Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase II study of biweekly pralatrexate and docetaxel in patients with advanced esophageal and gastroesophageal carcinoma that have failed first-line platinum-based therapy.

BACKGROUND The appropriate second-line therapy for patients with advanced gastroesophageal (GE) or esophageal (E) cancer after failure of first-line platinum-based therapy is unclear. Pralatrexate and docetaxel have independently been shown to have efficacy in the treatment of these cancers. Thus, we performed a clinical trial examining the efficacy of the combination of these agents in the treatment of GE and E cancer. METHODS A Fleming phase II design with a single stage of 32 patients was planned. Pralatrexate 120 mg/m(2) and docetaxel 35 mg/m(2) were administered on day 1 of 14-day cycles. The primary end-point was to evaluate the overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and secondary end-points were to evaluate for progression-free survival (PFS) and overall survival (OS). RESULTS The study was halted prematurely due to loss of funding after the accrual of six patients. Two patients had stable disease (SD) and four patients had disease progression per RECIST. When applying PERCIST criteria in four evaluable patients, two had a partial response (PR) and two had SD. Median PFS was 1.9 months (95% CI, 0.8-7.2) and median OS was 5.5 (0.8-11.7) months. CONCLUSIONS Pralatrexate and docetaxel as therapy in refractory esophageal and GE adenocarcinoma did not demonstrate meaningful preliminary activity. PERCIST may prove to better assess the meaningfulness of anatomic SD.
The effects of yoga on physical functioning and health related quality of life in older adults: a systematic review and meta-analysis.

OBJECTIVE The goal was to review systematically the comparative effectiveness of yoga, compared with other exercise interventions, for older adults as shown on measures of health and physical functioning. DESIGN This was a systematic review with both narrative synthesis and meta-analysis. DATA SOURCES Searches were conducted in MEDLINE®/PUBMED, PSYCINFO, CINAHL, Web of Science, and SCOPUS; bibliographies of selected articles; and one systematic review on the effects of yoga on cardiovascular disease. METHODS Original studies from 1950 to November 2010 were sought, evaluating the effects of yoga on older adults. The search was restricted to randomized controlled trials of yoga in subjects ≥age 60, and published in English. Data were extracted and evaluated regarding setting, population size and characteristics, intervention type and duration, comparison group, outcome assessment, data analysis, follow-up, key results, and the quality of each study according to specific predetermined criteria. RESULTS The search yielded 18 eligible studies (N=649). The studies reported on older adults across a range of settings, intervention intensity, and outcome measures. The majority of the studies had<35 participants (range 9-77). Quantitative and qualitative synthesis of the studies suggested that the benefits of yoga may exceed those of conventional exercise interventions for self-rated health status, aerobic fitness, and strength. However, the effect sizes were modest, and the evidence was mixed for yoga's effect on depression, sleep, and bone-mineral density. Studies did not find an effect on cognition. CONCLUSIONS Small studies with mixed methodological quality suggested that yoga may be superior to conventional physical-activity interventions in elderly people. The precision of the estimates remains low. Larger studies are necessary to define better the intersection of populations, settings, and interventions in which yoga is most beneficial.
Test of YBCO thin films based fault current limiters with a newly designed meander

To facilitate the up scaling of thin film based fault current limiters (FCL), a complete control of the localization of the dissipated power is needed. This control can be achieved by a new design where constrictions, which are regularly located along the YBCO/Au meander, have the aim of localizing and homogenizing this dissipated power at the beginning of a short circuit. To minimize the initial power peak, the resistivity of the constrictions has to be as small as possible whereas the resistivity of the connecting paths should be increased in order to lower the long-term power. We have tested these expected improvements on 5 kW (340 V, 16 A) FCL, on 2'' wafers, in AC conditions. The observed behavior of the FCL during short circuits, initiated at fault angles, confirm that the dissipated power is minimized and distributed, in a controlled way, along the meander. Finally we present measurements of the self-restoring time of the FCL and test on a 10 kW FCL made of two wafers connected in parallel.
Biodegradation of Ether Pollutants by Pseudonocardia sp. Strain ENV478

ABSTRACT A bacterium designated Pseudonocardia sp. strain ENV478 was isolated by enrichment culturing on tetrahydrofuran (THF) and was screened to determine its ability to degrade a range of ether pollutants. After growth on THF, strain ENV478 degraded THF (63 mg/h/g total suspended solids [TSS]), 1,4-dioxane (21 mg/h/g TSS), 1,3-dioxolane (19 mg/h/g TSS), bis-2-chloroethylether (BCEE) (12 mg/h/g TSS), and methyl tert-butyl ether (MTBE) (9.1 mg/h/g TSS). Although the highest rates of 1,4-dioxane degradation occurred after growth on THF, strain ENV478 also degraded 1,4-dioxane after growth on sucrose, lactate, yeast extract, 2-propanol, and propane, indicating that there was some level of constitutive degradative activity. The BCEE degradation rates were about threefold higher after growth on propane (32 mg/h/g TSS) than after growth on THF, and MTBE degradation resulted in accumulation of tert-butyl alcohol. Degradation of 1,4-dioxane resulted in accumulation of 2-hydroxyethoxyacetic acid (2HEAA). Despite its inability to grow on 1,4-dioxane, strain ENV478 degraded this compound for >80 days in aquifer microcosms. Our results suggest that the inability of strain ENV478 and possibly other THF-degrading bacteria to grow on 1,4-dioxane is related to their inability to efficiently metabolize the 1,4-dioxane degradation product 2HEAA but that strain ENV478 may nonetheless be useful as a biocatalyst for remediating 1,4-dioxane-contaminated aquifers.
How might ZNF804A variants influence risk for schizophrenia and bipolar disorder? A literature review, synthesis, and bioinformatic analysis

The gene that encodes zinc finger protein 804A (ZNF804A) became a candidate risk gene for schizophrenia (SZ) after surpassing genome‐wide significance thresholds in replicated genome‐wide association scans and meta‐analyses. Much remains unknown about this reported gene expression regulator; however, preliminary work has yielded insights into functional and biological effects of ZNF804A by targeting its regulatory activities in vitro and by characterizing allele‐specific interactions with its risk‐conferring single nucleotide polymorphisms (SNPs). There is now strong epidemiologic evidence for a role of ZNF804A polymorphisms in both SZ and bipolar disorder (BD); however, functional links between implicated variants and susceptible biological states have not been solidified. Here we briefly review the genetic evidence implicating ZNF804A polymorphisms as genetic risk factors for both SZ and BD, and discuss the potential functional consequences of these variants on the regulation of ZNF804A and its downstream targets. Empirical work and predictive bioinformatic analyses of the alternate alleles of the two most strongly implicated ZNF804A polymorphisms suggest they might alter the affinity of the gene sequence for DNA‐ and/or RNA‐binding proteins, which might in turn alter expression levels of the gene or particular ZNF804A isoforms. Future work should focus on clarifying the critical periods and cofactors regulating these genetic influences on ZNF804A expression, as well as the downstream biological consequences of an imbalance in the expression of ZNF804A and its various mRNA isoforms. © 2013 Wiley Periodicals, Inc.
Shocks fiscales y tasas de ahorro nacional. Alguna evidencia para la economía argentina

Este trabajo analiza los efectos de los shocks fiscales sobre las tasas de ahorro nacional, utilizando modelos de SVAR, con restricciones contemporaneas, y datos trimestrales de la economia Argentina, que cubren el periodo del primer trimestre de 1993 al cuarto trimestre de 2009. Mientras la teoria de la Equivalencia Ricardiana considera que los desequilibrios presupuestarios del gobierno serian neutrales, otras corrientes sostienen que los deficit publicos no serian plenamente compensados por un incremento en el ahorro privado, afectando por tanto al ahorro nacional. Los resultados de las estimaciones muestran que los shocks en los gastos del gobierno reducen permanentemente las tasas de ahorro nacional, mientras que los shocks en la brecha del producto y en los ingresos tributarios tienen un impacto positivo sobre el ahorro a corto plazo. Asimismo, los shocks en los gastos explicarian en proporcion mayor la variacion de las tasas de ahorro nacional, que las innovaciones en los ingresos tributarios, a corto plazo
Demonstration of a [K+,Cl-]-cotransport system in human red cells by its sensitivity to [(dihydroindenyl)oxy]alkanoic acids: regulation of cell swelling and distinction from the bumetanide-sensitive [Na+,K+,Cl-]-cotransport system.

A screening of several families of compounds on NEM-stimulated K+ efflux in human red cells allowed us to select a [(dihydroindenyl)oxy] alkanoic acid (DIOA) as the first potent inhibitor of this K+ flux (IC50 of 10(-5) M) without side effects on the bumetanide-sensitive [Na+,K+,Cl-]-cotransport system. Incubation of human red cells in hypotonic media (179 mosm) increased cell volume (by 18-20%) and provoked the appearance of a DIOA-sensitive K+ efflux of 4.48 +/- 0.83 mmol. (liter of cells X hr)-1 (mean +/- SD of nine experiments). This DIOA-sensitive K+ efflux exhibited a Michaelian-like dependence on the Cl- concentration of the incubation media (freely equilibrated with intracellular Cl-) with an apparent dissociation constant of 39.6 +/- 14.7 mM and a maximal rate of 4.7 +/- 0.9 mmol. (liter of cells X hr)-1 (mean +/- SD of five experiments). The chloride effect was mediated by intracellular and not by extracellular Cl-, as expected for an outward [K+,Cl-]-cotransport. The above properties of DIOA-sensitive K+ efflux clearly confirm that human red cells have a [K+,Cl-]-cotransport system that regulates cell swelling. The regulatory response to hypotonic media was also strongly depressed by cytochalasin B at a concentration of 1 mM, suggesting that the activating signal is probably transduced by the cytoskeleton.
Random plasma glucose and the glucose challenge test in pregnancy.

BACKGROUND The oral glucose tolerance test for detecting women with gestational diabetes is too complicated and prolonged for routine use. Similar and less time consuming screening tests have been proposed including random plasma glucose estimation and the glucose challenge test (blood glucose estimation one hour after a 50 g glucose load). However, in practice, correct timing of the blood sample, which is of critical importance in the interpretation of the results of these tests, is difficult to ensure. This study was designed to evaluate these two screening tests in identifying women with abnormal glucose tolerance in pregnancy. METHODS One hundred and eleven consecutive pregnant women at risk for gestational diabetes and 121 consecutive pregnant women with no risk factors had random plasma glucose estimation followed by the 50 g glucose challenge test at 26 to 30 weeks of gestation. A 100 g 3 hour oral glucose tolerance test was done within two weeks of the screening tests. The sensitivity and specificity of screening tests in predicting abnormal glucose tolerance were calculated. RESULTS Seven (6.3%) women in the high risk group and four (3.3%) in the low risk group had gestational diabetes, while 11 (9.9%) and 8 (6.6%) had impaired glucose tolerance. Random plasma glucose level of 90 mg/dl or greater had a sensitivity of 63% and specificity of 66% in predicting abnormal glucose tolerance, while a threshold level of 115 mg/dl for the glucose challenge test yielded a sensitivity of 63% and a specificity of 55%. CONCLUSIONS Neither random plasma glucose estimation nor the glucose challenge test is a useful screening procedure for abnormal glucose tolerance in pregnancy.
Public Health and Alcohol Licensing in the UK

This article discusses the role of public health in alcohol licensing in the UK, with a particular focus on the implementation of national legislation and guidance in local regulatory environments. It identifies a number of practical and theoretical challenges through an analysis of historical trends in licensing practice, recent policy developments, and key licensing decisions and appeals. There are strong historical precedents for a focus on strategic harm reduction in UK licensing; however, because licensing primarily addresses the proximate effects of retail, the incorporation of health considerations presents novel difficulties. These center on the identification and deployment of data, the attribution of population-level harms to individual outlets, alcohol industry resistance, local authority risk aversion, and epistemological tensions between public health and licensing. The conclusion proposes that for public health perspectives to gain traction in the licensing environment, clear and realistic goals need to be established, research needs to emphasize local data, and there needs to be a better understanding of the approaches to evidence, knowledge, and decision making that characterize licensing and other local regulatory services.
Mini Transsternal Approach to the Anterior High Thoracic Spine (T1–T4 Vertebrae)

Purpose. The anterior high thoracic spine is one of the most complex segments to be accessed surgically due to anatomical constraints and transitional characteristics. We describe in detail the mini transsternal approach to metastatic, infective, traumatic, and degenerative pathologies of T1 to T4 vertebral bodies. We analyse our surgical series, indications, and outcomes. Methods. Over a 5-year period 18 consecutive patients with thoracic myelopathy due to metastatic, infective, traumatic, and degenerative pathologies with T1 to T4 vertebral bodies involvement received a mini transsternal approach with intraoperative monitoring. Frankel scoring system was used to grade the neurological status. Results. Mean follow-up was 40 months. 78% patients improved in Frankel grade after surgery and 22% patients remained unchanged. Average operation time was 210 minutes. There were no intraoperative complications. One patient developed postoperative pneumonia successfully treated with antibiotics. Conclusion. The mini transsternal is a safe approach for infective, metastatic, traumatic, and degenerative lesions affecting the anterior high thoracic spine and the only one allowing an early and direct visualisation of the anterior theca. This approach overcomes the anatomical constraints of this region and provides adequate room for optimal reconstruction and preservation of spinal alignment in the cervicothoracic transition zone with good functional patient outcomes.
Influence of L-Carnitine Supplementation on Serum Lipid Profile in Hemodialysis Patients: A Systematic Review and Meta-Analysis

Background/Aims: An increasing body of evidence demonstrates that L-carnitine plays a pivotal role in lipid metabolism of hemodialysis (HD) patients. However, there are still some reservations about its benefits. Therefore, we performed a meta-analysis to assess the effects of L-carnitine supplementation on lipid profile in HD patients. Methods: Literature search was performed to identify the relevant randomized controlled trials that investigated the effects of L-carnitine on the lipid profile of subjects. Two independent authors used an Excel file to extract data and assess trials quality. The primary effect measure was the difference in means of the final lipid measurements between the intervention and control groups. The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. Results: Twelve studies with a total of 391 patients met the inclusion criteria. The use of L-carnitine was not associated with a reduction in the total cholesterol (SMD, -0.11; 95% CI, -0.31 to 0.09), HDL-cholesterol (SMD, 0.01; 95% CI, -0.36 to 0.39), VLDL-cholesterol (SMD, 0.54; 95% CI, -0.06 to 1.14), and the serum triglycerides (SMD, -0.12; 95% CI, -0.36 to 0.12). However, L-carnitine can significantly decrease the LDL-cholesterol (SMD, -0.29; 95% CI, -0.53 to -0.06) in HD patients. In a subgroup meta-analysis, a significant LDL-cholesterol-lowering effect of L-carnitine supplementation was observed in intravenous application group, and patients with longer interventional duration and renal diseases. Conclusion: The limited evidence suggests that there was no effect of L-carnitine on serum total cholesterol, HDL-cholesterol, VLDL-cholesterol and serum triglycerides. By contrast, this meta-analysis suggests a promising effect of L-carnitine on LDL-cholesterol. Further large-scale, well-designed randomized controlled trials are urgently needed
Multiple functions of GABAA and GABAB receptors during pattern processing in the zebrafish olfactory bulb

γ‐Aminobutyric acid (GABA)ergic synapses are thought to play pivotal roles in the processing of activity patterns in the olfactory bulb (OB), but their functions have been difficult to study during odor responses in the intact system. We pharmacologically manipulated GABAA and GABAB receptors in the OB of zebrafish and analysed the effects on odor responses of the output neurons, the mitral cells (MCs), by electrophysiological recordings and temporally deconvolved two‐photon Ca2+ imaging. The blockade of GABAB receptors enhanced presynaptic Ca2+ influx into afferent axon terminals, and changed the amplitude and time course of a subset of MC responses, indicating that GABAB receptors have a modulatory influence on OB output activity. The blockade of GABAA receptors induced epileptiform firing, enhanced excitatory responses and abolished fast oscillations in the local field potential. Moreover, the topological reorganization and decorrelation of MC activity patterns during the initial phase of the response was perturbed. These results indicate that GABAA receptor‐containing circuits participate in the balance of excitation and inhibition, the regulation of total OB output activity, the synchronization of odor‐dependent neuronal ensembles, and the reorganization of odor‐encoding activity patterns. GABAA and GABAB receptors are therefore differentially involved in multiple functions of neuronal circuits in the OB.
Radon and lung cancer: a cost-effectiveness analysis.

OBJECTIVES This study examined the cost-effectiveness of general and targeted strategies for residential radon testing and mitigation in the United States. METHODS A decision-tree model was used to perform a cost-effectiveness analysis of preventing radon-associated deaths from lung cancer. RESULTS For a radon threshold of 4 pCi/L, the estimated costs to prevent 1 lung cancer death are about $3 million (154 lung cancer deaths prevented), or $480,000 per life-year saved, based on universal radon screening and mitigation, and about $2 million (104 lung cancer deaths prevented), or $330,000 per life-year saved, if testing and mitigation are confined to geographic areas at high risk for radon exposure. For mitigation undertaken after a single screening test and after a second confirmatory test, the estimated costs are about $920,000 and $520,000, respectively, to prevent a lung cancer death with universal screening and $130,000 and $80,000 per life-year for high risk screening. The numbers of preventable lung cancer deaths are 811 and 527 for universal and targeted approaches, respectively. CONCLUSIONS These data suggest possible alternatives to current recommendations.
Vascular CXCR4 Expression Promotes Vessel Sprouting and Sensitivity to Sorafenib Treatment in Hepatocellular Carcinoma

Purpose: C-X-C chemokine receptor type 4 (CXCR4) is known to be involved in both developmental and adult angiogenesis; however, its role in tumor angiogenesis remains largely unknown. Here, the role of vascular CXCR4 in regulating vascular structure in hepatocellular carcinoma (HCC) was assessd, and the clinical value of CXCR4 was explored. Experimental Design: The expression of CXCR4 in HCC was determined by IHC and immunofluorescence. Characteristics of CXCR4+ cells were determined by in vitro and mice experiments. Kaplan–Meier survival analysis was used to determine the correlation of CXCR4 expression with prognosis. Results: We found that CXCR4 is selectively expressed on a fraction of tumor endothelial cells (TECs) in HCC tissues, but not on the hepatic endothelium in peritumoral area. High levels of CXCR4 on TECs tended to develop a sinusoidal vasculature in tumors and predicted poor prognosis for patients with HCC. CXCR4+ endothelial cells (EC) displayed the functional features of tip cells, with increased expression of tip cell–related markers. Functional studies revealed that CXCR4 could directly promote vessel sprouting in vitro and in vivo. Interestingly, sorafenib treatment reduced the frequency of CXCR4+ ECs in culture and inhibited the formation of sinusoidal vasculature and growth of CXCR4High xenograft tumors. Moreover, high CXCR4 vascular density in resected tumor tissues before sorafenib treatment was associated with prolonged survival in patients with advanced HCC treated with sorafenib. Conclusions: These data revealed that CXCR4 is a novel HCC vascular marker for vessel sprouting and could serve as a potential therapeutic target and a predictive factor for sorafenib treatment in patients with HCC. Clin Cancer Res; 23(15); 4482–92. ©2017 AACR.
Expression of DBC1 and Androgen Receptor Predict Poor Prognosis in Diffuse Large B Cell Lymphoma.

BACKGROUND Recently, deleted in breast cancer 1 (DBC1) has been suggested as a poor prognostic indicator of various human cancers and may possibly have a role as a coactivator of androgen receptor (AR). However, their roles in lymphoma are still unknown. MATERIALS AND METHODS We investigated the effect of the expression of DBC1 and AR in diffuse large B cell lymphoma (DLBCL). Immunohistochemical expression of DBC1 and AR were evaluated in 101 DLBCL samples by tissue microarray. RESULTS Positive expression of DBC1 and AR was seen in 73% and 70% of DLBCL, respectively. In total DLBCL patients, DBC1 and AR expression were significantly associated with high clinical stage, elevated serum lactate dehydrogenase levels, and high international prognostic index scores, and they predicted shorter overall survival (OS) and relapse-free survival (RFS) by univariate analysis. DBC1 expression was also an independent prognostic indicator by multivariate analysis (OS, P = .017; RFS, P = .004). Especially, both DBC1 and AR expression significantly correlated with shorter OS and RFS in non-germinal center B cell (non-GCB)-type DLBCL by univariate analysis. In multivariate analysis, DBC1 expression was an independent prognostic predictor for OS (P = .035) and AR expression significantly correlated with RFS (P = .005). CONCLUSION We demonstrate that the expression of DBC1 and AR are significant prognostic indicators for DLBCL patients, especially for unfavorable non-GCB-type DLBCL.