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['Nuclear factor-κB (NF-κB) has been implicated in tumor cell proliferation and survival and in tumor angiogenesis. We sought to evaluate the effects of curcumin, an inhibitor of NF-κB, on a xenograft model of disseminated neuroblastoma.', 'For in\xa0vitro studies, neuroblastoma cell lines NB1691, CHLA-20, and SK-N-AS were treated with various doses of liposomal curcumin. Disseminated neuroblastoma was established in\xa0vivo by tail vein injection of NB1691-luc cells into SCID mice, which were then treated with 50 mg/kg/day of liposomal curcumin 5 days/week intraperitoneally.', 'Curcumin suppressed NF-κB activation and proliferation of all neuroblastoma cell lines in\xa0vitro. In\xa0vivo, curcumin treatment resulted in a significant decrease in disseminated tumor burden. Curcumin-treated tumors had decreased NF-κB activity and an associated significant decrease in tumor cell proliferation and an increase in tumor cell apoptosis, as well as a decrease in tumor vascular endothelial growth factor levels and microvessel density.'] Does liposome-encapsulated curcumin suppress neuroblastoma growth through nuclear factor-kappa B inhibition? | qiaojin/PubMedQA | 2 | [
-2.466501474380493,
-1.3311803340911865,
2.815441846847534
] |
['The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis.', 'A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation (N = 49), ALK (anaplastic lymphoma receptor tyrosine kinase) gene rearrangement (N = 41), or wild-type for all 3 (triple negative, N = 80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort (EGFR, KRAS, or ALK) and the triple negative cohort.', 'ALK gene rearrangement was significantly associated with pericardial disease (odds ratio [OR] = 4.61; 95% confidence interval [CI] = 1.30, 16.37; P = .02) and pleural disease (OR = 4.80; 95% CI = 2.10, 10.97; P < .001). Patients with ALK gene rearrangements (OR = 5.50; 95% CI = 1.76, 17.18; P = .003) and patients with EGFR mutations (OR = 5.17; 95% CI = 1.63, 16.43; P = .006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, or adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001).'] Does oncogene status predict patterns of metastatic spread in treatment-naive nonsmall cell lung cancer? | qiaojin/PubMedQA | 2 | [
-1.5644158124923706,
-1.6817502975463867,
2.154616355895996
] |
['Bupivacaine extended-release liposome injection is an investigational local analgesic intended for use in postsurgical pain management. In recognition of the incompletely characterized association of bupivacaine use and cardiac effects, this article reviews the cardiac safety profile of this novel formulation of bupivacaine.', 'Findings from paired electrocardiograms (ECGs), corresponding pharmacokinetic assessments, and cardiovascular adverse events (AEs) in a phase 2, randomized, double-blind, dose-ranging study of bupivacaine extended-release (150, 300, 450, or 600 mg) or bupivacaine HCl 150 mg with epinephrine administered intraoperatively via wound infiltration in patients undergoing total knee arthroplasty (n = 138), were assessed for potential causality. Results from 4 phase 1 bupivacaine extended-release studies that also obtained ECG and/or Holter monitor findings (n = 169) were assessed. In addition, incidences of cardiovascular AEs reported across 10 bupivacaine extended-release wound infiltration studies (n = 1459) were pooled and assessed.', 'In the phase 2 study, mean change from baseline in QRS duration and QTcF duration across dose levels of bupivacaine extended-release was similar (range, -1 to +4 milliseconds and -7 to -10 milliseconds) compared with bupivacaine HCl (-1 millisecond and -6 milliseconds). Mean change from baseline in heart rate, PR interval, and QRS interval was similar between treatment groups as well. No clinically relevant ECG changes or cardiac AEs with bupivacaine extended-release were observed in the other clinical studies.'] Does bupivacaine extended-release liposome injection exhibit a favorable cardiac safety profile? | qiaojin/PubMedQA | 2 | [
-2.1367135047912598,
-1.4938699007034302,
2.646439552307129
] |
['Difficult cannulation is a well known risk for post-ERCP pancreatitis. This study evaluated the outcomes of needle-knife fistulotomy (NKF) used prior to being faced with difficult biliary cannulation.', 'Patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of biliary endotherapy between January 2007 and December 2008 were eligible for this study; 218 patients were recruited. Biliary cannulation was performed only by a standard catheter or a pull type papillotome, without wire-guided assistance in all patients. If selective cannulation was not achieved within five cannulation attempts, NKF was performed, and the results were compared with the easy cannulation group that succeeded biliary cannulation within five attempts.', 'Needle-knife fistulotomy (NKF) was performed in 72 (33.0%) of the 218 patients. The total success rate of the ERCP was 98.2% (214/218), and for the NKF group the success rate was 94.4% (68/72). The rate of complications in patients with NKF did not increase compared to patients in the easy cannulation group (P\xa0>\xa00.05): 4.2% (3/72) versus 3.4% (5/146) for acute pancreatitis, 6.9% (5/72) versus 6.8% (10/146) for bleeding, and 1.4% (1/72) versus 0% (0/146) for perforation, respectively.'] Is early use of needle-knife fistulotomy safe in situations where difficult biliary cannulation is expected? | qiaojin/PubMedQA | 2 | [
-1.2932168245315552,
-1.7017933130264282,
1.922530174255371
] |
['Some studies have reported that serum CA125 level is elevated in SLE patients, and elevated CA125 level may be associated with kidney involvement and disease activity in SLE. However, none of the previous studies controlled confounding variables and the results remained controversial. The present study was aimed to investigate whether elevated serum CA125 level is independently associated with clinical and laboratory features of SLE by excluding various confounders in Chinese patients.', 'A total of 156 SLE patients, consisting of 139 women and 17 men, were included in the study. Some clinical and laboratory characteristics of the patients were obtained by medical record review. Serum CA125 levels were measured by electrochemiluminescence immunoassays.', 'Compared with patients with normal CA125, those with elevated CA125 had significantly more serositis (37.5% vs. 1.9%, p<0.001) and lung involvement (37.5% vs. 12%, p=<0.001), higher SLEDAI scores (p<0.007). Furthermore, disease duration was significantly longer in those with elevated CA125. Univariate logistic regression analysis showed that elevated serum CA125 level was closely associated with disease duration (OR, 95%CI:1.005, 1.001-1.010; p=0.014), serositis (OR, 95%CI: 32.258, 6.993-142.857; p<0.001), renal involvement (OR, 95%CI: 2.283, 1.114-4.673; p=0.024), lung involvement (OR, 95%CI: 4.386, 1.927-10.000; p<0.001) and SLEDAI scores (OR, 95%CI: 1.098, 1.027-1.174; p=0.006). After controlling for various confounding variables, serositis and disease duration were the only two clinical variables significantly associated with elevation of serum CA125 level. The best cut-off value for CA125 using the ROC curve was 38 kU/L (sensitivity 85%, specificity 75%) and the area under the ROC curve was 0.777 with 95%CI of 0.685-0.868 (p<0.001). Furthermore, the serum CA125 levels can fall into the normal range again with the improvement of serositis.'] Is serum CA125 elevation independently associated with serositis in SLE patients? | qiaojin/PubMedQA | 2 | [
-1.166843295097351,
-1.6626330614089966,
1.8250854015350342
] |
['Bone marrow (BM)-derived cells were demonstrated within intestines after radiation damage and were reported to be responsible for intestine repair. However, there was a discrepancy between intestine epithelial clonogenic regeneration, and mouse survival after BM transplantation (BMT) and radiation. The contribution of BM to acute intestine repair after radiation needed further investigation.', 'Mouse survival, intestine microcolony assay, immunohistochemical studies of both intestine and BM were evaluated in mice after whole body irradiation (WBI) and BMT. Immunoblotting, flowcytometry, and double immunostaining were used to evaluate the amount and the character of stroma cells within intestines of recipient mice after receiving gender-mismatched BMT or BMT from green fluorescence donors.', 'Stromal cell proliferation within the lamina propria correlated with the beneficial effect of BMT to intestine recovery and day-8 survival of mice. Few donor-derived cells were found before the completion of intestine repair. The number of host but not donor-derived myelomonocytic and stromal cells increased dramatically within one week after radiation and BMT. Depletion of myelomonocytic cells of recipient mice abolished the mitigating effect of BMT.'] Does bone marrow transplantation enhance trafficking of host-derived myelomonocytic cells that rescue intestinal mucosa after whole body radiation? | qiaojin/PubMedQA | 2 | [
-2.5273916721343994,
-1.150037407875061,
2.779883861541748
] |
['The presence of microorganisms in gastric fluid in neonates at birth is postulated to reflect antenatal infection and also to be associated with the development of bronchopulmonary dysplasia (BPD).', 'A logistic regression analysis, after controlling for other risk factors, indicated that Ureaplasma-positive infants were not at increased risk for moderate/severe BPD (adjusted odds ratio (OR): 2.58, 95% confidence interval (CI): 0.57-6.89, P = 0.12). However, the association between the presence of Ureaplasma species and the risk for moderate/severe BPD increased significantly in infants on mechanical ventilation (MV) ≥2 wk (adjusted OR: 4.17, 95% CI: 1.62-44.1, P = 0.009). An analysis using a lung injury marker indicated that Ureaplasma-positive infants with MV ≥2 wk, but not other infants, showed higher serum KL-6 levels in samples taken from cord blood, and that KL-6 levels increased time-dependently up to 4 wk of age.'] Does antenatal exposure to Ureaplasma species exacerbate bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants? | qiaojin/PubMedQA | 2 | [
-2.112658977508545,
-1.3352136611938477,
2.476822853088379
] |
['In our earlier paper we demonstrated that opening of the blood-brain barrier with an osmotic insult induces brain oedema which represents a factor triggering axonal impairment accompanied with myelin disintegration. The aim of the present study was to find whether methylprednisolone can reduce such axonal impairment in our model of brain oedema.', 'Brain oedema was induced by osmotic blood-brain barrier opening with 20% mannitol applied selectively into the internal carotid. Axonal changes were recognized as signs of myelin disintegration (oedematous vesicles, varicosity, myelin fragmentation) at histological sections stained with Black Gold in hippocampal areas CA1 and CA3 and in the dentate gyrus at time intervals of 30 minutes (acute group) or one week (chronic group) after the blood-brain barrier opening. At the same time intervals methylprednisolone was applied in two different ways - into peritoneal cavity or into the right carotid artery.', 'Impairment of the axonal integrity (changes of the myelin sheet integrity) was identified in all areas studied in both experimental groups. Whereas in the control group axons were of the uniform diameter, in the experimental groups various forms of myelin disintegration were observed. Methylprednisolone reduced the degree of myelin disintegration in both time intervals with the highest effect in the acute group with the intracarotic administration.'] Does methylprednisolone reduce axonal impairment in the experimental model of brain oedema? | qiaojin/PubMedQA | 2 | [
-2.4754297733306885,
-1.129706621170044,
2.6604652404785156
] |
['Acute right ventricular afterload increase is a known perioperative challenge for the anaesthetic regime especially for patients with a compromised right ventricle. The accused negative inotropic action of volatile anaesthetics, with the exception of xenon, might be crucial for the adaptation of the right ventricle.', 'Reversible pulmonary hypertension (mean pressure 40 mmHg) was induced by an infusion of the stable thromboxane A(2) analog U46619 in a porcine model (n = 35). The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were studied by conductance catheter technique. Inflammation and myocardial injury was quantified using serum probes [tumour necrosis factor α (TNFα), interleukin 6 (IL-6), troponin] and myocardial tissue [B natriuretic peptide (BNP), TNFα, activated caspase 3] by enzyme-linked immunosorbance assays and reverse-transcription polymerase chain reaction.', 'After wash in of xenon global haemodynamic parameters remained stable whereas isoflurane caused a systemic vasodilation. This led to a significant decrease in mean arterial pressure in the isoflurane group whereas cardiac output remained stable. Both substances did not alter the biventricular contractility nor did they induce changes in preload for both ventricles. Xenon led to an additional increase in right ventricular afterload, whereas isoflurane reduced pulmonary vascular resistance. No effects on systemic inflammatory response and myocardial injury were found, whereas higher apoptosis rate and expression of BNP and IL-6 was determined in the right ventricle.'] Is xenon superior to isoflurane on cardiovascular function during experimental acute pulmonary hypertension? | qiaojin/PubMedQA | 2 | [
-2.4335777759552,
-1.385770320892334,
2.861525058746338
] |
['To quantitatively estimate tongue function, we developed a handy device for intraoral pressure measurement. The objective of this study was to assess maximum voluntary tongue pressure (MVTP) in Japanese frail elderly persons receiving nursing care services.', 'The study included 42 men and 87 women, aged 58-100 years. To record MVTP, the participants were asked to compress the balloon (diameter: 18 mm) of the disposable intraoral pressure probe onto their palates for 7 s using the maximum voluntary effort of the tongue. Pressures were recorded three times at 1 min intervals.', 'Maximum voluntary tongue pressure was successfully measured in 111 persons. Mean (standard deviation) MVTP was 18 (12) kPa, with a range of 0-63 kPa. The remaining 18 persons could not accurately follow our instructions and MVTP could not be measured.'] Is maximal voluntary tongue pressure decreased in Japanese frail elderly persons? | qiaojin/PubMedQA | 2 | [
0.2448756992816925,
-1.3390846252441406,
0.25322985649108887
] |
['Chromosome rearrangements are caused by many mutational mechanisms; of these, recurrent rearrangements can be particularly informative for teasing apart DNA sequence-specific factors. Some recurrent translocations are mediated by homologous recombination between large blocks of segmental duplications on different chromosomes. Here we describe a recurrent unbalanced translocation casued by recombination between shorter homologous regions on chromosomes 4 and 18 in two unrelated children with intellectual disability.', 'Array CGH resolved the breakpoints of the 6.97-Megabase (Mb) loss of 18q and the 7.30-Mb gain of 4q. Sequencing across the translocation breakpoints revealed that both translocations occurred between 92%-identical human endogenous retrovirus (HERV) elements in the same orientation on chromosomes 4 and 18. In addition, we find sequence variation in the chromosome 4 HERV that makes one allele more like the chromosome 18 HERV.'] Is a recurrent translocation mediated by homologous recombination between HERV-H elements? | qiaojin/PubMedQA | 2 | [
-1.9575148820877075,
-1.0438942909240723,
2.115878105163574
] |
['Psychometric study design.', 'To assess the test-retest reliability and convergent validity of the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) in patients with shoulder disorders.', 'Performance tests that assess functional ability of patients with shoulder disorders can provide useful information for making clinical or return-to-activity decisions. No performance-based shoulder test has yet demonstrated sufficient relevance or clinical measurement properties. The FIT-HaNSA examines upper extremity performance during repetitive tasks that emphasize shoulder reaching and static postures and, therefore, has greater relevance for assessing performance.', 'Thirty-six patients with shoulder disorders and 65 healthy controls were recruited for the study. The FIT-HaNSA, the Disabilities of the Arm, Shoulder and Hand questionnaire, the Shoulder Pain and Disability Index, isometric shoulder strength, and shoulder range of motion were assessed at baseline and repeated 2 to 7 days later. Test-retest reliability was described using intraclass correlation coefficient (ICC(2,1)) and standard error of measurement. Pearson correlation coefficients were used to examine the level of association between the FIT-HaNSA scores and the other measures.', 'The ICCs for test-retest reliability for the FIT-HaNSA ranged from 0.89 to 0.97 in the patient group and 0.79 to 0.91 in the control group. The FIT-HaNSA showed high correlation with the Disabilities of the Arm, Shoulder and Hand and the Shoulder Pain and Disability Index, and moderate correlations with shoulder range of motion and muscle strength.'] Does the FIT-HaNSA demonstrate reliability and convergent validity of functional performance in patients with shoulder disorders? | qiaojin/PubMedQA | 2 | [
-2.0024526119232178,
-0.7707438468933105,
1.9143867492675781
] |
['Burn induces a hypermetabolic state characterized by alterations in protein metabolism, which is associated with increased morbidity and mortality. Eukaryotic elongation factor 2 (eEF2) plays a crucial role in regulating protein synthesis in many diseases, but whether it participates in burn-induced hypermetabolism is unclear. The aim of this study was to determine the expression of eEF2 and the upstream eEF2-inactivating kinase, eEF2K, in severely burned pediatric patients.', 'Eight pediatric patients (> 40% total body surface area) and 3 nonburned pediatric volunteers were enrolled. Muscle and skin biopsies were collected at early (0-10 days postburn [dpb]), middle (11-49 dpb), and late (50-365 dpb) time points. Resting energy expenditure (REE), body composition, and muscle protein fractional synthesis rate (FSR) were measured. Proteins were extracted and analyzed by Western blotting. To further investigate the protein synthesis pathway, microarray data from muscle and skin were examined from 22 nonburned and 20 burned children.', 'Burn patients exhibited a profound hypermetabolic response, as seen by a significant increase in REE (P < .05) and loss of lean body mass without altered muscle FSR, indicating a shift to catabolism after thermal injury. In muscle, the phosphorylation of eEF2K-dependent eEF2 was down regulated early and middle postburn. Similar changes in eEF2K and eEF2 levels occurred in skin at the early time point. Total amounts of eEF2 and eEF2K were not altered.'] Does thermal injury activate the eEF2K-dependent eEF2 pathway in pediatric patients? | qiaojin/PubMedQA | 2 | [
-2.2990081310272217,
-1.3150888681411743,
2.651883602142334
] |
['Arginine deficiency and chronic inflammation may cause immune dysfunction. The authors previously showed that a pharmacological dose of parenteral arginine facilitates ornithine rather than nitric oxide production in subacute peritonitis. Herein, they investigated the effects of different doses of parenteral arginine supplementation on immunocytic subpopulation distribution and function.', 'Male Wistar rats that underwent cecal punctures for induction of subacute peritonitis were infused with conventional parenteral nutrition solution (1.61% of total calories as arginine) or solutions supplemented with low-, medium-, or high-dose arginine (2.85%, 4.08%, and 6.54% of total calories, respectively) for 7 days. Distributions of T cells, B cells, and monocytes/macrophages and cytokine productions of peripheral blood lymphocytes (PBLs) and splenocytes were analyzed.', 'There were no significant differences in circulating white blood cell numbers and serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ concentrations among groups. Serum nitrate/nitrite (NOx) and interleukin (IL)-2 levels were significantly decreased by arginine in a dose-dependent manner. Animals supplemented with parenteral arginine had significantly decreased productions of concanavalin (Con) A- and lipopolysaccharide (LPS)-stimulated TNF-α in PBLs and splenocytes, spontaneous IL-6 and LPS-stimulated IFN-γ in PBLs, and LPS-stimulated IL-6 in splenocytes. In addition, low-dose arginine significantly increased production of spontaneous IFN-γ in PBLs and splenocytes. High-dose arginine significantly increased spontaneous TNF-α, and Con A stimulated IL-4 and IL-6 in PBLs.'] Does appropriate dose of parenteral arginine enhance immunity of peripheral blood cells and splenocytes in rats with subacute peritonitis? | qiaojin/PubMedQA | 2 | [
-2.42057466506958,
-1.3581387996673584,
2.8380730152130127
] |
['Hepatocellular carcinoma (HCC) is a typical inflammation-associated cancer, but may also provoke antitumour immune responses whose significance and underlying mechanisms are incompletely understood.', 'To characterise immune responses in the diethylnitrosamine (DEN)-liver cancer mouse model.', 'Tumour development and immune cell functions upon DEN treatment were compared between C57BL/6 wild-type (WT), chemokine scavenging receptor D6-deficient, B cell- (Igh6), CD4 T cell- (MHC-II) and T-/B cell-deficient (Rag1) mice. Relevance for human HCC was tested by comparing gene array results from 139 HCC tissues.', "The induction of premalignant lesions after 24 weeks and of HCC-like tumours after 42 weeks by DEN in mice was accompanied by significant leucocyte infiltration in the liver and upregulation of distinct intrahepatic chemokines (CCL2, CCL5, CXCL9). Macrophages and CD8 (cytotoxic) T cells were most prominently enriched in tumour-bearing livers, similar to samples from human HCC. Myeloid-derived suppressor cells (MDSC) increased in extrahepatic compartments of DEN-treated mice (bone marrow, spleen). The contribution of immune cell subsets for DEN-induced hepatocarcinogenesis was functionally dissected. In D6(-/-) mice, which lack the chemokine scavenging receptor D6, hepatic macrophage infiltration was significantly increased, but tumour formation and progression did not differ from that of WT mice. In contrast, progression of hepatic tumours (numbers, diameters, tumour load) was strikingly enhanced in T-/B cell-deficient Rag1(-/-) mice upon DEN treatment. When mice deficient for B cells (Igh6(-/-), μMT) or major histocompatibility complex II were used, the data indicated that T cells prevent initial tumour formation, while B cells critically limit growth of established tumours. Accordingly, in tumour-bearing mice antibody production against liver-related model antigen was enhanced, indicating tumour-associated B cell activation. In agreement, T and B cell pathways were differentially regulated in gene array analyses from 139 human HCC tissues and significantly associated with patients' survival."] Does adaptive immunity suppress formation and progression of diethylnitrosamine-induced liver cancer? | qiaojin/PubMedQA | 2 | [
-2.3822269439697266,
-1.3965864181518555,
2.8219547271728516
] |
['Metastatic colorectal cancer (CRC) cells have a selective preference for certain target organs that cannot be explained by circulatory patterns alone. This study aimed to identify clinicopathological features and chromosomal aberrations of primary tumours associated with organ-specific CRC metastasis.', 'Clinicopathological features were investigated in patients with CRC who had exclusively hepatic (n=182) versus exclusively extrahepatic (n=139) metastases. A total of 139 primary tumours of patients with hepatic (n=85) and extrahepatic metastases (n=54) were screened for chromosomal aberrations by microarray-based comparative genomic hybridisation, and the findings were validated in an independent set of 80 primary tumours. A publicly available database was used to correlate chromosomal aberrations with gene expression. Protein expression was evaluated by immunohistochemistry on tissue microarrays.', 'Patients with hepatic metastases were significantly more often male (71% vs 53% p=0.002), more often had abnormal lactate dehydrogenase activity (37% vs 14% p<0.0001), exhibited primary tumour localisation in the colon (52% vs 40% p=0.03) and had synchronous onset of metastases (70% vs 19% p<0.0001). Primary tumours of patients with hepatic metastases were more commonly T3 tumours (79% vs 63% p=0.006) and less commonly of mucinous histology (5% vs 16% p=0.02). Gain of 20p11 was more often observed in patients with hepatic metastases (p<0.05), which was confirmed in an independent dataset (p<0.05; false discovery rate <0.05). Twelve genes mapping at 20p11 were significantly overexpressed as a consequence of 20p11 copy number gain. C20orf3 showed the strongest correlation between RNA expression and DNA copy number. This was reflected in significantly higher protein expression in patients with hepatic metastases (59%; n=325) than in those with extrahepatic metastases (41%; n=256) (p=0.01).'] Are chromosome 20p11 gains associated with liver-specific metastasis in patients with colorectal cancer? | qiaojin/PubMedQA | 2 | [
-1.871390461921692,
-1.5609592199325562,
2.4003896713256836
] |
['The aim of this study was to evaluate the separate impact of insulin resistance and impaired glucose tolerance (IGT) on the incretin effect.', 'Twenty-one healthy glucose-tolerant first-degree relatives of patients with type 2 diabetes underwent a 75 g OGTT, an isoglycaemic i.v. glucose test and a mixed meal to evaluate the incretin effect before and after treatment with dexamethasone to increase insulin resistance. Beta cell glucose sensitivity, beta cell index and fasting proinsulin were measured as indices of beta cell function.', 'After dexamethasone, ten individuals had increased insulin resistance but normal glucose tolerance (NGT), while 11 individuals with an equal increase in insulin resistance developed IGT. In the NGT and IGT groups, the incretin effects were 71 ± 3.2% and 67 ± 4.6% (p = 0.4) before treatment, but decreased significantly in both groups to 58 ± 5.2% and 32 ± 8.8% (p < 0.05 between groups) after treatment. Dexamethasone increased total glucagon-like peptide-1 and glucose-dependent insulinotropic peptide responses to the OGTT. The impaired incretin effect in NGT was observed in the absence of reductions in beta cell glucose sensitivity and beta cell index during i.v. glucose, corrected for insulin resistance, but in parallel with increased proinsulin/C-peptide ratio.'] Are steroid-induced insulin resistance and impaired glucose tolerance both associated with a progressive decline of incretin effect in first-degree relatives of patients with type 2 diabetes? | qiaojin/PubMedQA | 2 | [
-2.3685669898986816,
-1.2642385959625244,
2.715120792388916
] |
['Apoptosis in irradiated normal lung tissue has been observed several weeks after radiation. However, the signaling pathway propagating cell death after radiation remains unknown.', 'C57BL/6J mice were irradiated with 15 Gy to the whole thorax. Pro-apoptotic signaling was evaluated 6 weeks after radiation with or without administration of AEOL10150, a potent catalytic scavenger of reactive oxygen and nitrogen species.', 'Apoptosis was observed primarily in type I and type II pneumocytes and endothelium. Apoptosis correlated with increased PTEN expression, inhibition of downstream PI3K/AKT signaling, and increased p53 and Bax protein levels. Transforming growth factor-β1, Nox4, and oxidative stress were also increased 6 weeks after radiation. Therapeutic administration of AEOL10150 suppressed pro-apoptotic signaling and dramatically reduced the number of apoptotic cells.'] Does oxidative stress mediate radiation lung injury by inducing apoptosis? | qiaojin/PubMedQA | 2 | [
-2.4963021278381348,
-1.096077799797058,
2.6158931255340576
] |
['The objective of this study was to compare the biomechanical outcomes of a new method of anterior cruciate ligament (ACL) treatment, bioenhanced ACL repair, with ACL reconstruction in a large animal model.', 'Twenty-four skeletally immature pigs underwent unilateral ACL transection and were randomly allocated to receive bioenhanced ACL repair with a collagen-platelet composite, allograft (bone-patellar tendon-bone) reconstruction, or no further treatment (n = 8 for each group). The structural properties and anteroposterior laxity of the experimental and contralateral ACL-intact knees were measured 15 weeks postoperatively. All dependent variables were normalized to those of the contralateral knee and compared by use of generalized linear mixed models.', 'After 15 weeks, bioenhanced ACL repair and ACL reconstruction produced superior biomechanical outcomes to ACL transection. However, there were no significant differences between bioenhanced ACL repair and ACL reconstruction for maximum load (P = .4745), maximum displacement (P = .4217), or linear stiffness (P = .6327). There were no significant differences between the 2 surgical techniques in anteroposterior laxity at 30° (P = .7947), 60° (P = .6270), or 90° (P = .9008).'] Are biomechanical outcomes after bioenhanced anterior cruciate ligament repair and anterior cruciate ligament reconstruction equal in a porcine model? | qiaojin/PubMedQA | 2 | [
-1.9483143091201782,
-1.5091761350631714,
2.4632508754730225
] |
['Our previous study showed that administration of nicotine is capable to protect the neurons of hippocampus against the kainic acid induced damage. Here we tested the hypotheses that multiple nicotine administration would prevent the effects of kainic acid on neuronal nicotinic receptor subtypes densities (α-bungarotoxin sensitive and α-bungarotoxin insentive) and on hippocampal cell degeneration.', 'Radioligand binding study was used to detect the particular nAChR subtypes densities. Two histochemical methods (bis-benzimide staining and Fluoro-Jade B dye) were used to detect and evaluate neuronal degeneration.', 'Our study shows that: a) kainic acid single administration increased the number of α-bungarotoxin insentive nicotinic receptors, b) nicotine was able to prevent such changes, c) repeated nicotine administration is capable to attenuate the damage of CA1 and CA3 areas of the hippocampus. No effect on α-bungarotoxin sentive nicotinic receptors was observed. Our data therefore reveal the importance of α-bungarotoxin insentive nicotinic receptors in the response to kainite and the ability of nicotine to prevent such changes both in the cell degeneration and in number of receptors.'] Is neuroprotective effect of nicotine against kainic acid excitotoxicity associated with alpha-bungarotoxin insensitive receptors subtype of nAChRs? | qiaojin/PubMedQA | 2 | [
-2.6154427528381348,
-1.123902440071106,
2.801541328430176
] |
['Prostaglandin E(2) (PGE(2)) is an important mediator in tumor-promoting inflammation. High expression of cyclooxygenase-2 (COX-2) has been detected in the embryonic childhood tumor neuroblastoma, and treatment with COX inhibitors significantly reduces tumor growth. Here, we have investigated the significance of a high COX-2 expression in neuroblastoma by analysis of PGE(2) production, the expression pattern and localization of PGE(2) receptors and intracellular signal transduction pathways activated by PGE(2).', 'A high expression of the PGE(2) receptors, EP1, EP2, EP3 and EP4 in primary neuroblastomas, independent of biological and clinical characteristics, was detected using immunohistochemistry. In addition, mRNA and protein corresponding to each of the receptors were detected in neuroblastoma cell lines. Immunofluorescent staining revealed localization of the receptors to the cellular membrane, in the cytoplasm, and in the nuclear compartment. Neuroblastoma cells produced PGE(2) and stimulation of serum-starved neuroblastoma cells with PGE(2) increased the intracellular concentration of calcium and cyclic AMP with subsequent phosphorylation of Akt. Addition of 16,16-dimethyl PGE(2) (dmPGE(2)) increased cell viability in a time, dose- and cell line-dependent manner. Treatment of neuroblastoma cells with a COX-2 inhibitor resulted in a diminished cell growth and viability that was reversed by the addition of dmPGE(2). Similarly, PGE(2) receptor antagonists caused a decrease in neuroblastoma cell viability in a dose-dependent manner.'] Does autocrine prostaglandin E2 signaling promote tumor cell survival and proliferation in childhood neuroblastoma? | qiaojin/PubMedQA | 2 | [
-2.418635129928589,
-1.3023803234100342,
2.7643749713897705
] |
['Following major lung resection, patients have routinely been monitored in the intensive care unit (ICU). Recently, however, patients are increasingly being placed in a general thoracic ward (GTW). We investigated the safety and efficacy of the GTW care after lobectomy for lung cancer.', '316 patients who had undergone lobectomy for lung cancer were reviewed. These patients were divided into two groups: 275 patients were cared for in the ICU while 41 patients were care for in the GTW immediately post-operation. After propensity score matching, postoperative complications and hospital costs were analyzed. Risk factors for early complications were analyzed with the whole cohort.', 'Early complications (until the end of the first postoperative day) occurred in 11 (3.5%) patients. Late complications occurred in 42 patients (13.3%). After propensity score matching, the incidence of early complications, late complications, and mortality were not different between the two groups. The mean expense was higher in the ICU group. Risk factors for early complications were cardiac comorbidities and low expected forced expiratory volume in one second. The location of postoperative care had no influence on outcome.'] Does immediate Postoperative Care in the General Thoracic Ward be Safe for Low-risk Patients after Lobectomy for Lung Cancer? | qiaojin/PubMedQA | 2 | [
-2.020909070968628,
0.1832369565963745,
0.8351521492004395
] |
['Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months.', 'IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months.'] Does intermittent preventive treatment with sulfadoxine-pyrimethamine modify plasma cytokines and chemokines or intracellular cytokine responses to Plasmodium falciparum in Mozambican children? | qiaojin/PubMedQA | 2 | [
-2.1581571102142334,
-1.4062955379486084,
2.5779058933258057
] |
['Tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. Here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk.', 'We measured midregional proatrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), and C-terminal preprovasopressin (copeptin) in fasting plasma from participants of the Malmö Diet and Cancer Study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). We used Cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactive peptides during a median follow-up of 15 years.', 'First cancer events occurred in 366 males and in 368 females. In males, one SD increase of MR-proANP, copeptin, and MR-proADM was independently related to incident cancer [HR (95% CI)] by 0.85 (0.74-0.96), P = 0.012; 1.17 (1.04-1.32), P = 0.009; and 1.12 (0.99-1.26), P = 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (P < 0.001). In younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (P < 0.001). Among females, we found no relationship between biomarkers and cancer incidence.'] Do vasoactive peptides with angiogenesis-regulating activity predict cancer risk in males? | qiaojin/PubMedQA | 2 | [
-1.8943442106246948,
-1.4567619562149048,
2.3698792457580566
] |
['ZNF143 is a sequence-specific DNA-binding protein that stimulates transcription of both small RNA genes by RNA polymerase II or III, or protein-coding genes by RNA polymerase II, using separable activating domains. We describe phenotypic effects following knockdown of this protein in developing Danio rerio (zebrafish) embryos by injection of morpholino antisense oligonucleotides that target znf143 mRNA.', 'The loss of function phenotype is pleiotropic and includes a broad array of abnormalities including defects in heart, blood, ear and midbrain hindbrain boundary. Defects are rescued by coinjection of synthetic mRNA encoding full-length ZNF143 protein, but not by protein lacking the amino-terminal activation domains. Accordingly, expression of several marker genes is affected following knockdown, including GATA-binding protein 1 (gata1), cardiac myosin light chain 2 (cmlc2) and paired box gene 2a (pax2a). The zebrafish pax2a gene proximal promoter contains two binding sites for ZNF143, and reporter gene transcription driven by this promoter in transfected cells is activated by this protein.'] Is the transcriptional activator ZNF143 essential for normal development in zebrafish? | qiaojin/PubMedQA | 2 | [
-2.4343130588531494,
-1.1945347785949707,
2.663839817047119
] |
['C-type natriuretic peptide (CNP) might be an important regulator of vasodilatation, fluid and sodium balance in liver cirrhosis. We aimed at assessing its regulation and prognostic relevance in liver disease patients.', 'We analyzed NT-proCNP serum levels in 193 patients with chronic liver diseases and 43 healthy controls.', 'Serum NT-proCNP concentrations were significantly elevated in liver disease patients compared to healthy controls, with highest levels in established hepatic cirrhosis, independent of disease etiology. NT-proCNP was associated with complications of liver diseases and portal hypertension, namely ascites, esophageal varices and hepatic encephalopathy. Circulating NT-proCNP correlated inversely with renal function. Importantly, elevated NT-proCNP levels were identified as a predictor of mortality or necessity for transplantation. NT-proCNP levels >2 pmol/L indicated adverse prognosis (sensitivity 66.7%, specificity 72.8%, RR 5.4 [95%-CI 2.6-11.2]).'] Are serum NT-proCNP concentrations elevated in patients with chronic liver diseases and associated with complications and unfavorable prognosis of cirrhosis? | qiaojin/PubMedQA | 2 | [
-1.9988410472869873,
-1.4428845643997192,
2.516563892364502
] |
["Parkinson's disease is a neurodegenerative disorder involving the basal ganglia. Type-2 Diabetes Mellitus is an important risk factor for Alzheimer disease and vascular dementia. However, the association between Parkinson's disease and Diabetes Mellitus is controversial.", "To investigate glucose metabolism abnormalities in 110 Parkinson's disease patients with and without dementia.", "We evaluated Insulin Resistance, glucose and insulin levels after a 2-h-oral-glucose-tolerance-test in 53 Parkinson's disease with dementia and 57 with Parkinson's disease without dementia, with normal fasting glucose.", "BMI, waist circumference, fasting glucose and insulin values, HbA1c, triglycerides, blood lipid profile, depression rating, educational levels, levodopa-dosage and antipsychotic use were similar in both groups. Disease duration and motor impairment were higher in patients with Parkinson's disease and dementia group. After 2-h-oral-glucose-tolerance-test, the prevalence of glucose metabolism abnormalities was significantly higher in group with Parkinson's disease and dementia group (p=0.03). The insulin resistance was present in 62% patients with Parkinson's disease with dementia, of whom 30% had also impaired glucose tolerance, 5,6% newly diagnosed Diabetes Mellitus and 26% only Insulin Resistance. These percentages were significantly higher in group with Parkinson's disease and dementia, also after adjustment for disease duration and motor disability."] Is dementia associated with insulin resistance in patients with Parkinson 's disease? | qiaojin/PubMedQA | 2 | [
-2.3829147815704346,
-0.5888128876686096,
2.0500471591949463
] |
['Glucagon-like peptide 1 (GLP-1), one of the incretin hormones, has been reported to increase positive inotropic activity in cardiac myocytes and protect against myocardial injury. However, the effects upon endothelial cells and the mechanisms involved are not fully understood. We assessed the hypothesis that GLP-1 has protective effects against inflammation and oxidative stress on human endothelial cells.', 'The effects of the GLP-1 analog liraglutide upon TNF-α-induced injury of the human umbilical vein endothelial cells (HUVECs) were evaluated. First, ROS induced by TNF-α was measured by staining with CM-H(2)DCFDA. Intracellular ROS production of HUVECs was significantly decreased in a dose-dependent manner until 30 nM while liraglutide inhibited the induction of gp91(phox) and p22(phox), subunit of NADPH oxidase, by TNF-α. In addition, protein levels of SOD-2, catalase and GPx were significantly increased by liraglutide. Second, rapid translocation of PKC-α into the membrane following TNF-α was evident. Liraglutide significantly inhibited this very rapid TNF-α-induced translocation of PKC-α into membrane at 2.5 min. Third, liraglutide significantly inhibited NF-κB activation and upregulated I-κB family while phosphorylation of IKK-α/β, which is upstream of NF-κB signaling, was also downregulated after 15 min of TNF-α treatment. Finally, liraglutide inhibited apoptosis of HUVEC and expression of Pentraxin-3 induced by TNF-α.'] Does the glucagon-like peptide 1 analog liraglutide reduce TNF-α-induced oxidative stress and inflammation in endothelial cells? | qiaojin/PubMedQA | 2 | [
-2.4161291122436523,
-1.3350403308868408,
2.783411979675293
] |
['Cell-to-cell virus transmission of Human immunodeficiency virus type-1 (HIV-1) is predominantly mediated by cellular structures such as the virological synapse (VS). The VS formed between an HIV-1-infected T cell and a target T cell shares features with the immunological synapse (IS). We have previously identified the human homologue of the Drosophila Discs Large (Dlg1) protein as a new cellular partner for the HIV-1 Gag protein and a negative regulator of HIV-1 infectivity. Dlg1, a scaffolding protein plays a key role in clustering protein complexes in the plasma membrane at cellular contacts. It is implicated in IS formation and T cell signaling, but its role in HIV-1 cell-to-cell transmission was not studied before.', 'Kinetics of HIV-1 infection in Dlg1-depleted Jurkat T cells show that Dlg1 modulates the replication of HIV-1. Single-cycle infectivity tests show that this modulation does not take place during early steps of the HIV-1 life cycle. Immunofluorescence studies of Dlg1-depleted Jurkat T cells show that while Dlg1 depletion affects IS formation, it does not affect HIV-1-induced VS formation. Co-culture assays and quantitative cell-to-cell HIV-1 transfer analyses show that Dlg1 depletion does not modify transfer of HIV-1 material from infected to target T cells, or HIV-1 transmission leading to productive infection via cell contact. Dlg1 depletion results in increased virus yield and infectivity of the viral particles produced. Particles with increased infectivity present an increase in their cholesterol content and during the first hours of T cell infection these particles induce higher accumulation of total HIV-1 DNA.'] Is the scaffolding protein Dlg1 a negative regulator of cell-free virus infectivity but not of cell-to-cell HIV-1 transmission in T cells? | qiaojin/PubMedQA | 2 | [
-2.3776559829711914,
-1.1986124515533447,
2.700798511505127
] |
['The aim of this study is to determine whether computer-assisted surgery (CAS) can gain more precision by utilizing information from pre-operative computed tomography (CT).', 'Sixty-five patients undergoing total knee arthroplasty in 2008 were included. On pre- and post-operative CT, epicondylar and posterior condylar lines were drawn and the posterior condylar angle between these two lines measured. During the surgery, epicondylar and posterior condylar lines were also registered before and after CAS-guided cuts were made. CAS was used to fix the orientation of the cutting guide on the distal femur at 3° of external rotation from the posterior condylar line.', 'There was no correlation between CT measurements and CAS measurements. All orientations of the lines (relative to the horizontal) and angles measured using CT were significantly different (p < 0.05).'] Do cT measurements prior to computer-assisted total knee arthroplasty improve rotational placement of the femoral component? | qiaojin/PubMedQA | 2 | [
-1.8304392099380493,
-1.1621098518371582,
2.020106315612793
] |
["Hypercholesterolemia is known to be a risk factor for Alzheimer's disease (AD), and diet-induced hypercholesterolemia has been shown to accelerate amyloid pathology in animals. While growing evidence has shown that synaptic and cognitive dysfunction in AD is associated with intraneuronal accumulation of Aβ, the relationships between hypercholesterolemia, memory impairment, and intraneuronal Aβ remains unclear. The present study aims to clarify this association.", 'Transgenic mice expressing amyloid precursor protein (APP) harboring the Osaka (E693∆) mutation (APP(OSK)-Tg mice) were used. These mice exhibit intraneuronal Aβ oligomers and memory impairment from 8months of age. Five-month-old male APP(OSK)-Tg mice and non-Tg littermates were fed a high-cholesterol diet for 1 month to induce hypercholesterolemia. At 6 months of age, their cognitive function was evaluated by the Morris water maze. Intraneuronal Aβ, synaptic density, and tau phosphorylation were examined by immunohistochemistry.', 'Serum and brain cholesterol levels were significantly higher in APP(OSK)-Tg mice and non-Tg littermates that were fed a high-cholesterol diet than in control mice that were fed normal chow, indicating that hypercholesterolemia was successfully induced. Hypercholesterolemic APP(OSK)-Tg mice, but not control APP(OSK)-Tg mice or hypercholesterolemic non-Tg littermates, exhibited impaired spatial reference memory, which was accompanied with intraneuronal accumulation of Aβ oligomers, reduced synaptophysin immunoreactivity, and abnormal tau phosphorylation in the hippocampus. Hypercholesterolemia-accelerated accumulation of intraneuronal Aβ oligomers was also observed in another model mouse, Tg2576.'] Does hypercholesterolemia accelerate intraneuronal accumulation of Aβ oligomers resulting in memory impairment in Alzheimer 's disease model mice? | qiaojin/PubMedQA | 2 | [
-2.342289447784424,
-1.3027236461639404,
2.6605095863342285
] |
['Multiple sclerosis (MS) shows evidence of many distinctive aspects of an autoimmune disorder, including a polygenic inheritance. A recent candidate gene for susceptibility to MS is CD24, which has also been shown to be associated with disease progression. This study was designed to examine whether there is a relationship between the CD24 genotype, oligoclonal band (OCB) status and IgG index in the cerebrospinal fluid (CSF) of MS patients.', 'A total of 27 definite MS patients were enrolled in this cross-sectional study. Blood samples were collected from a peripheral vein, and CSF was obtained by lumbar puncture. The CD24 gene was sequenced in the blood specimen, and albumin and IgG concentrations were measured in both CSF and serum. We compared both IgG index and OCB status in patients with and without CD24V/V. The correlation between MS severity score (MSSS), OCB status, CD24 genotype and IgG index was studied.', 'Only 15 patients were OCB positive. Among patients with negative OCBs, only 2 patients had the V/V genotype. Furthermore, in those with the V/V genotype, IgG index was not significantly elevated (p = 0.322). Patients with the V/V genotype had a significantly higher MSSS (p = 0. 04), but neither the presence of OCBs nor the IgG index showed significant correlation with MSSS (p = 0.379 and 0.20, respectively).'] Is cD24 gene allele variation associated with oligoclonal IgG bands and IgG index of multiple sclerosis patients? | qiaojin/PubMedQA | 2 | [
-1.523949146270752,
-1.5680818557739258,
2.121340751647949
] |
['The major aim of this study was to investigate the role of DNA methylation (referred to as methylation) on miRNA silencing in non-small cell lung cancers (NSCLC).', "We conducted microarray expression analyses of 856 miRNAs in NSCLC A549 cells before and after treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (Aza-dC) and with a combination of Aza-dC and the histone deacetylase inhibitor trichostatin A. miRNA methylation was determined in 11 NSCLC cell lines and in primary tumors and corresponding nonmalignant lung tissue samples of 101 patients with stage I-III NSCLC.", 'By comparing microarray data of untreated and drug-treated A549 cells, we identified 33 miRNAs whose expression was upregulated after drug treatment and which are associated with a CpG island. Thirty (91%) of these miRNAs were found to be methylated in at least 1 of 11 NSCLC cell lines analyzed. Moreover, miR-9-3 and miR-193a were found to be tumor specifically methylated in patients with NSCLC. We observed a shorter disease-free survival of patients with miR-9-3 methylated lung squamous cell carcinoma (LSCC) than patients with miR-9-3 unmethylated LSCC by multivariate analysis [HR = 3.8; 95% confidence interval (CI), 1.3-11.2, P = 0.017] and a shorter overall survival of patients with miR-9-3 methylated LSCC than patients with miR-9-3 unmethylated LSCC by univariate analysis (P = 0.013).'] Does genome-wide miRNA expression profiling identify miR-9-3 and miR-193a as targets for DNA methylation in non-small cell lung cancers? | qiaojin/PubMedQA | 2 | [
-1.8323206901550293,
-1.5528194904327393,
2.3458333015441895
] |
['Gastrointestinal stromal tumors (GIST) are characterized by gain-of-function mutations in KIT/PDGFRA genes leading to a constitutive receptor activation which is well counteracted by imatinib. However, cases in which imatinib as first-line treatment has no effects are reported (primary resistance). Our purpose is to investigate alterations in downstream effectors, not reported so far in mutated GIST, possibly explaining the primary resistance to targeted treatments.', 'Two independent naive GIST cohorts have been analyzed for KIT, PDGFRA, KRAS, and BRAF mutations by direct sequencing. Cell lines expressing a constitutively activated and imatinib-responding KIT, alone or in combination with activated KRAS and BRAF, were produced and treated with imatinib. KIT receptor and its downstream effectors were analyzed by direct Western blotting.', 'In naive GISTs carrying activating mutations in KIT or PDGFRA a concomitant activating mutation was detected in KRAS (5%) or BRAF (about 2%) genes. In vitro experiments showed that imatinib was able to switch off the mutated receptor KIT but not the downstream signaling triggered by RAS-RAF effectors.'] Do kRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors? | qiaojin/PubMedQA | 2 | [
-2.40922474861145,
-1.2714027166366577,
2.7334933280944824
] |
['To find out membrane tolerance strategy to ethanol in Bacillus subtilis that possesses a powerful system of protection against environmental stresses.', 'Cytoplasmic membranes of B. subtilis were severely affected by even short-term exposure to 3% (v/v) ethanol: the growth rate and membrane protein synthesis were markedly reduced, and no adaptive alterations in phospholipids were detected. Simultaneously, steady-state DPH fluorescence anisotropy (r(ss)) showed that the membrane rigidity increased substantially. Analysis of the membrane phosphoproteome using in vitro labelling with [γ-(32) P]ATP revealed the association of DnaK and GroEL chaperones with membrane, indicating a stress induction process. Upon a long-term 3% (v/v) ethanol stress, the cell growth accelerated slightly and the composition of polar head groups and fatty acids of membrane phospholipids underwent an extensive reconstruction. Correspondingly, membrane fluidity turned back to the original r(ss) values of the control cells.'] Are dnaK and GroEL chaperones recruited to the Bacillus subtilis membrane after short-term ethanol stress? | qiaojin/PubMedQA | 2 | [
-2.524421215057373,
-1.104274034500122,
2.6836729049682617
] |
['An inflammatory reaction in vascular tissue is a potential factor linking restenosis after angioplasty. Although cilostazol, a selective phosphodiesterase type 3 inhibitor that is a unique antiplatelet drug and vasodilator, has been reported to be anti-inflammatory, its effect on the inflammatory action of mononuclear cells homing to endothelial cells is not clearly understood. In this study, whether cilostazol inhibits neointimal formation and improves inflammatory actions by inhibiting sialyl Lewis X (SLX) expression on mononuclear cells and E-selectin expression on endothelial cells was evaluated.', 'The effect of cilostazol (1, 3, 10, 30 μM) on expression of E-selectin in human umbilical vein endothelial cells and SLX in rat mononuclear cells stimulated with lipopolysaccharide by immunofluorescence and real-time polymerase chain reaction (n = 3) was studied. Additionally, a double-balloon injury model was used on rat carotid arteries to evaluate vascular intimal hyperplasia. 0.1% cilostazol was administered 3 days before the first balloon injury, and the second balloon injury was performed 7 days after the first injury. Cilostazol administration was continued until rats were sacrificed 14 days after the second angioplasty. The expression of SLX on mononuclear cells and E-selectin on endothelial cells by immunofluorescence (n = 10) and real-time polymerase chain reaction (n = 5) were studied.', 'Cilostazol effectively inhibited the expression of SLX on mononuclear cells and E-selectin on endothelial cells. Cilostazol inhibited the migration of mononuclear cells in neointimal regions and neointimal hyperplasia after balloon injury. The numbers of macrophages and T-lymphocytes and the hyperplasia area in neointimal regions decreased from 71.06 ± 20.04, 1121 ± 244.4 cells per section, 206,400 ± 96,150 mm(2) to 29.65 ± 16.73, 374.2 ± 124.5 cells per section, and 101,900 ± 16,150 mm(2) due to the administration of cilostazol.'] Is cilostazol suppression of arterial intimal hyperplasia associated with decreased expression of sialyl Lewis X homing receptors on mononuclear cells and E-selectin in endothelial cells? | qiaojin/PubMedQA | 2 | [
-2.1853268146514893,
-1.4553279876708984,
2.6624202728271484
] |
['The authors aimed to investigate the role of anti-tumor necrosis factor (TNF)-α monoclonal antibody treatment in a mouse model of parenteral nutrition-associated liver disease (PNALD).', 'C57BL/6J male mice (aged 6-8 weeks) were randomly assigned to 3 groups: parenteral nutrition (PN), PN with anti-TNF-α monoclonal antibody treatment (PN + mAb), and controls. A central venous catheter was inserted for intravenous infusion of a PN solution (PN and PN + mAb groups) or saline (controls) for 7 days. Liver pathology, hepatic biochemical indicators, and serum TNF-α concentrations were analyzed. Levels of hepatic bsep, mdr1a/mdr1b, mdr2, and mrp2 mRNA were also evaluated in each group.', 'The PN group showed significant increases in serum transaminase, direct bilirubin, and bile acids relative to the control group (P < .05). Histopathological changes in this group were consistent with early stage cholestasis. The pathological score and serum alanine aminotransferase, total bilirubin, and direct bilirubin levels were improved in the PN + mAb group relative to the PN group (P < .05). The PN group showed significantly lower hepatic bsep, mdr1a/mdr1b, mdr2, and mrp2 mRNA expression than the controls (P < .05), but these were significantly increased compared to the PN group (P < .05).'] Does anti-tumor necrosis factor-α monoclonal antibody alleviate parenteral nutrition-associated liver disease in mice? | qiaojin/PubMedQA | 2 | [
-2.170396089553833,
-1.4966100454330444,
2.6766226291656494
] |
["We sought to investigate whether variants in genes involved in bacterial sensing and autophagy (NOD2, TLR5, IRGM, ATG16L1) and the interleukin-23 signaling pathway (IL12B, IL23R, STAT3) were associated with development of antimicrobial antibodies in patients with Crohn's disease (CD).", 'A cohort of 616 CD patients from a tertiary referral hospital (Mount Sinai Hospital, Toronto) was evaluated. DNA was tested for three CD-associated NOD2 variants (3020insC, G908R, R702W), variants in IRGM, ATG16L1, IL12B, IL23R, STAT3, and a TLR5-stop mutation. Serum was analyzed by enzyme-linked immunosorbent assay (ELISA) for anti-Saccharomyces cerevisiae (ASCA) IgG and IgA, anti-outer membrane porin C (anti-ompC), anti-Cbir1 flagellin, and anti-Pseudomonas fluorescens (anti-I2).', 'NOD2 3020insC was associated with cumulative seroreactivity by quartile sum (P = 0.003) and number of positive antibodies (P = 0.02). NOD2 G908R was also associated with quartile sum (P = 0.05). Increased ASCA seropositivity was associated with NOD2 3020insC (odds ratio [OR] = 1.9, P = 0.02) and G908R (OR = 1.8, P = 0.05), and ATG16L1 T300A (OR = 1.4, P = 0.01) variants; ASCA-positive patients had an increased cumulative number of NOD2 3020insC and ATG16L1 T300A variants (P = 0.007). TLR5-stop mutation abrogated development of anti-flagellin in a dominant-negative fashion (OR = 0.5, P = 0.009). The IRGM CD risk variant was associated with increased anti-flagellin seropositivity (OR = 1.5, P = 0.03). IL12B, IL23R, and STAT3 variants did not contribute to development of antimicrobial antibodies.'] Are pattern recognition receptor and autophagy gene variants associated with development of antimicrobial antibodies in Crohn 's disease? | qiaojin/PubMedQA | 2 | [
-1.8903748989105225,
-1.5736327171325684,
2.4557414054870605
] |
['Malignant mesothelioma is an aggressive tumor of serosal surfaces that is closely associated with asbestos exposure which induces oxidative stress. Heme oxygenase (HO)-1, a rate-limiting enzyme of heme degradation, plays a protective role against oxidative stress. The HO-1 gene promoter carries (GT)n repeats whose number is inversely related to transcriptional activity of the HO-1 gene.', 'To investigate the relationship between the length polymorphism of (GT)n repeats and mesothelioma susceptibility, we analyzed the HO-1 promoter in 44 asbestos-exposed subjects without mesothelioma and 78 asbestos-exposed subjects with mesothelioma using PCR-based genotyping.', 'The number of repeats ranged from 16 to 38, with two peaks at 23 and 30 repeats. Polymorphisms of (GT)n repeats were grouped into two classes of alleles, short (S) (<24) and long (L) (≥24), and three genotypes: L/L, L/S, and S/S. The proportions of allele frequencies in class L as well as genotypic frequencies of L allele carriers (L/L and L/S) were significantly higher in the asbestos-exposed subjects with mesothelioma than in those without mesothelioma.'] Is heme oxygenase-1 promoter polymorphism associated with risk of malignant mesothelioma? | qiaojin/PubMedQA | 2 | [
-2.0649032592773438,
-1.3425838947296143,
2.4236268997192383
] |
['Osteonecrosis, also known as avascular necrosis, of the femoral head is a debilitating disorder that commonly affects 30- to 50-year-old individuals. Currently, definitive treatment is limited to total hip replacement. However, recent studies have demonstrated bone regeneration in the femoral head after the infusion of bone marrow-derived mesenchymal stem cells. In addition, local injection of adipose tissue-derived stem cells has been shown to regenerate medullary bone-like tissue 3 months after treatment. However, there have been no long-term follow-up studies on humans treated with adipose tissue-derived stem cells for osteonecrosis.', 'To determine if treatment with adipose tissue-derived stem cells and platelet-rich plasma leads to the regeneration of medullary bone-like tissue and long-term reduction of hip pain in patients with femoral head osteonecrosis.', 'This report of two clinical cases was in compliance with the Declaration of Helsinki. Also, the Korean Food and Drug Administration has allowed the use of adipose tissue-derived stem cells (ADSCs) in medical treatments since 2009. To obtain ADSCs, lipoaspirates were obtained from lower abdominal subcutaneous adipose tissue. The stromal vascular fraction was separated from the lipoaspirates by centrifugation after treatment with collagenase. The stem-cell-containing stromal vascular fraction was mixed with calcium chloride-activated platelet rich plasma and hyaluronic acid, and this mixture was then injected into the diseased hip. The affected hip was reinjected with calcium chloride-activated platelet rich plasma weekly for 4 weeks. Patients were subjected to pre- and post-treatment magnetic resonance imaging (MRI) scans.', 'Two patients (34- and 39-year-old men) with femoral head osteonecrosis and severe hip pain were treated with adipose-derived stem cells. The MRI scans of the affected hip in both patients showed segmental areas of low signal intensity (T1 axial views) in the subchondral bones with a "double line sign" consistent with osteonecrosis. The visual analog scale score, physical therapy testing, and Harris Hip score of both patients improved after stem cell treatment. Both patients also demonstrated post-procedure improvement in their MRI scans, evidenced by positive T1 signal changes consistent with medullary bone regeneration. Further, the long-term reduction in hip pain was correlated with the MRI findings indicative of bone regeneration.'] Do autologous adipose tissue-derived stem cells induce persistent bone-like tissue in osteonecrotic femoral heads? | qiaojin/PubMedQA | 2 | [
-2.4661102294921875,
-1.3444420099258423,
2.8370237350463867
] |
['Limited data is available upon the distribution of different HIV-1/2 genotypes in the blood donor population from Guinea Conakry.', 'To investigate the prevalence of HIV-1/2 subtypes in asymptomatic blood donors in Guinea Conakry, in order to update knowledge of HIV-1/2 epidemiology within this country.', 'Samples from 104 blood donors seropositive for HIV-1/2 were tested for HIV-1 by real-time RT-PCR. Those negative for HIV-1 were tested with HIV-2 nested RT-PCR. Positive samples were further amplified in the HIV-1 gag and pol regions and sequenced. Subtypes were determined by phylogenetic analysis on amplicon sequences.', '61 samples were positive by HIV-1 real-time RT-PCR. Of the 43 negative, 2 (4.6%) were positive for HIV-2. 52/61 (85.3%) samples were positive by nested RT-PCR. Of the 52, 43 (70.5%) and 31(59.6%) sequences were obtained in the gag and pol regions, respectively; 23 for both regions. HIV-1 subtype distribution was 1 B (2.1%), 8 F (17%), 8 D (17%) and 28 CRF02_AG (59.6%) with 2 unclassified recombinants (4.3%). Unique clusters for subtype D and F distinguished Guinea from HIV-1 subtype distribution in neighboring countries.'] Are hIV-1 subtypes D and F prevalent in Guinea Conakry? | qiaojin/PubMedQA | 2 | [
-1.5384408235549927,
-0.8882778286933899,
1.4701141119003296
] |
['Visual recovery after rhegmatogenous retinal detachment (RRD) repair depends upon various anatomical factors. We investigated spectral-domain optical coherence tomography (SD-OCT) abnormalities, pre- and postoperatively, in patients with nontraumatic RRD and correlated these findings with visual outcome.', 'The medical records of all patients presenting to Weill Cornell Medical College with nontraumatic macula-involving RRD from August 2010 to September 2011 were retrospectively reviewed in this single-center, consecutive case series. All patients underwent pre- and postoperative visual acuity (VA) testing, slit-lamp biomicroscopy, and dilated fundus examination. Spectral domain optical coherence tomography was obtained preoperatively in twelve patients and postoperatively in ten patients.', 'Twelve patients (12 eyes) were included in the final analysis. Preoperative optical coherence tomography revealed that the inner segment/outer segment (IS/OS) junction was disrupted in 10/12 eyes (83%), the external limiting membrane (ELM) was disrupted in 9/12 (75%) eyes, cystoid macular edema (CME) was present in 10/12 (83%) eyes, an epiretinal membrane (ERM) was present in 2/12 eyes (17%) and outer retinal corrugation was present in 7/12 (58%) eyes. In postoperative imaging of 10 eyes, the IS/OS junction was disrupted in 4/10 (40%), the ELM was disrupted in 3/10 (30%) eyes, CME was present in 2/10 (20%), and an ERM in 1/10 (10%). All retinas were attached postoperatively. Outer retinal corrugation was the most predictive of worse preoperative (P = 0.0016) and 1-month postoperative visual acuity (P = 0.05).'] Does optical coherence tomography predict visual outcome in macula-involving rhegmatogenous retinal detachment? | qiaojin/PubMedQA | 2 | [
-1.9558359384536743,
-1.5142579078674316,
2.4752726554870605
] |
['Cell surface proteoglycans play vital functional roles in various biological processes such as cell proliferation, differentiation, adhesion, inflammation, immune response, sustentation of cartilage tissue and intensity of tissues. We show here that serglycin-like synthetic glycopeptides function efficiently as a molecular shuttle to hijack glycosaminoglycan (GAG) biosynthetic pathway within cells across the plasma membrane.', 'Fluorescence (FITC)-labeled tetrapeptide (H-Ser(1)-Gly(2)-Ser(3)-Gly(4)-OH) carrying Galβ(1➝4)Xylβ1➝ defined as proteoglycan initiator (PGI) monomer and its tandem repeating PGI polymer was employed for direct imaging of cellular uptake and intracellular traffic by confocal laser-scanning microscopy. Novel method for enrichment analysis of GAG-primed PGIs by combined use of anti-FITC antibody and LC/mass spectrometry was established.', 'PGI monomer was incorporated promptly into human articular chondrocytes and distributed in whole cytoplasm including ER/Golgi while PGI polymer localized specifically in nucleus. It was demonstrated that PGIs become good substrates for GAG biosynthesis within the cells and high molecular weight GAGs primed by PGIs is chondroitin sulfate involving N-acetyl-d-galactosamine residues substituted by 4-O-sulfate or 6-O-sulfate group as major components. PGIs activated chondrocytes proliferation and induced up-regulation of the expression level of type II collagen, suggesting that PGIs can function as new class cytokine-like molecules to stimulate cell growth.'] Does molecular shuttle between extracellular and cytoplasmic space allow for monitoring of GAG biosynthesis in human articular chondrocytes? | qiaojin/PubMedQA | 2 | [
-2.4207990169525146,
-1.345430612564087,
2.853127956390381
] |
["Uveitis, or intraocular inflammatory disease, is a frequent extra-articular manifestation of several forms of arthritis. Despite the frequent co-occurrence of uveitis and arthritis, little is understood of the eye's predisposition to this disease. We recently described a previously unreported uveitis in a murine model of spondyloarthropathy triggered by autoimmunity to aggrecan, a prominent proteoglycan (PG) macromolecule in cartilage. In contrast to the joint and spine, wherein interferon-gamma (IFNγ) deficiency reduced disease, IFNγ deficiency worsened uveitis. Given the regulatory role of IFNγ on the Th17 response and the current focus of anti-interleukin-17 therapeutics in patients with uveitis and spondyloarthritis, we sought to determine the extent to which interleukin (IL)-17 mediates uveitis in the absence of IFNγ.", 'Antigen specific T cell cytokine production was measured in splenocyte cultures using multiplex-ELISA. Transgenic (Tg) mice expressing the T cell receptor (TCR) recognizing the dominant arthritogenic epitope in the G1 domain of PG (TCR-Tg), also lacking IFNγ, were immunized with PG. Mice were then systemically administered an anti-IL-17 neutralizing antibody. The onset and severity of peripheral arthritis was evaluated by clinical scoring criteria and histology. Uveitis was assessed using intravital videomicroscopy, which visualizes leukocyte trafficking within the vasculature and tissue of the iris, and by histology.', 'TCR-Tg splenocytes stimulated in vitro with recombinant G1 peptide demonstrated exacerbated production of cytokines, such as macrophage inflammatory protein (MIP)-1α, MIP-1β, IL-1β, and most notably IL-17A as a consequence of IFNγ deficiency. In vivo, IL-17 inhibition prevented the component of PG-induced arthritis that occurs independently of IFNγ. Blockade of IL-17 ameliorated the ongoing leukocyte trafficking responses within the iris vasculature and tissue, which coincided with reduced infiltration of leukocytes within the anterior and posterior eye segments. However, the anti-IL-17 treatment resulted in unanticipated photoreceptor toxicity.'] Does neutralization of IL-17 ameliorate uveitis but damages photoreceptors in a murine model of spondyloarthritis? | qiaojin/PubMedQA | 2 | [
-2.433469533920288,
-1.4028692245483398,
2.903595209121704
] |
['To determine how often patients diagnosed with bulimia nervosa (BN) surpass their highest pre-morbid weight during the course of their disorder.', 'The weight histories of individuals with BN were determined using retrospective weight data (Study 1) and combined retrospective/prospective data (Study 2).', 'Retrospective analyses indicated that 59.0% (n = 46) and 61.8% (n = 110), respectively, reported that their highest weight was reached after developing BN. In Study 2, 35.3% of participants superseded their highest pre-enrollment weights during 8 years of follow-up, and 71.6% reached a post-morbid highest weight before remission. Across studies, the primary difference between patients who did and did not reach their highest weight post-morbidly was that those who did had an earlier age of onset and longer duration of BN.'] Are elevated pre-morbid weights in bulimic individuals usually surpassed post-morbidly : implications for perpetuation of the disorder? | qiaojin/PubMedQA | 2 | [
-2.633800745010376,
0.8016334176063538,
0.9944424629211426
] |
['The Frontonasal Ectodermal Zone (FEZ) is a signaling center in the face that expresses Sonic hedgehog (Shh) and regulates patterned growth of the upper jaw. Blocking SHH in the forebrain blocks Shh expression in the FEZ and creates malformations resembling holoprosencephaly (HPE), while inhibition of BMP signaling in the mesenchyme blocks FEZ formation and causes similar dysmorphology. Thus, the brain could regulate FEZ formation by SHH or BMP signaling, and if so, activating one of these pathways in the face might alleviate the effects of repression of SHH in the brain.', 'We blocked SHH signaling in the brain while adding SHH or BMP between the neural and facial ectoderm of the frontonasal process. When applied early, SHH restored Shh expression in the FEZ and significantly improved shape outcomes, which contrasts with our previous experiments that showed later SHH treatments have no effect. BMP-soaked beads introduced early and late caused apoptosis that exacerbated malformations. Finally, removal of Smoothened from neural crest cells did not inhibit Shh expression in the FEZ.'] Does signaling by SHH rescue facial defects following blockade in the brain? | qiaojin/PubMedQA | 2 | [
-2.7790157794952393,
-0.5166541934013367,
2.3207180500030518
] |
['12/15-Lipoxygenase (12/15-LO) is an enzyme widely distributed in the central nervous system, and it has been involved in the neurobiology of Alzheimer disease (AD). However, the mechanism involved remains elusive.', 'We investigated the molecular mechanism by which 12/15-LO regulates amyloid β (Aβ)/Aβ precursor protein (APP) metabolism in vivo and in vitro by genetic and pharmacologic approaches.', 'Here we show that overexpression of 12/15-LO leads to increased levels of β-secretase-1 (BACE1) mRNA and protein, a significant elevation in Aβ levels and deposition, and a worsening of memory deficits in AD transgenic mice. In vitro and in vivo studies demonstrate that 12/15-LO regulates BACE1 mRNA expression levels via the activation of the transcription factor Sp1. Thus, 12/15-LO-overexpressing mice had elevated levels of Sp1 and BACE1, whereas 12/15-LO-deficient mice had reduced levels of both. Preventing Sp1 activation by pharmacologic inhibition or dominant-negative mutant blocks the 12/15-LO-dependent elevation of Aβ and BACE1 levels.'] Does transcriptional regulation of β-secretase-1 by 12/15-lipoxygenase result in enhanced amyloidogenesis and cognitive impairments? | qiaojin/PubMedQA | 2 | [
-2.4903533458709717,
-0.9381449222564697,
2.4179983139038086
] |
['The major form of magnetic resonance imaging-defined white matter injury (WMI) comprises diffuse lesions where the burden of small necrotic foci (microscopic necrosis) is poorly defined. We hypothesized that myelination failure associated with diffuse WMI involves an aberrant injury response linked to arrested preoligodendrocyte (preOL) maturation in reactive astrocyte-rich lesions.', 'A retrospective autopsy series (1983-2000) was selected for cases with diffuse WMI and analyzed relative to prospectively collected contemporary cases (2003-2010). Controls were age- and region-matched to address regional variation in preOL maturation. Successive oligodendrocyte stages were analyzed with lineage-specific markers. Microscopic necrosis was quantified with microglial markers. Axon injury markers defined the burden of axonopathy. Extracellular matrix remodeling was defined by detection of hyaluronic acid (HA), an inhibitor of preOL maturation, and the HA receptor, CD44.', 'In the contemporary case series, diffuse WMI was accompanied by a significant reduction in the burden of microscopic necrosis and axonopathy. Diffuse astrogliosis extended into the lesion surround with elevated HA and astrocyte-expressed CD44. The total population of OL lineage stages was significantly increased in lesions. This increase coincided with significant expansion of the preOL pool.'] Does arrested preoligodendrocyte maturation contribute to myelination failure in premature infants? | qiaojin/PubMedQA | 2 | [
-2.5205461978912354,
-1.2281572818756104,
2.835327386856079
] |
['On the basis of the hypothesis that copy number mutations of the genes encoding myelin compact proteins are responsible for myelin disorders in humans, we have explored the possibility of copy number mutations in patients with Charcot-Marie-Tooth disease (CMT) whose responsible genes remain undefined.', 'A family with 6 affected members in 3 consecutive generations, presenting with motor and sensory demyelinating polyneuropathy, was investigated. Characteristic clinical features in this pedigree include Adie pupils and substantial intrafamilial variability in the age at onset, electrophysiological findings, and clinical severity. Nucleotide sequence analyses of PMP22, MPZ, or GJB1 and gene dosage study of PMP22 did not reveal causative mutations. Hence, we applied a custom-designed array for comparative genomic hybridization (CGH) analysis to conduct a comprehensive screening of copy number mutations involving any of the known causative genes for CMT other than PMP22.', 'The array CGH analyses revealed increased gene dosage involving the whole MPZ, and the flanking genes of SDHC and C1orf192. The gene dosage is estimated to be 5 copies. This mutation showed complete cosegregation with the disease phenotype in this pedigree.'] Does increased gene dosage of myelin protein zero cause Charcot-Marie-Tooth disease? | qiaojin/PubMedQA | 2 | [
-2.445993661880493,
-1.1847033500671387,
2.6673951148986816
] |
['Connexin hemichannels can open during ischemia, resulting in loss of membrane potential, calcium influx, and release of glutamate. In this study, we tested the hypothesis that opening of hemichannels after cerebral ischemia may contribute to delayed evolution of injury.', 'We infused a mimetic peptide that blocks connexin 43 hemichannels into the lateral ventricle of chronically instrumented fetal sheep in utero at 128 ± 1 days gestation (term is 147 days), starting 90 minutes after 30 minutes of severe ischemia induced by reversible bilateral carotid artery occlusion, for either 1 or 25 hours. Sheep were killed 7 days later.', 'Peptide infusion was associated with a graded improvement in recovery of electroencephalographic power after 7 days recovery, from -13 ± 1.9 dB (n = 7) after ischemia-vehicle to -9 ± 1.6 dB (n = 7) after ischemia-short infusion and -5 ± 1.6 dB after ischemia-long infusion (n = 6, p < 0.05). Peptide infusion was associated with reduced seizure activity after ischemia, less frequent status epilepticus (p < 0.05), and earlier return of sleep state cycling (p < 0.05). Ischemia-long infusion (but not ischemia-short infusion) was associated with improved survival of oligodendrocytes in intragyral and periventricular white matter (p < 0.05) and increased brain weight (p < 0.05). Ischemia-long infusion was associated with an intermediate estimate of surviving neurons in the parasagittal cortex of 2.9 ± 0.8 × 10(6), in comparison to sham control (4.3 ± 0.9 × 10(6)) or ischemia-vehicle (1.5 ± 0.4 × 10(6); p < 0.05 vs sham control).'] Does connexin hemichannel blockade improve outcomes in a model of fetal ischemia? | qiaojin/PubMedQA | 2 | [
-2.1211631298065186,
-1.4460060596466064,
2.6379480361938477
] |
["Interleukin 6 (IL-6) has been related to beta-amyloid aggregation and the appearance of hyperphosphorylated tau in Alzheimer's disease (AD) brain. However, previous studies relating IL-6 genetic polymorphisms to AD included few and unrepresentative single nucleotide polymorphisms (SNPs) and the results were inconsistent.", 'This is a case-control study. A total of 266 patients with AD, aged≧65, were recruited from three hospitals in Taiwan (2007-2010). Controls (n = 444) were recruited from routine health checkups and volunteers of the hospital during the same period of time. Three common IL-6 haplotype-tagging SNPs were selected to assess the association between IL-6 polymorphisms and the risk of late-onset AD (LOAD).', 'Variant carriers of IL-6 rs1800796 and rs1524107 were significantly associated with a reduced risk of LOAD [(GG + GC vs. CC): adjusted odds ratio (AOR) = 0.64 and (CC + CT vs. TT): AOR = 0.60, respectively]. Haplotype CAT was associated with a decreased risk of LOAD (0 and 1 copy vs. 2 copies: AOR = 0.65, 95% CI = 0.44-0.95). These associations remained significant in ApoE e4 non-carriers only. Hypertension significantly modified the association between rs2069837 polymorphisms and the risk of LOAD (pinteraction = 0.03).'] Are sequence variants of interleukin 6 ( IL-6 ) significantly associated with a decreased risk of late-onset Alzheimer 's disease? | qiaojin/PubMedQA | 2 | [
-1.9195287227630615,
-1.4491597414016724,
2.353360414505005
] |
['To identify whether epistasis between TG and HSD17B4 and whether polymorphisms in HSD17B4 are associated with premature ovarian failure (POF).', 'Case-control genetic association study.', 'Research laboratory of a university.', 'Female patients with POF (98) and controls (218) of Korean ethnicity participated in this study.', 'None.', 'Genotype distribution, haplotype (HT) inference, and gene-gene interaction.', 'Distribution of one haplotype (A-G-A-A-G-G) on the HSD17B4 gene was significantly different between the POF group and the control group in a dominant model. In addition, the combined effect of the single nucleotide polymorphisms (SNPs) HSD17B4 rs28943592 and TG rs2076740 was significantly associated with POF (odds ratio = 7.74, 95% confidence interval = 1.67-35.94), although a significant association was not observed in the single SNP model.'] Is epistasis between the HSD17B4 and TG polymorphisms associated with premature ovarian failure? | qiaojin/PubMedQA | 2 | [
-1.954979419708252,
-0.7939955592155457,
1.8595519065856934
] |
['The objective was to determine the prevalence of, and factors that predict, detrusor underactivity (DU) in patients presenting with incontinence or lower urinary tract symptoms (LUTS) following radical prostatectomy (RP). We also determined the prevalence of bladder outlet obstruction (BOO) and detrusor overactivity (DO) in this population.', 'Patients who underwent urodynamics post-RP were identified. Detrusor underactivity was defined as a maximum flow rate (Qmax) of ≤15 mL/s and detrusor pressure (Pdet) Qmax <20 cmH20 or maximum Pdet <20 cmH20 during attempted voiding. Abdominal voiding (AV) was defined as sustained increase in abdominal pressure during voiding. Bladder outlet obstruction and DO were identified using the Abrams-Griffiths nomogram and the International Continence Society criteria. Univariate logistic regression was used to determine factors predicting DU. The following factors were analyzed: age, year of RP, procedure type (minimally-invasive surgery [MIS] or open), postoperative radiation, nerve-sparing, clinical stage, biopsy Gleason grade and interval between RP and evaluation.', 'Between 2005 and 2008, 264 patients underwent urodynamics post-RP. Detrusor underactivity was observed in 108 patients (41%; 95% CI 35%, 47%), of whom 48% demonstrated AV. Overall, BOO and DO were present in 17% (95% CI 12%, 22%) and 27% (95% CI 22%, 33%), respectively. On univariate analysis, only MIS RP was predictive of DU (univariate odds ratio 2.05 for MIS vs. open; p = 0.009).'] Is detrusor underactivity prevalent after radical prostatectomy : A urodynamic study including risk factors? | qiaojin/PubMedQA | 2 | [
-1.9014939069747925,
-1.4926018714904785,
2.4288899898529053
] |
['Pemphigus vulgaris (PV) is a chronic, autoimmune blistering disease. Most patients require long term therapy with systemic steroids as a first line of treatment. Immunosuppressive agents such as methotrexate (MTX) are administrated as second line therapy. Only a few reports have assessed MTX efficacy, with contradictory results.', 'The aim of this study was to evaluate MTX as an adjuvant therapy in patients with PV.', 'A retrospective study of 30 PV patients treated with MTX as an adjuvant therapy. Disease severity score and prednisone dosage served as assessing measures.', 'All patients were treated with 15 mg MTX per week. Of the 25 patients defined as severe or moderate disease at the beginning of treatment, 21 (84%) improved and downgraded their severity status at 6 months of treatment. In 21 patients (76.6%) we were able to reduce the prednisone dose. There was a significant improvement in the severity score (p=0.00001) and in prednisone dose (p=0.0001). Four patients (13%) suffered from mild side effects.'] Is methotrexate an effective and safe adjuvant therapy for pemphigus vulgaris? | qiaojin/PubMedQA | 2 | [
-1.5844347476959229,
-1.4835803508758545,
2.1255269050598145
] |
['Breast augmentation by autologous fat transfer is an appealing alternative in need of scientific validation.', 'In a prospective multicenter study, 81 women (age range, 17 to 63 years) wore the Brava device, a bra-like vacuum-based external tissue expander, for 4 weeks and then underwent autologous fat injection using 10 to 14 needle puncture sites into each breast in a three-dimensional fanning pattern (average, 277 ml volume injected per breast). Patients resumed Brava wear within 24 hours for 7 or more days. Pretreatment and posttreatment breast volumes were derived from three-dimensional volumetric reconstruction of magnetic resonance imaging scans, and outcomes were compared with a meta-analysis of six recent published reports on autologous fat transfer breast augmentation without expansion. Follow-up ranged from 12 months to 6 years (average, 3.7 years).', 'Breast volume was unchanged between 3 and 6 months. Seventy-one of the treated women were compliant with Brava wear and had a mean augmentation volume at 12 months of 233 ml per breast compared with 134 ml per breast in published series without Brava (p < 0.00001). Graft survival was 82 ± 18 percent compared with 55 ± 18 percent without Brava (p < 0.00001). There was a strong linear correlation (R = 0.87) between pregrafting Brava expansion and the resultant breast augmentation. There were no suspicious breast masses or nodules. Magnetic resonance imaging recognized a 16 percent incidence of fat necrosis easily identified at 1-year mammographic evaluation.'] Is brava and autologous fat transfer a safe and effective breast augmentation alternative : results of a 6-year , 81-patient , prospective multicenter study? | qiaojin/PubMedQA | 2 | [
-1.7950186729431152,
-1.6065868139266968,
2.4411373138427734
] |
['Astacin-like metallo-proteases are zinc endopeptidases conserved among vertebrates and invertebrates. First described as hatching gland enzymes, many members of the family possess other functions during embryonic development. In the chick, however, functions of Astacin-like proteins remain elusive.', 'We report here that Astacin-like (ASTL) is strongly expressed in mouse and chicken embryonic stem (ES) cells and exhibits a very dynamic expression pattern during embryogenesis and organogenesis, mostly in remodeled epithelia. Consistent with its expression in ES cells, chick ASTL is detected in vivo in the pluripotent cells of the epiblast and then disappears from the newly induced neural plate. ASTL expression remains at the junction of non-neural and neural ectoderm, just before neural tube closure. At later stages, chick ASTL is detected in the ventral epidermis before ventral closure, in the intermediate mesoderm, in the gonads and in the forming nephric duct and tubules of the mesonephros and metanephros.'] Is astacin-like metallo-endopeptidase dynamically expressed in embryonic stem cells and embryonic epithelium during morphogenesis? | qiaojin/PubMedQA | 2 | [
-2.53351092338562,
-1.0228134393692017,
2.6486687660217285
] |
['Proper neurogenesis in the developing Drosophila retina requires the regulated expression of the basic helix-loop-helix (bHLH) proneural transcription factors Atonal (Ato) and Daughterless (Da). Factors that control the timing and spatial expression of these bHLH proneural genes in the retina are required for the proper formation and function of the adult eye and nervous system.', 'Here we report that lilliputian (lilli), the Drosophila homolog of the FMR2/AF4 family of proteins, regulates the transcription of ato and da in the developing fly retina. We find that lilli controls ato expression at multiple enhancer elements. We also find that lilli contributes to ato auto-regulation in the morphogenetic furrow by first regulating the expression of da prior to ato. We show that FMR2 regulates the ato and da homologs MATH5 and TCF12 in human cells, suggesting a conservation of this regulation from flies to humans.'] Is drosophila lilliputian required for proneural gene expression in retinal development? | qiaojin/PubMedQA | 2 | [
-2.7897729873657227,
-0.38459011912345886,
2.220885753631592
] |
['β-Blockers (BB) are a mainstay of heart failure (HF) treatment, yet there are inconclusive data regarding their efficacy in African American individuals.', 'We performed a retrospective study of insured patients who received care from a large health system who were hospitalized for HF between January 2000 and June 2008 and had a documented ejection fraction <50%. BB exposure was estimated over 6-month rolling windows, using pharmacy claims data. Proportional hazards regression was used to test the association between BB exposure and all-cause hospitalization or death with adjustment for baseline covariates and other HF medication exposure. We performed analyses stratified by race and overall with a BB exposure×race interaction term. A total of 1094 patients met inclusion criteria (476 white and 618 African American individuals). Median follow-up was 2.1 years. In adjusted models, BB exposure was associated with lower risk of death or hospitalization in both groups, but more so in white individuals (hazard ratio, 0.40; 95% confidence interval, 0.27, 0.60; P<0.001) compared with African American individuals (hazard ratio, 0.67; 95% confidence interval, 0.48, 0.94; P=0.024). A formal test for interaction indicated that the protection association for BB exposure differed by race (P=0.098, β=0.40). Reanalysis restricted to BBs approved for HF or HF-specific hospitalizations did not substantively alter the findings.'] Does association of β-blocker exposure with outcomes in heart failure differ between African American and white patients? | qiaojin/PubMedQA | 2 | [
-1.838243842124939,
-1.2596189975738525,
2.1715586185455322
] |
['It is unclear whether and how elite athletes process physiological or psychological challenges differently than healthy comparison subjects. In general, individuals optimize exercise level as it relates to differences between expected and experienced exertion, which can be conceptualized as a body prediction error. The process of computing a body prediction error involves the insular cortex, which is important for interoception, i.e. the sense of the physiological condition of the body. Thus, optimal performance may be related to efficient minimization of the body prediction error. We examined the hypothesis that elite athletes, compared to control subjects, show attenuated insular cortex activation during an aversive interoceptive challenge.', 'Elite adventure racers (n\u200a=\u200a10) and healthy volunteers (n\u200a=\u200a11) performed a continuous performance task with varying degrees of a non-hypercapnic breathing load while undergoing functional magnetic resonance imaging. The results indicate that (1) non-hypercapnic inspiratory breathing load is an aversive experience associated with a profound activation of a distributed set of brain areas including bilateral insula, dorsolateral prefrontal cortex and anterior cingulated; (2) adventure racers relative to comparison subjects show greater accuracy on the continuous performance task during the aversive interoceptive condition; and (3) adventure racers show an attenuated right insula cortex response during and following the aversive interoceptive condition of non-hypercapnic inspiratory breathing load.'] Does subjecting elite athletes to inspiratory breathing load reveal behavioral and neural signatures of optimal performers in extreme environments? | qiaojin/PubMedQA | 2 | [
-2.9363162517547607,
0.23210686445236206,
1.7486917972564697
] |
['Toll-like receptors (TLRs) are important in sinonasal mucosal innate immunity. Previous studies demonstrate that sinonasal epithelial cell (SNEC) TLR9 expression is reduced in T-helper 2 (Th2) cytokine-predominant chronic rhinosinusitis with polyps, and with the in vitro application of Th2 cytokines. To further investigate in vivo modulation of TLR9 by the local cytokine environment, this study examines TLR9 expression in freshly isolated SNECs from subjects with and without active allergic rhinitis (AR).', 'SNECs were gathered via endoscopic-guided middle meatal brushings from 9 AR subjects who were skin-prick test (SPT)-positive to environmental allergens in season at the time of study, and 8 controls. Flow cytometry was utilized to compare SNEC TLR9 expression in the 2 groups.', 'TLR9 expression by SNEC in the AR group was significantly reduced compared to normals (35% ± 26% vs 76% ± 10%, p = 0.002).'] Is allergic rhinitis associated with decreased expression of Toll-like receptor 9 by sinonasal epithelial cells? | qiaojin/PubMedQA | 2 | [
-2.171083688735962,
-1.4276257753372192,
2.583547592163086
] |
['Inflammatory bowel disease (IBD) is characterized by an injured epithelium. Development of agents that could enhance mucosal healing is a major goal in IBD therapeutics. The 18-kDa antrum mucosal protein (AMP-18) and a 21-mer peptide derived from AMP-18 stimulate accumulation of tight junction (TJ) proteins in cultured epithelial cells and mouse colonic mucosa to protect the mucosal barrier, suggesting it might be a useful agent to treat IBD.', 'We searched for molecular mechanisms by which AMP peptide or recombinant AMP-18 act on TJs in intact cell monolayers, or those disrupted by low-calcium medium. Roles of the p38 mitogen-activated protein kinase (MAPK) / heat shock protein (hsp)25 pathway and PKCζ were investigated by immunoblotting and confocal microscopy.', 'AMP peptide activated p38 MAPK, which subsequently phosphorylated hsp25. Accumulated phospho-hsp25 was associated with perijunctional actin. AMP-18 also induced rapid phosphorylation of PKCζ and its colocalization with perijunctional actin in Caco2/bbe cells, which was accompanied by translocation and formation of complexes of "polarity proteins" in the TJ-containing detergent-insoluble fraction. Treatment with AMP-18 also stimulated accumulation of ZO-1, ZO-2, and JAM-A in nascent TJs known to associate with the multimeric p-PKCζ/Par6/ Cdc42/ECT2·GTP/Par3 polarity protein complex.'] Does aMP-18 facilitate assembly and stabilization of tight junctions to protect the colonic mucosal barrier? | qiaojin/PubMedQA | 2 | [
-2.474637269973755,
-1.3265159130096436,
2.8594446182250977
] |
['B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS). A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR). Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs) of MRZR with magnetic resonance imaging (MRI) findings in patients with first MS diagnosis.', 'MRZR was determined in 68 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting MS (RRMS). Absolute AI values for measles virus, rubella virus, and varicella zoster virus were correlated with T2 lesion load and gadolinium enhancing lesions on cerebral MRI (cMRI) and cMRI combined with spinal MRI (sMRI). Measles virus AI correlated significantly with T2 lesion load on cMRI (p\u200a=\u200a0.0312, Mann-Whitney U test) and the sum of lesions on cMRI and sMRI (p\u200a=\u200a0.0413). Varicella zoster virus AI also showed a correlation with T2 lesion load on cMRI but did not reach statistical significance (p\u200a=\u200a0.2893).'] Does measles IgG antibody index correlate with T2 lesion load on MRI in patients with early multiple sclerosis? | qiaojin/PubMedQA | 2 | [
-2.1494100093841553,
-1.500596284866333,
2.7214365005493164
] |
['The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. Therefore several pathological conditions associated with oedema formation result in deficient lymphatic function. However, the role of the lymphatic system in the pathogenesis of ascites and oedema formation in cirrhosis has not been fully clarified. The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the oedema observed in cirrhosis.', 'Cirrhosis was induced in rats by CCl(4) inhalation. Lymphatic drainage was evaluated using fluorescent lymphangiography. Expression of endothelial nitric oxide synthase (eNOS) was measured in primary lymphatic endothelial cells (LyECs). Inhibition of eNOS activity in cirrhotic rats with ascites (CH) was carried out by L-N(G)-methyl-L-arginine (L-NMMA) treatment (0.5 mg/kg/day).', 'The (CH) rats had impaired lymphatic drainage in the splanchnic and peripheral regions compared with the control (CT) rats. LyECs isolated from the CH rats showed a significant increase in eNOS and nitric oxide (NO) production. In addition, the lymphatic vessels of the CH rats showed a significant reduction in smooth muscle cell (SMC) coverage compared with the CT rats. CH rats treated with L-NMMA for 7 days showed a significant improvement in lymphatic drainage and a significant reduction in ascites volume, which were associated with increased plasma volume. This beneficial effect of L-NMMA inhibition was also associated with a significant increase in lymphatic SMC coverage.'] Does increased nitric oxide production in lymphatic endothelial cells cause impairment of lymphatic drainage in cirrhotic rats? | qiaojin/PubMedQA | 2 | [
-2.3634755611419678,
-1.341364860534668,
2.7155938148498535
] |
['Although breast cancers expressing estrogen receptor-α (ERα) and progesterone receptors (PR) are the most common form of mammary malignancy in humans, it has been difficult to develop a suitable mouse model showing similar steroid hormone responsiveness. STAT transcription factors play critical roles in mammary gland tumorigenesis, but the precise role of STAT1 remains unclear. Herein, we show that a subset of human breast cancers display reduced STAT1 expression and that mice lacking STAT1 surprisingly develop ERα+/PR+ mammary tumors.', 'We used a combination of approaches, including histological examination, gene targeted mice, gene expression analysis, tumor transplantaion, and immunophenotyping, to pursue this study.', 'Forty-five percent (37/83) of human ERα+ and 22% (17/78) of ERα- breast cancers display undetectable or low levels of STAT1 expression in neoplastic cells. In contrast, STAT1 expression is elevated in epithelial cells of normal breast tissues adjacent to the malignant lesions, suggesting that STAT1 is selectively downregulated in the tumor cells during tumor progression. Interestingly, the expression levels of STAT1 in the tumor-infiltrating stromal cells remain elevated, indicating that single-cell resolution analysis of STAT1 level in primary breast cancer biopsies is necessary for accurate assessment. Female mice lacking functional STAT1 spontaneously develop mammary adenocarcinomas that comprise > 90% ERα+/PR+ tumor cells, and depend on estrogen for tumor engraftment and progression. Phenotypic marker analyses demonstrate that STAT1-/- mammary tumors arise from luminal epithelial cells, but not myoepithelial cells. In addition, the molecular signature of the STAT1-/- mammary tumors overlaps closely to that of human luminal breast cancers. Finally, introduction of wildtype STAT1, but not a STAT1 mutant lacking the critical Tyr701 residue, into STAT1-/- mammary tumor cells results in apoptosis, demonstrating that the tumor suppressor function of STAT1 is cell-autonomous and requires its transcriptional activity.'] Do sTAT1-deficient mice spontaneously develop estrogen receptor α-positive luminal mammary carcinomas? | qiaojin/PubMedQA | 2 | [
-2.348863124847412,
-1.2479082345962524,
2.6722192764282227
] |
['Hepatocellular carcinoma (HCC) and cholangiolar carcinoma (CC) cell lines are used to analyze the basic mechanisms of carcinogenesis and target therapies. However, it is not yet clear which chromosomal aberrations are to be typically expected in such cell lines. It is also not clear whether there are prerequisites for in vitro growth on the genomic and/or expression level. We therefore analyzed HCC and CC cell lines for typical genetic settings.', 'The HCC cell lines HLE, HLF, Huh7, HepG2 and Hep3b and the CC cell lines EGI1, MzCha1 and TFK-1 were analyzed using high-density arrays for comparative genomic hybridization (aCGH; 244,000 oligonucleotides). Additional fluorescence in situ hybridization analyses were done to confirm the aCGH results and to add information regarding the aneuploidy of cell lines.', 'The gain of 1q, in particular q21-22, was detected in all HCC cell lines also as a partial loss of 13q. In contrast, a loss of 8p in combination with a relative gain of 8q was seen in all CC but no HCC cell lines. Interestingly, a gain of 17q was seen in all cell lines. These aberrations are also well documented for surgical tumor specimens. Besides these imbalances, the cell lines revealed imbalances for 11p, 12p, 14q, 16p, 16q, 21q and 22q, respectively, only rarely seen in surgical tumor specimens. These aberrations could be of importance for the in vitro cultivation of tumor cells. Structural aberrations were accompanied by aneuploidy in 3 of 5 HCC cell lines and 2 of 3 CC cell lines. Ploidy status was not correlated to any of the imbalances mentioned above.'] Do hepatocellular and cholangiolar carcinoma-derived cell lines reveal distinct sets of chromosomal imbalances? | qiaojin/PubMedQA | 2 | [
-2.038965940475464,
-1.5151973962783813,
2.55686092376709
] |
['To examine the hypothesis that genetic variation in enzymes and transporters associated with synthesis, storage, release, and metabolism of catecholamines contributes to the interindividual variability in plasma catecholamine concentrations at rest and after exercise.', 'We measured plasma norepinephrine (NE) and epinephrine concentrations at rest and after a standardized exercise protocol in 165 healthy individuals (60% White, 40% African-American) and examined 29 functional or common variants in 14 genes involved in synthesis, transport, or metabolism of catecholamines. We examined the relationship between genotypes and NE concentrations at rest and the increase after exercise (ΔNE) by multiple linear regression with adjustment for covariates [age, race, sex, BMI, fitness, and resting NE (for ΔNE)]. As a secondary outcome, we carried out similar analyses for epinephrine concentrations.', 'There was large interindividual variability in resting NE (mean, 204±102 pg/ml; range, 39-616 pg/ml) and ΔNE (mean, 256±206 pg/ml; range, -97 to 953 pg/ml). Resting NE was significantly associated with variants of four genes: CYB561 (P<0.001), VMAT2 (P=0.016), CHGA (P=0.039), and PNMT (P=0.038). ΔNE after exercise was associated with three variants of PNMT (P=0.041) and COMT (P=0.033 and 0.035), and resting and exercise epinephrine concentrations were associated with two variants each.'] Is catecholamine pathway gene variation associated with norepinephrine and epinephrine concentrations at rest and after exercise? | qiaojin/PubMedQA | 2 | [
-2.0635008811950684,
-1.310195803642273,
2.424410343170166
] |
['Cognitive abilities, such as working memory, differ among people; however, individuals also vary in their own day-to-day cognitive performance. One potential source of cognitive variability may be fluctuations in the functional organization of neural systems. The degree to which the organization of these functional networks is optimized may relate to the effective cognitive functioning of the individual. Here we specifically examine how changes in the organization of large-scale networks measured via resting state functional connectivity MRI and graph theory track changes in working memory capacity.', 'Twenty-two participants performed a test of working memory capacity and then underwent resting-state fMRI. Seventeen subjects repeated the protocol three weeks later. We applied graph theoretic techniques to measure network organization on 34 brain regions of interest (ROI). Network modularity, which measures the level of integration and segregation across sub-networks, and small-worldness, which measures global network connection efficiency, both predicted individual differences in memory capacity; however, only modularity predicted intra-individual variation across the two sessions. Partial correlations controlling for the component of working memory that was stable across sessions revealed that modularity was almost entirely associated with the variability of working memory at each session. Analyses of specific sub-networks and individual circuits were unable to consistently account for working memory capacity variability.'] Does functional brain network modularity capture inter- and intra-individual variation in working memory capacity? | qiaojin/PubMedQA | 2 | [
-2.5399210453033447,
0.498768150806427,
1.2235957384109497
] |
['OTUB1 is a member of OTUs (Ovarian-tumor-domain-containing proteases), a deubiquitinating enzymes family (DUBs), which was shown as a proteasome-associated DUB to be involved in the proteins Ub-dependent degradation. It has been reported that OTUB1 was expressed in kidney tissue. But its concrete cellular location and function in the kidney remain unclear. Decorin (DCN) in mesangial cells (MC) is considered to be a potentially important factor for antagonizing glomerulonephritides, and its degradation is mediated by ubiquitination. The aim of this study is to investigate the role of OTUB1 expression in MC and its relationship with DCN during glomerulonephritis.', 'Using quantitative RT-PCR and Western blot, we demonstrated that OTUB1 mRNA and protein were constitutively expressed in cultured rat MC and found to be upregulated by the stimulation of IL-1β or ATS. OTUB1 overexpression was detected in the mesangial area of glomeruli in some immunocomplex mediated nephritides such as IgA nephropathy, acute diffuse proliferative glomerulonephritis and lupus nephritis by immunohistochemistry. The immunoprecipitation assay demonstrated that OTUB1 interacted with DCN. The overexpression of OTUB1 enhanced the ubiquitination and degradation of DCN in MC.'] Is oTUB1 overexpression in mesangial cells a novel regulator in the pathogenesis of glomerulonephritis through the decrease of DCN level? | qiaojin/PubMedQA | 2 | [
-2.4268343448638916,
-1.3106335401535034,
2.771040678024292
] |
['The activation of transglutaminase 2 (TG2) by oxidative stress through TGFβ has been reported to play a crucial role in cataract formation. The authors investigated whether TG2 is involved in selenite-induced cataract formation in rats and whether cysteamine, a chemical inhibitor of TG2, can prevent cataract formation in this model.', 'Intracellular TG2 activity was monitored in a human lens epithelial cell (HLE-B3) line and cultured rat lenses after treatment with selenite. Rat pups (13 days old) were injected subcutaneously with sodium selenite (Na(2)SeO(3); 20 μmol/kg) and intraperitoneally with cysteamine (30, 40, and 60 mg/kg) for 14 days. Lenses were evaluated photographically at days 7 and 14. The concentrations of malondialdehyde and glutathione in the lenses were determined.', 'In HLE-B3 cells or rat lenses, selenite induced intracellular TG activity, which was inhibited by cysteamine. In selenite-treated rats, the rate of cataract formation was significantly reduced by cysteamine (P < 0.001). The mean cataract area in the lenses of cysteamine-treated rats was smaller than that of control rats (P < 0.01). The levels of total and reduced glutathione in the lenses of cysteamine-treated rats extracted at day 14 were higher than those of control rats.'] Does cysteamine prevent the development of lens opacity in a rat model of selenite-induced cataract? | qiaojin/PubMedQA | 2 | [
-2.192190170288086,
-1.4449141025543213,
2.577160120010376
] |
['Nicotinic receptors (nAChRs) are part of a heterogeneous family of pentameric ligand-gated ion channels that are widely expressed in the visual system. The impact of α7 homomeric nAChRs on visual function was investigated using mutant mice lacking the α7 nicotinic receptor subunit.', 'The spatial resolution limit was measured in α7 knockout (α7 KO) and age-matched control mice using three independent methods: an operant behavioral visual task (Prusky maze), cortical visual evoked potentials (VEPs), and the pattern electroretinogram (PERG) evoked by alternating gratings of different spatial frequencies and contrasts.', 'Visual acuity measured by means of the visual water maze task was significantly decreased in the α7 KO mice and, concordantly, there was a reduction of the cortical spatial resolution limit measured by VEPs. However, the PERG was normal in α7 KO mice, compared with control mice. The use of fluorescently tagged cholera toxin showed that projections from the retina segregate normally in α7 KO mice and, in line with this, the visual cortical responses elicited by stimulating either eye were normally balanced in both visual cortices and showed no retinotopic anomalies.'] Is visual acuity reduced in alpha 7 nicotinic receptor knockout mice? | qiaojin/PubMedQA | 2 | [
-2.3677828311920166,
-1.321829080581665,
2.6631436347961426
] |
['To investigate the role of anti-vascular endothelial growth factor (VEGF)-C therapy in corneal graft survival and concomitant suppression of hem- and lymph-angiogenesis.', 'Corneal suture model in BALB/c mice was placed and immunohistochemical staining was performed with CD31/PECAM-1 and LYVE-1 to quantify the level of blood and lymphatic vessels. Corneal transplants were done in BALB/c mice from C57BL/6 mice donors; grafts were subsequently scored for opacity. VEGF-C was blocked in the angiogenesis and transplant model using neutralizing monoclonal anti-VEGF-C (VGX-100) by intraperitoneal injection. To determine the function of VEGF-C in maturation of antigen-presenting cells (APCs), bone marrow-derived dendritic cells were generated and matured in the presence or absence of VEGF-C.', 'VEGF-C expression was demonstrated to be markedly upregulated in corneal graft rejection. VEGF-C blockade, through administration of a VEGF-C blocking monoclonal antibody, suppresses corneal angiogenic responses, inhibits trafficking and maturation of APCs, and significantly improves allotransplant survival.'] Does vascular endothelial growth factor-C promote alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis? | qiaojin/PubMedQA | 2 | [
-2.4450490474700928,
-1.3373479843139648,
2.8166089057922363
] |
['IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract.', 'To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens.', 'Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131).', 'Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001).'] Is galactose-α-1,3-galactose-specific IgE associated with anaphylaxis but not asthma? | qiaojin/PubMedQA | 2 | [
-2.327423572540283,
-1.2228527069091797,
2.6397933959960938
] |
['New ventilators have simplified the use of supraglottic superimposed high-frequency jet ventilation (SHFJV(SG)), but it has not been systematically compared with other modes of jet ventilation (JV) in humans. We sought to investigate whether SHFJV(SG) would provide more effective ventilation compared with single-frequency JV techniques.', 'A total of 16 patients undergoing minor laryngeal surgery under general anaesthesia were included. In each patient, four different JV techniques were applied in random order for 10-min periods: SHFJV(SG), supraglottic normal frequency (NFJV(SG)), supraglottic high frequency (HFJV(SG)), and infraglottic high-frequency jet ventilation (HFJV(IG)). Chest wall volume variations were continuously measured with opto-electronic plethysmography (OEP), intratracheal pressure was recorded and blood gases were measured.', 'Chest wall volumes were normalized to NFJV(SG) end-expiratory level. The increase in end-expiratory chest wall volume (EEV(CW)) was 239 (196) ml during SHFJV(SG) (P<0.05 compared with NFJV(SG)). EEV(CW) was 148 (145) and 44 (106) ml during HFJV(SG) and HFJV(IG), respectively (P<0.05 compared with SHFJV(SG)). Tidal volume (V(T)) during SHFJV(SG) was 269 (149) ml. V(T) was 229 (169) ml (P=1.00 compared with SHFJV(SG)), 145 (50) ml (P<0.05), and 110 (33) ml (P<0.01) during NFJV(SG), HFJV(SG), and HFJV(IG), respectively. Intratracheal pressures corresponded well to changes in both EEV(CW) and V(T). All JV modes resulted in adequate oxygenation. However, was lowest during HFJV(SG) [4.3 (1.3) kPa; P<0.01 compared with SHFJV(SG)].'] Do comparison of superimposed high-frequency jet ventilation with conventional jet ventilation for laryngeal surgery? | qiaojin/PubMedQA | 2 | [
-0.3216167092323303,
-1.9416083097457886,
1.2530286312103271
] |
['The six-minute walk test (6MWT) is a validated field test in the assessment of interstitial lung disease but may not be so useful in scleroderma (SSc) lung disease. The aim of this study was to determine the reliability of the 6MWT in patients with SSc and correlate results with morphological and functional measures of disease severity.', 'Thirty patients (24 female, mean age 47, mean diffusing capacity of carbon monoxide 65%, vital capacity 77% predicted) with American College of Rheumatology classification of SSc performed two 6MWT using various oximetry sites, 1 week apart, and underwent SSc-specific disease severity and quality-of-life measurements, lung function, high-resolution computed tomography and echocardiography.', 'There was good reliability between the two 6MWT (distance; intraclass correlation coefficient 0.95, r = 0.89, Borg; intraclass correlation coefficient 0.85, r = 0.91, both P < 0.00 for r), and Bland Altman plots demonstrate good agreement between measures 1 week apart. Forehead and finger oximetry were more reliable than earlobe (intraclass correlation coefficient 0.64, 0.60, 0.24; r = 0.46, 0.47, 0.14; n = 22, 17, 7, respectively). Forehead desaturation correlated with forced expiratory volume in 1 s (r = 0.55, P = 0.01) and forced vital capacity (r = 0.59, P = 0.01). Distance correlated with all physiological measures: forced expiratory volume in 1 s (r = 0.55, P = 0.01), forced vital capacity (r = 0.61, P = 0.01) and diffusing capacity of carbon monoxide (r = 0.42, P = 0.05). Computed tomography extent and patterns of disease correlated poorly with 6MWT measures, and global measures of SSc correlated only with post-test Borg score.'] Is the six-minute walk test using forehead oximetry reliable in the assessment of scleroderma lung disease? | qiaojin/PubMedQA | 2 | [
-1.2809958457946777,
-1.7071924209594727,
1.986921787261963
] |
['D2-40 staining has been reported to be useful for both identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) in various cancers. The aim of this study was to clarify the prognostic significance of D2-40 staining in patients with esophageal squamous cell carcinoma (ESCC).', 'A total of 159 consecutive patients with ESCC who underwent an esophagectomy with lymph node dissection were eligible. LVI was diagnosed by both hematoxylin-eosin (LVI-HE) and D2-40 staining (LVI-D2-40) in the largest central sections of the entire tumors, while both the intratumoral and peritumoral LVD were counted by D2-40 staining. The correlation between the prognosis and clinicopathological factors was investigated.', "An univariate analysis revealed that tumor invasion beyond the muscularis propria, lymph node metastasis (LNM), LVI-HE, LVI-D2-40, high intratumoral LVD, and blood vessel invasion correlated with worse patients' prognosis (P\u2009<\u20090.05). A multivariate analysis revealed LNM to be the only independent prognostic factor in all cases (P\u2009=\u20090.0083). On the other hand, when the prognostic factors of 83 patients without LNM were investigated, LVI-D2-40 was revealed to be the only independent prognostic factor (P\u2009=\u20090.048)."] Is lymphatic vessel invasion detected by the D2-40 monoclonal antibody an independent prognostic factor in node-negative esophageal squamous cell carcinoma? | qiaojin/PubMedQA | 2 | [
-2.048051118850708,
-1.5219485759735107,
2.597834587097168
] |
['Human MxA, an interferon-inducible cytoplasmic dynamin-like GTPase, possesses antiviral activity against multiple RNA viruses. Recently, MxA has also been demonstrated to have activity against the hepatitis B virus (HBV), a well-known DNA virus responsible for acute and chronic liver disease in humans. We investigated the molecular mechanism for the anti-HBV activity of MxA. Our results demonstrated that in HepG2.2.15 cells, MxA GTPase independently suppressed the production of hepatitis B surface antigen and HBV DNA without changing the level of hepatitis B core antigen (HBcAg) and the distribution of HBV mRNA. MxA significantly reduced the level of the encapsidated pregenomic RNA. Through its central interactive domain, MxA interacted with HBcAg, causing accumulation of the proteins in perinuclear compartments. MxA-HBcAg interaction significantly affected the dynamics of HBcAg by immobilizing HBcAg in the perinuclear structures.'] Does mxA inhibit hepatitis B virus replication by interaction with hepatitis B core antigen? | qiaojin/PubMedQA | 2 | [
-2.3758180141448975,
-1.0969767570495605,
2.499657154083252
] |
['Increased β-oxidation of branched-chain fatty acids provides an additional metabolic advantage for cancer cells thereby enhancing tumour development and progression. Alpha-methylacyl coenzyme A racemase (AMACR) is an enzyme essential for the catabolism of branched-chain fatty acids that allows their subsequent β-oxidation and thus plays an important role in generating biological energy. However, the expression of AMACR has never been systemically investigated in gallbladder carcinoma. This study evaluated the expression status, associations with clinicopathological variables and prognostic implications of AMACR in a well-defined cohort of gallbladder carcinoma and confirmed their expression status in gallbladder carcinoma cells.', 'AMACR immunostaining was assessable in 89 cases on tissue microarrays of gallbladder carcinoma, and it was correlated with clinicopathological factors and patient survival. In three gallbladder carcinoma cell lines and one non-tumorigenic cholangiocyte, AMACR mRNA expression was measured by real-time reverse transcription PCR and the endogenous expression of AMACR protein was analysed by western blotting.', 'AMACR overexpression was significantly associated with an advanced primary tumour status (p=0.027) and American Joint Committee on Cancer stage (p=0.027), an increased histological grade (p=0.002) and vascular invasion (p=0.017). Importantly, AMACR overexpression independently predicted worse disease-specific survival (p=0.0452, RR 1.887). Expression levels of AMACR mRNA and total protein in various cells were comparable. The abundance of AMACR expression increased in tumour cells and was even higher in the metastatic cell line.'] Does alpha-methylacyl coenzyme A racemase overexpression in gallbladder carcinoma confer an independent prognostic indicator? | qiaojin/PubMedQA | 2 | [
-2.2808377742767334,
-1.4284265041351318,
2.749255418777466
] |
['This study examined volatile anesthetic-mediated protection against intestinal ischemia-reperfusion injury (IRI).', 'Intestinal IRI is a devastating complication in the perioperative period leading to systemic inflammation and multiorgan dysfunction. Volatile anesthetics, including isoflurane, have anti-inflammatory effects. We aimed to determine whether isoflurane, given after intestinal ischemia, protects against intestinal IRI and the mechanisms involved in this protection.', ': After IACUC approval, mice were anesthetized with pentobarbital and subjected to 30 minutes of superior mesenteric artery ischemia, followed by 4 hours of equianesthetic doses of pentobarbital or isoflurane. Five hours after reperfusion, small intestine tissues were analyzed for morphological injury, apoptosis, neutrophil infiltration, proinflammatory mRNAs, and TGF-(Transforming Growth Factor-)β1 levels. We also assessed hepatic and renal injury after intestinal IRI.', 'Intestinal IRI with pentobarbital led to significant small intestinal dysfunction with increased mucosal injury, TUNEL (transferase biotin-dUTP nick end-labeling)-positive cells, neutrophil infiltration, and proinflammatory mRNAs as well as elevated plasma alanine aminotransferase and creatinine levels. Isoflurane exposure after IRI led to significant attenuation of intestinal, hepatic, and renal injuries. Furthermore, the protective effects of isoflurane were abolished by treatment with a TGF-β1 neutralizing antibody before induction of IRI. Finally, isoflurane exposure led to increased TGF-β1 levels in intestinal epithelial cells and in plasma.'] Does isoflurane post-conditioning protect against intestinal ischemia-reperfusion injury and multiorgan dysfunction via transforming growth factor-β1 generation? | qiaojin/PubMedQA | 2 | [
-2.512920618057251,
-1.2659639120101929,
2.861333131790161
] |
['To determine whether matrix metalloproteinase-12 (MMP-12) plays a functional role in renal interstitial macrophage accumulation, interstitial fibrosis or tubular apoptosis in the unilateral ureteric obstruction (UUO) model.', 'MMP-12 is an enzyme that can cleave a number of extracellular matrix proteins and plays a role in macrophage-mediated injury in experimental models of emphysema and antibody-dependent glomerular disease. Macrophages are thought to promote renal fibrosis and tubular damage in the obstructed kidney. Furthermore, upregulation of MMP-12 expression by infiltrating macrophages in the obstructed kidney has been described, but the potential role of MMP-12 in renal injury induced by this non-immune insult is unknown.', 'Groups of eight MMP-12 gene deficient (MMP-12(-/-)) and wild type (WT) C57BL/6J mice were killed 3, 7 or 14 days after UUO.', 'Analysis of three different lineage markers found no difference in the degree of interstitial macrophage accumulation between MMP-12(-/-) and WT UUO groups at any time point. Examination of renal fibrosis by total collagen staining, α-SMA + myofibroblast accumulation, and TGF-β1, PAI-1 and collagen IV mRNA levels showed no difference between MMP-12(-/-) and WT UUO groups. Finally, tubular damage (KIM-1 levels) and tubular apoptosis (cleaved caspase-3) in the obstructed kidney was not affected by MMP-12 gene deletion.'] Are macrophage infiltration and renal damage independent of matrix metalloproteinase 12 in the obstructed kidney? | qiaojin/PubMedQA | 2 | [
-2.324882745742798,
-1.3770482540130615,
2.7504405975341797
] |
['To examine changes in motor cortical excitability in adolescent subjects receiving 30 sessions of high-frequency prefrontal repetitive transcranial magnetic stimulation (rTMS).', 'Eight adolescents with treatment-resistant major depressive disorder (MDD) enrolled in an open augmentation trial of 10 Hz rTMS. Resting motor thresholds were obtained by the visualization of movement method with a maximum likelihood threshold hunting computer algorithm at baseline and after every five sessions of rTMS. Motor threshold was recorded as the percentage of total machine output at each measurement.', 'Motor threshold data from baseline, weeks 2, 4, and 5 were included in a mixed model repeated measure analysis to examine a change in least square mean effect over time. The omnibus effect did not reach statistical significance (F=1.25, p=0.32). However, multiple comparisons from the overall model demonstrated a decrease in the least square mean motor threshold. The mean contrast from baseline to week 5 approached significance (p=0.07). Moreover, a post-hoc analysis with a Wilcoxon signed ranks test demonstrated a significant decrease at week 5 (p=0.03).'] Do increased cortical excitability with prefrontal high-frequency repetitive transcranial magnetic stimulation in adolescents with treatment-resistant major depressive disorder? | qiaojin/PubMedQA | 2 | [
-1.8953014612197876,
-1.2563015222549438,
2.2359440326690674
] |
['Obesity-associated hyperlipidemia and hyperlipoproteinemia are risk factors for cardiovascular disease (CVD). Recently, ceramide-derived sphingolipids were identified as a novel independent CVD risk factor. We hypothesized that the beneficial effect of Roux-en-Y gastric bypass (RYGB) on CVD risk is related to ceramide-mediated improvement in lipoprotein profile.', "A prospective study of patients undergoing RYGB was conducted. The patients' clinical data and biochemical markers related to cardiovascular risk were documented. Plasma ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1), apolipoprotein (Apo)B100 and ApoA1 were quantified preoperatively and 3 and 6 months after RYGB, as was the Framingham risk score. Brachial artery reactivity testing was performed before and 6 months after RYGB.", 'Ten patients (9 women; age 48.6 ± 9.6 yr; body mass index, 48.5 ± 5.8 kg/m(2)) were included in the present study. At 6 months postoperatively, the mean body mass index had decreased to 35.7 ± 5.0 kg/m(2), corresponding to 51.3% ± 10.0% excess weight loss. The fasting total cholesterol, triglycerides, low-density lipoprotein, free fatty acids, ApoB100, ApoB100/ApoA1 ratio and insulin resistance estimated from Homeostasis Model of Assessment of Insulin Resistance were significantly reduced compared with the preoperative values. The ApoB100/ApoA1 ratio correlated with a reduction in ceramide subspecies (C18:0, C18:1, C20:0, C24:0, and C24:1; P < .05). ApoB100 and the ApoB100/ApoA1 ratio also correlated positively with the reduction in triglycerides, low-density lipoprotein, and Homeostasis Model of Assessment of Insulin Resistance (P < .05). Brachial artery reactivity testing correlated inversely with ApoB100 and total ceramide (P = .05). Furthermore, the change in brachial artery reactivity testing correlated with the decrease in C16:0 (P < .03).'] Is reduced cardiovascular risk after bariatric surgery linked to plasma ceramides , apolipoprotein-B100 , and ApoB100/A1 ratio? | qiaojin/PubMedQA | 2 | [
-1.7101852893829346,
-1.6695358753204346,
2.3628897666931152
] |
['To report the audiological outcomes of cochlear implantation in two patients with severe to profound sensorineural hearing loss secondary to superficial siderosis of the CNS and discuss some programming peculiarities that were found in these cases.', 'Retrospective review. Data concerning clinical presentation, diagnosis and audiological assessment pre- and post-implantation were collected of two patients with superficial siderosis of the CNS.', 'Both patients showed good hearing thresholds but variable speech perception outcomes. One patient did not achieve open-set speech recognition, but the other achieved 70% speech recognition in quiet. Electrical compound action potentials could not be elicited in either patient. Map parameters showed the need for increased charge. Electrode impedances showed high longitudinal variability.'] Do programming peculiarities in two cochlear implant users with superficial siderosis of the central nervous system? | qiaojin/PubMedQA | 2 | [
-2.7769742012023926,
-0.7587857842445374,
2.6063780784606934
] |
['The idiopathic generalized epilepsies (IGE) are the most common genetically determined epilepsies. However, the underlying genes are largely unknown. We screened the SLC2A1 gene, encoding the glucose transporter type 1 (GLUT1), for mutations in a group of 95 European patients with familial IGE.', 'The affected individuals were examined clinically by EEG and brain imaging. The coding regions of SLC2A1 were sequenced in the index cases of all families. Wild-type and mutant transporters were expressed and functionally characterized in Xenopus laevis oocytes.', 'We detected a novel nonsynonymous SLC2A1 mutation (c.694C>T, p.R232C) in one IGE family. Nine family members were affected mainly by absence epilepsies with a variable age at onset, from early childhood to adulthood. Childhood absence epilepsy in one individual evolved into juvenile myoclonic epilepsy. Eight affected and 4 unaffected individuals carried the mutation, revealing a reduced penetrance of 67%. The detected mutation was not found in 846 normal control subjects. Functional analysis revealed a reduced maximum uptake velocity for glucose, whereas the affinity to glucose and the protein expression were not different in wild-type and mutant transporters.'] Are gLUT1 mutations a rare cause of familial idiopathic generalized epilepsy? | qiaojin/PubMedQA | 2 | [
-2.331406354904175,
-1.264081358909607,
2.5707459449768066
] |
["We hypothesized that quantitative PET parameters may have predictive value beyond that of traditional clinical factors such as the International Prognostic Score (IPS) among Hodgkin's disease (HD) patients.", 'Thirty HD patients treated at presentation or relapse had staging and interim-treatment PET-CT scans. The majority of patients (53%) had stage III-IV disease and 67% had IPS ≥ 2. Interim-treatment scans were performed at a median of 55 days from the staging PET-CT. Chemotherapy regimens used: Stanford V (67%), ABVD (17%), VAMP (10%), or BEACOPP (7%). Hypermetabolic tumor regions were segmented semiautomatically and the metabolic tumor volume (MTV), mean standardized uptake value (SUV mean), maximum SUV (SUV max) and integrated SUV (iSUV) were recorded. We analyzed whether IPS, absolute value PET parameters or the calculated ratio of interim- to pre-treatment PET parameters were associated with progression free survival (PFS) or overall survival (OS).', 'Median follow-up of the study group was 50 months. Six of the 30 patients progressed clinically. Absolute value PET parameters from pre-treatment scans were not significant. Absolute value SUV max from interim-treatment scans was associated with OS as determined by univariate analysis (p < 0.01). All four calculated PET parameters (interim/pre-treatment values) were associated with OS: MTV int/pre (p < 0.01), SUV mean int/pre (p < 0.05), SUV max int/pre (p = 0.01), and iSUV int/pre (p < 0.01). Absolute value SUV max from interim-treatment scans was associated with PFS (p = 0.01). Three calculated PET parameters (int/pre-treatment values) were associated with PFS: MTV int/pre (p = 0.01), SUV max int/pre (p = 0.02) and iSUV int/pre (p = 0.01). IPS was associated with PFS (p < 0.05) and OS (p < 0.01).'] Do interim-treatment quantitative PET parameters predict progression and death among patients with Hodgkin 's disease? | qiaojin/PubMedQA | 2 | [
-0.8764218091964722,
-1.8392655849456787,
1.6976873874664307
] |
['DNA methylation, histone modifications and nucleosome occupancy act in concert for regulation of gene expression patterns in mammalian cells. Recently, G9a, a H3K9 methyltransferase, has been shown to play a role in establishment of DNA methylation at embryonic gene targets in ES cells through recruitment of de novo DNMT3A/3B enzymes. However, whether G9a plays a similar role in maintenance of DNA methylation in somatic cells is still unclear.', 'Here we show that G9a is not essential for maintenance of DNA methylation in somatic cells. Knockdown of G9a has no measurable effect on DNA methylation levels at G9a-target loci. DNMT3A/3B remain stably anchored to nucleosomes containing methylated DNA even in the absence of G9a, ensuring faithful propagation of methylated states in cooperation with DNMT1 through somatic divisions. Moreover, G9a also associates with nucleosomes in a DNMT3A/3B and DNA methylation-independent manner. However, G9a knockdown synergizes with pharmacologic inhibition of DNMTs resulting in increased hypomethylation and inhibition of cell proliferation.'] Is lysine methyltransferase G9a required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells? | qiaojin/PubMedQA | 2 | [
-2.45449161529541,
-1.088198184967041,
2.545431613922119
] |
['Neurotrophins (NTs) and their receptors play crucial roles in the development, functions and maintenance of nervous systems. It is widely believed that NT-induced dimerization of the receptors initiates the transmembrane signaling. However, it is still controversial whether the receptor molecule has a monomeric or dimeric structure on the cell surface before its ligand binding.', 'Using chemical cross-linking, bimolecular fluorescence complementation (BiFC) and luciferase fragment complementation (LFC) assays, in this study, we show the brain-derived neurotrophic factor (BDNF) receptor TrkB exists as a homodimer before ligand binding. We have also found by using BiFC and LFC that the dimer forms in the endoplasmic reticulum (ER), and that the receptor lacking its intracellular domain cannot form the dimeric structure.'] Does brain-derived neurotrophic factor receptor TrkB exist as a preformed dimer in living cells? | qiaojin/PubMedQA | 2 | [
-2.5453100204467773,
-0.9494638442993164,
2.565190315246582
] |
['The role of insulin resistance in predicting virological response to therapy of chronic hepatitis C is debated. We assessed the association between basal (defined as homeostasis model assessment of insulin resistance (HOMA-IR)>2) and post-load insulin resistance (as oral glucose insulin sensitivity index<9.8 mg/kg/min) with the rapid and sustained virological responses in chronic hepatitis C.', 'Observational prospective study of 124 treatment-naïve patients with chronic hepatitis C not fulfilling the metabolic syndrome criteria, adherent to a standard treatment with pegylated interferon alpha plus ribavirin.', 'Insulin resistance was detected in 50% (by HOMA-IR) and 29% (by oral glucose insulin sensitivity index) of patients. Independent predictors of rapid virologic response were hepatitis C virus (HCV) genotype 2 (odds ratio 5.66; 95% confidence interval 1.88-17.01), HCV genotype 3 (odds ratio 5.23; 95% confidence interval 1.84-14.84) and lower basal ferritin levels (odds ratio 0.99; 95% confidence interval 0.993-0.998). Independent predictors of sustained virologic response were HCV genotype 2 (odds ratio 19.54; 95% confidence interval 2.29-166.41) and HCV genotype 3 (odds ratio 3.24; 95% confidence interval 1.10-9.58). Rapid virologic response was by itself predictive of sustained virologic response (odds ratio 40.90; 95% confidence interval 5.37-311.53).'] Does post-load insulin resistance predict virological response to treatment of chronic hepatitis C patients without the metabolic syndrome? | qiaojin/PubMedQA | 2 | [
-1.8313044309616089,
-1.4799985885620117,
2.4030754566192627
] |
['Patients, especially young children, with atopic dermatitis are at an increased risk of developing eczema vaccinatum, a severe reaction to the smallpox vaccine, either through direct vaccination or indirect contact with a person recently vaccinated.', 'Using a mouse model of infection, the severity of vaccinia-induced lesions was assessed from their appearance and viral DNA content. The response to vaccinia inoculation was assessed in young and adult mice, allergen-sensitized mice, and in mast cell-deficient mice.', 'Young age, sensitization to an allergen prior to infection, and a mast cell deficit, accomplished by using mast cell-deficient mice, resulted in more severe viral lesions at the site of inoculation, according to lesion appearance and viral DNA content. All three factors combined demonstrated maximal susceptibility, characterized by the severity of primary lesions and the development of secondary (satellite) lesions, as occurs in eczema vaccinatum in humans. Resistance to the appearance of satellite lesions could be restored by adoptive transfer of bone marrow-derived mast cells from either wild-type or cathelicidin-related antimicrobial peptide-deficient mice. Primary lesions were more severe following the latter transfer, indicating that cathelicidin-related antimicrobial peptide does contribute to the protective activity of mast cells against infection.'] Is susceptibility to vaccinia virus infection and spread in mice determined by age at infection , allergen sensitization and mast cell status? | qiaojin/PubMedQA | 2 | [
-2.605468988418579,
-1.0820386409759521,
2.823782444000244
] |
['This study aimed to investigate a wide variety of factors that influence auditory, speech, and language development following pediatric cochlear implantation (CI).', 'Prospective collection of language tested data in profound hearing-impaired children.', 'Pediatric CI can potentially be effective to development of practical communication skills and early implantation is more effective.', "We proposed a set of language tests (assessment package of the language development for Japanese hearing-impaired children; ALADJIN) consisting of communication skills testing (test for question-answer interaction development; TQAID), comprehensive (Peabody Picture Vocabulary Test-Revised; PVT-R and Standardized Comprehension Test for Abstract Words; SCTAW) and productive vocabulary (Word Fluency Test; WFT), and comprehensive and productive syntax (Syntactic processing Test for Aphasia; STA). Of 638 hearing-impaired children recruited for this study, 282 (44.2%) with >70 dB hearing impairment had undergone CI. After excluding children with low birth weight (<1800 g), those with >11 points on the Pervasive Developmental Disorder ASJ Rating Scale for the test of autistic tendency, and those <2 SD on Raven's Colored Progressive Matrices for the test of non-verbal intelligence, 190 children were subjected to this set of language tests.", 'Sixty children (31.6%) were unilateral CI-only users, 128 (67.4%) were CI-hearing aid (HA) users, and 2 (1.1%) were bilateral CI users. Hearing loss level of CI users was significantly (p<0.01) worse than that of HA-only users. However, the threshold level, maximum speech discrimination score, and speech intelligibility rating in CI users were significantly (p<0.01) better than those in HA-only users. The scores for PVT-R (p<0.01), SCTAW, and WFT in CI users were better than those in HA-only users. STA and TQAID scores in CI-HA users were significantly (p<0.05) better than those in unilateral CI-only users. The high correlation (r=0.52) has been found between the age of CI and maximum speech discrimination score. The scores of speech and language tests in the implanted children before 24 months of age have been better than those in the implanted children after 24 months of age.'] Do language development in Japanese children who receive cochlear implant and/or hearing aid? | qiaojin/PubMedQA | 2 | [
-1.107458472251892,
-1.231791377067566,
1.4224827289581299
] |
['Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na(+) transport in the lung.', 'We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderate to severe intoxication and measured the rate of alveolar fluid clearance and Na,K-ATPase expression in peripheral lung tissue and assessed the effect of alcohol on survival during exposure to hyperoxia. We used primary rat alveolar type II cells to investigate the mechanisms by which alcohol regulates alveolar Na(+) transport.', 'Exposure to alcohol reduced alveolar fluid clearance, downregulated Na,K-ATPase in the lung tissue and worsened hyperoxia-induced lung injury. Alcohol caused an increase in BAL fluid adenosine levels. A similar increase in lung adenosine levels was observed after exposure to hyperoxia. In primary rat alveolar type II cells alcohol and adenosine decreased the abundance of the Na,K-ATPase at the basolateral membrane via a mechanism that required activation of the AMPK.'] Does alcohol worsen acute lung injury by inhibiting alveolar sodium transport through the adenosine A1 receptor? | qiaojin/PubMedQA | 2 | [
-2.80436110496521,
-0.8930057287216187,
2.7289721965789795
] |
['\u2002Merkel cell carcinoma (MCC) is a highly aggressive skin cancer, associated with advanced age, immunosuppression and Merkel cell polyomavirus (MCV) infections. As development and progression of cancer can be promoted by changes in cell adhesion proteins, we have previously analysed homo- and heterotypic cell-cell contacts of normal Merkel cells and MCCs and obtained indications for cadherin switching.', 'To examine the prevalence and prognostic relevance of E-, N- and P-cadherin in MCCs.', 'Paraffin-embedded MCC samples (n\u2003= 148) from 106 different patients were analysed by double-label immunostaining and immunofluorescence microscopy. MCV status was determined by real-time polymerase chain reaction. The cadherin repertoire and MCV status were correlated to clinical data, including tumour stage and recurrence-free survival.', 'Ninety-one per cent of all MCC were positive for N-cadherin whereas only 61·6% and 70·3% expressed E- and P-cadherin, respectively. P-cadherin was significantly more frequent in primary tumours than in lymph node metastases (81·9% vs. 40·9%, P = 0·0002). Patients with P-cadherin-positive primary tumours were in earlier tumour stages at initial diagnosis (P = 0·0046). Both in log-rank tests (P\u2003= 0·0474) and in multiple Cox regression analysis including age, sex, immunosuppression, stage at initial diagnosis and MCV status (hazard ratio 0·193, P = 0·0373), patients with P-cadherin-positive primary MCCs had significantly prolonged recurrence-free survival (mean 25·2 vs. 10·6 months; median 9·0 vs. 4·0 months). MCV DNA was detected in 78·2% of all MCC, more frequently in P-cadherin-positive MCC (P = 0·0008).'] Is p-cadherin expression in Merkel cell carcinomas associated with prolonged recurrence-free survival? | qiaojin/PubMedQA | 2 | [
-1.805350661277771,
-1.6361007690429688,
2.485382556915283
] |
['Increased common carotid artery intima-media thickness has been associated with an increased risk of vascular ischemic events. We investigated the relationship between common carotid artery intima-media thickness and extracranial vascular events (coronary heart disease and peripheral arterial disease) or stroke recurrence in a cohort of transient ischemic attack patients from the REGITELL registry.', 'High-resolution B-mode ultrasonographic measurements of the common carotid artery intima-media thickness were performed in a series of 283 consecutive transient ischemic attack patients. Clinical, neuroimaging, ultrasonographic, and etiological data were collected. Patients were followed prospectively for six-months or more. Extracranial vascular events and stroke recurrence were recorded.', 'Fifteen extracranial vascular events (12 coronary heart disease and three peripheral arterial disease) and 29 recurrent strokes occurred during a median follow-up period of 12.3 months. Patients who experienced extracranial vascular events had significantly (P < 0.001) higher common carotid artery intima-media thickness values (1.087 (standard deviation 0.189) mm) than subjects who were free of extracranial vascular events (0.887 (standard deviation 0.195) mm). Nevertheless, common carotid artery intima-media thickness was not found to correlate with stroke recurrence. Cox proportional hazards multivariate analyses identified hypercholesterolemia (hazard ratio 6.87, 95% confidence interval: 1.93-24.39, P =\u20090.003) and common carotid artery intima-media thickness > 0.939 \u2009mm (hazard ratio 8.90, 95% confidence interval: 2.00-39.49, P = 0.004) as independent predictors of extracranial vascular events after transient ischemic attack. Almost one of every three patients with hypercholesterolemia and high common carotid artery intima-media thickness had extracranial vascular events.'] Does higher carotid intima media thickness predict extracranial vascular events and not stroke recurrence among transient ischemic attack patients? | qiaojin/PubMedQA | 2 | [
-1.5463298559188843,
-1.6000604629516602,
2.2089285850524902
] |
['Convection-enhanced delivery (CED), a direct method for drug delivery to the brain through intraparenchymal microcatheters, is a promising strategy for intracerebral pharmacological therapy. By establishing a pressure gradient at the tip of the catheter, drugs can be delivered in uniform concentration throughout a large volume of interstitial fluid. However, the variables affecting perivascular distribution of drugs delivered by CED are not fully understood. The aim of this study was to determine whether the perivascular distribution of solutes delivered by CED into the striatum of rats is affected by the molecular weight of the infused agent, by co-infusion of vasodilator, alteration of infusion rates or use of a ramping regime. We also wanted to make a preliminary comparison of the distribution of solutes with that of nanoparticles.', 'We analysed the perivascular distribution of 4, 10, 20, 70, 150 kDa fluorescein-labelled dextran and fluorescent nanoparticles at 10 min and 3 h following CED into rat striatum. We investigated the effect of local vasodilatation, slow infusion rates and ramping on the perivascular distribution of solutes. Co-localisation with perivascular basement membranes and vascular endothelial cells was identified by immunohistochemistry. The uptake of infusates by perivascular macrophages was quantified using stereological methods.', 'Widespread perivascular distribution and macrophage uptake of fluorescein-labelled dextran was visible 10 min after cessation of CED irrespective of molecular weight. However, a significantly higher proportion of perivascular macrophages had taken up 4, 10 and 20 kDa fluorescein-labelled dextran than 150 kDa dextran (p < 0.05, ANOVA). Co-infusion with vasodilator, slow infusion rates and use of a ramping regime did not alter the perivascular distribution. CED of fluorescent nanoparticles indicated that particles co-localise with perivascular basement membranes throughout the striatum but, unlike soluble dextrans, are not taken up by perivascular macrophages after 3 h.'] Does intrastriatal convection-enhanced delivery result in widespread perivascular distribution in a pre-clinical model? | qiaojin/PubMedQA | 2 | [
-2.3468096256256104,
-1.4286895990371704,
2.8429927825927734
] |
['Iliofemoral deep vein thrombosis (DVT) is associated with severe postthrombotic morbidity when treated with anticoagulation alone. Catheter-directed thrombolysis (CDT), with or without the addition of mechanical techniques, is increasingly recommended for patients with iliofemoral DVT, although its effect on postthrombotic syndrome is not established. This study examined the correlation of residual thrombus with postthrombotic syndrome after catheter-based attempts at thrombus removal in patients with iliofemoral DVT.', 'Seventy-one consecutive patients with iliofemoral DVT were treated with CDT. Pretreatment and posttreatment phlebograms were evaluated for quantity of residual thrombus by physicians blinded to clinical patient outcomes. Postthrombotic syndrome was assessed using CEAP and Villalta scores by examiners blinded to phlebographic results. Patients were grouped by the amount of residual thrombus in treated vein segments (group 1, ≤50%; group 2, >50%). Clinical score and postthrombotic outcomes were plotted vs residual thrombus.', 'Sixty-three of 71 patients completed CEAP and Villalta analyses. Groups 1 and 2 had median CEAP scores of 1 and 4 (P = .025) and mean Villalta scores of 2.21 and 7.13, respectively (P = .011). There was a direct and significant correlation of clinical class of CEAP with residual thrombus (R(2) = .74; P = .004) and a direct linear correlation of Villalta score with residual thrombus (R(2) = .61; P = .0014).'] Does postthrombotic morbidity correlate with residual thrombus following catheter-directed thrombolysis for iliofemoral deep vein thrombosis? | qiaojin/PubMedQA | 2 | [
-1.7976104021072388,
-1.6389422416687012,
2.4183273315429688
] |
['To determine if there are any differences in outcomes between infrarenal fixation (IF) and suprarenal fixation (SF) endograft systems for the endovascular treatment (endovascular aneurysm repair [EVAR]) of abdominal aortic aneurysms (AAAs) with short, straight proximal aortic necks (<1.5 cm).', "A retrospective review of 1379 EVAR procedures was performed between the years of 2002 and 2009 at a single institution. The charts and radiographic images of all patients were reviewed. Patients who underwent EVAR with AAA morphology with short proximal necks were stratified into two groups: IF, Gore Excluder (W. L. Gore, Flagstaff, Ariz) group and SF, Cook Zenith (Cook, Bloomington, Ind) group. The primary end point for the study was the presence of proximal type 1 endoleaks. Secondary end points were graft migration at 1- and 2-year follow-up and aneurysm sac regression. The groups' demographics and comorbidities were also compared.", 'A total of 1379 EVARS were performed during the study period and 84 were identified as having a short proximal aortic neck. Sixty patients were in the IF group and 24 in the SF group. The average follow-up period was 18.6 months (IF) and 18.5 months (SF). There was no difference in the average proximal neck length (1.19 cm IF vs 1.14 cm SF; P = not significant [NS]) or the preoperative AAA size (5.8 cm IF vs 5.9 cm SF; P = NS). There were no significant differences in age (76.6 years IF vs 74.8 years SF; P = .32), gender (IF 66.7% vs SF 21.88% men; P = .053), or length of stay (2.2 days IF vs 1.9 days SF; P = .39). The comorbidities (diabetes, hypertension, and warfarin use) were also similar. There were five type 1a endoleaks in group IF and one in group SF (P = .44) identified at the 1-month follow-up; however, only one patient in the IF group underwent intervention for enlargement of the AAA sac. At 1 year, there was persistence of one type 1a endoleak in both groups, but these were deemed dead-end leaks as they did not fill the sac nor lead to aneurysm growth. There were no migrations (>0.5 cm) noted in either group. Sac regression was observed at an average rate of 0.24 cm/year in the IF group and 0.26 cm/year in the SF group (P = NS). There were no aneurysm ruptures during the study period.'] Do endografts with suprarenal fixation perform better than those with infrarenal fixation in the treatment of patients with short straight proximal aortic necks? | qiaojin/PubMedQA | 2 | [
-1.0492593050003052,
-1.8234914541244507,
1.7978317737579346
] |
['Evolutionarily conserved genes and their associated molecular pathways can serve as a translational bridge between human and mouse research, extending our understanding of biological pathways mediating individual differences in behavior and risk for psychopathology.', 'Comparative gene array analysis in the amygdala and cingulate cortex between the serotonin transporter knockout mouse, a genetic animal model replicating features of human depression, and existing brain transcriptome data from postmortem tissue derived from clinically depressed humans was conducted to identify genes with similar changes across species (i.e., conserved) that may help explain risk of depressive-like phenotypes. Human neuroimaging analysis was then used to investigate the impact of a common single-nucleotide polymorphism (rs1064448) in a gene with identified conserved human-mouse changes, adenylate cyclase 7 (ADCY7), on threat-associated amygdala reactivity in two large independent samples.', 'Comparative analysis identified genes with conserved transcript changes in amygdala (n = 29) and cingulate cortex (n = 19), both critically involved in the generation and regulation of emotion. Selected results were confirmed by real-time quantitative polymerase chain reaction, including upregulation in the amygdala of transcripts for ADCY7, a gene previously implicated in human depression and associated with altered emotional responsiveness in mouse models. Translating these results back to living healthy human subjects, we show that genetic variation (rs1064448) in ADCY7 biases threat-related amygdala reactivity.'] Is adenylate cyclase 7 implicated in the biology of depression and modulation of affective neural circuitry? | qiaojin/PubMedQA | 2 | [
-2.540492057800293,
-0.9377299547195435,
2.500671863555908
] |
['Cannabinoid CB(1) receptors (CB(1)Rs) mediate the effects of ▵(9)-tetrahydrocannabinol (THC), the psychoactive component in marijuana. Repeated THC administration produces tolerance and dependence, which limit therapeutic development. Moreover, THC produces motor and psychoactive side effects. β-arrestin2 mediates receptor desensitization, internalization, and signaling, but its role in these CB(1)R effects and receptor regulation is unclear.', 'CB(1)R signaling and behaviors (antinociception, hypothermia, catalepsy) were assessed in β-arrestin2-knockout (βarr2-KO) and wild-type mice after THC administration. Cannabinoid-stimulated [(35)S]GTPγS and [(3)H]ligand autoradiography were assessed by statistical parametric mapping and region-of-interest analysis.', 'β-arrestin2 deletion increased CB(1)R-mediated G-protein activity in subregions of the cortex but did not affect CB(1)R binding, in vehicle-treated mice. βarr2-KO mice exhibited enhanced acute THC-mediated antinociception and hypothermia, with no difference in catalepsy. After repeated THC administration, βarr2-KO mice showed reduced CB(1)R desensitization and/or downregulation in cerebellum, caudal periaqueductal gray, and spinal cord and attenuated tolerance to THC-mediated antinociception. In contrast, greater desensitization was found in hypothalamus, cortex, globus pallidus, and substantia nigra of βarr2-KO compared with wild-type mice. Enhanced tolerance to THC-induced catalepsy was observed in βarr2-KO mice.'] Does β-arrestin2 regulate cannabinoid CB1 receptor signaling and adaptation in a central nervous system region-dependent manner? | qiaojin/PubMedQA | 2 | [
-2.363112211227417,
-1.3612074851989746,
2.708033800125122
] |
['This study evaluates intra- and interobserver variability of automatic diameter and volume measurements of colorectal liver metastases (CRLM) before and after chemotherapy and its influence on response classification.', 'Pre-and post-chemotherapy CT-scans of 33 patients with 138 CRLM were evaluated. Two observers measured all metastases three times on pre-and post-chemotherapy CT-scans, using three different techniques: manual diameter (MD), automatic diameter (AD) and automatic volume (AV). RECIST 1.0 criteria were used to define response classification. For each technique, we assessed intra- and interobserver reliability by determining the intraclass correlation coefficient (α-level 0.05). Intra-observer agreement was estimated by the variance coefficient (%). For inter-observer agreement the relative measurement error (%) was calculated using Bland-Altman analysis. In addition, we compared agreement in response classification by calculating kappa-scores (κ) and estimating proportions of discordance between methods (%).', 'Intra-observer variability was 6.05%, 4.28% and 12.72% for MD, AD and AV, respectively. Inter-observer variability was 4.23%, 2.02% and 14.86% for MD, AD and AV, respectively. Chemotherapy marginally affected these estimates. Agreement in response classification did not improve using AD or AV (MD κ=0.653, AD κ=0.548, AV κ=0.548) and substantial discordance between observers was observed with all three methods (MD 17.8%, AD 22.2%, AV 22.2%).'] Does semi-automatic software increase CT measurement accuracy but not response classification of colorectal liver metastases after chemotherapy? | qiaojin/PubMedQA | 2 | [
-1.5172157287597656,
-1.6815646886825562,
2.1988654136657715
] |
['The prognostic value of the model for end-stage liver disease (MELD) and sodium-based MELD variants in predicting survival following paracetamol overdose remains unclear.', 'To examine the prognostic accuracy of sodium-based MELD variants in paracetamol-induced acute liver injury compared with the sequential organ failure assessment (SOFA) score.', 'Retrospective analysis of 138 single time point paracetamol overdoses admitted to a tertiary liver centre. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily MELD, MELD-Na, MELDNa, MESO, iMELD, UKELD, updated MELD and SOFA scores were calculated.', 'Sixty-six (47.8%) patients developed hepatic encephalopathy, of whom 7 were transplanted and 21 died without liver transplantation. SOFA had a significantly greater area under the receiver operator characteristic for the prediction of spontaneous survival compared with MELD at both 72 (P\xa0=\xa00.024) and 96 (P\xa0=\xa00.017)\xa0h post-overdose. None of the sodium-based MELD variants improved the prognostic accuracy of MELD. A SOFA score >6 by 72\xa0h or >7 by 96\xa0h, post-overdose predicted death/transplantation with a negative predictive value of 96.9 (95% CI 90.2-99.4) and 98.8 (95% CI 93.6-99.9) respectively. SOFA and MELD had similar accuracy for predicting the development of hepatic encephalopathy (P\xa0=\xa00.493).'] Is the sequential organ failure assessment ( SOFA ) score prognostically superior to the model for end-stage liver disease ( MELD ) and MELD variants following paracetamol ( acetaminophen ) overdose? | qiaojin/PubMedQA | 2 | [
-1.1892434358596802,
-1.7041577100753784,
1.8954977989196777
] |
['Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these "excessive" responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself.', 'Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([(3)H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4(+)CD25(high)FoxP3(+) T cells were characterized by mRNA analysis and flow cytometry.', 'Cord blood derived CD4(+)CD25(high) cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4(+)CD25(high) cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3(+)CD4(+)CD25(high)cells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4(+)CD25(+)CD127(low)) is highly suppressive even without prior antigen exposure.'] Do cord blood derived CD4+ CD25 ( high ) T cells become functional regulatory T cells upon antigen encounter? | qiaojin/PubMedQA | 2 | [
-2.2089476585388184,
-1.3473330736160278,
2.647871494293213
] |
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