Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell sorting enables interphase fluorescence in situ hybridization detection of low BCR‐ABL1 producing stem cells in chronic myeloid leukaemia patients beyond deep molecular remission

The exact disease state of chronic myeloid leukaemia (CML) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (qPCR) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate this, CD34+ stem cell and progenitor cell subpopulations were isolated by fluorescence‐activated cell sorting (FACS), and their content of residual Philadelphia positive (Ph+) cells was evaluated in 17 CML patients (major molecular response, n = 6; 4‐log reduction in BCR‐ABL1 expression (MR4), n = 11) using both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH). Despite evaluating fewer cells, iFISH proved superior to mRNA‐based qPCR in detecting residual Ph+ stem cells (P = 0·005), and detected Ph+ stem‐ and progenitor cells in 9/10 patients at frequencies of 2–14%. Moreover, while all qPCR+ samples also were iFISH+, 9/33 samples were qPCR‐/iFISH+, including all positive samples from MR4 patients. Our findings show that residual Ph+ cells are low BCR‐ABL1 producers, and that DNA‐based methods are required to assess the content of persisting Ph+ stem cells in these patients. This approach demonstrates a clinically applicable manner of assessing residual disease at the stem cell level in CML patients in MR4, and may enable early and safe identification of candidates for tyrosine kinase inhibitor withdrawal.
Efficacy and safety of nifedipine GITS in Chinese patients with hypertension – A post‐marketing surveillance study

Purpose. This post‐marketing surveillance study assessed the efficacy, safety and tolerability of the treatment with nifedipine GITS (gastro‐intestinal therapeutic system) in hypertensive patients under normal daily practice conditions in China. Patients and methods. A total of 3003 patients were included in 174 outpatient clinics. Patients received 30 mg or 60 mg of nifedipine GITS. Data were collected at up to three follow‐up visits. Results. At the end of the observation period, mean treatment duration was 13.3 weeks. Mean blood pressure reduction was 27.6/13.6 mmHg, 62.1% of patients had a systolic blood pressure <140 mmHg, and 82.2% had a diastolic blood pressure <90 mmHg. Blood pressure control according to international guidelines was achieved in 45.0% of all patients. A total of 1515 patients received additional antihypertensive medications, of which angiotensin‐converting enzyme (ACE) inhibitors were mostly used (42.2%) followed by beta‐blockers (33.7%). Twenty‐two patients (0.7%) experienced 27 adverse events. Physicians' assessments of efficacy, tolerability and patient acceptance had ratings of “very good” and “good” in 88.7% (efficacy), 92.8% (tolerability) and 89.1% (patient acceptance) of patients. Conclusions. Nifedipine GITS proved to be effective and well tolerated for the treatment of hypertension in 3003 Chinese patients. The results confirm the findings of previously performed clinical studies.
Prevalence of current and chronic pain and their influences upon work and healthcare-seeking: a population study.

OBJECTIVE To investigate the prevalence of current and chronic pain and their relationship to pain intensity, sex, age, income, employment status, citizenship, marital status, urban residence, occupational activity, and healthcare-seeking based on a representative sample from a Swedish county. METHODS A cross-sectional survey using a postal questionnaire was sent to a representative sample (n = 9952) of the target population (284,073 people, age 18-74 yrs) in a county (Ostergötland) in southern Sweden. A questionnaire was mailed and followed by 2 postal reminders if necessary. RESULTS The participation rate was 76.7% (n = 7637); nonparticipants were on average younger, male, and earned less money. The overall point prevalence of pain was 48.9%. The corresponding one-month period prevalence was 63.0%, and pain on several occasions during the previous 3 months was reported by 61.3% of participants. The prevalence of chronic pain (pain > 3 months) was 53.7%. Female sex, age, and sick leave/early retirement were generally of significant importance in the regressions of pain. No sex factor was found in the regressions of pain frequency and pain intensity. Chronic pain especially frequent and intensive pain showed clear associations with healthcare-seeking and occupational activity. CONCLUSION High prevalence of current pain (48.9%) and chronic pain (53.7%) were found in this community-based study. Being female, older, and on sick leave or early retirement were generally of significant importance in the regressions of pain. Chronic pain showed clear associations with healthcare-seeking and occupational activity, indicating considerable socioeconomic costs.
Anomaly detection from multivariate time-series with sparse representation

Anomaly detection from sensor data is an important data mining application for efficient and secure operation of complicated systems. In this study, we propose a novel anomaly detection method for multivariate time-series to capture relationships of variables and time-domain correlations simultaneously, without assuming any generative models of signals. The supposed framework in this study is a semi-supervised anomaly detection where we seek unusual parts of test data compared with reference data. The proposed method is based on feature extraction with sparse representation and relationship learning with dimensionality reduction. Our idea comes from the similarity between a sparse feature matrix extracted from multivariate time-series and a term-document matrix. We conducted experiments with synthetic and simulated data, and confirmed that the proposed method successfully detected anomalies in multivariate time-series signals. Especially, it demonstrated superior performance with anomalies in which only relationships of time-series patterns are changed from reference data (multivariate anomalies).
Rising Out-of-Pocket Spending for Medical Care: A Growing Strain on Family Budgets

Since the late 1990s, accelerated growth in health care spending has translated into increased burdens on family budgets. In 2001–02, an average of 13 million families per year had direct out-of-pocket (OOP) costs equal to or exceeding 10 percent of family income. When premium costs are added into the equation, even more families are devoting a substantial share of resources to health care expenses. Using data from the Medical Expenditure Panel Survey to examine trends in family OOP spending between 1996–97 and 2001–02, this report examines the components of OOP spending and characteristics of families with high OOP costs, including income level and insurance coverage. Families struggling with high OOP expenses are more likely than other families to report difficulties in obtaining needed care, and often have trouble paying their bills—increasing the possibility that they may face debt or bankruptcy or drop coverage altogether. Support for this research was provided by The Commonwealth Fund. The views presented here are those of the authors and not necessarily those of The Commonwealth Fund or its directors, officers, or staff. This and other Fund publications are online at www.cmwf. org. To learn more about new publications when they become available, visit the Fund’s Web site and register to receive e-mail alerts. Commonwealth Fund pub. no. 887.
Toll-like receptor 4 involvement in hepatic ischemia/reperfusion injury in mice.

BACKGROUND Toll-like receptor 4 (TLR4) is involved in innate immunity by recognizing endotoxin resulting in a burst of inflammatory cascade. We investigated the relation between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice. METHODS TLR4-deficient mice (C3H/Hej) and wild type mice (WT, C3H/Heouj) were used in the model of I/R injury. Partial hepatic ischemia was produced by occlusion of inflow to the median and left lobes for 45 minutes. Blood was drawn at 1 and 3 hours after reperfusion. The blood was analyzed for aspartate aminotransferase (AST) and tumor necrosis factor alpha (TNF-alpha). TNF-alpha mRNA expression and myeloperoxidase (MPO) level in the ischemic lobes were examined by northern blot and myeloperoxidase assay respectively. RESULTS AST levels were significantly decreased in TLR4deficient mice compared with WT mice at both time points (WT: 1215.5+/-174.03, 2958.17+/-186.81 IU/L at 1 and 3 hours respectively vs TLR4def: 661.83+/-106.09, 1145.17+/-132.43 IU/L at 1 and 3 hours, mean+/-SD, 6 mice/group, t=-6.65 and -5.57, P<0.001). Consistent with the role of TNF-alpha in hepatic I/R, serum TNF-alpha was decreased in TLR4 deficient mice at 3 hours after reperfusion compared with WT (152.39+/-43.3 vs 249.12+/-51.89, n=6, t=-3.13, P<0.05). MPO level in the ischemic lobes in TLR4 deficient mice at 3 hours after reperfusion was significantly lower than that in WT mice (0.059 +/-0.004 vs 0.173+/-0.025, n=6, F=33.49, P<0.001). This difference appears to be mediated at the gene level since TLR4 deficient mice had decreased TNF-alpha mRNA expression at 1 hour after reperfusion compared with WT mice (80.3+/-28.8 vs 189.4+/-24.6, t=-3.25, P<0.05). CONCLUSIONS Compared with WT mice, TLR4-deficient mice appear to have a mild I/R injury. Regulation of TNF-alpha at mRNA level seems to have a critical effect. These suggest TLR4 be involved in the mechanism of hepatic I/R injury in mice.
Risk of myocardial infarction associated with chronic hepatitis C virus infection: a population‐based cohort study *

Summary. Hepatitis C virus (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis. However, it remains unclear if HCV infection increases the risk of acute myocardial infarction (MI). To determine whether HCV infection is an independent risk factor for acute MI among adults followed in general practices in the United Kingdom (UK), a retrospective cohort study was conducted in The Health Improvement Network, from 1996 through 2008. Patients ≥18 years of age with at least 6 months of follow‐up and without a prior history of MI were eligible for study inclusion. HCV‐infected individuals, identified with previously validated HCV diagnostic codes (n = 4809), were matched on age, sex and practice with up to 15 randomly selected patients without HCV (n = 71 668). Rates of incident MI among patients with and without a diagnosis of HCV infection were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards regression, controlling for established cardiovascular risk factors. During a median follow‐up of 3.2 years, there was no difference in the incidence rates of MI between HCV‐infected and ‐uninfected patients (1.02 vs 0.92 events per 1000 person‐years; P = 0.7). HCV infection was not associated with an increased risk of incident MI (adjusted HR, 1.10; 95% confidence interval [CI], 0.67–1.83). Sensitivity analyses including the exploration of a composite outcome of acute MI and coronary interventions yielded similar results (adjusted HR, 1.16; 95% CI, 0.77–1.74). In conclusion, HCV infection was not associated with an increased risk of incident MI.
Enabling Smart Transportation Systems: A Parallel Spatio-Temporal Database Approach

We are witnessing increasing interests in developing “smart cities” which helps improve the efficiency, reliability, and security of a traditional city. An important aspect of developing smart cities is to enable “smart transportation,” which improves the efficiency, safety, and environmental sustainability of city transportation means. Meanwhile, the increasing use of GPS devices has led to the emergence of big trajectory data that consists of large amounts of historical trajectories and real-time GPS data streams that reflect how the transportation networks are used or being used by moving objects, e.g., vehicles, cyclists, and pedestrians. Such big trajectory data provides a solid data foundation for developing various smart transportation applications, such as congestion avoidance, reducing greenhouse gas emissions, and effective traffic accident response, etc. Instead of proposing yet another specific smart transportation application, we propose the parallel-distributed network-constrained moving objects database (PD-NMOD), a general framework that manages big trajectory data in a scalable manner, which provides an infrastructure that is able to support a wide variety of smart transportation applications and thus benefiting the smart city vision as a whole. The PD-NMOD manages both transportation networks and trajectories in a distributed manner. In addition, the PD-NMOD is designed to support general SQL queries over moving objects and to efficiently process the SQL queries on big trajectory data in parallel. Such design facilitates smart transportation applications to retrieve relevant trajectory data and to conduct statistical analyses. Empirical studies on a large trajectory data set collected from 3,500 taxis in Beijing offer insight into the design properties of the PD-NMOD and offer evidence that the PD-NMOD is efficient and scalable.
Association of iron overload and oxidative stress with insulin resistance in transfusion-dependent beta-thalassemia major and beta-thalassemia/HbE patients.

BACKGROUND Beta-thalassemia causes a severe hemolytic anemia in patients necessitating frequent transfusions leading to iron overload and endocrine complications, especially diabetes mellitus. We tried to determine the change or effect on carbohydrate physiology and oxidation markers and the association of these markers in chronic transfusion-dependent beta-thalassemia major and beta-thalassemia/HbE (beta-TM) patients. METHODS Prospective study on 60 beta-TM patients, receiving only regular blood transfusions, and 20 healthy controls were enrolled for oral glucose tolerance test, fasting insulin, Homeostasis Model Assessment of insulin resistance (HOMA-IR), liver function test, iron overload, oxidative stress, and lipid profile at baseline. The same tests were repeated after 6 months. RESULTS One beta-TM patient had impaired glucose tolerance. Fasting glucose, insulin, ferritin, MDA, TG concentrations, HOMA-IR, and liver profiles were significantly higher while Hb, Hct, TC, HDL-C, LDL-C concentrations and TAC were significantly lower in beta-TM patients than controls (p < 0.001). Fasting glucose, HOMA-IR and beta-cell function were significantly correlated with MDA and glucose, AST, ALT, MDA were significantly correlated with ferritin (p < 0.05). Multiple forward stepwise linear regression analyses of the significant variables showed that in these beta-TM patients, independent predictors of HOMA-IR were fasting glucose (beta = 0.634, r2 = 0.374, p < 0.001), HDL-C (beta = 0.249, r2 = 0.418, p = 0.043) and MDA (beta = 0.225, r2 = 0.466, p = 0.029). CONCLUSIONS Progression of iron overload, oxidative stress and hyperinsulinemia were substantially and persistently higher in beta-TM patients. We observed a positive association between oxidative stress, iron overload and insulin resistance in these beta-TM patients.
Association games in IEEE 802.11 wireless local area networks

In IEEE 802.11 wireless networks, users associate with access points that can provide the best service quality. In this paper, we analyze the convergence and steady state performance of a practically well performing load-based user association scheme. The analysis is based on a novel game theoretical model, which extends the results on atomic congestion games. We prove the existence of and convergence to a Nash equilibrium for this game. The bounds on the efficiency of equilibrium compared to centralized optimum solutions are established under different system costs.
IVIG‐bound IgG and IgM cloned by phage display from a healthy individual reveal the same restricted germ‐line gene origin as in autoimmune thrombocytopenia

Intravenous immunoglobulin preparations (IVIG) have shown positive effects in the treatment of immune defects and autoimmune diseases. It is not clear how IVIG interacts with the components of the immune system. To investigate this, we cloned previously a large number of phage displayed IgG Fab fragments derived from three patients with autoimmune thrombocytopenia (AITP) that were specifically bound by IVIG molecules. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used germ‐line gene segments of all IVIG‐bound Fabs were identical to those observed for many other autoantibodies. Particularly, the loci 3–30 or 3–30/3–30.5, 3–23 and 3r, 3l, and 2a2 represented the most abundant genes used for the heavy (VH) and light chain V region (VL), respectively. This suggested a specific interaction of IVIG molecules with B cells that present B cell receptors derived from these germ‐line genes. In the current study we determined the genetic origin of IVIG‐reactive IgG and IgM cloned from a healthy person. A favoured selection of antibodies derived from the same germ‐line origins as in AITP was observed. Because 3–30 and 3–23 are the most frequently rearranged VH germ‐line gene segments among human B cells, our results suggest that this favoured anti‐idiotypic interaction may have an important role for the development and control of the normal B cell repertoire.
Cloning and bacterial expression of the CYS3 gene encoding cystathionine gamma-lyase of Saccharomyces cerevisiae and the physicochemical and enzymatic properties of the protein

By screening a yeast genomic library, we isolated and characterized a gene rescuing the cysteine requirement in a "cys1" strain of Saccharomyces cerevisiae. Except for four residues in the open reading frame composed of 1,182 nucleotides, the DNA sequence was the same as that for the CYS3 (CYI1) gene, encoding cystathionine gamma-lyase (EC 4.4.1.1), and isolated previously as a cycloheximide-induced gene (B. Ono, K. Tanaka, K. Naito, C. Heike, S. Shinoda, S. Yamamoto, S. Ohmori, T. Oshima, and A. Toh-e, J. Bacteriol. 174:pp.3339-3347, 1992). S. cerevisiae "cys1" strains carry two closely linked mutations; one (cys1) causes a defect in serine O-acetyltransferase (EC 2.3.1.30), and another, designated cys3, impairs cystathionine gamma-lyase activity. Rescue of the cysteine requirement by the gene encoding cystathionine gamma-lyase is consistent with both defects being responsible for the cysteine auxotrophy. In an effort to further determine the physicochemical and enzymatic properties of this enzyme, a coding fragment was cloned into an Escherichia coli expression plasmid, and the protein was produced in the bacteria. The induced protein was extracted by sonication and purified to homogeneity through one course of DEAE-cellulose column chromatography. The yield of the protein was approximately 150 mg from cells cultured in 1 liter of L broth. The protein showed molecular weights of approximately 194,000 and 48,000 (for the subunit), suggesting a tetrameric structure. An s20,w value of 8.8 was estimated by centrifugation in a sucrose concentration gradient. No sulfhydryl groups were detected, which is consistent with the absence of cysteine residues in the coding sequence. The isoelectric point was at pH 5.2. The protein showed a number of cystathionine-related activities, i.e., cystathionine beta-lyase (EC 4.4.1.8), cystathionine gamma-lyase, and cystathionine gamma-synthase (EC 4.2.99.9) with L-homoserine as substrate. In addition, we demonstrated L-homoserine sulfhydrylase (adding H2S) activity but could find no detectable serine O-acteyltransferease activity. In this paper, we compare the enzymatic properties of the protein with those of homologous enzymes previously reported and discuss the possibility that this enzyme has a physiological role as cystathionine Beta-lyase and cystathionine gamma-synthase in addition to its previously described role as cystathionine gamma-lyase.
Distributional Implications of Joint Tax Evasion

Both buyers and sellers of goods and services may bene.t from letting their economic transactions go unrecorded for tax purposes. The supplier reduces his tax burden by underreporting income, whereas the consumer gains from buying a non-taxed lower-priced product. The distributional implications of such joint tax evasion depend on the amounts evaded, on where the evaders on both sides of the market are found in the income distribution and how the financial gain is split between the suppliers and demanders. We use various data sources to identify tax evasion among sellers and buyers of goods and services. Results clearly suggest that the tax-evasion-controlled estimate of income inequality in Norway exhibits more income dispersion than official estimates.
Measuring Participants' Attitudes Toward Mobile Device Conference Applications in Continuing Medical Education: Validation of an Instrument

Introduction: Mobile device applications (apps) may enhance live CME courses. We aimed to (1) validate a measure of participant attitudes toward using a conference app and (2) determine associations between participant characteristics and attitudes toward CME apps with conference app usage. Methods: We conducted a cross-sectional validation study of participants at the Mayo Clinic Selected Topics in Internal Medicine Course. A conference app was developed that included presentation slides, note-taking features, search functions, social networking with other attendees, and access to presenter information. The CME app attitudes survey instrument (CMEAPP-10) was designed to determine participant attitudes toward conference apps. Results: Of the 602 participants, 498 (82.7%) returned surveys. Factor analysis revealed a two-dimensional model for CMEAPP-10 scores (Cronbach &agr;, 0.97). Mean (SD) CMEAPP-10 scores (maximum possible score of five) were higher for women than for men (4.06 [0.91] versus 3.85 [0.92]; P = .04). CMEAPP-10 scores (mean [SD]) were significantly associated (P = .02) with previous app usage as follows: less than once per month, 3.73 (1.05); monthly, 3.41 (1.16); weekly, 4.03 (0.69); and daily or more, 4.06 (0.89). Scores were unrelated to participant age, specialty, practice characteristics, or previous app use. Discussion: This is the first validated measure of attitudes toward CME apps among course participants. App usage was higher among younger participants who had previously used educational or professional apps. Additionally, attitudes were more favorable among women and those who had previously used apps. These findings have important implications regarding efforts to engage participants with portable and accessible technology.
The absence of the Isw2p–Itc1p chromatin‐remodelling complex induces mating type‐specific and Flo11p‐independent invasive growth of Saccharomyces cerevisiae

The Isw2p–Itc1p chromatin remodelling complex of Saccharomyces cerevisiae is a member of the ISWI class of ATPases with a nucleosome spacing activity, involved in regulation of expression of a broad spectrum of genes. Its absence causes derepression of a‐specific genes and aberrant morphology in α‐mating type cells. We report here that the deletion of the ISW2 gene in the originally non‐invasive BY strain induces mating type‐specific invasive growth strongly affected by nitrogen starvation. Although the Flo11 protein was postulated to be critical for haploid invasive growth, we showed that the invasive growth caused by the isw2 and itc1 deletions in α‐mating type cells was Flo11p‐independent. This type of invasive growth was proved to be a consequence of the activation of the pheromone response pathway. Our results suggest that Isw2 and Itc1 proteins do not have the same impact on the described phenomenon. Copyright © 2004 John Wiley & Sons, Ltd.