Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas.

BACKGROUND Limited knowledge exists about the effects chronic hepatitis C virus (HCV) infection has in the development of colorectal adenomas (CRA). Data regarding the association between chronic HIV infection and the development of CRA is scarce as well. We aim to determine if there is an association between the development of CRA and chronic infection with HCV and HCV/HIV co-infection. METHODS From July 1, 2009 to March 31, 2011 a total of 2,051 patients that underwent colonoscopy were included in our study. The population was divided into 2 study groups: those patients who tested positive for HCV, and HCV/HIC; the control groups consisted of patients whose results were negative. Fisher's exact χ(2) test for categorical variables and t-test for continuous variables was used to analyze data between groups. Logistic regression was performed to obtain odds ratios (OR). RESULTS CRA detection was higher in the HCV than in the control group (26.3% vs. 20.2%; P=1.02); Likewise, the incidence of CRA (25.5% vs. 20.8%; P=0.63) was higher in the co-infection group. However, in both of the study groups this difference was non-statistical. CONCLUSIONS A higher detection rate of CRP was seen in the HCV population; however, it failed to reach statistical significance. Whether co-infection with HIV/HCV increases the incidence of CRA and/or has a synergistic effect remains to be determined. The small sample population and the retrospective single institution nature of our study, as well as other confounders may have contributed to our negative results. However, our findings question whether HCV and HIV/HCV co-infected patients will benefit from screening colonoscopy at an earlier age. This issue merits further investigation with a large multi-center prospective study.
Comparison of a xylanase and a complex of non starch polysaccharide-degrading enzymes with regard to performance and bacterial metabolism in weaned piglets

Abstract Weaned piglets were fed a wheat based diet either non-supplemented or supplemented with a multi-enzyme preparation or a xylanase mono-enzyme preparation, respectively. Both enzyme preparations increased live weight gain nonsignificantly, but only animals of the xylanase group showed a trend (p = 0.076) for an improved feed conversion. Only precaecal digestibility of total amino acids was improved significantly when the mono-enzyme preparation was added. Improvements of digestibility of crude fat, crude protein and starch did not reach the significance level. Both enzyme preparations reduced jejunal viscosity, however viscosity in the colon was only reduced by the mono-enzyme preparation. Both enzymes significantly reduced Lactobacillus spp. cell numbers as well as bacterial metabolites in the stomach and showed similar nonsignificant modifications in jejunum contents except for acetate in the mono-enzyme group. Total jejunal bile acids were unchanged. Compared to the control, the ratio of the main conjugated to the main deconjugated bile acid was significantly higher in the mono-enzyme group. This study has shown that the mono- and multi-enzyme preparation can lead to improved performance in wheat based diets for piglets. Like in poultry, the main mode of action seems to be the reduction of small intestinal viscosity. However, the generation of fermentable carbohydrates by the multi-enzyme preparation may mask beneficial effects on performance due to the development of an active bile acid deconjugating microbiota in the small intestine.
Rapid emergence of novel antigenic and genetic variants of equine infectious anemia virus during persistent infection

Previous results from our laboratory have demonstrated that equine infectious anemia virus displays structural variations in its surface glycoproteins and RNA genome during passage and chronic infections in experimentally infected Shetland ponies (Montelaro et al., J. Biol. Chem. 259:10539-10544, 1984; Payne et al., J. Gen. Virol. 65:1395-1399, 1984). The present study was undertaken to obtain an antigenic and biochemical characterization of equine infectious anemia virus isolates recovered from an experimentally infected pony during sequential disease episodes, each separated by intervals of only 4 to 8 weeks. The virus isolates could be distinguished antigenically by neutralization assays with serum from the infected pony and by Western blot analysis with a monoclonal antibody against the major surface glycoprotein gp90, thus demonstrating that novel antigenic variants of equine infectious anemia virus predominate during each clinical episode. The respective virion glycoproteins displayed different electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gels, indicating structural variation. Tryptic peptide and glycopeptide maps of the viral proteins of each virus isolate revealed biochemical alterations involving amino acid sequence and glycosylation patterns in the virion surface glycoproteins gp90 and gp45. In contrast, no structural variation was observed in the internal viral proteins pp15, p26, and p9 from any of the four virus isolates. Oligonucleotide mapping experiments revealed similar but unique RNase T1-resistant oligonucleotide fingerprints of the RNA genomes of each of the virus isolates. Localization of altered oligonucleotides for one virus isolate placed two of three unique oligonucleotides within the predicted env gene region of the genome, perhaps correlating with the structural variation observed in the envelope glycoproteins. Thus these results support the concept that equine infectious anemia virus is indeed capable of relatively rapid genomic variations during replication, some of which result in altered glycoprotein structures and antigenic variants which are responsible for the unique periodic disease nature observed in persistently infected animals. The findings of envelope specific differences in isolates of visna virus and of human T-cell lymphotropic virus III (acquired immune deficiency syndrome-related virus) suggest that this variation may be a common characteristic of the subfamily Lentivirinae.
Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome

Liddle's syndrome is an autosomal dominant form of human hypertension, caused by gain‐of‐function mutations of the epithelial sodium channel (ENaC) which is expressed in aldosterone target tissues including the distal colon. We used a mouse model for Liddle's syndrome to investigate ENaC‐mediated Na+ transport in late distal colon by measuring the amiloride‐sensitive transepithelial short circuit current (ΔISC‐Ami) ex vivo. In Liddle mice maintained on a standard salt diet, ΔISC‐Ami was only slightly increased but plasma aldosterone (PAldo) was severely suppressed. Liddle mice responded to a low or a high salt diet by increasing or decreasing, respectively, their PAldo and ΔISC‐Ami. However, less aldosterone was required in Liddle animals to achieve similar or even higher Na+ transport rates than wild‐type animals. Indeed, the ability of aldosterone to stimulate ΔISC‐Ami was about threefold higher in Liddle animals than in the wild‐type controls. Application of aldosterone to colon tissue in vitro confirmed that ENaC stimulation by aldosterone was not only preserved but enhanced in Liddle mice. Aldosterone‐induced transcriptional up‐regulation of the channel's β‐ and γ‐subunit (βENaC and γENaC) and of the serum‐ and glucocorticoid‐inducible kinase 1 (SGK1) was similar in colon tissue from Liddle and wild‐type animals, while aldosterone had no transcriptional effect on the α‐subunit (αENaC). Moreover, Na+ feedback regulation was largely preserved in colon tissue of Liddle animals. In conclusion, we have demonstrated that in the colon of Liddle mice, ENaC‐mediated Na+ transport is enhanced with an increased responsiveness to aldosterone. This may be pathophysiologically relevant in patients with Liddle's syndrome, in particular on a high salt diet, when suppression of PAldo is likely to be insufficient to reduce Na+ absorption to an appropriate level.
The impact of increased post-progression survival on the cost-effectiveness of interventions in oncology

Purpose: Cost-effectiveness analyses (CEA) of new technologies typically include “background” costs (eg, all “related” health care costs other than the specific technology under evaluation) as well as drug costs. In oncology, these are often expensive. The marginal cost-effectiveness ratio (ie, the extra costs and QALYs associated with each extra period of survival) calculates the ratio of background costs to QALYs during post-progression. With high background costs, the incremental cost-effectiveness ratio (ICER) can become less favorable as survival increases and the ICER moves closer to the marginal cost-effectiveness ratio, making cost-effectiveness prohibitive. This study assessed different methods to determine whether high ICERs are caused by high drug costs, high “background costs” or a combination of both and how different approaches can alter the impact of background costs on the ICER where the marginal cost-effectiveness ratio is close to, or above, the cost-effectiveness threshold. Methods: The National Institute for Health and Care Excellence oncology technology appraisals published or updated between October 2012 and October 2017 were reviewed. A case study was selected, and the CEA was replicated. Three modeling approaches were tested on the case study model. Results: Applying one-off “transition” costs during post-progression reduced the ongoing “incremental” costs of survival, which meant that the marginal cost-effectiveness ratio was substantially reduced and problems associated with additional survival were less likely to impact the ICER. Similarly, the use of two methods of additional utility weighting for end-of-life cases meant that the marginal cost-effectiveness ratio was reduced proportionally, again lessening the impact of increased survival. Conclusion: High ICERs can be caused by factors other than the cost of the drug being assessed. The economic models should be correct and valid, reflecting the true nature of marginal survival. Further research is needed to assess how alternative approaches to the measurement and application of background costs and benefits may provide an accurate assessment of the incremental benefits of life-extending oncology drugs. If marginal survival costs are incorrectly calculated (ie, by summing total post-progressed costs and dividing by the number of baseline months in that state), then the costs of marginal survival are likely to be overstated in economic models.
A proinvasive role for the Ca2+‐activated K+ channel KCa3.1 in malignant glioma

Glioblastoma multiforme are highly motile primary brain tumors. Diffuse tissue invasion hampers surgical resection leading to poor patient prognosis. Recent studies suggest that intracellular Ca2+ acts as a master regulator for cell motility and engages a number of downstream signals including Ca2+‐activated ion channels. Querying the REepository of Molecular BRAin Neoplasia DaTa (REMBRANDT), an annotated patient gene database maintained by the National Cancer Institute, we identified the intermediate conductance Ca2+‐activated K+ channels, KCa3.1, being overexpressed in 32% of glioma patients where protein expression significantly correlated with poor patient survival. To mechanistically link KCa3.1 expression to glioma invasion, we selected patient gliomas that, when propagated as xenolines in vivo, present with either high or low KCa3.1 expression. In addition, we generated U251 glioma cells that stably express an inducible knockdown shRNA to experimentally eliminate KCa3.1 expression. Subjecting these cells to a combination of in vitro and in situ invasion assays, we demonstrate that KCa3.1 expression significantly enhances glioma invasion and that either specific pharmacological inhibition with TRAM‐34 or elimination of the channel impairs invasion. Importantly, after intracranial implantation into SCID mice, ablation of KCa3.1 with inducible shRNA resulted in a significant reduction in tumor invasion into surrounding brain in vivo. These results show that KCa3.1 confers an invasive phenotype that significantly worsens a patient's outlook, and suggests that KCa3.1 represents a viable therapeutic target to reduce glioma invasion. GLIA 2014;62:971–981
Elevated serum levels of a c-erbB-2 oncogene product in oral squamous cell carcinoma patients.

OBJECTIVES Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in many kinds of cancer including oral squamous cell carcinoma (OSCC). In order to obtain further information on the c-erbB-2 gene product p185, it is necessary to quantify expression levels. In this study we used an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of OSCC patients. METHOD Sera from 84 OSCC patients, 51 breast cancer patients (as positive controls), and 15 healthy controls were assayed in an ELISA. To study c-erbB-2 overexpression in OSCC, and breast cancer tissue samples we used an immunohistochemical technique. RESULTS The mean serum value (ng/ml, mean/SD) for the normal controls was 8.46/1.29. We chose the 95% level of normal controls as a cut-off to distinguish individuals with elevated levels. The breast cancer patients' and OSCC patients' serum values were 13.83/6.82 and 13.1/4.56, respectively. Significant differences (P < 0.0001) were observed between normal control and OSCC, normal control and the breast cancer group. Immunohistochemically detectable p185 (intermediate to high) was noted in 30 of 61 OSCC, and 24 of 51 breast cancer patients. There was a trend of association of serum oncoprotein fragment levels with tumor stages, but not with tumor sizes, nodal stages, metastases, and oral habits including betel quid chewing, alcohol drinking and smoking in the OSCC group. CONCLUSION The results of the present study raise the possibility that soluble c-erbB-2 protein levels in serum is a useful parameter for monitoring the disease status as well as the effect of therapy on patients with OSCC.
Infection of simian B lymphoblastoid cells with simian immunodeficiency virus is associated with upregulation of CD23 and CD40 cell surface markers

Simian immunodeficiency virus (SIV) as well as human immunodeficiency virus (HIV) induce polyclonal B‐cell activation and are associated with the appearance of lymphomas in their respective hosts in either the presence or the absence of other co‐infecting viruses such as Epstein‐Barr virus (EBV). However, the pathogenic role of these retroviruses in the development of lymphoproliferative disorders remains poorly understood. To explore the virus–B‐cell interactions, two immortalized lymphoblastoid B‐cell lines (SL‐P1 and SL‐691) were established from cynomolgus monkeys that were naturally co‐infected with a simian type D retrovirus‐2 (SRV‐2) and with the herpes virus Macaca fascicularis (HVMF‐1). We addressed their susceptibility to SIV infection and the phenotypic modifications associated with SIV infection. In response, both cell lines (1) were co‐infected with HVMF‐1 (latent infection) and with SRV‐2 (productive infection), (2) had a transformed phenotype because they did not require exogenous growth factors, and (3) when injected into mice with severe combined immunodeficiency (SCID), generated serially transplantable tumors. The B‐cell origin of SL cells was demonstrated by the presence of rearrangements of the IgH gene and by the expression of typical B‐cell lineage markers, such as CD20. SL‐P1 and SL‐691 could be discriminated on the basis of different expressions of CD23 and CD40 and of κ‐ and λ‐chains. Most importantly, SL‐691 cells, but not SL‐P1 cells, were susceptible to chronic noncytolytic SIV infection. This infection occurred in a CD4/CCR5/CXCR4‐independent manner and was associated with the upregulated expression of CD23 and CD40 cell surface markers. In addition, CD20 expression, which progressively disappeared in SL‐691 noninfected cells, was maintained in the SIV‐infected counterpart. These findings support the hypothesis that SIV induce phenotypic perturbations in B cells that might eventually contribute to the development of lymphoproliferative disease. J. Med. Virol. 68:129–140, 2002. © 2002 Wiley‐Liss, Inc.
On-the-Road Driving Performance the Morning after Bedtime Use of Suvorexant 20 and 40 mg: A Study in Non-Elderly Healthy Volunteers.

STUDY OBJECTIVE To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg. DESIGN Double-blind, placebo-controlled, 4-period crossover study. SETTING Maastricht University, The Netherlands. PARTICIPANTS 28 healthy volunteers (15 females), aged 23 to 64 years. INTERVENTIONS Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo. MEASUREMENTS Performance on day 2 and 9 (9 h after dosing) using a one-hour standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo changes in SDLP > 2.4 cm were considered to reflect meaningful driving impairment. RESULTS Mean drug-placebo changes in SDLP following suvorexant 20 and 40 mg were 1.01 and 1.66 cm on day 2, and 0.48 and 1.31 cm on Day 9, respectively. The 90% CIs of these changes were all below 2.4 cm. Symmetry analysis showed that more subjects had SDLP changes > 2.4 cm than < -2.4 cm following suvorexant 20 and 40 mg on day 2, and following suvorexant 40 mg on day 9. Four female subjects requested that a total of 5 driving tests--all following suvorexant--stop prematurely due to self-reported somnolence. CONCLUSIONS As assessed by mean changes in standard deviation of lateral position (SDLP), there was no clinically meaningful residual effect of suvorexant in doses of 20 and 40 mg on next-morning driving (9 h after bedtime dosing) in healthy subjects < 65 years old. There may be some individuals who experience next-day effects, as suggested by individual changes in SDLP and prematurely stopped tests. CLINICAL TRIAL REGISTRATION clinicaltrials.gov NCT01311882.
Legionella Effector AnkX Disrupts Host Cell Endocytic Recycling in a Phosphocholination-Dependent Manner

The facultative intracellular bacterium Legionella pneumophila proliferates within amoebae and human alveolar macrophages, and it is the causative agent of Legionnaires' disease, a life-threatening pneumonia. Within host cells, L. pneumophila establishes a replicative haven by delivering numerous effector proteins into the host cytosol, many of which target membrane trafficking by manipulating the function of Rab GTPases. The Legionella effector AnkX is a phosphocholine transferase that covalently modifies host Rab1 and Rab35. However, a detailed understanding of the biological consequence of Rab GTPase phosphocholination remains elusive. Here, we broaden the understanding of AnkX function by presenting three lines of evidence that it interferes with host endocytic recycling. First, using immunogold transmission electron microscopy, we determined that GFP-tagged AnkX ectopically produced in mammalian cells localizes at the plasma membrane and tubular membrane compartments, sites consistent with targeting the endocytic recycling pathway. Furthermore, the C-terminal region of AnkX was responsible for association with the plasma membrane, and we determined that this region was also able to bind the phosphoinositide lipids PI(3)P and PI(4)P in vitro. Second, we observed that mCherry-AnkX co-localized with Rab35, a regulator of recycling endocytosis and with major histocompatibility class I protein (MHC-I), a key immunoregulatory protein whose recycling from and back to the plasma membrane is Rab35-dependent. Third, we report that during infection of macrophages, AnkX is responsible for the disruption of endocytic recycling of transferrin, and AnkX's phosphocholination activity is critical for this function. These results support the hypothesis that AnkX targets endocytic recycling during host cell infection. Finally, we have demonstrated that the phosphocholination activity of AnkX is also critical for inhibiting fusion of the Legionella-containing vacuole (LCV) with lysosomes.
Recalling Safety: Cooperative Functions of the Ventromedial Prefrontal Cortex and the Hippocampus in Extinction

ABSTRACT Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.
Is Self-Reflectiveness an Unhealthy Aspect of Private Self-Consciousness?

Abstract A number of researchers (M. Conway & C. Giannopoulos, 1993; P. J. Watson & M. D. Biderman, 1993) have suggested that self-reflectiveness is an unhealthy aspect of private self-consciousness related to psychopathology. However, these studies did not control for the significant correlation that exists between self-reflectiveness and subscale factors of public self-consciousness: style consciousness and appearance consciousness. The purpose of this research was to address these interrelationships by comparing correlational results with those obtained from multiple regression analyses. Participants (N =111) completed the Self-Consciousness Scale (A. Fenigstein, M. F. Scheier, & A. H. Buss, 1975) and the NEO-Five Factor Inventory (P. T. Costa & R. R. McCrae, 1992). The results suggested that when the effects of style consciousness and appearance consciousness are controlled, the relationship between self-reflectiveness and neuroticism is nonsignificant. Furthermore, multiple regression analyses suggested a significant relationship between self-reflectiveness and low levels of agreeableness. Aspects of self-consciousness may be better understood in the context of overlapping domains that consider both common and unique variance.