Miracle-dz/UniFAR-FTUs huggingface dataset:
Re: novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations.

We have read with interest the article by Xu et al. in a recent issue of the Journal (1). In this study, the authors carried out the first multiethnic genome-wide association study with pediatric acute lymphoblastic leukemia (ALL), and in addition to replicating previously described loci, they found a new association locus in the PIP4K2A gene. This association was confirmed in three replication cohorts of different ethnicities (European American, African American, and Hispanic American). In our group, we tried to replicate this association in a Spanish population of 191 B cell ALL (B-ALL) patients and 342 unrelated healthy control subjects to verify whether this is a general mechanism involved in ALL risk. We made a linkage disequilibrium analysis of the four single nucleotide polymorphisms (SNPs) in PIP4K2A that were associated with ALL risk in the article by Xu et al., using Hapmap database and Haploview version 4.2 software (Daly lab at the Broad Institute, Cambridge, MA, USA). Because the four SNPs were in linkage disequilibrium with an r2 greater than 0.8, we decided to analyze rs7088318 as a tagSNP of this association hotspot. We carried out an allelespecific polymerase chain reaction and carried out the genotyping with a 100% success. Both case patients and control subjects were in Hardy–Weinberg equilibrium. We carried out an association study under the codominant, dominant, recessive, and log-additive models. However, we did not replicate the statistically significant association between rs7088318 genotype and ALL risk under any of the inheritance models analyzed (Table 1). Differences in results might be because of differences in genetic composition among populations. In fact, if we have a look at the risk allele frequency (RAF) in our control population, it is higher (RAF = 0.646) than that in the control European American population analyzed by Xu et al. (RAF = 0.59) and similar to what they observed in the case European American population (RAF = 0.65). This peculiarity makes it difficult to find statistically significant differences in frequency between case patients and control subjects. Therefore, we conclude that SNPs in PIP4K2A may be associated with pediatric ALL risk in some populations but it does not seem to be a good susceptibility marker in the Spanish population. Consequently, it does not seem to be as general of a susceptibility marker as other previously proposed SNPs, such as those in ARID5B or IKZF1, which have been replicated in multiple populations.
Rimonabant inhibits proliferation, collagen secretion and induces apoptosis in hepatic stellate cells.

BACKGROUND/AIMS Liver fibrosis represents a significant health problem worldwide. Hepatic stellate cells (HSCs) play a critical role in the live fibrosis. Rimonabant (SR141716) is cannabinoid receptor type 1 (CB1) antagonist. The pharmacological effects of rimonabant on HSCs are not well characterized in HSCs. METHODS CB1 receptor was detected by immunohistochemistry in human liver fibrosis specimens. Cell proliferation was detected by MTT assay. Cell apoptosis, caspase-3 protein expression and cell cycle were detected by TEM and flow cytometry, respectively. Caspase-3 activity was measured using caspase-3 activity assay kit. Collagen secretion was evaluated by radioimmunoassay. CB1 receptor and signaling molecules were evaluated by qRTPCR and Western blot. RESULTS Immunohistochemistry showed a discrete, punctuated CB1 immunoreactivity in human liver fibrosis specimens. Rimonabant reduced HSC proliferation and increased HSC apoptosis. Cell cycle analysis showed a decrease in G2/M phase cells and an increase in G0/G1 phase cells in HSC-T6 cells treated with rimonabant. Caspase-3 protein expression and activity were increased by rimonabant. Rimonabant decreased collagen secretion in HSC-T6 cells. Moreover, rimonabant inhibited the expression of phosphorylated FAK and ERK and down-regulated CB1 mRNA expression. CONCLUSION The study provides new insights toward the pharmacological effect of rimonabant on HSCs in vitro. Rimonabant inhibits proliferation, collagen secretion and induces apoptosis in HSCs.
Self-reported adherence to antiretroviral therapy in HIV+ population from Bata, Equatorial Guinea

ABSTRACT The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June–July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p < .001). Overall, 55% patients had low or insufficient adherence. CEAT-VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives.
Femoroacetabular Impingement Is Associated With Sports-Related Posterior Hip Instability in Adolescents

Background: Femoroacetabular impingement (FAI) deformity has been associated with posterior hip instability in adult athletes. Purpose: To determine if FAI deformity is associated with posterior hip instability in adolescents, the femoral head-neck junction or acetabular structure in a cohort of adolescent patients who sustained a low-energy, sports-related posterior hip dislocation was compared with that in a group of healthy age- and sex-matched controls with no history of hip injury or pain. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We identified 12 male patients (mean age, 13.9 years; range, 12-16 years) who sustained a sports-related posterior hip dislocation and underwent a computed tomography (CT) scan after closed reduction. For each patient, 3 age- and sex-matched healthy controls were identified. Femoral head-neck type was assessed by measurement of the alpha angle on the radially oriented CT images at the 12-, 1-, 2-, and 3-o’clock positions. Age, body mass index (BMI), alpha angle at each position, acetabular version, Tönnis angle, and lateral center-edge angle (LCEA) on the involved hip in the dislocation group were compared with those of the matched controls using a mixed-effects model. A logistic regression analysis using a generalized estimating equation was used to compare the percentage of subjects with cam-type FAI deformity (alpha angle >55°) in each group. Results: The dislocation and control groups were similar in age distribution and BMI (P > .05). The mean alpha angles were statistically significantly higher in the dislocation group compared with the control group at the superior (46.3° ± 1.1° vs 42.7° ± 0.6°; P = .0213), superior-anterior (55.5° ± 1.9° vs 46.0° ± 1.3°; P = .0005), and anterior-superior (54.9° ± 1.5° vs 48.9° ± 1.0°; P = .0045) regions. Cam deformity was present in a larger proportion of patients in the dislocation group than in the control group (P < .0035). An alpha angle greater than 55° was present in 16.7% of the dislocation group and 0% of the control group at the 12-o’clock position (P = .1213), 41.7% versus 0% at the 1-o’clock position (P = .0034), 58% versus 6% at the 2-o’clock position (P = .0004), and 25% versus 2.8% at the 3-o’clock position (P = .0929). Acetabular anteversion was lower in the dislocation group (9.6° ± 1.4°) compared with the control group (15.1° ± 0.8°) (P = .0068). Mean acetabular LCEA was within a normal range in both groups. Conclusion: A significantly higher mean alpha angle from the superior to the anterior-superior regions of the femoral head-neck junction and lower acetabular version were found in adolescents who sustained low-energy, sports-related posterior hip dislocations.
Sphingosine-1-phosphate activation of TRPC 5 in vascular smooth muscle cells

Calcium signalling is a complex and diverse system utilized in many cellular processes and in the transmission of cellular information. A number of transient receptor potential (TRP) proteins have been identified in humans and other mammals; these proteins are implicated as having a role in calcium signalling. TRPC5 is a member of this protein family which combines with TRPC1 to form non-selective cation channels in human saphenous vein cells, a type of smooth muscle cell. The exact function of TRPC5 remains elusive, however, it can be activated by sphingosine-1-phosphate (S1P), an endogenous signalling phospholipid involved in SMC migration. The aim of these experiments was to investigate the effects of S1P on the intracellular calcium concentration, [Ca]i, in HSV cells, utilizing dominant-negative (DN)-TRPC5 transfected cells to establish the role played by TRPC5 in this response. A secondary aim was to establish the effect of SMC migration on the above response parameters to S1P using the HSV scratch assay, where a 2 mm line of cells was scraped away from the surface of a glass cover slip and the remaining cells incubated for 24 h. Concurrent with the literature, S1P evoked a significant response in HSV cells (n1⁄423; P1⁄40.001). The baseline was significantly lower in the DN-TRPC5 cells compared with the control cells (P,0.001), and the maximum response in the DN-TRPC5 transfected HSV cells reached only 60% of the maximum response in control cells. This suggested that TRPC5 was involved with maintaining basal [Ca2þ]i levels and indicated the proportion of the response for which TRPC5 was responsible. The response to S1P was significantly larger in migrated (n1⁄47) compared with static (n1⁄411) HSV cells (P1⁄4,0.001) and this response was delayed by 2.3 min; the baseline was also higher in the latter group. This suggested a functional change in the cell following migration that may have been attributable to TRPC5, for example, channel up-regulation. In conclusion, TRPC5-like channels are responsible for a proportion of the S1P response and are implicated in SMC migration. This highlights potential pharmacological targets for the treatment of atherosclerosis, neointimal hyperplasia and coronary heart disease.
Antioxidant and DNA damage protective properties of anthocyanin-rich extracts from Hibiscus and Ocimum: a comparative study

Anthocyanin extracts (AEs) from Ocimum tenuiflorum (leaf), Hibiscus rosa-sinensis (petal) and Hibiscus sabdariffa (calyx) were investigated and compared for in vitro antioxidant activity and DNA damage protective property. Total phenolic content (TPC) and total anthocyanin content (TAC) of the AEs were determined and the major anthocyanins were characterised. In vitro antioxidant activities were assessed by ferric-reducing antioxidant power (FRAP) assay, 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical-scavenging activity, 2-deoxy-d-ribose degradation assay and lipid peroxidation assay. The protective property of the AEs was also examined against oxidative DNA damage by H2O2 and UV using pUC19 plasmid. All the AEs particularly those from O. tenuiflorum demonstrated efficient antioxidant activity and protected DNA from damage. Strong correlation between antioxidant capacity and TPC and TAC was observed. Significant correlation between antioxidant capacity and TPC and TAC ascertained that phenolics and anthocyanins were the major contributors of antioxidant activity.
A Higher Gradient Theory of Multiphase Solid Mixtures and its Application to Lead-Free Solder Micro-Morphology

In order to analyze the micro-morphology evolution in today's (lead-free) solders we present a theory of multi- component heterogeneous solid mixtures based on fundamental thermodynamic principles. We derive an extended diffusion equation, which allows to predict the diffusion-induced phase separation and coarsening process within solids under the presence of local (thermo-)mechanical strains on a theoretical basis. As an example we specialize to the lead-free binary case study alloy Ag-Cu and simulate the spinodal decomposition and coarsening process. We end with a model for the formation and growth of pores within the solder material, which is particularly driven by the so-called Kirkendall effect in the different phases of the composite material.
Exclusive Control in Boolean

In the typical framework for boolean games (BG) each player can change the truth value of some propositional atoms, while attempting to make her goal true. In standard BG goals are propositional formulas, whereas in iterated BG goals are formulas of Linear Temporal Logic. Both notions of BG are characterised by the fact that agents have exclusive control over their set of atoms, meaning that no two agents can control the same atom. In the present contribution we drop the exclusivity assumption and explore structures where an atom can be controlled by multiple agents. We introduce Concurrent Game Structures with Shared Propositional Control (CGS-SPC) and show that they account for several classes of repeated games, including iterated boolean games, influence games, and aggregation games. Our main result shows that, as far as verification is concerned, CGS-SPC can be reduced to concurrent game structures with exclusive control. This result provides a polynomial reduction for the model checking problem of specifications in Alternating-time Temporal Logic on CGS-SPC.
The ratio of red cell distribution width to mean corpuscular volume in patients with diabetic ketoacidosis.

BACKGROUND The relationship between erythrocyte parameters and diabetic ketoacidosis (DKA) remains uncertain. This study aimed to investigate the potential role of erythrocyte indices in type 1 diabetes (T1D) patients with DKA. METHODS This study included 48 patients with T1D, 26 patients with DKA, and 30 age- and gender-matched controls. Erythrocyte parameters were measured and evaluated at the time of admission and after treatment. RESULTS Data were analyzed by One-Way ANOVA Tukey analysis with SPSS software. The DKA patients had higher levels of plasma glucose (28.87 +/- 9.01 mmol/L), HbA1c (13.08 +/- 3.10%), osmotic pressure (332.11 +/- 11.67 mosm/L), red cell distribution width (RDW, 41.24 +/- 3.08 fL), and the RDW to mean corpuscular volume (MCV) ratio (47.50 +/- 3.70%) compared to non-DKA cases and controls (all p < 0.05). Pearson's correlation test showed that osmolality was positively correlated with plasma glucose (r = 0.699, p < 0.001) and negatively correlated with mean corpuscular hemoglobin concentration (MCHC) (r = -0.409, p = 0.049). Receiver operating characteristic curve analyses demonstrated that the areas under the curves were 0.924 for the RDW/MCV ratio and 0.802 for RDW in the ability of reflecting DKA (z = 2.086, p = 0.0369). A logistic regression revealed that the RDW/MCV ratio can act as a robust risk marker for the presence of DKA (OR = 1.548, p = 0.0360, 95% CI: 1.029 - 2.330). The RDW returned to normal, and plasma glucose levels and metabolic acidosis were well controlled following treatment. CONCLUSIONS The RDW and the RDW/MCV ratio were significantly correlated with DKA. The RDW/MCV ratio can act as a robust biomarker that is more sensitive than RDW in reflecting the presence of DKA.
Chronic Helminth Infection Induces Alternatively Activated Macrophages Expressing High Levels of CCR5 with Low Interleukin-12 Production and Th2-Biasing Ability

ABSTRACT Helminth infections induce Th2-type biased immune responses. Although the mechanisms involved in this phenomenon are not yet clearly defined, antigen-presenting cells (APC) could play an important role in this process. Here, we have used peritoneal macrophages (F4/80+) recruited at different times after challenge with Taenia crassiceps as APC and tested their ability to regulate Th1/Th2 differentiation. Macrophages from acute infections produced high levels of interleukin-12 (IL-12) and nitric oxide (NO), paralleled with low levels of IL-6 and prostaglandin E2 (PGE2) and with the ability to induce strong antigen-specific CD4+ T-cell proliferation in response to nonrelated antigens. In contrast, macrophages from chronic infections produced higher levels of IL-6 and PGE2 and had suppressed production of IL-12 and NO, associated with a poor ability to induce antigen-specific proliferation in CD4+ T cells. Failure to induce proliferation was not due to a deficient expression of accessory molecules, since major histocompatibility complex class II, CD40, and B7-2 were up-regulated, together with CD23 and CCR5 as infection progressed. These macrophages from chronic infections were able to bias CD4+ T cells to produce IL-4 but not gamma interferon (IFN-γ), contrary to macrophages from acute infections. Blockade of B7-2 and IL-6 and inhibition of PGE2 failed to restore the proliferative response in CD4+ T cells. Furthermore, studies using STAT6−/− mice revealed that STAT6-mediated signaling was essential for the expansion of these alternatively activated macrophages. These data demonstrate that helminth infections can induce different macrophage populations that have Th2-biasing properties.
Protective Mucosal Th2 Immune Response against Toxoplasma gondii by Murine Mesenteric Lymph Node Dendritic Cells

ABSTRACT Toxoplasma gondii, an obligate intracellular parasite pathogen which initially invades the intestinal epithelium before disseminating throughout the body, may cause severe sequelae in fetuses and life-threatening neuropathy in immunocompromised patients. Immune protection is usually thought to be performed through a systemic Th1 response; considering the route of parasite entry it is important to study and characterize the local mucosal immune response to T. gondii. Despite considerable effort, Toxoplasma-targeted vaccines have proven to be elusive using conventional strategies. We report the use of mesenteric lymph node dendritic cells (MLNDCs) pulsed ex vivo with T. gondii antigens (TAg) as a novel investigation approach to vaccination against T. gondii-driven pathogenic processes. Using a murine model, we demonstrate in two genetically distinct mouse strains (C57BL/6 and CBA/J) that adoptively transferred TAg-pulsed MLNDCs elicit a mucosal Toxoplasma-specific Th2-biased immune response in vivo and confer strong protection against infection. We also observe that MLNDCs mostly traffic to the intestine where they enhance resistance by reduction in the mortality and in the number of brain cysts. Thus, ex vivo TAg-pulsed MLNDCs represent a powerful tool for the study of protective immunity to T. gondii, delivered through its natural route of entry. These findings might impact the design of vaccine strategies against other invasive microorganisms known to be delivered through digestive tract.
The Curious Case of Indian Ocean Warming

AbstractRecent studies have pointed out an increased warming over the Indian Ocean warm pool (the central-eastern Indian Ocean characterized by sea surface temperatures greater than 28.0°C) during the past half-century, although the reasons behind this monotonous warming are still debated. The results here reveal a larger picture—namely, that the western tropical Indian Ocean has been warming for more than a century, at a rate faster than any other region of the tropical oceans, and turns out to be the largest contributor to the overall trend in the global mean sea surface temperature (SST). During 1901–2012, while the Indian Ocean warm pool went through an increase of 0.7°C, the western Indian Ocean experienced anomalous warming of 1.2°C in summer SSTs. The warming of the generally cool western Indian Ocean against the rest of the tropical warm pool region alters the zonal SST gradients, and has the potential to change the Asian monsoon circulation and rainfall, as well as alter the marine food webs in t.
Developing attitudes and intentions among potential entrepreneurs

Purpose – The purpose of this paper is to explore the attitudes and intentions of individuals towards entrepreneurship with the support of theory of planned behaivour (TPB). This research may contribute to the growing body of knowledge that has begun to explore attitudes and intentions of individuals for self-employment in a developing country. Design/methodology/approach – This is an initial part of a longitudinal study in which survey instrument has been adapted for data collection. A random sampling was applied to the students of public and private higher educational institutions of a developing country. For data analysis, Statistical Package for Social Science 20 versions for Windows were used to test the hypotheses through descriptive, Pearson’s correlations and multiple regression analysis techniques. Findings – Results of the study showed that all variables are reliable and valid. However, internal consistency among the variables has been found. By using Pearson’s correlations, entrepreneurship int.
Safety and usefulness of emergency maternal transport using helicopter

Aim: Japan has a shortage of tertiary medical care facilities for maternal and fetal medicine. Establishment of efficient medical transport systems is needed for pregnant women and fetuses with severe complications. Maternal transport by helicopters is expected to shorten transportation time to advanced facilities, although its feasibility has not yet been evaluated. The aim of the present study was to investigate the status of maternal helicopter transport, and conditions of the pregnant patients and children transferred by helicopter to Kameda Medical Center (KMC).
Insulin-Glucagon Substrate Interrelations in the Fetal Sheep

Extract: Twenty-four studies were conducted in 14 sheep fetuses to investigate the pancreatic islet α and β cell responses to substrate infusions. The studies were conducted between 100 days gestation and near term, using indwelling vascular catheters for infusions and blood sampling. Constant glucose infusions (6 mg/kg/min) produced a significant rise in the mean concentration of insulin in plasma by 105 min, but no change in glucagon in plasma was observed. Near term (>135 days) the mean plasma insulin increment with constant glucose infusion was significantly greater and occurred sooner than in fetuses early in gestation (<110 days), but again no plasma glucagon response was observed. The mean steady state glucose concentration in response to the 6 mg/kg/min glucose infusion was similar early and late in gestation, even though the steady state plasma level of insulin in plasma was higher in the late gestation fetuses. Alanine infused into the fetus did not alter concentrations of glucose, insulin, or glucagon in plasma. These data suggest that changes in plasma concentrations of insulin and glucagon are not important in the regulation of substrate metabolism during fetal life. Moreover, the pancreatic islet β cell secretion response seems to mature earlier than the α cell response.Speculation: The failure of glucagon to respond to alanine stimulation during fetal life suggests immaturity of glucagon control of gluconeogenesis from amino acids. The low levels of activity of key glucagon-dependent gluconeogenic enzymes reported in liver of the newborn rat (7, 8) supports this view. These observations suggest the possibility that gluconeogenesis from amino acids may not represent a major metabolic pathway in the sheep fetus.