Miracle-dz/UniFAR-FTUs huggingface dataset:
Exacerbation of Granuloma Formation in IL-1 Receptor Antagonist-Deficient Mice with Impaired Dendritic Cell Maturation Associated with Th2 Cytokine Production1

Dendritic cell (DC) maturation at the site of inflammation and migration into draining lymph nodes is fundamental to initiate Ag-specific immune responses. Although several proinflammatory cytokines, including IL-1, are known to promote DC maturation in vitro, their contributions to DC activation and migration within peripheral inflamed tissue compartments are not yet fully understood. We show here that endogenous IL-1 receptor antagonist (IL-1ra) controls the activation state of liver-recruited DCs and their migration in a Propionibacterium acnes-induced murine granulomatous liver disease model. After P. acnes treatment, formation of portal tract-associated lymphoid tissue was conversely impaired in IL-1ra-deficient mice. IL-1ra-deficient mice developed hepatic granulomas within 3 days after P. acnes administration and showed a more pronounced granuloma formation than wild-type mice. Although sinusoidal granulomas contained numerous CD11c+ DCs at day 7, expressions of CCR7, IL-12p40 by these DCs were dramatically decreased in IL-1ra-deficient mice, suggesting aberrant DC maturation and sinusoid portal migration in the absence of endogenous IL-1ra. This was accompanied with enhanced intrahepatic Th2 cytokine production and severe hepatocellular damage. Thus, hepatocyte-derived IL-1ra may control optimal activation and migration of inflammatory DCs within the liver and thereby determine the local immune responses in granulomatous liver disease.
3-O-(3′,3′-Dimethysuccinyl) Betulinic Acid Inhibits Maturation of the Human Immunodeficiency Virus Type 1 Gag Precursor Assembled In Vitro

ABSTRACT 3-O-(3′,3′-Dimethysuccinyl) betulinic acid (PA-457) has been shown to potently inhibit human immunodeficiency virus (HIV) replication in culture. In contrast to inhibitors that act upon the viral proteinase, PA-457 appears to block only the final maturational cleavage of p25CA-p2 to p24CA. However, attempts to replicate this effect in vitro using recombinant Gag have failed, leading to the hypothesis that activity is dependent upon the assembly state of Gag. Using a synthesis/assembly system for chimeric HIV type 1 Gag proteins, we have replicated the activity of PA-457 in vitro. The processing of assembled chimeric Gag can be inhibited by the addition of drug with only the final cleavage of p25CA-p2 to p24CA blocked. Consistent with our hypothesis and with previous findings, inhibition appears specific to Gag assembled into an immature capsid-like structure, since synthetic Gag that remains unassembled is properly processed in the presence of the compound. To further analyze the authenticity of the assay, PA-457 was tested in parallel with its inactive parental compound, betulinic acid. Betulinic acid had no effect upon p25 processing in this system. Analysis of a PA-457-resistant mutant, A1V, in this system pointed to more rapid cleavage as a possible mechanism for resistance. However, characterization of additional mutations at the cleavage site and in p2 suggests that resistance does not strictly correlate with the rate of cleavage. With the establishment of an in vitro assay for the detection of PA-457 activity, a more detailed characterization of its mechanism of action will be possible.
An evaluation of visfatin levels in obese subjects.

INTRODUCTION Visfatin is a protein secreted by adipose tissue, which shows insulin mimetic properties. The role of visfatin in the development of obesity, diabetes mellitus, and metabolic syndrome continues to raise controversy. The aim of the study was to evaluate visfatin levels and to attempt to establish the relationship between visfatin and selected anthropometric and biochemical parameters in obese individuals. MATERIAL AND METHODS The study included 68 obese subjects (15 men and 53 women) aged 37.8 +/- 13.2 years with body mass index (BMI) values of 39.4 +/- 6.4 kg/m(2) without a previous diagnosis of abnormal glucose metabolism. The control group comprised 30 healthy nonobese volunteers (6 men and 24 women) with normal glucose metabolism, aged 38.2 +/- 14.9 years with BMI values of 22.8 +/- 3.0 kg/m(2). RESULTS We found significantly higher visfatin levels in the obese subjects compared to the control group (median visfatin level of 39.6 v. 17.3 ng/ml, p = 0.0006). In the obese group there was a statistically significant negative correlation between visfatin levels and age (r = -0.26, p = 0.034), waist-to-hip ratio (WHR) (r = -0.28, p = 0.031) and glycated haemoglobin (HbA(1c)) (r = -0.36, p = 0.0037). No statistically significant correlations were found between visfatin levels and the remaining parameters under study. In the control group, visfatin levels did not show any significant correlation with any of the parameters under study. CONCLUSIONS We found elevated levels of visfatin in obese subjects, which did not correlate with the majority of anthropometric parameters with the exception of WHR (negative correlation). This correlation may suggest that elevated visfatin levels are associated with the distribution of adipose tissue characteristic of gynoid rather than visceral obesity. In the group of obese subjects, visfatin levels decreased with age and glycated haemoglobin levels.
The risk of hepatitis B virus reactivation and the role of antiviral prophylaxis in hepatitis B surface antigen negative/hepatitis B core antibody positive patients with diffuse large B-cell lymphoma receiving rituximab-based chemotherapy

Abstract The risk factors and the role of prophylactic antiviral therapy of hepatitis B virus (HBV) reactivation in patients with hepatitis B surface antigen (HBsAg) negative/hepatitis B core antibody (HBcAb) positive disease remain controversial. We reviewed 629 patients with diffuse large B-cell lymphoma (DLBCL). Among 629 patients, 150 of 246 patients with resolved HBV (HBsAg negative and HBcAb positive) were treated with rituximab-combined therapy. Among these 150 patients, none of 104 patients (0.0%) who were hepatitis B surface antibody (HBsAb) positive experienced HBV reactivation versus four of 46 patients (8.7%) who were HBsAb negative (p = 0.008). One of 113 patients (0.9%) with International Prognostic Index (IPI) 0–2 suffered HBV reactivation versus three of the remaining 37 patients (8.1%) with IPI 3–5 (p = 0.047). HBsAb and IPI are potential risk factors for HBV reactivation. The use of prophylactic agents may not be recommended for these patients until the occurrence of HBV reactivation.
Deficiency of PTEN in Jurkat T Cells Causes Constitutive Localization of Itk to the Plasma Membrane and Hyperresponsiveness to CD3 Stimulation

ABSTRACT Pleckstrin homology (PH) domain binding to D3-phosphorylated phosphatidylinositides (PI) provides a reversible means of recruiting proteins to the plasma membrane, with the resultant change in subcellular localization playing a key role in the activation of multiple intracellular signaling pathways. Previously we found that the T-cell-specific PH domain-containing kinase Itk is constitutively membrane associated in Jurkat T cells. This distribution was unexpected given that the closely related B-cell kinase, Btk, is almost exclusively cytosolic. In addition to constitutive membrane association of Itk, unstimulated JTAg T cells also exhibited constitutive phosphorylation of Akt on Ser-473, an indication of elevated basal levels of the phosphatidylinositol 3-kinase (PI3K) products PI-3,4-P2 and PI-3,4,5-P3 in the plasma membrane. Here we describe a defect in expression of the D3 phosphoinositide phosphatase, PTEN, in Jurkat and JTAg T cells that leads to unregulated PH domain interactions with the plasma membrane. Inhibition of D3 phosphorylation by PI3K inhibitors, or by expression of PTEN, blocked constitutive phosphorylation of Akt on Ser-473 and caused Itk to redistribute to the cytosol. The PTEN-deficient cells were also hyperresponsive to T-cell receptor (TCR) stimulation, as measured by Itk kinase activity, tyrosine phosphorylation of phospholipase C-γ1, and activation of Erk compared to those in PTEN-replete cells. These data support the idea that PH domain-mediated association with the plasma membrane is required for Itk activation, provide evidence for a negative regulatory role of PTEN in TCR stimulation, and suggest that signaling models based on results from Jurkat T-cell lines may underestimate the role of PI3K in TCR signaling.
Serum matrix metalloproteinase‐1 in patients with chronic viral hepatitis

Background and Aims: Previously we found that serum matrix metalloproteinase (MMP)‐1 activity decreased with progression of chronic liver disease. Our objectives in the present study were to observe the change in the serum MMP‐1 protein concentration using recently developed specific enzyme immunoassays for MMP‐1 and MMP‐1 complexed with tissue inhibitor of metalloproteinases (TIMP)‐1 and to elucidate the clinical usefulness of the serum MMP‐1 test in chronic viral hepatitis. We measured the serum concentrations of MMP‐1 and MMP‐1/TIMP‐1 complex using these immunoassays in 64 patients with histologically characterized chronic viral hepatitis.
Site‐directed spin labeling electron paramagnetic resonance study of the ORF1 protein from a mouse L1 retrotransposon

Long interspersed nuclear element‐1 is a highly abundant mammalian retrotransposon that comprises 17% of the human genome. L1 retrotransposition requires the protein encoded by open reading frame‐1 (ORF1p), which binds single‐stranded RNA with high affinity and functions as a nucleic acid chaperone. ORF1p has been shown to adopt a homo‐trimeric, asymmetric dumbbell‐shaped structure. However, its atomic‐level structure and mechanism of RNA binding remains poorly understood. Here, we report the results of a site‐directed spin labeling electron paramagnetic resonance (SDSL‐EPR) study of 27 residues within the RNA binding region of the full‐length protein. The EPR data are compatible with the large RNA binding lobe of ORF1p containing a RNA recognition motif (RRM) domain and a carboxyl‐terminal domain (CTD) that are predicted from crystallographic and NMR studies of smaller fragments of the protein. Interestingly, the EPR data indicate that residues in strands β3 and β4 of the RRM are structurally unstable, compatible with the previously observed sensitivity of this region to proteolysis. Affinity measurements and RNA‐dependent EPR spectral changes map the RNA binding site on ORF1p to residues located in strands β3 and β4 of the RRM domain and to helix α1 of the CTD. Complementary in vivo studies also identify residues within the RRM domain that are required for retrotransposition. We propose that in the context of the full‐length trimeric protein these distinct surfaces are positioned adjacent to one another providing a continuous surface that may interact with nucleic acids.
Use and misuse of antibiotics in the neonatal intensive care unit

Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units (NICUs) and in industrialized countries about 1% of neonates are exposed to antibiotic therapy. Signs and symptoms of sepsis are nonspecific, and empiric antimicrobial therapy is promptly initiated after obtaining appropriate cultures in order to prevent deleterious consequences. However, many preterm infants who do not have infection receive antimicrobial agents during hospital stay and antibiotic treatment in the setting of negative cultures can have serious adverse effects like: promotion of bacterial antibiotic resistance, alteration of gut colonization, increase risk of Candida colonization and subsequent invasive candidiasis, increase risk of death, necrotizing enterocolitis and late-onset sepsis. Appropriate choice of antimicrobial agents and optimal duration of therapy in neonates with suspected or culture-proven sepsis is essential in order to prevent serious consequences. Moreover the establishment of an antibiotic stewardship programme in the NICUs is the best way of ensuring neonatal infections remain treatable while efforts are made for the developing of optimal antibiotic prescribing.
Overexpression of NOTCH-regulated ankyrin repeat protein is associated with breast cancer cell proliferation.

BACKGROUND/AIM NOTCH-regulated ankyrin repeat protein (NRARP) has been implicated in crosstalk between NOTCH and wingless-type mouse mammary tumor virus integration site (WNT) signals during development. Our study aimed to clarify its role in breast cancer cells. MATERIALS AND METHODS Public microarray data were used to analyze gene expression in human and rat breast cancer. A short interfering RNA was introduced into MCF7 and T47D human breast cancer cells for NRARP silencing. Gene expression was analyzed by quantitative polymerase chain reaction. RESULTS The NRARP transcript was commonly overexpressed in various rat mammary cancer models. In addition, a subset of human breast cancer also expressed high levels of NRARP transcript, which correlated positively with up-regulation of cell proliferation-related genes. Silencing of NRARP suppressed the growth of MCF7 and T47D cells and lowered the expression of cell cycle-related genes in MCF7 cells. CONCLUSION NRARP may stimulate cell proliferation in human breast cancer.
Common leadership strategies and practices among authentic senior leaders

From the early 2000s onwards, authentic leadership has continued to garner growing interest from academia, the public sector, and across multiple industries. Perhaps the reason for the increased focus on authenticity is the unethical behavior demonstrated by a number of leaders from 2000 to 2010. While there is growing interest in demonstrating authenticity as a situational leadership style or even an inherent trait, there is limited research on what leadership strategies or practices are most effective for authentic leaders. This study was designed to apply a common definition, or set of criteria, to identify leaders that are authentic. Once this group of authentic leaders has been identified, research can be conducted to understand common characteristics, traits, styles, practices, and strategies. Conversely, the opportunity exists to understand what common challenges authentic leaders face to determine mitigation strategies. The findings of this study provided exemplary best practices for leaders in business and other fields. To help ground the study, a detailed literature review of leadership theory, and authentic leadership’s place within the study of leadership, was completed. The historical examination of leadership is important as it adds richness and context to how authenticity has risen to prominence within empirical and theoretical research. This research showed that common leadership strategies and practices among authentic leaders include the ability to connect and engage through honest and transparent storytelling. Authentic leaders are vulnerable and transparent, and they enable and engage people and organizations through sharing a compelling vision. Their core leadership approach of honesty and transparency does not change, but they will flex how direct they are based on the situation and audience. In terms of challenges, authentic senior leaders have a high desire for their authentic approach to be reciprocated, and they can be too demanding. In order to overcome
Expression profile of apoptotic mediators and proliferative markers in oral squamous cell carcinoma.

BACKGROUND Oral squamous cell carcinoma (OSCC) represents a major health problem worldwide. It is therefore essential to develop a deeper understanding of its biology. Beside the recent hypothesis of cancer stem cells, the consideration of its cell death and cell proliferation has emerged as important diagnostic and prognostic tools. PURPOSE OD THE STUDY: Detection of the proportion of cell loss monitored by apoptosis-related genes, p53, p21 and Bcl2, and their relationship to the pathological proliferation parameter, PCNA in OSCC. Furthermore, discussion of the hypothesis of cancer stem cell biology in OSCC would be anticipated. MATERIAL AND METHODS Archival 35 tissue embedded paraffin blocks, that were previously diagnosed as well to moderately differentiated OSCC, were immunohistochemically stained using a panel of antibodies including apoptotic mediators, p53, p21, Bcl2, and proliferation marker, PCNA. Immunoexpression was scored using a semiquantitative scale and statistically analyzed. RESULTS The clinico-pathological data revealed that mean age was 46.9±8.2 and the tongue was the most affected site, followed by the palate then the floor of the mouth. There was no significant difference between metastasizing and non-metastasizing patients regarding age or gender (p=0.174, 0.404, respectively). On the other hand, variable profile patterns of the investigated indicators existed, where PCNA positively immunostaining cells was 100%while P21 recorded the higher percentage of negatively immunoreactive cells (42.9%). A common trait for the studied cell cycle indicators was that the basal and suprabasal epithelial cells as well as the peripheral cells of the invading nests were the harbor of immunoreactivity. Meanwhile, PCNA immunopositivity was revealed in all epithelial layers plus stromal cells. CONCLUSIONS Assessment of the studied cell cycle regulators may be valuable to judge tumorigenesis of OSCC. Furthermore, deregulation of cell cycle control might aid in the attainment of genetic changes in normal stem cells to be altered to cancer stem cells.
Global Banking: Recent Developments and Insights from Research

Following recent crises, cross-border capital flows have declined considerably, and many advanced countries' banks are retrenching. At the same time, banks from emerging and developing countries continue to expand abroad, and banking has become more regional. Research highlights that long-term debt flows are less volatile and that foreign banks with larger presence, more domestic funding, and closer relationships provide more finance and share risks better. While ongoing changes in global banking influence its overall benefits, the crises also revealed the need for a consistent framework for supervising and resolving globally active banks, with the European Banking Union an important model.
Online narratives about medical tourism in Malaysia and Thailand: a qualitative content analysis

ABSTRACT This study explored the written online narratives about medical tourism in Malaysia and Thailand using qualitative content analysis. The Google search engine was used for narrative search. Multiple search terms including medical, health, wellness tourism; treatment abroad; medical or health travel; treatment, surgery, or plastic surgery; dental treatment or braces were used to obtain related blog posts, discussions, and forums via a purposeful sampling method. A total of 43 online narratives were included in this study. Themes were then created after an iterative analysis of the selected online comments or posts. The push factors that act as motivators were: cost (100%), attractions (81%), availability of facilitators (62%), physician’s background and expertise (58%), bandwagon effect (42%). The majority of the subjects (88%) stated that they were satisfied with the outcomes of their medical treatments received in Malaysia and Thailand.
Cytokeratin Markers Come of Age

Cytokeratins have been extensively used as serum tumour markers for monitoring of disease progression in cancer patients. The source of cytokeratins in the circulation as well as the mechanisms of release from cells have long been unclear. Recent evidence suggests that cytokeratins present in the circulation of cancer patients are released from apoptotic or necrotic tumour cells. CK18 is cleaved by caspases during apoptosis and a monoclonal antibody (M30) specific to caspase-cleaved forms is available. The molecular form of CK18 released from cells (caspase-cleaved or not) can conveniently be determined by immunoassays (M30-Apoptosense® and M65® ELISA assays; Peviva AB, Bromma, Sweden) to determine cell death mode – apoptosis or necrosis. Recent studies where these assays were used to evaluate the response to cytotoxic anticancer drugs using cancer patient serum have been encouraging. CK18 is attracting considerable interest as a response biomarker during clinical trials of anticancer drugs. Properties such as excellent antigen stability and the epithelial specificity of cytokeratins contribute to make this biomarker attractive.
Psychometric Validation of the Bahasa Malaysia Version of the EORTC QLQ-CR29.

BACKGROUND This study examined the psychometric properties of the Bahasa Malaysia (BM) version of the European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer-specific Quality Of Life Questionnaire (QLQ-CR29). MATERIALS AND METHODS We studied 93 patients recruited from University Malaya and Universiti Kebangsaan Medical Centers, Kuala Lumpur, Malaysia using a self-administered method. Tools included QLQ-C30, QLQ-CR29 and Karnofsky Performance Scales (KPS). Statistical analyses included Cronbach's alpha, test-retest correlations, multi-traits scaling and known-groups comparisons. A p value ≤ 0.05 was considered significant. RESULTS The internal consistency coefficients for body image, urinary frequency, blood and mucus and stool frequency scales were acceptable (Cronbach's alpha α ≥ 0.65). However, the coefficients were low for the blood and mucus and stool frequency scales in patients with a stoma bag (α = 0.46). Test-retest correlation coefficients were moderate to high (range: r = 0.51 to 1.00) for most of the scales except anxiety, urinary frequency, buttock pain, hair loss, stoma care related problems, and dyspareunia (r ≤ 0.49). Convergent and discriminant validities were achieved in all scales. Patients with a stoma reported significantly higher symptoms of blood and mucus in the stool, flatulence, faecal incontinence, sore skin, and embarrassment due to the frequent need to change the stoma bag (p < 0.05) compared to patients without stoma. None of the scales distinguished between patients based on the KPS scores. There were no overlaps between scales in the QLQ-C30 and QLQ-CR29 (r < 0.40). CONCLUSIONS the BM version of the QLQ-CR29 indicated acceptable psychometric properties in most of the scales similar to original validation study. This questionnaire could be used to complement the QLQ-C30 in assessing HRQOL among BM speaking population with colorectal cancer.
Lotharmeyerite, Ca(Zn,Mn)2(AsO4)2(H2O,OH)2

Lotharmeyerite, calcium bis(zinc/manganese) bis(arsenate) bis(hydroxide/hydrate), Ca(Zn,Mn3+)2(AsO4)2(H2O,OH)2, is a member of the natrochalcite group of minerals, which are characterized by the general formula AM 2(XO4)2(H2O,OH)2, where A may be occupied by Pb2+, Ca2+, Na+, and Bi3+, M by Fe3+, Mn3+, Cu2+, Zn2+, Co2+, Ni2+, Al3+, and Mg2+, and X by PV, AsV, VV, and SVI. The minerals in the group display either monoclinic or triclinic symmetry, depending on the ordering of chemical components in the M site. Based on single-crystal X-ray diffraction data of a sample from the type locality, Mapimi, Durango, Mexico, this study presents the first structure determination of lotharmeyerite. Lotharmeyerite is isostructural with natrochalcite and tsumcorite. The structure is composed of rutile-type chains of edge-shared MO6 octahedra (site symmetry ) extending along [010], which are interconnected by XO4 tetrahedra (site symmetry 2) and hydrogen bonds to form [M 2(XO4)2(OH,H2O)2] sheets parallel to (001). These sheets are linked by the larger A cations (site symmetry 2/m), as well as by hydrogen bonds. Bond-valence sums for the M cation, calculated with the parameters for Mn3+ and Mn2+ are 2.72 and 2.94 v.u. , respectively, consistent with the occupation of the M site by Mn3+. Two distinct hydrogen bonds are present, one with O⋯O = 2.610 (4) Å and the other O⋯O = 2.595 (3) Å. One of the H-atom positions is disordered over two sites with 50% occupancy, in agreement with observations for other natrochalcite-type minerals, such as natrochalcite and tsumcorite.