Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Direct Thrombin Inhibition with Dabigatran on Plaque Formation and Endothelial Function in Apolipoprotein E-Deficient Mice

The recently developed oral anticoagulant dabigatran (Dabi) etexilate directly inhibits thrombin after activation by plasma esterases to dabigatran. Thrombin is involved in the pathogenesis of atherosclerosis. We investigated the effects of direct thrombin inhibition on atherosclerosis and endothelial function in a hypercholesterolemic mouse model with accelerated atherosclerosis {[apolipoprotein E-deficient (ApoE(−/−)] mice}. ApoE(−/−) mice were treated with a cholesterol-rich diet for 12 weeks and either dabigatran etexilate (900 mg/kg body weight) or vehicle. Wild-type (C57/B6) mice served as control. Endothelial function was assessed with carbachol (endothelium dependent) by using glyceroltrinitrate (endothelium independent) as control in aortic rings. Atherosclerotic lesion formation was evaluated with Oil Red staining, and vascular collagen content was determined by Sirius Red staining. Reactive oxygen species (ROS) production was determined by semiquantitative immunohistochemical staining. Measurement of dabigatran plasma levels (622.3 ± 169 ng/ml) and a performed coagulation test (diluted thrombin time) revealed a relevant anticoagulatory concentration. Dabigatran etexilate attenuated increased atherosclerotic plaque formation [ApoE(−/−) Dabi: 16.1 ± 3.8% of ApoE(−/−) control; p < 0.001], decreased collagen content [ApoE(−/−) Dabi: 49.1 ± 10% of ApoE(−/−) control; p = 0.01], and ROS production in dihydroethidium staining [ApoE(−/−) Dabi: 46.3 ± 5.4% of ApoE(−/−) control; p = 0.005] in parallel to an improvement of endothelial function [ApoE(−/−) control 42.6 ± 2.7 versus ApoE(−/−) Dabi 62.9 ± 3.3% of phenylephrine-induced contraction; p = 0.001] at 100 μmol carbachol. These data suggest that direct thrombin inhibition in a relevant dosage improved endothelial function and reduced atherosclerotic lesion size, collagen content, and oxidative stress in hypercholesterolemic atherosclerosis. Interference with the coagulation system might provide a therapeutic target to modify atherosclerotic disease progression.
Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study

Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months’ triple combination therapy in 18 patients (p<0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean±sd 32±19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68–82%), 60% (95% CI 50–70%) and 49% (95% CI 38–60%) at 1, 2 and 3 years, respectively. This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH. Upfront triple combination therapy shows promising long-term efficacy in severe pulmonary arterial hypertension http://ow.ly/tKgHX
Associations of Rsf-1 overexpression with poor therapeutic response and worse survival in patients with nasopharyngeal carcinoma

Aims Deregulated chromatin remodelling often leads to aberrant gene expression in cells, thereby implicating tumour development and progression. As a subunit of remodelling and spacing factor complex, Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness in common carcinomas. However, the expression of Rsf-1 has never been reported in nasopharyngeal carcinoma (NPC). This study aimed at evaluating the expression status, associations with clincopathological variables and prognostic implications of Rsf-1 in a well-defined cohort of NPC. Methods Rsf-1 immunoexpression was retrospectively assessed in biopsies of 108 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The results were correlated with the clinicopathological features, therapeutic response, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-specific survival (DSS). Results Present in 49 cases (45%), Rsf-1 overexpression was associated with N2,3 status (p=0.016), American Joint Committee on Cancer stage 3, 4 (p=0.004), and incomplete therapeutic response (p=0.041). In multivariate analyses, Rsf-1 overexpression not only emerged as the sole independent adverse prognosticator for LRFS (p=0.0002, RR 5.287) but also independently predicted worse DMFS (p=0.0011, RR 3.185) and DSS (p<0.0001, RR 4.442), along with T3,4 (p=0.0454) and N2,3 (p=0.0319), respectively. Conclusion Rsf-1 overexpression is common and is associated with adverse prognosticators and therapeutic response, which confers tumour aggressiveness through chromatin remodelling, and represents a potential prognostic biomarker in NPC.
Aerobic exercise training attenuates obesity-related hypogonadism in male rats.

INTRODUCTION Hypogonadism is associated with obesity and other features of metabolic syndrome in males. PURPOSE The purpose of this study was to compare lean and obese male Zucker rats on their reproductive endocrine function in response to aerobic exercise training. METHODS Lean (Fa/Fa) and obese (fa/fa) male Zucker rats at 2 months of age were randomly assigned to a sedentary and an aerobic exercise training group (lean sedentary, n = 7; lean exercise, n = 8; obese sedentary, n = 7; obese exercise, n = 7). The exercise group walked on a rat treadmill, starting at 10 m · min(-1) for 20 min and building up to 20 m · min(-1) for 60 min, five times per week for 8 wk. Serum levels of total and free testosterone and testicular levels of testosterone, as well as epididymal and inguinal adipose tissue monocyte chemotactic protein 1 release levels, were measured. RESULTS There were significant obesity-by-exercise interactions on serum levels of total and free testosterone and testicular levels of testosterone (all P < 0.05). Compared to lean sedentary rats, obese sedentary rats had lower serum and testicular testosterone levels (0.72- to 0.74-fold, all P < 0.001). There were no group differences between lean sedentary and lean exercise rats on serum and testicular testosterone levels. However, compared to the obese sedentary group, the obese exercise group had higher serum and testicular testosterone levels (1.37- to 1.47-fold, all P < 0.05). In the whole cohort, serum and testicular testosterone levels were inversely related to epididymal adipose tissue monocyte chemotactic protein 1 secretion (r = -0.40 to r = -0.45, all P < 0.05). CONCLUSIONS Our results support that aerobic exercise training could improve severe obesity-related hypogonadism in male Zucker rats. The underlying mechanism needs to be further clarified.
Coordination Avoidance in Database Systems

Minimizing coordination, or blocking communication between concurrently executing operations, is key to maximizing scalability, availability, and high performance in database systems. However, uninhibited coordination-free execution can compromise application correctness, or consistency. When is coordination necessary for correctness? The classic use of serializable transactions is sufficient to maintain correctness but is not necessary for all applications, sacrificing potential scalability. In this paper, we develop a formal framework, invariant confluence, that determines whether an application requires coordination for correct execution. By operating on application-level invariants over database states (e.g., integrity constraints), invariant confluence analysis provides a necessary and sufficient condition for safe, coordination-free execution. When programmers specify their application invariants, this analysis allows databases to coordinate only when anomalies that might violate invariants are possible. We analyze the invariant confluence of common invariants and operations from real-world database systems (i.e., integrity constraints) and applications and show that many are invariant confluent and therefore achievable without coordination. We apply these results to a proof-of-concept coordination-avoiding database prototype and demonstrate sizable performance gains compared to serializable execution, notably a 25-fold improvement over prior TPC-C New-Order performance on a 200 server cluster.
Eaton‐lambert myasthenic syndrome: Long‐term treatment of three patients with prednisone

Three patients with the myasthenic syndrome of Eaton‐Lambert (ELS) were treated with prednisone for 6 and 12 months and more than 3 years, respectively. Muscle strength increased considerably in all, reaching a peak after 3 to 4 months, and was accompanied by simultaneous electromyographic improvement. Reduction of prednisone led to deterioration in all 3 patients; strength was regained when the higher dosage of prednisone was resumed. Prednisone is an alternative form of treatment for ELS, although the mechanism for its action is unclear.
Importance of Enhanced Surveillance for Prevention of Pertussis in Children

Background: Bordetella pertussis infection causes considerable morbidity, even in countries with high vaccination coverage. Surveillance of pertussis is usually passive and based on mandatory reporting. We assessed the epidemiologic and clinical characteristics of pertussis cases detected by passive or enhanced surveillance. Methods: A prospective population-based study was carried out from January 2012 to December 2013 in Catalonia and Navarre, 2 Spanish regions with a total population of 8.2 million. For each confirmed case, variables of age, sex, clinical symptoms, laboratory results and vaccination status were investigated. Associations between the variables studied and the type of surveillance were assessed by odds ratio (OR) and its 95% confidence interval (CI). Logistic regression was used to estimate adjusted OR (aOR). Results: In children <18 years of age, passive surveillance was the most important source of detection (95.7% in <1 year). In children 5–10 years of age, passive surveillance detected 67.5% of cases. In those ≥18 years, enhanced surveillance was the most frequent source of case detection (82.5%). Inspiratory whoop (aOR: 1.94; 95% CI: 1.40–2.70), apnea (aOR: 1.92; 95% CI: 1.28–2.87) and posttussive vomiting (aOR: 1.43; 95% CI: 1.04–1.96) were symptoms included in the clinical case definition that were associated with passive surveillance. Conclusions: Underreporting of symptomatic cases is important not only in adults, but also in children >1 year of age and suggests that providing clinics with free, fast laboratory diagnostic tests, together with enhanced surveillance of family contacts of any age is necessary to better determine existing cases. Enhanced surveillance may be helpful to better understand transmission patterns in the family and in the community.
Dynamic Integrated Algorithm for Production Scheduling Based on Iterative Search

It is quite difficult to adapt to the changing production scheduling problem for an algorithm of a certain question. According to this, a strategy of dynamic integrated iterative search algorithm is proposed. Firstly, the relationship model of production problem and algorithm is built. Secondly, the framework of the iterative search algorithm is proposed. On the basis of these, the strategy of dynamic integrated iterative search algorithm based on multi agent is put forward, which can easily adapt to the changeable workshop production environment. The experimental results show the effectiveness and adaptability of the system.
Longitudinal analysis of standardized test scores of students in the science writing heuristic approach

The purpose of this study was to examine the longitudinal impacts of the Science Writing Heuristic (SWH) approach on student science achievement measured by the Iowa Test of Basic Skills (ITBS). A number of studies have reported positive impact of an inquiry-based instruction on student achievement, critical thinking skills, reasoning skills, attitude toward science, etc. So far, studies have focused on exploring how an intervention affects student achievement using teacher/researcher-generated measurement. Only a few studies have attempted to explore the long-term impacts of an intervention on student science achievement measured by standardized tests. The students’ science and reading ITBS data was collected from 2000 to 2011 from a school district which had adopted the SWH approach as the main approach in science classrooms since 2002. The data consisted of 12,350 data points from 3,039 students. The multilevel model for change with discontinuity in elevation and slope technique was used to analyze changes in student science achievement growth trajectories prior and after adopting the SWH approach. The results showed that the SWH approach positively impacted students by initially raising science achievement scores. The initial impact was maintained and gradually increased when students were continuously exposed to the SWH approach. Disadvantaged students who were at risk of having low science achievement had bigger benefits from experience with the SWH approach. As a result, existing problematic achievement gaps were narrowed down. Moreover, students who started experience with the SWH approach as early as elementary school seemed to have better science
Colonial dissociation and susceptibility to phagocytosis of Pseudomonas aeruginosa grown in a chamber implant model in mice

Pseudomonas aeruginosa strains were grown in 1-cm plastic chambers sealed at both ends with porous Millipore filters and implanted in the peritonea of mice. Mucoid and nonmucoid strains of P. aeruginosa isolated from a patient with cystic fibrosis largely retained their phenotypes when grown for up to 1 year in this in vivo system, although colonial dissociation occurred, as observed in chronic lung infections of patients with cystic fibrosis. In the absence of added opsonins, P. aeruginosa M2 cells taken directly from the in vivo system were significantly more susceptible to phagocytosis than were the same P. aeruginosa cells after being washed in buffer. Phagocytosis of in vivo-grown P. aeruginosa cells could be further enhanced by using a porin protein F-specific monoclonal antibody.
DNA MICROARRAY TECHNOLOGY FOR TARGET IDENTIFICATION AND VALIDATION

1 Microarrays, a recent development, provide a revolutionary platform to analyse thousands of genes at once. They have enormous potential in the study of biological processes in health and disease and, perhaps, microarrays have become crucial tools in diagnostic applications and drug discovery. 2 Microarray based studies have provided the essential impetus for biomedical experiments, such as identification of disease‐causing genes in malignancies and regulatory genes in the cell cycle mechanism. Microarrays can identify genes for new and unique potential drug targets, predict drug responsiveness for individual patients and, finally, initiate gene therapy and prevention strategies. 3 The present article reviews the principles and technological concerns, as well as the steps involved in obtaining and analysing of data. Furthermore, applications of microarray based experiments in drug target identifications and validation strategies are discussed. 4 To exemplify how this tool can be useful, in the present review we provide an overview of some of the past and potential future aspects of microarray technology and present a broad overview of this rapidly growing field.
Hot and bothered: The role of arousal and rejection sensitivity in dual process sexual decision making for gay and bisexual men

HOT AND BOTHERED: THE ROLE OF AROUSAL AND REJECTION SENSITIVITY IN DUAL PROCESS SEXUAL DECISION MAKING FOR GAY AND BISEXUAL MEN by H. Jonathon Rendina Advisors: Professors Sarit A. Golub and Jeffrey T. Parsons Dual process theories of decision making acknowledge the functioning of two distinct yet simultaneous processes termed System 1 and System 2. While System 1 relies more heavily on automatic and affective processing, System 2 relies more heavily on effortful and cognitive processing. Over the past several decades, many lines of research have shown the importance of System 1 in decision making and several prominent social psychological theories of interpersonal behavior, such as rejection sensitivity, rely on this dual distinction between affective and cognitive processing. Despite the prominence of dual process theories in many areas of psychology, the role of System 1 has been largely absent from psychological inquiries into sexual decision making. As such, the aims of this dissertation were to: (1) investigate a dual process model of sexual decision making by incorporating the role of anxious and sexual arousal into a model with known System 2 predictors of sexual behavior; and (2) examine whether rejection sensitivity as a dispositional trait can be applied to condom use as a behavior and whether it acts upon condom use via interactions within the dual process framework investigated within the first aim. To achieve these aims, data were collected as part of a larger, longitudinal study of highly sexually active gay and bisexual men in New York City. As part of the project, men completed a one-hour survey from home (i.e., computer-assisted survey interviewing or CASI) as part of their
Isolation of Key Methanogens for Global Methane Emission from Rice Paddy Fields: a Novel Isolate Affiliated with the Clone Cluster Rice Cluster I

ABSTRACT Despite the fact that rice paddy fields (RPFs) are contributing 10 to 25% of global methane emissions, the organisms responsible for methane production in RPFs have remained uncultivated and thus uncharacterized. Here we report the isolation of a methanogen (strain SANAE) belonging to an abundant and ubiquitous group of methanogens called rice cluster I (RC-I) previously identified as an ecologically important microbial component via culture-independent analyses. To enrich the RC-I methanogens from rice paddy samples, we attempted to mimic the in situ conditions of RC-I on the basis of the idea that methanogens in such ecosystems should thrive by receiving low concentrations of substrate (H2) continuously provided by heterotrophic H2-producing bacteria. For this purpose, we developed a coculture method using an indirect substrate (propionate) in defined medium and a propionate-oxidizing, H2-producing syntroph, Syntrophobacter fumaroxidans, as the H2 supplier. By doing so, we significantly enriched the RC-I methanogens and eventually obtained a methanogen within the RC-I group in pure culture. This is the first report on the isolation of a methanogen within RC-I.
Converting Cascade-Correlation Neural Nets into Probabilistic Generative Models

Humans are not only adept in recognizing what class an input instance belongs to (i.e., classification task), but perhaps more remarkably, they can imagine (i.e., generate) plausible instances of a desired class with ease, when prompted. Inspired by this, we propose a framework which allows transforming Cascade-Correlation Neural Networks (CCNNs) into probabilistic generative models, thereby enabling CCNNs to generate samples from a category of interest. CCNNs are a well-known class of deterministic, discriminative NNs, which autonomously construct their topology, and have been successful in giving accounts for a variety of psychological phenomena. Our proposed framework is based on a Markov Chain Monte Carlo (MCMC) method, called the Metropolis-adjusted Langevin algorithm, which capitalizes on the gradient information of the target distribution to direct its explorations towards regions of high probability, thereby achieving good mixing properties. Through extensive simulations, we demonstrate the efficacy of our proposed framework.
Discordancy between clinical predictions vs lymphoscintigraphic and intraoperative mapping of sentinel lymph node drainage of primary melanoma.

OBJECTIVE To evaluate discordancy between clinical predictions and lymphatic drainage patterns of primary cutaneous melanoma as determined by preoperative lymphoscintigraphy and intraoperative lymphatic mapping of sentinel lymph nodes (SLNs). DESIGN Before selective SLN dissection, 226 consecutive patients with melanoma underwent preoperative lymphoscintigraphy. SETTING Teaching hospital tertiary care center. MAIN OUTCOME MEASURE Correlation of lymphatic drainage patterns from the following 3 data sources: clinical predictions preoperatively based on anatomical location of primary melanoma, lymphatic drainage patterns as determined by preoperative lymphoscintigraphy, and identification of SLNs during surgery. RESULTS Preoperative lymphoscintigraphy was successful in identifying at least 1 SLN in all 226 patients. In head and neck melanomas, at least 1 SLN was identified in an area outside what would have been clinically predicted in 11 (36.7%) of 30 cases. Discordancy for trunk melanomas was seen in 24 (25.3%) of 95 cases. Extremity melanomas showed drainage to unexpected SLNs in 6 (13.6%) of 44 and 3 (5.3%) of 57 patients for the upper and lower extremities, respectively. The overall rate of discordancy was 44 (19.5%) of 226. The SLNs were identified in surgery in all but 4 cases. CONCLUSIONS Discordancy is most frequent in melanomas of the head and neck region, followed by that of the trunk. Preoperative lymphoscintigraphy identifies the occasional cases in the upper and lower extremities where drainage occurs to a basin that is not clinically predictable. Preoperative lymphoscintigraphy is a prerequisite for characterizing the lymphatic drainage pattern in patients with primary melanoma, especially for sites such as head and neck as well as trunk, before selective SLN dissection.
Dynamic word problems

Let M be a fixed finite monoid. We consider the problem of implementing a data type containing a vector x=(x/sub 1/,x/sub 2/,.,x/sub n/)/spl isin/M/sup n/, initially (1,1,.,1) with two kinds of operations, for each i/spl isin/{1,. ,n}, a/spl isin/M, an operation change/sub i,a/ which changes x/sub i/ to a and a single operation product returning /spl Pi//sub i=1//sup n/x/sub i/. This is the dynamic word problem. If we in addition for each j/spl isin/{1,. ,n} have an operation prefix/sub j/ returning /spl Pi//sub i=1//sup j/x/sub i/, we talk about the dynamic prefix problem. We analyze the complexity of these problems in the cell probe or decision assignment tree model for two natural cell sizes, 1 bit and log n bits. We obtain a classification of the complexity based on algebraic properties of M. <<ETX>>