Miracle-dz/UniFAR-FTUs huggingface dataset:
Determining minimally important differences for the PDQ-39 Parkinson's disease questionnaire.

OBJECTIVE To determine minimally important differences for dimensions of the PDQ-39, a 39-item Parkinson's disease questionnaire. A minimally important difference is defined as the smallest change between two scores that is subjectively meaningful to patients. Data on minimally important differences are essential for the calculation of sample sizes in trials and surveys. METHODS We conducted a postal survey of randomly selected members of 13 local branches of the Parkinson's Disease Society, asking them to complete the PDQ-39 on two occasions, 6 months apart. On the first occasion respondents received the PDQ-39, demographic questions and a request to provide their name and address if they were willing to take part in the follow-up survey. After 6 months, we sent those who had agreed another copy of the questionnaire and also asked them to indicate how much change they had experienced since baseline in overall health and in each of the eight domains of the questionnaire. RESULTS We calculated minimally important difference for each dimension and the index score for those reporting minor change since baseline. The minimally important difference varied across dimensions. CONCLUSIONS These results indicate the minimum magnitude of change that should be sought when designing studies to evaluate change over time in Parkinson's disease. Since minimally important differences differ across dimensions, those designing studies in which sample size calculations are based on the PDQ-39 as an outcome measure should select the dimension which is the primary variable of interest.
Is Type 1 Diabetes in the Japanese Population the Same as among Caucasians?

Abstract: In the Japanese population, the incidence of type 1 diabetes is as low as ∼2 cases/year/100,000 children, which is much lower compared to that in countries with populations predominantly of Caucasian origin. However, the prevalences of anti‐islet autoantibodies in patients with Japanese type 1 diabetes are 60‐70% for GAD autoantibodies, 45‐50% for insulin autoantibodies (IAA), and 60‐65% for IA‐2 autoantibodies at disease onset, which are similar to those reported in Caucasian patients. With combinatorial analysis of these autoantibodies, 90% of patients express at least one of these autoantibodies and are classified as type 1A diabetics. There is a significant number of patients with latent autoimmune diabetes in adults (LADA) in Japan, and a high level of GAD autoantibodies has a high predictive value for future insulin deficiency in such patients. Recently, it has been reported that a group of extremely rapid‐onset patients presented with diabetic ketoacidosis and a low HbA1c level, called fulminant diabetes mellitus. Although they had severe hyperglycemia, these individuals lacked the expression of anti‐islet autoantibodies. With a nationwide survey, it was documented that fulminant type 1 diabetes accounts for ∼20% of the ketosis‐onset patients with type 1 diabetes in Japan. It is currently unknown whether the pathogenesis of fulminant type 1 diabetes is associated with autoimmune response to pancreatic islet β cells. Japanese patients with type 1 diabetes are clinically heterogeneous, and further investigations are required to clarify the underlying pathogenesis for each subgroup of type 1 diabetes.
Epstein‐Barr virus and gastric carcinoma

Epstein‐Barr virus (EBV) has been accepted as an infective agent causing gastric carcinoma (GC). Epstein‐Barr virus‐associated GC, comprising nearly 10% of all cases of GC, is the monoclonal growth of EBV‐infected epithelial cells, which express several EBV‐latent genes (latency I program). Sequential events in the gastric mucosa could be traced from EBV infection of the pit cells to fully developed carcinomas by EBV encoded small RNA (EBER)‐in situ hybridization. The histological features of the carcinoma consist of a lace pattern of carcinoma cells within the mucosa and the dense infiltration of lymphocytes and macrophages at the invasive site, which might be due to cytokines produced by neoplastic cells. The primary molecular abnormality in EBV‐associated GC is global and non‐random CpG island methylation in the promoter region of many cancer‐related genes. The experimental system of recombinant EBV infection using GC cell lines demonstrated that viral latent membrane protein 2A (LMP2A) is responsible for the promotion of DNA methylation. LMP2A up‐regulates cellular DNMT1 through the phosphorylation of STAT3, causing CpG methylation of a tumor suppressor gene, PTEN. DNA methylation in EBV‐infected stomach cells may be due to overdrive of the cellular defense against foreign DNA, which eventually leads to the development of EBV‐associated GC.
Human immunodeficiency virus-related microbial translocation and progression of hepatitis C.

BACKGROUND & AIMS Human immunodeficiency virus (HIV)-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation. METHODS We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized. RESULTS HIV-related CD4(+) lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS-binding protein, soluble CD14, and fucose-binding lectin (AAL) reactive to immunoglobulin G specific for the alpha-galactose epitope and suppressed levels of endotoxin core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIV-uninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), eg, LPS, odds ratio, 19.0 (P = .002); AAL, odds ratio, 27.8 (P < .0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis. CONCLUSIONS Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.
Ethical issues in the managed care setting: a new curriculum for primary care physicians

Several challenging ethical issues have been associated with the shift to managed healthcare in the United States. Our objective was to develop, implement, and evaluate a curriculum designed to help physicians identify and examine ethical issues encountered in the managed care setting. The curriculum was developed during a year-long workshop at Johns Hopkins Bayview Medical Center. The content of the curriculum was established through literature review, focus group discussions with physicians, and a needs assessment of targeted learners (primary care physicians practicing in managed care settings). Some of the key issues addressed in the curriculum include: changing professional responsibilities of physicians; fair use of resources; and threats to the doctor-patient relationship as a consequence of the new healthcare delivery system. The 7.5-h curriculum was taught over five sessions using varied teaching methods. Evaluations demonstrated that the curriculum was successful in increasing learner awareness of ethical issues confronted in the managed care environment and improved learner knowledge in these areas. The physician-learners reported that this educational experience would change their teaching of medical students and residents. After completing the curriculum, learners felt that they were at least somewhat better able to cope with ethical challenges encountered in the managed care setting. Future research might examine whether such a curriculum could positively affect physician behavior or enhance physician satisfaction with the managed care setting.
Disparity in Performance of the Czech Construction Sector: Evidence from the Markov-Switching Model

Activities in the construction sector are assumed to be influenced by inflow of mortgage funding in the private housing sector and public finances targeted at large infrastructure projects, apart from climate variables. In this study, we modeled seasonal time series representing monthly output in the Czech construction sector in CZK mil. during 2000:1 through 2016 : 12 (T = 204) adjusted for calendar variations and seasonal movements via TRAMO‑SEATS and then transformed to natural logarithms of gross returns. A Markov‑Switching model with two states, no intercept, average monthly temperature, average monthly precipitation and parameters of first‑order autoregression process was specified and estimated by the Expectation‑Maximization. In State 1 of regular performance, the log‑differenced returns were significantly and positively influenced by precipitation levels, but not by ambient outdoor temperature. In State 2 of non‑standard operation of the construction sector, the transformed series was unaffected by precipitation levels, but instead by ambient outdoor temperatures. First‑order autocorrelation dependency in both regimes was established. Changes in legal and macroeconomic environment pertinent to tax law amendments affecting VAT or corporate tax, country’s accession to EU or large construction project deadlines were shown to induce nonstandard regime in the construction sector (State 2). The model classified 91 % observations in the first state, while only 9 % data belonged to the State 2. Transition probability matrix indicates that change from model State 1 to State 2 is difficult to attain. At the same time, once State 2 was established, it tends to persist or change to State 1 with near equal probability. Ability of the Markov‑Switching model to identify both states is reasonably good.
Intracellular FRET-based probes: a review

Probes that exploit Förster resonance energy transfer (FRET) in their feedback mechanism are touted for their sensitivity, robustness, and low background, and thanks to the exceptional distance dependence of the energy transfer process, they provide a means of probing lengthscales well below the resolution of light. These attributes make FRET-based probes superbly suited to an intracellular environment, and recent developments in biofunctionalization and expansion of imaging capabilities have put them at the forefront of intracellular studies. Here, we present an overview of the engineering and execution of a variety of recent intracellular FRET probes, highlighting the diversity of this class of materials and the breadth of application they have found in the intracellular environment.
CRITICAL PEDAGOGY - MOVEMENT FOR STUDENTS VOICE, TEACHER′S AUTHORITY AND EQUALITY IN EDUCATION

Critical pedagogy has significant place among the papers of numerous researchers and theoretician of education especially in the USA. The central focus of this paper is directed to historical development of critical pedagogy, the most significant postulates and on ideas of their bearer. The starting points for considering presents the ideas of critical pedagogues as Paulo Freire and Henry Giroux, ideas of Jean Jacques Rousseau and John Dewey that are considered as forerunners of this movement, until the contemporary representatives of critical pedagogy who continued to support and develop this approach. The aim of this paper is to consider the influence of critical pedagogy and its representatives on school practice and education. It can be concluded that promoted idea, which was created and developed in critical pedagogy that education is never „sterile clean“, is impregnated with reflections of numerous political, economic and social circumstances, and it stayed as future vision to be considered by theoretician of education, pedagogues and pedagogy of future. At the end, some of the implications for modern pedagogical practice, formed by analyzing the critical pedagogy and needed to nurture in school practice are separated, those implications are developing teachers’ critical spirit and its autonomy, nurturing the quality in relations with students that induce their development and improve outcomes, the strength of the dialogue culture which respects the right to be different and which straightens the ethical responsibility of teachers that represents the basics of teachers’ identity development and building of their profession.
Lifestyles, flying and associated health problems in flight attendants

Aims: This study was conducted in order to investigate the effect of flying on Indian male and female flight attendants (FAs), flying for over 10 years and up to 30 years. Methods: The FAs selected for this study were subjected to the same set of conditions, such as number of hours flown per month and flight routes. Questionnaires were prepared, based on complaints heard on a regular basis, and also after talking to a small sample of FAs. Nearly 100 completed questionnaires were returned, from 500 delivered directly to FAs by post. In addition to this, we met 130 FAs either before their departure or after their arrival and secured completed questionnaires from them, being sure to maintain anonymity. Results: According to this study there are five major problems faced by the FAs: Stress (88.85%) Back pain (72.65%) Loss of memory (67.47%) Headaches (58.42%) Loss of hearing (51.37%) 88.85% of FAs have reported feeling stressed `often' or `sometimes'. Many participants felt that if the work environment were more employee-friendly their stress level might come down. Back pain was reported by 72.65% of FAs which, according to them, could be largely remedied by being provided with better equipment and user-friendly galleys. Loss of memory was prevalent in 67.47% of FAs studied. 58.42% of FAs suffer from headaches. Stress, loss of memory and headaches seem to share the same etiology such as hypoxia, jetlag and irregular sleep. Diminished hearing, prevalent in 51.37% of FAs, was not a major cause of worry but was largely perceived as an inconvenience. Conclusions: These occupational health problems of flight attendants require serious and immediate attention.
Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population.

BACKGROUND Cleft lip with or without cleft palate (CL/P) is one of the most common craniofacial malformations, with a complex and multifactorial etiology. Because of the genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported candidate genes and chromosomal loci to the risk of CL/P in the Polish population. METHODS We performed an analysis of 18 polymorphisms of FOXE1, IRF6, MSX1, PAX9, TBX10, FGF10, FGFR1, TGFalpha, TGFbeta3, SUMO1, and the chromosomal region 8q24 in a group of 175 patients with CL/P and a properly matched control group. RESULTS Highly significant results were observed for the IRF6 rs642961 variant and the 8q24 region's rs987525 (odds ratio [OR](AG+AAvsGG), 1.635; 95% confidence interval [CI], 1.153-2.319; p = 0.005; and OR(AC+AAvsCC), 1.962; 95% CI, 1.382-2.785; p = 1.4 x 10(-4), respectively). For rs987525, the results were also significant after correction for multiple comparisons. Borderline association with an increased risk of CL/P was also identified for the SUMO1 locus (rs2350350; OR(CGvsGG), 1.580; 95% CI, 1.056-2.363; p = 0.025). CONCLUSIONS Our findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample.
Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations

Elevation in plasma homocysteine concentration has been associated with vascular disease and neural tube defects. Methionine synthase is a vitamin B12‐dependent enzyme that catalyses the remethylation of homocysteine to methionine. Therefore, defects in this enzyme may result in elevated homocysteine levels. One relatively common polymorphism in the methionine synthase gene (D919G) is an A to G transition at bp 2,756, which converts an aspartic acid residue believed to be part of a helix involved in co‐factor binding to a glycine. We have investigated the effect of this polymorphism on plasma homocysteine levels in a working male population (n = 607) in which we previously described the relationship of the C677T “thermolabile” methylenetetrahydrofolate reductase (MTHFR) polymorphism with homocysteine levels. We found that the methionine synthase D919G polymorphism is significantly (P = 0.03) associated with homocysteine concentration, and the DD genotype contributes to a moderate increase in homocysteine levels across the homocysteine distribution (OR = 1.58, DD genotype in the upper half of the homocysteine distribution, P = 0.006). Unlike thermolabile MTHFR, the homocysteine‐elevating effects of the methionine synthase polymorphism are independent of folate and B12 levels; however, the DD genotype has a larger homocysteine‐elevating effect in individuals with low B6 levels. This polymorphism may, therefore, make a moderate, but significant, contribution to clinical conditions that are associated with elevated homocysteine. Genet. Epidemiol. 17:298–309, 1999. © 1999 Wiley‐Liss, Inc.
Patient‐centered care and adherence: Definitions and applications to improve outcomes

PurposeThe implementation of patient-centered care (PCC) has been hampered by the lack of a clear definition and method of measurement. The purpose of this review is to identify the fundamental characteristics of PCC to clarify its definition, propose a method for measurement of PCC, and recommend effective PCC practices. Data sourcesReview of literature related to PCC, adherence and communication from Cinahl, PubMed Academic Search Premier, and Cochrane Library databases. ConclusionsResearch has shown that patient-centered interactions promote adherence and lead to improved health outcomes. The fundamental characteristics of PCC were identified as (a) patient involvement in care and (b) the individualization of patient care. The use of a numeric rating scale to measure the presence of these characteristics allows quantification from the patient perspective. Effective PCC practices were related to communication, shared decision making, and patient education. Implications for practicePCC is a measure of the quality of health care. Understanding the characteristics of PCC facilitates its implementation and measurement. Promoting PCC activities will improve adherence and encourage patient responsibility for health status.
The global currency tango — The relationship between the carry trade, emerging/commodity currencies and risk

ABSTRACT This study has foci on the global drivers of currencies and their relationship to economic jurisdiction in the presence of global risk appetite. We focus on a comprehensive basket of global currencies, deriving three statistically motivated currency market factors. We cluster on these factor loadings and find three currency groupings – Developed/European, Emerging/Commodity as well as an Asian currency cluster. Constructing ‘risk states’ based on the VIX Volatility Index, we find that Developed/European and Emerging/Commodity cluster currencies are better explained by the first three principal components when in the ‘Low’ and ‘High’ risk states respectively. As previously corroborated in the literature, we find evidence that the second principal component is a ‘carry trade factor’. We detail that the impact of this factor on currencies in the Emerging/Commodity cluster is heightened (for both positive and negative changes) by ‘High’ risk states.
Cloning of genes encoding a 15,000-dalton peptidoglycan-associated outer membrane lipoprotein and an antigenically related 15,000-dalton protein from Haemophilus influenzae

We have cloned and expressed in Escherichia coli a gene encoding a 15,000-apparent-molecular-weight peptidoglycan-associated outer membrane lipoprotein (PAL) of Haemophilus influenzae. The nucleotide sequence of this gene encodes an open reading frame of 153 codons with a predicted mature protein of 134 amino acids. The amino acid composition and sequence of the predicted mature protein agree with the chemically determined composition and partial amino acid sequence of PAL purified from H. influenzae outer membranes. We have also identified a second gene from H. influenzae that encodes a second 15,000-apparent-molecular-weight protein which is recognized by antiserum against PAL. This protein has been shown to be a lipoprotein. The nucleotide sequence of this gene encodes an open reading frame of 154 codons with a predicted mature protein of 136 amino acids and has limited sequence homology with that of the gene encoding PAL. Southern hybridization analysis indicates that both genes exist as single copies in H. influenzae chromosomal DNA. Both genes encode polypeptides which have amino-terminal sequences similar to those of reported membrane signal peptides and are associated primarily with the outer membrane when expressed in E. coli.
Intravenous Transfusion of BCR-Activated B Cells Protects NOD Mice from Type 1 Diabetes in an IL-10-Dependent Manner1

Although B cells play a pathogenic role in the initiation of type 1 diabetes (T1D) in NOD mice, it is not known whether activated B cells can maintain tolerance and transfer protection from T1D. In this study, we demonstrate that i.v. transfusion of BCR-stimulated NOD spleen B cells into NOD mice starting at 5–6 wk of age both delays onset and reduces the incidence of T1D, whereas treatment initiated at 9 wk of age only delays onset of T1D. This BCR-activated B cell-induced protection from T1D requires IL-10 production by B cells, as transfusion of activated B cells from NOD.IL-10−/− mice does not confer protection from T1D. Consistent with this result, severe insulitis was observed in the islets of NOD recipients of transfused NOD.IL-10−/− BCR-stimulated B cells but not in the islets of NOD recipients of transfused BCR-stimulated NOD B cells. The therapeutic effect of transfused activated NOD B cells correlates closely with the observed decreased islet inflammation, reduced IFN-γ production and increased production of IL-4 and IL-10 by splenocytes and CD4+ T cells from NOD recipients of BCR-stimulated NOD B cells relative to splenocytes and CD4+ T cells from PBS-treated control NOD mice. Our data demonstrate that transfused BCR-stimulated B cells can maintain long-term tolerance and protect NOD mice from T1D by an IL-10-dependent mechanism, and raise the possibility that i.v. transfusion of autologous IL-10-producing BCR-activated B cells may be used therapeutically to protect human subjects at risk for T1D.