Miracle-dz/UniFAR-FTUs huggingface dataset:
The renal natriuretic peptide urodilatin is present in human kidney.

BACKGROUND The natriuretic peptide urodilatin was first isolated from human urine and may be one of the important mediators of natriuresis, while the atrial natriuretic peptide alpha-ANP, the circulating member of the family, rather seems to play a role in cardiovascular regulation. Although the renal expression of the common propeptide for urodilatin and alpha-ANP has been detected in rat and pig, it is not yet shown that urodilatin is synthesized in human kidney. METHODS Immunohistochemically we localized urodilatin with an urodilatin-antibody, which does not cross-react with alpha-ANP, the ANP propeptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Radiolabelled urodilatin binding was examined autoradiographically. RESULTS We could demonstrate that urodilatin is present in human distal tubular cells, in which we could also localize propeptide immunoreactivity. The glomeruli, the cells of the proximal tubule, and the collecting duct did not show any urodilatin immunoreactivity. In human kidney homogenate the urodilatin content was 4600 + 520 fmol/g protein (n = 6). The renal concentration of BNP and CNP, mainly localized in the distal tubule, was much lower at 40 + 8 and 400+/-50 fmol/g protein (n=6) respectively. Furthermore the autoradiographic examinations showed that radiolabelled urodilatin binds to natriuretic peptide receptors in the glomeruli, blood vessels, and collecting ducts. CONCLUSIONS Our data suggest that urodilatin may be the predominant representative of natriuretic peptides in human kidneys. Urodilatin being synthesized in the distal tubular region may be transported as a paracrine factor to the collecting duct, where it exerts its suppressing effect on the sodium reabsorption by stimulating the guanylyl cyclase A.
Increased atherothrombotic markers and endothelial dysfunction in steroid users

Background: The use of androgenic anabolic steroids (AAS) may be associated with changes in atherothrombotic markers and endothelial function. The purpose of this study was to compare atherothrombotic markers and endothelial function of AAS users and non-users. Design: Cross-sectional study. Methods: Ten athletes who were users of AAS (confirmed by urine analysis) and 12 non-user athletes were evaluated. Body weight, blood pressure, exercise load (hours/week), complete blood count (CBC), platelets, fibrinogen, lipids, high-sensitivity C-reactive protein (hs-CRP), follicle-stimulating hormone, testosterone and estradiol were measured. Endothelium-dependent and independent functions were assessed by brachial artery ultrasound. Results: AAS users had higher body mass and blood pressure (p < 0.05). Platelet count was higher whereas HDL-cholesterol was lower in AAS users compared with non-users (p < 0.05). Levels of hs-CRP were higher in AAS users (p < 0.001). Follicle-stimulating hormone was suppressed in all users and not suppressed in non-users (p < 0.001). Compared with non-users, flow-mediated dilation was significantly reduced in AAS users (p = 0.03), whereas endothelium-independent function was similar in both groups. Additionally, flow-mediated dilation was positively associated with levels of HDL- cholesterol (r = 0.49, p = 0.03). Conclusions: AAS users present important changes in blood lipids as well as in inflammatory markers, which are compatible with increased cardiovascular risk. Furthermore, this profile is accompanied by a reduction in the endothelial function.
Recruitment and phosphorylation of SH2-containing inositol phosphatase and Shc to the B-cell Fc gamma immunoreceptor tyrosine-based inhibition motif peptide motif

Recently, we and others have demonstrated that negative signaling in B cells selectively induces the tyrosine phosphorylation of a novel inositol polyphosphate phosphatase, p145SHIP. In this study, we present data indicating that p145SHIP binds directly a phosphorylated motif, immunoreceptor tyrosine-based inhibition motif (ITIM), present in the cytoplasmic domain of Fc gammaRIIB1. Using recombinant SH2 domains, we show that binding is mediated via the Src homology region 2 (SH2)-containing inositol phosphatase (SHIP) SH2 domain. SHIP also bound to a phosphopeptide derived from CD22, raising the possibility that SHIP contributes to negative signaling by this receptor as well as Fc gammaRIIB1. The association of SHIP with the ITIM phosphopeptide was activation independent, while coassociation with Shc was activation dependent. Furthermore, experiments with Fc gammaRIIB1-deficient B cells demonstrated a genetic requirement for expression of Fc gammaRIIB1 in the induction of SHIP phosphorylation and its interaction with Shc. Based on these results, we propose a model of negative signaling in which co-cross-linking of surface immunoglobulin and Fc gammaRIIB1 results in sequential tyrosine phosphorylation of the ITIM, recruitment and phosphorylation of p145SHIP, and subsequent binding of Shc.
Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: Analysis of instances of therapeutic misadventure

Hepatic injury in alcoholics due to intake of acetaminophen (APAP or acetylparaaminophenol) with therapeutic intent has been reported, but the extent of the phenomenon is not clear, pertinent details of the association remain insufficiently clarified, and the importance of the phenomenon is not widely appreciated. The present report describes 67 patients who developed hepatic injury after ingestion of APAP with therapeutic intent. All were regular users of alcohol. Sixty‐four percent of the patients were considered to be “alcoholic” or reported intakes greater than 80 g/d, 35% took 60 g/d or less, and the remainder were vague in their reporting. Doses of APAP were in the “nontoxic” range (<6 g/d) in 60% of the group, within the recommended range (<4 g/d) in 40%, and at 4.1 to 6 g/d in 20%. Characteristic feature was the towering level reached by aspartate transaminase (AST) with figures ranging from 3,000 to 48,000 IU in more than 90% of cases. Almost 20% of the patients died. The data on these patients were similar to 94 cases of injury from APAP taken with therapeutic intent reported in the literature. This study provides further evidence of hepatic injury in regular users of alcohol, especially chronic alcoholics, who take APAP with therapeutic intent. Susceptibility is presumably caused by induction of cytochrome P‐4502EI by ethanol and by depletion of glutathione (GSH) because of the effects of alcohol, the malnutrition often associated with alcoholism, and the depletion associated with chronic use of APAP and impaired glucuronidation caused by fasting perhaps as well. The syndrome of liver injury is distinctive, marked by uniquely elevated levels of AST, and poses a significant threat. A greater awareness of the phenomenon by the medical and lay community is essential. (Hepatology 1995;22:767–773.)
Genotype distribution amongst hepatitis C patients in The Netherlands.

BACKGROUND The prevalence of the genotypes of the hepatitis C virus (HCV) differs according to geographical location. In the United States and in European countries, the majority of patients are infected with genotype 1, 2 or 3. There is a lack of data on the distribution of HCV genotypes in The Netherlands. METHODS The current survey determined the distribution of HCV genotypes amongst recently genotyped patients seen by physicians treating hepatitis C in The Netherlands. RESULTS Almost half of the 351 patients (49.3%) were infected with genotype 1. Genotype 3 was the second most dominant genotype with a prevalence of 29.3%. Genotypes 2 and 4 were found in 9.7 and 10.5% of the patients, respectively. For 61.5% of the patients (n=216), the subtype was available. For genotype 1 the prevalence of subtype 1a and 1b was very similar, while for genotype 3 a large majority of patients were infected with subtype 3a. CONCLUSION This survey gives the first estimation of the distribution of HCV genotypes amongst unselected HCV patients in The Netherlands.
Multiple Imputation for Nonresponse in Surveys.

Demonstrates how nonresponse in sample surveys and censuses can be handled by replacing each missing value with two or more multiple imputations. Clearly illustrates the advantages of modern computing to such handle surveys, and demonstrates the benefit of this statistical technique for researchers who must analyze them. Also presents the background for Bayesian and frequentist theory. After establishing that only standard complete-data methods are needed to analyze a multiply-imputed set, the text evaluates procedures in general circumstances, outlining specific procedures for creating imputations in both the ignorable and nonignorable cases. Examples and exercises reinforce ideas, and the interplay of Bayesian and frequentist ideas presents a unified picture of modern statistics.
Role of Androgen and Estrogen Receptors as Prognostic and Potential Predictive Markers of Ductal Carcinoma in Situ of the Breast

Background Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has not been investigated as widely as invasive breast cancer. Thus, the search for biomarkers capable of identifying DCIS lesions that may recur or progress to invasive cancer is ongoing. Although conventional steroid hormone receptors, cell proliferation and other important tumor markers have been extensively studied in invasive tumors, little is known about the role played by androgen receptors (ARs), widely expressed in breast cancer, in DCIS. Methods We performed a retrospective study in a series of 43 DCIS patients treated with quadrantectomy only and followed up for a period ranging from 5 to 13 years, to evaluate the prognostic relevance of conventional biomarkers (estrogen receptor [ER], progesterone receptor [PgR], Ki67, human epidermal growth factor receptor 2 [HER2]) and AR. Results Our findings showed that AR and ER were not independent prognostic variables and that an AR/ER ratio cutoff of 1.13 showed a sensitivity of 75% and a specificity of 94% in predicting in situ relapse or progression to the invasive phenotype. Moreover, while the variables considered singly showed area under the curve (AUC) values ranging from 0.52% to 0.77%, the AR/ER ratio reached a very high AUC (0.92%). Conclusions These preliminary results highlight the potentially important role of AR and ER and, in particular, of their ratio, as prognostic indicators of DCIS evolution.
Assessment of Diabetics with Various Degrees of Autonomic Neuropathy Using Power Spectral Analysis

In this study, we investigate the feasibility of using power spectral density (PSD) analysis to assess the healthy subjects and diabetics with mild, moderate and severe autonomic neuropathy. Continuous cerebral blood flow velocity (CBFV) was measured using transcranial Doppler ultrasound (TCD), and continuous arterial blood pressure (ABP) was measured using Finapres device under supine and hyperventilation conditions. Four groups of subjects were recruited in this study including 11 healthy adults (56.4±8.1 years), 15 diabetics with mild autonomic neuropathy (50.8±15.7 years), 21 diabetics with moderate autonomic neuropathy (61.8±9.0 years), and 25 diabetics with severe autonomic neuropathy (61.4±10.0 years). According to the results of PSD, it can be speculated that while the diabetic autonomic neuropathy of a patient becomes more serious, the function of cerebral auto regulation (CA) tends to be more imbalance. In conclusion, sympathetic activity was different on diabetics with autonomic neuropathy from supine to hyperventilation by the analysis of power spectrum. Sympathetic activity was increased to reduce CBFV from supine to hyperventilation. Due to hyperventilation make oxygen increase in the brain, cerebral auto regulation can make sympathetic activity increased. Therefore, power spectral analysis can be a useful tool to investigate autonomic neuropathy in diabetics.
Development of renal failure in endotoxemic rats: can it be explained by early changes in renal energy metabolism?

Endotoxin shock not only causes renal failure, endotoxemia also leads to metabolic impairment, resulting in energy shortage and loss of cellular integrity; therefore, we tested the hypothesis that early changes in renal metabolism contribute to the development of acute renal failure during endotoxin shock. Endotoxin (Escherichia coli 127B8; 8 mg/kg from t = 0 to 60 min) was infused in three groups of 8 rats, in which renal biopsies were taken at t = 30, 50 and 90 min, respectively; a fourth group (n = 8) served as control. In the biopsies, glucose, lactate, ATP, ADP, AMP and creatine phosphate concentrations were determined. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured from the clearances of 131I-hippurate and 125I-thalamate, respectively. We also assayed urine flow (V; catheter in the bladder), cardiac output (CO), blood pressure (MAP), heart rate (HR) and arterial lactate, glucose and creatinine concentrations. During the first 30 min of endotoxemia, we found no systemic hemodynamic or biochemical changes. From t = 30 to t = 90, CO and MAP decreased to 59 and 70%, respectively, while HR and serum levels rose to 110 and 800%, respectively (p < 0.05), indicating progression of shock. Renal function clearly deteriorated from t = 30; at t = 90 RPF, GFR and V had decreased by 86, 84 and 86%, respectively, plasma creatinine being 193% of the baseline value (p < 0.05). (ABSTRACT TRUNCATED AT 250 WORDS)
Concept clarification of grief in mothers of children with an addiction.

AIM To report an analysis of the concept of grief in mothers of children with an addiction. BACKGROUND The concept of grief in this context is poorly understood and often synonymously used with concepts depression, loss and chronic sorrow. In the US, the core concept grief has been recently revised by both NANDA and the DSM-V in efforts to better understand and characterize the concept. The plethora of literature on grief worldwide often characterizes grief as a response to a death. DESIGN Concept analysis. DATA SOURCES Search terms 'parental grief' and 'substance abuse' yielded 30 articles. A second review using terms 'grief' and 'substance abuse' yielded 323 articles, in PsychInfo, CINAHL, PubMed databases from 1980-2013. Limits for articles in English and for the terms 'death' and 'child' yielded 13 usable articles. METHODS The hybrid model of concept analysis, using a theoretical phase, an empirical phase and a final phase when a clarified definition of grief emerged. RESULTS Definitions in the literature and defining characteristics of grief outline bio-psycho-social aspects of the concept. For one mother grief was accompanied by recurring feelings of sadness across time, while for the other mother grief was seen as coping, after having passed through a variety of stages of grief. For both, grief was seen to fall on a continuum. CONCLUSIONS Grief is a universal concept and has a trajectory. Case study data have been essential in clarifying understandings of grief as experienced by mothers of addicted children and will provide direction for meaningful and tailored interventions.
Antibodies to Tamm-Horsfall Protein in Patients with Acute Pyelonephritis

The role of antibodies to Tamm-Horsfall protein in the diagnosis of acute pyelonephritis was studied. Antibodies to Tamm-Horsfall protein were also determined in a group of normal subjects. Patients with acute pyelonephritis were divided into subgroups according to the concurrent presence of vesicoureteral reflux or nephrolithiasis. No statistically significant differences (p > 0.05) were observed for any class of antibodies (IgG, IgA and IgM) between the groups of healthy subjects and patients with acute pyelonephritis, regardless of the presence or absence of vesicoureteral reflux or nephrolithiasis. Values for different antibody classes showed that IgM antibodies were the most abundant in all the groups examined. A difference in the values of IgM relative to IgA and IgG antibodies was found to be statistically significant in the patient group only (p < 0.05). In patients with vesicoureteral reflux, there was no statistically significant difference (p > 0.05) between the values of IgM and of other antibody classes. In these patients, however, the highest values of all the three antibody classes were obtained, although these differences were also not statistically significant (p > 0.05). The results pointed to the need of further studies of the role of antibodies to Tamm-Horsfall protein in the diagnosis and pathogenesis of tubulointerstitial nephritis.
Phagocytic Roles of Glial Cells in Healthy and Diseased Brains

Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as β-amyloid, huntingtin, and α-synuclein. Here we reivew recent findings showing that glial cells are active regulators in brain functions through phagocytosis and that changes in glial phagocytosis contribute to the pathogenesis of various neurodegenerative diseases. A better understanding of the cellular and molecular mechanisms of glial phagocytosis in healthy and diseased brains will greatly improve our current approach in treating these diseases.
Cross-Section of Asset Returns: Emerging Markets and Market Integration

Asset pricing in its essence is a very controversial topic. Despite numerous research papers criticising traditional approaches, such as linear factor models, practitioners as well as academics repeatedly return to the milestone models such as the Capital Asset Pricing Model (CAPM), mainly due to their attractive simplicity. This article focuses on the risk-return relationship by comparing the power of traditional and alternative asset pricing models in explaining the cross-section of asset returns. The focus is on unconditional models, commonly used among investors and equity analysts. This paper is based on the research performed by Estrada in 2004 and it extends his approach by introducing the use of GMM. The results suggest that for Emerging markets’ investors should give preference to total risk measures over systematic risk measures. Within the category of systematic risk measures, downside beta proved its superiority to traditional CAPM beta. The results can be attributed to delayed integration process, partially justified by the lower FDI and portfolio investments into Emerging markets.
Will the assassination of Daphne Caruana Galizia lead to wholesale institutional reform in Malta

Journalist Daphne Caruana Galizia was killed in a car bomb attack in Malta on 16 October. Her death prompted widespread international condemnation and has refocused attention on the need for institutional reforms within Malta to protect the rule of law and freedom of the press. Roderick Pace writes that with the recent Paradise Papers leak also portraying off-shore financial centres like Malta in a poor light, there is now impetus for genuine reforms to take place, but questions remain over whether the state has the capacity to implement them.
Pulmonary hypertension after pneumonectomy for lung cancer

Background We aimed to consolidate our clinical observations regarding the development of pulmonary hypertension following pneumonectomy for lung cancer. Methods Sixty-nine of 82 initially selected patients without pulmonary or cardiac comorbidities, who underwent pneumonectomy for lung cancer between October 2009 and October 2011, accomplished our protocol. Mean patient age was 60.6 years (range 44–78 years) and 10.1% were women. Results Postoperative complications occurred in 16 (23.2%) patients. Mortality at 1, 12, and 18 months postoperatively was 4.3%, 15.9%, and 29%, respectively. One year postoperatively, 37.9% of patients developed mild to moderate pulmonary hypertension and 3.4% had severe pulmonary hypertension. The calculated mean pulmonary artery systolic pressure at 1, 6, and 12 months postoperatively was 21.9 ± 6.6, 27.3 ± 9.3, and 34.1 ± 14 mm Hg, respectively (p < 0.001). Receiver operating characteristic curve analysis showed a cutoff point at 35.5 mm Hg for late postoperative (at 12 months) pulmonary artery systolic pressure (sensitivity 80%, specificity 82%; p < 0.001) related to suboptimal clinical outcomes (decreased performance status or death), with a detected 18-fold risk for these patients (p < 0.001). Conclusions Pulmonary hypertension may occur after pneumonectomy with its known adverse effects. Patients with late postoperative pulmonary artery systolic pressure > 35.5 mm Hg are at higher risk of a suboptimal clinical outcome.
A Study on the Control of Nonlinear System Using Growing RBFN and Reinforcement Learning

The proposed approach is neural-network based and combines the self-tuning principle with reinforcement learning. The proposed control scheme consists of a controller, a utility estimator, an exploration module, a learning module and a rewarding module. The controller and the utility estimator are implemented together in a single radial basis function network (RBFN). The learning method involves structural adaptation (growing RBFN) and parameter adaptation. No prior knowledge of the plant is assumed, and the controller has to begin with exploration of the state space. The exploration versus exploitation dilemma of reinforcement learning is solved through smooth transitions between the two modes. The controller is capable of asymptotically approaching the desired reference trajectory, which is showed in simulation result.
Dabigatran Etexilate: Future Directions in Anticoagulant Treatment

Dabigatran etexilate is a novel, oral reversible direct thrombin inhibitor in the clinical development for the treatment and prevention of thromboembolic diseases. Clinical data indicate that dabigatran etexilate has immediate onset of effect, no need for monitoring, predictable and consistent pharmacokinetics and pharmacodynamics—all features that differentiate it from oral vitamin K antagonists (VKAs). Completed phase III studies demonstrated a comparable efficacy and safety profile to enoxaparin in the prevention of venous thromboembolism (VTE) after orthopedic surgery. Ongoing phase III trials are now evaluating the long-term use of dabigatran etexilate for the treatment and secondary prevention of VTE and for prevention of stroke in patients with atrial fibrillation, as a replacement for VKAs. With an immediate, reliable, and predictable anticoagulant effect without the need for coagulation monitoring and the lack of long-term safety concerns, dabigatran etexilate may be a prospective candidate that offers additional benefit over VKAs and parenteral anticoagulants in these settings.