Miracle-dz/UniFAR-FTUs huggingface dataset:
Thrombocytopenia as a mortality risk factor in acute respiratory failure in H1N1 influenza.

BACKGROUND A small proportion of patients with influenza H1N1 rapidly develop acute respiratory failure and are a problem for intensive care units (ICUs). Although certain clinical risk factors have been identified, few measurable biochemical/haematological markers able to predict poor outcome have been reported. The aims of the present report are to show which variables on and during admission are associated with increased in-hospital mortality in patients admitted to the ICU with acute respiratory failure due to H1N1 influenza. METHODS A prospective observational study at two ICUs was carried out between August 2009 and March 2011. The study period covered two waves of pandemic influenza A H1N1 in Spain. Clinical and laboratory data on and during ICU admission were recorded for the purpose of analysis. RESULTS Sixty patients with acute respiratory failure due to H1N1 influenza were admitted during the period described above; 63.3% (n = 38) were male and the mean age was 49.2 ± 14 years. Regarding comorbidities, 46.7% (n = 28) were smokers, 38% (n = 23) had hypertension, 30% (n = 18) had a body mass index (BMI) >30 kg/m2, 30% (n = 18) had chronic obstructive pulmonary disease and 26% (n = 16) had cardiac insufficiency; 16.6% (n = 10) had bacterial co-infection, 70% (n = 42) required invasive mechanical ventilation and 48.3% (n = 29) non-invasive mechanical ventilation. Mortality was 20% (n = 12). Comparing survivors with non-survivors, univariate analysis revealed significant differences in BMI, creatinine, haemoglobin, platelets, arterial pH, pCO2, and the rate of bacterial co-infection. In the multivariate analysis, only the presence of lower platelet count was statistically significant (214 ± 101 vs 113 ± 82 ×109/L; p = 0.009). Patients with thrombocytopenia showed a lower in-hospital survival rate (55%vs92.5%; Log Rank = 0.008). CONCLUSIONS Thrombocytopenia could be valuable marker of in-hospital mortality in patients with respiratory failure due to H1N1 influenza in the ICU scenario.
Scrutinizing “Invisible” astatine: A challenge for modern density functionals

The main‐group 6p elements did not receive much attention in the development of recent density functionals. In many cases it is still difficult to choose among the modern ones a relevant functional for various applications. Here, we illustrate the case of astatine species (At, Z = 85) and we report the first, and quite complete, benchmark study on several properties concerning such species. Insights on geometries, transition energies and thermodynamic properties of a set of 19 astatine species, for which reference experimental or theoretical data has been reported, are obtained with relativistic (two‐component) density functional theory calculations. An extensive set of widely used functionals is employed. The hybrid meta‐generalized gradient approximation (meta‐GGA) PW6B95 functional is overall the best choice. It is worth noting that the range‐separated HSE06 functional as well as the old and very popular B3LYP and PBE0 hybrid‐GGAs appear to perform quite well too. Moreover, we found that astatine chemistry in solution can accurately be predicted using implicit solvent models, provided that specific parameters are used to build At cavities. © 2016 Wiley Periodicals, Inc.
Effects of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice

The present study was designed to investigate the effect of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice. Mice were immunized subcutaneously at the base of the tail with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0) and were treated daily with oral administration of various doses of rolipram from days 0 to 20. On day 21, production of anti‐OVA IgG and proliferative responses to the antigen were determined. Anti‐OVA IgG2a and interferon‐γ (IFN‐γ), as indicators of Th1 responses, and anti‐OVA IgG1 and interleukin‐10 (IL‐10), as indicators of Th2 responses, were also measured. The results showed that treatment with rolipram failed to affect the production of OVA‐specific IgG but decreased the proliferation of spleen cells to the antigen. Its inhibitory effect on these immune responses was correlated with a marked decrease in IFN‐γ but not IL‐10 production, although neither anti‐OVA IgG2a nor IgG1 production was affected by rolipram. These results suggest that rolipram may preferentially inhibit Th1 responses more effectively than Th2 responses. Administration of rolipram resulted in suppression of antigen (OVA)‐induced arthritis in mice. The suppression of joint inflammation by rolipram was associated with the inhibition of the OVA‐specific proliferative responses of spleen cells and IFN‐γ secretion. These results indicate that rolipram may be effective in regulating Th1‐mediated diseases such as rheumatoid arthritis.
The Medical Council of Canada's key features project: a more valid written examination of clinical decision‐making skills

In 1986 the Medical Council of Canada (MCC) commissioned a six-year research and development project to create a new, more valid written examination of clinical decision-making skills for the Canadian Qualifying Examination in Medicine. At that time, the qualifying examination consisted of three booklets of multiple-choice questions and one booklet of patient management problems administered over a two-day period. All graduates of Canadian and foreign medical schools must pass this examination before practicing medicine anywhere in Canada except Quebec. The project was undertaken because (1) numerous studies do not support the use of patient management problems (PMPs) to assess clinical decision-making skills, and (2) research results on the characteristics of clinical decision-making skills offered guidance to develop new approaches to their assessment. In particular, research suggested that these skills are specific to the case or problem encountered and are contingent on the effective manipulation of a few elements of the problem that are crucial to its successful resolution–the problem's key features. The problems developed by this project focused only on the assessment of these key features. The project was implemented in three overlapping phases over a six-year period, 1986–1992, each containing a development component followed by a pilot test through which the research studies were carried out. The pilot tests were conducted by presenting sets of new key feature problems to classes of graduating students in medical schools across Canada. (ABSTRACT TRUNCATED AT 250 WORDS)
R-TNCES: A Novel Formalism for Reconfigurable Discrete Event Control Systems

This study deals with the formal modeling and verification of reconfigurable discrete event control systems (RDECSs). The behavior of an RDECS is represented by that of control components (CCs) and the communication among them. A new formalism, called Reconfigurable Timed Net Condition/Event Systems (TNCES) (R-TNCES), is proposed for the optimal functional and temporal specification of RDECS, which is defined by a behavior module and a control module. The former is a union of various superposed TNCESs, where TNCES-based CC modules are basic units. The latter is a set of reconfiguration functions dealing with the automatic transformations of these TNCESs in response to errors or user requirements by enabling or disabling CC modules, changing condition signals and/or event signals among them, and also treating the state feasibility before and after reconfigurations. To control the verification complexity of R-TNCES, a layer-by-layer verification method is developed, where the similarities of different TNCESs in the behavior module are considered. The contribution of this original paper is applied to a benchmark production system.
A Novel Bis-Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI), GRL-98065, Is Potent against Multiple-PI-Resistant Human Immunodeficiency Virus In Vitro

ABSTRACT We designed, synthesized, and identified GRL-98065, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF), and a sulfonamide isostere, which is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50], 0.0002 to 0.0005 μM) with minimal cytotoxicity (50% cytotoxicity, 35.7 μM in CD4+ MT-2 cells). GRL-98065 blocked the infectivity and replication of each of the HIV-1NL4-3 variants exposed to and selected by up to a 5 μM concentration of saquinavir, indinavir, nelfinavir, or ritonavir and a 1 μM concentration of lopinavir or atazanavir (EC50, 0.0015 to 0.0075 μM), although it was less active against HIV-1NL4-3 selected by amprenavir (EC50, 0.032 μM). GRL-98065 was also potent against multiple-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents, HIV-1 isolates of various subtypes, and HIV-2 isolates examined. Structural analyses revealed that the close contact of GRL-98065 with the main chain of the protease active-site amino acids (Asp29 and Asp30) is important for its potency and wide-spectrum activity against multiple-PI-resistant HIV-1 variants. The present data demonstrate that the privileged nonpeptide P2 ligand, bis-THF, is critical for the binding of GRL-98065 to the HIV protease substrate binding site and that this scaffold can confer highly potent antiviral activity against a wide spectrum of HIV isolates.
Fbxw7 Limits Myelination by Inhibiting mTOR Signaling

An important characteristic of vertebrate CNS development is the formation of specific amounts of insulating myelin membrane on axons. CNS myelin is produced by oligodendrocytes, glial cells that extend multiple membrane processes to wrap multiple axons. Recent data have shown that signaling mediated by the mechanistic target of rapamycin (mTOR) serine/threonine kinase promotes myelination, but factors that regulate mTOR activity for myelination remain poorly defined. Through a forward genetic screen in zebrafish, we discovered that mutation of fbxw7, which encodes the substrate recognition subunit of a SCF ubiquitin ligase that targets proteins for degradation, causes hypermyelination. Among known Fbxw7 targets is mTOR. Here, we provide evidence that mTOR signaling activity is elevated in oligodendrocyte lineage cells of fbxw7 mutant zebrafish larvae. Both genetic and pharmacological inhibition of mTOR function suppressed the excess myelin gene expression resulting from loss of Fbxw7 function, indicating that mTOR is a functionally relevant target of Fbxw7 in oligodendrocytes. fbxw7 mutant larvae wrapped axons with more myelin membrane than wild-type larvae and oligodendrocyte-specific expression of dominant-negative Fbxw7 produced longer myelin sheaths. Our data indicate that Fbxw7 limits the myelin-promoting activity of mTOR, thereby serving as an important brake on developmental myelination. SIGNIFICANCE STATEMENT Myelin, a specialized, proteolipid-rich membrane that ensheaths and insulates nerve fibers, facilitates the rapid conduction of electrical impulses over long distances. Abnormalities in myelin formation or maintenance result in intellectual and motor disabilities, raising a need for therapeutic strategies designed to promote myelination. The mTOR kinase is a powerful driver of myelination, but the mechanisms that regulate mTOR function in myelination are not well understood. Our studies reveal that Fbxw7, a subunit of a ubiquitin ligase that targets other proteins for degradation, acts as a brake on myelination by limiting mTOR function. These findings suggest that Fbxw7 helps tune the amount of myelin produced during development and raise the possibility that Fbxw7 could be a target of myelin-promoting therapies.
Arrangement and innervation of the glutei medius and minimus and the piriformis: A morphological analysis

In order to examine the relationships between the positional arrangement and supplying nerves of the glutei medius and minimus and the piriformis, we investigated 49 pelvic halves of 28 cadavers. The superior gluteal nerve ran on the ventral surface of the piriformis in 44 cases (89.8%) (Type A), and some branches of the nerve perforated the piriformis in five cases (10.2%) (Type B). Based on the detailed findings of the innervation of the three muscles, the piriformis is chiefly composed of the caudal element of the gluteus medius (Type A) and in some cases the caudal element of the gluteus minimus as well (Type B). © 1994 Wiley‐Liss, Inc.
Pharmacogenetics of isoniazid-induced hepatotoxicity

Abstract Tuberculosis is still a major problem in some developed and developing countries. The poor compliance to the treatment of tuberculosis patients due to the adverse events was supposed to be an important factor contributing to the high prevalence. This review aims to clarify the role and the pharmacological mechanism of the genes involved in the isoniazid-induced hepatotoxicity. We selected English articles of studies in human from PubMed up to May 2014 with the keywords pharmacogenetic, isoniazid and hepatotoxicity, N-acetyl transferase 2 (NAT2), CYP2E1 and glutathione S transferase (GST). Polymorphisms of NAT2, CYP2E1 and GST1 could increase patients’ susceptibility to isoniazid-induced hepatotoxicity. The rapid acetylators of NAT2 and rapid metabolizers of CYP2E1 showed increased concentrations of hepatotoxic metabolites. However, the rapid metabolizers of GST1 could decrease the concentration of hepatotoxic metabolites. Some studies of human leukocyte antigen (HLA), Uridine 5′-dipphospho (UDP) glucuronosyltransferase (UGT), nitric oxide synthase (NOS), Broad complex, Tramtrack, Bric-a-brac (BTB) and cap'n'collar type of basic region leucine zipper factor family (CNC) homolog (BACH) and Maf basic leucine zipper protein (MAFK) polymorphisms showed their roles in isoniazid-induced hepatotoxicity by modifying the expression of antioxidant enzymes. A better insight into the role of polymorphisms of HLA, UGT, NOS, BACH and MAFK in addition to NAT2, CYP2E1 and GST1 in the hepatotoxicity of isoniazid may support physicians in monitoring patients hepatotoxicity symptoms and laboratory data and optimizing pharmacotherapy. Future studies about the role of such polymorphisms in different ethnicities are suggested.
Evaluation of Gamma Interferon and Antibody Tuberculosis Tests in Alpacas

ABSTRACT We describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-γ) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas from Mycobacterium bovis culture-confirmed breakdown herds and TB-free alpacas from geographical areas with no history of bovine TB, respectively. Our results show that while the sensitivities of the IFN-γ and antibody tests were similar (range of 57.7% to 66.7%), the specificity of the IFN-γ test (89.1%) was lower than those of any of the antibody tests (range of 96.4% to 97.4%). This lower specificity of the IFN-γ test was at least in part due to undisclosed Mycobacterium microti infection in the TB-free cohort, which stimulates a positive purified protein derivative (PPD) response. The sensitivity of infection detection could be increased by combining two antibody tests, but even the use of all four antibody tests failed to detect all diseased alpacas. These antibody-negative alpacas were IFN-γ positive. We found that the maximum sensitivity could be achieved only by the combination of the IFN-γ test with two antibody tests in a “test package,” although this resulted in decreased specificity. The data from this evaluation of tests with defined sensitivity and specificity provide potential options for antemortem screening of SAC for TB in herd breakdown situations and could also find application in movement testing and tracing investigations.
Corporate Governance and Firm Performance: A Study of Indian Listed Firms

The focus of corporate governance (CG) systems is the agency problem, and it refers to the set of mechanisms that influences managerial decisions when there is a separation of ownership and control. Better CG may or may not be related to higher organizational performance. In this article, we propose to study whether firm level good CG lead to better firm performance and higher value creation in the form of share price returns. We use a panel of 58 top Indian listed companies in terms of market capitalization—BSE 100 and NSE 100—over the five-year period from 2007–2008 to 2011–2012 for our analysis. Our measurement analysis starts with a broad sample of 25 structural indicators of CG relating to directors, boards committees, audit considerations, ownership and capital structure characteristics, and our defined set of control variables. We have used two measures of firm performance, Market to Book Value Ratio (MTBVR) and Return on Equity (ROE). We used principal component analysis to identify the underlying dimensions of CG and determined which indicators are associated with each factor. We regressed MTBVR and ROE against the factor scores generated. MTBVR resulted in an R-square of 34.9 per cent and has a strong association with five factors. ROE resulted in an R-square of 48.6 per cent and was significantly influenced by the five factors.
Stability Analysis of a Class of Nonlinear Fractional-Order Systems

In this paper, a stability theorem of nonlinear fractional-order differential equations is proven theoretically by using the Gronwall-Bellman lemma. According to this theorem, the linear state feedback controller is introduced for stabilizing a class of nonlinear fractional-order systems. And, a new criterion is derived for designing the controller gains for stabilization, in which control parameters can be selected via the pole placement technique of the linear fractional-order control theory. Finally, the theoretical results are further substantiated by simulation results of the fractional-order chaotic Lorenz system with desired design requirements.
Quantitation of Muscles and Fat by Ultrasonography: A Useful Method in the Assessment of Malnutrition in Children

ABSTRACT. We used ultrasonography to measure muscles in the arms and thighs of 16 children with malignant diseases. Thicknesses of transverse sections of the brachial biceps muscle and the femoral quadriceps muscle were measured by ultrasound at the midpoint of the right arm and thigh. These two measures had a linear correlation (r=0.76). The ultrasound measurements did not differ from those obtained by the CT scan which was used as a reference standard. The reproducibility of the measurements was good, the coefficient of variation was 2.4% for the midarm muscles and 2.8% for the midthigh muscles. We conclude that the ultrasound method combined with simple anthropometric measurements is helpful in the assessment of nutritional status of children with potential malnutrition.
Down‐regulation of insulin‐degrading enzyme by presenilin 1 V97L mutant potentially underlies increased levels of amyloid beta 42

Amyloid beta (Aβ)42 plays a pivotal role in Alzheimer's disease. We previously reported a novel presenilin (PS)1 mutant (V97L) that was expressed in related patients with early onset Alzheimer's disease. We found that patients with the V97L mutation had increased levels of extracellular and intracellular Aβ42. Here we found that the increased extracellular level of Aβ42 was always accompanied by a reduction of insulin‐degrading enzyme (IDE) activity on the plasma membranes. However, increase of intracellular Aβ42 was associated with decreased expression and activity of IDE in the cytosol and endoplasmic reticulum in the PS1 V97L mutant‐transfected human SH‐SY5Y cell line. These studies indicate that pathological levels of Aβ42 may be caused by the negative effects of PS1 (V97L) on IDE expression and activity. Our findings provide evidence for the molecular basis of familial Alzheimer's disease pathogenesis.
Female mating strategy in an enclosed group of Japanese macaques

Female Japanese macaques (Macaca fuscata) are noted for mating with multiple males and for their ability to exert mate choice. In a captive group of Japanese macaques housed at the Primate Research Institute of Kyoto University, Japan, behavioral and endocrine data were combined to examine female mating strategies. During one breeding season, daily behavioral observations were conducted on females who exhibited copulatory behavior. Blood was collected from females twice weekly and their ovulatory periods estimated by analyzing hormone profiles. Females began mating shortly before ovulation, peaked at ovulation, and continued receiving ejaculations for up to ten weeks after conception. Females were more responsible than males for inbreeding avoidance with matrilineal kin. Males sometimes approached females from their own matriline, but females avoided such males and expressed mate choice behavior preferentially toward non‐matrilineal males. Over the entire mating season, females did not choose non‐matrilineal males on the basis of displays, dominance rank, age, weight, or weight change during the mating season. When females were likely to conceive, however, they expressed mate choice behavior toward males who displayed most frequently. Female mating strategy may include both mate choice at ovulation and other, non‐procreative functions. Am. J. Primatol. 47:263–278, 1999. © 1999 Wiley‐Liss, Inc.
The effect of PAMAM dendrimer concentration, generation size and surface functional group on the aqueous solubility of candesartan cilexetil

Abstract This article investigates the aqueous solubility of the poorly soluble drug candesartan cilexetil (CC) in the presence of poly(amidoamine) (PAMAM) dendrimers. The effect of variables such as concentration, generation size (G2–G4), and surface groups (NH2, COOH and TRIS) of PAMAMs on the aqueous solubility of CC was studied. A two-factor factorial (3 × 3) ANOVA design was used to study the effect of generation size and surface functional group of the PAMAMs. The results showed that the aqueous solubility of CC in the presence of carboxyl and TRIS-terminated PAMAMs was higher than those of amine-terminated PAMAMs, and the effect of surface functional group of the PAMAMs on the aqueous solubility of CC was dependent on the generation size (p < 0.05). The sequence of the observed solubility fold enhancement due to PAMAMs was G4.COOH (8378)>G3.COOH (3456)>G4.TRIS (2362)>G2.COOH (1013)>G3.TRIS (749)>G2.TRIS (293)>G4.NH2 (91)>G3.NH2 (50)>G2.NH2 (37). The CC-PAMAM dendrimer inclusion complexes were characterized by UV–Vis, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and differential thermal analysis (DTA) techniques. Regarding the results of these techniques, improvement in the solubility of CC is expected primarily through the intermolecular hydrogen bonding between the drug and internal tertiary and surface functional groups of the studied PAMAMs.