Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Diagnosis of 5α-Reductase Deficiency in Newborns

5α-reductase-2 deficiency is a rare autosomal recessive form of 46,XY disorders of sex differentiation (DSD), caused by mutations in the steroid 5α-reductase type 2 gene (SRD5A2), presenting at birth with variable degrees of undervirilization. We report on three Italian newborns with 46,XY DSD in whom the evaluation of testosterone, dihydrotestosterone, testosterone/dihydrotestosterone (T/DHT) ratio and molecular analysis of the 5α-reductase type 2 gene was made in their first month of life. Baseline T/DHT ratio suggested 5α-reductase-2 deficiency; the diagnosis was confirmed by molecular genetics (homozygous mutation in exon 4 [G196S], heterozygous mutation in exon 1 and 5 [W35X/Y235F], heterozygous mutation plus polymorphism in exon 1 [G34W/A49T]). Proper investigation permitted early reassignment to male sex in two babies, assigned to female sex just after birth. In infancy, the T/DHT ratio, assessed by suitable assay methods and evaluated by age-appropriate reference values, seems to be able to select newborns affected by 5α-reductase-2 deficiency. Molecular analysis of the SRD5A2 gene should be warranted in newborns with abnormal ratio before sex assignment.
Shocks and Volatility Spillover Between Stock Markets of Developed Countries and GCC Stock Markets

ABSTRACT The purpose of this paper is to examine the spillover of returns, information and volatility of returns, and conditional variance-covariance between the stock markets of developed countries namely the United States of America, the United Kingdom and China (US, UK and CH) and the stock markets of Gulf Cooperation Council (GCC) countries (Kuwait, United Arab Emirates, Qatar, Saudi Arabia, Oman, and Bahrain) using daily returns spanned from 2 March 2003 to 9 December 2010. We consider shocks and volatility spillover model by applying a multivariate generalized autoregressive conditional heteroskedasticity (MGARCH) model using; MGARCH-BEKK to identify the source and magnitude of volatility and shock spillover. We get the correlation between GCC markets is positive, indicating that there is a common factor which is driving the markets towards the same direction. Evidence shows that the own-shocks and volatility in GCC markets are highly significant. Cross-information spillover effects, as another observable trend, are found between Qatar and Oman. Furthermore, the results show that UA is significantly affected by spillover (return, shocks and volatility) from developed markets, while there have been no significant effects seen from Kuwait markets. This study takes a new empirical look in the sense that the models incorporating all the countries under investigation are estimated jointly utilizing multivariate GARCH-BEKK formulation. In addition, this paper should be interesting for academicians as well as practitioners. Including those interested in modelling multivariate volatility for financial market risk management.
Income Taxes, Political Accountability and Public Goods Provision

This paper proposes and analyzes an unexplored mechanism through which in- creases in income taxes -understood as increases in either marginal tax rates or tax progressivity- might positively affect the degree of political accountability (PA), and consequently, the provision of public goods (PG) in a democratic environment. To do this, we build a voting-agency model with income-heterogeneous voters and different tax schedules. Our main result is that, in fact, the provided mechanism uncovers a direct link between income taxes and the degree of PA. A crucial condition for observing a positive effect of an increase in income taxes on both voters' political demands for PG and the provision of PG is that said increase must negatively affect the median voter's disposable income. If this does not occur, which may well be the case in low-income countries, the effect of an increase in income taxes on the degree of PA is ambiguous. We also explore how agency problems a affect the majority-voting equilibrium income tax rate.
Bioactivity and Pharmakokinetics of Human Proinsulin in Comparison to Human Insulin after Intravenous and Subcutaneous Injection

The hypoglycemic actions of human insulin (1 IU/kg b.w.) and biosynthetic human proinsulin in about equimolar amounts were studied after intravenous and subcutaneous injection in rabbits. Blood samples were taken up to four hours after injection for the determination of blood glucose and immunoreactive levels of both insulin and human C-peptide. For the determination of human C-peptide, serum taken after proinsulin injection was divided into two fractions. One was examined directly by the human C-peptide radioimmunoassay and the other after incubation with a protein-A-sepharose coupled insulin antibody to find "free human C-peptide". Proinsulin in amounts equimolar to 1 IU insulin/kg b.w. , exerted a 34% stronger hypoglycemic action after subcutaneous injection than after intravenous administration (area under curve estimation). Proinsulin-induced hypoglycemia did not last longer after intravenous administration than that induced by intravenous insulin. Although subcutaneous proinsulin did not show the same maximum decrease of blood glucose compared to subcutaneous insulin, its action was significantly prolonged (up to 180 min). Specific measurement of free human C-peptide showed no evidence of conversion of proinsulin to insulin and C-peptide.
Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum‐sensitive epithelial ovarian carcinoma

The benefit of cytoreductive surgery for patients with recurrent epithelial ovarian cancer has not been defined clearly. The objective of this study was to identify prognostic factors for survival in patients who underwent secondary cytoreduction for recurrent, platinum‐sensitive epithelial ovarian cancer and to establish generally applicable guidelines and selection criteria.
Activation of yeast polymerase II transcription by herpesvirus VP16 and GAL4 derivatives in vitro

Fusion proteins known to activate transcription in vivo were tested for the ability to stimulate transcription in vitro in a recently developed Saccharomyces cerevisiae RNA polymerase II transcription system. One fusion protein, whose activation domain was derived from the herpesvirus transcriptional activator VP16, gave more than 100-fold stimulation in the in vitro system. The order of effects of the various proteins was the same for transcription in vitro and in vivo, suggesting that the natural mechanism of activation is preserved in vitro.
Derepression of MicroRNA-mediated Protein Translation Inhibition by Apolipoprotein B mRNA-editing Enzyme Catalytic Polypeptide-like 3G (APOBEC3G) and Its Family Members*

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) and its fellow cytidine deaminase family members are potent restrictive factors for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. A3G interacts with a vast spectrum of RNA-binding proteins and is located in processing bodies and stress granules. However, its cellular function remains to be further clarified. Using a luciferase reporter gene and green fluorescent protein reporter gene, we demonstrate that A3G and other APOBEC family members can counteract the inhibition of protein synthesis by various microRNAs (miRNAs) such as mir-10b, mir-16, mir-25, and let-7a. A3G could also enhance the expression level of miRNA-targeted mRNA. Further, A3G facilitated the association of microRNA-targeted mRNA with polysomes rather than with processing bodies. Intriguingly, experiments with a C288A/C291A A3G mutant indicated that this function of A3G is separable from its cytidine deaminase activity. Our findings suggest that the major cellular function of A3G, in addition to inhibiting the mobility of retrotransposons and replication of endogenous retroviruses, is most likely to prevent the decay of miRNA-targeted mRNA in processing bodies.
An electronic health records study of long-term weight gain following antidepressant use.

IMPORTANCE Short-term studies suggest antidepressants are associated with modest weight gain but little is known about longer-term effects and differences between individual medications in general clinical populations. OBJECTIVE To estimate weight gain associated with specific antidepressants over the 12 months following initial prescription in a large and diverse clinical population. DESIGN, SETTING, AND PARTICIPANTS We identified 22,610 adult patients who began receiving a medication of interest with available weight data in a large New England health care system, including 2 academic medical centers and affiliated outpatient primary and specialty care clinics. We used electronic health records to extract prescribing data and recorded weights for any patient with an index antidepressant prescription including amitriptyline hydrochloride, bupropion hydrochloride, citalopram hydrobromide, duloxetine hydrochloride, escitalopram oxalate, fluoxetine hydrochloride, mirtazapine, nortriptyline hydrochloride, paroxetine hydrochloride, venlafaxine hydrochloride, and sertraline hydrochloride. As measures of assay sensitivity, additional index prescriptions examined included the antiasthma medication albuterol sulfate and the antiobesity medications orlistat, phentermine hydrochloride, and sibutramine hydrochloride. Mixed-effects models were used to estimate rate of weight change over 12 months in comparison with the reference antidepressant, citalopram. MAIN OUTCOME AND MEASURE Clinician-recorded weight at 3-month intervals up to 12 months. RESULTS Compared with citalopram, in models adjusted for sociodemographic and clinical features, significantly decreased rate of weight gain was observed among individuals treated with bupropion (β [SE]: -0.063 [0.027]; P = .02), amitriptyline (β [SE]: -0.081 [0.025]; P = .001), and nortriptyline (β [SE]: -0.147 [0.034]; P < .001). As anticipated, differences were less pronounced among individuals discontinuing treatment prior to 12 months. CONCLUSIONS AND RELEVANCE Antidepressants differ modestly in their propensity to contribute to weight gain. Short-term investigations may be insufficient to characterize and differentiate this risk.
Early assessment of renal resistance index after kidney transplant can help predict long-term renal function.

BACKGROUND Color Doppler ultrasonography of intrarenal arterial resistance index (RI), performed early after kidney transplant, has proven to reliably predict short-term allograft function. The aim of this study was to assess whether it could also predict long-term renal function. METHODS We retrospectively analysed 76 kidney transplant patients who underwent RI assessment within 1 month after the transplant, subdivided into two groups according to RI values, lower (group A) or higher (group B) than its median value (0.635). RESULTS Compared with group A subjects, the patients of group B were older at the time of transplant (42 +/- 9 vs 35 +/- 8 years; P = 0.001), the donor age was also older (41 +/- 16 vs 33 +/- 13 years; P = 0.02) and had a slightly higher proteinuria (0.54 +/- 0.5 vs 0.32 +/- 0.2 g/24 h; P = 0.02). Serum creatinine, ciclosporin or tacrolimus trough level, arterial blood pressure, number of human leukocyte antigen (HLA) mismatches, anti-hypertensive medications and incidence of delayed graft function were not significantly different between the two groups. By univariate analysis, RI turned out to directly correlate with the recipient age, donor age and daily proteinuria (P = 0.007, P = 0.0007 and P = 0.02, respectively). Multivariate analysis showed that only donor and recipient age maintained their independent predictive value on RI. Kaplan-Meier analysis, considering a serum creatinine increase >50% as the endpoint of the study, showed a statistically significant different graft survival in the two groups (log-rank test = 5.489; P = 0.01). The univariate relative risk of deterioration of graft function among patients with higher RI was 3.77. Proteinuria and recipient age increased the risk as well. CONCLUSIONS Our data seem to suggest that early determination of RI can help predict long-term graft function in kidney transplant recipients.
Feeling old today? Daily health, stressors, and affect explain day-to-day variability in subjective age

Objectives: Subjective age is an important correlate of health, well-being, and longevity. So far, little is known about short-term variability in subjective age and the circumstances under which individuals feel younger/older in daily life. This study examined whether (a) older adults’ felt age fluctuates on a day-to-day basis, (b) daily changes in health, stressors, and affect explain fluctuations in felt age, and (c) the daily associations between felt age and health, stressors, or affect are time-ordered. Method: Using an eight-day daily diary approach, N = 43 adults (60–96 years, M = 74.65, SD = 8.19) filled out daily questionnaires assessing subjective age, health, daily stressors, and affect. Data were analysed using multilevel modelling. Main outcome measures: Subjective age, health, daily stressors, affect. Results: Intra-individual variability in felt age was not explained by time but by short-term variability in other variables. Specifically, on days when participants experienced more than average health problems, stress, or negative affect they felt older than on days with average health, stress, or negative affect. No time-ordered effects were found. Conclusion: Bad health, many stressors, and negative affective experiences constitute circumstances under which older adults feel older than they typically do. Thus, daily measures of subjective age could be markers of health and well-being.
Prognostic significance of nuclear morphometry in superficial bladder cancer.

OBJECTIVE To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer. STUDY DESIGN The study included 73 patients with superficial transitional cell carcinoma of the bladder who were followed for a median of 21 months (range, 1-90). Nuclear morphometry was performed by a computer-assisted image analyzer system on hematoxylineosin-stained histologic sections and characterized by five nuclear variables: area, perimeter, major and minor diameter, and form factor. Patient charts and microscopic slides were reviewed to record tumor stage, grade and size. Tumor proliferative activity was assessed by immunohistochemical staining with Ki-67 antibody. RESULTS None of the morphometric variables showed a significant relation to tumor progression and recurrence. Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher grade and proliferative activity. Mean nuclear area and minor diameter were associated with advanced stage. Of established prognostic factors, only histologic grade was significant in predicting progression. CONCLUSION The results suggest that nuclear morphometry may be valuable in determining proliferative activity and may be well correlated with histologic grade in superficial bladder cancer. However, like many other potential prognostic factors, it seems to be unreliable in predicting clinical behavior.
Discursive Opportunities for the Estonian Populist Radical Right in a Digital Society

This article analyzes the discursive opportunities, narratives, and dominant themes used by the Conservative People’s Party of Estonia (EKRE), a new populist radical right party, to achieve increasing visibility. Applying thematic analysis of EKRE’s social media content, we identify four main groups of issues that have formed the mainstay of EKRE’s political communication and framed the narrative that social media channels have disseminated: an anti-Russian stance, Euroskepticism, promotion of family values, and an anti-refugee discourse. We conclude that EKRE has successfully capitalized on specific conditions in the public sphere to increase its popularity.
β-Catenin Overexpression Reduces Myocardial Infarct Size through Differential Effects on Cardiomyocytes and Cardiac Fibroblasts*

β-Catenin is a transcriptional regulator of several genes involved in survival and proliferation. Although previous studies suggest that β-catenin may be involved in the process of preconditioning and healing after myocardial infarction (MI), little is known regarding the role of β-catenin in cardiomyocytes and cardiac fibroblasts. We investigated the role of β-catenin in cardiomyocytes and cardiac fibroblasts and whether β-catenin overexpression could reduce MI size. Adenovirus-mediated gene transfer of nonphosphorylatable constitutively active β-catenin (Ad-catenin) decreased apoptosis in cardiomyocytes and cardiac fibroblasts with increased expression of survivin and Bcl-2. Although Ad-catenin increased the percentage of cells in the S phase with enhanced expression of cyclin D1 and E2 in both cell types, the increase in cell number was only evident in cardiac fibroblasts, whereas hypertrophy and binuclear cells were more prominent in cardiomyocytes. All of these effects of β-catenin gene transfer were blocked by inhibition of its nuclear translocation. Furthermore, Ad-catenin enhanced the expression of vascular endothelial growth factor in both cells and induced differentiation of cardiac fibroblasts into myofibroblasts. In a rat MI model, injection of Ad-catenin into the infarct border zone resulted in a significantly decreased MI size with anti-apoptotic effect and cell cycle activation in both cardiomyocytes and myofibroblasts. β-Catenin may play an important role in the healing process after MI by promoting survival and cell cycle not only in cardiomyocytes but also in cardiac fibroblasts with its differentiation into myofibroblasts.
Efficacy of Orlistat as an Adjunct to Behavioral Treatment in Overweight African American and Caucasian Adolescents with Obesity-related Co-morbid Conditions

This pilot study compared the efficacy of orlistat as an adjunctive treatment for obesity between African American and Caucasian adolescents. Twenty obese adolescents with obesity-related co-morbid conditions underwent measurements of body composition, glucose homeostasis by frequently sampled intravenous glucose tolerance test (FSIGT), and fasting lipids before and after 6 months treatment with orlistat 120 mg tid in conjunction with a comprehensive behavioral program. Weight (p < 0.05), BMI (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), fasting insulin (p < 0.02) and fasting glucose (p < 0.003) were lower after treatment. Insulin sensitivity, measured during the FSIGT, improved significantly (p < 0.02), as did fasting indices such as the homeostasis model assessment for insulin resistance (p < 0.01). African American subjects exhibited significantly less improvement in weight (p < 0.05), BMI (p < 0.01), waist circumference (p = 0.03), and insulin sensitivity (p = 0.05). Improvements in cholesterol were not significantly different between African Americans and Caucasians. We conclude that Caucasians lost more weight and had greater improvements in insulin sensitivity than African Americans, but both exhibited improvements in plasma lipids. The true benefit of orlistat treatment over a comprehensive behavioral program remains to be determined in placebo-controlled trials.
Differential effects of selective agonists of neuromedin U1 and U2 receptors in obese and diabetic mice

Neuromedin U (NmU) may be a novel target for obesity treatment owing to its anorectic and energy expenditure enhancing effects. Although two receptors, NMU1 and NMU2, are both responsible for the NmU‐mediated anti‐obesity effects, the receptor agonist with the most appropriate profiles for treating obesity and diabetes in terms of efficacy and safety is as yet unknown. Thus, we developed and evaluated novel NMU1/2 receptor‐selective agonists.
Screening for new MTHFR polymorphisms and NTD risk

The enzyme, 5,10‐methylenetetrahydrofolate reductase (MTHFR) plays a key role in cellular folate metabolism. The A222V (677C‐>T) polymorphism is a confirmed neural tube defect (NTD) risk factor within Irish and other populations. To search for other unknown single nucleotide polymorphisms (SNPs) that might play a role in the etiology of NTDs, we examined the entire MTHFR coding region in healthy individuals (n = 100). SNPs were identified using sequencing and database analysis and allele frequencies were determined in our Irish population. We identified P39P (116C‐>T; T allele frequency 0.13) and previously reported R594Q (1793G‐>A; Q allele frequency 0.07). We screened a large ethnically homogeneous Irish NTD cohort (n>1,300) for P39P and R594Q. A possible association between NTD cases and P39P (P = 0.034) was found but this was not confirmed by transmission disequilibrium testing. R594Q also showed some evidence of a NTD case association (P = 0.07). Further analysis indicated these observations are due to linkage disequilibrium with A222V (677C‐>T), and therefore these new SNPs are unlikely to be independent risk factors for NTDs. As rates of NTDs differ between ethnic groups, we examined allele and genotype frequencies of P39P and R594Q within African‐American and American‐Caucasian populations. This is the first NTD association study of both R594Q and the novel P39P. The association with NTD risk reported for these SNPs is driven by the linkage disequilibrium with the A222V (677C‐>T) NTD risk factor. Published 2005 Wiley‐Liss, Inc.
Sexuality and intimacy issues facing women with breast cancer.

PURPOSE/OBJECTIVES To explore the sexuality and intimacy experiences facing women with breast cancer. DATA SOURCES Published articles; OVID, PsycINFO, and Florida Atlantic University databases; Web sites; and books. DATA SYNTHESIS Patient perceptions and knowledge of mastectomy and chemotherapy-induced menopause in regard to lifelong sexual experiences are lacking. Healthcare providers must institute much-needed education and open lines of communication. CONCLUSIONS The physical and psychological results of breast cancer diagnosis and treatment alter human sexuality. Breast cancer's survival rate is at an all-time high, increasing the number of people who will be living with such issues on a daily basis and shifting the focus from acute care concerns to chronic disease concerns. IMPLICATIONS FOR NURSING Healthcare providers should assess individual patients for potential issues they may face. By identifying problems, they can challenge health care to focus on the long-term problems associated with sexuality and intimacy issues facing patients.