Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of an NO-Synthase Inhibitor L-NMMA in the Hepatopulmonary Syndrome

Increased nitric oxide (NO) levels in expired air have been reported in patients with hepatopulmonary syndrome (HPS) [1] and have been suggested to be an important mediator of hyperdynamic circulation and impaired oxygenation, which is typical in HPS patients [2]. In one patient with HPS, we have studied the effects of the intravenous administration of NG-monomethyl-L-arginine (L-NMMA), a specific NO-synthase inhibitor. A 31-year-old male nonsmoker had cryptogenic cirrhosis confirmed by liver biopsy. He was in stable clinical condition without ascites, but he had profound arterial hypoxemia, with orthodeoxia (supine PaO2 = 7.3 kPa and upright PaO2 = 4.3 kPa). The chest radiograph was normal as was the FEV1 of 3.9 litres, but he had a reduced diffusion coefficient for carbon monoxide of 30% of predicted. The lung perfusion scan revealed a shunt fraction of 13.7%. There was no evidence of an intracardiac shunt by echocardiogram. The right heart catheter study showed a mean pulmonary artery pressure of 12 mm Hg, cardiac output of 8.2 litres/min and a pulmonary vascular resistance of 0.73 IU. The patient was studied in both supine and upright positions prior to and following an intravenous infusion of L-NMMA (8 mg/kg in normal saline) over a 5-min period. Control infusion of normal saline was also performed. Cardiac output, mean arterial pressure (MAP), heart rate and transcutaneous oxygen tension were measured. NO production was recorded as mixed exhaled breath NO concentration (NO ppb) by chemiluminescence and the rate of NO production was calculated. NO measurements were made while the patient was supine and after 10 min of an upright posture at the end of the infusion of both saline solution and L-NMMA (table 1). The patient had high concentrations of exhaled NO, which increased threefold from the supine to the upright posture. L-NMMA infusion decreased the levels of NO in both postures with a persistence of greater NO levels in upright in comparison to supine. An increase in MAP and a decrease in cardiac output was shown after L-NMMA, which lasted over 1 h. Neither the impaired oxygenation nor the orthodeoxia were modified by L-NMMA administration. (All the results are reported in the table.) In conclusion, our findings indicate an increased pulmonary release of NO, which increased further in the upright posture, in this severely hypoxemic cirrhotic patient. The administration of NO-synthase inhibitors was able to restore near-normal NO expired levels and the NO decrease was associated with changes in systemic haemodynamics, without significant improvement in oxygenation and orthodeoxia. The relevance of changes in NO production to systemic and pulmonary abnormalities in HPS patients warrant further studies.
Rural African American parents' knowledge and decisions about human papillomavirus vaccination.

PURPOSE To identify predictors of human papillomavirus (HPV) vaccination among rural African American families. DESIGN Cross-sectional descriptive study in schools in three rural counties in southeastern United States. The sample consisted of African American parents or caregivers with children 9 to 13 years of age who attended elementary or middle school in 2010-2011. METHODS Using an anonymous, 26-item survey, we collected descriptive data during parent-teacher events from African American parents with children in elementary or middle school. The main outcome was measured as a response of "yes" to the statement "I have or will vaccinate my child with the HPV vaccine. " In addition, composite scores of knowledge and positive attitudes and beliefs were compared. No interventions were conducted. FINDINGS We identified predictors of HPV vaccination and found that religious affiliation had a correlation with vaccinating or planning to vaccinate a child. CONCLUSIONS Results indicate a need for further research on the role of local culture, including religion and faith, in rural African Americans' decisions about giving their children the HPV vaccination. CLINICAL RELEVANCE This study emphasizes the importance of understanding rural African American parents' knowledge, attitudes, and spiritual beliefs when designing health education programs and public health interventions to increase HPV vaccination uptake among African American boys and girls living in rural areas.
Heparanase Is Essential for the Development of Diabetic Nephropathy in Mice

Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permselectivity of glomerular basement membrane (GBM) plays an important role in DN pathogenesis. Heparanase is the predominant enzyme that degrades heparan sulfate (HS), the main polysaccharide of the GBM. Loss of GBM HS in diabetic kidney was associated with increased glomerular expression of heparanase; however, the causal involvement of heparanase in the pathogenesis of DN has not been demonstrated. We report for the first time the essential involvement of heparanase in DN. With the use of Hpse-KO mice, we found that deletion of the heparanase gene protects diabetic mice from DN. Furthermore, by investigating the molecular mechanism underlying induction of the enzyme in DN, we found that transcription factor early growth response 1 (Egr1) is responsible for activation of heparanase promoter under diabetic conditions. The specific heparanase inhibitor SST0001 markedly decreased the extent of albuminuria and renal damage in mouse models of DN. Our results collectively underscore the crucial role of heparanase in the pathogenesis of DN and its potential as a highly relevant target for therapeutic interventions in patients with DN.
Breeding performance, age effects and territory occupancy in a Bonelli's Eagle Hieraaetus fasciatus population

Bonelli’s Eagle Hieraaetus fasciatus is one of the most endangered birds of prey in Europe. Despite mounting interest and research, several questions regarding the conservation implications of territory occupancy and site-dependent population regulation remain insufficiently explored for this species. Here, we report on a 12-year study of the territorial structure of a Bonelli’s Eagle population in southeastern Spain. No signals of population decline were found in the breeding population, as mean annual productivity was stable and the presence of mixed-age pairs in the population decreased with the years. However, the average proportion of subadults occupying territories was larger than that observed in other Spanish populations. Contrary to the predictions of a despotic distribution model, we found no significant relationship between occupancy rates and breeding parameters. Our results showed significant variations in productivity attributable to differences in the quality of individuals (i.e. mixed versus adult pairs), but no variability among territories per se (i.e. caused by habitat heterogeneity). Moreover, coexistence with intraguild species did not have any significant effect on productivity, although the proximity of Eagle Owls Bubo bubo affected the occupation rate of territories. Finally, our population does not appear to experience sitedependent population regulation, as a positive relation between mean annual productivity and density was found. The threat posed by changes in land use in the study area leads us to suggest that strict protection of current territories is necessary to ensure population persistence, and we suggest that a significant population increase is only likely if new or deserted territories become available.
Integrin-mediated Signals Regulated by Members of the Rho Family of GTPases

The organization of the actin cytoskeleton can be regulated by soluble factors that trigger signal transduction events involving the Rho family of GTPases. Since adhesive interactions are also capable of organizing the actin-based cytoskeleton, we examined the role of Cdc42-, Rac-, and Rho-dependent signaling pathways in regulating the cytoskeleton during integrin-mediated adhesion and cell spreading using dominant-inhibitory mutants of these GTPases. When Rat1 cells initially adhere to the extracellular matrix protein fibronectin, punctate focal complexes form at the cell periphery. Concomitant with focal complex formation, we observed some phosphorylation of the focal adhesion kinase (FAK) and Src, which occurred independently of Rho family GTPases. However, subsequent phosphorylation of FAK and paxillin occurs in a Rho-dependent manner. Moreover, we found Rho dependence of the assembly of large focal adhesions from which actin stress fibers radiate. Initial adhesion to fibronectin also stimulates membrane ruffling; we show that this ruffling is independent of Rho but is dependent on both Cdc42 and Rac. Furthermore, we observed that Cdc42 controls the integrin-dependent activation of extracellular signal–regulated kinase 2 and of Akt, a kinase whose activity has been demonstrated to be dependent on phosphatidylinositol (PI) 3-kinase. Since Rac-dependent membrane ruffling can be stimulated by PI 3-kinase, it appears that Cdc42, PI 3-kinase, and Rac lie on a distinct pathway that regulates adhesion-induced membrane ruffling. In contrast to the differential regulation of integrin-mediated signaling by Cdc42, Rac, and Rho, we observed that all three GTPases regulate cell spreading, an event that may indirectly control cellular architecture. Therefore, several separable signaling pathways regulated by different members of the Rho family of GTPases converge to control adhesion-dependent changes in the organization of the cytoskeleton, changes that regulate cell morphology and behavior.
Foveation-based Mechanisms Alleviate Adversarial Examples

We show that adversarial examples, i.e., the visually imperceptible perturbations that result in Convolutional Neural Networks (CNNs) fail, can be alleviated with a mechanism based on foveations---applying the CNN in different image regions. To see this, first, we report results in ImageNet that lead to a revision of the hypothesis that adversarial perturbations are a consequence of CNNs acting as a linear classifier: CNNs act locally linearly to changes in the image regions with objects recognized by the CNN, and in other regions the CNN may act non-linearly. Then, we corroborate that when the neural responses are linear, applying the foveation mechanism to the adversarial example tends to significantly reduce the effect of the perturbation. This is because, hypothetically, the CNNs for ImageNet are robust to changes of scale and translation of the object produced by the foveation, but this property does not generalize to transformations of the perturbation. As a result, the accuracy after a foveation is almost the same as the accuracy of the CNN without the adversarial perturbation, even if the adversarial perturbation is calculated taking into account a foveation.
Specialized Functions of Nav1.5 and Nav1.9 Channels in Electrogenesis of Myenteric Neurons in Intact Mouse Ganglia

Voltage-gated sodium (Nav) channels play a central role in gastrointestinal physiology because they transmit depolarizing impulses in enteric neurons, thereby enabling the coordination of intestinal motility. However, little is known about the ion channel machinery that specifies firing pattern of enteric neurons. Here, we used in situ patch-clamp recording of myenteric neurons from mice to define functionally the Nav channel subtypes responsible for the electrical signature of myenteric neurons. We found that mouse myenteric neurons exhibit two types of tetrodotoxin-resistant Na+ currents: an early inactivating Na+ current (INaT) and a persistent Na+ current (INaP). INaT was encountered in all myenteric neurons, whereas INaP was preferentially found in Dogiel type II sensory neurons. Knock-out mouse studies, in combination with pharmacological assays, indicate that INaT is carried by the Scn5a-encoded “cardiac” Nav1.5, whereas INaP is attributed to the Scn11a-encoded Nav1.9. Current-clamp experiments show that Nav1.9 flows at subthreshold voltages, generating tonic firing. In addition, action potential (AP) clamp reveals that Nav1.5 contributes to the upstroke velocity of APs, whereas Nav1.9, which remains active during the falling phase, opposes AP repolarization. We developed a computational model of a Dogiel type II myenteric neuron that successfully reproduces all experimentally observed phenomena and highlights the differential roles of Nav1.5 and Nav1.9 in the control of excitability. Our data illustrate how excitability can be finely tuned to provide specific firing templates by the selective deployment of Nav1.5 and Nav1.9 isoforms. We propose that Nav-dependent ENS disorders of excitability may play important roles in the pathogenesis of digestive diseases.
Semantic memory as assessed by the Pyramids and Palm Trees Test: The impact of sociodemographic factors in a Spanish-speaking population

The objective of this study is to obtain preliminary normative data on the performance the Pyramids and Palm Trees Test (PPT) for a Spanish-speaking population. The effects of age, gender, and educational level on the PPT test were also analyzed. A total of 234 healthy participants, with a broad range of age (18–80 years) and education (1–20 years) performed the three-picture version of the PPT. The mean performance was 51.1 out of 52 possible points (SD = 1.3). PPT performance did not vary with age or gender. However, subjects with less than 6 years of formal education scored significantly lower than those with more than 6 years of education though this effect was confounded with age because the group with lower education was also older. Given the ceiling effects of the PPT, further investigation is needed to determine if the visual PPT is sensitive to mild semantic memory impairment. (JINS, 2008, 14, 148–151.)
Meta-analysis and meta-regression analysis of outcomes of carotid endarterectomy and stenting in the elderly.

IMPORTANCE Uncertainty exists about the influence of advanced age on the outcomes of carotid revascularization. OBJECTIVE To undertake a comprehensive review of the literature and conduct an analysis of the outcomes of carotid interventions in the elderly. DESIGN AND SETTING A systematic literature review was conducted to identify articles comparing early outcomes of carotid endarterectomy (CEA) or carotid stenting (CAS) in elderly and young patients. MAIN OUTCOMES AND MEASURES Combined overall effect sizes were calculated using fixed or random effects models. Meta-regression models were formed to explore potential heterogeneity as a result of changes in practice over time. RESULTS Our analysis comprised 44 studies reporting data on 512,685 CEA and 75,201 CAS procedures. Carotid stenting was associated with increased incidence of stroke in elderly patients compared with their young counterparts (odds ratio [OR], 1.56; 95% CI, 1.40-1.75), whereas CEA had equivalent cerebrovascular outcomes in old and young age groups (OR, 0.94; 95% CI, 0.88-0.99). Carotid stenting had similar peri-interventional mortality risks in old and young patients (OR, 0.86; 95% CI, 0.72-1.03), whereas CEA was associated with heightened mortality in elderly patients (OR, 1.62; 95% CI, 1.47-1.77). The incidence of myocardial infarction was increased in patients of advanced age in both CEA and CAS (OR, 1.64; 95% CI, 1.57-1.72 and OR, 1.30; 95% CI, 1.16-1.45, respectively). Meta-regression analyses revealed a significant effect of publication date on peri-interventional stroke (P = .003) and mortality (P < .001) in CAS. CONCLUSIONS AND RELEVANCE Age should be considered when planning a carotid intervention. Carotid stenting has an increased risk of adverse cerebrovascular events in elderly patients but mortality equivalent to younger patients. Carotid endarterectomy is associated with similar neurologic outcomes in elderly and young patients, at the expense of increased mortality.
Detection of a Very Bright Optical Flare from the Gamma-Ray Burst GRB 050904 at Redshift 6.29

In this Letter, we discuss the flux and the behavior of the bright optical flare emission detected by the 25 cm TAROT robotic telescope during the prompt high-energy emission and the early afterglow. We combine our data with simultaneous observations performed in X-rays, and we analyze the broadband spectrum. These observations lead us to emphasize the similarity of GRB 050904 with GRB 990123, a remarkable gamma-ray burst whose optical emission reached 9th magnitude. While GRB 990123 was, until now, considered as a unique event, this observation suggests the existence of a population of GRBs that have very large isotropic equivalent energies and extremely bright optical counterparts. The luminosity of these GRBs is such that they are easily detectable through the entire universe. Since we can detect them to very high redshift even with small-aperture telescopes like TAROT, they will constitute powerful tools for the exploration of the high-redshift universe and might be used to probe the first generation of stars.
NOD2/CARD15 polymorphism in patients with rectal cancer.

BACKGROUND Reports published in the past several years have not provided conclusive evidence regarding a relationship between the development of colorectal cancer and NOD2 gene mutations, though some geographic variability has been shown. MATERIAL/METHODS The goal of the current project was to analyze the frequency of selected NOD2 gene variants, including P286S, R702W, G908R, and 1007fs, in the Polish population of patients with rectal cancer. Fifty-one rectal cancer patients undergoing treatment were included in the study. As a control group to provide a reference point for NOD2 polymorphism in the population, DNA obtained from cord blood collected from the placenta of 100 patients immediately after parturition was used. RESULTS It was found that the aforementioned mutations were more frequent among the colorectal cancer patients and that the presence of the 1007fs variant might also be associated with young patient age. CONCLUSIONS The analysis of the material does not allow presenting a conclusive answer as to whether the 1007fs, G908R, and R702W mutations or P268S polymorphism contribute to the development of sporadic colorectal cancer in the Polish population. Patients in some populations could likely benefit from instituting earlier colorectal cancer screening studies following the detection of the 1007fs mutation.
Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases

Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for “moderate drinkers” versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85–1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73–0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre- or postdiagnosis alcohol consumption is associated with breast cancer–specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer–specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer–specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer–specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. Cancer Epidemiol Biomarkers Prev; 23(6); 934–45. ©2014 AACR.
Endothelial dysfunction of hindquarter resistance vessels in experimental heart failure.

Local vascular alterations may contribute to increased peripheral vasoconstriction in chronic heart failure. To test whether endothelial dysfunction might be involved, the effect of acetylcholine, nitroglycerin, and NG-monomethyl-L-arginine (L-NMMA) was investigated in a constant-flow perfused hindquarter of rats with and without chronic heart failure (CHF) due to myocardial infarction. Changes in perfusion pressure were measured as an index of changes in hindlimb vascular resistance. The endothelium-dependent vasodilator effect of acetylcholine was significantly reduced in rats with large infarcts (greater than 40% of the left ventricle). However, the endothelium-independent vasodilator effect of nitroglycerin and the vasoconstrictor effect of L-NMMA were similar for infarct and normal animals. The vasodilator response to acetylcholine was partially inhibited by pretreatment with L-NMMA. Thus the basal release of nitric oxide from hindquarter resistance vessels is preserved in CHF. However, the endothelium-mediated dilation in response to acetylcholine is attenuated, in part, due to a depressed stimulated release of nitric oxide. The latter mechanism might be involved in the impaired vasodilatory capacity in the peripheral circulation in CHF, e.g., during exercise.
Adaptive Hierarchical Kinematics in Modeling Progressive Damage and Global Failure in Fiber-reinforced Composite Laminates

This article investigates the feasibility of utilizing adaptive kinematics to reduce the computational effort of finite element modeling of progressive damage and global failure in fiber-reinforced composite laminates. In the present context, adaptive kinematics refers to the selective use of different types of macroscopic laminate models for different regions of the computational domain, based on the solution complexity within each region. Each of these macroscopic laminate models can be distinguished by the manner in which the displacement field is assumed to vary through the thickness of the laminate. In the present study, kinematic adaptivity is made possible through the use of variable kinematic finite elements (VKFE) that are developed by hierarchically combining two or more types of assumed displacement fields in a single finite element domain. The hierarchical data structure of the VKFE greatly simplifies the process of connecting elements that represent different types of laminate theories, thus facilitating adaptive analysis. The adaptive kinematic concept is demonstrated for the bending of simply supported laminates that exhibit diffuse, widespread damage and laminate tensile test specimens that exhibit very intense localized damage due to the free edge effect. The results obtained in this study clearly demonstrate that the use of adaptive kinematics can significantly reduce the overall computational effort of progressive damage solutions without compromising solution accuracy.