Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality Of Life Measurement Clarifies The Cost-Effectiveness Of Helicobacter Pylori Eradication In Peptic Ulcer Disease And Uninvestigated Dyspepsia

OBJECTIVES:Previous economic studies of Helicobacter pylori eradication in dyspepsia and peptic ulcer disease have not measured quality of life using utilities (preference probabilities), which are needed to compare the cost-effectiveness of such treatment to other health care interventions. The goals of this study were to measure quality of life in patients with dyspepsia or peptic ulcer and apply these measurements to published models of disease management to determine cost-effectiveness in dollars per quality-adjusted life year (QALY) gained.METHODS:Utilities for dyspepsia and peptic ulcer disease were measured in adult patients (n = 73) on chronic acid suppression for peptic ulcer or ulcer-like dyspepsia. Median utility values were applied to the results of published cost-effectiveness analyses and a previously validated dyspepsia model. Cost-utility ratios for early H. pylori eradication in uninvestigated dyspepsia and peptic ulcer disease were then computed.RESULTS:The total disutility, or lost quality of life, for an ulcer was 0.11 QALY, of which 0.09 QALY was attributed to dyspeptic symptoms. After these results were incorporated into published studies, cost-utility ratios for ulcer treatment varied from $3,100 to $12,500 per QALY gained, whereas estimates for uninvestigated dyspepsia management ranged from $26,800 to $59,400 per QALY. Sensitivity analyses indicated a range of $1,300 to $27,300 per QALY for management of duodenal ulcer and $15,000 to $129,700 per QALY for dyspepsia.CONCLUSIONS:Strategies that emphasize early H. pylori eradication were cost-effective for patients with peptic ulcer and possibly cost-effective for patients with uninvestigated dyspepsia, relative to other medical interventions. Dyspeptic symptoms cause significant disutility that should be incorporated in future cost-effectiveness analyses of treatment strategies.
Discussion of "The Discrete Infinite Logistic Normal Distribution for Mixed-Membership Modeling"

Mixed-membership models (e.g. “topic models”) are inarguably popular; especially latent Dirichlet allocation (LDA) [Blei et al., 2003] and its variants. Such models have become a fundamental tool in the analysis and exploration of many types of data. Originally designed to model text documents as per-word draws from a document-specific weighting of a finite collection of “topics” (distributions over words), mixedmembership models now are applied very broadly. Example usage includes applications in information retrieval, image processing, audio classification, and more. Because of the wide applicability of mixedmembership modeling, improving models of this type has the potential to have significant impact. The discrete infinite logistic normal distribution (DILN) for mixed-membership modeling is a significant advance in mixed-membership modeling.
Perceptions of oral health adequacy and access in Michigan nursing facilities.

OBJECTIVE To determine practices and perceived access barriers (facility resources, attitudes and professional dental involvement) related to oral health by surveying directors of nursing (DONs) in Michigan nursing homes (NHs). BACKGROUND DONs are crucial to NH practice and policy, so understanding their perceptions of oral health care is vital. METHODS A 27-item questionnaire exploring aspects of oral health was mailed to all 402 Michigan NH. Descriptive statistics were calculated for response items. RESULTS Facility response rate was 32% (n = 129). Sixty-three per cent of facilities had a written dental care plan primarily co-ordinated by nursing staff and social workers. Stationary dental equipment was available in 3% of facilities. Thirty-eight per cent stated an examination by a dentist was provided to new residents. Seventy-five per cent of residents identified as needing dental treatment were likely to receive it. Of the 28% of residents receiving dental treatment beyond an examination in the past year, 28% received emergent care. Over 50% of responding DONs indicated satisfaction with how oral hygiene needs were met in their facilities. The greatest perceived barriers were willingness of general and specialty dentists to treat residents at the nursing facility and/or their private offices as well as financial concerns of the resident and/or family. Generally, greater resources were available in urban facilities, but substantial barriers to care were uniformly perceived. CONCLUSION Oral health policies and practices within Michigan NH vary, as measured by resources, attitudes, and the availability of professional care. Dental involvement in policy creation, provision of consultation, and service is limited.
Expression and role of phosphatidylcholine‐specific phospholipase C in human NK and T lymphocyte subsets

We recently reported evidence of phosphatidylcholine‐specific phospholipase C (PC‐PLC) involvement in NK cell‐mediated cytotoxicity and in lytic granule exocytosis. In the present study, different subpopulations of human PBL were investigated in relation to PC‐PLC enzyme expression. While a substantial intracellular amount of PC‐PLC was detected in all lymphoid subsets, expression of this enzyme on the outer membrane surface reached high levels only in NK cells, was present at low levels in B lymphocytes and in some TCR gamma/delta T cells and was practically absent in CD4+ and CD8+ T lymphocytes. Moreover, in NK cells two different subpopulations were identified, CD56dim PC‐PLCbright and CD56bright PC‐PLClow/– cells, corresponding to distinct subsets with cytolytic and immunoregulatory functions, respectively. Interestingly, the PC‐PLC expression level on the NK membrane surface correlated closely with that of the CD16 receptor, suggesting a possible relationship between enzyme externalization and NK cell maturation. In summary, our results suggest that a high PC‐PLC expression on the cell membrane surface of PBL is a peculiarity of NK cytolytic cells, in which the enzyme is apparently involved in the ability of this subset to lyse sensitive target cells.
Protein-bound uraemic toxins, dicarbonyl stress and advanced glycation end products in conventional and extended haemodialysis and haemodiafiltration.

BACKGROUND Protein-bound uraemic toxins (PBUT), dicarbonyl stress and advanced glycation end products (AGEs) associate with cardiovascular disease in dialysis. Intensive haemodialysis (HD) may have significant clinical benefits. The aim of this study was to evaluate the acute effects of conventional and extended HD and haemodiafiltration (HDF) on reduction ratio (RR) and total solute removal (TSR) of PBUT, dicarbonyl stress compounds and AGEs. METHODS Thirteen stable conventional HD patients randomly completed a single study of 4-h HD (HD4), 4-h HDF (HDF4), 8-h HD (HD8) and 8-h HDF (HDF8) with a 2-week interval between the study sessions. RR and TSR of PBUT [indoxyl sulphate (IS), p-cresyl sulphate (PCS), p-cresyl glucuronide, 3-carboxyl-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indole-3-acetic acid (IAA) and hippuric acid] of free and protein-bound AGEs [N(ε)-(carboxymethyl)lysine (CML), N(ε)-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine, pentosidine], as well as of dicarbonyl compounds [glyoxal, methylglyoxal, 3-deoxyglucosone], were determined. RESULTS Compared with HD4, HDF4 resulted in increased RR of total and/or free fractions of IAA and IS as well as increased RR of free CML and CEL. HD8 and HDF8 showed a further increase in TSR and RR of PBUT (except CMPF), as well as of dicarbonyl stress and free AGEs compared with HD4 and HDF4. Compared with HD8, HDF8 only significantly increased RR of total and free IAA and free PCS, as well as RR of free CEL. CONCLUSIONS Dialysis time extension (HD8 and HDF8) optimized TSR and RR of PBUT, dicarbonyl stress and AGEs, whereas HDF8 was superior to HD8 for only a few compounds.
Site‐Specific Recombinational Cloning Using Gateway and In‐Fusion Cloning Schemes

The comprehensive study of protein structure and function, or proteomics, depends on the obtainability of full‐length cDNAs in species‐specific expression vectors and subsequent functional analysis of the expressed protein. Recombinational cloning is a universal cloning technique based on site‐specific recombination that is independent of the insert DNA sequence of interest, which differentiates it from classical restriction enzyme−based cloning methods. Recombinational cloning enables rapid and efficient parallel transfer of DNA inserts into multiple expression systems. This unit summarizes strategies for generating expression‐ready clones using the most popular commercial recombinational cloning technologies, Gateway (Life Technologies) and In‐Fusion (Clontech). © 2015 by John Wiley & Sons, Inc.
Established T Cell–Inflamed Tumors Rejected after Adaptive Resistance Was Reversed by Combination STING Activation and PD-1 Pathway Blockade

Many patients with head and neck squamous cell carcinomas do not respond to current immunotherapies. Antitumor responses, with protective memory and control of distant tumors, developed in mouse models after treatment with PD-L1 mAb and synthetic cyclic dinucleotides. Patients with head and neck squamous cell carcinoma harbor T cell–inflamed and non–T cell–inflamed tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack of induction of innate immunity through pattern-recognition receptors, such as the stimulator of interferon (IFN) genes (STING) receptor, may represent a significant barrier to the development of effective antitumor immunity. Here, we demonstrate robust control of a T cell–inflamed (MOC1), but not non–T cell–inflamed (MOC2), model of head and neck cancer by activation of the STING pathway with the synthetic cyclic dinucleotide RP,RP dithio-c-di-GMP. Rejection or durable tumor control of MOC1 tumors was dependent upon a functional STING receptor and CD8 T lymphocytes. STING activation resulted in increased tumor microenvironment type 1 and type 2 IFN and greater expression of PD-1 pathway components in vivo. Established MOC1 tumors were rejected and distant tumors abscopally controlled, after adaptive immune resistance had been reversed by the addition of PD-L1 mAb. These findings suggest that PD-1 pathway blockade may reverse adaptive immune resistance following cyclic dinucleotide treatment, enhancing both local and systemic antitumor immunity. Cancer Immunol Res; 4(12); 1061–71. ©2016 AACR.
Protein Modification by ADP-ribose via Acid-labile Linkages (*)

As substrate for protein-mono-ADP-ribosyltransferases, NAD has been shown to be the donor of ADP-ribose to many different nucleophiles found in proteins. This post-translational modification of proteins has been implicated in the regulation of membrane-associated processes including signal transduction, muscle cell differentiation, and protein trafficking and secretion. Described here is the preparation and chemical characterization of low molecular weight conjugates that were used as models for an acetal linkage between ADP-ribose and the hydroxyl group of a protein acceptor such as serine, threonine, tyrosine, hydroxyproline, or hydroxylysine residues. Model conjugates of ADP-ribose containing an acetal linkage were prepared, their structures were established by NMR, and the chemical stability of the linkage to ADP-ribose was studied and compared to the other known ADP-ribosyl-amino acid linkages. The rapid release of intact ADP-ribose from the acetal model conjugates in 44% formic acid distinguished them chemically from all the other known ADP-ribosyl-amino acid modifications. Rat liver proteins were shown to be modified by ADP-ribose in vivo by acid-labile linkages, providing evidence for a new class of endogenous ADP-ribose modification of animal cell proteins. The amount of modification was approximately 16 pmol of ADP-ribose per mg of total protein, and proteins modified by acid-labile linkages were detected in all subcellular fractions examined, suggesting that the scope of this modification in vivo is broad.
SMT-based architecture modelling for safety assessment

Safety is one of the main guidelines for critical systems design. Designers are in charge of developing architectures that comply with the safety requirements. Thus they must ensure that qualitative safety indicators such as the minimal size of failures scenario leading to a failure condition fc and quantitative indicators such as the probability to reach fc after a certain time interval, are kept below a given threshold. In this paper, we propose efficient minimal cutsets computation and analysis methods fully based on state-of-the-art Satisfiability Modulo Theory (SMT) and Boolean satisfiability (SAT) solvers. The efficiency of minimal cutsets computation, which does not rely on any intermediate model of the system such as fault trees is compared to classic formal analysis methods.
Polynomial modeling for the identification of lactate minimum velocity by different methods.

AIM The lactate minimum (LM) protocol has been used to assess aerobic fitness and to predict exercise intensity associated with the maximal blood lactate steady state. The aim of this study was to compare different methods to identify the lactate minimum velocity (LMV) on cycling. METHODS Fourteen male cyclists (26.8+/-4.5 years; 173.2+/-6.1 cm; 67.3+/-5.2 kg; 5,8+/-2.9 years of training) performed the LM test in a velodrome. The protocol consisted of an all out 2 km time trial to elevate blood lactate (bLAC), followed by 8 min of recovery and then 6 bouts of 2 km starting 5 kmxh(-1) below the individual mean velocity for the 6 km performance. The velocity was incremented by 1 kmxh(-1) at each bout with 25 microL of capillary blood being collected for bLAC measurements (YSI 2700 STAT). The LMV was identified visually (vLMV), and by applying a second grade polynomial function on 6 (pLMV(6)) and 3 (pLMV(3)) incremental bouts. Additionally, a method where the bLACx work velocity(-1) quotients (LMVQ) were plotted against the correspondent velocity during the incremental test, identified the LMV by considering 6 (LMVQ(6)) or 3 bouts (LMVQ(3)). RESULTS ANOVA showed no differences between vLMV (33.1+/-2.5 kmxh(-1)), pLMV(6) (32.9+/-2.5 kmxh(-1)), pLMV(3) (33.2+/-2.3 kmxh(-1)), LMVQ(6) (32.8+/-2.5 kmxh(-1)) and LMVQ(3) (33.4+/-2.3 kmxh(-1)), with high correlation among them. CONCLUSIONS It was possible to identify the LMV by the methods proposed in the present study, even when the results of only 3 bouts of the test were modeled by polynomial function. Such an approach enables a more practical and economical test in addition to minimizing the discomfort due to several blood collections.
Prevalence and outcome of portal thrombosis in a cohort of cirrhotic patients undergoing liver transplantation.

INTRODUCTION The prevalence of portal vein thrombosis (PVT) in patients that have undergone liver transplantation (LT) is 9.7% (SD 4.5). The aim of our study was to determine the prevalence, assess the factors that are associated with PVT and clarify their association with prognosis in patients with liver cirrhosis (LC) and LT. AIMS AND METHODS From 2005 to 2014, laboratory, radiological and surgical data were collected from patients with LC in our center who had undergone LT for the first time. RESULTS One hundred and ninety-one patients were included. The mean age was 55 (SD 9), 75.4% of patients were male and 48.7% had HCV. The Child-Pugh scores were A/B/C 41.9%/35.9%/25.5% and the MELD score was 15 (SD 6). Previous decompensations were: ascites (61.4%), hepatic encephalopathy (34.4%), variceal bleeding (25.4%), hepatocellular carcinoma (48.9%) and spontaneous bacterial peritonitis (SPB) (14.3%). The mean post-transplant follow-up was 42 months (0-113). PVT was diagnosed at LT in 18 patients (9.4%). Six patients were previously diagnosed using imaging tests (33.3%): 2 patients (11.1%) by DU and 4 patients (22.2%) by CT scan. All patients with PVT had DU in a mean time of 6 months before LT (0-44) and 90 patients (47.1%) had a CT scan in a median time of 6 months before LT (0-45). PVT was significantly related to the presence of SBP (33.3% vs 12.6%; p = 0.02) and lower levels of albumin (3.1g/dl vs 3.4g/dl; p = 0.05). MELD was higher in patients with PVT (16.6 vs 14.9; p = 0.3). There were no significant differences with regard to the need for transfusion of blood components. Moreover, the surgery time was similar in both groups. PVT correlated with a higher mortality in the first 30 days (8.8% vs 16.7%; p = 0.2). CONCLUSION Prior history of SBP and lower levels of albumin were identified as factors associated with PVT. The pre-transplant diagnosis rate is very low and the presence of PVT may have implications for short-term mortality.
Collaborative Governance in Health and Technology Policy: The Use and Effects of Procedural Policy Instruments

Stimulating technological innovations and limiting access to expensive health technology require the coordination and coherence of overlapping policy sub-systems: research, market access, and reimbursement. This study investigates which procedural policy instruments proved more successful in integrating collaborative governance arrangements in Great Britain and Germany. A new classification of procedural policy instruments is developed based on the targeted dimensions of collaborative governance (network structure and policy phase). The comparative analysis rests on expert interviews and meeting records and reveals that, in Great Britain, active leadership prevails during the consultations, while Germany, in contrast, presents a case of inconsistent governance.
Prior immunologic experience potentiates the subsequent antibody response when Salmonella strains are used as vaccine carriers

Prior immunologic experience with homologous and heterologous serotype Salmonella strains potentiated the subsequent antibody response when the same strains were used as vaccine carriers of foreign antigens. This potentiation was positively correlated with the appearance of antibody directed against the lipopolysaccharide of the carrier strain. Both serum and mucosal antibody responses against the foreign antigen increased over time. Antibody responses in sera of animals primed with either the homologous or heterologous serotype strain were not statistically significantly different, while animals primed with the homologous serotype strain developed significantly better mucosal antibody responses against the foreign antigen.
Admission hyperglycemia and outcomes in large vessel occlusion strokes treated with mechanical thrombectomy

Background and purpose Higher admission serum glucose levels have been associated with poor outcomes in patients with acute ischemic stroke (AIS) treated with IV thrombolysis. We sought to evaluate the association of admission serum glucose with early outcomes of patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT). Methods Consecutive AIS patients due to ELVO treated with MT in three tertiary stroke centers were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), complete reperfusion, mortality, functional independence (modified Rankin Scale (mRS) score of 0–2), and functional improvement (shift in mRS score) at 3 months. The association of admission serum glucose and admission hyperglycemia (>140 mg/dL) with outcomes was evaluated using univariable and multivariable binary and ordinal logistic regression models. Results 231 AIS patients with ELVO (mean age 62±14 years, 51% men, median admission National Institute of Health Stroke Scale score 16 points (IQR 12–21), median admission serum glucose 125 mg/dL (IQR 104–162)) were treated with MT. Admission hyperglycemia was associated with a lower likelihood of functional improvement (common OR 0.53; 95% CI 0.31 to 0.97; p=0.027) and higher odds of 3 month mortality (OR 2.76; 95% CI 1.40 to 5.44; p=0.004) in multivariable analyses adjusting for potential confounders. A 10 mg/dL increase in admission blood glucose was associated with a higher likelihood of sICH (OR 1.07; 95% CI 1.01 to 1.13; p=0.033) and 3 month mortality (OR 1.07; 95% CI 1.02 to 1.12; p=0.004) in multivariable models. There was no association between admission serum glucose or hyperglycemia and complete reperfusion. Conclusions Higher admission serum glucose and admission hyperglycemia are independent predictors of adverse outcomes in ELVO patients treated with MT.
Comparison of Abbott RealTime genotype II, GeneMatrix restriction fragment mass polymorphism and Sysmex HISCL HCV Gr assays for hepatitis C virus genotyping

Abstract Background: Hepatitis C virus (HCV) genotype is a predictive marker for treatment response. We sequentially evaluated the performances of two nucleic acid amplification tests (NAATs) and one serology assay for HCV genotype: Abbott RealTime genotype II (RealTime II), GeneMatrix restriction fragment mass polymorphism (RFMP), and Sysmex HISCL HCV Gr (HISCL Gr). Methods: We examined 281 clinical samples with three assays. The accuracy was assessed using the HCV Genotype Performance Panel PHW204 (SeraCare Life Sciences) for two NAATs. Discrepant cases were re-genotyped by the Versant HCV v.2.0 (line probe 2.0) assay. Results: With the RealTime II assay, clinic samples were analyzed as follows: genotypes 1b (43.1%), 2 (40.2%), 1 subtypes other than 1a and 1b (12.5%), 3 (1.8%), 4 (1.4%), 1a (0.7%), 6 (0.4%), and mixed (1.1%). The RealTime II and RFMP assays showed a type concordance rate of 97.5% (274/281) (κ=0.80) and no significant discordance (p=0.25). Both assays accurately genotyped all samples in the Performance Panel by the subtype level. The HISCL Gr assay showed concordance rates of about 91% (κ<0.40) and statistically significant discordances with two NAATs (p<0.05). In confirmation tests, the results of RFMP assay were the most consistent with those of Versant 2.0 assay. Conclusions: The three HCV assays provided genotyping and serotyping results with good concordance rates. The two NAATs (RealTime II and RFMP) showed comparable performance and good agreement. However, the results of the HISCL Gr assay showed statistically significant differences with those of the NAATs.
Obesity Reduction and Awareness and Screening of Noncommunicable Diseases through Group Education in Children and Adolescents (ORANGE): Methodology Paper (ORANGE-1)

Aim: Our goal is to estimate the prevalence of obesity, glucose intolerance, hypertension, dyslipidemia, and metabolic syndrome among urban children and adolescents aged 6–19 years and to raise awareness about noncommunicable diseases (NCDs) among school children in Chennai, South India. Methods: The Obesity Reduction and Awareness and Screening of Noncommunicable Diseases through Group Education project plans to reach out to children and adolescents using two approaches: The school and the community approach. The school approach aims to reach out to a representative sample of approximately 20,000 urban school children and adolescents, aged 6–19 years, covering 50 schools from all parts of Chennai. Anthropometric measures will include height, weight, waist, body fat, and blood pressure. Data on demographics, family Profile, behavioral aspects, physical activity, and food pattern will be obtained by using a validated questionnaire. Awareness about metabolic NCDs like obesity and diabetes will be increased by educating the children and adolescents about healthy lifestyles. Through the community approach, 2000 children and adolescents from randomly selected residential colonies in Chennai will be screened for obesity, glucose intolerance, hypertension, dyslipidemia, and metabolic syndrome. Expected Outcomes: Awareness about NCDs will be increased among children and their parents in Chennai. This study will also provide valuable epidemiological data on obesity, glucose intolerance, dyslipidemia, hypertension and metabolic syndrome in children and adolescents in urban India.