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['Serum levels of soluble interleukin-2 receptor (sIL-2R) are known to serve as a marker for the activation of T lymphocytes. We measured serum levels of sIL-2R in patients with chronic hepatitis C (CHC) during interferon (IFN)-based treatment to determine the correlation between those levels and therapeutic efficacy, and to clarify whether there is a difference in the activation of T lymphocytes among HCV genotypes after the treatment.', 'Forty-four patients received IFN-alpha2b monotherapy (group IFN-M), whereas 82 patients received the combination therapy with IFN-alpha2b and ribavirin (group IFN+R). We measured serum sIL-2R levels in these patients before (T0) and 2 weeks (T2) after the treatment.', 'The sustained virologic response rates in genotype 2a/2b patients were significantly higher than those in genotype 1b patients in both groups (P<0.005). In sustained virologic responders, sIL-2R levels at T2 were significantly higher than those at T0 in both groups (P<0.001). In nonresponders, sIL-2R levels at T2 were not different from those at T0 in group IFN-M, but were significantly higher than those at T0 in group IFN+R (P=0.0072). In genotype 1b patients, sIL-2R levels at T2 were not different from those at T0 in group IFN-M, but were significantly higher than those at T0 in group IFN+R (P=0.0064). In genotype 2a/2b patients, sIL-2R levels at T2 were significantly higher than those at T0 in both groups (P<0.0005).'] Are increased soluble IL-2 receptor levels during interferon and ribavirin treatment associated with a good response in genotype 2a/2b patients with chronic hepatitis C? | qiaojin/PubMedQA | 2 | [
-1.3482638597488403,
-1.6832467317581177,
1.964992642402649
] |
['To investigate the effect of increased fucosyltransferase VII (FUT7) on sialyl Lewis X (sLeX) synthesis and their impact on embryo implantation.', 'Cell and animal study.', 'Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Department of Biochemistry and Molecular Biology, Dalian Medical University.', 'Adult female mice of Kunming species.', 'A pIRES2-EGFP-FUT7 expression plasmid containing full-length human FUT7 cDNA was constructed and transiently transfected into RL95-2 or injected into the uteri of early pregnant mice. Control subjects received the mock pIRES2-EGFP or anti-sLeX antibody.', 'The expression of FUT7 and sLeX was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and indirect immunofluorescence. The embryo adhesion rate was assayed in vitro with the cocultured RL95-2 and JAR implantation model. In vivo embryo implantation was investigated using a mouse model.', 'Expression of FUT7 was significantly increased after transfection of pIRES2-EGFP-FUT7 into RL95-2 cells compared with the parental control and mock vector transfectants, as demonstrated by fluorescent microscopy and RT-PCR. Expression of sLeX was also increased in FUT7 overexpressers, as detected by indirect immunofluorescence. Consistent with the elevated expression of FUT7 and sLeX, embryo adhesion rate and embryo implantation competence were significantly increased (P<.01) in both in vitro and in vivo models.'] Does overexpression of fucosyltransferase VII ( FUT7 ) promote embryo adhesion and implantation? | qiaojin/PubMedQA | 2 | [
-2.409431219100952,
-1.309478998184204,
2.764659881591797
] |
['To investigate the effects of an aromatase inhibitor, letrozole, on the growth of human endometrium in a three-dimensional fibrin matrix model of endometriosis.', 'Experimental study of human endometrial biopsies in a three-dimensional fibrin matrix culture system.', 'Academic research center.', 'Eight normal women with benign gynecologic problems.', 'Endometrial biopsy samples were washed, cut into small pieces, and placed between two layers of fibrin gel in the presence or absence of letrozole in the culture medium. Tissue changes were assessed by histological and immunohistochemical staining using an inverted microscope, image analysis, and a semiquantitative scoring system.', 'Stromal and epithelial cell outgrowth into the fibrin matrix and angiogenesis comprising endothelial cell invasion of the matrix.', 'Letrozole (0.1 micromol/L, 1 micromol/L, and 10 micromol/L) exerted a significant growth stimulation effect on endometrial tissue in this model.'] Does letrozole stimulate the growth of human endometrial explants cultured in three-dimensional fibrin matrix? | qiaojin/PubMedQA | 2 | [
-2.50890851020813,
-1.2687909603118896,
2.8492133617401123
] |
['The MRL/MpJ (healer) mouse is an established model for autoimmune studies and was recently identified as having a profound ability to undergo scarless regeneration of the tissue in the ear and heart. This regenerative capacity has been linked to elevated matrix metalloproteinase (MMP)-2 and -9 expression, giving this mouse the ability to degrade and remove inhibitory basement membrane molecules. Although elevated MMP expression has been reported in somatic tissues in this strain, little is known about MMP expression and the response to injury in the MRL/MpJ mouse retina. The purpose of this study was to investigate whether increased MMP expression and subsequent decreased inhibitory extracellular matrix molecule deposition in the MRL/MpJ mouse retina produces a permissive regenerative environment.', 'Experiments were performed using 3- to 4-week-old MRL/MpJ, retinal degenerative (rd1), and C57BL/6 (wild-type) mice. Western blotting, oligo-microarray, and immunohistochemical analyses were used to determine the level and location of MMP and extracellular matrix (ECM) protein expression. Retinal responses to injury were modeled by retinal detachment in vivo and in retinal explantation in vitro. The capacity of the retinal environment to support photoreceptor cell migration, integration, or regeneration was analyzed using hematoxylin-eosin, immunohistochemical staining, and cell counting.', 'Compared with C57BL/6J animals, MRL/MpJ mice exhibit elevated levels of MMP-2, -9, and -14 and decreased levels of the inhibitory proteins neurocan and CD44 within the retina. Although similar increases in MMP-2, -9, and CD44s (CD44 degradation product) were observed in the rd1 retina, elevated levels of the inhibitory ECM molecules (neurocan and CD44) remained. Thus, the MRL retinal environment, which expresses lower levels of inhibitory ECM molecules after injury, was more conducive to regeneration and enhanced photoreceptor integration in vitro than C57BL/6J or rd1 controls.'] Does elevated MMP Expression in the MRL Mouse Retina create a Permissive Environment for Retinal Regeneration? | qiaojin/PubMedQA | 2 | [
-2.313117027282715,
-1.3540499210357666,
2.702827215194702
] |
['Several fibroblast growth factors (FGFs) exhibit neuroprotective influences against retinal photoreceptor degeneration. The expression of FGF receptor (FGFR) 4 on photoreceptors suggests a specific ligand, FGF-19, might also be beneficial. The authors hence examined the potential role of FGF-19 in this regard.', 'Adult human retinal sections were processed for anti-FGFR-4 immunohistochemistry. Total RNA and proteins were extracted from parallel cultures of human Y79 retinoblastoma and primary adult pig photoreceptors; RNA samples were used for RT-PCR analysis of FGF-19, and proteins were subjected to immunoprecipitation for FGFR-1 and FGFR-4 or to Western blotting of FGF-19. Cultures were incubated with increasing concentrations of FGF-19 before extraction and Western blotting for phosphotyrosine. Photoreceptor cultures were screened for cell survival and processed for immunocytochemistry using anti-neural retina leucine zipper (Nrl) antibody.', 'FGF-19 mRNA was detected in adult pig retinal pigment epithelial cells, and FGF-19 protein was found in cell extracts and conditioned medium prepared from retinal pigment epithelium. The addition of FGF-19 to Y79 retinoblastoma or primary adult pig photoreceptor cultures led to time- and dose-dependent changes in proliferation (for Y79) or survival (for primary photoreceptors). FGF-19 induced the phosphorylation of an FGFR-4-immunoreactive band of approximately 80 kDa and led to the heterodimerization of FGFR-1 and FGFR-4. Y79 and primary photoreceptor cells maintained in serum-supplemented media exhibited Nrl immunoreactivity by Western blotting, which decreased after serum deprivation. The addition of FGF-19 led to the reexpression of Nrl immunoreactivity in both culture models.'] Does fGF19 exhibit neuroprotective effects on adult mammalian photoreceptors in vitro? | qiaojin/PubMedQA | 2 | [
-2.3543379306793213,
-1.3649945259094238,
2.7413554191589355
] |
['Precocious puberty (PP) in girls with McCune-Albright syndrome (MAS) is characterized by episodic development of large unilateral ovarian cysts followed by sudden onset of vaginal bleeding. Some patients experience frequent bleeding as well as accelerated linear growth and advanced skeletal maturation. The use of anastrozole for the treatment of PP in this condition has not been well studied.', 'The objective of the study was to determine the safety and efficacy of the aromatase inhibitor anastrozole for the treatment of PP in girls with MAS.', 'This was a prospective international multicenter study in which subjects received anastrozole 1 mg daily for 1 yr.', 'Twenty-eight girls 10 years of age or younger with MAS and progressive PP were enrolled.', 'Vaginal bleeding, rate of skeletal maturation (change in bone age over change in chronological age), growth velocity, and uterine/ovarian volumes were measured. These indices were compared with a 6-month pretreatment interval.', 'No difference in vaginal bleeding (mean number of days per year) was noted. Mean change in DeltaBA/DeltaCA, which was 1.25 +/- 0.77 at baseline, was -0.25 +/- 1.02 at study end (P = 0.22). Average growth velocity z score was 1.40 +/- 3.15 at study entry and 0.26 +/- 2.71 at 12 months (P = 0.10). Mean ovarian/uterine volumes were unaffected by anastrozole, and no significant adverse events occurred.'] Is the aromatase inhibitor anastrozole ineffective in the treatment of precocious puberty in girls with McCune-Albright syndrome? | qiaojin/PubMedQA | 2 | [
-2.0001330375671387,
-1.4139862060546875,
2.4790802001953125
] |
['Numerous and compelling evidence shows that high level of reactive oxygen species (ROS) plays a key role in prostate cancer occurrence, recurrence and progression. The molecular mechanism of ROS overproduction in the prostate gland, however, remains mostly unknown. Unique AP-1 transcription factor JunD has been shown to inhibit cell proliferation, promote differentiation and mediate stress responses in a variety of eukaryotic cells. We previously reported that androgen-androgen receptor induced ROS production in androgen-dependent LNCaP human prostate cancer cells is associated with increased JunD level/AP-1 transcriptional activity.', 'LNCaP cells constitutively overexpressing a functionally inactive form of JunD (JunDDeltaTA) or stably transfected with JunD siRNA (siJunD) to suppress JunD protein expression were established. Overexpression of JunD in LNCaP cells using transient transfection method was applied to assess the induction of ROS production in LNCaP cells. DCF assay was used to measure the ROS concentrations in the transfected as well as non-transfected control cells. RT-PCR and Western blot analyses were used to confirm silencing or overexpression of JunD in the transfected cells.', 'In the absence of androgen, LNCaP cells transiently transfected with a JunD overexpressing vector have relatively enhanced cellular ROS levels as compared to LNCaP cells transfected with a vector control. LNCaP cells that fail to express functional JunD (JunDDeltaTA or siJunD) do not exhibit any increase in ROS production in response to androgen.'] Does junD mediate androgen-induced oxidative stress in androgen dependent LNCaP human prostate cancer cells? | qiaojin/PubMedQA | 2 | [
-2.5099871158599854,
-1.2388455867767334,
2.8061439990997314
] |
['Polymorphous light eruption (PLE) is a very common photodermatosis in which patient history is highly specific. Phototesting is used to confirm the diagnosis and to determine the action spectrum and the severity of this disease. In daily practice and in research studies, it would be convenient to assess disease severity by patient history only.', 'This study aims to assess PLE disease severity via patient history and compares this with severity assessment via phototesting.', 'Sixty-one patients with PLE were asked 10 standard questions and all were phototested. The answers to the standard questions were coded with linear scores ranging from 0 to 10. The score of each question was plotted as independent variable in a multiple linear regression model against the score of the phototest (minimal number of irradiations necessary to elicit a positive skin lesion, with a maximum of 6 irradiations) as dependent variable using an enter approach. Furthermore, the scores of the separate questions were added to form a total score, the PLE-severity assessment score (PLE-SAS). The medians of these PLE-SASs were compared with the result scores obtained by phototesting. Phototesting was done with ultraviolet A and ultraviolet B irradiation.', 'Fifty-seven of the 61 patients had a positive test result (93%). Using the multiple linear regression model, the severity assessment by patient history (PLE-SAS) compared with the result of phototesting showed two significant contributing questions (adjusted PLE-SAS) (P < 0.05) but with a regression coefficient of 0.2. A significant difference in median scores with the severity assessment (PLE-SAS and adjusted PLE-SAS) between patients testing positive after 1-3 irradiations compared with those testing positive after 4-6 irradiations was present (P < 0.05). However, the overlap quartile range between both groups was such that the PLE-SAS and the adjusted PLE-SAS have little predictive value in individual patients.'] Does the polymorphous light eruption-severity assessment score reliably predict the results of phototesting? | qiaojin/PubMedQA | 2 | [
-0.9189226627349854,
-1.5413947105407715,
1.507676362991333
] |
["Magnetic resonance (MRI) studies rely on sulcal boundaries to delineate the human entorhinal cortex (EC) and typically show that EC size is reduced in Alzheimer's disease (AD) and a predictor of future dementia. However, it is unknown if variations in the EC sulcal patterns are associated with AD. We classified the lateral EC sulcal boundary as either a rhinal or collateral pattern and tested the hypotheses that the rhinal pattern was (1) more common in AD and (2) associated with a smaller EC size.", 'MRI was used to determine the prevalence of the rhinal and collateral EC patterns in 421 subjects (212 AD, 107 old normal (ONL), and 102 young NL (YNL). Anatomical validation studies of normal subjects were conducted at postmortem in 34 brain hemispheres and in vivo with 21 MRI volume studies. EC pattern reliability was studied with MRI in both cross-sectional and longitudinal designs.', 'The rhinal pattern was more frequent in the right hemisphere in AD (47%) compared with ONL (28%, odds ratio = 2.25, P = 0.001). EC pattern was not related to ApoE genotype. The validations showed that the EC sulcal pattern was not associated with the neuronal number, surface area, or volume of the EC. In patients with antemortem MRI studied at postmortem it was equivalently determined, that EC patterns are reliably determined on MRI and do not change with the progressive atrophy of AD.'] Is an entorhinal cortex sulcal pattern associated with Alzheimer 's disease? | qiaojin/PubMedQA | 2 | [
-2.269751787185669,
-1.212977647781372,
2.574631690979004
] |
['To explain differences in survival in the first three years of combination anti-retroviral therapy (cART) between HIV treatment centres in The Netherlands.', 'We developed a mathematical simulation model, parameterised using data from the ATHENA cohort that describes patients entering care, being monitored and starting cART. Three scenarios were used to represent three treatment centres with widely varying mortality rates on cART that were differentiated by: (i) the distribution of CD4 counts of patients entering care; (ii) the age distribution of patients entering care; (iii) the average rate of monitoring the patients not on cART. At the level of the treatment centre, the fraction of Dutch MSM dying in the first three years of treatment ranged from 0% to 8%. The mathematical model captured the large variation in observed mortality between the three treatment centres. Manipulating the age-distribution of patients or the frequency of monitoring did not affect the model predictions. In contrast, when the same national average distribution of CD4 count at entry was used in all the scenarios, the variation in predicted mortality between all centres was diminished.'] Does late entry to HIV care limit the impact of anti-retroviral therapy in The Netherlands? | qiaojin/PubMedQA | 1 | [
-0.7051267623901367,
1.1604199409484863,
-1.022884488105774
] |
['The intervertebral disc has been reported to be an immunologically privileged environment, possibly mediated by Fas ligand (FasL) expression. On the other hand, recent studies have shown the infiltration of host immune cells into the degenerated disc, which may indicate the failure of the immune-privilege feature of the disc with degeneration. However, the relationship between FasL expression and disc degeneration is still unclear. Therefore, the purpose of this study was to clarify the relationship between FasL expression and disc degeneration.', 'Ten human degenerated disc specimens were obtained from spondylolisthesis patients and ten nondegenerated discs from idiopathic scoliosis patients during surgical procedures. Immunohistochemical staining was performed to determine the presence of FasL in cross-sections of those discs. Parts of the disc tissues were used to examine FasL expression quantitatively with Western blot analysis. To examine whether the change in FasL expression was influenced by aging, an animal study comparing the discs from young and old rats were performed using magnetic resonance imaging (MRI) and real-time polymerase chain reaction (PCR) assessment.', 'Nucleus pulposus cells showed strong positive staining for FasL in all specimens examined. Quantitative examination demonstrated a significant decrease in FasL expression in the degenerated group compared with the nondegenerated group (average 67.6%, P<0.05). MRI showed no significant differences in the grade of disc degeneration between young and old rats, and also no significant difference in FasL mRNA in real-time PCR assay.'] Does fas ligand expression on human nucleus pulposus cells decrease with disc degeneration processes? | qiaojin/PubMedQA | 2 | [
-2.294970750808716,
-1.3201580047607422,
2.700005054473877
] |
['Binding of integrins to the extracellular matrix elicits various responses. We have previously reported a megakaryocytic-erythroid cell line (JAS-R) that showed phenotypic changes after adhesion to plastic dishes. However, the matrix protein and the mechanism responsible for megakaryocytic differentiation still remain unknown.', 'JAS-REN (erythroid) cells were cultured on dishes coated with various proteins. The cells were treated with RGDS, a tetrapeptide ligand to integrins, or phorbol ester (12-o-tetradecanoylphorbol-13-acetate, TPA) for 48 hours and then were harvested. Subsequently, the cell surface markers were analyzed using flow cytometry and gene expression was studied by RT-PCR.', 'The JAS-REN cells adhered to fibronectin-coated dishes, but showed poor adhesion to dishes coated with collagen, laminin or poly-D-lysine. The TPA-stimulated JAS-REN cells showed an increase in the expression of integrin alphaIIbbeta3 complex (CD41a) and integrin beta3 (CD61), while glycophorin A (CD235a) expression was decreased. JAS-REN cells that were adherent to fibronectin-coated dishes also showed a similar pattern of phenotype to TPA-treated cells, but the changes were not so prominent. RT-PCR revealed that TPA treatment altered the gene expression profile of JAS-REN cells, making it similar to that of JAS-RAD (megakaryocytic) cells. The RGDS-treated and fibronectin adherent JAS-REN cells also showed a mostly similar expression profile to JAS-RAD cells, but these two stimuli did not alter the gene expression profile as TPA stimulation did. Transcription factors, FLI1 and GFI1, were induced by all stimuli.'] Does adhesion to fibronectin induce megakaryocytic differentiation of JAS-REN cells? | qiaojin/PubMedQA | 2 | [
-2.4050848484039307,
-1.3453388214111328,
2.7689101696014404
] |
['The DNA repair gene XRCC4, an important caretaker of the overall genome stability, is thought to play a major role in the human carcinogenesis. Some new and important polymorphic variants of XRCC4, at codon 247 (rs 3734091), G-1394T (rs 6869366), and Intron 7 (rs 28360317), and their association with breast cancer susceptibility was investigated in a Taiwanese population.', 'In a hospital-based case-control study, 432 female patients with breast cancer and 432 age-matched healthy controls recruited from the China Medical Hospital in Central Taiwan were genotyped.', 'A significant difference in the frequency of the XRCC4 G-1394T genotype, but not the XRCC4 codon 247, or intron 7 genotypes was found between the breast cancer and control groups. Individuals with G/T or T/T at the XRCC4 G-1394T locus showed a 2.33-fold (95% confidence interval=1.37-3.98) increased risk of breast cancer compared to those with G/G. For XRCC4 codon 247 or intron 7, there was no difference in distribution between the breast cancer and control groups.'] Is a new single nucleotide polymorphism in XRCC4 gene associated with breast cancer susceptibility in Taiwanese patients? | qiaojin/PubMedQA | 2 | [
-2.0201528072357178,
-1.184654712677002,
2.2369308471679688
] |
['Stromal derived factor-1 (SDF-1), a protein related to angiogenesis and inflammation, has been correlated with the progression of a number of malignancies, but not with oral squamous cell carcinoma. In light of the known contribution to the development of oral cancer of other gene polymorphisms for proteins responsible for angiogenesis, inflammation and thrombosis, this study investigated whether the G801A polymorphism in the SDF-1 gene is associated with this malignancy.', 'The G801A polymorphism was examined by restriction fragment length polymorphism analysis in DNA samples from 159 patients with oral squamous cell carcinoma and 101 matched healthy controls.', 'The detected allele frequency of the "high production related" A allele in the control group was 25.3%. There was a slight decrease in allele frequency in patients (18.6%), but it was not statistically significant. The same pattern was observed in subgroups of patients in regard to smoking habits and family history of cancer or thrombosis. Interestingly, in comparison to controls, the A allele frequency was significantly lower in patients with advanced cancer stages III and IV (12.5%, p=0.005) and in patients with alcohol abuse (12.5%, p=0.02).'] Is a DNA polymorphism of stromal-derived factor-1 associated with advanced stages of oral cancer? | qiaojin/PubMedQA | 2 | [
-2.1263272762298584,
-1.3286725282669067,
2.50081729888916
] |
['To test the efficacy of resveratrol, a nontoxic plant product, in the treatment of uveal melanoma.', 'The effect of oral administration and peritumor injection of resveratrol was tested on tumor growth in two animal models of uveal melanoma. The mechanism of resveratrol action on uveal melanoma cells was studied in vitro in a cell-viability assay: with JC-1 dye, to measure mitochondrial membrane potential; by Western blot analysis, to analyze the cellular redistribution of cytochrome c and Smac/diablo; and in a fluorescence assay with specific substrates, to measure activation of different caspases.', 'Resveratrol treatment inhibited tumor growth in animal models of uveal melanoma. Since oral administration resulted in relatively low bioavailability of resveratrol, the effect of increased local levels was tested by peritumor injection of the drug. This method resulted in tumor cell death and tumor regression. In vitro experiments with multiple uveal melanoma cell lines demonstrate that resveratrol causes a decrease in cell viability, resulting at least in part from an increase in apoptosis through a mitochondrial pathway. An early event in drug action is the direct targeting of mitochondria by resveratrol, which leads to a decrease in mitochondrial membrane potential and the eventual activation of caspase-3.'] Does resveratrol inhibit uveal melanoma tumor growth via early mitochondrial dysfunction? | qiaojin/PubMedQA | 2 | [
-2.488060712814331,
-1.22200345993042,
2.8179616928100586
] |
['The excessive proliferation and migration of vascular smooth muscle cells (SMCs) and angiogenesis of endothelial cells (ECs) participate in the growth and instability of atherosclerotic plaques. It is unclear whether Jun N-terminal kinase (JNK) is pro-or anti-atherogenic.', 'We examined the direct effect of JNK inhibitor (JNK-I) on the proliferation and formation of tubes by human coronary SMCs and human coronary ECs.', 'Culture medium from JNK-I-treated SMCs prevented ECs from forming tubes in an in vitro model of angiogenesis indirectly by reducing the amount of vascular endothelial growth factor (VEGF) released from SMCs. In addition, JNK-I attenuated the expression of pro-matrix metalloproteinase-2 in ECs. When added back to the medium of SMCs treated with JNK-I, VEGF blocked the inhibitory effect on the formation of tubes.'] Does jun N-terminal kinase inhibitor block angiogenesis by blocking VEGF secretion and an MMP pathway? | qiaojin/PubMedQA | 2 | [
-2.5184690952301025,
-1.1180741786956787,
2.651944160461426
] |
['Resistin in serum is associated with high risk in patients with atherosclerosis. This clinical study aimed to investigate whether pitavastatin can regulate the serum level of resistin, together with levels of other inflammatory cytokines and adipocytokines.', 'Forty two outpatients (mean age 65.2 +/- 12.6 yr, M/F: 21/21) with hypercholesterolemia were administered 2 mg of pitavastatin and serum levels of resistin, together with serum levels of adiponectin, leptin, TNF-alpha and hsCRP, were measured before, and 12 weeks after enrollment.', 'There was no significant gender-related difference in initial serum resistin levels. Pitavastatin significantly decreased LDL-cholesterol after 12 weeks. Initial levels of resistin showed a significant correlation with those of hsCRP (r=0.38, p=0.013), but not TNF-alpha or HOMA-R. Serum resistin, but not adiponectin and leptin, levels were significantly decreased, dropping from 17.1 +/- 9.9 ng/ dL to 15.2+/-10.0 (p=0.001) after 12 weeks of administration. The patient group with a baseline hsCRP > or = 0.1 at enrollment (n=17) had decreased levels of both resistin and hsCRP (p=0.011 and p=0.022, respectively).'] Does pitavastatin improve serum resistin levels in patients with hypercholesterolemia? | qiaojin/PubMedQA | 2 | [
-1.7615169286727905,
-1.4991984367370605,
2.2669663429260254
] |
['Recently, a segregation study in families with uveal and cutaneous melanoma identified 9q21 as a potential locus harboring a tumor-suppressor gene (TSG). One of the genes in this area, RASEF, was then analyzed as a candidate TSG, but lack of point mutations and copy number changes could not confirm this. In this study, the RASEF gene was investigated for potential mutations and gene silencing by promoter methylation in uveal melanoma.', 'Eleven uveal melanoma cell lines and 35 primary uveal melanoma samples were screened for mutations in the RASEF gene by high-resolution melting-curve and digestion analysis. Expression of RASEF was determined by real-time RT-PCR in all cell lines and 16 primary uveal melanoma samples, and the methylation status of the promoter of the RASEF gene was analyzed and confirmed by direct sequencing.', 'Mutation screening revealed a known polymorphism (R262C; C-->T) in exon 5 of the RASEF gene that displayed a normal frequency (54%). Of the primary uveal melanomas, 46% presented a heterozygous genotype, and 10 (91%) of 11 cell lines showed a homozygous genotype. Melting-curve analysis indicated loss of heterozygosity in at least two primary tumors. Low RASEF expression in the cell lines and primary tumors correlated with methylation of the RASEF promoter region. Homozygosity and methylation of the RASEF gene in primary tumors were associated with decreased survival (P = 0.019).'] Does epigenetic regulation identify RASEF as a tumor-suppressor gene in uveal melanoma? | qiaojin/PubMedQA | 2 | [
-2.1584599018096924,
-1.3403048515319824,
2.5887222290039062
] |
['To investigate the enhancing effect of all-trans retinoic acid (ATRA) on the bystander effect of the herpes simplex virus thymidine kinase(HSV-TK)/ganciclovir (GCV) against androgen unresponsive prostate cancer.', 'The bystander effect of the HSV-TK/GCV system was measured by methyl thiazolyl tetrazolium (MTT) assay on PC-3 cells before and after ATRA treatment. The growth and the histopathology of transplant tumors were observed in 4 groups of nude mice with prostate cancer.', 'ATRA augmented significantly the bystander effect of the HSV-TK/GCV system by reducing TK positive PC-3 cells from 50% to 30% (P < 0.05). HSV-TK showed an inhibiting effect, while ATRA with the HSV-TK/GCV system produced significant effect on prostate cancer 1 week earlier than the former (P < 0.05).'] Does [ All-trans retinoic acid enhance bystander effect of suicide-gene therapy against androgen-unresponsive prostate cancer ]? | qiaojin/PubMedQA | 2 | [
-2.4873087406158447,
-1.161970853805542,
2.7045578956604004
] |
['To investigate the role of advanced glycation end products (AGEs) and their receptors (RAGE) in the pathogenesis of diabetic mellitus erectile dysfunction (DMED) and the effects of AGEs and RAGE on the activity of endothelin-1 (ET-1) in rat cavernosum.', 'Forty male Sprague-Dawley rats were taken at random to construct 2 groups of diabetes mellitus (DM) models of equal number, one given free access to water and the other administered aminoguanidine hydrochloride (DM + AG) in water at the dose of 1 g/L. Another 20 male SD rats were equally divided into a normal control and an AG control group. After 8 weeks, the cavernosum tissues were harvested from all groups of rats, part of the isolated penile tissues homogenated to detect the content of AGE-peptide (AGE-P) and the activity of ET-1, and the AGEs and RAGE in the rest of the penile tissues analyzed by immunohisto- chemical assay.', 'Compared with the normal controls, the expressions of AGEs and RAGE, the content of AGE-P and the activity of ET-1 in the cavernosum tissues were significantly high in the DM group (P < 0.05), while the administration of AG to the DM rats reversed the above results. No significant difference was observed between the normal control and AG control groups in any of the data (P > 0.05).'] Do [ Advanced glycation end products and their receptors elevate the activity of endothelin-1 in rat cavernosum ]? | qiaojin/PubMedQA | 2 | [
-2.3792998790740967,
-1.0782554149627686,
2.552671432495117
] |
['Fruit flies (Diptera: Tephritidae) represent a major biosecurity threat to the horticulture sector of New Zealand, which is entirely free of these invasive pests. A nationwide surveillance programme is conducted to ensure any incursion is detected as early as possible. A review of the lure dispensers used is reported here.', 'Lure dispenser emission trials found that the currently used lure plugs release lure more slowly under New Zealand subtropical to temperate climates than wafer dispensers. Subsequent trapping experiments at high altitude in Hawaii (as a mimic of New Zealand meteorological and expected fruit fly ecological conditions) compared Lynfield traps baited with the existing lure plug dispensers and newer wafer dispensers. Catches of wild Oriental fruit flies, Bactrocera dorsalis (Hendel), were 9.5-fold higher with methyl eugenol wafers than with the plugs. Recaptures of sterile melon flies, Bactrocera cucurbitae (Coquillet), were 2.6-fold higher with cuelure wafers than with the plugs. Recaptures of sterile Mediterranean fruit flies, Ceratitis capitata Weid., were not significantly higher with trimedlure wafers than with the plugs.'] Do evaluation of lure dispensers for fruit fly surveillance in New Zealand? | qiaojin/PubMedQA | 2 | [
-2.180743932723999,
0.18942497670650482,
1.1209088563919067
] |
['To evaluate the management of cardiovascular risk factors in a population-based cohort of adults with diabetes mellitus in Germany.', 'For the 9953 participants (50-74 years of age) of the ESTHER study, diabetes mellitus, hypertension, dyslipidemia and the respective medication were documented at baseline by their primary care physician. Blood pressure was taken and lipid levels were determined from a blood sample drawn at recruitment. Lifestyle factors (smoking, BMI, physical activity) were documented by the participants. Prevalence of pharmacotherapy for and control of hypertension and dyslipidemia among diabetic patients with these diagnoses were assessed and determinants were evaluated by multiple logistic regression.', 'Diabetes mellitus was present in 1375 participants (14.2%). Almost 78% of diabetic participants had physician diagnosed hypertension, 86.0% received pharmacotherapy, but only 12.8% of those with anti-hypertensive medication achieved blood pressure levels below 130/85 mmHg. Obese participants were more likely to receive anti-hypertensive pharmacotherapy than non-obese ones: adjusted odds ratio (OR, 95% confidence interval (CI)): 3.58 (1.86-6.87). Gender had no influence on anti-hypertensive pharmacotherapy. Older diabetic patients with hypertension were less likely to have sufficient blood pressure control than younger ones. Dyslipidemia was documented in 50% of diabetic patients. Diabetic participants with coronary heart disease or hypertension were more likely to receive lipid-lowering pharmacotherapy than those without these conditions (adjusted OR 1.85 (95%CI 1.19-2.89) and 2.59 (95%CI 1.41-4.74), respectively).'] Is for the majority of patients with diabetes blood pressure and lipid management in line with recommendations . Results from a large population-based cohort in Germany? | qiaojin/PubMedQA | 2 | [
-1.1098968982696533,
-1.2625155448913574,
1.4083917140960693
] |
['To investigate the predictive value of overgeneral memory (OGM) for outcome of electroconvulsive therapy (ECT) for depression.', 'The Autobiographical Memory Test was used to measure OGM in 25 patients with depression before ECT. The Hamilton Rating Scale for Depression (HRSD) was administered weekly to 1 week posttreatment.', 'Overgeneral memory did not predict HRSD scores from the last ECT treatment, but did predict HRSD change scores from the last treatment to 1-week follow-up: patients high in OGM experienced a relatively greater increase in HRSD scores after the last treatment.'] Does overgeneral memory predict stability of short-term outcome of electroconvulsive therapy for depression? | qiaojin/PubMedQA | 2 | [
-2.432140588760376,
-0.10404498130083084,
1.556473731994629
] |
['The aim of this study was to determine the influence of gender on in hospital outcome in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary angioplasty (PA).', 'Prospective study of a cohort of patients consecutively admitted to the Coronary Unit of a tertiary hospital in the period of January to October 2004 with the diagnoses of IAMEST and treated with PA.', 'Consecutive sample of 86 patients with this diagnosis divided into two groups based on sex: 52 men and 34 women.', 'In both groups, we analyzed the baseline clinical-demographic characteristics, extension of the coronary disease (ECD), success of the PA, appearance of heart failure (HF) and in-hospital mortality in the first 28 days after admission. We analyzed predictors of mortality in a multivariate model.', 'The women were older (70+/-8 versus 65+/-11; p=0.02) and had greater prevalence of diabetes (37% versus 18%; p=0.002) and hypertension (58% versus 37%; p<0.001) than the men while the men had greater frequency of smoking (34% versus 22%; p=0.001). There were no differences in the presence of hyperlipidemia, ECD or the success of PA. Women had a higher incidence of HF on admission (22% versus 12%; p=0.01) and in-hospital mortality (17% versus 8%; p=0.002). In the multivariate analyses, female sex and HF on admission continued to be predictors of in-hospital mortality.'] Is [ Female gender an independent predictor of in-hospital mortality in patients with ST segment elevation acute myocardial infarction treated with primary angioplasty ]? | qiaojin/PubMedQA | 2 | [
-1.917312502861023,
-0.8325222134590149,
1.8747003078460693
] |
['The status of estrogen receptor-alpha (ER-alpha) expression is one of the most important diagnostic and prognostic factors of breast cancer. ER-alpha is a 66-kDa, ligand-induced transcription factor, characteristically detected in the cell nucleus by immunohistochemistry (IHC) in breast cancer specimens. Recently, we identified and cloned a 36-kDa novel variant of ER-alpha, ER-alpha36, which lacks both transactivation domains and functions as a dominant-negative effector of transactivation activities of the full-length ER-alpha (ER-alpha66) and ER-beta. ER-alpha36 primarily localizes to the cytoplasm and plasma membrane, and responds to both estrogens and antiestrogens by transducing membrane-initiated signaling cascades, stimulating proliferation and possibly contributing to a more aggressive phenotype in breast carcinomas. ER-alpha36 is expressed in established ER-positive and -negative breast cancer cell lines. However, its expression and localization in breast cancer specimens have not been evaluated. As ER-alpha36 may play important roles in breast cancer tumorigenesis, it is of clinical importance to examine the expression pattern of ER-alpha36, in addition to that of ER-alpha66, for more comprehensive molecular profiling of breast carcinomas.', 'Thirty-one breast cancer patient tissues were evaluated for ER-alpha36 and ER-alpha66 protein expression status by IHC and six additional patient tissue samples were analyzed by Western blot analysis using antibodies specific to ER-alpha66 or ER-alpha36.', 'Our experiments reveal a cytoplasmic and plasma-membrane-associated expression pattern of ER-alpha36 in both ER-alpha66-positive and -negative breast cancer samples. Furthermore, ER-alpha36 expression appears to be associated with decreasing nuclear and/or cytoplasmic ER-alpha66 expression, suggesting its potential use as a diagnostic and prognostic marker.'] Is eR-alpha36 , a novel variant of ER-alpha , expressed in ER-positive and -negative human breast carcinomas? | qiaojin/PubMedQA | 2 | [
-2.3077898025512695,
-1.2856335639953613,
2.6559154987335205
] |
['Uterine leiomyoma produce an extracellular matrix (ECM) that is abnormal in its volume, content, and structure. Alterations in ECM can modify mechanical stress on cells and lead to activation of Rho-dependent signaling and cell growth. Here we sought to determine whether the altered ECM that is produced by leiomyoma was accompanied by an altered state of mechanical homeostasis.', 'We measured the mechanical response of paired leiomyoma and myometrial samples and performed immunogold, confocal microscopy, and immunohistochemical analyses.', 'Leiomyoma were significantly stiffer than matched myometrium. The increased stiffness was accompanied by alteration of the ECM, cell shape, and cytoskeleton in leiomyoma, compared with myometrial samples from the same uterus. Levels of AKAP13, a protein that is known to activate Rho, were increased in leiomyoma compared to myometrium. AKAP13 was associated with cytoskeletal filaments of immortalized leiomyoma cells.'] Is mechanical homeostasis altered in uterine leiomyoma? | qiaojin/PubMedQA | 2 | [
-2.5109636783599854,
-1.1443839073181152,
2.8060851097106934
] |
['Chemoresistance, due to inhibition of apoptotic response, is the major reason for the failure of anticancer therapies. HIPK2 regulates p53-apoptotic function via serine-46 (Ser46) phosphorylation and activation of p53 is a key determinant in ovarian cancer cell death. In this study we determined whether HIPK2 overexpression restored apoptotic response in chemoresistant cancer cells.', 'Using cisplatin chemosensitive (2008) and chemoresistant (2008C13) ovarian cancer cell lines we compared drug-induced activation of the HIPK2/p53Ser46 apoptotic pathway. The levels of HIPK2, Ser46 phosphorylation, and PARP cleavage were detected by Western blotting. The p53Ser46 apoptotic commitment was evaluated by luciferase assay using the Ser46 specific AIP1 target gene promoter. The apoptotic pathway was detected by caspase-3, -8, and -9 activities.', 'HIPK2 was expressed differently in sensitive versus chemoresistant cells in response to different chemotherapeutic drugs (i.e., cisplatin and adriamycin), though the p53Ser46 apoptotic pathway was not defective in chemoresistant 2008C13 cells. Thus, 2008C13 cells were resistant to cisplatin but sensitive to adriamycin-induced apoptosis through activation of the HIPK2/p53Ser46 pathway. HIPK2 knock-down inhibited the adriamycin-induced apoptosis in 2008C13 cells. Exogenous HIPK2 triggered apoptosis in chemoresistant cells, associated with induction of p53Ser46-target gene AIP1.'] Does overexpression of HIPK2 circumvent the blockade of apoptosis in chemoresistant ovarian cancer cells? | qiaojin/PubMedQA | 2 | [
-2.3530972003936768,
-1.3797266483306885,
2.7109766006469727
] |
['It is asserted that the more immediate and observable consequences of pediatric obesity are psychosocial in nature. This study examines the peer relations of clinically referred obese youth compared to demographically comparable nonoverweight peers within the classroom environment.', 'Peer-, teacher-, and self-reports of behavioral reputation (Revised Class Play (RCP)), and peer reports of social acceptance, nonsocial attributes (attractiveness, athleticism, academic competence), and health interference (school absence, illness, fatigue) were obtained regarding 90 obese youth (BMI > 95th percentile; 8-16 years, 57% girls, 50% African American) and 76 nonoverweight demographically similar comparison classmates.', "Relative to comparison peers, obese children were nominated significantly less often as a best friend and rated lower in peer acceptance, although the two groups did not differ in the number of reciprocated friendships. Obese youth were described by peer, teacher, and self-report as more socially withdrawn and by peers as displaying less leadership and greater aggressive-disruptive behavior. Peers also described obese youth as less physically attractive, less athletic, more sick, tired, and absent from school. Being seen as less attractive and less athletic by peers helped to explain differences in obese and nonoverweight youth's levels of peer acceptance."] Do negative peer perceptions of obese children in the classroom environment? | qiaojin/PubMedQA | 1 | [
-2.396840810775757,
1.640446424484253,
-0.0077451858669519424
] |
['Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha. We assessed the effects of TNF-alpha neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome.', 'Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with metabolic syndrome, before and after administration of infliximab.', 'Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with control subjects; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with metabolic syndrome, but its effect was not further enhanced by concurrent administration of infliximab.'] Does tumor necrosis factor-alpha antagonism improve vasodilation during hyperinsulinemia in metabolic syndrome? | qiaojin/PubMedQA | 2 | [
-2.6172902584075928,
-1.10152006149292,
2.7954061031341553
] |
['To investigate the association between dietary adherence and glycemic control among youth with type 1 diabetes.', 'We conducted a cross-sectional analysis of 119 youth aged 9-14 years (mean +/- SD 12.1 +/- 1.6 years) with diabetes duration > or =1 year (5.4 +/- 3.1 years). Dietary adherence was assessed using the Diabetes Self-Management Profile diet domain. Higher score defined greater dietary adherence. Glycemic control was determined by A1C.', 'Dietary adherence score was inversely correlated with A1C (r = -0.36, P < 0.0001). In a multivariate model (R(2) = 0.34, P < 0.0001), dietary adherence (P = 0.004), pump use (P = 0.03), and caregiver education (P = 0.01) were associated with A1C. A1C of youth in the lowest (9.0%) tertile of diet score was higher than A1C of youth in the middle (8.1%, P = 0.004) and upper (8.4%, P = 0.06) tertiles. Dietary adherence uniquely explained 8% of the variance in A1C in the model.'] Do dietary behaviors predict glycemic control in youth with type 1 diabetes? | qiaojin/PubMedQA | 2 | [
-0.8130525350570679,
-1.2868115901947021,
1.2318572998046875
] |
['Remifentanil is known to cause vasodilation at standard anesthetic concentrations. The intracellular mechanisms underlying its vasodilator action may involve the activation of ion channels. The purpose of this study was to examine whether remifentanil inhibits L-type calcium channels (Ca.(L)) and provides dose-dependent effects on L-type calcium channel Ba(2+) currents (I(Ba.L)) in human mesenteric arterial smooth muscle cells.', 'Using the whole-cell patch-clamp method, an in depth analysis of the mechanism of the I(Ba.L) induced by remifentanil was performed in cells which were enzymatically isolated from human mesenteric arterial smooth muscle. Ten millimolars Ba(2+) was used to replace 1.5 mM Ca(2+) to increase the amplitude of the inward current through Ca(2+)channels. L-type calcium channel Ba(2+) was elicited during 50 msec depolarizing test pulses (150 msec duration) to +80 mV (10 mV increments) from a holding potential of -60 mV. The effects of remifentanil on Ca.(L) were observed at the following concentrations: 1.21, 4.84, and 19.4 nmol.L(-1) and were compared with control.', 'Remifentanil produced a concentration-dependent block of I(Ba,L) with IC(50) values of 38.90 +/- 3.96 x 10(-3) micromol.L(-1). The L-type calcium channel blocker, nifedipine, antagonized these remifentanil-induced currents. Remifentanil, at all concentrations, shifted the maximum of the current-voltage relationship in the hyperpolarizing direction of I(Ba.L).'] Does remifentanil induce L-type Ca2+ channel inhibition in human mesenteric arterial smooth muscle cells? | qiaojin/PubMedQA | 2 | [
-1.9556939601898193,
-1.5042543411254883,
2.5044493675231934
] |
['Aminoglycosides are mandatory in the treatment of severe infections in burns. However, their pharmacokinetics are difficult to predict in critically ill patients. Our objective was to describe the pharmacokinetic parameters of high doses of tobramycin administered at extended intervals in severely burned patients.', 'We prospectively enrolled 23 burned patients receiving tobramycin in combination therapy for Pseudomonas species infections in a burn ICU over 2 years in a therapeutic drug monitoring program. Trough and post peak tobramycin levels were measured to adjust drug dosage. Pharmacokinetic parameters were derived from two points first order kinetics.', 'Tobramycin peak concentration was 7.4 (3.1-19.6)microg/ml and Cmax/MIC ratio 14.8 (2.8-39.2). Half-life was 6.9 (range 1.8-24.6)h with a distribution volume of 0.4 (0.2-1.0)l/kg. Clearance was 35 (14-121)ml/min and was weakly but significantly correlated with creatinine clearance.'] Do pharmacokinetic variability of extended interval tobramycin in burn patients? | qiaojin/PubMedQA | 2 | [
-2.1677019596099854,
-1.4148417711257935,
2.691889762878418
] |
['To evaluate whether intravascular Fluorinert (FC-77) attenuates phorbol myristate acetate (PMA)-induced acute lung injury in rats.', 'Randomized, controlled animal study.', 'Animal care facility procedure room in a medical center.', 'Thirty-six adult male Sprague-Dawley rats each weighing 250-350 g.', 'PMA (2 microg/kg) was injected into lung perfusate and induced acute lung injury. Different doses of FC-77 were given before PMA administration. The isolated rat lungs were randomly assigned to two control groups (saline and 1% FC-77 only) and four PMA groups (PMA, 0.1% FC-77 + PMA, 0.5% FC-77+PMA, and 1% FC-77+PMA); each condition was maintained for 60 mins.', 'The extent of acute lung injury was assessed by microvascular permeability (measured using the capillary filtration coefficient), lung weight gain, wet lung-to-body weight ratio, pulmonary arterial pressure, and protein concentration of the bronchoalveolar lavage fluid. The concentration of tumor necrosis factor-alpha in lung perfusate was determined. Parts of the right lung were excised for myeloperoxidase and malondialdehyde measurements, whereas the rest was examined for histopathological changes. PMA produced a significant increase in the capillary filtration coefficient, lung weight gain, wet lung-to-body weight ratio, pulmonary arterial pressure, and protein concentration of the bronchoalveolar lavage fluid. Tumor necrosis factor-alpha in lung perfusate and myeloperoxidase and malondialdehyde in lung tissue were also significantly increased. In addition, the pathologic picture showed increased neutrophil infiltration in lung tissues. In contrast, pretreatment with intravascular FC-77 significantly attenuated these variables in a dose-dependent manner compared with the PMA group.'] Does intravascular FC-77 attenuate phorbol myristate acetate-induced acute lung injury in isolated rat lungs? | qiaojin/PubMedQA | 2 | [
-2.336984395980835,
-1.4346539974212646,
2.8139162063598633
] |
['We hypothesized that nitric oxide derived from the neuronal nitric oxide synthase (NOS) is responsible for much of the injury resulting from skin burn and smoke inhalation. Therefore, we aimed to examine the effects of selective neuronal NOS inhibition on cardiopulmonary functions and cellular injury in sheep with acute respiratory distress syndrome secondary to combined burn and smoke inhalation injury.', 'Prospective, randomized, controlled laboratory experiment.', 'Investigational intensive care unit.', 'A total of 22 chronically instrumented adult ewes.', 'Sheep were randomly assigned to either healthy controls (sham), injured controls (40% third-degree flame burn; 48 breaths of cotton smoke), or an injury group treated with the specific neuronal NOS inhibitor 7-nitroindazole (1 mg x kg(-1) x hr(-1)) from 1 hr postinjury to the end of the 48-hr study period. Hypoxic pulmonary vasoconstriction was assessed as decrease in left pulmonary blood flow in response to single-lung hypoxic challenges (100% nitrogen) at baseline, 24 hrs, and 48 hrs.', 'The combination injury contributed to a approximately 90% loss of hypoxic pulmonary vasoconstriction and was associated with significant pulmonary shunting and death of one animal. The increase in nitrate/nitrite plasma levels in injured controls (12 hrs: 17 +/- 2 vs. 6 +/- 1 microM in sham animals; p < .001) was linked to increases in inducible NOS messenger RNA and 3-nitrotyrosine formation in lung tissue (48 hrs: 22 +/- 1 vs. 0.8 +/- 0.3 nM in sham animals; p < .001). 7-Nitroindazole treatment prevented the injury-associated changes in inducible NOS messenger RNA, nitrate/nitrite, and 3-nitrotyrosine, thereby attenuating the loss of hypoxic pulmonary vasoconstriction and improving gas exchange. In addition, 7-nitroindazole decreased lung tissue concentrations of hemoxygenase-1 and ameliorated myocardial depression, airway obstruction, pulmonary edema, ventilatory pressures, and histopathologic changes seen in injured controls.'] Does neuronal nitric oxide synthase inhibition attenuate cardiopulmonary dysfunctions after combined burn and smoke inhalation injury in sheep? | qiaojin/PubMedQA | 2 | [
-2.2304530143737793,
-1.4562230110168457,
2.7209558486938477
] |
['TAR DNA-binding protein 43 (TDP-43) is one of the major disease proteins in frontotemporal lobar degeneration with ubiquitin immunoreactivity. Approximately one-fourth of subjects with pathologically confirmed Alzheimer disease (AD) have abnormal TDP-43 (abTDP-43) immunoreactivity. The aim of this study was to determine whether subjects with pathologically confirmed AD and abTDP-43 immunoreactivity have distinct clinical, neuropsychological, imaging, or pathologic features compared with subjects with AD without abTDP-43 immunoreactivity.', 'Eighty-four subjects were identified who had a pathologic diagnosis of AD, neuropsychometric testing, and volumetric MRI. Immunohistochemistry for TDP-43 was performed on sections of hippocampus and medial temporal lobe, and positive cases were classified into one of three types. Neuropsychometric data were collated and compared in subjects with and without abTDP-43 immunoreactivity. Voxel-based morphometry was used to assess patterns of gray matter atrophy in subjects with and without abTDP-43 immunoreactivity compared with age- and sex-matched controls.', 'Twenty-nine (34%) of the 84 AD subjects had abTDP-43 immunoreactivity. Those with abTDP-43 immunoreactivity were older at onset and death and performed worse on the Clinical Dementia Rating scale, Mini-Mental State Examination, and Boston Naming Test than subjects without abTDP-43 immunoreactivity. Subjects with and without abTDP-43 immunoreactivity had medial temporal and temporoparietal gray matter loss compared with controls; however, those with abTDP-43 immunoreactivity showed greater hippocampal atrophy. Multivariate logistic regression adjusting for age at death demonstrated that hippocampal sclerosis was the only pathologic predictor of abTDP-43 immunoreactivity.'] Does abnormal TDP-43 immunoreactivity in AD modify clinicopathologic and radiologic phenotype? | qiaojin/PubMedQA | 2 | [
-2.113086462020874,
-1.4099419116973877,
2.5287113189697266
] |
['To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD).', 'Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)--and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample.', 'The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses.'] Does aPOE epsilon 4 allele predict faster cognitive decline in mild Alzheimer disease? | qiaojin/PubMedQA | 2 | [
-1.6490601301193237,
0.31296026706695557,
0.44502949714660645
] |
['Subjects with diabetes are reported to have an increased risk of dementia and cognitive impairment. However, the underlying causes remain unknown. We investigated the longitudinal associations between midlife insulin secretion, glucose metabolism, and the subsequent development of Alzheimer disease (AD) and dementia.', 'The population-based Uppsala Longitudinal Study of Adult Men started 1970 when the 2,322 participants were 50 years old. Investigation at baseline included determinations of acute insulin response and glucose tolerance using the IV glucose tolerance test and Homeostasis Model Assessment insulin resistance index. During a median follow up of 32 years, 102 participants were diagnosed with AD, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. Associations were analyzed using Cox proportional hazard models.', 'A low insulin response at baseline was associated with a higher cumulative risk of AD (hazard ratio for 1 SD decrease, 1.31; 95% CI, 1.10-1.56) also after adjustment for age, systolic blood pressure, body mass index, serum cholesterol, smoking, education level, and insulin resistance. This association was stronger in subjects without the APOE epsilon4 allele. Impaired glucose tolerance increased the risk of vascular dementia (hazard ratio for 1 SD decrease, 1.45; 95% CI, 1.05-2.00) but not AD. Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment.'] Does impaired insulin secretion increase the risk of Alzheimer disease? | qiaojin/PubMedQA | 2 | [
-2.030438184738159,
-0.7426181435585022,
1.8002915382385254
] |
['One of the major challenges in currently chemotherapeutic theme is lacking effective biomarkers for drug response and sensitivity. Our current study focus on two promising biomarkers, ERCC1 (excision repair cross-complementing group 1) and BRCA1 (breast cancer susceptibility gene 1). To investigate their potential role in serving as biomarkers for drug sensitivity in cancer patients with metastases, we statistically measure the mRNA expression level of ERCC1 and BRCA1 in tumor cells isolated from malignant effusions and correlate them with cisplatin and/or docetaxel chemosensitivity.', 'Real-time quantitative PCR is used to analysis related genes expression in forty-six malignant effusions prospectively collected from non-small cell lung cancer (NSCLC), gastric and gynecology cancer patients. Viable tumor cells obtained from malignant effusions are tested for their sensitivity to cisplatin and docetaxel using ATP-TCA assay.', 'ERCC1 expression level is negatively correlated with the sensitivity to cisplatin in NSCLC patients (P = 0.001). In NSCLC and gastric group, BRCA1 expression level is negatively correlated with the sensitivity to cisplatin (NSCLC: P = 0.014; gastric: P = 0.002) while positively correlated with sensitivity to docetaxel (NSCLC: P = 0.008; gastric: P = 0.032). A significant interaction is found between ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P = 0.010, n = 45).'] Is eRCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions associated with chemosensitivity to cisplatin and/or docetaxel? | qiaojin/PubMedQA | 2 | [
-2.1382296085357666,
-1.4015532732009888,
2.5782313346862793
] |
['Hypopituitarism is associated with dyslipidemia, and feeding hypophysectomized rats cholesterol induces severe hypercholesterolemia. This study aimed to unravel further how hypophysectomy alters cholesterol and bile acid metabolism.', 'Intact and hypophysectomized rats were studied during challenge with dietary cholesterol and ezetimibe and upon hormonal substitution with growth hormone, cortisone, and thyroid hormone.', 'Five findings were established in hypophysectomized rats: (1) The intestinal absorption of cholesterol is doubled. (2) Treatment with ezetimibe abolishes the increases in serum and liver cholesterol. (3) Only thyroid hormone treatment normalizes the increased absorption of cholesterol. (4) The intestinal gene expression of cholesterol transporters NPC1L1 and ABCG5/G8 is unaltered, whereas the hepatic expression of ABCG5/G8 is diminished but strongly stimulated by thyroid hormone. The latter mechanism was supported by measurements of biliary cholesterol and of fecal neutral steroids. (5) The reduced hepatic expression of ABCG5/G8 and Cyp7a1 was normalized by cholesterol feeding, suggesting that other nonestablished mechanisms under pituitary control are important to maintain rats resistant to dietary cholesterol.'] Is dramatically increased intestinal absorption of cholesterol following hypophysectomy normalized by thyroid hormone? | qiaojin/PubMedQA | 2 | [
-2.670450448989868,
-1.0356390476226807,
2.7835512161254883
] |
['The orphan nuclear receptor HNF4alpha is a member of the hepatic transcription factor network. This protein plays a pivotal role in liver development and hepatocellular differentiation. Nine splice variants have been identified, some of which are specifically regulated in disease. The role of HNF4alpha splice variants in hepatocellular carcinomas (HCC) is unknown. Here, we report an identification of novel candidate genes targeted by splice variants of HNF4alpha.', 'We used chromatin immunoprecipitation followed by cloning and sequencing of DNA. Expression of HNF4alpha P1 and P2 promoter-driven isoforms and of genes targeted by HNF4alpha were analyzed by quantitative reverse-transcription polymerase chain reaction, Western blotting, electrophoretic mobility shift assay, and immunohistochemistry.', 'We observed a remarkable switch in gene and protein expression from P1 to P2 promoter-driven fetal isoforms of HNF4alpha in transgenic livers and HCCs of epidermal growth factor (EGF) overexpressing mice and in human HCCs. We further identified EGF-receptor substrate (EPS15R), related EPS15, the premessenger RNA processing factor 3 (PRPF3), and taspase 1 (TASP1) as novel HNF4alpha disease regulated genes with induced expression in mouse and in human HCCs. We suggest EPS15 and EPS15R mediated internalization of activated EGF receptor to result in receptor recycling as to reinforce the proliferative response to EGF. Regulation of the type 2 asparaginase TASP1 and of the splicing factor PRPF3 further documents a switch to fetal liver programs in HCC.'] Are ePS15R , TASP1 , and PRPF3 novel disease candidate genes targeted by HNF4alpha splice variants in hepatocellular carcinomas? | qiaojin/PubMedQA | 2 | [
-2.4068853855133057,
-1.1908929347991943,
2.647717237472534
] |
['The transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2(-/-)) is essential for protecting cells against xenobiotic and oxidative stress. Increased oxidative stress has been implicated in the pathophysiology of many diseases including ethanol-induced liver disease. Therefore, the role of Nrf2(-/-) in ethanol-induced liver injury was investigated.', 'Wild-type and Nrf2(-/-) mice were fed with the ethanol diet, followed by examination of liver pathology, mortality, and ethanol metabolism.', 'Nrf2(-/-) mice displayed a dramatically increased mortality associated with liver failure when fed doses of ethanol that were tolerated by WT mice. Nrf2(-/-) mice showed a significantly reduced ability to detoxify acetaldehyde, leading to an accumulation of the toxic metabolite. Loss of Nrf2(-/-) caused a marked steatosis in livers of ethanol-fed mice, and Srebp1 was identified as a candidate transcription factor responsible for lipogenic enzyme induction. Furthermore, ethanol consumption led to a progressive depletion of total and mitochondrial reduced glutathione, which was associated with more pronounced structural and functional changes to mitochondria of Nrf2(-/-) mice. In addition, ethanol feeding elicited an aggravated inflammatory response mediated by Kupffer cells in Nrf2(-/-) mice as shown by an increased tumor necrosis factor-alpha secretion and activation of the interleukin-6/Stat-3 pathway. Together these changes lead to a vicious cycle of accumulating hepatocellular damage, ultimately leading to liver failure and death of Nrf2(-/-) mice.'] Does nuclear factor-eythroid 2-related factor 2 prevent alcohol-induced fulminant liver injury? | qiaojin/PubMedQA | 2 | [
-2.508408546447754,
-1.1900863647460938,
2.709717035293579
] |
['Clinical management of the chronic autoimmune liver disease, Primary Biliary Cirrhosis (PBC) involves addressing the underlying liver disease and a range of symptoms independent of liver disease severity. We have formally explored how these two perspectives of chronic disease management can be combined into a clinic consultation and impact upon quality of life (QOL) in PBC.', 'To develop and implement the first Integrated Care Pathway (ICP) for the management of liver disease progression and symptom management in PBC.', 'Process mapping of current practice by a multidisciplinary group developed a flowchart of care from which the clinical record evolved. Symptom assessment is incorporated into the PBC ICP (QOL; PBC-40, autonomic symptoms; Orthostatic Grading Scale, daytime sleepiness; Epworth Sleepiness Scale). All patients were considered who attended clinic between July 2005 and June 2006. Symptom assessment was repeated after 1 year in those participating in the initial clinic cohort.', 'The PBC ICP was successfully introduced into our clinical environment with high levels of patient satisfaction. A total of 225 PBC patients attended over 12 months. Initial QOL assessments were in 195 (87%). Five patients died (3%). Repeat assessment 1 year later occurred in 149 subjects (149/190; 78%). All symptom domains improved after ICP implementation with significant improvements in those with moderate and severe symptoms in all PBC-40 symptom domains (P < 0.02). In those with severe fatigue (n = 38) symptom improvement was even more dramatic (P = 0.002).'] Does an integrated care pathway improve quality of life in Primary Biliary Cirrhosis? | qiaojin/PubMedQA | 2 | [
-1.6911779642105103,
-1.072399616241455,
1.7843393087387085
] |
['To evaluate the signalment, clinical signs, diagnosis, treatment, and outcome associated with esophageal obstruction caused by a dental chew treat in dogs.', 'Retrospective case series.', '31 dogs.', 'Medical records were contributed from 19 hospitals via responses to a questionnaire that was developed for veterinarians who managed the cases.', 'Esophageal obstructions with the dental chew treat occurred primarily in small dogs (26/31 [83.9%]). The most common clinical signs were gagging, regurgitation, vomiting, anorexia, and lethargy. Diagnosis was usually made via survey thoracic radiography. Obstructions were most commonly located in the distal portion of the esophagus (23/31; 74.2%). Esophageal lesions were moderate or severe in 86.7% (26/30) of the dogs. Orad endoscopic removal of the foreign bodies was uncommon (8/31 [25.8%]); most were pushed into the stomach. Thoracotomy was necessary in 6 dogs. Esophageal strictures developed in 6 of 25 (24%) dogs that survived initial hospitalization. Overall mortality rate was 25.8%.'] Do esophageal foreign body obstruction caused by a dental chew treat in 31 dogs ( 2000-2006 )? | qiaojin/PubMedQA | 2 | [
-2.124124526977539,
-0.638001024723053,
1.919630527496338
] |
['Among elderly allograft recipients non-melanoma skin cancer (NMSC) is the most common malignancy. We have previously shown that malignancies are associated with a higher intensity of ciclosporin A (CsA)-induced immunosuppression.', 'Fifty-five long-term elderly renal transplant patients with a stable transplant function had regular skin examinations. The expression of the nuclear factor of activated T cells (NFAT)-regulated genes (interleukin-2, granulocyte-macrophage colony stimulating-factor, interferon-gamma) was determined by real-time PCR at CsA trough levels and two h after oral intake.', 'The CsA dose was 2.0 mg/kg (0.95-3.50), with CsA trough level (C0) level 97 microg/L (33-157) and CsA two-h level (C2) 538 microg/L (350-1228). NMSC was diagnosed in 14/55 patients (25.4%). A total of 85.7% of allograft recipients with NMSC were male (p < 0.005). Age, time after transplantation, CsA dose, CsA C0 and C2 level were comparable in both groups. NFAT-regulated gene expression was signficantly lower in patients with skin cancer compared with patients without skin cancer [4.94% (0.91-13.4) vs. 11.6% (3.3-40.8), p < 0.001).'] Does pharmacodynamic immune monitoring of NFAT-regulated genes predict skin cancer in elderly long-term renal transplant recipients? | qiaojin/PubMedQA | 2 | [
-1.8112274408340454,
-1.6036298274993896,
2.4107742309570312
] |
['The pathogenesis of normal tension glaucoma (NTG) might be related to impaired autoregulation of ocular blood flow. The purpose of the study is to evaluate retinal haemodynamics by fluorescein angiography and to correlate arteriovenous passage times (AVP) with ocular perfusion pressure in patients with NTG and controls.', 'Thirty-five patients with NTG without any topical treatment (mean age 53 +/- 11 years) and 35 age-matched controls (mean age 53 +/- 11 years) were included in this study. Retinal AVP was assessed by video fluorescein angiography using a scanning laser ophthalmoscope (Rodenstock, Germany). Dye dilution curves of temporal superior and inferior arterioles and venules were evaluated by digital image analysis. AVP was correlated to mean arterial blood pressure and ocular perfusion pressure.', 'The AVP was significantly prolonged in patients with NTG compared to controls (1.82 +/- 0.57 versus 1.42 +/- 0.46, p = 0.002). Patients with NTG and controls showed no significant differences in intraocular pressure, mean arterial pressure and mean and diastolic ocular perfusion pressure. The AVP was significantly correlated to mean arterial pressure and mean and diastolic ocular perfusion pressure in patients with NTG (r = -0.54; p = 0.0006, r = -0.51; p = 0.002, r = -0.49, p = 0.002), but not in controls (r = -0.21; p = 0.23, r = -0.19; p = 0.27, r = 0.02, p = 0.93).'] Is prolonged retinal arteriovenous passage time correlated to ocular perfusion pressure in normal tension glaucoma? | qiaojin/PubMedQA | 2 | [
-1.7492157220840454,
-1.6359046697616577,
2.3759605884552
] |
['This study aimed to investigate temperament and character correlates of panic disorder (PD) comorbidity in euthymic patients with bipolar disorder (BD) or unipolar depression (UD).', 'Temperament and character were assessed using the Temperament and Character Inventory Revised (TCI-R) in 181 patients (70 patients with BD-I, 51 patients with BD-II and 60 with UD) in a euthymic state for at least 2 months.', 'PD was diagnosed in 14.3% of BD-I patients, 31.4% of BD-II and 40% of UD. BD patients with PD, when compared with BD patients without PD, had higher scores on harm avoidance (OR=1.04; 95% CI=1.02-1.07; p=0.002). Patients with UD and PD, when compared to patients with UD without PD, had higher scores on social acceptance (OR=1.27; 95% CI=1.08-1.49; p=0.004).'] Do different temperament and character dimensions correlate with panic disorder comorbidity in bipolar disorder and unipolar depression? | qiaojin/PubMedQA | 2 | [
-1.1163336038589478,
-0.3417784869670868,
0.5895535945892334
] |
['Due to the late introduction of oral isotretinoin, there is only a single report of the use of this drug from India.', 'To evaluate the efficacy, acceptability and side effects of oral isotretinoin in Indian conditions and to compare the efficacy of oral isotretinoin monotherapy with that of a combination of oral isotretinoin and topical anti-acne agents.', 'Sixty clinically diagnosed patients of nodulocystic acne were divided into two groups of 30 each. Patients in group A were administered oral isotretinoin 20 mg twice a day along with topical clindamycin (1%) and adapalene (0.1%) for 24 weeks. Patients in group B were given only oral isotretinoin. An objective clinical scoring was repeated every four weeks and patients were followed up for six months on completion of treatment.', 'Out of the 60 patients, 50 completed the treatment and 35 completed the follow-up at six months. The mean pretreatment score in group A came down from 12.8 to 1.24 and in group B from 12.4 to 1.48, thus showing a 90.55% and 88% reduction in pretreatment scores respectively. There was no statistical difference in the results obtained from the two groups. Side effects were common but minor in nature.'] Is oral isotretinoin as effective as a combination of oral isotretinoin and topical anti-acne agents in nodulocystic acne? | qiaojin/PubMedQA | 2 | [
-1.8474782705307007,
-1.3436405658721924,
2.2495815753936768
] |
['Heat stress prior to induction of various forms of cardiac injury has been shown to result in preconditioning and attenuation of subsequent damage. We evaluated the effects of whole-body hyperthermia (WBH) on experimental autoimmune myocarditis (EAM) induced either by injection of myosin or by adoptive transfer of lymphocytes.', 'Lewis rats were pretreated with WBH either 24 h prior to EAM induction (Group A1) or 14 days following EAM induction (Group A2). The control group included myocarditic rats that were not exposed to WBH (Group A3). Rats from Group A1 exhibited significant protection from myocarditis as compared to rats from Group A3, evidenced by reduced myocarditis scores (1.60+/-0.96 vs. 2.88+/-0.35, P=.016). Rats from Group A2 also exhibited protection from myocarditis although not significantly. In a second experiment, we used adoptive transfer of myosin-reactive lymphocytes to study the mechanism of WBH effect on myocarditis. There was evidence of microscopic myocarditis in four out of five rats that were injected with active lymphocytes (the Control Group B3). Myocarditis was not observed in rats adoptively transferred with preheated rat lymphocyes (Group B1) nor in preheated rats, which underwent administration of nonheated rat lymphocyes (Group B2).'] Does whole-body hyperthermia attenuate experimental autoimmune myocarditis in the rat? | qiaojin/PubMedQA | 2 | [
-2.2089602947235107,
-1.317072868347168,
2.5147581100463867
] |
['To determine the effects of anemia on local relapse-free, relapse-free, and overall survival (LRFS, RFS, and OS, respectively) in premenopausal, primary breast cancer patients receiving adjuvant polychemotherapy, and to determine which conventional prognostic factors affected these outcomes.', 'Four hundred twenty-four premenopausal patients with early-stage primary breast cancer and hormone receptor-expressing tumors were treated with i.v. cyclophosphamide/methotrexate/5-fluorouracil (CMF) polychemotherapy as part of an adjuvant phase III trial (Austrian Breast and Colorectal Cancer Study Group Trial 5). The influence of anemia (hemoglobin <12 g/dL) on LRFS, RFS, and OS was evaluated in a retrospective analysis.', 'Of 424 patients, 77 (18.2%) developed anemia on CMF chemotherapy. After a median follow-up time of 5 years, 8.9% of nonanemic patients had local relapse compared with 19.6% of anemic patients (P=0.0006). Although mastectomy was associated with anemia (26% versus 13.7% in breast conserving surgery; P=0.002), multivariate analysis did not show mastectomy per se to be a significant risk factor for LRFS. Age, lymph node status, and hemoglobin had an independent significant influence on LRFS (P<0.005). Anemic patients had a relative risk of 2.96 (95% confidence interval, 1.41-6.23) for developing local relapse in comparison with nonanemic patients.'] Is anemia a significant prognostic factor in local relapse-free survival of premenopausal primary breast cancer patients receiving adjuvant cyclophosphamide/methotrexate/5-fluorouracil chemotherapy? | qiaojin/PubMedQA | 2 | [
-2.1452972888946533,
-1.4541980028152466,
2.599471092224121
] |
['Colorectal cancer patients receiving neoadjuvant treatment with bevacizumab, a monoclonal antibody neutralizing vascular endothelial growth factor (VEGF), may suffer from wound healing complications after surgery as the antibody persists in patient blood. We characterized the systemic angiogenic balance in the perioperative period to evaluate its effect on physiologic angiogenesis.', 'Nineteen patients receiving combination chemotherapy and bevacizumab for six neoadjuvant cycles were compared with 14 patients receiving chemotherapy without bevacizumab. Plasma from perioperative days -1, +1, +7, and +21 was analyzed for VEGF, thrombospondin-1 (TSP-1), and PD-ECGF concentrations. The angiogenic capacity was further tested in an in vitro assay of endothelial cell proliferation and migration.', 'On day +1, the onset of wound healing was reflected in a change of balance, i.e., an increase of proangiogenic factors VEGF and platelet-derived endothelial cell growth factor compared with low TSP-1 inhibitor levels in both treatment groups. Patients with bevacizumab therapy showed significantly higher blood levels of total VEGF throughout the evaluation period. However, most VEGF molecules were inactive, i.e., complexed with antibody. Nevertheless, the capacity to stimulate endothelial growth was higher for these plasma samples and was reflected in low TSP-1 levels and an altered TSP-1 sensitivity. When purified TSP-1 protein was added, plasma samples of the bevacizumab but not the chemotherapy group showed reduced endothelial growth.'] Is neoadjuvant treatment of colorectal cancer with bevacizumab : the perioperative angiogenic balance sensitive to systemic thrombospondin-1 levels? | qiaojin/PubMedQA | 2 | [
-2.3593924045562744,
-1.396559476852417,
2.811556577682495
] |
['To evaluate response and survival according to (18)F-fluoro-2-deoxy-glucose uptake at presentation in patients with gefitinib-treated non-small cell lung cancer.', 'We retrospectively analyzed 84 positron emission tomography/computed tomography findings. Patient characteristics, response rates, and survivals were evaluated according to the maximum standardized uptake value (SUV) of primary tumor. The cutoff value of SUVs was obtained from receiver operating characteristic analysis.', 'The response rate (RR) was higher for never-smokers (41%) than ever-smokers (9%; P=0.001). Patients with adenocarcinoma showed higher RR than those with other tumor histopathology (35% versus 9%; P=0.009). The SUV was significantly lower in patients who were never-smokers (P=0.005), patients with adenocarcinoma (P<0.001), and female patients (P=0.017). Patients with a low SUV showed higher RR compared with those with a high SUV (53% versus 18%; P=0.003). Prolonged progression-free survival was observed in patients with low SUVs compared with those with high SUVs (median, 33.1 weeks versus 8.6 weeks; P=0.003). While controlling for performance status, smoking history, and pathology, the high SUV conferred unfavorable outcome (hazard ratio, 2.3; P=0.012). In terms of overall survival, a low SUV was associated with favorable outcome in univariate analysis (P=0.011). Patients with a low SUV showed prolonged survival in multivariate analysis (P=0.043).'] Does 18F-fluoro-2-deoxy-glucose uptake predict clinical outcome in patients with gefitinib-treated non-small cell lung cancer? | qiaojin/PubMedQA | 2 | [
-1.7324234247207642,
-1.5913975238800049,
2.344093084335327
] |
['The goals of this study were to determine if single-nucleotide polymorphisms in DNA damage repair genes and cell cycle regulating genes affect clinical response to combined gemcitabine radiation therapy and the overall survival (OS) of patients with pancreatic cancer.', 'We evaluated six single-nucleotide polymorphisms of the ATM, ATM and Rad3-related (ATR), CHEK1, and CHEK2 genes in 119 patients with potentially resectable pancreatic cancer who were enrolled in clinical trials at The University of Texas M. D. Anderson Cancer Center from February 1999 to January 2006, with follow-up until February 2007. Patients received neoadjuvant concurrent gemcitabine and radiation therapy with or without gemcitabine-cisplatin induction therapy. Genotypes were determined and tested for associations with OS by Kaplan-Meier estimation, the log-rank test, and Cox regression analysis. P values of <or=0.05 were considered significant.', 'The ATM G60A and CHEK1 G35A genotypes were significant (P<0.05), and the ATR C340T genotype borderline significantly (P=0.079) associated with OS. The hazard ratio of CHEK1 35AA was 2.01 (95% confidence interval, 1.20-3.37; P=0.007) compared with CHEK1 35GG/GA with adjustments for race, sex, diabetes status, CA19-9 level, and success of tumor resection. A significant combined genotype effect was observed between ATM 60GA/GG, ATR 340CT/CC, and CHEK1 35AA with median OS times of 31.0, 16.2, and 10.5 months for patients carrying <or=1, 2, and 3 deleterious alleles, respectively (P=0.004).'] Are single-nucleotide polymorphisms of DNA damage response genes associated with overall survival in patients with pancreatic cancer? | qiaojin/PubMedQA | 2 | [
-1.842221975326538,
-1.6050505638122559,
2.4356188774108887
] |
['To measure changes in suicidal behaviours during 6 months of treatment with antidepressants.', 'A group of depressed patients (n = 195) were assessed for suicidal behaviours in the 6 months prior to treatment. They were prospectively assessed for suicidal behaviours during 6 months of treatment with antidepressants.', 'Patients who made suicide attempts fell from 39 in the 6 months prior to treatment to 20 during treatment. Significant suicidal ideation reduced from 47% at baseline to 14% at 3 weeks remaining below this during the rest of the treatment. Twenty patients had emergent suicidal ideation; five of them had not experienced some level of suicidal behaviour in the 6 months prior to treatment.'] Is antidepressant treatment associated with a reduction in suicidal ideation and suicide attempts? | qiaojin/PubMedQA | 1 | [
-1.3528573513031006,
0.8995051383972168,
-0.38359761238098145
] |
['By using the age-adjusted Charlson comorbidity index (ACCI), the authors characterized the impact of age and comorbidity on disease progression and overall survival after radical cystectomy (RC) for transitional cell carcinoma of the bladder. Also evaluated was whether ACCI was associated with clinicopathologic and treatment characteristics.', 'The authors evaluated 1121 patients treated by RC for transitional cell carcinoma of the bladder at a single institution (1990-2004). Logistic regression was used to determine the relation between ACCI and clinical features. They evaluated the association between ACCI and overall and progression-free survival by using multivariate survival-time models with pathologic stage and nodal status as covariates.', 'ACCI scores increased during the study period (P = .009). Extravesical disease was present in 43% of patients with ACCI <or=2, 49% with ACCI 3-5, and 56% with ACCI >5 (P = .051). Despite their higher prevalence of extravesical disease, patients with higher ACCI were less likely to have lymph-node dissection (odds ratio, 0.55 and 0.35, respectively, for ACCI 3-5 and >5 vs <or=2; P = .005), and when it was performed, fewer lymph nodes were evaluated (P < .0005). Patients with higher ACCI were also less likely to have postoperative chemotherapy (odds ratio, 0.70 and 0.66, respectively, for ACCI 3-5 and >5 vs <or=2; P = .04). Higher ACCI was significantly associated with lower overall (P < .005) but not recurrence-free (P = .17) survival after RC.'] Is age-adjusted Charlson comorbidity score associated with treatment decisions and clinical outcomes for patients undergoing radical cystectomy for bladder cancer? | qiaojin/PubMedQA | 2 | [
-0.9936829805374146,
-1.734278917312622,
1.585468053817749
] |
['Acute liver failure is associated with significant mortality. However, the underlying pathophysiological mechanism is not yet fully understood. Suppressor of cytokine signaling-1 (SOCS1), which is a negative-feedback molecule for cytokine signaling, has been shown to be rapidly induced during liver injury. Here, using liver-specific SOCS1-conditional-knockout mice, we demonstrated that SOCS1 deletion in hepatocytes enhanced concanavalin A (ConA)-induced hepatitis, which has been shown to be dependent on activated T and natural killer T (NKT) cells. Although serum cytokine level and NKT cell activation were similar in wild-type (WT) and SOCS1-deficient mice after ConA treatment, proapoptotic signals, including signal transducers and activators of transcription 1 (STAT1) and Jun-terminal kinase (JNK) activation, were enhanced in SOCS1-deficient livers compared with those in WT livers. SOCS1-deficient hepatocytes had higher expression of Fas antigen and were more sensitive to anti-Fas antibody-induced apoptosis than were WT hepatocytes. Furthermore, SOCS1-deficient hepatocytes were more sensitive to tumor necrosis factor (TNF)-alpha-induced JNK activation and apoptosis. These data indicate that SOCS1 is important to the prevention of hepatocyte apoptosis induced by Fas and TNF-alpha. In contrast, SOCS1 overexpression in the liver by adenoviral gene transfer prevented ConA-induced liver injury.'] Does suppressor of cytokine signaling 1 protect mice against concanavalin A-induced hepatitis by inhibiting apoptosis? | qiaojin/PubMedQA | 2 | [
-2.398286819458008,
-1.2811371088027954,
2.7293190956115723
] |
['Enuresis and nocturia are common among children with sickle cell anemia (SCA). The objectives of this study were to describe the prevalence of enuresis and nocturia among children and young adults with SCA and determine the relationship, if any, between these symptoms and SCA-related morbidity.', 'A prospective infant cohort of African-American children with SCA was previously established from the Cooperative Study for Sickle Cell Disease. Included in this cohort were children with SCA enrolled before 6 months of age for whom questions about enuresis and nocturia had been completed.', 'A total of 213 participants were included in this analysis. Sixty-nine individuals (33%) experienced enuresis over the course of the study. No children under 6 years of age were asked about enuresis. Thereafter, enuresis was most prevalent between the ages of 6 and 8 years (42%) and continued to be common in young adults ages 18 to 20 years (9%). Seventy-nine percent of individuals reported a history of nocturia. There was no association between enuresis or nocturia and an increased rate of pain or acute chest syndrome (ACS) episodes.'] Is enuresis a common and persistent problem among children and young adults with sickle cell anemia? | qiaojin/PubMedQA | 2 | [
-2.225825071334839,
0.4392593801021576,
0.9957441687583923
] |
['Elevated levels of retinol binding protein-4 (RBP4) are positively correlated with insulin resistance, obesity, diabetes mellitus, and cardiovascular disease (CVD). Subclinical hypothyroidism (SCH) has also been associated with CVD; however, the factors linking SCH to CVD are not clear.', 'The objective of the study was to evaluate risk factors for CVD in elderly patients grouped according to thyroid function.', '217 subjects (> or =65 yr old) were randomly selected from a population and allocated to a euthyroid group (n = 177) and an SCH group (n = 40) on the basis of plasma concentrations of TSH and free T(4). We included subjects with normal glucose tolerance by a 75-g oral glucose tolerance test and subjects with impaired fasting glucose. We measured anthropometric parameters, levels of fasting glucose and insulin, hemoglobin A(1c), adiponectin, RBP4, lipid profiles, total body fat content, and the area of sc and visceral fat.', 'The SCH group had higher RBP4 levels than the euthyroid group, irrespective of body mass index and fat content. Subcutaneous and visceral fat areas and total body fat percentage did not differ between groups and were not correlated with RBP4 level. Other CVD risk factors did not differ between groups. RBP4 level was positively correlated with TSH level (r = 0.241, P = 0.001) after adjustment for age, sex, and body mass index.'] Is retinol binding protein-4 elevation associated with serum thyroid-stimulating hormone level independently of obesity in elderly subjects with normal glucose tolerance? | qiaojin/PubMedQA | 2 | [
-1.8250216245651245,
-1.4235811233520508,
2.282611846923828
] |
['Postsystolic wall thickening (PSWT) occurs after aortic valve closure. We investigated the influence of ischemia location and wall interactions on PSWT in normal and stunned myocardium.', 'Twenty-two dogs were studied. Seven chronically instrumented dogs (sonomicrometry) underwent 10-min coronary artery occlusion (CAO) of left circumflex artery ("LCX stunning") and seven other dogs underwent 10-min CAO of the anterior descending artery ("LAD stunning") followed by reperfusion. At baseline, there was no PSWT in the anterior wall whereas posterior wall started and finished to thicken after the anterior wall, demonstrating PSWT. With LCX stunning, PSWT was observed in the posterior wall without affecting the remote anterior wall. With LAD stunning, PSWT in the anterior wall was transient and of lower magnitude Vs. posterior wall; in the remote posterior wall, PSWT previously observed at baseline, almost vanished. Postsystolic to systolic wall thickening ratio identified (ROC analysis) normal, ischemic and stunned myocardium with different amplitudes between walls. Tissue Doppler Imaging demonstrated similar pattern in basal, mid and apical segments (additional n = 4 for both LCX and LAD stunning).'] Is regional and temporal heterogeneity of postsystolic wall thickening associated with left ventricular asynchrony in normal and experimental stunned myocardium? | qiaojin/PubMedQA | 2 | [
-2.2330541610717773,
-1.459288239479065,
2.798182964324951
] |
['In the present study, we attempted to develop a simulated model to explore the causal effects of periodontal pathogens on skeletal homeostasis in postmenopausal osteoporosis.', 'Fifty-three female adult ICR mice were randomly assigned to an experimental group (ovariectomized) or a control group. A single injection of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS, ATCC 33277) or Escherichia coli lipopolysaccharide (E. coli-LPS) was administered intraperitoneally 4 weeks after an ovariectomy. Concentrations of interleukin-6 (IL-6), osteoprotegerin (OPG), and the receptor activator of nuclear factor-kappaB ligand (RANKL) in serum were subsequently analyzed using an enzyme-linked immunosorbent assay (ELISA).', 'Under stimulation with P. gingivalis-LPS or E. coli-LPS, the concentration of OPG rose in both groups. The serum level of RANKL showed a decreasing trend 24 h after the injection in both groups. After injection of P. gingivalis-LPS in both the experimental and control animals, the OPG : RANKL ratio increased 24 h after the booster (22.26-620.99, P < 0.05). The serum level of IL-6 in the experimental group significantly increased 1-6 h after administration of E. coli-LPS and 1-3 h after administration of P. gingivalis-LPS (P < 0.05).'] Does an acute injection of Porphyromonas gingivalis lipopolysaccharide modulate the OPG/RANKL system and interleukin-6 in an ovariectomized mouse model? | qiaojin/PubMedQA | 2 | [
-2.18660831451416,
-1.5080041885375977,
2.7251453399658203
] |
['Few in vivo studies have demonstrated whether Toll-like receptor 4 (TLR4) is indispensable for lipopolysaccharide (LPS)-induced bone resorption and little is known about the receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) expression induced by LPS under conditions of lack of TLR4.', 'We compared bone resorption histomorphometrically in C3H/HeN and C3H/HeJ mice that were repeatedly injected with Actinobacillus actionmycetemcomitans LPS into their gingiva every 48 h. RANKL-, interleukin-1beta- and OPG-positive cells in the connective tissue were also compared immunohistochemically.', 'Bone resorption in C3H/HeJ mice in the fourth, seventh, and tenth injection groups was significantly less than that C3H/HeN mice (P < 0.05). The number of RANKL-positive cells in C3H/HeJ mice in the 10th injection group was significantly smaller than that in C3H/HeN mice (P < 0.05). The numbers of interleukin-1beta-positive cells in C3H/HeJ mice in the seventh and tenth injection groups were significantly decreased compared with those in C3H/HeN mice (P < 0.05). The numbers of OPG-positive cells in C3H/HeN and C3H/HeJ mice gradually increased, but there was no significant difference between the two strains of mice.'] Does lack of Toll-like receptor 4 decrease lipopolysaccharide-induced bone resorption in C3H/HeJ mice in vivo? | qiaojin/PubMedQA | 2 | [
-1.5688979625701904,
-1.6261066198349,
2.085127830505371
] |
['Transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. The purpose of this study was to analyze the effect of TGF-beta targeting on the expression of matrix metalloproteinases (MMPs) in fibroblasts isolated from radiation-induced chronic dermal wounds.', 'The expression of MMPs in tissue samples from radiation-induced chronic dermal wounds was investigated by immunohistochemistry and microarray technique. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of MMPs in isolated fibroblasts was analysed by ELISA and multiplex RT-PCR.', 'Immunohistochemical investigation and microarray analysis demonstrated an increased expression of MMP protein and mRNA in tissue samples from radiation-induced chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment significantly down-regulated MMP secretion in vitro.'] Do tGF-beta antisense oligonucleotides modulate expression of matrix metalloproteinases in isolated fibroblasts from radiated skin? | qiaojin/PubMedQA | 2 | [
-2.502946376800537,
-1.1993048191070557,
2.783196449279785
] |
['To investigate the capacity of cultured Müller cells to synthesize collagens, since previous studies indicated that Müller cells could be involved in collagen remodeling at the vitreoretinal border in adult human eyes.', 'Spontaneously immortalized cultured human Müller cells were analyzed for the presence of mRNA of types I-VII, IX, XI, and XVII collagen by RT-PCR. Furthermore, Müller cells were immunocytochemically stained for light microscopic (LM) evaluation of these collagens and their main characteristics. Finally, cell extracts and culture medium were evaluated by western blot (WB) analysis using anticollagen antibodies.', 'Cultured Müller cells contained mRNA for types I-VII, IX, and XI collagen, but not for type XVII collagen. LM and WB confirmed the intracellular expression of all the above-mentioned collagens with the exception of type XVII. Collagen secretion into the medium was established for types I-VII, IX, and XI collagen.'] Do human retinal Müller cells synthesize collagens of the vitreous and vitreoretinal interface in vitro? | qiaojin/PubMedQA | 2 | [
-2.510730266571045,
-1.0684788227081299,
2.676225423812866
] |
['Multicenter, double-blind, placebo-controlled, parallel-group study.', 'To assess the effect of the oral phosphodiesterase type-5 inhibitor, vardenafil, on ejaculation rates and self-confidence in men with spinal cord injury (SCI).', "Spinal command of male sexual functions is often seriously impaired by traumatic spinal cord injury (SCI). A high proportion of men with SCI cannot ejaculate during sexual intercourse. SCI-related ejaculatory disorders are often responsible for male infertility. Sexual dysfunction associated with SCI can also affect men's self-confidence.", 'In this 12-week study, 418 men aged >or=18 years with erectile dysfunction >6 months resulting from a traumatic SCI were randomized to vardenafil (n = 207) or placebo (n = 211) 10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8. Assessments included questions of the International Index of Erectile Function (IIEF) about ejaculation success and orgasmic perception; the Global Confidence Question; and quality-of-life scales to measure psychological well-being, self-esteem, depression, and mental health status.', 'Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment (19% vs. 10%; P < 0.001). At last observation carried forward, the IIEF "orgasmic function" score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo. Sixteen percent of men receiving vardenafil and 8% receiving placebo felt orgasm "almost always" or "always" at weeks 8-12, compared with 4% and 6%, respectively, at baseline. Significant improvements in confidence scores were observed with vardenafil compared with placebo (P < 0.0001). There were no clinically significant differences between vardenafil and placebo in the quality-of-life measures at the study endpoint, but these had been in the normal range at baseline.'] Does vardenafil improve ejaculation success rates and self-confidence in men with erectile dysfunction due to spinal cord injury? | qiaojin/PubMedQA | 2 | [
-1.777596116065979,
-1.2342193126678467,
2.0192697048187256
] |
['Retrospective studies provide evidence that rhinitis is associated with more severe asthma. The aim of this study was to evaluate prospectively whether rhinitis is a predictor of increased asthma severity.', 'Five hundred and fifty-seven patients with severe asthma were enrolled. During 1 year of follow-up, each patient was evaluated every 3 months with a record of emergency room visits and supply of topical corticosteroids for asthma and rhinitis. In the 1 year of follow-up visit, the patients were checked for rhinitis diagnosis, severity and answered questionnaires for asthma symptoms and quality of life.', 'Eighty-two (15%) patients had no rhinitis, 299 (54%) had mild rhinitis and 176 (31%) moderate/severe rhinitis. In logistic regression models, moderate/severe rhinitis was a predictor for any emergency room visit in the follow-up period [3.83 (2.00-7.35)], for the presence of uncontrolled asthma after 1 year of follow-up [12.68 (1.73-92.85)], for <10% improvement of the airway obstruction [2.94 (1.48-5.85)] and <50% reduction in the number of emergency room visits [2.90 (1.02-8.26)] in the year of follow-up. It was also associated with a smaller chance of more than 90% reduction in the number of emergency room visits in the year of follow-up [0.27 (0.12-0.60)]. In a multivariate linear regression model, severity of rhinitis was positively correlated with a score of asthma severity and inversely correlated to an index of quality of life.'] Is lack of control of severe asthma associated with co-existence of moderate-to-severe rhinitis? | qiaojin/PubMedQA | 2 | [
-1.2273893356323242,
-1.3854422569274902,
1.6424851417541504
] |
['Toll-like receptors (TLR) 2 and TLR4 expressed on innate immune cells are important mediators of the immune response to pathogens. In this study, we hypothesized that burn injury results in altered cytokine secretion profiles after TLR2 or TLR4 ligation that is associated with altered TLR expression on innate immune cells.', 'Female C56BL/6 mice were subjected to 20% full thickness burn or sham injury. Three or 14 days after injury whole splenocytes or purified splenic macrophages were cultured with TLR2 ligand peptidoglycan or TLR4 ligand lipopolysaccharide. Supernatants were assayed for TNF-alpha, MCP-1, IL-6 and IL-10. Cell death was assessed using flow cytometry. Innate CD11b F4/80 macrophages were sorted 14 days after burn injury and TLR2 and 4 expression was determined by quantitative reverse-transcriptase polymerase chain reaction and flow cytometry.', 'Burn injury results in a steady accumulation in the periphery of CD11bF4/80 macrophages. Macrophages purified early after burn injury upregulated TLR2 and 4, followed by a decrease of TLR2 and TLR4 expression late after burn injury. TLR2 and TLR4 ligation of an equivalent number of purified macrophages 3 days after burn injury revealed no significant differences in cytokine secretion compared with sham. Stimulation 14 days after burn injury revealed a significant reduction in tumor necrosis factor-alpha secretion by macrophages compared with sham mice. In contrast, interleukin-10 was significantly increased (mean, approximately 1.8-fold) late after burn injury after either TLR2 or TLR4 stimulation. Interleukin-6 and monocyte chemotactic protein-1 secretion was unchanged from sham levels. In contrast, whole splenocyte stimulation resulted in increased cytokine 3 days and 14 days after burn injury. This effect is likely caused by the accumulation of TLR macrophages, which are resistant to TLR-induced cell death.'] Does toll-like receptor 2 and 4 ligation result in complex altered cytokine profiles early and late after burn injury? | qiaojin/PubMedQA | 2 | [
-2.1830978393554688,
-1.4171080589294434,
2.6073436737060547
] |
['Polymorphonuclear neutrophil (PMN) apoptosis is suppressed after acute lung injury (ALI), and strategies aimed at inducing PMN apoptosis are thought to be promising therapies for ALI. However, the mechanisms underlying PMN apoptotic suppression are unknown. Cyclo-oxygenase-2 (COX-2) has been shown to regulate tumor cell apoptosis and is up-regulated by inflammatory mediators in PMN. Therefore, we set out to determine whether up-regulation of COX-2 expression contributes to PMN apoptosis after ALI.', 'Experimental ALI was established in New Zealand rabbits by blunt chest trauma, and a correlation analysis of COX-2 immunohistochemical staining in lung tissue and PMN apoptosis in bronchoalveolar lavage fluid (BALF) was performed. Apoptosis was measured by flow cytometric analysis of annexin V and propidium iodide dual staining. As an in vitro correlate, normal PMNs were treated with BALF from injured lung (BALFALI) in the presence or absence of the COX-2 inhibitor, NS398. COX-2 mRNA levels and PMN apoptosis were then measured.', 'PMN apoptosis was significantly decreased in BALF after injury. In contrast, COX-2 expression was significantly increased after injury. COX-2 protein expression and PMN apoptosis exhibited a strong inverse correlation (gamma = -0.75, p < 0.01). In vitro experiments revealed apoptosis of normal PMNs was significantly decreased by the addition of BALFALI. The addition of BALFALI was also associated with increased COX-2 mRNA levels. Treatment of cultures with NS398, 10 minutes before BALFALI addition, partially reversed all of these effects.'] Does cyclooxygenase-2 suppress polymorphonuclear neutrophil apoptosis after acute lung injury? | qiaojin/PubMedQA | 2 | [
-2.2228965759277344,
-1.396662950515747,
2.6202616691589355
] |
['We sought to determine any differences between myocardial velocities in healthy children and pediatric heart transplant recipients without acute allograft rejection and to study the clinical factors that could alter these velocities.', 'Fifty-eight pediatric heart transplant recipients without rejection and 27 healthy controls were prospectively enrolled. Doppler tissue imaging (DTI) was performed at the tricuspid annulus, septum, and mitral annulus. The influence of the following factors on DTI was assessed: time since transplant, extracorporeal membrane oxygenation, systemic hypertension, graft atherosclerosis, pulmonary hypertension, donor heart ischemic time, and previous rejection.', 'The mean tricuspid annular and septal tissue velocities were significantly reduced in the transplant group compared with controls. The mitral annular velocities were similar in the two groups. Donor heart ischemic time and previous rejection significantly altered DTI velocities.'] Are tricuspid annular and septal Doppler tissue velocities reduced in pediatric heart transplant recipients without acute rejection? | qiaojin/PubMedQA | 2 | [
-2.287597894668579,
-1.0795977115631104,
2.417696714401245
] |
["Electronic monitoring devices (EMDs) are regarded as the gold standard for assessing medication adherence in clinical research. However, little is known about the effect of patients' acceptance of EMDs on medication adherence in African Americans with hypertension who are followed in primary care practices", "To assess patients' perceptions of EMDs, their acceptance of EMDs, and the relationship of these perceptions to medication adherence in African Americans with hypertension who are followed in community-based practices.", "Patients were recruited from a larger randomized controlled trial assessing the effect of motivational interviewing on medication adherence and blood pressure in hypertensive African American patients followed in 2 New York City primary care practices. Medication adherence was assessed with a Medication Event Monitoring System (MEMS) during a 12-month monitoring period. At the 12-month follow-up, patients' perceptions of the MEMS were assessed with a 17-item questionnaire. ANOVA was used to compare patients' responses (agree, neither, disagree) with the MEMS adherence over the monitoring period. Tukey's post hoc tests were used to determine whether there were significant differences among the 3 groups.", 'Participants were predominantly women, low-income, unemployed, had a high school education, and were a mean age of 53 years. Approximately two-thirds of the participants stated that the MEMS helped them remember to take their medications, 93% reported that the MEMS was easy to open, 85% did not find it stressful, and 75% liked the MEMS and used it everyday. One-third of patients preferred using a pillbox and 25% did not like traveling with the MEMS. Patients who stated that they used the MEMS every day, felt comfortable using it in front of others, and remembered to put refills in the MEMS had significantly better adherence over the study period than did those who disagreed (p </= 0.05).'] Do patients ' perceptions of electronic monitoring devices affect medication adherence in hypertensive African Americans? | qiaojin/PubMedQA | 2 | [
-1.2108330726623535,
-0.5065057873725891,
0.7683435678482056
] |
['Oxidative stress is implicated in cardiac remodeling and failure. We tested whether xanthine oxidase (XO) inhibition could decrease myocardial oxidative stress and attenuate left ventricular (LV) remodeling and dysfunction in the TO-2 hamster model of dilated cardiomyopathy.', 'TO-2 hamsters were randomized to treatment with the XO inhibitor, allopurinol, or vehicle from 6 to 12 weeks of age. F1B hamsters served as controls. TO-2 hamsters treated with vehicle progressively developed severe LV systolic dysfunction and dilation between 6 and 12 weeks. Marked cardiac fibrosis was apparent in these hamsters at 12 weeks in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and malondialdehyde levels were increased in the hearts of vehicle-treated TO-2 hamsters. Treatment with allopurinol from 6 to 12 weeks attenuated LV dysfunction and dilation as well as myocardial fibrosis and the upregulation of a fetal-type cardiac gene. Allopurinol also inhibited both the decrease in GSH/GSSG ratio and the increase in malondialdehyde levels in the heart.'] Does xanthine oxidase inhibition improve left ventricular dysfunction in dilated cardiomyopathic hamsters? | qiaojin/PubMedQA | 2 | [
-2.4677734375,
-1.155419111251831,
2.6386032104492188
] |
['We have shown previously that 17beta-estradiol (E2) increases left ventricular (LV) and cardiomyocyte hypertrophy after myocardial infarction (MI). However, E2 decreases hypertrophy in pressure overload models. We hypothesized that the effect of estrogen on cardiac hypertrophy was dependent on the type of hypertrophic stimulus.', 'Ovariectomized wild-type female mice (n = 192) were given vehicle or E2 treatment followed by coronary ligation (MI), transverse aortic constriction (TAC), or sham operation. Signaling pathway activation was studied at 3, 24, and 48 hours, whereas echocardiography and hemodynamic studies were performed at 14 days. MI induced early but transient activation of p38 and p42/44 MAPK pathways, whereas TAC induced sustained activation of both pathways. E2 had no effect on these pathways, but increased Stat3 activation after MI while decreasing Stat3 activation after TAC. MI caused LV dilation and decreased fractional shortening (FS) that were unaltered by E2. TAC caused LV dilation, reduced FS, and increased LV mass, but in this model, E2 improved these parameters. After MI, E2 led to increases in myocyte cross-sectional area, atrial natriuretic peptide (ANP) and beta-myosin heavy chain (MHC) gene expression, but E2 diminished TAC-induced increases ANP and beta-MHC gene expression.'] Does 17 Beta-estradiol differentially affect left ventricular and cardiomyocyte hypertrophy following myocardial infarction and pressure overload? | qiaojin/PubMedQA | 2 | [
-2.3258860111236572,
-1.4127907752990723,
2.7785820960998535
] |
['The expression pattern of stress (heat shock) proteins (HSPs) in cancer cells is frequently different from that observed in normal cells; most often some stress-inducible HSPs are constitutively and highly expressed. The objective of this study was to determine the prognostic significance of stress proteins HSP70i and HSP27 in non-small cell lung carcinoma (NSCLC).', 'An immunohistochemical procedure that enables unambiguous detection of HSP70i protein was used.', 'Strong HSP70i staining showed a survival advantage, although multivariate analysis did not confirm this result. There was an evident correlation between HSP27 overexpression and survival of patients and the results were confirmed by multivariate analysis: 70% of patients with HSP27-negative tumors died within one year after the surgery.'] Do stress proteins HSP27 and HSP70i predict survival in non-small cell lung carcinoma? | qiaojin/PubMedQA | 2 | [
-2.429506540298462,
-1.1081370115280151,
2.6083083152770996
] |
['Using a recombinant rat leptin antagonist, we investigated the effects of early postnatal leptin disruption on long-term leptin sensitivity and metabolic phenotype.', 'Three groups of 10 newborn female Wistar rats were injected subcutaneously with either saline (control) or leptin antagonist (at 2.5 or 7.5 microg g(-1) day(-1)) from postnatal day 2 to day 13.', 'At weaning (day 28), antagonist-treated rats presented similar body weight (BW) compared to control animals. At 3 months of age, there was no significant change in BW, food intake and leptin or insulin levels between groups. Only a disturbed relationship between circulating insulin and glucose levels was observed in antagonist-treated animals. At 4 months of age, treated animals developed a leptin resistance appreciated by the lack of response to a 7-days leptin treatment (1 mg kg(-1) day(-1)) in term of decrease in food intake and BW. At 8 months of age, following 3 months of high-energy diet, rlepm7.5 animals presented higher BW gain associated with increased body fatness and striking hyperleptinaemia as compared to control animals.'] Does early postnatal leptin blockage lead to a long-term leptin resistance and susceptibility to diet-induced obesity in rats? | qiaojin/PubMedQA | 2 | [
-2.14469313621521,
-1.295135736465454,
2.3996903896331787
] |
['To study the predictive power of respiratory screening examinations a cohort of asbestos workers was followed from active work in an asbestos cement plant until death.', 'From a cohort with data on individual exposure since first employment 309 workers who had a preventive medical examination in 1989/1990 were observed until death or the end of 2006. The impact of asbestos exposure (fibre years) and of smoking history on lung function was examined by linear regression, on specific causes of death and total mortality by Cox regression. The prognostic value of lung function, chest X-ray, and various clinical findings regarding total mortality was also examined by Cox regression.', 'Lung function proved to be the best predictor of survival apart from current smoking. Depending on the lung function variable an impairment by the interquartile range resulted in a hazard ratio of 1.5-1.6 while for current smokers it was 2.3. An increase of 70 fibre years (interquartile range) led to a hazard ratio of only 1.1. Lung function was influenced by asbestos exposure, current (but not former) smoking, and by pathological X-ray findings. The risk for pleural mesothelioma was dominated by time since first exposure to crocydolite in the pipe factory while the risk for bronchial cancer increased with smoking and total fibre years. An unexpected finding was an increase of gastric cancer in asbestos cement workers.'] Does lung function predict survival in a cohort of asbestos cement workers? | qiaojin/PubMedQA | 2 | [
-2.216549873352051,
-0.38735756278038025,
1.7519679069519043
] |
['To study the effect of botulinum toxin A in the subscapular muscle on shoulder pain and humerus external rotation.', '22 stroke patients with spastic hemiplegia, substantial shoulder pain and reduced external rotation of the humerus participated in a randomised, double blind, placebo controlled effect study. Injections of either botulinum toxin A (Botox, 2x50 units) or placebo were applied to the subscapular muscle at two locations. Pain was scored on a 100 mm vertical Visual Analogue Scale; external rotation was recorded by means of electronic goniometry. Assessments were carried out at 0 (baseline), 6 and 12 weeks.', '21 patients completed the study. We observed no significant changes in pain or external rotation as a result of administration of botulinum toxin A. External rotation improved significantly (p = 0.001) for both the treatment group (20.4 degrees (16.6) to 32.1 degrees (14.0)) and the control group (10.3 degrees (19.5) to 23.7 degrees (20.7)) as a function of time.'] Do shoulder pain and external rotation in spastic hemiplegia improve by injection of botulinum toxin A into the subscapular muscle? | qiaojin/PubMedQA | 2 | [
-2.1552751064300537,
-1.3239538669586182,
2.5319125652313232
] |
['Suprarenal clamping in abdominal aortic surgery is associated with a significant risk of postoperative renal failure, general morbidity, and mortality. Arterial access for temporary shunting in these patients is difficult, and arterial perfusion techniques are typically complex. This study evaluated if renal perfusion with venous blood using a minimal pump setup and intermediate-level heparinization prevents a decline in postoperative renal function in patients requiring suprarenal clamping for aortic reconstructive surgery.', 'Renal perfusion was achieved using a roller pump supplied with venous blood from a central venous catheter under medium-level heparinization to feed two perfusion balloon catheters. The calculated glomerular filtration rate was observed for 10 postoperative days and compared with the rate in patients with suprarenal clamping without renal perfusion.', 'From 2001 to 2007, 158 patients underwent surgical reconstruction involving the pararenal aorta through a midline abdominal incision. Renal perfusion was started in 2006 and was always attempted if suprarenal clamping was anticipated preoperatively. Twenty-six patients received renal perfusion, and 132 also requiring suprarenal clamping did not. Of the latter, 109 were included in the control group. Five patients died <or=30 days (3.7%), one in the perfusion group. On average, there was a postoperative loss of renal performance in both groups. Dialysis was required postoperatively in 13 patients without renal perfusion, 4 of them long term (3.7%), but not in patients with renal perfusion. The reduction in glomerular filtration rate at 10 days in the nonperfused group was significantly higher than in the perfused group (7.24 vs 0.89 mL/min) despite a significantly longer suprarenal clamp time in the latter (25.5 vs 45.5 minutes). Multivariate analysis showed a significant reduction in the loss of glomerular filtration rate with perfusion (P = .007) if clamp time and preoperative renal function were taken into account. Patients with preoperative renal impairment showed the greatest benefit from the perfusion.'] Does renal perfusion with venous blood extend the permissible suprarenal clamp time in abdominal aortic surgery? | qiaojin/PubMedQA | 2 | [
-1.7151097059249878,
-1.642765998840332,
2.2958221435546875
] |
['We compared pressure and volume-controlled ventilation (PCV and VCV) in morbidly obese patients undergoing laparoscopic gastric banding surgery.', "Thirty-six patients, BMI>35 kg m(-2), no major obstructive or restrictive respiratory disorder, and Pa(CO(2))<6.0 kPa, were randomized to receive either VCV or PCV during the surgery. Ventilation settings followed two distinct algorithms aiming to maintain end-tidal CO(2) (E'(CO(2))) between 4.40 and 4.66 kPa and plateau pressure (P(plateau)) as low as possible. Primary outcome variable was peroperative P(plateau). Secondary outcomes were Pa(O(2)) (Fi(O(2)) at 0.6 in each group) and Pa(CO(2)) during surgery and 2 h after extubation. Pressure, flow, and volume time curves were recorded.", "There were no significant differences in patient characteristics and co-morbidity in the two groups. Mean pH, Pa(O(2)), Sa(O(2)), and the Pa(O(2))/Fi(O(2)) ratio were higher in the PCV group, whereas Pa(CO(2)) and the E'(CO(2))-Pa(CO(2)) gradient were lower (all P<0.05). Ventilation variables, including plateau and mean airway pressures, anaesthesia-related variables, and postoperative cardiovascular variables, blood gases, and morphine requirements after the operation were similar."] Does pressure-controlled ventilation improve oxygenation during laparoscopic obesity surgery compared with volume-controlled ventilation? | qiaojin/PubMedQA | 2 | [
-1.9427496194839478,
-1.2861573696136475,
2.238825798034668
] |
['In a primate model of Parkinson disease (PD), intrastriatal infusion of an adeno-associated viral (AAV) vector containing the human aromatic l-amino acid decarboxylase (hAADC) gene results in robust gene expression. After gene transfer, low doses of systemically administered l-dopa are converted to dopamine in the transduced striatal neurons, resulting in behavioral improvement without the side effects typically associated with higher doses of l-dopa. These studies led to the initiation of a phase I safety trial. Here we report the findings for the first cohort of five patients.', 'Patients with moderate to advanced PD received bilateral infusion of a low dose of the AAV-hAADC vector into the putamen. PET scans using the AADC tracer, 6-[18F]fluoro-l-m-tyrosine (FMT), were performed at baseline and at 1 and 6 months after infusion as an in vivo measure of gene expression.', 'PET results showed an average 30% increase in FMT uptake (K(i)(c)) in the putamen after gene transfer. Preliminary analysis of clinical data indicates a modest improvement, but absence of a control and the nonblinded analyses make interpretation difficult.'] Do results from a phase I safety trial of hAADC gene therapy for Parkinson disease? | qiaojin/PubMedQA | 2 | [
-2.486907720565796,
-1.323240041732788,
2.8469438552856445
] |
['Examine the validity of preference-weighted health-related quality of life measures in a sample of substance use disorder (SUD) patients. The implications of cost-utility analyses (CUAs) of SUD interventions are discussed.', 'Cross-sectional analysis of subjects seeking SUD treatment.', 'Seven SUD treatment centers in a medium-sized Midwestern metropolitan area in the United States.', 'Data from 574 SUD subjects were analyzed from a study to test interventions to improve linkage and engagement with substance abuse treatment.', 'Subjects completed the following preference-weighted measures: self-administered Quality of Well-Being scale (QWB-SA) and Medical Outcomes Study SF-12 (standard gamble weighted or SF-12 SG); and clinical measures: Addiction Severity Index (ASI) and a symptom checklist based on the DSM-IV.', 'In unadjusted analyses, the QWB-SA was correlated significantly with six of seven ASI subscales and the SF-12 SG was correlated with four of seven. In adjusted analyses, both preference-weighted measures were significantly correlated with diagnostic, physical health, mental health and drug use measures, but not with legal or alcohol use measures. The QWB-SA was also correlated with employment problems and the SF-12 SG was correlated with family/social problems.'] Do preference-weighted health-related quality of life measures and substance use disorder severity? | qiaojin/PubMedQA | 2 | [
-1.9341360330581665,
-0.3048170804977417,
1.3182803392410278
] |
['To determine whether children with asthma and on inhaled corticosteroids have more behavioural problems, such as aggressiveness and hyperactivity, as compared with healthy controls and with children under medical care because of other disorders.', 'Questionnaires were given to three groups of children: a group of asthmatic children with inhaled corticosteroids (ICS), a group of children attending the ear, nose and throat (ENT) outpatient clinic and the healthy controls. Included were questions about health, medication use, demographical data and about behaviour, including the child behaviour check list (CBCL) and questions about attention deficit hyperactivity disorder (ADHD).', 'Forty asthmatic children on ICS, 50 children visiting the ENT outpatient clinic and 183 healthy controls were studied. The total CBCL and mean ADHD scores of the children on ICS were 28.1 and 9.1, which were both significantly higher than the scores of the healthy controls (20.4 and 7.1), but not when compared with the ENT outpatient group (26.2 and 8.6). Further analysis revealed statistically significant differences between the ICS group and healthy controls in CBCL-axes. There were, however, no differences between the ENT group and the ICS on one side and the healthy controls on the other.'] Do inhaled corticosteroids affect behaviour? | qiaojin/PubMedQA | 2 | [
-2.012557029724121,
-0.19374847412109375,
1.2979583740234375
] |
["Bilirubin is a newly discovered modulator of the gut barrier in vitro and in vivo. We studied the effect of bilirubin on the serosal to mucosal intestinal permeability in vivo. We also investigated the prevalence of cow's milk protein intolerance (CMPI) in infants with moderate hyperbilirubinemia versus matched controls.", 'Faecal alpha 1 antitrypsin (a1AT) was used to monitor intestinal protein loss; a large cohort was prospectively followed for 12 months for sign and symptoms of CMPI.', 'Neonates with hyperbilirubinemia had higher stool excretion of a1AT than controls (0.68 +/- 0.28 mg/g vs. 0.25 +/- 0.11 mg/g; p < 0.01). Faecal a1AT correlates with total serum bilirubin (TSB) (r = 0.85; p < 0.01). Also, in the first 12 months of life, formerly hyperbilirubinemic infants had an higher prevalence of CMPI (14/353 vs. 4/339; chi2= 4.018, p = 0.045).'] Does neonatal hyperbilirubinemia increase intestinal protein permeability and the prevalence of cow 's milk protein intolerance? | qiaojin/PubMedQA | 2 | [
-2.083209753036499,
-1.4174683094024658,
2.4872934818267822
] |
['Krüppel-like factor 5 (KLF5) is a transcription factor that is highly expressed in proliferating crypt cells of the intestinal epithelium. KLF5 has a pro-proliferative effect in vitro and is induced by mitogenic and stress stimuli. To determine whether KLF5 is involved in mediating proliferative responses to intestinal stressors in vivo, we examined its function in a mouse model of transmissible murine colonic hyperplasia triggered by colonization of the mouse colon by the bacteria Citrobacter rodentium.', 'Heterozygous Klf5 knockout (Klf5(+/-)) mice were generated from embryonic stem cells carrying an insertional disruption of the Klf5 gene. Klf5(+/-) mice or wild-type (WT) littermates were infected with C rodentium by oral gavage. At various time points postinfection, mice were killed and distal colons were harvested. Colonic crypt heights were determined morphometrically from sections stained with H&E. Frozen tissues were stained by immunofluorescence using antibodies against Klf5 and the proliferation marker, Ki67, to determine Klf5 expression and numbers of proliferating cells per crypt.', 'Infection of WT mice with C rodentium resulted in a 2-fold increase in colonic crypt heights at 14 days postinfection and was accompanied by a 1.7-fold increase in Klf5 expression. Infection of Klf5(+/-) mice showed an attenuated induction of Klf5 expression, and hyperproliferative responses to C rodentium were reduced in the Klf5(+/-) animals as compared with WT littermates.'] Does krüppel-like factor 5 mediate transmissible murine colonic hyperplasia caused by Citrobacter rodentium infection? | qiaojin/PubMedQA | 2 | [
-2.24190354347229,
-1.371565818786621,
2.636638641357422
] |
['We used the rhesus macaque model to study the effects of the cag pathogenicity island (cag PAI) on the H pylori host-pathogen interaction.', 'H pylori-specific pathogen-free (SPF) monkeys were experimentally challenged with wild-type (WT) H pylori strain J166 (J166WT, n = 4) or its cag PAI isogenic knockout (J166Deltacag PAI, n = 4). Animals underwent endoscopy before and 1, 4, 8, and 13 weeks after challenge. Gastric biopsies were collected for quantitative culture, histopathology, and host gene expression analysis.', 'Quantitative cultures showed that all experimentally challenged animals were infected with J166WT or its isogenic J166Deltacag PAI. Histopathology demonstrated that inflammation and expansion of the lamina propria were attenuated in animals infected with J166Deltacag PAI compared with J166WT. Microarray analysis showed that of the 119 up-regulated genes in the J166WT-infected animals, several encode innate antimicrobial effector proteins, including elafin, siderocalin, DMBT1, DUOX2, and several novel paralogues of human-beta defensin-2. Quantitative RT-PCR confirmed that high-level induction of each of these genes depended on the presence of the cag PAI. Immunohistochemistry confirmed increased human-beta defensin-2 epithelial cell staining in animals challenged with J166WT compared with either J166Deltacag PAI-challenged or uninfected control animals.'] Does helicobacter pylori induce an antimicrobial response in rhesus macaques in a cag pathogenicity island-dependent manner? | qiaojin/PubMedQA | 2 | [
-2.338623046875,
-1.3498289585113525,
2.74747633934021
] |
['Cardiovascular magnetic resonance (CMR) can provide quantitative data of the myocardial tissue utilizing high spatial and temporal resolution along with exquisite tissue contrast. Previous studies have correlated myocardial scar tissue with the occurrence of ventricular arrhythmia. This study was conducted to evaluate whether characterization of myocardial infarction by CMR can predict cardiovascular events in patients with ischemic cardiomyopathy (ICM).', 'We consecutively studied 86 patients with ICM (LVEF < 50%, mean LVEF: 26 +/- 12%) with CMR before revascularization or medication therapy +/- implantable cardiac defibrillator, determined the amount of myocardial scar, and followed for development of cardiovascular events. Thirty-three patients (38%) had cardiovascular events (mean follow-up: 20 +/- 16 months). Patients who developed cardiovascular events had larger scar volume and scar percentage of the myocardium than those who did not develop cardiovascular events (16.8 +/- 12.4 cm3 vs. 11.7 +/- 12.6 cm3, p = 0.023 and 10.2 +/- 6.9% vs. 7.2 +/- 6.7%, p = 0.037, respectively). There were no significant differences in LVEDV, LVESV and LVEF between the patients with and without cardiovascular events (231 +/- 76 ml vs. 230 +/- 88 ml; 180 +/- 73 ml vs. 175 +/- 90 ml; and 25 +/- 10% vs. 27 +/- 13%, respectively).'] Does quantitative characterization of myocardial infarction by cardiovascular magnetic resonance predict future cardiovascular events in patients with ischemic cardiomyopathy? | qiaojin/PubMedQA | 2 | [
-1.5190773010253906,
-1.4769357442855835,
2.028827428817749
] |
['Comparative analysis of genomes is valuable to explore evolution of genomes, deduce gene functions, or predict functional linking between proteins. Here, we have systematically analyzed the genomic environment of all known DNA replication genes in 27 archaeal genomes to infer new connections for DNA replication proteins from conserved genomic associations.', 'Two distinct sets of DNA replication genes frequently co-localize in archaeal genomes: the first includes the genes for PCNA, the small subunit of the DNA primase (PriS), and Gins15; the second comprises the genes for MCM and Gins23. Other genomic associations of genes encoding proteins involved in informational processes that may be functionally relevant at the cellular level have also been noted; in particular, the association between the genes for PCNA, transcription factor S, and NudF. Surprisingly, a conserved cluster of genes coding for proteins involved in translation or ribosome biogenesis (S27E, L44E, aIF-2 alpha, Nop10) is almost systematically contiguous to the group of genes coding for PCNA, PriS, and Gins15. The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis. Interestingly, the gene encoding the S27E protein, also known as metallopanstimulin 1 (MPS-1) in human, is overexpressed in multiple cancer cell lines.'] Does genomic context analysis in Archaea suggest previously unrecognized links between DNA replication and translation? | qiaojin/PubMedQA | 2 | [
-2.5883443355560303,
-0.27007290720939636,
1.954879879951477
] |
['Stimulation of nitric oxide (NO) synthesis similar to the application of NO donors could be of benefit in liver fibrosis. Many authors believe that activation of NO synthesis by pharmacological agents is promising in the treatment of liver fibrosis. However, there is considerable controversy in understanding the role of NO in fibrogenesis and fibrolysis. The aims of our study were to evaluate the effects of L-arginine, as an NO metabolic precursor, and those of NO synthase (NOS) inhibitors, L-nitroarginine methyl ester (L-NAME) and aminoguanidine (AG) in rats with thioacetamide (TAA)-induced liver fibrosis reversal.', 'Male Wistar rats, 230-240 g, received TAA (200 mg kg(-1), intraperitoneally) twice a week for 3 months. Liver resolution was simulated by withdrawal of TAA administration. Thereafter the animals were subdivided into five groups and treated by intragastric intubation with: L-arginine (100 and 300 mg kg(-1)); L-NAME as an inhibitor of both constitutively expressed NOS (eNOS) and inducible NOS (iNOS) (20 mg kg(-1)), AG as a specific inhibitor of iNOS (100 mg kg(-1)) or placebo. The severity of liver fibrosis was assessed by morphometric evaluation of liver slides stained with Azan-Mallory, hydroxyproline (Hyp) determination and mRNA steady state levels of collagen I, transforming growth factor (TGF)-beta1, metalloproteinases (MMP)-13, -14, tissue inhibitor of MMP (TIMP)-1 and plasminogen activator inhibitor (PAI)-1 were quantified by real time PCR. The activities of serum marker enzyme, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, were measured.', 'TAA treatment during 3 months induced micronodular liver fibrosis with a pronounced deposition of collagen fibres. L-Arginine did not affect this deposition nor did it affect both relative and total liver hydroxyproline content. Both NOS inhibitors significantly increased the square of the liver connective tissue stained by Azan-Mallory and the above parameters characterizing liver hydroxyproline content. Both NOS inhibitors up-regulated procollagen alpha1 (I), MMP-13, TIMP-1 and PAI-1 mRNA expression. The AG effects were more pronounced. than those of L-NAME. AG treatment also increased mRNA expression of TGF-beta1 and PAI-1.'] Does inhibition of inducible nitric oxide synthase activity prevent liver recovery in rat thioacetamide-induced fibrosis reversal? | qiaojin/PubMedQA | 2 | [
-2.399519443511963,
-1.4171514511108398,
2.8758556842803955
] |
['Pancreatic ductal adenocarcinoma (PDAC) progresses rapidly and exhibits profound resistance to treatment. We recently reported that a great majority of PDAC tumors and tumor cell lines express elevated levels of tissue transglutaminase (TG2). Here, we provide first evidence that TG2 expression in PDAC cells results in constitutive activation of focal adhesion kinase/AKT by modulating the expression of the tumor suppressor phosphatase PTEN.', 'Using PDAC cell lines, we determined the effect of TG2 overexpression on PTEN stability and functions. We confirmed the correlation between TG2 expression and PTEN levels in a few (n=51) PDAC tumor samples.', 'We observed that expression of TG2 is inversely correlated with PTEN expression in PDAC cells. Ectopic expression of TG2 inhibited PTEN phosphorylation and promoted its degradation by ubiquitin-proteasomal pathway. Conversely, down-regulation of TG2 by small interfering RNA up-regulated PTEN expression. Clinical relevance of these results was evident in an athymic nude mouse model where down-regulation of endogenous TG2 caused a significant retardation in PDAC xenograft growth. Importantly, the analysis of 51 tumor samples from patients with stage II PDAC revealed that overexpression of TG2 was associated with loss of PTEN expression (P=0.023; odds ratio, 4.1). In multivariate analysis, TG2-mediated loss of PTEN was a prognostic factor for overall survival in patients with stage II pancreatic ductal carcinoma independent of tumor stage/lymph node status and tumor differentiation (P=0.01).'] Does tissue transglutaminase regulate focal adhesion kinase/AKT activation by modulating PTEN expression in pancreatic cancer cells? | qiaojin/PubMedQA | 2 | [
-2.304145574569702,
-1.3830008506774902,
2.7061023712158203
] |
['Four members of the fibroblast growth factor receptor (FGFR) family transduce signals of a diverse group of FGF ligands. The FGFR2-IIIb isoform is abundantly present in the normal pituitary gland with contrasting down-regulation in neoplastic pituitary cells. cDNA profiling identified the cancer-testis antigen melanoma-associated antigen A3 (MAGE-A3) as a putative target negatively regulated by FGFR2.', 'Comparisons were made between normal and neoplastic human and mouse pituitary cells. Gene expression was examined by reverse transcription-PCR, DNA methylation was determined by methylation-specific PCR and combined bisulfite restriction analysis, and histone modification marks were identified by chromatin immunoprecipitation.', 'Normal human pituitary tissue that expresses FGFR2-IIIb does not express MAGE-A3; in contrast, pituitary tumors that are FGFR2 negative show abundant MAGE-A3 mRNA expression. MAGE-A3 expression correlates with the presence and extent of DNA promoter methylation; more frequent and higher-degree methylation is present in the normal gland compared with pituitary tumors. Conversely, pituitary tumors are hypomethylated, particularly in females where MAGE-A3 expression is nearly thrice higher than in males. Estradiol treatment induces MAGE-A3 through enhanced histone 3 acetylation and diminished methylation. The effects of estradiol are directly opposed by FGF7/FGFR2-IIIb. Down-regulation of MAGE-A3 results in p53 transcriptional induction, also through reciprocal histone acetylation and methylation modifications.'] Do fibroblast growth factor 2 and estrogen control the balance of histone 3 modifications targeting MAGE-A3 in pituitary neoplasia? | qiaojin/PubMedQA | 2 | [
-2.4161336421966553,
-1.3271729946136475,
2.768003463745117
] |
['RAG1 and RAG2 initiate V(D)J recombination by assembling a synaptic complex with a pair of antigen receptor gene segments through interactions with their flanking recombination signal sequence (RSS), and then introducing a DNA double-strand break at each RSS, separating it from the adjacent coding segment. While the RAG proteins are sufficient to mediate RSS binding and cleavage in vitro, these activities are stimulated by the architectural DNA binding and bending factors HMGB1 and HMGB2. Two previous studies (Bergeron et al., 2005, and Dai et al., 2005) came to different conclusions regarding whether only one of the two DNA binding domains of HMGB1 is sufficient to stimulate RAG-mediated binding and cleavage of naked DNA in vitro. Here we test whether this apparent discrepancy is attributed to the choice of divalent metal ion and the concentration of HMGB1 used in the cleavage reaction.', 'We show here that single HMG-box domains of HMGB1 stimulate RAG-mediated RSS cleavage in a concentration-dependent manner in the presence of Mn2+, but not Mg2+. Interestingly, the inability of a single HMG-box domain to stimulate RAG-mediated RSS cleavage in Mg2+ is overcome by the addition of partner RSS to promote synapsis. Furthermore, we show that mutant forms of HMGB1 which otherwise fail to stimulate RAG-mediated RSS cleavage in Mg2+ can be substantially rescued when Mg2+ is replaced with Mn2+.'] Is hMG-box domain stimulation of RAG1/2 cleavage activity metal ion dependent? | qiaojin/PubMedQA | 2 | [
-2.388775587081909,
-0.9469872713088989,
2.396757125854492
] |
['The purpose of this study was to compare vaccination coverage among children 19 to 35 months of age with and without special health care needs overall and among demographic subgroups.', "Data are from the National Survey of Children With Special Health Care Needs, a module of the State and Local Area Integrated Telephone Survey, which was sponsored by the Health Resources and Services Administration Maternal and Child Health Bureau and conducted in 2000-2002 by the Centers for Disease Control and Prevention National Center for Health Statistics. We used data from the National Immunization Survey and the National Survey of Children With Special Health Care Needs to examine immunization coverage rates for individual vaccines and an array of combined series vaccinations. The relationship between special needs and immunization status was analyzed by age, gender, and race or ethnicity of the child; the child's health insurance type; the mother's educational attainment and presence in the household; and household income relative to the federal poverty level.", 'Overall, there were no significant differences between children with and without special needs for any of the individual antigens or combined immunization series. Some significant differences by special needs status were found within certain demographic subgroups.'] Does vaccination coverage by special health care need status in young children? | qiaojin/PubMedQA | 1 | [
-2.0673601627349854,
1.2457224130630493,
0.11234516650438309
] |
['The aim of this study was to seek an association between the control of type 2 diabetes mellitus (T2DM), as determined by hemoglobin A1c (HbA1c) levels, and the outcome of colorectal cancer (CRC).', 'We performed a retrospective review of patients with T2DM who had CRC diagnosed between 1997 and 2001. We defined well-controlled T2DM as HbA1c < 7.5% and poorly controlled T2DM as HbA1c > or = 7.5%. A group of age- and gender-matched patients who had CRC without T2DM were used as controls. Forty clinical factors were reviewed, and those associated with poor clinical outcome in each group were examined by univariate analysis (UA) and by the maximum likelihood analysis of logistic regression to determine the independent predictors of cancer outcome.', 'We identified 155 patients with T2DM and CRC, and 114 control patients who had CRC without T2DM. We found no significant differences in any clinical factor by UA between the patients with well-controlled T2DM and the patients who had CRC without T2DM. Compared to both of those patients groups, in contrast, the patients with poorly controlled T2DM had more right-sided CRCs (P = 0.04, OR = 2, 95% CI = 1-4.1), more advanced CRCs (P = 0.02, OR = 2.1, 95% CI = 1-4.4), a younger age of presentation (P = 0.05), greater use of exogenous insulin (P = 0.002), and a poorer 5-year survival (P = 0.001) by UA. Logistic regression showed that poorly controlled T2DM independently predicted the early onset of CRC, a more advanced stage at the time of presentation, poorer 5-year survival, and an increased incidence of right-sided CRCs.'] Is elevated HbA1c an independent predictor of aggressive clinical behavior in patients with colorectal cancer : a case-control study? | qiaojin/PubMedQA | 2 | [
-1.573154091835022,
-1.425641417503357,
1.9415645599365234
] |
['The orphan nuclear hormone receptor small heterodimer partner (SHP) regulates the expression of several genes involved in bile acid homeostasis in the liver. Because bile acid toxicity is a major source of liver injury in cholestatic disease, we explored the role of SHP in liver damage induced by common bile duct ligation (BDL). Shp(-/-) mice show increased sensitivity in this model of acute obstructive cholestasis, with greater numbers of bile infarcts and higher mortality than wild-type C57BL/6 mice. This increased sensitivity could not be accounted for by differences in expression of bile acid homeostatic genes 2 or 5 days after BDL. Instead, higher basal expression of such genes, including the key biosynthetic enzyme cholesterol 7alpha hydroxylase (Cyp7A1) and the bile salt export pump, is associated with both an increase in bile flow prior to BDL and an increase in acute liver damage at only 1.5 hours after BDL in Shp(-/-) mice, as shown by bile infarcts. At 3 hours, Cyp7A1 expression still remained elevated in Shp(-/-) with respect to wild-type mice, and the hepatic and serum bile acid levels and total hepatobiliary bile acid pool were significantly increased. The increased sensitivity of mice lacking SHP contrasts with the decreased sensitivity of mice lacking the farnesoid X receptor (FXR; nuclear receptor subfamily 1, group H, member 4) to BDL, which has been associated with decreased intraductal pressure and fewer bile infarcts.'] Does loss of orphan receptor small heterodimer partner sensitize mice to liver injury from obstructive cholestasis? | qiaojin/PubMedQA | 2 | [
-2.423820734024048,
-1.3120827674865723,
2.765859603881836
] |
['Expenditures related to the use of medical androgen deprivation led in part to the Medicare Modernization Act (MMA) in 2003. This mandated a decline in reimbursement to 80% to 85% of the average wholesale price starting in 2004 followed by a more significant reduction in 2005 to 106% of the average sales price, which effectively reduced the reimbursement by approximately 50% of 2003 values. The authors hypothesized that these changes in reimbursement may affect the way practitioners administer these treatments.', 'The publicly available dataset Medicare Part B Extract Summary System was examined from 2001 to 2005 for trends in the number of allowed services and dollar amounts of allowed charges and payments. The reimbursable Medicare codes of J9217 (leuprolide acetate), J9202 (goserelin acetate), J9219 (leuprolide acetate implant), and J3315 (triptorelin pamoate) were examined for medical castration. The code for simple orchiectomy, 54520, was used for surgical castration.', 'The use of medical castration increased from 2001 to 2003, whereas, over the same period, surgical castration decreased. Total allowed charges for medical castration peaked in 2003 at $1.23 billion. After the enactment of the MMA, surgical castration rates increased, and medical castration decreased. Total allowed charges for medical castration in 2005 dropped 65% from the 2003 peak.'] Does androgen deprivation fall as orchiectomy rates rise after changes in reimbursement in the U.S. Medicare population? | qiaojin/PubMedQA | 2 | [
-1.8259190320968628,
-0.06755511462688446,
0.9863839149475098
] |
['Recent studies detailing how the built environment affects health have found that land use and community design may have an impact on reducing sedentary lifestyles and increasing physical activity.', 'However, there is little information available about the attitudes of local officials and professional staff who often are directly responsible for making decisions about land use and community design.', 'This opportunistic study reports findings across five major surveys that investigated healthy community design knowledge, attitudes, and practice among local officials and professional staff. When possible, comparisons and contrasts of survey responses and policy implications are discussed.'] Are the surveys in ! The role of local government in supporting active community design? | qiaojin/PubMedQA | 1 | [
-2.124732255935669,
3.143852472305298,
-1.4325499534606934
] |
['This analysis was done to compare the risk of development of diabetes among subjects with impaired glucose tolerance (IGT) and early glucose intolerance (EGI; intermediary post glucose level > or = 160 mg/dl) when compared with normal (NGT). Profile of insulin secretion and insulin resistance was compared in a subgroup of subjects with EGI, IGT and diabetes.', "A program on 'primary prevention of diabetes' was initiated and high risk subjects were encouraged to join the program and were followed up. Out of 4084 (M:F 2344:1740) subjects enrolled in the program, a total of 1659 (M:F 1044:615) subjects with mean age 41.3 +/- 10.2 years who had at least two follow up visits were selected for this analysis. OGTTs were performed once in every 6 months. The median follow up duration was 5 years. The conversion rate to diabetes in subjects with persistent IGT or EGI was determined. In a subgroup of subjects, NGT (n = 118), IGT (n = 68), EGI (n = 106) and new DM (n = 126), plasma insulin at fasting, 30 min and 2 hr were measured and insulin resistance (HOMA-IR) was calculated by HOMA method. Insulinogenic index (DeltaI/G) was also calculated.", 'The rate of conversion of IGT 251 (40.5%) and EGI 210 (36.5%) subjects to diabetes was similar and significantly higher when compared with the NGT subjects 99 (21.3%). Similar results were noted both in men and women. By using ROC procedure, a cut - off value of one hour post glucose of > or = 160 mg/dl gave a sensitivity of 80% and specificity of 70% to detect abnormal glucose tolerance. In a subset of subjects studied, it was noted that subjects with EGI had significantly higher fasting insulin values than NGT. Insulin resistance (IR) was the highest in DM [Geometric mean (SD)] 6.6 (1.9)), followed by EGI (4.5 (2.3)) (p < 0.0001 vs NGT, 2.9 (2.4)) and IGT (3.9 (2.2)). Insulinogenic index was normal in EGI, NGT and IGT, and it was lower in DM in comparison with other groups. The multiple logistic regression analysis showed that EGI (odds ratio (OR) 2.11) and development of diabetes was strongly associated. The survival curve (time free from diabetes) showed that the median survival time for NGT, EGI and IGT were 18.7, 11.6 and 9.6 yrs respectively.'] Is risk of future diabetes as high with abnormal intermediate post-glucose response as with impaired glucose tolerance? | qiaojin/PubMedQA | 2 | [
0.21996843814849854,
-1.8645321130752563,
0.7513144016265869
] |
['Collagen phagocytosis by fibroblasts is involved in the intracellular pathway related to collagen breakdown in soft connective tissues. The possible role of lipopolysaccharide (LPS) in regulating this fibroblast function has not been elucidated so we investigated the effect of LPS from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, on collagen phagocytic activity in human gingival fibroblasts and associated regulatory mechanisms.', 'LPS pretreatment stimulated binding of collagen-coated beads to cells and, subsequently, their internalization.', 'The LPS-activated collagen phagocytic process was enhanced in the presence of the soluble form of CD14 (sCD14) or LPS-binding protein (LBP), while the LPS/LBP treatment activated Akt and induced actin reorganization. Furthermore, these LPS/LBP-induced effects were partially suppressed by adding phosphatidyl-inositol-3 kinase (PI3K) inhibitors.'] Does actinobacillus actinomycetemcomitans lipopolysaccharide stimulate collagen phagocytosis by human gingival fibroblasts? | qiaojin/PubMedQA | 2 | [
-2.5728085041046143,
-1.2150423526763916,
2.848184585571289
] |
['Chromatin remodeling complexes facilitate the access of enzymes that mediate transcription, replication or repair of DNA by modulating nucleosome position and/or composition. Ino80 is the DNA-dependent Snf2-like ATPase subunit of a complex whose nucleosome remodeling activity requires actin-related proteins, Arp4, Arp5 and Arp8, as well as two RuvB-like DNA helicase subunits. Budding yeast mutants deficient for Ino80 function are not only hypersensitive to reagents that induce DNA double-strand breaks, but also to those that impair replication fork progression.', 'To understand why ino80 mutants are sensitive to agents that perturb DNA replication, we used chromatin immunoprecipitation to map the binding sites of the INO80 chromatin-remodeling complex on four budding yeast chromosomes. We found that Ino80 and Arp5 binding sites coincide with origins of DNA replication and tRNA genes. In addition, Ino80 was bound at 67% of the promoters of genes that are sensitive to ino80 mutation. When replication forks were arrested near origins in the presence of hydroxyurea (HU), the amount of INO80 complex at stalled forks and at unfired origins increased selectively. Importantly, the resumption of DNA replication after release from a HU block was impaired in ino80 mutants. These cells accumulated double-strand breaks as they attempted to restart replication. Consistently, ino80-deficient cells, although proficient for checkpoint activation, delay recovery from the checkpoint response.'] Does ino80 chromatin remodeling complex promote recovery of stalled replication forks? | qiaojin/PubMedQA | 2 | [
-2.463275671005249,
-0.9034115672111511,
2.4040207862854004
] |
['Individuals with spinal cord injury (SCI) develop a severe form of osteoporosis below the level of injury that is poorly understood. We conducted a preliminary investigation to assess whether circulating markers of bone turnover and circulating RANKL/OPG levels are related to the severity of SCI, aging, or to differences in mobility (i.e., walking or using a wheelchair).', 'Sixty-four caucasian men >or=1.6 years since injury selected based on locomotive mode provided blood samples and completed a health questionnaire at the VA Boston Healthcare System from 10/2003 to 6/2005. Plasma sRANKL, osteoprotegerin (OPG), osteocalcin and carboxyterminal telopeptide of type I collagen (CTx) levels were determined.', 'Increasing age was significantly associated with increased OPG and CTx. Injury severity was predictive of OPG levels, and adjusting for age, participants with cervical motor complete and ASIA C SCI (n=11) had significantly lower mean OPG (46.1 pg/ml) levels than others (63.4 pg/ml). Locomotive mode was not associated with differences in bone markers.'] Do age and motor score predict osteoprotegerin level in chronic spinal cord injury? | qiaojin/PubMedQA | 2 | [
-1.7892283201217651,
-1.3908495903015137,
2.208785057067871
] |
['The objective of the study was to compare sonographic fetal weight estimates with newborn weight charts and analyze the predictive accuracy of the ponderal index (PI) in preterm infants.', 'We generated sonographic reference curves for fetal weight and PI estimates from a database of fetal biometric records from 12,589 term deliveries. We then plotted sonographic and newborn weight and PI of 2406 preterm newborns on these curves and compared them with published newborn weight charts.', 'The third centiles of sonographic and newborn weights diverged markedly between 25 and 36 weeks of gestation and by more than 400 g at 32-33 weeks. In contrast, sonographic and newborn PI values were similar despite uncertainties as to fetal length.'] Do newborn weight charts underestimate the incidence of low birthweight in preterm infants? | qiaojin/PubMedQA | 0 | [
-0.04764188453555107,
-0.4618745446205139,
-0.3711245357990265
] |
['To analyze the drug use in our burn ward, and to investigate the methods in controlling the proportion of drug expenses, as well as the rational use of antibiotics.', 'A randomized sample of 290 burn-patients with hospital stay more than 5 days in 2005 were enrolled in the study, and information about their drug use, (especially that of antibiotics), the drug expenses and its proportion in the total medical expenses, the total therapeutic expenses, and the healing rate of the patients were statically analyzed.', 'Sulfamido was dominant among the topically applied antibiotics, while cephalosporins was dominant among the systemic applied antibiotics. The drug expenses accounted for (11 +/- 5)% in the therapy expenses, while the antibiotics expenses accounted for (5.8 +/- 1.7)% in the therapy expenses, but it accounted for (51 +/- 17)% in the drug expenses. The average expense of every patient was 22026.09 RMB, and the healing rate of the patients was 96.90%.'] Do [ Analysis of drug use of 290 burn patients ]? | qiaojin/PubMedQA | 2 | [
-0.9302231073379517,
-0.08068718016147614,
0.15452022850513458
] |
['To investigate the distribution of burn pathogens and their antibiotic resistance in a burn unit, so as to provide reference for clinical practice.', 'Three hundred and forty-eight burn patients hospitalized in our department were enrolled in this study. The pathogens isolated from the wounds, blood, venous catheter, sputum, urine, purulent discharge of wounds in these patients, and their antibiotic resistance were surveyed by retrospective analysis from Jan, 2001 to Dec, 2006.', 'Total-ly 464 strains were isolated, among which Gram negative (G-) bacilli accounted for 52.6%, Gram positive microorganisms (G+) accounted for 40.5%, and fungi accounted for 6.9%. The main pathogens were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species and Escherichia coli, among which Staphylococcus aureus (MRSA) was predominant (93.5%). MRSA was 100% resistant to levofloxacin, penicillium, oxacillin, and it was also resistant to other antibiotics except Vancomycin. The resistance rate of Pseudomonas aeruginosa to Cefoperazone/Sulbactam, Imipenem and cefepime were 15.8%, 36.8%, 33.3%, respectively.'] Do [ Survey on the distribution of burn pathogens and their antibiotic resistance in burn unit ]? | qiaojin/PubMedQA | 2 | [
-2.3763749599456787,
-0.36288902163505554,
1.9712650775909424
] |
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