Miracle-dz/UniFAR-FTUs huggingface dataset:
Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility

We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL) among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70–3.14, p = 1.7×10−8 and rs7089424, RR = 2.22, 95% CI = 1.64–3.01, p = 5.2×10−8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63–3.02, p = 9.63×10−8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57–2.88, p = 2.81×10−7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.
Telomere repeats induce domains of H3K27 methylation in Neurospora

Development in higher organisms requires selective gene silencing, directed in part by di-/tri-methylation of lysine 27 on histone H3 (H3K27me2/3). Knowledge of the cues that control formation of such repressive Polycomb domains is extremely limited. We exploited natural and engineered chromosomal rearrangements in the fungus Neurospora crassa to elucidate the control of H3K27me2/3. Analyses of H3K27me2/3 in strains bearing chromosomal rearrangements revealed both position-dependent and position-independent facultative heterochromatin. We found that proximity to chromosome ends is necessary to maintain, and sufficient to induce, transcriptionally repressive, subtelomeric H3K27me2/3. We ascertained that such telomere-proximal facultative heterochromatin requires native telomere repeats and found that a short array of ectopic telomere repeats, (TTAGGG)17, can induce a large domain (∼225 kb) of H3K27me2/3. This provides an example of a cis-acting sequence that directs H3K27 methylation. Our findings provide new insight into the relationship between genome organization and control of heterochromatin formation.
Molecular Signaling and Dysfunction of the Human Reactive Enteric Glial Cell Phenotype: Implications for GI Infection, IBD, POI, Neurological, Motility, and GI Disorders

Background:Clinical observations or animal studies implicate enteric glial cells in motility disorders, irritable bowel syndrome, inflammatory bowel disease, gastrointestinal (GI) infections, postoperative ileus, and slow transit constipation. Mechanisms underlying glial responses to inflammation in human GI tract are not understood. Our goal was to identify the “reactive human enteric glial cell (rhEGC) phenotype” induced by inflammation, and probe its functional relevance. Methods:Human enteric glial cells in culture from 15 GI-surgical specimens were used to study gene expression, Ca2+, and purinergic signaling by Ca2+/fluo-4 imaging and mechanosensitivity. A nanostring panel of 107 genes was designed as a read out of inflammation, transcription, purinergic signaling, vesicular transport protein, channel, antioxidant, and other pathways. A 24-hour treatment with lipopolysaccharide (200 &mgr;g/mL) and interferon-&ggr; (10 &mgr;g/mL) was used to induce inflammation and study molecular signaling, flow-dependent Ca2+ responses from 3 mL/min to 10 mL/min, adenosine triphosphate (ATP) release, and ATP responses. Results:Treatment induced a “rhEGC phenotype” and caused up-regulation in messenger RNA transcripts of 58% of 107 genes analyzed. Regulated genes included inflammatory genes (54%/IP10; IFN-&ggr;; CxCl2; CCL3; CCL2; C3; s100B; IL-1&bgr;; IL-2R; TNF-&agr;; IL-4; IL-6; IL-8; IL-10; IL-12A; IL-17A; IL-22; and IL-33), purine-genes (52%/AdoR2A; AdoR2B; P2RY1; P2RY2; P2RY6; P2RX3; P2RX7; AMPD3; ENTPD2; ENTPD3; and NADSYN1), channels (40%/Panx1; CHRNA7; TRPV1; and TRPA1), vesicular transporters (SYT1, SYT2, SNAP25, and SYP), transcription factors (relA/relB, SOCS3, STAT3, GATA_3, and FOXP3), growth factors (IGFBP5 and GMCSF), antioxidant genes (SOD2 and HMOX1), and enzymes (NOS2; TPH2; and CASP3) (P < 0.0001). Treatment disrupted Ca2+ signaling, ATP, and mechanical/flow-dependent Ca2+ responses in human enteric glial cells. ATP release increased 5-fold and s100B decreased 33%. Conclusions:The “rhEGC phenotype” is identified by a complex cascade of pro-inflammatory pathways leading to alterations of important molecular and functional signaling pathways (Ca2+, purinergic, and mechanosensory) that could disrupt GI motility. Inflammation induced a “purinergic switch” from ATP to adenosine diphosphate/adenosine/uridine triphosphate signaling. Findings have implications for GI infection, inflammatory bowel disease, postoperative ileus, motility, and GI disorders.
Ternary mixes with high mineral additions contents and corrosion related properties

The choice of blended cements and materials with cementitious properties in concrete is currently seen as a choice that increases the environmental sustainability of the construction industry. The developments with non‐traditional binders (such as the simultaneous incorporation of several types of supplementary cementitious materials) have highlighted new challenges to be researched. In the present paper ternary binders were prepared by mixing ordinary Portland cement (OPC) plus two blended components: low calcium fly ash, blast furnace slag, and/or limestone filler. Several physical and mechanical properties of ternary blend systems have been analyzed in mortar form at several curing ages: 2, 7, 28, and 90 days. Additionally preliminary tests of corrosion performance of reinforcement in these types of mixes have been considered. The results indicate that the use of appropriate content components in ternary blends will allow binders to fulfill the specified mechanical requirements. The best results are obtained when two additions with antagonist properties are mixed, as fly ashes and slags or slags and filler limestone. Besides, certain influence of the effect on durability performance is detected, in particular associated with the stability of the passive state and corrosion of reinforcements in presence of chlorides.
Bivalent oral cholera vaccine in participants aged 1 year and older in the Dominican Republic: A phase III, single-arm, safety and immunogenicity trial

ABSTRACT The Dominican Republic, historically non-endemic for cholera, is experiencing an ongoing cholera epidemic. We assessed the safety and immunogenicity of two doses of the killed bivalent (O1 and O139) whole-cell oral cholera vaccine (OCV) on day (D)0 and D14 in healthy participants aged ≥1 year. Immediate unsolicited systemic adverse events (AEs) were monitored up to 30 minutes and solicited systemic reactions, up to 7 days after each vaccination. Unsolicited AEs were recorded up to D14 (post-dose 1) and 30 days post-dose 2. A vibriocidal antibody assay with microtiter technique was used to measure serum antibodies to V. cholerae strains (O1 El Tor Inaba, O1 El Tor Ogawa, O139) on D0, D14 and D28. Geometric mean titers (GMTs) and seroconversion (≥4-fold increase from D0) rates were calculated. We recruited 336 participants; 112 in three age groups (1–4, 5–14 and ≥15 years). No safety concerns were observed. GMTs increased from baseline for all serotypes, with marked increases for O1 Inaba and Ogawa post-dose 1. Post-dose 2 GMTs tended to be equal or slightly lower, with ranges: O1 Inaba, 283 (95% confidence interval 191–419) to 612 (426–880); O1 Ogawa, 346 (223–536) to 754 (553–1028); and O139, 20.3 (13.5–30.6) to 43.8 (30.1–63.7). Seroconversion rates post-dose 2 for O1 Inaba and Ogawa were high (≥87%) for all age groups. OCV demonstrated an acceptable safety profile and robust immunogenicity in these participants, in-line with previous observations in epidemic and endemic settings.This study is registered on www.clinicaltrials. gov (NCT02434822).
Population‐based screening program for reducing oral cancer mortality in 2,334,299 Taiwanese cigarette smokers and/or betel quid chewers

To reduce oral cancer mortality, an organized, population‐based screening program for the early detection of oral premalignancy and oral cancer was designed for high‐risk individuals with habits of betel quid chewing, cigarette smoking, or both. The objective of this report was to evaluate the long‐term effectiveness of this program in reducing the incidence of advanced disease and deaths from oral cancer.
Validation of EuroSCORE II in Chinese Patients Undergoing Coronary Artery Bypass Surgery.

BACKGROUND Comparisons between the EuroSCORE and EuroSCORE II in the patient populations for coronary artery bypass grafting are limited. The aim of the study was to compare the use of the EuroSCORE and EuroSCORE II as risk model for predicting in-hospital mortality in Chinese patients undergoing coronary artery bypass grafting (CABG). METHODS Patients (n = 1598) with complete records of baseline and operative data were retrospectively collected from computerized records. The expected mortality rate for logistic EuroSCORE and EuroSCORE II was determined. Performance of the logistic EuroSCORE and EuroSCORE II model was assessed by comparing the observed and expected in-hospital mortality. The area under the receiver operating characteristics curve (AUC) values were calculated for these models to compare predictive power. RESULTS Observed in-hospital overall mortality rate was 3.19%. The logistic EuroSCORE model (Hosmer-Lemeshow: P < .05, O/E = 0.73) over-predicted mortality (4.39%) and the EuroSCORE II model showed good calibration and discriminative capacity (area 0.762) in predicting in-hospital mortality (Hosmer-Lemeshow: P = .191, O/E = 1.24). CONCLUSION EuroSCORE II model reduces the overestimation of the calculated risk by logistic EuroSCORE in this population. EuroSCORE II risk model may be suitable in patients undergoing coronary artery bypass surgery in China.
Loss of Skeletal Mineralization by the Simultaneous Ablation of PHOSPHO1 and Alkaline Phosphatase Function: A Unified Model of the Mechanisms of Initiation of Skeletal Calcification

Endochondral ossification is a carefully orchestrated process mediated by promoters and inhibitors of mineralization. Phosphatases are implicated, but their identities and functions remain unclear. Alkaline phosphatase (TNAP) plays a crucial role promoting mineralization of the extracellular matrix by restricting the concentration of the calcification inhibitor inorganic pyrophosphate (PPi). Mutations in the TNAP gene cause hypophosphatasia, a heritable form of rickets and osteomalacia. Here we show that PHOSPHO1, a phosphatase with specificity for phosphoethanolamine and phosphocholine, plays a functional role in the initiation of calcification and that ablation of PHOSPHO1 and TNAP function prevents skeletal mineralization. Phospho1−/− mice display growth plate abnormalities, spontaneous fractures, bowed long bones, osteomalacia, and scoliosis in early life. Primary cultures of Phospho1−/− tibial growth plate chondrocytes and chondrocyte‐derived matrix vesicles (MVs) show reduced mineralizing ability, and plasma samples from Phospho1−/− mice show reduced levels of TNAP and elevated plasma PPi concentrations. However, transgenic overexpression of TNAP does not correct the bone phenotype in Phospho1−/− mice despite normalization of their plasma PPi levels. In contrast, double ablation of PHOSPHO1 and TNAP function leads to the complete absence of skeletal mineralization and perinatal lethality. We conclude that PHOSPHO1 has a nonredundant functional role during endochondral ossification, and based on these data and a review of the current literature, we propose an inclusive model of skeletal calcification that involves intravesicular PHOSPHO1 function and Pi influx into MVs in the initiation of mineralization and the functions of TNAP, nucleotide pyrophosphatase phosphodiesterase‐1, and collagen in the extravesicular progression of mineralization. © 2011 American Society for Bone and Mineral Research.
How do Swiss general practitioners agree with and report adhering to a top-five list of unnecessary tests and treatments? Results of a cross-sectional survey

Abstract Background: In 2014, the ‘Smarter Medicine’ campaign released a top five list of unnecessary tests and treatments in Swiss primary care, such as imaging for acute low-back pain and long-term prescribing of proton pump inhibitors. Objectives: Measure general practitioners’ (GPs) agreement with the recommendations and self-reported adherence. Methods: Cross-sectional, online survey of GPs in the ‘Swiss primary care active monitoring’ (SPAM) network, which assessed awareness of ‘Smarter Medicine’ and views on each recommendation. Questions included whether the clinical situation is common, whether the recommendation is followed, whether GPs agree with the recommendation and reasons why the recommendation would not be followed. Results: One-hundred-and-sixty-seven of 277 GPs from the SPAM network participated (60%), of which 104 (62%) knew of ‘Smarter Medicine’, including 79% in German areas, 49% in French areas and 38% in Italian areas (P < 0.001). Agreement with the five recommendations was high, with scores around nine out of 10. The proportion saying they typically follow each recommendation was 68 to 74%, except not continuing long-term PPI prescriptions without attempting dose reduction, with only 34%. Common reasons for not following the recommendations were patient or other provider requests and situations that might suggest the need for more aggressive care. Conclusion: Two years after the launch of the campaign, awareness and acceptance of ‘Smarter Medicine’ appear to be high among Swiss GPs. By self-report, the recommendations are adhered to by most of the respondents but there may be room for improvement, especially for long-term PPI prescriptions.
Efficacy of Balance and Eye-Movement Exercises for Persons With Multiple Sclerosis (BEEMS)

Objective To determine whether a multifaceted vestibular-related rehabilitation program (Balance and Eye-Movement Exercises for Persons with Multiple Sclerosis; BEEMS) improves balance in persons with MS and whether there are differences in outcomes based on brainstem/cerebellar lesion involvement. Methods A 2-arm, examiner-blinded, stratified (involvement vs no involvement of brainstem/cerebellar structures), randomized controlled trial was implemented. Eighty-eight participants were allocated to BEEMS or no treatment control. Computerized Dynamic Posturography-Sensory Organization Test (CDP-SOT) measured balance control. The Dizziness Handicap Inventory (DHI), Modified Fatigue Impact Scale (MFIS), and Short Form-36 Health Status Questionnaire (SF-36) were also administered. Linear mixed models were used to investigate the primary and secondary aims. Results From baseline to 6 weeks, BEEMS participants experienced greater improvements compared to control participants in CDP-SOT composite (model-estimated difference in change 4.9, 95% confidence interval 1.39–8.38, p = 0.006), DHI total (−13.5, −17.7 to −7.25, p < 0.0001), MFIS total (−11.4, −15.7 to −7.0, p < 0.0001), SF-36 Mental (5.6, 2.43–8.71, p = 0.0006), and SF-36 Physical (3.5, 1.12–5.81, p = 0.004) scores and from baseline to 14 weeks in CDP-SOT composite (8.3, 4.73–11.9, p < 0.0001), DHI total (−13.9, −19.3 to −8.62, p < 0.0001), MFIS total (−12.3, −16.7 to −7.79, p < 0.0001), SF-36 Mental (3.9, 0.70–7.16, p = 0.02), and SF-36 Physical (3.2, 0.79–5.62, p = 0.01) scores. From baseline to 6 weeks, BEEMS participants with brainstem/cerebellar lesion involvement experienced greater improvements compared to those without in CDP-SOT composite (5.26, 0.34–10.2, p = 0.04) and MFIS total (−7.6, −14.0 to −1.33, p = 0.02) scores. Conclusion BEEMS improved multiple outcomes regardless of whether brainstem/cerebellar lesions were present, supporting the generalizability of BEEMS for ambulatory people with MS who have at least minimally impaired balance and fatigue. Clinical trials.gov identifier NCT01698086. Classification of evidence This study provides Class I evidence that BEEMS training improves dynamic posturography-based balance, dizziness, fatigue, and quality of life in persons with MS.
Performance of Dissimilar Welds in Service

Dissimilar metal welds (DMWs) between austenitic and ferritic steel tubing and piping are commonly employed in high-temperature applications in energy conversion systems. Differences in coefficient of thermal expansion between the two types of steel induce thermal stresses at the welds and local metallurgical changes near the low alloy steel/weld metal interface due to prolonged service at an elevated temperature. These phenomena, together with the differences in creep behavior of the materials joined, render the DMWs more prone to failure than welds between similar steels. This has been reflected in relatively high failure rates in DMWs in certain service applications (e.g., in utility power plant boiler tubing). Typically these welds fail by low ductility cracking in the low alloy steel at, or very close to, the fusion line. A project, sponsored by the Electric Power Research Institute (EPRI) and managed by the Metal Properties Council (MPC), has made significant headway over the last three years in understanding the failure modes and causes involved and in developing methods to assess residual life of DMWs. Welds from service in superheaters and reheater tubes and from laboratory simulation tests were examined to establish metallurgical characteristics and failure modes. Three failure modes were identified: (i) Prior austenite grain boundary cracking in the ferritic steel, one or two grains away from the fusion line; this mode was mainly observed in DMWs made with stainless steel filler metal. (ii) Cracking along the weld interface, which occurred in DMWs made with nickel-base filler metal. (iii) Propagation of cracks initiating from oxide notches formed at the weld outside surface; this mode occurred mainly in thin-walled tubes. Creep damage induced by steady and cyclic loading was found to be the predominant mechanism for damage and failure; therefore a dependence of damage on loading levels and service temperature was established. It was also determined that failure susceptibility in DMWs made with nickel-base filler was strongly influenced by the type of microstructure that formed at the low alloy steel/weld metal interface. The technique developed for estimating the condition and remaining life of DMWs in service involves detailed assessment of loading histories to which the welds are subjected, along with the use of empirical quantitative relationships established from both laboratory and service data. The methodology assumes that damage results from the combined effects of self damage (caused by thermal cycling of materials of different expansion coefficients) and service loadings, including both primary loads (e.g., pressure and deadweight) and secondary, or cyclic, loads due to the constrained thermal expansion of the system as a whole. The technique, Prediction Of Damage In Service (designated PODIS), has been found to adequately predict levels of damage in stainless-based DMWs in service. It is currently being developed further to embrace nickel-based DMWs.
Thermogravimetric and Kinetics of Thermal Degradation of Powdered Laboratory Examination Gloves: 1. Analysis of Thermal Scan Traces from 310-455ºC

This work was carried out in collaboration between all authors. Author NH designed and set-up the experiments, selected the materials, performed the experiment, operated the TGA instrument and, analyzed the results, wrote the first draft and finalized the manuscript. Author RM provided kinetics and thermodynamics expertise; participate on the revision of the manuscript. Authors SS, MM, and SC participated in performing the experiments, collecting the data, and analyzing the results. Author LW had the original idea and supported the work in all steps. All authors read and approved the final manuscript. ABSTRACT The aim of this study was to develop an energy efficient method to decompose powdered laboratory safety examination gloves (PLEG). This paper reports on the results of thermogravimetric analysis (TGA) of PLEG without a catalyst. The study was conducted in the Department of Biological and Physical Sciences at South Carolina State University (SCSU), Orangeburg, SC, USA, during the spring of 2014. Twelve samples of PLEG were studied under three types of operating conditions. First a sample was scanned from 50°C to 800°C with a heating rate of 10°C/min while it was purged with 10 mL/min argon. The results of this study determined the thermal stability of PLEG and the temperature of highest weight loss rate (~410°C). The second approach used two sequential dynamic thermal scans with a linear and fast (200°C/min) increase of the temperature over time, and two sequential isothermal steps for 30 minutes; one below 410°C and the other at 410°C. The third approach used a dynamic thermal scan and a sequential isothermal step for 30 minutes at a temperature over 410°C. From the thermal scans and isotherms, the highest rate of weight loss, the temperature at the maximum weight loss, the acceleration of weight loss by thermal scan, the deceleration of weight loss at the isotherms, the rate constant and the activation energy of weight loss (Ea) were estimated. The experimental results confirmed that Ea of weight loss of the PLEG samples depended on the temperature of operation. At temperatures below 430°, the amount of Ea for the weight loss of sample were higher than those above 430°C temperatures. Also, internal reactions of the sample of PLEG at 340°C resulted on thermally stable materials, which slowed down the thermolysis rate of the sample at higher temperatures. poly (methyl methacrylate); PS: poly (styrene); PE: poly (ethylene); PET: poly (ethylene terephthalate); RT: retention time, TIC: total ion chromatogram; GC-MS: gas chromatography-mass spectrometry, WHO: world health organization, Ea: activation energy, TGA: thermogravimetric analysis.