Miracle-dz/UniFAR-FTUs huggingface dataset:
Defects in α-Cell Function in Patients With Diabetes Due to Chronic Pancreatitis Compared With Patients With Type 2 Diabetes and Healthy Individuals

OBJECTIVE Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis. RESEARCH DESIGN AND METHODS Ten patients with diabetes secondary to chronic pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance test (OGTT) were performed. RESULTS Glucose levels during the OGTT were higher in patients with diabetes and chronic pancreatitis and lower in control subjects (P < 0.0001). Insulin and C-peptide levels were reduced, and the glucose-induced suppression of glucagon was impaired in both groups with diabetes (all P < 0.0001 vs. control subjects). During hypoglycemia, glucagon concentrations were reduced in patients with chronic pancreatitis and with type 2 diabetes (P < 0.05). The increase in glucagon during the clamp was inversely related to the glucose-induced glucagon suppression and positively related to β-cell function. Growth hormone responses to hypoglycemia were lower in patients with type 2 diabetes (P = 0.0002) but not in patients with chronic pancreatitis. CONCLUSIONS α-Cell responses to oral glucose ingestion and to hypoglycemia are disturbed in patients with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The similarities between these defects suggest a common etiology.
Evidence That Bimanual Motor Timing Performance Is Not a Significant Factor in Developmental Stuttering.

PURPOSE Stuttering involves a breakdown in the speech motor system. We address whether stuttering in its early stage is specific to the speech motor system or whether its impact is observable across motor systems. METHOD As an extension of Olander, Smith, and Zelaznik (2010), we measured bimanual motor timing performance in 115 children: 70 children who stutter (CWS) and 45 children who do not stutter (CWNS). The children repeated the clapping task yearly for up to 5 years. We used a synchronization-continuation rhythmic timing paradigm. Two analyses were completed: a cross-sectional analysis of data from the children in the initial year of the study (ages 4;0 [years;months] to 5;11) compared clapping performance between CWS and CWNS. A second, multiyear analysis assessed clapping behavior across the ages 3;5-9;5 to examine any potential relationship between clapping performance and eventual persistence or recovery of stuttering. RESULTS Preschool CWS were not different from CWNS on rates of clapping or variability in interclap interval. In addition, no relationship was found between bimanual motor timing performance and eventual persistence in or recovery from stuttering. The disparity between the present findings for preschoolers and those of Olander et al. (2010) most likely arises from the smaller sample size used in the earlier study. CONCLUSION From the current findings, on the basis of data from relatively large samples of stuttering and nonstuttering children tested over multiple years, we conclude that a bimanual motor timing deficit is not a core feature of early developmental stuttering.
Troponin T release is associated with silent myocardial ischaemia in black men: The SABPA Study

Background High sensitivity cardiac troponin T (hs-cTnT) is a validated marker of myocardial damage and may reflect the degree of silent myocardial ischaemia (SMI) and ventricular strain. Our aim was to compare hs-cTnT levels in black and white South Africans taking SMI into consideration. We further explored the capability of hs-cTnT to predict the presence of compensatory systolic hypertension in this South African cohort. Methods A bi-ethnic sex cohort (n = 404) with similar socioeconomic status (198 black participants and 206 white participants, aged 20–65 years) participated in this target population study where 24 h ambulatory blood pressure, electrocardiogram and overnight fasting cardiometabolic variables were measured. Results Hypertension, higher glycated haemoglobin levels and more frequent and longer SMI events were observed more often in the black participants. Multivariate linear regression analysis showed positive associations between SMI events [Adj. R2 = 0.19; β 0.35 (0.08–0.62); p < 0.01], SMI event maximum duration [Adj. R2 = 0.17, β 0.43 (0.16–0.70), p < 0.01], SMI total duration [Adj. R2 = 0.12; β 0.37 (0.10; 0.65), p = 0.05] and hs-cTnT in black males only. ] A lower hs-cTnT cut-point ≥4.2 pg/ml for 24 h systolic hypertension was predicted in the black participants compared with ≥5.6 pg/ml in the white participants (area under the curve 0.66–67 (95% CI: 0.57–0.75), p < 0.001) with a respective sensitivity/specificity of 64/68% and 61/71%. Conclusions hs-cTnT may be a potential marker of SMI in the prediction of systolic blood pressure increases, as well as clusters of risk factors for cardiovascular disease. Ethnic- and possibly sex-specific references values for hs-cTnT should be considered for risk stratification.
State helmet laws and helmet use among fatally injured moped riders in the United States, 2011–2015

ABSTRACT Objective: Research has found that mandatory motorcycle helmet laws increase helmet use and reduce motorcycle-related fatalities. However, the association between state moped helmet laws and helmet use in the United States has not been examined. This study investigated this association among a census of fatally injured moped riders in the United States. Methods: A logistic regression model was constructed to analyze data extracted from the Fatality Analysis Reporting System (FARS) to examine risk factors for helmet nonuse among 572 moped riders fatally injured between 2011 and 2015. Results: Fatally injured moped riders in states with universal helmet laws had 69 times the odds of wearing a helmet (P < .001). Conclusions: Findings suggest that universal moped helmet laws increase helmet use. However, additional research is needed to examine helmet laws and use among nonfatally injured moped riders.
Dexamethasone Down-regulates Osteocalcin in Bone Cells through Leptin Pathway

Glucocorticoid therapy, especially at higher doses, is associated with significant adverse side effects including osteoporosis. Leptin, secreted from adipose tissue, has diverse effects on bone tissue regulation. As glucocorticoids stimulate leptin synthesis and secretion directly in adipose tissue we hypothesised that dexamethasone (DEX) induced osteoporosis may, in part, be mediated by an osteoblast dependent leptin-leptin receptor pathway. Human bone cells expressed leptin and leptin receptors (Ob-Ra and Ob-Rb). DEX increased leptin, Ob-Ra and Ob-Rb expression in a dose-dependent manner while decreasing expression of osteocalcin. In the presence of leptin, Cbfa1 and osteonectin expression showed no significant change, whereas osteocalcin expression was decreased. Recombinant human quadruple antagonist leptin suppressed DEX-induced osteocalcin downregulation. The signaling pathway involved up-regulation of JAK2. In conclusion, upregulation of leptin and Ob-Rb in human bone cells by DEX is associated with down-regulation of osteocalcin expression. The down regulation of osteocalcin by DEX was partially through a leptin autocrine/paracrine loop. Adverse effects of DEX on the skeleton may be modified by targeting leptin signaling pathways.
Impact of copper toxicity on stone-head cabbage (Brassica oleracea var. capitata) in hydroponics

Arable soils are frequently subjected to contamination with copper as the consequence of imbalanced fertilization with manure and organic fertilizers and/or extensive use of copper-containing fungicides. In the present study, the exposure of stone-head cabbage (Brassica oleracea var. capitata) to elevated Cu2+ levels resulted in leaf chlorosis and lesser biomass yield at ≥2 µ M. Root nitrate content was not statistically affected by Cu2+ levels, although it was substantially decreased at ≥5 µ M Cu2+ in the shoot. The decrease in nitrate contents can be related to lower nitrate uptake rates because of growth inhibition by Cu-toxicity. Shoot sulfate content increased strongly at ≥2 µ M Cu2+ indicating an increase in demand for sulfur under Cu stress. Furthermore, at ≥2 µM concentration, concentration of water-soluble non-protein thiol increased markedly in the roots and to a smaller level in the shoot. When exposed to elevated concentrations of Cu2+ the improved sulfate and water-soluble non-protein thiols need further studies for the evaluation of their direct relation with the synthesis of metal-chelating compounds (i.e., phytochelatins).
Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis.

Importance The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined. Objectives To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging. Design, Setting, and Participants Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014. Main Outcome and Measures Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5-year follow-up. Results One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five-year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004). Conclusions and Relevance An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging.
Dietary Balance Index-07 and the Risk of Anemia in Middle Aged and Elderly People in Southwest China: A Cross Sectional Study

A balanced diet is essential to achieve and maintain good health. In this study, we assessed diet quality of middle aged and elderly people based on Chinese Diet Balance Index-07 (DBI-07) and explored the associations between DBI-07 and anemia. Data analyzed for this study was from the 2010–2012 National Nutrition and Health Survey in Yunnan province, southwest China (n = 738, aged 50–77 years). Dietary recalls over there consecutive days were done in a face-to-face interview. The scores of DBI-07 for each component and three DBI-07 indicators ((Lower Bound Score (LBS), Higher Bound Score (HBS), Diet Quality Distance (DQD)) were calculated according to compliance with the Dietary Guidelines for Chinese residents. Hemoglobin (Hb) concentration was determined using the cyanmethemoglobin method. Univariate and multivariate linear regression models were used to explore the associations between DBI-07 indicators and anemia, as well as scores of DBI-07 components and Hb level. The sample included 336 men and 402 women. Inadequate intakes of vegetables, fruits, dairy, soybean, eggs, fish and excessive intakes of cereals, meat, cooking oil, salt were both common. 91.3% of the participants had moderate or high levels of inadequate food intake, while 37.7% had moderate or high levels of excessive food intake. The mean Hb was 14.2 ± 1.7 g/dL, with a prevalence of anemia of 13.0%. Subjects with high LBS and DQD were more likely to be anemic (all p < 0.05). After adjustment for potential confounders, there were positive correlations between Hb level and the intakes of vegetables and soybean (βvegetables = 1.04, p < 0.01; βsoybean = 0.82, p = 0.04). In conclusion, dietary imbalance and anemia are common in middle aged and elderly population in southwest China and inadequate intakes of vegetables and soybean may increase the risk of anemia.
Conformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C Virus Glycoprotein E2

ABSTRACT The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site. A detailed interaction analysis of DAO5 and cross-competing neutralizing antibodies with soluble E2 revealed that the Ig-like domain is trapped by different antibodies in at least two distinct conformations. DAO5 specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp) and infectious cell culture-derived HCV particles (HCVcc). Infection of cells by DAO5-captured HCVpp can be blocked by a cross-competing neutralizing antibody, indicating that a single virus particle simultaneously displays E2 molecules in more than one conformation on its surface. Such conformational plasticity of the HCV E2 receptor binding site has important implications for immunogen design. IMPORTANCE Recent advances in the treatment of hepatitis C virus (HCV) infection with direct-acting antiviral drugs have enabled the control of this major human pathogen. However, due to their high costs and limited accessibility in combination with the lack of awareness of the mostly asymptomatic infection, there is an unchanged urgent need for an effective vaccine. The viral glycoprotein E2 contains regions that are crucial for virus entry into the host cell, and antibodies that bind to these regions can neutralize infection. One of the major targets of neutralizing antibodies is the central immunoglobulin (Ig)-like domain within E2. We show here that this Ig-like domain is conformationally flexible at the surface of infectious HCV particles and pseudoparticles. Our study provides novel insights into the interactions of HCV E2 with the humoral immune system that should aid future vaccine development. IMPORTANCE Recent advances in the treatment of hepatitis C virus (HCV) infection with direct-acting antiviral drugs have enabled the control of this major human pathogen. However, due to their high costs and limited accessibility in combination with the lack of awareness of the mostly asymptomatic infection, there is an unchanged urgent need for an effective vaccine. The viral glycoprotein E2 contains regions that are crucial for virus entry into the host cell, and antibodies that bind to these regions can neutralize infection. One of the major targets of neutralizing antibodies is the central immunoglobulin (Ig)-like domain within E2. We show here that this Ig-like domain is conformationally flexible at the surface of infectious HCV particles and pseudoparticles. Our study provides novel insights into the interactions of HCV E2 with the humoral immune system that should aid future vaccine development.
Maximizing the functional lifetime of Protein A resins

Protein A chromatography is currently the industry gold‐standard for monoclonal antibody and Fc‐fusion protein purification. The high cost of Protein A, however, makes resin lifetime and resin reuse an important factor for process economics. Typical resin lifetime studies performed in the industry usually examine the effect of resin re‐use on binding capacity, yield, and product quality without answering the fundamental question of what is causing the decrease in performance. A two part mechanistic study was conducted in an attempt to decouple the effect of the two possible factors (resin hydrolysis and/or degradation vs. resin fouling) on column performance over lifetime of the most commonly used alkali‐stable Protein A resins (MabSelect SuRe and MabSelect SuRe LX). The change in binding capacity as a function of sodium hydroxide concentration (rate of hydrolysis), temperature, and stabilizing additives was examined. Additionally, resin extraction studies and product cycling studies were conducted to determine cleaning effectiveness (resin fouling) of various cleaning strategies. Sodium hydroxide‐based cleaning solutions were shown to be more effective at preventing resin fouling. Conversely, cold temperature and the use of stabilizing additives in conjunction with sodium hydroxide were found to be beneficial in minimizing the rate of Protein A ligand hydrolysis. An effective and robust cleaning strategy is presented here to maximize resin lifetime and thereby the number of column cycles for future manufacturing processes. © 2017 American Institute of Chemical Engineers Biotechnol. Prog. , 33:708–715, 2017
Legislative Constraints on Executive Unilateralism in Separation of Powers Systems

Can legislatures effectively check unilateral executive power? One prominent and counterintuitive finding in previous work is that executives pursue unilateralism less often under divided government. While executives see greater potential policy gains through unilateral action during divided government, we argue that their likelihood of acting unilaterally depends on an opposed legislature’s ability to retaliate. When polarization is high and majorities are marginal, executives are freer to act unilaterally given the difficulties legislatures have in statutorily responding. unilateralism is also more likely when facing opposition if legislatures lack nonstatutory means of punishment, such as regulatory review. in the largest analysis of gubernatorial executive unilateralism to date, we use a new data set of 24,232 executive orders in the 50 american states between 1993 and 2013 to evaluate this argument and find strong support for its predictions. these results provide insights into how legislative policymaking capacity can influence the functioning of separation of powers systems.
Mixing dynamics of pulp suspensions in cylindrical vessels

Cylindrical agitated chests are frequently used to facilitate manufacturing processes in pulp and paper industry and one of their main functions is to attenuate any process disturbances. However, owing to the inherited non-Newtonian nature of pulp suspensions, it is not easy to achieve complete mixing and with the improper chest design, these agitated chests do not always perform ideally or satisfactorily. The cavern formation in incomplete mixing may induce bypassing and dead zones, which significantly affect the chest performance. A study of cavern formation in a cylindrical agitated chest was thus carried out. Also, a dynamic model developed by Soltanzadeh et al. (2009) was used to quantify the mixing dynamics of the cylindrical chest. In addition, using computational fluid dynamics (CFD), the simulated results of the flow in the chest were compared with the experimental results to verify the applicability of the CFD model on the study of pulp suspension agitation. To investigate the cavern formation in a lab-scale cylindrical chest, electrical resistance tomography (ERT) and ultrasonic Doppler velocimetry (UDV) were applied to estimate the cavern shape and size. Both methods gave satisfactory results and as expected, the cavern size was found to increase with impeller speeds. The cavern shape was best described as a truncated right-circular cylinder. Based on this observation, a model considering the interaction between the cavern and chest walls was developed to calculate the cavern volume. With the dynamic model, a series of dynamic tests were carried out to characterize the mixing behavior of the lab-scale cylindrical chest. It was found that the proposed flow configuration with the outlet close to the cavern could minimize the bypassing which affects mixing quality. Also, ERT verified the presence of cavern and dead zone when the chest was not completely agitated in continuous-flow operation.
Differentiation of AB-FUBINACA positional isomers by the abundance of product ions using electron ionization-triple quadrupole mass spectrometry.

Mass spectrometric differentiation of structural isomers is important for the analysis of forensic samples. Presently, there is no mass spectrometric method for differentiating halogen positional isomers of cannabimimetic compounds. We describe here a novel and practical method for differentiating one of these compounds, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA (para)), and its fluoro positional (ortho and meta) isomers in the phenyl ring by electron ionization-triple quadrupole mass spectrometry. It was found that the three isomers differed in the relative abundance of the ion at m/z 109 and 253 in the product ion spectra, while the detected product ions were identical. The logarithmic values of the abundance ratio of the ions at m/z 109 to 253 (ln(A109 /A253 )) were in the order meta < ortho < para and increased linearly with collision energy. The differences in abundances were attributed to differences in the dissociation reactivity between the indazole moiety and the fluorobenzyl group because of the halogen-positional effect on the phenyl ring. Our methodology, which is based on the abundance of the product ions in mass spectra, should be applicable to determination of the structures of other newly encountered designer drugs. Copyright © 2016 John Wiley & Sons, Ltd.