Miracle-dz/UniFAR-FTUs huggingface dataset:
Gaucher disease in Syrian children: common mutations identification and clinical futures

BACKGROUND AND OBJECTIVES Gaucher disease (GD) is caused by the deficiency of glucosidase beta acid (GBA). Three clinical forms of GD are available. Some mutations in the GBA gene have a high frequency in specific populations. The aim of this study was to analyze the characteristics of phenotypes and genotypes of GD in Syrian pediatric patients and assess whether a genotype-phenotype relationship could be helpful in treatment decision-making. DESIGN AND SETTINGS A cross-sectional clinical genetic study of 19 Syrian children admitted to Children’s Hospital, Damascus University. PATIENTS AND METHODS Nineteen Syrian children with GD were enrolled in the study; DNA was extracted from peripheral blood leukocytes. The GBA gene was amplified by polymerase chain reaction, and the 9 most common mutations were studied using a Gaucher Disease Strip Assay (ViennaLab Diagnostics GmbH, Vienna, Austria). RESULTS The majority of children had an early age of onset. A total of 17 patients presented severe hematological and skeletal complications. Neurological involvement was encountered in 2 patients. Twelve patients (63, 2%) were homozygous for the L444P mutation, 1 patient (5.3%) was homozygous for the N370S mutation, and 1 patient (5.3%) was heterozygous for the N370S mutation. Five patients (26.3%) had unknown mutations. CONCLUSION L444P/L444P was the most common genotype in the studied patients. GD3 with severe visceral presentation in childhood was the dominant phenotype; N370S was found in the heterozygote state in 1 case and in the homozygote state in 1 case. This phenotype and genotype pattern is encountered in the Middle East. There was no genotype-phenotype correlation.
A Distinctive Indian Political Economy: New Concepts and a Synthesizing Framework

This article discusses Rudolphs’ contribution to the study of India’s political economy. Taking off from the ideas they presented in their work, In Pursuit of Lakshmi, the article argues that certain concepts, such as Bullock capitalists, demand-led growth, involuted pluralism, federal market economy and state as a third actor, continue to be critical in understanding India. Through these conceptual innovations, Rudolph and Rudolph not only analyzed India at a given moment but also shaped the larger agenda of debates over India’s political economy.
Relations of Insulin Resistance and Glycemic Abnormalities to Cardiovascular Magnetic Resonance Measures of Cardiac Structure and Function: The Framingham Heart Study

Background—Data regarding the relationships of diabetes, insulin resistance, and subclinical hyperinsulinemia/hyperglycemia with cardiac structure and function are conflicting. We sought to apply volumetric cardiovascular magnetic resonance (CMR) in a free-living cohort to potentially clarify these associations. Methods and Results—A total of 1603 Framingham Heart Study Offspring participants (age, 64±9 years; 55% women) underwent CMR to determine left ventricular mass (LVM), LVM to end-diastolic volume ratio (LVM/LVEDV), relative wall thickness (RWT), ejection fraction, cardiac output, and left atrial size. Data regarding insulin resistance (homeostasis model, HOMA-IR) and glycemia categories (normal, impaired insulinemia or glycemia, prediabetes, and diabetes) were determined. In a subgroup (253 men, 290 women) that underwent oral glucose tolerance testing, we related 2-hour insulin and glucose with CMR measures. In both men and women, all age-adjusted CMR measures increased across HOMA-IR quartiles, but multivariable-adjusted trends were significant only for LVM/ht2.7 and LVM/LVEDV. LVM/LVEDV and RWT were higher in participants with prediabetes and diabetes (in both sexes) in age-adjusted models, but these associations remained significant after multivariable adjustment only in men. LVM/LVEDV was significantly associated with 2-hour insulin in men only, and RWT was significantly associated with 2-hour glucose in women only. In multivariable stepwise selection analyses, the inclusion of body mass index led to a loss in statistical significance. Conclusions—Although insulin and glucose indices are associated with abnormalities in cardiac structure, insulin resistance and worsening glycemia are consistently and independently associated with LVM/LVEDV. These data implicate hyperglycemia and insulin resistance in concentric LV remodeling.
Molecular Characterization of the First Two Enzymes of the Pentose-phosphate Pathway of Trypanosoma brucei GLUCOSE-6-PHOSPHATE DEHYDROGENASE AND 6-PHOSPHOGLUCONOLACTONASE

Trypanosomatids are parasitic protists that have part of their glycolytic pathway sequestered inside peroxisome-like organelles: the glycosomes. So far, at least one enzyme of the pentose-phosphate pathway has been found to be associated partially with glycosomes. Here, we describe how two genes from Trypanosoma brucei, coding for the first two enzymes of the pentose-phosphate pathway, i.e. glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase, were identified by in silico screening of trypanosome genome project data bases. These genes were cloned and sequenced. Analysis of the lactonase sequence revealed that it contained a C-terminal peroxisome targeting signal in agreement with its subcellular localization in the bloodstream form trypanosome (15% glycosomal and 85% cytosolic). However, the dehydrogenase sequence did not reveal any targeting signal, despite its localization inside glycosomes. The corresponding enzymes have been overexpressed in Escherichia coli and purified, and their biochemical characteristics have been determined.
Asymmetric Effects of Exchange Rate Changes And The J‐Curve: New Evidence from 61 Malaysia–Thailand Industries

Research on the impact of currency depreciation on the trade balance is now moving in a new direction by incorporating nonlinear dynamic adjustment of the exchange rate and by using a nonlinear approach to error&#8208;correction modeling and cointegration. Using these advances, researchers find not only more evidence of the J&#8208;curve effect, but also new evidence of asymmetric effects of exchange rate changes on the trade balance. We contribute to this line of research by using monthly trade flow data from 61 two&#8208;digit industries that trade between Malaysia and Thailand, and show that not only does currency depreciation have favorable effects on the trade balance of more industries, but the long&#8208;run effects are asymmetric in 26 out of 61 cases. In line with current literature, our nonlinear model performs much better than the linear model when industry level data are used.
Involvement of tumour necrosis factor‐α‐related apoptosis‐inducing ligand in enhanced cytotoxicity of lipopolysaccharide‐stimulated dendritic cells to activated T cells

Dendritic cells (DC) are potent antigen‐presenting cells (APC) specialized in T‐cell mediated immune responses, and also play critical roles in the homeostasis of T cells for controlling immune responses. In the present study, we demonstrated that during mouse bone‐marrow‐derived DC activation of ovalbumin (OVA)‐specific Ia‐kb‐restricted T hybridoma cells, MF2.2D9 and OVA257–264‐specific H‐2kb‐restricted RF33.70 T cells, respectively, both hybridomas undergo cell death, partially mediated via apoptotic ligand–tumour necrosis factor‐α (TNF‐α)‐related apoptosis‐inducing ligand (TRAIL). Lipopolysaccharide enhanced the cytotoxic effect on the two activated T hybridoma cells, which was correlated with up‐regulation of TRAIL‐expression on DC to some extent. The activation of caspase‐3 in activated T hybridoma cells cocultured with DC contributed to the programmed cell death pathway T cells underwent. Therefore, our results show that activation‐induced cell death of T hybridoma cells can be influenced by DC, suggesting that DC may be involved in elimination of activated T cells at the end of primary immune responses.
The Relationship Between Nurse Manager Leadership Style and Enculturation of Shared Governance

The Relationship Between Nurse Manager Leadership Style and Enculturation of Shared Governance by Anna E. Keane MA, Seton Hall University, 1994 MSN, Seton Hall University, 1993 BSN, College Misericordia, 1981 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Management Walden University December 2016 Abstract Shared governance, a participative model of governance, implemented by healthcare organizations for more than 30 years has been associated with empowerment, jobShared governance, a participative model of governance, implemented by healthcare organizations for more than 30 years has been associated with empowerment, job satisfaction, and retention of registered nurses. Recent studies document a lack of participation in shared governance by registered nurses; the reason for the change is unknown. The nurse managers’ role in this change is unknown. The purpose of this nonexperimental, cross-sectional survey design study was to test Bass’ theory of transformational leadership that examines the relationship between the leadership style of the manager and the enculturation of shared governance in acute care hospitals in the United States. A random sample of 111 nurse managers, who were members of the American Organization of Nurse Executives, were surveyed on leadership style using the Multi-factor Leadership Questionnaire and unit governance, using the Index of Professional Nursing Governance. Data was analyzed using Pearson’s Product Moment Correlation and a statistically significant positive relationship was found between transformational leadership style and shared governance. No relationship was found between other leadership styles and shared governance. There was no relationship between the achievement of a shared governance score on the participation subscale of the Index of Professional Nursing Governance and transformational leadership style. The study contributes to social change through the identification of the manager’s use of a transformational leadership style to foster the autonomy and empowerment of nurses to cultivate a positive the work environment using a shared governance model, which results in registered nurse retention and decreased organizational turnover costs. The Relationship Between Nurse Manager Leadership Style and Enculturation of Shared Governance
Impact of drought on the Ugandan economy

_____________________________________________________________________ Climate variability affects economies directly through its impact on agricultural output and indirectly through its effect on the activities of down-stream industries and household welfare. We use a Computable General Equilibrium model with a highly disaggregated agricultural sector to analyse the costs of a drought on the Ugandan economy. The case of Uganda is interesting because its economy is largely agro-based with a heavily rain-fed agricultural sector. In this paper, we assess the resulting losses with respect to GDP, employment, the trade balance and household welfare. The results show that the effects vary substantially by sector from moderate to severe overall impacts. There are macro level losses in terms of reduced exports while at a household level; the terms of trade gains mitigate part of the potential welfare losses with respect to consumption. At a sectoral level, the fall in employment within the agricultural industries is less compared to the output losses. Overall, we see that even a short term drought can cause substantial losses to the economy, hence the need for targeted interventions to mitigate such drought impacts. Given the multi-dimensional nature of drought impacts, a combination of findings from this study with other qualitative surveys can give a much wider picture of the full cost of a drought. JEL Classification code: D58, Q25, Q54
How Long is Your Arm? Using Multisensory Illusions to Modify Body Image from the Third Person Perspective

Updating body representations from the 3rd person perspectives (3PP) seems to require viewing the real body, unlike when viewing from a 1st person perspective. Here, 3PP updating was investigated through induction of a physically impossible multisensory illusion in which participants viewed real-time 3PP video of themselves having their arm pulled until it stretched to twice its normal length. The illusion elicited the subjective experience that the participant's own arm had been stretched and caused an overestimation of reaching distance, although actual reaches were unaffected. Multisensory illusions from the 3PP can alter body image when applied to real bodies.
Caveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction

Paradoxical observations have been made regarding the role of caveolin‐1 (Cav‐1) during cellular senescence. For example, caveolin‐1 deficiency prevents reactive oxygen species‐induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re‐addressed the role of caveolin‐1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav‐1−/− mouse embryonic fibroblasts. Cav‐1 deficiency (knockout or knockdown) induced cellular senescence via a p53‐p21‐dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav‐1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD+/NADH ratio. From these results, we concluded that Cav‐1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.
The Yo-Yo IR2 test: physiological response, reliability, and application to elite soccer.

PURPOSE To examine the physiological response, reliability, and validity of the Yo-Yo intermittent recovery level 2 test (Yo-Yo IR2). METHODS Thirteen normally trained male subjects carried out four Yo-Yo IR2 tests, an incremental treadmill test (ITT), and various sprint tests. Muscle biopsies and blood samples were obtained, and heart rate was measured before, during, and after the Yo-Yo IR2 test. Additionally, 119 Scandinavian elite soccer players carried out the Yo-Yo IR2 test on two to four occasions. RESULTS Yo-Yo IR2 performance was 591 +/- 43 (320-920) m or 4.3 (2.6-7.9) min. Test-retest coefficient of variation in distance covered was 9.6% (N = 29). Heart rate (HR) at exhaustion was 191 +/- 3 bpm, or 98 +/- 1% HRmax. Muscle lactate was 41.7 +/- 5.4 and 68.5 +/- 7.6 mmol x kg(-1) d.w. at 85 and 100% of exhaustion time, respectively, with corresponding muscle CP values of 40.4 +/- 5.2 and 29.4 +/- 4.7 mmol x kg(-1) d.w. Peak blood lactate was 13.6 +/- 0.5 mM. Yo-Yo IR2 performance was correlated to ITT performance (r = 0.74, P < 0.05) and VO2max (r = 0.56, P < 0.05) but not to 30- and 50-m sprint performance. Yo-Yo IR2 performance was better (P < 0.05) for international elite soccer players than for moderate elite players (1059 +/- 35 vs 771 +/- 26 m) and better (P < 0.05) for central defenders (N = 21), fullbacks (N = 20), and midfielders (N = 48) than for goalkeepers (N = 6) and attackers (N = 24). Fifteen elite soccer players improved (P < 0.05) Yo-Yo IR2 performance by 42 +/- 8% during 8 wk of preseasonal training. CONCLUSION This study demonstrates that the Yo-Yo IR2 test is reproducible and can be used to evaluate an athlete's ability to perform intense intermittent exercise with a high rate of aerobic and anaerobic energy turnover. Specifically, the Yo-Yo IR2 test was shown to be a sensitive tool to differentiate between intermittent exercise performance of soccer players in different seasonal periods and at different competitive levels and playing positions.
Repair of DNA Double-Strand Breaks is Not Modulated by Low-Dose Gamma Radiation in C57BL/6J Mice

In this study, we sought to determine whether low-dose ionizing radiation, previously shown to induce a systemic adaptive response in C57BL/6J mice, is capable of enhancing the rate of DNA double-strand break repair. Repair capacity was determined by measuring γ-H2AX levels in splenic and thymic lymphocytes, using flow cytometry, at different times after a challenge irradiation (2 Gy, 60Co). Irradiation with low doses (20 and 100 mGy) was conducted in vivo, whereas the challenge dose was applied to primary cultures of splenocytes and thymocytes in vitro 24 h later. Obtained kinetics curves of formation and loss of γ-H2AX indicated that cells from low-dose irradiated mice did not express more efficient DNA double-strand break repair compared to controls. Immunoblot analysis of γ-H2AX and Phospho-Ser-1981 ATM confirmed that DNA damage signaling was not modulated by preliminary low-dose radiation. Mouse embryonic fibroblasts of C57BL genetic background failed to show clonogenic survival radioadaptive response or enhanced repair of DNA double-strand breaks as evaluated by immunofluorescence microscopy of γ-H2AX foci. Our results indicate that radiation adaptive responses at systemic levels, such as increases in the tumor latency times in aging mice, may not be mediated by modulated DNA repair, and that the genetic background may affect expression of a radioadaptive response.
Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children.

BACKGROUND Although asthma diagnosed by a physician is known to be related to serum IgE levels, it is not known whether there is a relation between the level of IgE and airway hyperresponsiveness to a methacholine challenge. The characteristics of asymptomatic persons that predispose them to airway hyperresponsiveness are also unknown. METHODS We studied the relation between the serum total IgE level and airway hyperresponsiveness in the presence or absence of asthma and other atopic diseases in a birth cohort of children. Data from a questionnaire regarding respiratory symptoms, plus measurements of the serum total IgE level and airway responsiveness to inhaled methacholine, were obtained for 562 11-year-olds in New Zealand. RESULTS The boys had a higher prevalence than the girls of current diagnosed asthma (13 percent vs. 6 percent), current symptoms of wheezing (22 percent vs. 15 percent), and airflow obstruction at base line (6 percent vs. 1 percent) and had a wider distribution of IgE levels, although mean IgE levels (120.8 IU per milliliter in the boys and 98.1 IU per milliliter in the girls) did not differ significantly between the sexes. The prevalence of diagnosed asthma was strongly related to the serum IgE level (P for trend less than 0.0001). No asthma was reported in children with IgE levels less than 32 IU per milliliter, whereas 36 percent of those with IgE levels greater than or equal to 1000 IU per milliliter were reported to have asthma. This relation with the serum IgE level was not explained by a concomitant diagnosis of allergic rhinitis or eczema. Airway hyperresponsiveness to a methacholine challenge also correlated very highly (P less than 0.0001) with the serum IgE level. This relation remained significant even after the exclusion of children with diagnosed asthma (P less than 0.0001) and of all children with a history of wheezing, allergic rhinitis, or eczema (P less than 0.0001). CONCLUSIONS Even in children who have been asymptomatic throughout their lives and have no history of atopic disease, airway hyperresponsiveness appears to be closely linked to an allergic diathesis, as reflected by the serum total IgE level.
Detection of Circulating Mucorales DNA in Critically Ill Burn Patients: Preliminary Report of a Screening Strategy for Early Diagnosis and Treatment.

BACKGROUND Invasive wound mucormycosis (IWM) is associated with an extremely poor outcome among critically ill burn patients. We describe the detection of circulating Mucorales DNA (cmDNA) for the early diagnosis of IWM in those patients and report the potential value of detecting cmDNA for treatment guidance. METHODS Severely ill burn patients admitted to our tertiary referral center between October 2013 and February 2016 were included. Retrospective plasma samples were tested for the presence of cmDNA by quantitative real-time polymerase chain reaction (qPCR). Patients were then prospectively screened twice a week, and liposomal amphotericin-B therapy initiated based on a positive qPCR. The primary endpoint was the time between cmDNA detection and standard diagnosis. Secondary endpoints were the time from cmDNA detection and treatment initiation and mortality. RESULTS Seventy-seven patients (418 samples) were included. The average age was 46 (28-60) years, abbreviated burn severity index was 8 (7-10), and simplified acute physiology score was 33 (23-46). The total body surface area was 33% (22%-52%). cmDNA was detected 11 (4.5-15) days before standard diagnosis. The in-hospital mortality was 62% for patients with IWM and 24% for those without (P = .03). The mortality due to IWM was 80% during period A and 33% during period B (P = .46). CONCLUSIONS This study suggests that the detection of cmDNA allows earlier diagnosis of IWM in severely ill burn patients and earlier initiation of treatment. Further studies are needed to confirm the impact of earlier treatment initiation on patient outcome.
Overexpression of human transferrin in two oligodendroglial cell lines enhances their differentiation

We have previously demonstrated that the addition of apotransferrin (aTf) to oligodendroglial cell (OLGc) primary cultures accelerates their maturation. Cells treated with aTf developed a multipolar morphology and displayed increased expression of mature OLGc markers. In this work, we studied the effect of Tf overexpression in two OLGc lines, N19 and N20.1. The former cells exhibit characteristics of OLGc precursors (O2A), while N20.1 cells express markers of more mature OLGcs. Using the complete cDNA of the human Tf gene, we obtained clones overexpressing Tf in both cell lines. These clones were evaluated for the expression of OLGc differentiation markers. In agreement with our previous results, we found that in the cells overexpressing Tf, there was an increased O4, GC, and MBP immunoreactivity. To study the myelinogenic potential of these cells, we co‐cultured N19 and N20.1 Tf‐transfected cells together with cortical neurons. There was a dramatic increase in the morphological differentiation of the OLGcs accompanied by enhanced GC and MBP expression. The OLGcs appeared to establish contact with neurites and extend their processes along them. Only two MBP isoforms were detected in Tf‐overexpressing clones, while all the isoforms were present in the co‐cultures, suggesting that there was a modulation of MBP expression by neurons. Concomitantly, we found an increase in several proteins involved in axon–glia interaction, such as MAG, N‐CAM, and F3/Contactin. This co‐culture system represents a potentially powerful tool to study neuron–glia interactions that occur during myelinogenesis and the role of Tf in this process. © 2005 Wiley‐Liss, Inc.