Miracle-dz/UniFAR-FTUs huggingface dataset:
The Polyphenolic Ellagitannin Vescalagin Acts As a Preferential Catalytic Inhibitor of the α Isoform of Human DNA Topoisomerase II

Polyphenolic ellagitannins are natural compounds that are often associated with the therapeutic activity of plant extracts used in traditional medicine. They display cancer-preventing activity in animal models by a mechanism that remains unclear. Potential targets have been proposed, including DNA topoisomerases II (Top2). Top2α and Top2β, the two isoforms of the human Top2, play a crucial role in the regulation of replication, transcription, and chromosome segregation. They are the target of anticancer agents used in the clinic such as anthracyclines (e.g., doxorubicin) or the epipodophyllotoxin etoposide. It was recently shown that the antitumor activity of etoposide was due primarily to the inhibition of Top2α, whereas inhibition of Top2β was responsible for the development of secondary malignancies, pointing to the need for more selective Top2α inhibitors. Here, we show that the polyphenolic ellagitannin vescalagin preferentially inhibits the decatenation activity of Top2α in vitro, by a redox-independent mechanism. In CEM cells, we also show that transient small interfering RNA-mediated down-regulation of Top2α but not of Top2β conferred a resistance to vescalagin, indicating that the α isoform is a preferential target. We further confirmed that Top2α inhibition was due to a catalytic inhibition of the enzyme because it did not induce DNA double-strand breaks in CEM-treated cells but prevented the formation of Top2α- rather than Top2β-DNA covalent complexes induced by etoposide. To our knowledge, vescalagin is the first example of a catalytic inhibitor for which cytotoxicity is due, at least in part, to the preferential inhibition of Top2α.
Comparative study of Tc-99m MIBI and TI-201 SPECT in predicting chemotherapeutic response in non-small-cell lung cancer.

PURPOSE Tc-99m MIBI can be excluded from cytosol against its concentration gradient as a suitable transport substrate by P-glycoprotein. Tc-99m MIBI has also been shown to be more effective than TI-201 chloride for evaluating the response to chemotherapy in patients with small-cell lung cancer. The relation between Tc-99m MIBI accumulation by the tumor and its response to chemotherapy were evaluated in patients with non-small-cell lung cancer (NSCLC) and compared with the same parameters achieved using TI-201 chloride. METHODS Thirty-eight patients with NSCLC were examined before chemotherapy was begun. They were classified according to the results of a follow-up computed tomogram into two groups: responders were patients in whom there was a > or =50% decrease and nonresponders were patients in whom there was a <50% decrease in the sum of the product of the maximum perpendicular diameters of all measurable lesions. All patients underwent dual-isotope imaging with TI-201 chloride and Tc-99m MIBI just before chemotherapy. Regions of interest were placed over the tumor uptake (T) and contralateral normal lung tissue (N) areas on one coronal view with a clearly defined lesion, and the T:N ratio and retention index were calculated. RESULTS The delayed T:N ratio and retention index for Tc-99m MIBI in the responder group were significantly greater (P<0.05) than those in the nonresponder group. There was no significant correlation between the T:N ratio and retention index and tumor response using TI-201 chloride. CONCLUSION Tc-99m MIBI SPECT may be more effective than TI-201 chloride SPECT for evaluating the response to chemotherapy in patients with NSCLC.
Genetic Diversity and Mating Type Distribution of Tuber melanosporum and Their Significance to Truffle Cultivation in Artificially Planted Truffiéres in Australia

ABSTRACT Tuber melanosporum is a truffle native to Europe and is cultivated in countries such as Australia for the gastronomic market, where production yields are often lower than expected. We assessed the genetic diversity of T. melanosporum with six microsatellite loci to assess the effect of genetic drift on truffle yield in Australia. Genetic diversity as assessed on 210 ascocarps revealed a higher allelic diversity compared to previous studies from Europe, suggesting a possible genetic expansion and/or multiple and diverse source populations for inoculum. The results also suggest that the single sequence repeat diversity of locus ME2 is adaptive and that, for example, the probability of replication errors is increased for this locus. Loss of genetic diversity in Australian populations is therefore not a likely factor in limiting ascocarp production. A survey of nursery seedlings and trees inoculated with T. melanosporum revealed that <70% of seedlings and host trees were colonized with T. melanosporum and that some trees had been contaminated by Tuber brumale, presumably during the inoculation process. Mating type (MAT1-1-1 and MAT1-2-1) analyses on seedling and four- to ten-year-old host trees found that 100% of seedlings but only approximately half of host trees had both mating types present. Furthermore, MAT1-1-1 was detected significantly more commonly than MAT1-2-1 in established trees, suggesting a competitive advantage for MAT1-1-1 strains. This study clearly shows that there are more factors involved in ascocarp production than just the presence of both mating types on host trees.
Time-Varying Comovement of Foreign Exchange Markets

A time-varying cointegration model for foreign exchange rates is presented. Unlike previous studies, we allow the loading matrix in the vector error correction (VEC) model to be varying over time. Because the loading matrix in the VEC model is associated with the speed at which deviations from the long-run relationship disappear, we propose a new degree of market comovement\ based on the time-varying loading matrix to measure the strength or robustness of the long-run relationship over time. Since exchange rates are determined by macrovariables, cointegration among exchange rates implies those macroeconomic variables share common stochastic trends. Therefore, the proposed degree measures the degree of market comovement. Our main finding is that the market comovement has become stronger over the past quarter century, but the rate at which market comovement strengthens is decreasing with two major turning points: one in 1995 and the other one in 2008.
Bioaccumulation and distribution of trace elements in tissues of giant river prawn Macrobrachium rosenbergii (Decapoda: Palaemonidae) from South Vietnam

Accumulation profiles of 22 trace elements in abdominal muscle, abdominal exoskeleton and the hepatopancreas of the giant river prawn Macrobrachium rosenbergii were analyzed. The giant river prawn is an indigenous freshwater species from South Vietnam, and is cultured commercially and fished in the wild. Samples were collected from Ho Chi Minh City and the surrounding area (SKEZ, South Key Economic Zone), and from the Mekong River Delta between 2003 and 2005. Highest accumulations of essential (Cu, Se and Mo) and toxic (As, Ag, Cd and Hg) elements were observed in hepatopancreatic tissue, except for Mn, Sr, Sn, Ba and V in the exoskeleton and Rb and Cs in muscle tissue. Spatial differences showed concentrations of Cs and Pb in muscle and Sr in exoskeletons from the SKEZ were higher than those from the Mekong River Delta. The opposite trend was observed for Cr, Se and Sb in muscle, Mo, Sb and TI in exoskeleton, and Se, Hg, Mo, Cd, Sb, TI and Bi in the hepatopancreas. These differences in trace element concentrations in prawns likely reflect differences in industrialization and human activities between the two regions of South Vietnam.
A safety assessment of anti-tumor necrosis factor alpha therapy for treatment of Crohn’s disease

ABSTRACT Introduction: Anti-tumor necrosis factor-alpha (TNF-α) therapy has revolutionized the medical treatment of Crohn’s disease (CD). Nevertheless, anti-TNF-α therapy has been associated with serious adverse events (SAE) raising safety concerns. This review focuses on the safety profile of anti-TNF-α agents in CD. Areas covered: We performed a literature search until August 2015 to collect safety data on infliximab, adalimumab and certolizumab pegol monotherapy or combined with immunomodulators (IMM). We have mainly focused on infections and malignancies. Safety in pregnancy, the elderly and children are also presented. Expert opinion: Available data in CD suggest that anti-TNF-α monotherapy or in combination with IMM is relatively safe, although it may be associated with an elevated risk of serious infections, skin cancer and lymphoma. However, as this data derive mainly from cohort studies, post-marketing registries, and meta-analyses of RCTs, often characterized by inherited methodological weaknesses that may hinder their validity, data from large, statistically powered, prospective studies of sufficient follow up are required to define the actual risk of SAE during anti-TNF-α therapy in IBD. The role of therapeutic drug monitoring in predicting and preventing SAE awaits confirmation.
LACK, a RACK1 ortholog, facilitates cytochrome c oxidase subunit expression to promote Leishmania major fitness

Leishmania are kinetoplastid parasites that cause the sandfly‐transmitted disease leishmaniasis. To maintain fitness throughout their infectious life cycle, Leishmania must undergo rapid metabolic adaptations to the dramatically distinct environments encountered during transition between sandfly and vertebrate hosts. We performed proteomic and immunoblot analyses of attenuated L. major strains deficient for LACK, the Leishmania ortholog of the mammalian receptor for activated c kinase (RACK1), that is important for parasite thermotolerance and virulence. This approach identified cytochrome c oxidase (LmCOX) subunit IV as a LACK‐dependent fitness protein. Consistent with decreased levels of LmCOX subunit IV at mammalian temperature, and in amastigotes, LmCOX activity and mitochondrial function were also impaired in LACK‐deficient L. major under these conditions. Importantly, overexpression of LmCOX subunit IV in LACK‐deficient L. major restored thermotolerance and macrophage infectivity. Interestingly, overexpression of LmCOX subunit IV enhanced LmCOX subunit VI expression at mammalian temperature. Collectively, our data suggest LACK promotes Leishmania adaptation to the mammalian host environment by sustaining LmCOX subunit IV expression and hence energy metabolism in response to stress stimuli such as heat. These findings extend the repertoire of RACK1 protein utility to include a role in mitochondrial function.
MR angiography and dynamic flow evaluation of the portal venous system.

We studied the value of MR angiographic techniques in imaging the portal venous system. Projection angiograms were created by postprocessing a series of two-dimensional, flow-compensated gradient-echo images. Flow velocity was determined by a bolus-tracking method with radiofrequency tagging and multiple data readout periods. Each image was acquired during a breath-hold. MR angiography was applied to six normal subjects and four patients with abnormal hemodynamics in the portal venous system. Flow velocity determined by MR was correlated with the results of duplex sonography. The main portal vein and intrahepatic branches were shown in all cases. Portosystemic collaterals were identified in all patients with portal hypertension. In normal subjects, peak flow velocities (17.9 +/- 2.8 cm/sec) on MR correlated well with values determined by duplex sonography (17.5 +/- 2.2 cm/sec) (r = .846, p less than .04). Reversed portal blood flow was shown in two patients. One patient with portal vein thrombosis had no evidence of flow by MR angiography. Our results indicate that MR angiography can provide a three-dimensional display of normal and abnormal vascular anatomy as well as functional information in the portal venous system.
Case management in vocational rehabilitation: a case study with promising results.

PURPOSE The aim of the current study was to investigate whether Case Management and the strengths model could be a successful method in vocational rehabilitation of unemployed people on long term sick leave in Sweden. An additional aim was to further highlight the actual rehabilitation process. MATERIAL AND METHOD Ten clients, five men and five women aged between 35 and 40, were included in the project. All ten were at the project start both long-term unemployed (2-13 years) and on long term sick leave (2-6 years). The project was evaluated from four perspectives: Quality of life (SF 36), sickness absence, and contact with working life were investigated before and after the project. The rehabilitation process was investigated during and after the project. RESULTS AND CONCLUSION The result from the study was positive. Of the 10 clients who participated in the project, six have improved their quality of life, seven have a diminished sickness absence and seven have a closer contact to working life after the project than before. With regards to the rehabilitation process, the results here also impart a positive picture. It should be noted, however, that the study is small and not based on a random sample. The results should not be generalized, but recognized instead as a positive indication.
Psychotherapy with chronic inflammatory bowel disease patients: A Review

&NA; Two distinct factors have lead in the past to the development of several psychotherapeutic treatments for patients with inflammatory bowel diseases (IBD). First, clinicians and researchers believe that psychologic and somatic factors in chronic IBD, Crohn's disease, and ulcerative colitis) are connected. In addition, IBD reduces the health‐related quality of life for these patients. The purpose of the psychotherapies is to influence the somatic course of the disease, the psychological state of the patients, or the patients' health related quality of life. This report evaluates the existing studies with regard to the effectiveness of psychotherapy IBD patients received in addition to medical treatment. We have identified 10 psychotherapy studies and 4 additional studies on self management and patient education on this topic. The studies significantly differ from each other in regard to psychotherapeutic methods, inclusion criteria, and outcome assessments. The results so far lead to the conclusion that psychotherapy does not have an impact on the course of the disease but, in some cases, positively influences the patient's psychologic state (such as depression, anxiety, and health related quality of life or coping with the disease). Thus, psychotherapy cannot, in general, be recommended for all patients with chronic IBD. Patients, however, that display a tendency toward psychologic problems, especially as it pertains to their illness, might profit from it.
Chronic lymphatic leukemia evolving into chronic myelocytic leukemia

A diagnosis of chronic lymphatic leukemia (CLL) was made in an 83‐year‐old man on the basis of marked lymphocytosis (131.1 × 109/L) and infiltration of the marrow (77%) by small lymphoid cells. The hemoglobin was 11.8 g/dL and the platelet count was 427.5 × 109/L. With minimal and unsustained treatment, abrupt resolution of the lymphocytosis occurred with reciprocal emergence of a classic picture of chronic myelogenous leukemia (CML). During the hematologic evolution, blood lymphoid cells were isolated for surface marker, cytogenetic, and functional studies. E‐rosette receptors, Fcreceptors, and membrane immunoglobulins were found on only 7.5%, 7.4%, and 10.0% of these cells. These cells also failed to express a CLL‐associated antigen we have detected on ≈︁ 95% of the cells of all CLL patients studied, regardless of cell phenotype. In addition, the patient's lymphoid cells responded poorly to leucoagglutinin (LPHA) stimulation, showed increased spontaneous metabolic activity and exhibited the Philadelphia chromosome. These observations suggest that the patient's transient initial lymphocytosis was not due to CLL, but perhaps represented myeloid precursors in circulation prior to terminal differentiation.
Commercialisation of technology innovations: an empirical study on the influence of clusters and innovation networks

The current body of literature offers contradictory results concerning the role of clusters and innovation networks in the commercialisation of high technology. Whereas several previous studies verify the overall beneficial effects of cluster membership for knowledge-intensive firms, others report that clusters have only little or no influence on technology firms’ economic success. The major purpose of this study is therefore to conduct a comparative analysis between small and medium-sized firms within and outside clusters with regard to the commercialisation of their innovations in the emerging nanotechnology sector. Our results reveal several differences in the commercialisation process and activities between firms within and outside of nanotechnology clusters.
The Complete Genome Sequence of Actinobacillus pleuropneumoniae L20 (Serotype 5b)

ABSTRACT There are 16 capsule-based serotypes of Actinobacillus pleuropneumoniae, all of which are capable of causing disease in pigs. Here we report the finished and annotated genome sequence of the reference serotype 5b strain L20. This strain has a rough appearance and readily forms biofilms, as is typical for most field isolates (6).
Systematic Underestimation of Treatment Effects as a Result of Diagnostic Test Inaccuracy: Implications for the Interpretation and Design of Thromboprophylaxis Trials

Summary Many clinical trials that have assessed strategies for the prevention of deep vein thrombosis have employed diagnostic tests that are less accurate than venography. The correct interpretation of these trials has been the subject of considerable debate. This paper attempts to quantify the likely effects of the use of inaccurate diagnostic tests (in particular fibrinogen scanning) on the validity and precision of estimates of treatment effects. It is shown that, if there is no difference in the rate of misclassification of deep vein thrombosis between study and control groups, then treatment effects will tend to be systematically underestimated in trials that only use inaccurate diagnostic tests. However, for trials in which there are no false positive diagnoses, such as those employing venography, the estimate of relative treatment effects will be unbiased. This phenomenon is demonstrated empirically by data from randomised trials of antiplatelet therapy. The implications of these findings are two-fold. First, so long as the accuracy of the test is the same in study and control groups, positive trial results cannot be ascribed to diagnostic test inaccuracy. Second, unbiased estimates of relative treatment effects can be obtained by using cheap, practicable and non-invasive screening tests that are supplemented by venographic assessment of positive test results. This would facilitate the conduct of much larger randomised trials than has generally been possible when mandatory venography was used; if future trials randomised some thousands of patients and employed confirmatory venography then they would provide both unbiased and precise estimates of relative treatment effects.
Citizens by Design? Explaining Ex-Combatant Satisfaction with Reintegration Programming

Abstract After armed conflict, there is often a surge in programmes designed to consolidate the peace. During the transition to peace, the quality of programme management has been argued to shape public perceptions about government and citizenship. What aspects of programme management are most important? What implementation failures have the greatest negative effects? We study these questions in the context of a reintegration programme for former combatants in Colombia. We find evidence that programme implementation has strong impacts on participant satisfaction, regardless of programme outcomes. This suggests that how benefits are delivered matters as much as what is delivered.
Analysis of Nitric Oxide Synthase Genes in Cluster Headache

The aetiology of cluster headache is still not yet completely understood, but the potential relevance of genetic factors has been recognized during recent years. Nitric oxide (NO) plays a critical role in the regulation of vasodilation, neurotransmission, inflammation and many other events throughout the body. NO also appears to be an important mediator of vascular headache pathophysiology. In this study we have performed an association analysis of five polymorphic micro-satellite markers in the three different NO synthase (NOS) genes; nNOS (NOS1), iNOS (NOS2A) and eNOS (NOS3). Ninety-one cluster headache patients diagnosed according to International Headache Society criteria and 111 matched controls were studied. Phenotype and allele frequencies were similarly distributed in patients and controls except for an iNOS (NOS2A) pentanucleotide repeat allele which was significantly more common in controls. We observed a higher phenotype frequency of this allele in our control group compared with rates in control groups of other studies, whereas the frequency in our patients was similar to that in controls from previous reports. Thus, we conclude that it is unlikely that genetic variations within the NOS genes contribute greatly to cluster headache susceptibility.
Immunity to melanoma mediated by 4‐1BB is associated with enhanced activity of tumour‐infiltrating lymphocytes

4‐1BB costimulates T cells to carry out effector functions such as eradication of established tumours. 4‐1BB (CD137) is a member of the TNF receptor family, and its triggering by either 4‐1BB ligand or antibody ligation induces T‐cell activation and growth. We analysed tumour‐infiltrating lymphocytes (TIL) in the experimental B16F10 melanoma model to determine the mechanisms involved in 4‐1BB‐mediated tumour suppression. 4‐1BB+/+ mice survived longer than 4‐1BB–/– mice, and survival was further prolonged by triggering 4‐1BB with an agonistic mAb. The number of metastatic B16F10 colonies in the lung was much greater in 4‐1BB–/– mice than in their 4‐1BB+/+ littermates. Administration of agonistic anti‐4‐1BB mAb increased the number of TIL in the tumour masses in the lungs of 4‐1BB+/+ mice. The numbers of CD4+ T, CD8+ T and CD11b+ TIL increased in these mice. Anti‐4‐1BB mAb induced not only CD8+ 4‐1BB+ T cells but also a CD8+ IFN‐γ+ T‐cell population. B16F10 cells from the lungs of anti‐4‐1BB‐treated mice showed enhanced expression of MHC class Ι and II antigens compared with the same cells from control IgG‐treated mice. Thus, the increase in number of CD8+ T cells and enhanced MHC Ι and II expression in B16F10 cells that result from augmented IFN‐γ production in response to anti‐4‐1BB mAb may lead to suppression of tumour growth and metastasis.
Empirical Testing of Month of the Year Effect on Selected Commercial Banks and Services Sector Companies Listed on Bahrain Bourse

In financial literature we find numerous studies examining the presence of diverse types of calendar anomalies in different stock exchanges of the world. The current paper aims to investigate the month of the year effect in randomly selected ten companies from banking sector and service sector traded on the Bahrain Bourse for a period of five years commencing from 1st January 2010 to 31st December 2014. The empirical research was conducted using descriptive statistics and Kruskal-Wallis H Test. The findings of the study revealed that none of the companies selected for the study exhibited significant monthly returns for the study period except Bahrain Maritime & Mercantile International (BMMI). The paper suggests that the absence of said calendar anomaly may be due to thin trading practiced in the Bahrain Stock Exchange.