Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic Value of Child‐Turcotte Criteria in Medically Treated Cirrhosis

The Child‐Turcotte criteria (CTC) (based on serum bilirubin and albumin, ascites, neurological disorder and nutrition) are established prognostic factors in patients with cirrhosis having portacaval shunt surgery. The objective of this study was to evaluate the prognostic value of CTC in conservatively treated cirrhosis. Patients (n = 245) with histologically verified cirrhosis from a control group of a controlled clinical trial were studied. Data at entry into the trial were used to classify patients according to CTC. Survival curves for up to 16 years were made, and survival rates were compared using the log‐rank test. Survival decreased significantly with increasing degree of abnormality (A ± B ± C) of albumin (p < 0.001), ascites (p < 0.001), bilirubin (p = 0.02) and nutritional status (p = 0.03). Survival was insignificantly influenced by neurological status (p = 0.11) probably because none of the patients had hepatic coma at entry into the trial. The five variables in CTC were combined to a score. With increasing score, the median survival time decreased from 6.4 years (score 5) to 2 months (scores 12 or more). Furthermore, the mortality from hepatic failure, gastrointestinal bleeding or hepatocellular carcinoma increased significantly with increasing score. CTC provide valuable and easily obtainable prognostic information in cirrhosis. However, CTC are inferior to a prognostic index based on multivariate analysis of prognostic factors.
Images in cardiovascular medicine. Human atherosclerotic plaques contain gamma-glutamyl transpeptidase enzyme activity.

During the last decade, growing evidence has shown that serum gamma-glutamyl transpeptidase (GGT) is an independent prognostic marker for cardiac death and reinfarction, both in unselected populations and in patients with coronary artery disease. Clinical and epidemiological evidence indicates that the prognostic value of GGT is largely independent of other risk factors for cardiovascular disease and alcohol consumption. The catalytic activity of GGT, which is present on the surface of cell membranes and in serum, is …
TFE3 Expression in Tumors of the Microphthalmia-Associated Transcription Factor (MiTF) Family

The DNA-binding factor TFE3 is closely related to microphthalmia-associated transcription factor (MiTF) and is over-expressed in alveolar soft part sarcoma (ASPS) and select renal cell carcinomas. Reports of TFE3 expression in PEComa prompted investigation into TFE3 expression among other members of the putative MiTF group of neoplasms. The authors examined cases of PEComa (n = 6), conventional angiomyolipoma (AML; n = 22), metastatic melanoma (n = 16), and clear cell sarcoma (CCS; n = 9) for TFE3 expression. Nuclear immunostaining was observed in 74% (39/53) of cases, as follows: 5/6 PEComas, 18/22 AMLs, 10/16 metastatic melanomas, and 6/9 CCSs. However, with the exception of PEComas, compared with ASPS controls, TFE3 staining was significantly less intense in the tumors examined. These results illustrate that TFE3 immunoreactivity is detectable in other members of the MiTF family of neoplasms. For this reason, such neoplasms warrant consideration in the differential diagnosis with nuclear TFE3 immunoreactivity, particularly when staining is focal and less intense.
Gene co‐expression analysis identifies common modules related to prognosis and drug resistance in cancer cell lines

To discover a common gene co‐expression network in cancer cell, we applied weighted gene co‐expression network analysis to transcriptional profiles of 917 cancer cell lines. Fourteen biologically meaningful modules were identified, including cytoskeleton, cell cycle, RNA splicing, signaling pathway, transcription, translation and others. These modules were robust in an independent human cancer microarray dataset. Furthermore, we collected 11 independent cancer microarray datasets, and correlated these modules with clinical outcome. Most of these modules could predict patient survival in one or more cancer types. Some modules were predictive of relapse, metastasis and drug resistance. Novel regulatory mechanisms were also implicated. In summary, our findings, for the first time, provide a modular map for cancer cell lines, new targets for therapy and modules for regulatory mechanism of cancer development and drug resistance.
Simulation of the Working Process of an Oil Flooded Helical Screw Compressor with Liquid Refrigerant Injection

In this paper a mathematical model for the working process of a refriceration helical screw compressor is presented and discussed. The manner in which geometric parameters such as cell volume, sealing line length, blow hole are. ,, discharge port area etc. a.re related to rotation angle is established a.nd used in the thermodynamic model which is based on real cas laws. The influence of factors such as the Mgree of oil flooding, liquid refrigerant injection, vapour charge from the economizer, different refrigerants and partial loading etc., are considered simultaneously and separately in the model. The theoretical basis of the program is described in the paper. Moreover in order to confirm the computer model the performance predicted by it is compared with the results from compressor tests. The results are compa.red for different operating conditions.
Mitochondrial DNA Depletion and Thymidine Phosphate Pool Dynamics in a Cellular Model of Mitochondrial Neurogastrointestinal Encephalomyopathy*

Mitochondrial (mt) neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease associated with depletion, deletions, and point mutations of mtDNA. Patients lack a functional thymidine phosphorylase and their plasma contains high concentrations of thymidine and deoxyuridine; elevation of the corresponding triphosphates probably impairs normal mtDNA replication and repair. To study metabolic events leading to MNGIE we used as model systems skin and lung fibroblasts cultured in the presence of thymidine and/or deoxyuridine at concentrations close to those in the plasma of the patients, a more than 100-fold excess relative to controls. The two deoxynucleosides increased the mt and cytosolic dTTP pools of skin fibroblasts almost 2-fold in cycling cells and 8-fold in quiescent cells. During up to a two-month incubation of quiescent fibroblasts with thymidine (but not with deoxyuridine), mtDNA decreased to ∼50% without showing deletions or point mutations. When we removed thymidine, but maintained the quiescent state, mtDNA recovered rapidly. With thymidine in the medium, the dTTP pool of quiescent cells turned over rapidly at a rate depending on the concentration of thymidine, due to increased degradation and resynthesis of dTMP in a substrate (=futile) cycle between thymidine kinase and 5′-deoxyribonucleotidase. The cycle limited the expansion of the dTTP pool at the expense of ATP hydrolysis. We propose that the substrate cycle represents a regulatory mechanism to protect cells from harmful increases of dTTP. Thus MNGIE patients may increase their consumption of ATP to counteract an unlimited expansion of the dTTP pool caused by circulating thymidine.
p53 gene mutations in human endometrial carcinoma

Although carcinoma of the uterine endometrium is the most frequently diagnosed malignancy of the female reproductive tract, the molecular genetic features of this tumor have yet to be described in significant detail. Since mutations of the p53 tumor suppressor gene are the single most common genetic alteration found in human malignancies, we examined the hypothesis that p53 mutations occur in human endometrial carcinoma. Sequencing analysis of exons 5–8 revealed point mutations in 3 of 21 (14%) tumors; one mutation was an unusual single‐base insertion at codons 176–177, resulting in a premature stop codon, whereas the other two were CGG→TGG transitions at codon 248. Two of these tumors showed reduction to homozygosity at the p53 allele, but one tumor apparently retained heterozygosity. These data indicate that p53 mutations occur in human endometrial carcinoma, although relatively infrequently, and that loss of the normal p53 allele does not necessarily occur with point mutation of the p53 gene in this tumor type. © 1992 Wiley‐Liss, Inc.
The relationship of intrinsic fall risk factors to a recent history of falling in older women with osteoporosis.

STUDY DESIGN Cross-sectional descriptive analysis investigating intrinsic fall risk factors in postmenopausal women with osteoporosis. OBJECTIVE To examine the relationships between history of recent falls and balance, pain, quality of life, function, posture, strength, and mobility. BACKGROUND Women with osteoporosis who fall are at a high risk of fracture due to decreased bone strength. Identifying fall risk factors for older women with osteoporosis is a crucial step in decreasing the incidence of falls and fracture. METHOD AND MEASURES: Seventy-three women over 60 years of age with established osteoporosis participated in comprehensive testing of fall history, physical function, and quality of life. RESULTS Significant correlations were found between a recent history of falls and degree of kyphosis (r = 0.29), fear of falls/emotional status (r = -0.27), and balance (r = -0.27). Degree of kyphosis and fear of falls/emotional status explained 20% of the variance of recent fall history using binary logistic regression. Women with an increased kyphosis were more likely to have had a recent fall (odds ratio [OR], 1.17; 95% CI, 1.03-1.34) and those with better emotional status and less fear of falling were less likely to have had a recent fall (OR, 0.61; 95% CI, 0.38-0.97). CONCLUSION Increased thoracic kyphosis and fear of falling are 2 intrinsic factors associated with recent falls in women with osteoporosis. To design more effective interventions to decrease fall risk in this population, future prospective, longitudinal studies should monitor kyphosis, fear of falling, balance reactions, and other potential risk factors not identified in this study.
Perturbations of the Straight Transmembrane α-Helical Structure of the Amyloid Precursor Protein Affect Its Processing by γ-Secretase

Background: Amyloid-β neurotoxicity depends on the specificity of the proteolytic cleavage of the amyloid precursor protein (APP) transmembrane domain. Results: The APP transmembrane α-helix is straight in a biological membrane bilayer. Conclusion: The flexibility of APP is key for adapting to the lipid environment and modulating proteolytic processing by γ-secretase. Significance: The dynamic characterization of APP is expected to rationalize the design of γ-secretase modulators. The amyloid precursor protein (APP) is a widely expressed type I transmembrane (TM) glycoprotein present at the neuronal synapse. The proteolytic cleavage by γ-secretase of its C-terminal fragment produces amyloid-β (Aβ) peptides of different lengths, the deposition of which is an early indicator of Alzheimer disease. At present, there is no consensus on the conformation of the APP-TM domain at the biological membrane. Although structures have been determined by NMR in detergent micelles, their conformation is markedly different. Here we show by using molecular simulations that the APP-TM region systematically prefers a straight α-helical conformation once embedded in a membrane bilayer. However, APP-TM is highly flexible, and its secondary structure is strongly influenced by the surrounding lipid environment, as when enclosed in detergent micelles. This behavior is confirmed when analyzing in silico the atomistic APP-TM population observed by residual dipolar couplings and double electron-electron resonance spectroscopy. These structural and dynamic features are critical in the proteolytic processing of APP by the γ-secretase enzyme, as suggested by a series of Gly700 mutants. Affecting the hydration and flexibility of APP-TM, these mutants invariantly show an increase in the production of Aβ38 compared with Aβ40 peptides, which is reminiscent of the effect of γ-secretase modulators inhibitors.
Endocrinological and biochemical changes of scorpionism in children in Upper Egypt

Aim: The aim of this study was to determine some endocrinological and biochemical changes of scorpionism in children in Upper Egypt. In addition, it aimed to find any possible relationship between these changes and the severity of scorpionism. Patients and methods: The present study was carried out at two university hospitals in Upper Egypt and included 42 children with envenomation and 20 apparently healthy children as controls. In all subjects, levels were measured of noradrenaline, aldosterone, insulin and cortisol, and some biochemical parameters and electrolytes including nitric oxide (NO), creatine phosphokinase (CPK), Na+ and K+. Results: Na+, NO and CPK levels were significantly higher in children with envenomation compared with the controls. Also, there was a significant reduction in K+ in patients compared with controls. Children with severe envenomation had significantly higher levels of noradrenaline, cortisol and aldosterone compared with the controls and mild cases. However, insulin levels were significantly decreased in severe cases of scorpionism compared with mild ones. Moreover, hyperglycemia was detected in all patients with envenomation compared with controls, with significantly higher blood glucose levels among children with severe envenomation compared with mild cases. Conclusion: Endocrinological changes were common in all children with scorpion envenomation and more obvious in cases of severe envenomation. The released mediators may account for several inflammatory manifestations such as pulmonary edema, myocardial failure, systemic inflammatory response syndrome and multiple organ failure. The use of insulin is recommended in cases of severe envenomation to improve the outcome.
‘What Is, Is More than It Is’: Adorno and Heidegger on the Priority of Possibility

Taylor and Francis RIPH_A_539357. sgm 10.1080/09672 59.2011. 539357 International Journal of Philosophical Studies 0967-2559 (print)/1466-4542 (online) Original Article 2 11 & F ancis 00002011 ainM cdonald i . m l @u ontreal.ca Can any more be said today regarding Adorno and Heidegger? 1 Perhaps their historical opposition has become as devoid of interest as their attacks on each were polemical. As is well known, Adorno’s career-long critique of Heidegger is unremitting and extraordinarily severe: ‘being itself is too poor, too meagre, not to reek of poverty. One gets the impression that if the absolute is nothing more than the air wafting around a wretched stove bench, then one should prefer to have nothing to do with it. ’ 2 Although it is not widely known, things were not very different in the other camp. In an interview dating from 1969, Heidegger stated that he had no interest in reading Adorno, even though – or perhaps because – the substance of his critique had been reported to him. 3 For Heidegger, Adorno’s attacks were illegitimate in part because of their apparent malice – he had also been told that Adorno had vowed to ‘bring him down’ 4 – but, more importantly, because they seemed to miss the point: his thinking showed that he was a ‘sociologist, not a philosopher’. 5 Indeed, Heidegger even questions Adorno’s credentials: ‘With whom did Adorno study [philosophy]? Did he study under anyone at all? ’ 6
An open‐label, phase 1 study to evaluate the effects of hepatic impairment on edoxaban pharmacokinetics and pharmacodynamics

Edoxaban, a once‐daily, oral, direct factor Xa inhibitor, is approved for stroke prevention in nonvalvular atrial fibrillation and venous thromboembolism treatment. This study examined the effects of mild or moderate hepatic impairment on the pharmacokinetics of edoxaban and its metabolite M4. Thirty‐three subjects enrolled in 4 treatment cohorts—mild hepatic impairment (n = 8), moderate hepatic impairment (n = 9), and 2 cohorts of healthy controls matched for age, sex, and weight (each n = 8)—and received a single 15‐mg dose of edoxaban. Plasma pharmacokinetics for edoxaban and M4, prothrombin time (PT), activated partial thromboplastin time (aPTT), and safety data were measured over 72 hours. Edoxaban and M4 exposures were similar in subjects with mild or moderate hepatic impairment compared with matched controls. Higher PT and aPTT values were observed at baseline and after edoxaban dosing in the hepatic impairment groups compared with healthy controls. Edoxaban 15 mg was well tolerated in all cohorts. These results suggest that edoxaban exposure does not significantly increase in patients with mild or moderate hepatic impairment. However, because of the potential for underlying coagulopathy, edoxaban is not recommended for use in patients with moderate or severe hepatic impairment. No dose reduction is recommended for patients with mild hepatic impairment.
Toward a Criminology of International Criminal Law: An Integrated Theory of International Criminal Violations

Violations of international criminal law (i.e., genocide, crimes against humanity, and war crimes) are a common occurrence around the globe. One need only to read international news, visit intra‐governmental (e.g., United Nations or the International Committee Red Cross), or nongovernmental organizations (e.g., Human Rights Watch or Amnesty International) to be exposed to the vast numbers of crimes of states, paramilitaries, and/or militias. Nonetheless, there has been relatively little attention paid to these types of offenses by criminologists. While there have been developments in creating typologies (Smeulers, 2008) and predictive models for genocide (Harf, 2005), due to the complexities and various forms of these types of crimes, there has been little to no development of a criminological theoretical model that can aid in the analysis of such crimes. Our goal is to firmly place international crimes on the criminological agenda by creating additional awareness of and interest in the most massive, systematic, and gruesome types of crime‐genocide, crimes against humanity, war crimes, and crimes of aggression‐and to introduce an integrated theory that can provide a frame for a systematic analysis and understanding of the etiologi‐ cal factors at play.
Small-Sided Games in Team Sports Training: A Brief Review

Abstract Halouani, J, Chtourou, H, Gabbett, T, Chaouachi, A, and Chamari, K. Small-sided games in team sports training: A brief review. J Strength Cond Res 28(12): 3594–3618, 2014—Small-sided games (SSGs) incorporating skills, sport-specific movements, at intensities sufficient to promote aerobic adaptations, are being increasingly implemented in professional team sport environments. Small-sided games are often employed by coaches based on the premise that the greatest training benefits occur when training simulates the specific movement patterns and physiological demands of the sport. At present, there is relatively little information regarding how SSG can best be used to improve physical capacities and technical and tactical skills in team sports. It is possible that with some modifications (e.g., number of players, pitch size, coach encouragement, and wrestling), such games may be physiologically beneficial for athletes with relatively high initial aerobic fitness levels. For instance, it has been shown that 3-a-side soccer SSG resulted in higher intensity (i.e., greater overall distance, less jogging and walking, higher heart rate, and more tackling, dribbling, goal attempts, and passes) than 5-a-side SSG. Likewise, when player numbers were kept constant, a larger playing area increased the intensity of the SSG with a smaller playing area having the opposite effect. It has also been demonstrated that energy expenditure was similar between badminton and volleyball courts, but lower than that obtained in a basketball court. Moreover, it has been demonstrated in rugby that wrestling can increase the physical demands of SSG. Consistent coach encouragement can also increase training intensity, although most rule changes have trivial or no effect on exercise intensity. Further research is required to examine the optimal periodization strategies of SSG training for the long-term development of physiological capacity, technical skill, and tactical proficiency, while also minimizing the associated risk of injuries.
Neuroanatomical circuitry mediating the sensory impact of nicotine in the central nervous system

Direct actions of nicotine in the CNS appear to be essential for its reinforcing properties. However, activation of nicotinic acetylcholine receptors (nAChRs) on afferent sensory nerve fibers is an important component of addiction to, and withdrawal from, cigarette smoking. The aim of the present study was to identify the neuroanatomical substrates activated by the peripheral actions of nicotine and to determine whether these sites overlap brain structures stimulated by direct actions of nicotine. Mouse brains were examined by immunohistochemistry for c‐Fos protein after intraperitoneal injection of either nicotine hydrogen tartrate salt (NIC; 30 and 40 μg/kg) or nicotine pyrrolidine methiodide (NIC‐PM; 20 and 30 μg/kg). NIC‐PM induced c‐Fos immunoreactivity (IR) at multiple brain sites. In the brainstem, c‐Fos IR was detected in the locus coeruleus, laterodorsal tegmental nucleus, and pedunculotegmental nucleus. In the midbrain, c‐Fos IR was observed in areas overlapping the ventral tegmental area (VTA), which includes the paranigral nucleus, parainterfascicular nucleus, parabrachial pigmental area, and rostral VTA. Other structures of the nicotine brain‐reward circuitry activated by NIC‐PM included the hypothalamus, paraventricular thalamic nucleus, lateral habenular nucleus, hippocampus, amygdala, accumbens nucleus, piriform cortex, angular insular cortex, anterior olfactory nucleus, lateral septal nucleus, bed nucleus of stria terminalis, cingulate and medial prefrontal cortex, olfactory tubercle, and medial and lateral orbital cortex. NIC, acting through central and peripheral nAChRs, produced c‐Fos IR in areas that overlapped NIC‐PM‐induced c‐Fos‐expressing sites. These neuroanatomical data are the first to demonstrate that the CNS structures that are the direct targets of nicotine are also anatomical substrates for the peripheral sensory impact of nicotine. © 2014 Wiley Periodicals, Inc.
Flufenamic Acid Bi-Directionally Modulates the Transient Outward K+ Current in Rat Cerebellar Granule Cells

In this report, the effect of flufenamic acid on voltage-activated transient outward K+ current (IA) in cultured rat cerebellar granule cells was investigated. At a concentration of 20 μMto1 mM, flufenamic acid reversibly inhibited IA in a dose-dependent manner. However, flufenamic acid at a concentration of 0.1 to 10 μM significantly increased the current amplitude of IA. In addition to the current amplitude of IA, a higher concentration of flufenamic acid had a significant effect on the kinetic parameters of the steady-state activation and inactivation process, suggesting that the binding affinity of flufenamic acid to IA channels may be state-dependent. Silencing the Kv4.2, Kv4.3, and Kv1.1 genes of IA channels using small interfering RNA did not change the inhibitory effect of flufenamic on IA, indicating that flufenamic acid did not act specifically on any of the subunits of the IA-channel protein. Intracellular application of flufenamic acid could significantly increase the IA amplitude but did not alter the inhibited effect induced by extracellular application of flufenamic acid, implying that flufenamic acid may exert its effect from both the inside and outside sites of the channel. Furthermore, the activation of current induced by intracellular application of flufenamic acid could mimic other cyclooxygenase inhibitors and arachidonic acid. Our data are the first that demonstrate how flufenamic acid is able to bidirectionally modulate IA channels in neurons at different concentrations and by different methods of application and that two different mechanisms may be involved.