Miracle-dz/UniFAR-FTUs huggingface dataset:
Nafamostat Mesilate for Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Prospective, Randomized, Double-Blind, Controlled Trial

Objectives: Pancreatitis is the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). Efforts have been made to identify pharmacologic agents capable of reducing its incidence and severity. The aim of this trial was to determine whether prophylactic nafamostat mesilate, a synthetic protease inhibitor, would reduce the frequency and severity of post-ERCP pancreatitis. Methods: A total of 286 patients were randomized to receive either intravenous nafamostat mesilate or placebo 60 minutes before ERCP and for 6 hours after ERCP. A database was prospectively collected by a defined protocol. Standardized criteria were used to diagnose and grade the severity of pancreatitis. Results: The groups were similar with regard to patient demographics and to patient and procedure risk factors for pancreatitis. The overall incidence of pancreatitis was 5.9%. It occurred in 4 (2.8%) of 143 patients in the nafamostat group and in 13 (9.1%) of 143 patients in the control group (P = 0.03). Pancreatitis was graded mild in 2.1% and moderate in 0.7% of the nafamostat group and mild in 7.0% and moderate in 2.1% of the control group. There was no significant difference between the groups in the severity of pancreatitis. Conclusions: Prophylactic intravenous nafamostat mesilate reduces the frequency of post-ERCP pancreatitis.
PolyTOIL: A type-safe polymorphic object-oriented language

PolyTOIL is a new statically typed polymorphic object-oriented programming language that is provably typesafe. By separating the definitions of subtyping and inheritance, providing a name for the type of self, and carefully defining the type-checking rules, we have obtained a language that is very expressive while supporting modular type-checking of classes. The matching relation on types, which is related to F-bounded quantification, is used both in stating type-checking rules and expressing the bounds on type parameters for polymorphism. The design of PolyTOIL is based on a careful formal definition of type-checking rules and semantics. A proof of type safety is obtained with the aid of a subject reduction theorem.
Cyclin‐dependent kinase TPK2 is a critical cell cycle regulator in Toxoplasma gondii

The Apicomplexan parasite Toxoplasma gondii replicates by endodyogeny, an unusual form of binary fission. We tested the role of TPK2, a homologue of the CDC2 cyclin‐dependent kinases, in cell cycle regulation. TPK2 tagged with HA epitope (TPK2‐HA‐wt) was expressed in mammalian cells as confirmed by Western blot analysis using HA tag and PSTAIRE antibodies. TPK2‐HA‐wt phosphorylated a peptide from Histone H1, proving that TPK2 is a functional kinase. TPK2‐HA‐wt coimmunoprecipitated with mammalian cyclins A, B1, D3 and E. Despite being a functional kinase, TPK2 did not rescue Schizosaccharomyces pombe cdc2 and Saccharomyces cerevisiae cdc28 mutant strains. Overexpression of a dominant‐negative mutant of TPK2 (TPK2‐HA‐dn) in T. gondii tachyzoites arrested replication. FACS analysis of tachyzoites expressing TPK2‐HA‐dn revealed an increase in the fraction of cells in S‐phase when compared with TPK2‐HA‐wt transfected parasites. Expression of TPK2‐HA‐wt did not arrest tachyzoite replication. No discernable G2 cell cycle block was evident suggesting that cell cycle checkpoints differ in T. gondii from most other eukaryotic cells. These data suggest that TPK2 executes an essential function in T. gondii cell cycle and is likely to be the T. gondii CDC2 orthologue.
Do Xylem Fibers Affect Vessel Cavitation Resistance?1

Possible mechanical and hydraulic costs to increased cavitation resistance were examined among six co-occurring species of chaparral shrubs in southern California. We measured cavitation resistance (xylem pressure at 50% loss of hydraulic conductivity), seasonal low pressure potential (Pmin), xylem conductive efficiency (specific conductivity), mechanical strength of stems (modulus of elasticity and modulus of rupture), and xylem density. At the cellular level, we measured vessel and fiber wall thickness and lumen diameter, transverse fiber wall and total lumen area, and estimated vessel implosion resistance using (t/b)h2, where t is the thickness of adjoining vessel walls and b is the vessel lumen diameter. Increased cavitation resistance was correlated with increased mechanical strength (r2 = 0.74 and 0.76 for modulus of elasticity and modulus of rupture, respectively), xylem density (r2 = 0.88), and Pmin (r2 = 0.96). In contrast, cavitation resistance and Pmin were not correlated with decreased specific conductivity, suggesting no tradeoff between these traits. At the cellular level, increased cavitation resistance was correlated with increased (t/b)h2 (r2 = 0.95), increased transverse fiber wall area (r2 = 0.89), and decreased fiber lumen area (r2 = 0.76). To our knowledge, the correlation between cavitation resistance and fiber wall area has not been shown previously and suggests a mechanical role for fibers in cavitation resistance. Fiber efficacy in prevention of vessel implosion, defined as inward bending or collapse of vessels, is discussed.
The Necessity of Data Mining in Clinical Emergency Medicine; A Narrative Review of the Current Literatrue.

Clinical databases can be categorized as big data, include large quantities of information about patients and their medical conditions. Analyzing the quantitative and qualitative clinical data in addition with discovering relationships among huge number of samples using data mining techniques could unveil hidden medical knowledge in terms of correlation and association of apparently independent variables. The aim of this research is using predictive algorithm for prediction of trauma patients on admission to hospital to be able to predict the necessary treatment for patients and provided the necessary measures for the trauma patients who are before entering the critical situation. This study provides a review on data mining in clinical medicine. The relevant, recently-published studies of data mining on medical data with a focus on emergency medicine were investigated to tackle pros and cons of such approaches. The results of this study can be used in prediction of trauma patient’s status at six hours after admission to hospital.
The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry

Aims Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. Methods and results This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. Conclusion This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.
Treatment of adults with growth hormone (GH) deficiency with recombinant human GH.

In a double blind, cross-over placebo-controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered sc daily at bedtime. One patient was withdrawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bioelectric impedance, and total body potassium combined with total body water assessments. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology. After 26 weeks of treatment, adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13%, whereas visceral AT was reduced by 30%. Muscle volume increased by 2.5 kg (5%; P < 0.05). According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bioelectric impedance technique were similar. The mean (+/- SD) concentrations of insulin-like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.09 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin, and procollagen-III concentrations were significantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively. Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 concentrations had returned to pretreatment values. Finally, after 26 weeks of treatment, there was a decrease in the Comprehensive Psychological Rating Scale score (P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults.
Cellular and molecular basis of cadmium‐induced deformities in zebrafish embryos

Cadmium is known to cause developmental defects in a varietyof vertebrate species, but relatively little is known about the underlying molecular mechanisms. In this study, we used zebrafish (Danio rerio) embryos as a model system to investigate cadmium‐induced toxicities. Fertilized embryos collected at 5‐h after fertilization were incubated for 18 h in culture media containing 1 to 1, 000 μM CdCl2. The median embryolethal concentration (LC50) was 168 μM, whereas the median effect concentration (EC50) for total adverse effect (mortality and developmental defects) was 138 μM. Six major types of deformities were observed: head and eye hypoplasia, hypopigmentation, cardiac edema, yolk sac abnormalities, altered axial curvature, and tail malformations. The frequency of malformations increased with cadmium concentration. Somites of embryos with altered axial curvature were investigated using the antimyosin antibody MF‐20. This study demonstrated, to our knowledge for the first time, reduced myotome formation in cadmium‐induced spinal deformity. Embryos with head and eye hypoplasia were studied using the anti‐neural tissue antibody zns‐2, and a poorly developed central nervous system was revealed. Head and eye hypoplasia were associated with lack of expression of the sonic hedgehog gene, which controls the patterning of the neural tube and somites. Genes involved in tail formations, such as evenskipped 1 and no tail, were ectopically expressed in embryos with tail malformations. Our data support the hypothesis that fish embryonic malformations induced by cadmium might be mediated through ectopic expression of developmental regulatory genes.
To Sow One Acre More: Childbearing and Farm Productivity in the Antebellum North

Children supplied valuable labour on 19th-century American farms. But the value of that labour varied, and the children themselves represented economic costs as well as benefits. How did children affect a farmer's choices? Did bigger farms mean, in effect, bigger families? Drawing on census, wage and other data, Craig addresses such questions in offering a new econometric interpretation of productivity and fertility in the antebellum North. Craig argues that children did not provide a noteworthy advantage on the frontier, though they did in the settled but rocky-soiled Northeast. He concludes that a farmer's economic strategy depended not so much on the size of this holding or his age (and fertility), as it did on regional agricultural patterns and proximity to market. These findings contradict the now dominant view that farmers adjusted output according to the number of available labourers - including children. Distinguishing between the Northeast and Old Northwest, Craig constructs a model that incorporates both the advantages and monetary disadvantages of child labour, and accounts for the drop in fertility in regions where opportunities for children off the farm were greater than those at home.
Taste Masking by Spray-Drying Technique

The purpose of this research was to develop the taste-masked microspheres of intensely bitter drug ondansetron hydrochloride (OSH) by spray-drying technique. The bitter taste threshold value of OSH was determined. Three different polymers viz. Chitosan, Methocel E15 LV, and Eudragit E100 were used for microsphere formation, and the effect of different polymers and drug–polymer ratios on the taste masking and release properties of microspheres was investigated. The microspheres were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, Drug loading, in vitro bitter taste evaluation, and drug-release properties. The taste masking was absent in methocel microspheres at all the drug–polymer ratios. The Eudragit microspheres depicted taste masking at 1:2 drug–polymer ratio whereas with Chitosan microspheres the taste masking was achieved at 1:1 drug–polymer ratio. The drug release was about 96.85% for eudragit microspheres and 40.07% for Chitosan microspheres in 15 min.
Practical Protocol Composition, Encapsulation and Sharing in Kompics

At the core of any distributed system is a set of concurrent distributed algorithms that coordinate the functionality of the distributed system. We present a software architecture, Kompics that is component-based and compositional which facilitates building distributed protocols. The underlying computation model subsumes that of event-based systems, SEDA (staged event-driven architecture) and thread-based models. We illustrate various salient features of Kompics such as ease of use, compositionality and configurability through a series of well chosen distributed protocols.
OTMedia: the French TransMedia news observatory

Who said What, Where and How? How are images, video and stories spreading out? Who produces the information? OTMedia addresses these questions by collecting, enriching and analysing continuously more than 1500 streams of French media from TV Radio, Web, AFP, and Twitter. Two studies on media produced by end users with the OTMedia framework are presented.
Exchange of a nuclear corepressor between NF-kappaB and CREB mediates inhibition of phosphoenolpyruvate carboxykinase transcription by NF-kappaB.

BACKGROUND NF-kappaB p65 was shown to inhibit transcription of phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in gluconeogenesis in the liver. To understand the mechanism of action of NF-kappaB p65, we investigated the nuclear receptor corepressor in the regulation of PEPCK transcription. METHODS Rat H4IIE cells, human hepatoma HepG2 cells and human embryo kidney (HEK) 293 cells were used in this study. The transcriptional activity of a rat PEPCK gene promoter (-490/+100) was analyzed in HepG2 cells, a HepG2 super suppressor IkBalpha (ssIkBalpha) stable cell line, and HEK 293 cells. The effects of p65 and ssIkBalpha on a rat PEPCK gene promoter were observed using the PEPCK luciferase reporter system. The interaction of the cAMP-response- element-binding (CREB) protein, histone deacetylase 3 (HDAC3) and silencing mediator for retinoic and thyroid hormone receptors (SMRT) with the PEPCK gene promoter were investigated using the chromatin immunoprecipitation (ChIP) assay. p65 cotransfection and RNAi-mediated gene knockdown were used to determine the corepressor involved in the inhibition of PEPCK by NF-kappaB p65 and the transcriptional regulation of CREB by NF-kappaB p65. RESULTS NF-kappaB p65 inhibited PEPCK expression and the inhibition was blocked by ssIkBalpha. The inhibitory effect of p65 was completely blocked in a HepG2 stable cell line in which ssIkBalpha was expressed. HDAC3 or SMRT knockdown led to a significant up-regulation of PEPCK reporter activity in the presence of p65 cotransfection. In the ChIP assay the interaction of HDAC3 and SMRT with the PEPCK gene promoter was induced by p65 activation, but the CREB signal was reduced. Transcriptional activity of CREB was inhibited by NF-kappaB p65 cotransfection. The inhibitory effect of NF-kappaB p65 was blocked by HDAC3 RNAi or SMRT RNAi. CONCLUSIONS The study showed that the inhibition of PEPCK by NF-kappaB p65 was dependent on HDAC3 and SMRT, which form a nuclear corepressor complex for transcriptional inhibition. The transcription factors NF-kappaB p65 and CREB share the same corepressor HDAC3-SMRT, and the corepressor exchange leads to inhibition of PEPCK gene transcription by NF-kappaB p65.
Soluble Egg Antigen-Stimulated T Helper Lymphocyte Apoptosis and Evidence for Cell Death Mediated by FasL+ T and B Cells during Murine Schistosoma mansoni Infection

ABSTRACT Granuloma formation around schistosomal eggs is induced by soluble egg antigens (SEA) and mediated by the activity of CD4+ Th lymphocytes and their cytokines. Regulation of the inflammatory Th cell response during infection is still insufficiently understood. The hypothesis of this study was that activation-induced cell death (AICD) of CD4+ T cells is involved in the immune inflammatory response. This study investigated the dynamics of splenic and granuloma CD4+ Th cell apoptosis and Fas ligand (FasL) expression during the acute and chronic stages of murine schistosomal infection. Enhanced apoptosis of freshly isolated CD4+ Th lymphocytes commenced after egg deposition and persisted during the peak and modulated phases of granuloma formation. After oviposition, CD4+, CD8+, and CD19+ splenocytes and granuloma cells expressed elevated levels of FasL but FasL expression declined during the downmodulated stage of infection. In culture, SEA induced splenic and granuloma CD4+ T-cell apoptosis and stimulated expression of FasL on splenic but not granuloma CD4+ T cells, CD8+ T cells, and CD19+ B cells. SEA-stimulated splenocytes and granuloma cells preferentially lysed a Fas-transfected target cell line. Depletion of B cells from SEA-stimulated splenic cultures decreased CD4+ T cell apoptosis. Coculture of purified splenic B cells with CD4+ T cells and adoptive transfer of purified B cells indicated that antigen-stimulated B cells can kill CD4+ Th cells. However, CD4+ T cells were the dominant mediators of apoptosis in the granuloma. This study indicates that AICD is involved in the apoptosis of CD4+ T cells during schistosomal infection.
Genetic Analysis of Connective Tissue Growth Factor as an Effector of Transforming Growth Factor β Signaling and Cardiac Remodeling

ABSTRACT The matricellular secreted protein connective tissue growth factor (CTGF) is upregulated in response to cardiac injury or with transforming growth factor β (TGF-β) stimulation, where it has been suggested to function as a fibrotic effector. Here we generated transgenic mice with inducible heart-specific CTGF overexpression, mice with heart-specific expression of an activated TGF-β mutant protein, mice with heart-specific deletion of Ctgf, and mice in which Ctgf was also deleted from fibroblasts in the heart. Remarkably, neither gain nor loss of CTGF in the heart affected cardiac pathology and propensity toward early lethality due to TGF-β overactivation in the heart. Also, neither heart-specific Ctgf deletion nor CTGF overexpression altered cardiac remodeling and function with aging or after multiple acute stress stimuli. Cardiac fibrosis was also unchanged by modulation of CTGF levels in the heart with aging, pressure overload, agonist infusion, or TGF-β overexpression. However, CTGF mildly altered the overall cardiac response to TGF-β when pressure overload stimulation was applied. CTGF has been proposed to function as a critical TGF-β effector in underlying tissue remodeling and fibrosis throughout the body, although our results suggest that CTGF is of minimal importance and is an unlikely therapeutic vantage point for the heart.