.

INTRODUCTION/PURPOSE Limited studies have examined the association of physical activity with reproductive hormones, DNA methylation, and pubertal status among adolescents. METHODS Among 248 boys and 271 girls, we estimated daily physical activity levels based on 7 days of wrist-worn accelerometer data. We used an isotemporal substitution paradigm and sex-stratified regression models to examine the association of physical activity levels with 1) testosterone, cortisol, progesterone and androstenedione concentrations; 2) DNA methylation of long interspersed nucleotide (LINE-1) repeats, and the genes H19, hydroxysteroid (11-Beta) dehydrogenase 2 (HSD11B2) and peroxisome proliferator-activated receptor alpha (PPARA) from blood leukocytes; and 3) Tanner stages, adjusted for age, BMI and socioeconomic status. RESULTS In boys, substituting 30 minutes of moderate physical activity for 30 minutes of sedentary behavior per day was associated with 29% (-49%, 0%) of lower testosterone, and 29% (4%, 61%) of higher progesterone. Substituting 30 minutes of light physical activity for sedentary behavior was associated with 13% (-22%, -2%) of lower progesterone. Among girls, 30 minutes of additional sedentary behavior was associated with 8% (-15%, 0%) of lower testosterone, and 24% (8%, 42%) of higher progesterone concentrations. Substituting 30 minutes of moderate physical activity for sedentary behavior was associated with 15% (0%, 31%) of higher cortisol, while substituting the same amount of light physical activity for sedentary behavior was associated with 22% (-39%, 0%) of lower progesterone. Substituting 30 minutes of vigorous physical activity for sedentary behavior per day was associated with almost six times higher levels (5.83 (1.79, 9.86)) of HSD11B2 methylation in boys. CONCLUSIONS Accelerometer-measured daily physical activity was associated with reproductive hormones and HSD11B2 DNA methylation, differed by sex and activity intensity levels.
Sensitivity and Specificity of Pathologic Findings to Diagnose Lupus Nephritis.

BACKGROUND AND OBJECTIVES In 2012, the Systemic Lupus International Collaborating Clinics proposed that lupus nephritis, in the presence of positive ANA or anti-dsDNA antibody, is sufficient to diagnose SLE. However, this "stand-alone" kidney biopsy criterion is problematic because the ISN/RPS classification does not specifically define lupus nephritis. We investigated the combination of pathologic features with optimal sensitivity and specificity for the diagnosis of lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Three hundred consecutive biopsies with lupus nephritis and 560 contemporaneous biopsies with nonlupus glomerulopathies were compared. Lupus nephritis was diagnosed if there was a clinical diagnosis of SLE and kidney biopsy revealed findings compatible with lupus nephritis. The control group consisted of consecutives biopsies showing diverse glomerulopathies from patients without SLE, including IgA nephropathy, membranous glomerulopathy, pauci-immune glomerulonephritis, membranoproliferative glomerulonephritis (excluding C3 GN), and infection-related glomerulonephritis. Sensitivity and specificity of individual pathologic features and combinations of features were computed. RESULTS Five characteristic features of lupus nephritis were identified: "full-house" staining by immunofluorescence, intense C1q staining, extraglomerular deposits, combined subendothelial and subepithelial deposits, and endothelial tubuloreticular inclusions, each with sensitivity ranging from 0.68 to 0.80 and specificity from 0.8 to 0.96. The presence of at least two, three, or four of the five criteria had a sensitivity of 0.92, 0.8, and 0.66 for the diagnosis of lupus nephritis, and a specificity of 0.89, 0.95, and 0.98. CONCLUSIONS In conclusion, combinations of pathologic features can distinguish lupus nephritis from nonlupus glomerulopathies with high specificity and varying sensitivity. Even with stringent criteria, however, rare examples of nonlupus glomerulopathies may exhibit characteristic features of lupus nephritis.
The Intraocular Pressure-Lowering Effect of Persimmon leaves (Diospyros kaki) in a Mouse Model of Glaucoma

The aim of this study was to evaluate the pharmacological efficacy of persimmon leaves in two glaucoma models, microbeads-induced ocular hypertension (OHT) and DBA/2 mouse. Thus, we demonstrated that Ethanol Extract of Diospyros kaki (EEDK) reduced elevated intraocular pressure (IOP) in both mouse models of glaucoma by measurements with a tonometer. In particular, we revealed that retinal ganglion cell loss and optic nerve damage caused by IOP elevation were markedly diminished as assessed by TUNEL assay, H&E staining, and fluorescent staining, while the expression of soluble guanylate cyclase (sGCα-1) increased, when EEDK was administered, as revealed by western blot. Moreover, the b-wave magnitude indicating functional scotopic vision was significantly improved in EEDK-administered DBA/2 mice during the 10-week follow-up study, as observed with electroretinography. Collectively, our results suggested that EEDK could be an effective therapeutic and IOP-lowering agent for preventing and treating retinal degenerative diseases such as glaucoma.
Dental Epithelial Stem Cells as a Source for Mammary Gland Regeneration and Milk Producing Cells In Vivo

The continuous growth of rodent incisors is ensured by clusters of mesenchymal and epithelial stem cells that are located at the posterior part of these teeth. Genetic lineage tracing studies have shown that dental epithelial stem cells (DESCs) are able to generate all epithelial cell populations within incisors during homeostasis. However, it remains unclear whether these cells have the ability to adopt alternative fates in response to extrinsic factors. Here, we have studied the plasticity of DESCs in the context of mammary gland regeneration. Transplantation of DESCs together with mammary epithelial cells into the mammary stroma resulted in the formation of chimeric ductal epithelial structures in which DESCs adopted all the possible mammary fates including milk-producing alveolar cells. In addition, when transplanted without mammary epithelial cells, DESCs developed branching rudiments and cysts. These in vivo findings demonstrate that when outside their niche, DESCs redirect their fates according to their new microenvironment and thus can contribute to the regeneration of non-dental tissues.
Incidence and predictors of total mortality in 267 adults presenting with mitochondrial diseases

Assessing long‐term mortality and identifying predictors of death in adults with mitochondrial diseases. We retrospectively included adult patients with genetically proven mitochondrial diseases referred to our centre between January 2000 and June 2016, and collected information relative to their genetic testing, clinical assessments, and vital status. We performed single and multiple variable analyses in search of predictors of total mortality, and calculated hazard ratios (HR) and 95% confidence intervals (CI). We included 267 patients (women 59%; median age 43.3 [31.3‐54.2] years), including 111 with mitochondrial DNA (mtDNA) single large‐scale deletions, 65 with m.3243A>G, 24 with m.8344A>G, 32 with other mtDNA point mutations, and 36 patients with nuclear genes mutations. Over a median follow‐up of 8.9 years (0.3 to 18.7), 61 patients (22.8%) died, at a median age of 50.7 (37.9‐51.9) years. Primary cause of death was cardiovascular disease in 16 patients (26.2%), respiratory in 11 (18.0%), and gastrointestinal in 5 (8.1%). By multiple variable analysis, diabetes (HR 2.75; 95% CI 1.46‐5.18), intraventricular cardiac conduction defects (HR 3.38; 95% CI 1.71‐6.76) and focal brain involvement (HR 2.39; 95% CI 1.25‐4.57) were independent predictors of death. Adult patients with mitochondrial diseases present high morbidity that can be independently predicted by the presence of diabetes, intraventricular cardiac conduction defects, and focal brain involvement.
Twin to twin transfusion syndrome

Twin-to-Twin Transfusion Syndrome (TTTS) is a rare placental disease that can occur at any time during pregnancy [5] involving identical twins. TTTS occurs when there is an unequal distribution of placental blood vessels between fetuses, which leads to a disproportionate supply of blood delivered. This unequal allocation of blood leads to developmental problems in both fetuses that can range in severity depending on the type, direction, and number of interconnected blood vessels.
ATTITUDES TOWARD DEMOCRACY AND EU IN TRANSITIONAL SOCIETIES: THE BULGARIAN CASE

In 1989, like other countries from Central and Eastern Europe, Bulgaria began its transition to democracy. It started with enthusiasm and great expectations, which later led to disappointment and blaming the democracy for every negative situation, both on personal and national level. In 2007 Bulgaria became member of the EU, which gave the society a new hope for better life, especially in its financial and economic dimensions. Nevertheless, some challenges for the EU of the last few years have been leading to a rise of Euroscepticism. Thus, the purpose of the paper is to examine the transformation of the attitudes toward democracy and the EU since Bulgaria became member of the Union. The data used is from EIU Democracy Index and Standard Eurobarometer. The raw data of the Standard Eurobarometer from 2007 and 2017 was used and the results for Bulgaria were compared and analyzed. Alongside, the results from 2017 were compared to the results of the three most democratic countries in the EU (according to EIU Democracy Index). The results indicate that the share of Bulgarians with positive attitudes toward EU decreased but in many aspects Bulgarians share opinions very close to the countries who are ‘full democracies’.
Efficient Energy Management Technique for Optimal Resource Allocation in a Wireless Powered Communication Network

— The study focused on achieving optimal resource allocation for Wireless Powered Communication Network (WPCN) using efficient energy management scheme. The proposed WPCN model was developed, structured with two Radio frequency channels viz-the RF energy transfer channel and the data communication. Analytical expressions were deduced to obtain optimal transmission power and system efficiency. Energy Management Scheme was applied in the system design to minimize the amplifier power consumption in the power beacon and guarantees the power beacon in receiving sensor measurement reports from the sensor node as frequently as required by a sensor application. It ensures optimal consumption of the harvested energy for continuous operation by the sensor node. A testbed was developed to measure the parameters and the system model characteristics which facilitates adequate evaluation of the energy management scheme. The results obtained showed that the proposed scheme adaptively controls the WPCN for optimal energy neutrality and high-efficiency RF power transfer. The proposed energy management scheme was observed to consume less than 50% of the power consumed by the no amplifier duty cycling scheme.
Long non-coding RNAs (lncRNAs) and cardiovascular disease (CVD)

III Preface . IV Table of contents . V Intro . 1 1.1.1 The non-coding RNAs . 2 1.1.2 History of lncRNAs . 4 1.1. 3 lncRNA definition . 5 1.1. 4 Classification of lncRNAs . 5 1.1. 5 Localization and expression . 7 1.1. 6 Functions, mechanisms and secondary structure . 8 1.2 Cardiovascular disease . 10 1.2.1 Pathophysiology of atherosclerotic disease . 10 1.2. 2 LncRNAs in cardiovascular development and differentiation . 11 Table 1: List of lncRNA involved in tissue development and organogenesis . 12 Methods . 14 2.1 Search strategy . 14 Table 2: PICO table . 14 2.1.1 Databases and criteria . 14 Results . 16 3.1 Search results and included articles . 16 Table 3: Cochrane Library (04.01.2019) search results . 16 Table 4: PubMed (04.01.2019) search results: . 16 Table 5: Review articles . 17 Table 6: Meta-Analyses . 18 lncRNAs associated with cardiovascular disease . 20 4.1.1 MALAT1 . 21 4.1.2 MIAT . 22 4.1. 3 ANRIL / CDKN2B-AS1 . 23 4.1. 4 LIPCAR . 25