Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy

Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4) plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled. All the patients had integrated clinicopathological records and follow-up data. TLR4 and PD-L1 expression on NSCLC samples were determined by immunohistochemistry, and serum soluble TLR4 (sTLR4) levels were measured by enzyme-linked immunosorbent assay. Results showed that TLR4 expression level in cancer tissue was significantly higher than that in para-cancer tissue. Elevated TLR4 expression was significantly associated with histological type (adenocarcinoma higher than squamous cell carcinoma, P = 0.041), increased clinical TNM stage (P < 0.001), and presence of lymphatic invasion (P < 0.001). Besides, TLR4 expression level in cancer samples was inversely correlated with serum sTLR4 level in patients with early-stage NSCLC (r = −0.485, P = 0.003). TLR4 expression level was also positively correlated with the PD-L1 expression level (r = 0.545, P < 0.0001). Multivariate analysis showed that expression level of TLR4 was an independent prognostic factor and TLR4 overexpression indicated a poor overall survival and disease-free survival. Taken together, we conclude that expression of TLR4 in lung cancer is associated with PD-L1 and could predict the outcome of patients with NSCLC receiving pulmonary resection for cancer.
Analysis of immune responses against H pylori in rabbits.

AIM To investigate the immunogenicity of H pylori proteins, to evaluate the production rate of anti H pylori IgG antibodies in relation to time and to demonstrate the fidelity of newly optimized in-house enzyme-linked immunosorbent assay (ELISA) technique as an alternative for H pylori infection assay. METHODS In the present study, 100 microg of formalin-fixed H pylori whole cell antigens was injected into an experimental animal (New Zealand white female rabbit) intramuscularly on d 0, 16, 27 and 36. The first two doses were injected with adjuvants. On d 0, a serum sample was collected from the rabbit before immunization and this pre-immunized serum was used as a negative control for the whole study. To evaluate the immunogenic responses of the injected antigen, serum samples were collected from the rabbit at regular intervals up to d 42. The sera were analyzed using in-house ELISA and Western blot techniques. RESULTS The production of anti H pylori IgG antibodies in the rabbit in response to the injected antigen increased almost exponentially up to d 14 and after that it was maintained at the same level until the last day (d 42). By analyzing the immune profiles of immunized sera, 11 proteins were identified to be immunogenic, among them 2 (approximately 100 kDa and 85 kDa) were most prominent. CONCLUSION Analysis of the immune responses against pathogenic microorganisms like H pylori is necessary for the development of various diagnostic and preventive approaches. The results of this experiment reveal that the formalin-fixed H pylori whole cell antigens injected into the rabbit are highly immunogenic. These prominent proteins (approximately 100 kDa and 85 kDa) might have higher immunogenic effects among humans infected with H pylori and some of these immunogenic proteins can be included in diagnostic approaches based on serology and also for vaccine formulation. The in-house ELISA is a promising alternative compared to invasive techniques.
Antioxidant vitamin intake and risk of Alzheimer disease.

BACKGROUND The generation of oxygen free radicals is involved in the pathogenesis of Alzheimer disease (AD). OBJECTIVE To determine whether the intake of antioxidant vitamins decreases the risk of AD. METHODS We investigated the relationship between AD and the intake of carotenes, vitamin C, and vitamin E in 980 elderly subjects in the Washington Heights-Inwood Columbia Aging Project who were free of dementia at baseline and were followed for a mean time of 4 years. Semiquantitative food frequency questionnaires were administered between baseline and the first follow-up visit. Cox proportional hazards regression models were conducted with quartiles of each vitamin intake as the exposure of interest and incident AD as the outcome, adjusted for age, level of education, sex, APOE epsilon4 status, ethnicity, and smoking. RESULTS There were 242 incident cases of AD in 4,023 person-years of follow-up (6 per 100 person-years). Intake of carotenes and vitamin C, or vitamin E in supplemental or dietary (nonsupplemental) form or in both forms, was not related to a decreased risk of AD. Trend tests for the association between quartiles of total intake of vitamins C and E also were not significant. CONCLUSION Neither dietary, supplemental, nor total intake of carotenes and vitamins C and E was associated with a decreased risk of AD in this study.
Efficient and Competitive Rationing

Priority service rations available supplies according to contracts that specify each customer's priority or rank order. If customers' preferences are stable, this alternative market form can achieve most of the efficiency gains attributed to spot markets, which in some industries are expensive to organize. Rationing by priorities is prominent in capital-intensive industries with nonstorable outputs, as well as in service-sector and make-to-order industries where service is queued or congested. This paper describes the role of priority service and suggests a basic model. The main topic is efficient implementation by public enterprises and by competitive firms. Copyright 1989 by The Econometric Society.
Recurrent ulcer bleeding: is intravenous omeprazole the solution?

In this randomized, double-blinded, placebo-controlled study, 240 patients who underwent successful endoscopic treatment for bleeding peptic ulcers were divided into two groups of 120 patients. One group received an 80-mg bolus of intravenous omeprazole followed by an infusion of omeprazole at 8 mg/h for 72 h, whereas the second group received placebo infusion for the same duration. After 72 h, thei.v. omeprazole/placebo was stopped and patients in both groups were given 20 mg/day of omeprazole orally for 8 weeks. On endoscopy, all patients had one of the following findings: actively bleeding ulcer, ulcer with a nonbleeding visible vessel, and ulcer with a clot and underlying vessel. The therapeutic endoscopic technique consisted of sclerotherapy using 1:10,000 epinephrine followed by coaptive thermocoagulation. All patients underwent successful endoscopic treatment, defined as cessation of bleeding. All were tested forHelicobacter pyloriand underwent treatment if they were found to be positive. The primary endpoint of this study was to compare the rate of rebleeding among the two study groups within 30 days of initiating therapy. Rebleeding was considered to have occurred if more than 2 g/dl within 24 h after a transfusion to a level of 10 g/dl. Rebleeding utilizing these criteria occurred in eight patients in the omeprazole infusion group, as compared with 27 patients in the placebo group. Most cases of recurrent bleeding occurred within 72 hours of endoscopic therapy (5/8 in the omeprazole group and 24/27 in the placebo group). Recurrent bleeding was confirmed with endoscopy, and repeat sclerotherapy and thermocoagulation were performed. The authors concluded that after endoscopic treatment of bleeding peptic ulcers, a high dose infusion of omeprazole substantially reduces the risk of recurrent bleeding. (Am J Gastroenterol 2001;96:594–595. © 2001 by Am. Coll. of Gastroenterology)
A systematic review of experimental and clinical studies of sildenafil citrate for intrauterine growth restriction and pre-term labour

Summary Sildenafil could be an alternative in the treatment of intrauterine growth retardation (IUGR) and premature delivery. In order to systematically review the reproductive-related effects of sildenafil, a search was made on PubMed and the Science Citation Index for studies evaluating the effects of sildenafil on uterine vessels or myometrium either in vitro or in experimental animal models as well as for any clinical trial or case reporting the outcome of pregnant women treated with sildenafil. The information was obtained from: three in vitro studies, five studies performed in experimental animal models, four studies on women with fertility and sterility disorders receiving 100 mg/day of sildenafil intravaginally, and two case reports of pregnant women who received sildenafil for the treatment of pulmonary hypertension. Incubation with sildenafil of different in vitro preparations resulted in vasodilator and uterine relaxant effects. No evidence of teratogenicity was observed in the studies performed in mice, rats and dogs. Sildenafil increased fetal weight in rats. In women, contradictory results on uterine blood flow and endometrial development were reported after the intravaginal administration of sildenafil. No adverse fetal outcomes were reported in the two pregnant women with pulmonary hypertension receiving sildenafil late in their pregnancy. In conclusion, there is still limited information about the efficacy of sildenafil for the treatment of IUGR and premature delivery. However, studies in experimental animal models and two human case reports have reported no deleterious effects on the mother or offspring.
Genome-Wide Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing

OBJECTIVE: To prospectively determine the diagnostic accuracy of massively parallel sequencing to detect whole chromosome fetal aneuploidy from maternal plasma. METHODS: Blood samples were collected in a prospective, blinded study from 2,882 women undergoing prenatal diagnostic procedures at 60 U.S. sites. An independent biostatistician selected all singleton pregnancies with any abnormal karyotype and a balanced number of randomly selected pregnancies with euploid karyotypes. Chromosome classifications were made for each sample by massively parallel sequencing and compared with fetal karyotype. RESULTS: Within an analysis cohort of 532 samples, the following were classified correctly: 89 of 89 trisomy 21 cases (sensitivity 100%, 95% [confidence interval] CI 95.9–100), 35 of 36 trisomy 18 cases (sensitivity 97.2%, 95% CI 85.5–99.9), 11 of 14 trisomy 13 cases (sensitivity 78.6%, 95% CI 49.2–99.9), 232 of 233 females (sensitivity 99.6%, 95% CI 97.6 to more than 99.9), 184 of 184 males (sensitivity 100%, 95% CI 98.0–100), and 15 of 16 monosomy X cases (sensitivity 93.8%, 95% CI 69.8–99.8). There were no false-positive results for autosomal aneuploidies (100% specificity, 95% CI more than 98.5 to 100). In addition, fetuses with mosaicism for trisomy 21 (3/3), trisomy 18 (1/1), and monosomy X (2/7), three cases of translocation trisomy, two cases of other autosomal trisomies (20 and 16), and other sex chromosome aneuploidies (XXX, XXY, and XYY) were classified correctly. CONCLUSION: This prospective study demonstrates the efficacy of massively parallel sequencing of maternal plasma DNA to detect fetal aneuploidy for multiple chromosomes across the genome. The high sensitivity and specificity for the detection of trisomies 21, 18, 13, and monosomy X suggest that massively parallel sequencing can be incorporated into existing aneuploidy screening algorithms to reduce unnecessary invasive procedures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials. gov, NCT01122524. LEVEL OF EVIDENCE: II
Contribution of Electron and Confocal Microscopy in the Study of Leishmania–Macrophage Interactions

Promastigotes of the protozoan parasite genus Leishmania are inoculated into a mammalian host when an infected sand fly takes a bloodmeal. Following their opsonization by complement, promastigotes are phagocytosed by macrophages. There, promastigotes differentiate into amastigotes, the form of the parasite that replicates in the phagolysosomal compartments of host macrophages. Although the mechanisms by which promastigotes survive the microbicidal consequence of phagocytosis remain, for the most part, to be elucidated, evidence indicates that glycoconjugates play a role in this process. One such glycoconjugate is lipophosphoglycan, an abundant promastigote surface glycolipid. Using quantitative electron and confocal laser scanning microscopy approaches, evidence was provided that L. donovani promastigotes inhibit phagolysosome biogenesis in a lipophosphoglycan-dependent manner. This inhibition correlates with an accumulation of periphagosomal F-actin, which may potentially form a physical barrier that prevents L. donovani promastigote-containing phagosomes from interacting with endocytic vacuoles. Inhibition of phagosome maturation may constitute a strategy to provide an environment propitious to the promastigote-to-amastigote differentiation.
Dependency of Escherichia coli cell‐division size, and independency of nucleoid segregation on the mode and level of ftsZ expression

Expression of ftsZ in strain VIP205 is dissociated from its natural promoters, and is under the control of an inducible tac promoter. This abolishes the oscillation in ftsZ transcription observed in the wild type, allowing different levels of ftsZ expression. We demonstrate that this construction does not affect the expression of other genes, and has no effects on replication or nucleoid segregation. A shift in IPTG from 30 μM, that supports division at wild‐type sizes, to lower (6 μM) or higher (100μM) concentrations, indicates that VIP205 cells can divide within a broad range of FtsZ concentrations. Analysis of the morphological parameters during the transition from one IPTG concentration to another suggests that the correct timing of ftsZ expression, and the correct FtsZ concentration, are required for division to occur at normal cell sizes. After a transient division delay during the transition to lower IPTG concentrations, cells in which ftsZ is expressed continuously (yielding 80% of the wild‐type FtsZ levels) divide with the same division time as the wild type, but at the expense of becoming 1.5 times larger. A precise control of ftsZ expression is required for normal division, but the existence of additional regulators to maintain the correct timing during the cell cycle cannot be ruled out.
Mechanisms of aneuploidy in thyroid cancer cell lines and tissues: evidence for mitotic checkpoint dysfunction without mutations in BUB1 and BUBR1

objective Thyroid follicular adenomas (FA) and carcinomas (FC) have a high prevalence of aneuploidy. We examined the contribution of mitotic checkpoint dysfunction and mutations of BUB1 or BUBR1, components of the spindle assembly checkpoint pathway, to chromosomal instability in thyroid cancer.
Multiple myeloma--presenting as acute kidney injury.

BACKGROUND Multiple myeloma (MM) is a commonly encountered hematological malignancy with significant renal involvement and often presents as renal failure. The aim of the present study is to analyze clinical spectrum of acute renal failure (ARF) in patients with MM. MATERIAL AND METHODS We analyzed 26 (males 24; females 2) patients of multiple myeloma who were referred for evaluation of ARF between July 1994 - June 2007. The referral diagnosis did not include MM in majority 23 (88%) of the patients. Multiple myeloma was diagnosed by at least two of the four features; (1) lytic bone lesions, (2) serum or urine monoclonal peak, (3) Bence Jones proteinuria and (4) more than 20% plama cells in marrow aspirate. RESULTS Multiple myeloma contributes 1.93% of total ARF cases (26/1342) over a period of thirteen years. Mean age of patients was 59.3 +/- 7.4 years. The clinical manifestations of myeloma included; anemia (100%), Bence Jones proteinuria (80%), "M" peak in serum electrophoresis (69%), lytic bone lesions (62%), "M" peak in urine electrophoresis (54%), body pain (58%), plasma cells more than 20% in bone marrow aspirate (38%). Oliguric ARF was seen in 73% patients. The precipitating factors of ARF identified were; hypercalcemia (31%); infection (23%); volume depletion (19%); and NSAIDs in (15%). Dialysis support was needed in 77% of the patients because of severe renal failure at presentation with mean serum creatinine of 9.05 +/- 2.84 mg%. Seventeen patients completed chemotherapy, seven last to follow up and two patients died. Ten (38.5%) patients had complete recovery of renal function; three patients had partial recovery and off dialysis and four patients remained dialysis dependent. Remission of myeloma was achieved in nine of seventeen patients treated with chemotherapy Renal biopsy finding in nine patients revealed-cast nephropathy in (4), amyloidosis in (3), proliferative glomerulonephritis in (1) and cast nephropathy with chronic interstitial nephritis and plasma cell infiltration in one patient. CONCLUSION Acute reversible renal failure is a common complication in MM, multiple myeloma should be considered as cause a cause of unexplained ARF in middle aged and elderly patients.
Multiple Affinity States of cGMP-Specific Phosphodiesterase for Sildenafil Inhibition Defined by cGMP-Dependent and cGMP-Independent Mechanisms

cGMP-specific phosphodiesterase (PDE5) has become a target for drug development for the treatment of a number of physiological dysfunctions, affected by changes in the cGMP/cGMP-dependent protein kinase (PKG) signaling pathway. PDE5 has two highly homologous regulatory domains, GAF-A and GAF-B. We showed previously that PDE5 could be converted from a low-activity (nonactivated) state to a high-activity state upon cGMP binding to the GAF-A domain with higher sensitivities toward sildenafil (EMBO J 22:469–478, 2003). Here we investigated whether sildenafil sensitivity of PDE5 could be modified by cGMP-independent mechanisms. Individually expressed recombinant GAF-A and GAF-B proteins were tested for their ability to modulate full-length recombinant PDE5 affinity to sildenafil. The GAF-A domain protein had the most dramatic effect on the affinity of the nonactivated recombinant PDE5 for sildenafil, revealing much higher sensitivity to sildenafil inhibition. The apparent affinity for sildenafil increased from the nanomolar range to the picomolar range, providing evidence for the presence of a “super-high” sensitivity state of PDE5 for sildenafil inhibition. In human platelet, higher sensitivity of PDE5 for sildenafil inhibition has been detected after blocking cGMP-binding sites of the GAF-A domain. Thus, our data demonstrate that high sensitivity of PDE5 for sildenafil can be obtained not only through cGMP-induced activation of PDE, but also through cGMP-independent modulation of PDE5 in the nonactivated state, possibly through protein-protein interaction. Furthermore, data suggest that nonactivated PDE5 with “super-high” affinities for sildenafil inhibition may be responsible for therapeutic effects of long-term treatments with low doses of PDE5 inhibitors.
Effortful Control, Behavior Problems, and Peer Relations: What Predicts Academic Adjustment in Kindergartners from Low-Income Families?

This study used a short-term longitudinal design to examine the role of effortful control, behavior problems, and peer relations in the academic adjustment of 74 kindergarten children from primarily low-income families. Teachers completed standardized measures of children's effortful control, internalizing and externalizing problems, school readiness, and academic skills. Children participated in a sociometric interview to assess peer relations. Research Findings: Correlational analyses indicate that children's effortful control, behavior problems in school, and peer relations are associated with academic adjustment variables at the end of the school year, including school readiness, reading skills, and math skills. Results of regression analyses indicate that household income and children's effortful control primarily account for variation in children's academic adjustment. The associations between children's effortful control and academic adjustment do not vary across the sex of the child or ethnicity. Mediational analyses indicate an indirect effect of effortful control on school readiness through children's internalizing problems. Practice or Policy: Effortful control emerged as a strong predictor of academic adjustment among kindergarten children from low-income families. Strategies for enhancing effortful control and school readiness among low-income children are discussed.
Beyond the Visual Impedance Effect

Whether the mental representation of reasoning problems is spatial or visual (or mixed) in nature has been the subject of considerable debate for years. The visual impedance effect found in Knauff & Johnson-Laird (2002) has provided us with new insights into this question. The study found that the forming of excessive visual images induced by the premises can impede relational reasoning. This study aimed at investigating the factor of complexity on the visual impedance effect in two folds, namely number of term series (i.e., total number of premises plus the conclusion) and whether the entities in the premises are presented in a continuous manner (i.e., whether the subject of the argument is the same as the object of the previous argument). In line with previous studies, relational category, number of term series and successiveness were the main factors of the response time. Results of the parameter estimation by generalized estimating equation showed that visual relations, 5-term series and discontinuous problems were the only significant parameters. The results again suggested that irrelevant visual images can hinder reasoning processes, in addition to the complexity of the problem. We proposed a combined cognitive model of ACT-R and PRISM for the findings in this study.
Quantitative Analysis for Computed Tomography Findings of Various Diffuse Lung Diseases Using Volume Histogram Analysis

Objectives: The aim of this study was to achieve the quantitative analysis of the characteristic computed tomography (CT) findings and course of interstitial pneumonia using the volume histogram method. Methods: Contrast (CNT), variance (VAR), and entropy (EPY) values from whole-lung volume data were compared between normal lungs and 5 diseases that have characteristic CT findings. Thirteen cases with nonspecific interstitial pneumonia (NSIP) were evaluated before and after treatment. Results: In cases with thickening of the bronchovascular bundles and interlobular thickening, ground-glass attenuation, airspace consolidation, and honeycombing, the values of VAR and EPY were greater than those in the normal cases (P < 0.05). In the cases with NSIP, the CNT value after treatment was significantly greater and the values of VAR and EPY after treatment were significantly lower than those before treatment (P < 0.05). Conclusions: Volume histogram analysis is a promising method for the evaluation of diffuse lung diseases and the effectiveness of treatment.