Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Endoplasmic Reticulum Stress in Autoimmune-Mediated Beta-Cell Destruction in Type 1 Diabetes

Unlike type 2 diabetes which is caused by the loss of insulin sensitivity, type 1 diabetes (T1D) is manifested by the absolute deficiency of insulin secretion due to the loss of β mass by autoimmune response against β-cell self-antigens. Although significant advancement has been made in understanding the pathoetiology for type 1 diabetes, the exact mechanisms underlying autoimmune-mediated β-cell destruction, however, are yet to be fully addressed. Accumulated evidence demonstrates that endoplasmic reticulum (ER) stress plays an essential role in autoimmune-mediated β-cell destruction. There is also evidence supporting that ER stress regulates the functionality of immune cells relevant to autoimmune progression during T1D development. In this paper, we intend to address the role of ER stress in autoimmune-mediated β-cell destruction during the course of type 1 diabetes. The potential implication of ER stress in modulating autoimmune response will be also discussed. We will further dissect the possible pathways implicated in the induction of ER stress and summarize the potential mechanisms underlying ER stress for mediation of β-cell destruction. A better understanding of the role for ER stress in T1D pathoetiology would have great potential aimed at developing effective therapeutic approaches for the prevention/intervention of this devastating disorder.
Adrenal and gonadal contributions to urinary excretion and plasma concentration of epitestosterone in men — effect of adrenal stimulation and implications for detection of testosterone abuse

The ratio of urinary testosterone (T) to epitestosterone (EpiT) is used to detect T abuse in sport. Also, plasma or urinary concentrations of EpiT have been measured to assess testicular steroidogenesis during hormonal male contraception. Further investigations are required to evaluate the relative contributions of the testis and adrenal to EpiT production. To this purpose, we have compared basal urinary EpiT glucuronide and plasma EpiT and the response to synthetic adrenocorticotrophic hormone (ACTH) stimulation between eugonadal and hypogonadal men.
Evolutionary Insights from a Genetically Divergent Hantavirus Harbored by the European Common Mole (Talpa europaea)

Background The discovery of genetically distinct hantaviruses in shrews (Order Soricomorpha, Family Soricidae) from widely separated geographic regions challenges the hypothesis that rodents (Order Rodentia, Family Muridae and Cricetidae) are the primordial reservoir hosts of hantaviruses and also predicts that other soricomorphs harbor hantaviruses. Recently, novel hantavirus genomes have been detected in moles of the Family Talpidae, including the Japanese shrew mole (Urotrichus talpoides) and American shrew mole (Neurotrichus gibbsii). We present new insights into the evolutionary history of hantaviruses gained from a highly divergent hantavirus, designated Nova virus (NVAV), identified in the European common mole (Talpa europaea) captured in Hungary. Methodology/Principal Findings Pair-wise alignment and comparison of the full-length S- and L-genomic segments indicated moderately low sequence similarity of 54–65% and 46–63% at the nucleotide and amino acid levels, respectively, between NVAV and representative rodent- and soricid-borne hantaviruses. Despite the high degree of sequence divergence, the predicted secondary structure of the NVAV nucleocapsid protein exhibited the characteristic coiled-coil domains at the amino-terminal end, and the L-segment motifs, typically found in hantaviruses, were well conserved. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that NVAV formed a distinct clade that was evolutionarily distant from all other hantaviruses. Conclusions Newly identified hantaviruses harbored by shrews and moles support long-standing virus-host relationships and suggest that ancestral soricomorphs, rather than rodents, may have been the early or original mammalian hosts.
Precoded DDOSTBC with non-unitary constellations over correlated Rayleigh channels with carrier offsets

In this paper, we consider the effect of carrier offsets in arbitrarily correlated flat-fading multiple-input multiple-output (MIMO) Rayleigh channels. We propose a double-differential coding for square orthogonal space-time block code (OSTBC) with non-unitary constellations over flat-fading MIMO channels with carrier offsets. In order to improve the performance of the proposed double-differential orthogonal space-time block code (DDOSTBC) over arbitrarily correlated Rayleigh channel we introduce a full memoryless precoder matrix in the transmitter. For the proposed precoded DDOSTBC, a pair-wise error performance (PEP) analysis is conducted. Then we propose a precoder design based on the PEP upper bound. The proposed DDOSTBC differs from the previously proposed DDOSTBC by: 1) The previously proposed DDOSTBC is aplicable to only a specific class of OSTBC which follows diagonal group property, whereas, the proposed DDOSTBC is applicable to any square OSTBC. 2) The previously proposed DDOSTBC can work with M-PSK constelation only, whereas, the proposed DDOSTBC is applicable to M-QAM, M-PAM, or M-PSK constellations. The proposed DDOSTBC provides higher performance gain as compared to the same rate previously proposed DDOSTBC. In addition, the proposed precoded DDOSTBC is able to perform better than the unprecoded DDOSTBC over arbitrarily correlated Rayleigh channels.
Berberine protects against esophageal mucosal damage in reflux esophagitis by suppressing proinflammatory cytokines

This study was performed to investigate the effects of berberine (BB) in a rat model of gastroesophageal reflux disease (GERD), induced by pylorus and forestomach ligation. We evaluated cytotoxicity and proinflammatory biomarkers (nitric oxide, interleukin (IL)-1β and prostaglandin E2) in RAW 264.7 cells in vitro and anti-inflammatory effects in vivo. A total of 54 Sprague Dawley rats were divided into six groups: intact control rats; reflux esophagitis (RE) control rats; RE rats treated with 20 mg/kg omeprazole and RE rats treated with BB at doses of 20, 40 and 60 mg/kg, respectively. All rats were fasted. RE was induced by pylorus and forestomach ligation one hour subsequent to the oral treatment. Six hours subsequent to the surgery, the rats were sacrificed, blood was collected from the abdominal vein and the esophagus and stomach were dissected. The gastric volume and the pH of the gastric juice were evaluated, prior to the esophagus being cut longitudinally and an inner mucosal area being imaged, to analyze mucosal damage indices. Proinflammatory biomarkers in the serum, including tumor necrosis factor (TNF)-α, IL-1β, IL-6 and monocyte chemoattractant protein (MCP)-1 were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, while the mRNA expression of TNF-α, IL-1β, IL-6 and plasminogen activator inhibitor (PAI)-1 was analyzed using a quantitative polymerase chain reaction (qPCR). Esophagic tissue damage in the BB groups was dose-dependently decreased compared with that in the RE control group. This result was consistent with significant reductions in the levels of proinflammatory biomarkers in the serum and in the expression of proinflammatory mRNA, specifically, TNF-α, IL-1β, IL-6 and PAI-1. The results suggest that the anti-inflammatory and protective effects of BB may attenuate the severity of RE and prevent esophageal mucosal damage, in addition to validating the use of BB as a pharmacological treatment for esophageal reflux disease.
Prognostic value of troponin T and homocysteine in patients with end-stage renal disease.

OBJECTIVES The most important cause of increased mortality in end-stage renal disease (ESRD) is cardiovascular diseases. We investigated the prognostic value of cardiac troponin T (cTnT) and homocysteine in the long-term follow-up of ESRD patients. STUDY DESIGN The study included 78 patients (54 males, 24 females; mean age 53.2+/-16.6 years) with ESRD, who had been on hemodialysis treatment for at least three months. Baseline troponin T and homocysteine levels were measured and the patients were followed-up from March 2002 to May 2007 for major adverse cardiovascular events (MACE). RESULTS Major adverse cardiovascular events occurred in 26 patients (33.3%), including cerebrovascular events (n=3, 3.9%), congestive heart failure (CHF) (n=18, 23.1%), coronary artery disease (CAD) (n=19, 24.4%), and death (n=19, 24.4%). Two-thirds of diabetic patients developed MACE and the mean age in the MACE group was significantly greater (p<0.001). Troponin T levels were significantly higher in patients who developed MACE (0.21+/-0.43 ng/ml vs 0.06+/-0.28 ng/ml, p=0.002), whereas homocysteine levels did not differ significantly between the two groups (p=0.82). For a cutoff value of 0.10 ng/ml, cTnT was > or =0.1 ng/ml in 17 patients (21.8%), and <0.10 ng/ml in 61 patients (78.8%). Patients having a cTnT level of > or =0.10 ng/ml showed significantly higher rates of MACE (64.7% vs 24.6%; p=0.003), CHF (47.1% vs 16.4%; p=0.02), and death (52.9% vs 16.4%; p=0.004). There was also a greater tendency to CAD in this group (41.2% vs 19.7%, p=0.10). In multivariate logistic regression analysis, age and diabetes mellitus were the independent predictors of MACE development. CONCLUSION Homocysteine levels cannot predict MACE in ESRD patients in the long-term follow-up. Despite a significantly higher incidence of MACE in patients with high cTnT levels, cTnT was not an independent predictor of cardiovascular outcome.
Hypocholesterolaemic effects of lupin protein and pea protein/fibre combinations in moderately hypercholesterolaemic individuals

The present study was aimed to evaluate the effect of plant proteins (lupin protein or pea protein) and their combinations with soluble fibres (oat fibre or apple pectin) on plasma total and LDL-cholesterol levels. A randomised, double-blind, parallel group design was followed: after a 4-week run-in period, participants were randomised into seven treatment groups, each consisting of twenty-five participants. Each group consumed two bars containing specific protein/fibre combinations: the reference group consumed casein+cellulose; the second and third groups consumed bars containing lupin or pea proteins+cellulose; the fourth and fifth groups consumed bars containing casein and oat fibre or apple pectin; the sixth group and seventh group received bars containing combinations of pea protein and oat fibre or apple pectin, respectively. Bars containing lupin protein+cellulose ( − 116 mg/l, − 4·2 %), casein+apple pectin ( − 152 mg/l, − 5·3 %), pea protein+oat fibre ( − 135 mg/l, − 4·7 %) or pea protein+apple pectin ( − 168 mg/l, − 6·4 %) resulted in significant reductions of total cholesterol levels (P < 0·05), whereas no cholesterol changes were observed in the subjects consuming the bars containing casein+cellulose, casein+oat fibre or pea protein+cellulose. The present study shows the hypocholesterolaemic activity and potential clinical benefits of consuming lupin protein or combinations of pea protein and a soluble fibre, such as oat fibre or apple pectin.
Reducing loneliness amongst older people: a systematic search and narrative review

Objective: To investigate the effectiveness of recent social therapeutic interventions to reduce loneliness in older people. Method: To examine this matter, a literature review, using seven databases, was undertaken using search terms relating to the themes of ageing, loneliness and social support. A total of 17 relevant studies relating to loneliness interventions were analysed. Results: Three studies reporting on new technologies and one on a group work intervention identified significant reductions in loneliness.Conclusion: Further research into interventions using new technologies to reduce loneliness in older people is recommended.
DECREASE IN OVALBUMIN-INDUCED PULMONARY ALLERGIC RESPONSE BY BENZALDEHYDE BUT NOT ACETALDEHYDE EXPOSURE IN A GUINEA PIG MODEL

The pulmonary effects of two environmentally relevant aldehydes were investigated in nonsensitized or ovalbumin (OA)-sensitized guineapigs (GPs). Four-week-old male Hartley GPs, weighing about 400 g, were intraperitoneally injected with 1 ml of an NaCl solution containing 100 µ g OA and 100 mg Al(OH) 3 . They were then exposed to either acetaldehyde (200 ppb) or benzaldehyde (500 ppb) for 4 wk (6 h/d, 5 d/wk). At the end of exposure, GPs were challenged with an OA aerosol (0.1% in NaCl) and pulmonary functions were measured. The day after, guinea pigs were anesthetized and several endpoints related to inflammatory and allergic responses were assessed in blood, whole-lung histology, and bronchoalveolar lavage (BAL). Sensitized nonexposed GPs showed bronchial hyperresponsiveness to OA and an increased number of eosinophils in blood and BAL, together with a rise in total protein and leukotrienes (LTB 4 and LTC 4 /D 4 /E 4 ) in BAL. In nonsensitized GPs, exposure to acetaldehyde or benzaldehyde did not induce any change in the tested parameters, with the exception of irritation of the respiratory tract as detected by histology and an increased number of alveolar macrophages in animals exposed to acetaldehyde. In sensitized GPs, exposure to acetaldehyde induced a moderate irritation of the respiratory tract but no change in biological parameters linked to the inflammatory and allergic responses. In contrast, exposure to benzaldehyde induced a decrease both in OA-induced bronchoconstriction and in eosinophil and neutrophil numbers in BAL, an increase in the bronchodilatator mediator prostaglandin E 2 (PGE 2 ), and a decrease in the bronchoconstrictor mediators LTC 4 /D 4 /E 4 . Further investigations are needed to determine if the attenuated response observed in sensitized GPs exposed to benzaldehyde is due to an alteration of the mechanism of sensitization or to a more direct effect on various mechanisms of the allergic response.
The clinical efficacy and long-term prognostic value of stress echocardiography in octogenarians

Introduction Although stress echocardiography (SE) is invaluable in younger populations, its prognostic value may be attenuated in the elderly due to shorter life expectancy and the frequent presence of severe comorbidities. This study sought to evaluate the clinical effectiveness of SE in octogenarians, particularly its prognostic value over clinical variables, in predicting hard events. Methods A total of 374 consecutive octogenarians who underwent SE for evaluation of coronary artery disease (CAD) were assessed for feasibility, diagnostic accuracy and safety of the test, and followed up for hard outcomes (all-cause mortality, cardiovascular (CV) deaths and non-fatal myocardial infarction (NFMI)). Cox regression analysis was performed to identify predictors of outcome. Results Of the 374 tests, 360 (96.3%) were diagnostic. Of the 50 patients with inducible ischaemia, 33 patients (66%) proceeded to angiography of which 27 (82%) patients had significant CAD. During long-term follow-up of 4.0±2.0 years, there were 127 deaths and 36 NFMIs. The annualised mortality, NFMI and combined mortality /NFMI rates were 8.1%, 1.8% and 9.4% for patients with a normal SE and 12.1%, 5.5% and 14.1% for those with an abnormal SE, respectively. Predictors of NFMI on multivariate analysis were prior CAD (HR 2.89, CI 1.03 to 8.15, p=0.045), peripheral vascular disease (HR 3.33, CI 1.18 to 9.45, p=0.02), and inducible ischaemia (HR 3.97, CI 1.49 to 10.55, p=0.006). In patients without prior history of CAD, inducible ischaemia was the only independent predictor of NFMI (HR 8.72, CI 1.46 to 52.2, p=0.018). The larger the extent of ischaemia, the greater the incidence of NFMI. The independent predictors of CV events (NFMI or CV mortality) were PAD (HR 2.81, CI 1.21 to 6.52, p=0.016) and peak wall motion score index (HR 5.71, CI 1.67 to 19.6, p=0.006). Although inducible ischaemia predicted all-cause mortality on unadjusted analysis, it did not on multivariate analysis. Conclusions In octogenarians, SE demonstrated excellent feasibility, safety and diagnostic accuracy. SE parameters were independent predictors of NFMI and CV events, and the presence of inducible ischaemia was associated with a 50% increase in all-cause mortality.
Association of Lecithin Cholesterol Acyltransferase rs5923 Polymorphism in Iranian Individuals with Extremely Low High-Density Lipoprotein Cholesterol: Tehran Lipid and Glucose Study

Background: The serum concentration of high-density lipoprotein cholesterol (HDL-C) is one of the important heritable risk factors for cardiovascular disease and is a target for therapeutic intervention. In this study, we aimed to evaluate the effects of lecithin cholesterol acyltransferase (LCAT) gene polymorphism rs5923 on LCAT enzyme activity and serum HDL-C concentration. Methods: The study population was selected from consecutive individuals with HDL-C ≤ 5th percentile (n = 73) and extremely high HDL-C ≥ 95th percentile (n = 57) who had participated in the Tehran Lipid and Glucose Study. The rs5923 polymorphism was genotyped using direct sequencing. LCAT activity was measured by fluorometric assay kit, and lipid concentrations were measured using the enzymatic colorimetric method. Results: The genotype frequencies were significantly different between the high HDL-C group (CC 94.7%, CT 5.3%) and the low HDL-C group (CC 83.6%, CT 16.4%) (P = 0.048). The T-allele frequencies in subjects with low and high HDL-C were 0.082 and 0.026, respectively (P = 0.16). The association of the single-nucleotide polymorphism rs5923 with low HDL-C was not statistically significant after adjustment for age, sex, and BMI (odd ratio = 2.65, 95% confidence interval = 0.32-21.5, P = 0.36, regression logistic analysis). Also, the effects of LCAT enzyme activity did not depend on the HDL-C level (P = 0.24). Conclusion: rs5923 polymorphism is not associated with low HDL-C levels in Iranian population.
The Functional Lumen Imaging Probe Detects Esophageal Contractility Not Observed With Manometry in Patients With Achalasia.

BACKGROUND & AIMS The functional lumen imaging probe (FLIP) could improve the characterization of achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. METHODS Fifty-one treatment-naive patients with achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. RESULTS Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). CONCLUSIONS Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II achalasia. These findings could have implications for additional subclassification to supplement prediction of the achalasia disease course.
A Comparison of GARCH Models for VAR Estimation

This study is an attempt to compare a comprehensive list of GARCH models in quantifying risks of VaR under stress times. We gather data of stock market indices from both emerging (Brazil and Turkey) and developed (Germany and the USA) markets, over the period of global financial crisis and make use of numerous GARCH specifications to return VaR values. Then we compare the assessments of VaR with the realized returns by Kupiec and Christoffersen Tests. Besides, we calculate Quadratic Losses to evaluate the GARCH specifications in calculating VaR. The results reveal that the ARCH specification is the best performer followed by GARCH(1,1) and the Student's t distribution is slightly better than the Normal. The other outcome of the paper is that the worst performers are Non-Linear Power GARCH and Non-Linear Power GARCH with a shift. All GARCH estimations are carried out with STATA that uses the Maximum Likelihood method of estimation.
On the catalytic mechanism and stereospecificity of Escherichia coli l‐threonine aldolase

l‐Threonine aldolases (l‐TAs) represent a family of homologous pyridoxal 5′‐phosphate‐dependent enzymes found in bacteria and fungi, and catalyse the reversible cleavage of several l‐3‐hydroxy‐α‐amino acids. l‐TAs have great biotechnological potential, as they catalyse the formation of carbon–carbon bonds, and therefore may be exploited for the bioorganic synthesis of l‐3‐hydroxyamino acids that are biologically active or constitute building blocks for pharmaceutical molecules. Many l‐TAs, showing different stereospecificity towards the Cβ configuration, have been isolated. Because of their potential to carry out diastereoselective syntheses, l‐TAs have been subjected to structural, functional and mechanistic studies. Nevertheless, their catalytic mechanism and the structural bases of their stereospecificity have not been elucidated. In this study, we have determined the crystal structure of low‐specificity l‐TA from Escherichia coli at 2.2‐Å resolution, in the unliganded form and cocrystallized with l‐serine and l‐threonine. Furthermore, several active site mutants have been functionally characterized in order to elucidate the reaction mechanism and the molecular bases of stereospecificity. No active site catalytic residue was revealed, and a structural water molecule was assumed to act as the catalytic base in the retro‐aldol cleavage reaction. Interestingly, the very large active site opening of E. coli l‐TA suggests that much larger molecules than l‐threonine isomers may be easily accommodated, and l‐TAs may actually have diverse physiological functions in different organisms. Substrate recognition and reaction specificity seem to be guided by the overall microenvironment that surrounds the substrate at the enzyme active site, rather than by one ore more specific residues.
Unsupervised Text Segmentation Using Semantic Relatedness Graphs

Segmenting text into semantically coherent fragments improves readability of text and facilitates tasks like text summarization and passage retrieval. In this paper, we present a novel unsupervised algorithm for linear text segmentation (TS) that exploits word embeddings and a measure of semantic relatedness of short texts to construct a semantic relatedness graph of the document. Semantically coherent segments are then derived from maximal cliques of the relatedness graph. The algorithm performs competitively on a standard synthetic dataset and outperforms the best-performing method on a real-world (i.e., non-artificial) dataset of political manifestos.