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['Necrostatin-1 (Nec-1) inhibits necroptosis, a nonapoptotic cell death pathway. Acute kidney injury (AKI) is a clinical problem of high incidence and mortality. It involves several mechanisms of cell death. We aim to evaluate the effect of Nec-1 in the toxic kidney injury model by cisplatin.', 'We analyzed the effect of Nec-1 in AKI by cisplatin in human proximal tubule cells by flow cytometry.', 'Our results show that Nec-1 has no effect on apoptosis in renal tubular epithelial cells (Nec-1 + Cis group 13.4 ± 1.7% vs. Cis group 14.6 ± 1.4%) (p > 0.05). But, in conditions in which apoptosis was blocked by benzyloxy-carbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk) the use of Nec-1 completely reversed cell viability (Nec-1 + Cis + z-VAD group 72.9 ± 6.3% vs. Cis group 35.5 ± 2.2%) (p < 0.05) suggesting that Nec-1 has effect on nonapoptotic cell death (necroptosis).'] Does nec-1 protect against nonapoptotic cell death in cisplatin-induced kidney injury? | qiaojin/PubMedQA | 2 | [
-2.3400464057922363,
-1.2727441787719727,
2.6596291065216064
] |
['The aim of this study was to assess the applicability of knowledge discovery in database methodology, based upon data mining techniques, to the investigation of lung cancer surgery.', 'According to CRISP 1.0 methodology, a data mining (DM) project was developed on a data warehouse containing records for 501 patients operated on for lung cancer with curative intention. The modelling technique was logistic regression.', 'The finally selected model presented the following values: sensitivity 9.68%, specificity 100%, global precision 94.02%, positive predictive value 100% and negative predictive value 93.98% for a cut-off point set at 0.5. A receiver operating characteristic (ROC) curve was constructed. The area under the curve (CI 95%) was 0.817 (0.740- 0.893) (p < 0.05). Statistical association with perioperative mortality was found for the following variables [odds ratio (CI 95%)]: age over 70 [2.3822 (1.0338-5.4891)], heart disease [2.4875 (1.0089-6.1334)], peripheral arterial disease [5.7705 (1.9296-17.2570)], pneumonectomy [3.6199 (1.4939-8.7715)] and length of surgery (min) [1.0067 (1.0008-1.0126)].'] Is cross-industry standard process for data mining applicable to the lung cancer surgery domain , improving decision making as well as knowledge and quality management? | qiaojin/PubMedQA | 2 | [
-2.018669843673706,
-1.063759207725525,
2.3504862785339355
] |
['We aimed to examine the relationship between iron status and hypertension as few studies have addressed this.', 'We analyzed the association between ferritin/total iron-binding capacity (TIBC) and the subsequent development of hypertension. A total of 8,580 men who visited the Health Promotion Center for a medical checkup in 2005 were followed-up after 4 years.', 'Of the 8,580 men who were not hypertensive at baseline, 818 were found to be hypertensive at the 4-year follow-up. Compared with those who remained normotensive, these hypertensive subjects had higher levels of ferritin and TIBC at baseline, but had no significant difference in iron levels. After adjustment for age and body mass index (BMI), the odds ratios (OR) was substantially higher for new hypertension (OR 1.54, 95% confidence intervals (CIs) 1.26-1.88; P for trend <0.001) in subjects with the highest ferritin quartiles compared with those in the lowest quartiles. The association of serum ferritin levels with the incidence of hypertension was unchanged after adjustment for baseline blood pressure (BP). Adjustment for insulin resistance as measured by the homeostasis model assessment and the presence of a fatty liver reduced the magnitude of the OR for hypertension (first quartile reference, fourth quartiles OR 1.24, 95% CI 1.01-1.53, P for trend = 0.012), but did not affect their statistical significance.'] Does increased serum ferritin predict the development of hypertension among middle-aged men? | qiaojin/PubMedQA | 2 | [
-1.4745242595672607,
-1.2494003772735596,
1.762570858001709
] |
['In experimental models, hypothalamic inflammation is an early and determining factor in the installation and progression of obesity. Pharmacological and gene-based approaches have proven efficient in restraining inflammation and correcting the obese phenotypes. However, the role of nutrients in the modulation of hypothalamic inflammation is unknown.', 'Here we show that, in a mouse model of diet-induced obesity, partial substitution of the fatty acid component of the diet by flax seed oil (rich in C18:3) or olive oil (rich in C18:1) corrects hypothalamic inflammation, hypothalamic and whole body insulin resistance, and body adiposity. In addition, upon icv injection in obese rats, both ω3 and ω9 pure fatty acids reduce spontaneous food intake and body mass gain. These effects are accompanied by the reversal of functional and molecular hypothalamic resistance to leptin/insulin and increased POMC and CART expressions. In addition, both, ω3 and ω9 fatty acids inhibit the AMPK/ACC pathway and increase CPT1 and SCD1 expression in the hypothalamus. Finally, acute hypothalamic injection of ω3 and ω9 fatty acids activate signal transduction through the recently identified GPR120 unsaturated fatty acid receptor.'] Do unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity? | qiaojin/PubMedQA | 2 | [
-2.648651361465454,
-1.0055326223373413,
2.6638600826263428
] |
['Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.', 'We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998-1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.', 'Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10-6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.'] Is helicobacter pylori infection associated with an increased rate of diabetes? | qiaojin/PubMedQA | 2 | [
-2.2955663204193115,
-0.9140895009040833,
2.294123411178589
] |
['To describe the trend of blood glucose immediately after successful resuscitation from out-of-hospital ventricular fibrillation.', 'Data from cardiac arrest registry supplemented with blood glucose data were analyzed in this population-based observational study. Between 2005 and 2009, a total of 170 adult patients survived to hospital admission after resuscitation from bystander-witnessed cardiac arrest of cardiac origin and ventricular fibrillation as an initial rhythm.', 'Sufficient data for analysis were available in 134 (79%) patients, of whom 87 (65% [95% CI 57-73]) survived to hospital discharge in Cerebral Performance Category 1 or 2. Blood glucose did not change significantly between prehospital (10.5 ± 4.1 mmol/L) and admission (10.0 ± 3.7 mmol/L) in survivors (P = 0.3483), whereas in nonsurvivors, blood glucose increased from 11.8 ± 4.6 to 13.8 ± 3.3 mmol/L (P = 0.0025).'] Does early increase in blood glucose in patients resuscitated from out-of-hospital ventricular fibrillation predict poor outcome? | qiaojin/PubMedQA | 2 | [
-0.9843780398368835,
-1.1994602680206299,
1.3098405599594116
] |
['Cross-sectional cohort study.', 'To investigate the differences in the level of activation of neck-shoulder muscles between elite swimmers with and without shoulder pain during a functional upper-limb task.', 'Previous studies have reported altered motor control of the neck-shoulder muscles in patients with chronic neck-shoulder pain. Whether the activation of neck-shoulder muscles is altered among elite swimmers who have shoulder pain is unknown.', 'Surface electromyography from the sternocleidomastoid, upper trapezius, and anterior scalene (SCL) muscles was recorded bilaterally in 17 elite swimmers (9 men, 8 women; mean ± SD age, 21 ± 3 years) with unilateral shoulder pain, and 17 age- and sex-matched elite swimmers without pain. Root-mean-square values were calculated and normalized to assess the level of muscular activation 5 seconds before, 120 seconds into, 150 seconds into, and 10 seconds after a functional upper-limb task.', 'The data revealed significant differences between groups for the root-mean-square of both SCL muscles (F = 3.733, P = .016) but not for the sternocleidomastoid and upper trapezius muscles. Swimmers with shoulder pain had higher normalized root-mean-square values in both SCL muscles at 120 seconds (78% on average) and 150 seconds (86% on average) into the task and at 10 seconds after the task (40% on average), as compared with swimmers without shoulder pain (P<.05).'] Do elite swimmers with unilateral shoulder pain demonstrate altered pattern of cervical muscle activation during a functional upper-limb task? | qiaojin/PubMedQA | 2 | [
-1.715614676475525,
-0.8034696578979492,
1.6149721145629883
] |
['Cardiovascular complications are major causes of morbidity and mortality following non-cardiac thoracic operations. Recent studies have demonstrated that elevation of N-Terminal Pro-B-type natriuretic peptide (NT-proBNP) levels can predict cardiac complications following non-cardiac major surgery as well as cardiac surgery. However, there is little information on the correlation between lung resection surgery and NT-proBNP levels. We evaluated the role of NT-proBNP as a potential marker for the risk stratification of cardiac complications following lung resection surgery.', 'Prospectively collected data of 98 patients, who underwent elective lung resection from August 2007 to February 2008, were analyzed. Postoperative adverse cardiac events were categorized as myocardial injury, ECG evidence of ischemia or arrhythmia, heart failure, or cardiac death.', 'Postoperative cardiac complications were documented in 9 patients (9/98, 9.2%): Atrial fibrillation in 3, ECG-evidenced ischemia in 2 and heart failure in 4. Preoperative median NT-proBNP levels was significantly higher in patients who developed postoperative cardiac complications than in the rest (200.2 ng/L versus 45.0 ng/L, p=0.009). NT-proBNP levels predicted adverse cardiac events with an area under the receiver operating characteristic curve of 0.76 [95% confidence interval (CI) 0.545~0.988, p=0.01]. A preoperative NT-proBNP value of 160 ng/L was found to be the best cut-off value for detecting postoperative cardiac complication with a positive predictive value of 0.857 and a negative predictive value of 0.978. Other factors related to cardiac complications by univariate analysis were a higher American Society of Anesthesiologists grade, a higher NYHA functional class and a history of hypertension. In multivariate analysis, however, high preoperative NT-proBNP level (>160 ng/L) only remained significant.'] Does n-Terminal Pro-B-type Natriuretic Peptide be Useful to Predict Cardiac Complications Following Lung Resection Surgery? | qiaojin/PubMedQA | 2 | [
-1.4676719903945923,
-1.5796879529953003,
2.079376697540283
] |
['We investigated the stability, pharmacokinetic, and pharmacodynamic profile of the 2(nd) generation anti-von Willeband factor aptamer ARC15105.', 'Platelet plug formation was measured by collagen/adenosine diphosphate-induced closure time with the platelet function analyzer-100 and platelet aggregation by multiple electrode aggregometry. Platelet adhesion was measured on denuded porcine aortas and in a flow chamber. Aptamer stability was assessed by incubation in nuclease rich human, monkey, and rat serum for up to 72 hours. Pharmacokinetic and pharmacodynamic profiles were tested in cynomolgus monkeys after IV and SC administration. The median IC(100) and IC(50) to prolong collagen/adenosine diphosphate-induced closure timewere 27 nmol/L and 12 nmol/L, respectively. ARC15105 (1.3 μmol/L) completely inhibited ristocetin-induced platelet aggregation in whole blood (P<0.001), but also diminished collagen, ADP, arachidonic acid, and thrombin receptor activating peptide-induced platelet aggregation to some extent (P<0.05). ARC15105 (40 nmol/L) decreased platelet adhesion by >90% on denuded porcine aortas (P<0.001), which was comparable to the degree of inhibition obtained with abciximab. ARC15105 (100 nmol/L) also inhibited platelet adhesion to collagen under arterial shear in a flow chamber by >90% (P<0.001). The IV and SC terminal half-lives in cynomolgus monkeys were 67 and 65 hours, respectively, and the SC bioavailability was ≈98%. Allometric scaling estimates the human T(1/2) would be ≈217 hours. Pharmacodynamic analysis confirms that ARC15105 inhibits von Willeband factor activity >90% in blood samples taken 300 hours after a 20 mg/kg IV or SC dose in monkeys.'] Is aRC15105 a potent antagonist of von Willebrand factor mediated platelet activation and adhesion? | qiaojin/PubMedQA | 2 | [
-2.0186121463775635,
-1.5701079368591309,
2.584989070892334
] |
['Here, we assessed the presence of intrahepatic follicular helper T-cells (T(FH)) in a cohort of consecutive genotype 1 (G1) chronic hepatitis C (CHC) patients comprising non-responders (NRs), relapsers (RRs) or those with sustained virological response (SVR) to pegylated interferon and ribavirin, and tested their relation with the response to antiviral treatment.', 'A total of 78 patients with G1 CHC (30 SVR, 15 RR and 33 NR), comparable for sex, age, viral load and fibrosis were evaluated by immunohistochemistry for liver content of PD1+Bcl6+ T(FH) cells. The number of T(FH) cells in the immunostained sections was counted out of five representative high-power microscopic fields (400×) relative to areas involved by the inflammatory infiltrate. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated.', 'The absolute number of liver T(FH) progressively increased from NR to RR to a maximum in SVR patients (14.2 ±12.5 versus 24.5 ±12.5 versus 59.2 ±27.1; P<0.001). The mean absolute number of liver T(FH) was 24.3 ±21.1 in 18 TT polymorphism patients, 31.7 ±29.5 in 43 TC and 47.8 ±27.8 in 17 CC (P=0.01). SVR was achieved in 27/35 (77.1%) of patients with T(FH)≥28 and in only 3/43 (6.9%) of those with T(FH)<28. Similarly, 15/17 (88.2%) CC patients achieved SVR, compared with 15/61 (24.6%) TT/TC subjects. With the combination of T(FH) at the threshold of 28 and the rs12979860 polymorphism, the ability to predict SVR strongly increased.'] Do liver follicular helper T-cells predict the achievement of virological response following interferon-based treatment in HCV-infected patients? | qiaojin/PubMedQA | 2 | [
-0.9323387742042542,
-1.8133573532104492,
1.7272744178771973
] |
['We hypothesized that arachidonic acid produced by anandamide breakdown contributes to the vascular effects of anandamide.', 'Isolated, pressurized rat skeletal muscle arteries, which possess spontaneous myogenic tone, were treated with anandamide, arachidonic acid, capsaicin (vanilloid receptor agonist), WIN 55-212-2 (cannabinoid receptor agonist), URB-597 (FAAH inhibitor), baicalein (lipoxygenase inhibitor), PPOH (cytochrome P450 inhibitor), and indomethacin (cyclooxygenase inhibitor). Changes in the arteriolar diameter in response to the various treatments were measured. To assess the effect of anandamide metabolism, anandamide was applied for 20 min followed by washout for 40 min. This protocol was used to eliminate other, more direct effects of anandamide in order to reveal how anandamide metabolism may influence vasodilation.', 'Anandamide at a low dose (1μM) evoked a loss of myogenic tone, while a high dose (30 μM) not only attenuated the myogenic response but also evoked acute dilation. Both of these effects were inhibited by the FAAH inhibitor URB-597 and were mimicked by arachidonic acid. The CB1 and CB2 agonist R-WIN 55-212-2 and the vanilloid receptor agonist capsaicin were without effect on the myogenic response. The inhibition of the myogenic response by anandamide was blocked by indomethacin and PPOH, but not by baicalein or removal of the endothelium. FAAH expression in the smooth muscle cells of the blood vessels was confirmed by immunohistochemistry.'] Does vascular metabolism of anandamide to arachidonic acid affect myogenic constriction in response to intraluminal pressure elevation? | qiaojin/PubMedQA | 2 | [
-2.3884758949279785,
-1.3484753370285034,
2.7602171897888184
] |
['The proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes independently of its enzymatic activity the degradation of the low-density lipoprotein (LDL) receptor. PCSK9 gain of function in humans leads to autosomal dominant hypercholesterolemia, whereas the absence of functional PCSK9 results in ≈7-fold lower levels of LDL cholesterol. This suggests that lowering PCSK9 may protect against atherosclerosis.', 'We investigated the role of PCSK9 in atherosclerosis in C57BL/6 wild-type (WT), apolipoprotein E-deficient, and LDL receptor-deficient mouse models. Circulating cholesterol levels, fast protein liquid chromatography profiles, aortic cholesteryl esters (CE), and plaque sizes were determined. Intima-media thicknesses were measured by ultrasound biomicroscopy. First, mice expressing null (knockout [KO]), normal (WT), or high (transgenic [Tg]) levels of PCSK9 were fed a 12-month Western diet. KO mice accumulated 4-fold less aortic CE than WT mice, whereas Tg mice exhibited high CE and severe aortic lesions. Next we generated apolipoprotein E-deficient mice, known to spontaneously develop lesions, that expressed null (KO/e), normal (WT/e), or high (Tg/e) levels of PCSK9. After a 6-month regular diet, KO/e mice showed a 39% reduction compared with WT/e mice in aortic CE accumulation, whereas Tg/e mice showed a 137% increase. Finally, LDL receptor-deficient mice expressing no (KO/L), normal (WT/L), or high (Tg/L) levels of PCSK9 were fed a Western diet for 3 months. KO/L and Tg/L mice exhibited levels of plasma cholesterol and CE accumulation similar to those of WT/L mice, suggesting that PCSK9 modulates atherosclerosis mainly via the LDL receptor.'] Does gene inactivation of proprotein convertase subtilisin/kexin type 9 reduce atherosclerosis in mice? | qiaojin/PubMedQA | 2 | [
-1.9915388822555542,
-1.4736417531967163,
2.42905855178833
] |
['The sinoatrial node is the main impulse-generating tissue in the heart. Atrioventricular conduction block and arrhythmias caused by sinoatrial node dysfunction are clinically important and generally treated with electronic pacemakers. Although an excellent solution, electronic pacemakers incorporate limitations that have stimulated research on biological pacing. To assess the suitability of potential biological pacemakers, we tested the hypothesis that the spontaneous electric activity of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) exhibit beat rate variability and power-law behavior comparable to those of human sinoatrial node.', 'We recorded extracellular electrograms from hESC-CMs and iPSC-CMs under stable conditions for up to 15 days. The beat rate time series of the spontaneous activity were examined in terms of their power spectral density and additional methods derived from nonlinear dynamics. The major findings were that the mean beat rate of hESC-CMs and iPSC-CMs was stable throughout the 15-day follow-up period and was similar in both cell types, that hESC-CMs and iPSC-CMs exhibited intrinsic beat rate variability and fractal behavior, and that isoproterenol increased and carbamylcholine decreased the beating rate in both hESC-CMs and iPSC-CMs.'] Do human embryonic and induced pluripotent stem cell-derived cardiomyocytes exhibit beat rate variability and power-law behavior? | qiaojin/PubMedQA | 2 | [
-2.628465414047241,
-1.00077486038208,
2.675532341003418
] |
['It has been much debated whether atopic dermatitis (AD) is associated with contact sensitization as past findings have been conflicting. A positive association might change our clinical practice.', 'To investigate the association between AD and contact sensitization taking the likely route of allergen exposure into account.', 'Questionnaire and clinical data from a cross-sectional study performed in a general population in Copenhagen. In total, 3202 adults aged 18-69 years were patch tested, filaggrin genotyped for 2282del4 and R501X and questioned about AD.', "The variable 'contact sensitization to at least one allergen, but not nickel and thimerosal' was significantly associated with AD (odds ratio 2·53, 95% confidence interval 1·59-4·04). The higher prevalence of contact sensitization was driven mainly by fragrance chemicals. In a subanalysis in nonpierced women, a positive association was also found for nickel sensitization. Nickel and thimerosal sensitization may introduce bias in data analysis as these allergies often develop following skin piercing where the skin compartments are bypassed."] Is contact sensitization to common haptens associated with atopic dermatitis : new insight? | qiaojin/PubMedQA | 2 | [
-2.6739871501922607,
-0.8289906978607178,
2.630661964416504
] |
['To assess the potential of metastasin S100A4 as a biological marker in patients with RA.', 'A total of 87 unselected patients with established RA (disease duration 2-44 years) and treated with MTX and infliximab at a single rheumatology centre were included in a cross-sectional study. Radiographs of hands and feet were taken prior to infliximab treatment and at inclusion (time interval 48\u2009±\u200927 months) and scored for the radiographic damage. S100A4 levels were analysed in relation to radiographic damage, clinical disease activity (DAS-28), inflammation (IL-6, CRP, ESR), bone and cartilage markers [MMP-3, COMP, C-telopeptide of type I collagen (CTX-I)] and proto-oncogenes [survivin, insulin-like growth factor 1 (IGF-1), Flt3 ligand].', 'High levels of S100A4 were associated with severe radiographic damage (OR\u2009=\u20093.40, P\u2009=\u20090.025), non-response to infliximab (OR\u2009=\u20094.63, P\u2009=\u20090.003), presence of antibodies to infliximab (OR\u2009=\u20096.24, P\u2009=\u20090.003) and high levels of Flt3 ligand (OR\u2009=\u20092.73, P\u2009=\u20090.04). Regression analysis showed that high S100A4 was predictive for radiographic progression during infliximab treatment [positive predictive value (PPV) 0.68, P\u2009=\u20090.05]. Low levels of S100A4 were associated with response to infliximab (OR\u2009=\u20092.67, P\u2009=\u20090.049), clinical remission (OR\u2009=\u20094.01, P\u2009=\u20090.0047) and negative RF (OR\u2009=\u20099.22, P\u2009=\u20090.0047). S100A4 correlated with survivin (r\u2009=\u20090.71, P\u2009>\u20090.0001).'] Is metastasin S100A4 increased in proportion to radiographic damage in patients with RA? | qiaojin/PubMedQA | 2 | [
-1.8307106494903564,
-1.626067042350769,
2.493063449859619
] |
['It remains unclear if patients with clinical stage T2 N0 (cT2 N0) esophageal cancer should be offered induction therapy vs surgical intervention alone.', 'This was a retrospective cohort study of cT2 N0 patients undergoing induction therapy, followed by surgical resection, or resection alone, at the Johns Hopkins Hospital from 1989 to 2009. Kaplan-Meier analysis was used to compare all-cause mortality in cT2 N0 patients who had resection alone vs those who had induction chemoradiation therapy, followed by resection.', 'A study cohort of 69 patients was identified and divided into two groups: 55 patients (79.7%) received induction therapy and 14 (20.3%) did not. No statistically significant difference in 5-year survival rate was observed for the two groups: 49.5% for the resection-only group and 53.8% for the induction group. More than 50% of cT2 N0 patients were understaged.'] Is neoadjuvant chemoradiation therapy beneficial for clinical stage T2 N0 esophageal cancer patients due to inaccurate preoperative staging? | qiaojin/PubMedQA | 2 | [
-1.7564624547958374,
-1.4004236459732056,
2.196061849594116
] |
['Fenofibrate, an agonist of peroxisome proliferator-activated receptor-α (PPAR-α), has a vascular protective effect.', 'We investigated the effect of the PPAR-α agonist on coronary artery endothelial function in patients with hypertriglyceridemia.', 'Fifty-eight patients with hypertriglyceridemia were divided into two groups: control (no treatment; n = 23) and fenofibrate treatment (n = 35), 200 mg/d, for 6 months. The patients had undergone rest and adenosine treatment to induce hyperemia for quantification of coronary flow velocity reserve (CFVR) by noninvasive Doppler echocardiography before treatment and at 6-month follow-up. Pulse wave velocity (PWV) was measured before treatment and at 6-month follow-up.', 'CFVR was significantly improved with fenofibrate treatment as compared with baseline level and control group (3.14 ± 0.36 vs. 2.80 ± 0.58 and 2.79 ± 0.65, P < 0.01 and 0.05, respectively), with no difference between baseline levels and untreated controls. In addition, at 6 months, plasma level of homocysteine was significantly increased with fenofibrate treatment as compared with at baseline and control group (median 18.13 [range 14.46-22.02]μmol/L vs. 14.09 [12.01-18.81] and 13.34 [9.69-17.06]μmol/L, P < 0.001 and 0.01, respectively). Furthermore, at 6 months, PWV was significantly decreased with fenofibrate treatment as compared with control group (1446 ± 136 cm/s vs. 1570 ± 203 cm/s, P < 0.05).'] Is coronary flow velocity reserve improved by PPAR-α agonist fenofibrate in patients with hypertriglyceridemia? | qiaojin/PubMedQA | 2 | [
-1.4842523336410522,
-1.7284222841262817,
2.165390968322754
] |
['To describe the clinical outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS treated with ganciclovir implant.', 'Retrospective cohort study.', 'The charts of 115 patients (166 affected eyes) with CMV retinitis treated with ganciclovir implant in the Division of Ocular Immunology, Wilmer Eye Institute from April 1996 through November 2009 were reviewed. Ophthalmologic data collected included visual acuity, ocular complications, treatment, and presence of immune recovery. Kaplan-Meier analyses and Cox regression models were used to investigate relationships between potential risk factors and ocular outcomes.', 'At implantation, 55% of patients were prescribed highly active antiretroviral therapy (HAART), 21% were formerly on HAART, and 24% were HAART-naïve. One hundred sixty-six eyes received 257 ganciclovir implants. Fifty-seven of the implanted eyes were diagnosed with a total of 126 ocular complications after implant surgery (rate=0.19/eye-year [EY]), the 3 most common being cataract, vitreous hemorrhage, and retinal detachment. Despite these ocular complications, the development of severe vision loss (≥6 lines lost) was low (0.005/EY). Patients with immune recovery during follow-up were less likely to have ocular complications after implant surgery; however, only the risk reduction for retinal detachment achieved statistical significance (hazard ratio=0.29, 95% CI: 0.08, 0.98).'] Do clinical outcomes in patients with cytomegalovirus retinitis treated with ganciclovir implant? | qiaojin/PubMedQA | 2 | [
-1.863955020904541,
-1.5252466201782227,
2.369971752166748
] |
['The dsRNA-activated protein kinase (PKR) phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), a global regulator of protein synthesis in mammals. In addition, PKR activates several signal transduction pathways including STAT3 and AKT. PKR is activated by a number of inflammatory stimuli that are induced in the inflamed intestine. In this study we intended to determine the role of PKR in colonic epithelial cells during experimental colitis in mice.', 'Age- and sex-matched PKR(+/+,+/-) and PKR(-/-) littermate mice were reconstituted with wildtype bone marrow cells and subjected to dextran sodium sulfate (DSS)-induced colitis.', 'PKR(-/-) mice displayed more severe clinical and histological manifestations upon DSS colitis compared with their PKR(+/+,+/-) littermates. In response to DSS colitis, the colonic epithelial cells of PKR(-/-) mice exhibited impaired activation of the unfolded protein response (UPR) signaling, including eIF2α phosphorylation, endoplasmic reticulum (ER) chaperone response, and ER-associated degradation (ERAD) components, as well as antioxidative stress response. In addition, the phosphorylation of STAT3 and AKT, which are protective against epithelial cell death and colonic inflammation, was also impaired in the colonic epithelial cells of PKR(-/-) mice upon DSS colitis.'] Does pKR protect colonic epithelium against colitis through the unfolded protein response and prosurvival signaling? | qiaojin/PubMedQA | 2 | [
-2.4523894786834717,
-1.2327072620391846,
2.7115893363952637
] |
['The extent to which parent variables are associated with the level of disability experienced by children with persistent pain has been an area of increasing research.', "To evaluate the extent to which parent perceptions of their child's vulnerability are associated with functioning and health care utilization among children with persistent pain. We also evaluated whether perceptions of child vulnerability contribute to an indirect relationship between parent distress and child functioning and/or child health care utilization.", "The study sample comprised 87 patients aged 6-18 years and a parent attending a chronic pain clinic. Children completed questionnaires on functional limitations, and parents completed questionnaires on parent distress, perceptions of child vulnerability, and extent of the child's pain-related health care utilization. Hierarchical regression and bootstrapping mediation analyses were used to test study hypotheses.", 'Perceptions of child vulnerability were found to be clinically elevated in nearly half (46%) of parents/caregivers, and average child functional ability for the sample was substantially lower than healthy norms. Parent perceptions of greater child vulnerability were significantly associated with poorer child functioning and more child pain-related health care utilization regardless of child age, sex, and duration of persistent pain. Parent distress was found to be indirectly related to child health care utilization through parent perceptions of child vulnerability but directly related to child functioning.'] Are parent perceptions of child vulnerability associated with functioning and health care use in children with chronic pain? | qiaojin/PubMedQA | 1 | [
-2.0912578105926514,
1.3112382888793945,
0.11294029653072357
] |
['Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent neuroplasticity underlying learning and memory in the hippocampus. Schizophrenia has a range of cognitive deficits that may evolve from decreased BDNF, and this study examines this association of BDNF with cognitive deficits in schizophrenia.', 'We recruited 251 chronic schizophrenic patients and 206 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF in both groups. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale.', 'BDNF levels were significantly lower in patients than controls (p\u2009<\u20090.001). Cognitive scores on the RBANS and nearly all of its five subscales (all p\u2009<\u20090.001) except for the visuospatial/constructional index (p\u2009>\u20090.05) were significantly lower in schizophrenic patients than normal controls. For the patients, BDNF was positively associated with immediate memory in schizophrenia.'] Is low BDNF associated with cognitive impairment in chronic patients with schizophrenia? | qiaojin/PubMedQA | 2 | [
-1.9817299842834473,
-1.0998945236206055,
2.1004440784454346
] |
['Hyperbaric oxygen therapy is known to reduce fasting blood glucose in individuals with Type 2 diabetes. However, the mechanisms of this effect are not clear. The aim of this study was to determine whether peripheral insulin sensitivity by hyperinsulinaemic euglycaemic clamp is increased in patients presenting for hyperbaric oxygen therapy.', 'Participants were non-obese individuals without Type 2 diabetes (n=5) or obese patients with Type 2 diabetes (n=5). Patients were given 100% oxygen at 2.0 absolute atmospheres for 2 h, six sessions per week for 5 weeks.', 'Peripheral insulin sensitivity was increased in the whole cohort (P=0.04). Subsequent analysis revealed that this was significant at both treatment 3 (+37.3 ± 12.7%, P=0.02) and treatment 30 (+40.6 ± 12.6%, P=0.009). HbA(1c) was significantly reduced in subjects without diabetes only (P<0.05).'] Does hyperbaric oxygen therapy improve peripheral insulin sensitivity in humans? | qiaojin/PubMedQA | 2 | [
-1.912772297859192,
-1.0475176572799683,
2.0185747146606445
] |
['Epidemiological studies emphasize the possible role of persistent organic pollutants (POPs) in obesity and the metabolic syndrome. These pollutants are stored in adipose tissue (AT).', 'Our aim was to study the effects of POPs on human adipose cells and rodent AT.', 'Using human multipotent adipose-derived stem cells, we carried out large-scale gene expression analysis to identify the major pathways modified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyl (PCB) congener 126 (PCB-126), and PCB-153 and to evaluate their toxic effects. The effects of TCDD on gene expression and AT histology were also assessed in mice.', 'The most significantly regulated genes in both precursor cells and adipocytes were those involved in the inflammatory/immune response, cancer, and metabolism pathways. Interestingly, the fold induction and the number of modulated genes were higher in precursors than in adipocytes, suggesting that the former could be more sensitive to the effect of pollutants. When cells were treated with combinations of pollutants, the effects of the AhR ligands TCDD and PCB-126 were dominant compared with those of the non-dioxin-like PCB-153. The effects of AhR ligands were reduced by the AhR antagonist α-naphthoflavone. The regulation of inflammatory pathway was observed in wild-type AT but not in AhR-knockout mice.'] Do inflammatory pathway genes belong to major targets of persistent organic pollutants in adipose cells? | qiaojin/PubMedQA | 2 | [
-2.6198689937591553,
-1.089409351348877,
2.7302193641662598
] |
["Chronic kidney disease (CKD) is a major public health problem, and despite continued research in the field, there is still a need to identify both biomarkers of risk and progression, as well as potential therapeutic targets. Structural equation modeling (SEM) is a family of statistical techniques that has been utilized in the fields of sociology and psychology for many years; however, its utilization in the biological sciences is relatively novel. SEM's ability to investigate complex relationships in an efficient, single model could be utilized to understand the progression of CKD, as well as to develop a predictive model to assess kidney status in the patient.", 'Fischer 344 rats were fed either an ad libitum diet or a calorically restricted diet, and a time-course study of kidney structure and function was performed. EQS, a SEM software package, was utilized to generate five CKD models of the Fisher 344 rat and identify relationships between measured variables and estimates of kidney damage and kidney function.', 'All models identified strong relationships between a biomarker for CKD, kidney injury molecule-1 (Kim-1) and kidney damage, in the Fischer 344 rat CKD model. Models also indicate a strong relationship between age and renal damage and dysfunction.'] Does structural equation modeling highlight the potential of Kim-1 as a biomarker for chronic kidney disease? | qiaojin/PubMedQA | 2 | [
-2.582540273666382,
-0.3925594389438629,
2.1055784225463867
] |
['Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.', 'Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay.', 'We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells.'] Is anaphase-promoting complex/cyclosome protein Cdc27 a target for curcumin-induced cell cycle arrest and apoptosis? | qiaojin/PubMedQA | 2 | [
-2.449639081954956,
-1.2233543395996094,
2.788640022277832
] |
["More severe and persistent forms of affective disorders are accompanied by grey matter loss in key frontal and temporal structures. It is unclear whether such changes precede the onset of illness, occur early in the course or develop gradually with persistence or recurrence of illness. A total of 47 young people presenting with admixtures of depressive and psychotic symptoms were recruited from specialist early intervention services along with 33 age matched healthy control subjects. All participants underwent magnetic resonance imaging and patients were rated clinically as to current stage of illness. Twenty-three patients were identified as being at an early 'attenuated syndrome' stage, while the remaining were rated as having already reached the 'discrete disorder' or 'persistent or recurrent illness' stage. Contrasts were carried out between controls subjects and patients cohorts with attenuated syndromes and discrete disorders, separately.", 'The patients that were identified as having a discrete or persisting disorder demonstrated decreased grey matter volumes within distributed frontal brain regions when contrasted to both the control subjects as well as those patients in the attenuated syndrome stage. Overall, patients who were diagnosed as more advanced in terms of the clinical stage of their illness, exhibited the greatest grey matter volume loss of all groups.'] Do frontal lobe changes occur early in the course of affective disorders in young people? | qiaojin/PubMedQA | 2 | [
-2.1000895500183105,
0.5973363518714905,
0.6298320293426514
] |
['In HIV-infected patients, data on immunogenicity of Yellow fever immunization are scarce, and there is conflicting evidence of the influence of CD4 T-cell count and plasma HIV RNA on neutralizing antibody titer (NT) after vaccine injection.', 'In this prospective cohort study, NT was measured in all consecutive HIV outpatients who had previously received at least 1 injection of Yellow fever vaccine. Risk factors for vaccine failure (NT < 1:10) and magnitude of NT according to dates of HIV diagnosis and immunization were assessed by logistic regression and general linear models.', 'Among 364 included patients, 24 (7%) had NT <1:10 after a mean delay of 8.4 years after immunization. Among patients immunized after HIV diagnosis (n = 240), NT <1:10 was associated only with detectable plasma HIV RNA at immunization. Among 79 patients with primary vaccination after diagnosis of HIV infection, higher HIV RNA at immunization was the unique independent risk factor for NT <1:10 [adjusted odds ratio (OR) = 3.73 per log10, 95% confidence interval (CI): 1.14 to 12.28]. Lower values of NT were independently associated with a shorter duration of undetectable plasma HIV RNA (OR = 1.05 per year, 95% CI: 1.005 to 1.09) and higher plasma HIV RNA (OR = 0.91 per log10, 95% CI: 0.84 to 0.99) at immunization.'] Is plasma HIV-RNA the key determinant of long-term antibody persistence after Yellow fever immunization in a cohort of 364 HIV-infected patients? | qiaojin/PubMedQA | 2 | [
-0.9163687229156494,
-1.6893585920333862,
1.699568271636963
] |
['Proline-rich tyrosine kinase 2 (Pyk2) is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI) remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo.', 'C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically.', 'Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1) myeloperoxidase content in lung tissues, 2) vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3) the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment.'] Does inhibition of Pyk2 block lung inflammation and injury in a mouse model of acute lung injury? | qiaojin/PubMedQA | 2 | [
-2.3934638500213623,
-1.4148564338684082,
2.841923236846924
] |
['Fractionated radiotherapy allows for the safe administration of larger doses without the development of immediate or late toxicity. The influence of preoperative fractionated radiotherapy on neointima formation for expanded polytetrafluoroethylene (ePTFE) graft has not been determined.', 'Twenty mongrel dogs were randomly divided into radiotherapy group (a total dose of 35\xa0Gy) or control group (no radiation). The infrarenal abdominal aorta and inferior vena cava were replaced by ePTFE grafts at 3 months after irradiation in the radiotherapy group. Grafts were explanted at 4 weeks after surgery. Histopathological techniques were undertaken to evaluate graft neointima formation. The control group was managed the same as the radiotherapy group except for not receiving irradiation.', 'Four grafts implanted into inferior vena cava in the irradiated group and three in the control group were found to be completely occluded. None of the grafts implanted into abdominal aorta were obstructed. In the case of the inferior vena cava graft, the thickness of the graft neointima did not differ significantly between the irradiated and control groups. However, for the abdominal aorta graft, the neointima thickness in the irradiated groups was significantly thinner than that in the control group.'] Does high-dose preoperative fractionated radiotherapy affect the patency and healing of ePTFE vascular prosthesis after replacement of canine abdominal aorta and inferior vena cava? | qiaojin/PubMedQA | 2 | [
-2.244657278060913,
-1.3763058185577393,
2.6584434509277344
] |
['High concentrations of methylated thiopurine metabolites, such as 6-methyl mercaptopurine, are associated with hepatotoxicity during administration of the conventional thiopurines azathioprine or 6-mercaptopurine in IBD patients. Metabolization of the non-conventional thiopurine 6-thioguanine does not generate 6-methyl mercaptopurine. Hence, the aim of our study was to evaluate hepatotoxicity during 6-thioguanine in IBD patients who previously failed conventional thiopurines due to 6-methyl mercaptopurine associated hepatotoxicity.', 'A retrospective single center intercept cohort study was performed of IBD patients using 6-thioguanine between January 2006 and July 2010 after failing conventional thiopurine therapy due to 6-methyl mercaptopurine associated hepatotoxicity. The primary outcome was the occurrence of 6-thioguanine induced hepatotoxicity, scaled according to the Common Terminology Criteria for Adverse Events.', 'Nineteen patients were included. Median duration of 6-thioguanine therapy (median daily dosage 21 mg (9-24)) was 23 weeks (6-96). Hepatotoxicity did not reoccur in 15 out of 19, whereas grade 1 toxicity persisted in 4 patients (p<0.001). Median aspartate aminotransferase and alanine aminotransferase concentrations decreased from 34 U/l (20-59) and 64 U/l (15-175) to 23 U/l (18-40; p=0.003) and 20 U/l (14-48; p=0.019), respectively.'] Does hepatotoxicity associated with 6-methyl mercaptopurine formation during azathioprine and 6-mercaptopurine therapy occur on the short-term during 6-thioguanine therapy in IBD treatment? | qiaojin/PubMedQA | 2 | [
-1.8447439670562744,
-1.5454294681549072,
2.4258615970611572
] |
['Hypoxia is a critical pathological factor in a variety of retinal diseases, including age-related macular degeneration. It upregulates angiogenic growth factors and promotes neovascularization. Hypoxia changes the cellular redox state and activates class III histone deacetylase sirtuin1 (SIRT1). Activated SIRT1 signals hypoxia inducible factor (HIF)-2α, which transactivates vascular endothelial growth factor (VEGF) and erythropoietin. In this study, we investigated the role of hypoxia induced SIRT1 in choroidal neovascularization in relation to age-related macular degeneration.', 'Choroidal endothelial cells (RF/6A) were maintained in a semiconfluent state and hypoxia was induced by exposing the cells to cobalt chloride for 24 h. Induction of hypoxia was confirmed by flow cytometric analysis and the levels of SIRT1 were noted in a hypoxic condition as well in the cells after blocking SIRT1 activity using sirtinol. The role of SIRT1 in the activation of HIF-2α and nuclear factor-κB (RelA/p65) during hypoxia in the presence or absence of SIRT1 was assessed using immunoblot analysis. VEGF levels were quantified using enzyme-linked immunosorbent assay.', 'Hypoxic induction was confirmed using flow cytometric analysis, which showed cell cycle arrest starting at a 200 µM concentration of cobalt chloride. Hypoxic treatment (200 µM concentration of cobalt chloride) increased SIRT1 levels to 7.8%, which reduced to control level after its activity was inhibited (p<0.05). Activated SIRT1 mediates HIF-2α and nuclear factor-κB (RelA/p65) expression to 4.5 fold and fivefold, respectively, compared to control, and the levels were suppressed following sirtinol treatment (4.1% and 39.3% respectively; p=0.01). Hypoxic treatment increased VEGF levels by 94.9±19.6 pg/ml compared to control levels (25.58±3.58 pg/ml). These levels decreased to 10.29±0.2 pg/ml after blocking SIRT1 activity using sirtinol, compared to control (p<0.01).'] Does hypoxia initiate sirtuin1-mediated vascular endothelial growth factor activation in choroidal endothelial cells through hypoxia inducible factor-2α? | qiaojin/PubMedQA | 2 | [
-2.2617478370666504,
-1.4538601636886597,
2.72710919380188
] |
['Helicobacter pylori has been shown to cause atrophic gastritis and intestinal metaplasia (IM), both of which are precancerous lesions. To clarify the mechanism by which H. pylori eradication prevents gastric cancer, we monitored atrophy and IM improvement in gastric mucosa over a long period after H. pylori eradication.', 'We monitored 118 patients (72 males, 46 females; mean age 61.3 ± 5.1 years) for a mean of 8.6 years (range 5-13) after successful H. pylori eradication. Biopsy specimens were taken from the greater curvatures of the antrum (A2) and the corpus (B2).', 'Atrophy was significantly decreased in patients with successful H. pylori eradication, both at A2 (from 1.60 ± 0.09 to 1.02 ± 0.08; p < 0.001) and B2 (from 0.71 ± 0.10 to 0.02 ± 0.02; p < 0.001), and IM score was significantly decreased at B2 (from 0.17 ± 0.12 to 0.00 ± 0.00; p < 0.05), but not at A2 (from 0.60 ± 0.11 to 0.43 ± 0.09; p = NS). In patients without successful eradication, however, there were no differences in scores over time. Before eradication, IM score was significantly higher in males than in females, both at A2 (0.81 ± 0.12 vs. 0.25 ± 0.10; p < 0.05) and B2 (0.32 ± 0.08 vs. 0.07 ± 0.04; p < 0.05).'] Does helicobacter pylori eradication improve gastric atrophy and intestinal metaplasia in long-term observation? | qiaojin/PubMedQA | 2 | [
-1.1718688011169434,
-1.6496765613555908,
1.822434425354004
] |
['Results of meta-analyses typically conclude that future large studies may be mandated. However, the predictive ability of these estimates is deficient. We explored meta-analytic prediction intervals as means for providing a clear and appropriate future treatment summary reflecting current estimates.', 'A meta-epidemiological study of binary outcome critical care meta-analyses published between 2002 and 2010. Computation of 95% DerSimonian-Laird and Bayesian random-effects meta-analytic confidence intervals (CI) and 95% credible intervals (CrI), respectively, and frequentist (PI) and Bayesian (PrI) prediction intervals for odds ratio (OR) and risk ratio (RR) were undertaken. Bayesian calculations included the probability that the OR and RR point estimates ≥1.', 'Seventy-two meta-analyses from 70 articles were identified, containing between three and 80 studies each, with median nine studies. For both frequentist and Bayesian settings, 49-69% of the meta-analyses excluded the null. All significant CrI had high probabilities of efficacy/harm. The number of PI vs. PrI excluding 1 was 25% vs. 3% (OR), 26% vs. 3% (RR) of the total meta-analyses. Unsurprisingly, PI/PrI width was greater than CI/CrI width and increased with increasing heterogeneity and combination of fewer studies.'] Do robust meta-analytic conclusions mandate the provision of prediction intervals in meta-analysis summaries? | qiaojin/PubMedQA | 2 | [
-1.6441789865493774,
-1.0413599014282227,
1.7368781566619873
] |
['Plasma triglyceride (TG) levels are known to confer an increased risk of vascular disease in healthy populations, but data in high-risk patients are scarce. In this study we evaluated the risk on recurrent vascular events conferred by increased plasma TG levels in patients with various clinical manifestations of vascular disease.', 'Prospective cohort study of 5731 patients with clinically manifest vascular disease.', 'First new vascular events (myocardial infarction, ischemic stroke, vascular death) occurred in 782 subjects during a median follow-up of 4.9 years (interquartile range 2.5-8.1 years). Patients in the highest plasma TG quintile (>2.24 mmol/L) had a higher risk for recurrent vascular events (HR 1.45; 95%CI 1.13-1.86) compared with the lowest plasma TG quintile (<0.97 mmol/L) after adjustments for age, gender, body mass index, smoking, lipid-lowering medication and low-density lipoprotein-cholesterol. The increased risk associated with increasing plasma TG levels was irrespective of the presence of type 2 diabetes (T2DM), but only present in patients without the metabolic syndrome. Furthermore, the increased risk was particularly present in patients with coronary artery disease (CAD) (HR 1.45; 95%CI 1.02-2.08) and was not modified by other lipid levels (p-value for interaction >0.05). Plasma TG still contributed to vascular risk when other lipid levels were at target level.'] Do plasma triglyceride levels increase the risk for recurrent vascular events independent of LDL-cholesterol or nonHDL-cholesterol? | qiaojin/PubMedQA | 2 | [
-2.0824391841888428,
-1.3829467296600342,
2.476649761199951
] |
["Alzheimer's disease (AD) has a complex genetic etiology, and as a result many genes have been studied to determine how they might be involved with the disease. Amyloidogenic effects have been broadly linked with familial forms of the disease, though certain genes such as UBQLN1 could also play a role in prodromal phases such as amnesic mild cognitive impairment (MCI).", 'The aim of this study is to examine the role of the UBQ-8i (rs12344615) functional polymorphism in the UBQLN1 gene as a risk factor for MCI and AD and its possible synergies with apolipoprotein gene E (APOE).', '215 MCI patients, 347 sporadic AD sufferers and 238 healthy controls from the Basque Country (Spain) were analysed. Clinical criteria and neuro-psychiatric tests were used to establish the diagnostic groups. SNP, UBQ-8i and the APOE gene were genotyped via real-time polymerase chain reaction (rtPCR), polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) respectively. Multinomial logistic regression models were used to determine the risk for MCI and AD.', 'Allele C of rs12344615 of the UBQLN1 gene is not a risk factor for MCI or AD (OR = 0.88, CI95% 0.60-1.31 p7equal;s0.542 and OR = 0.73, CI95% 0.51-1.02 p=0.079, respectively). Moreover, genotypes with at least one C allele are observed not to show synergies with APOE*E4 in MCI or with AD sufferers.'] Is uBQ-8i polymorphism an independent risk factor for mild cognitive impairment and Alzheimer 's disease in APOE-4 carriers? | qiaojin/PubMedQA | 2 | [
-1.6473581790924072,
-1.5708143711090088,
2.15202260017395
] |
['Severe ureteropelvic junction obstruction is treated surgically. However, for milder cases most clinical teams adopt a watchful waiting approach and only operate in the presence of significant decline of renal function combined with severe hydronephrosis. Little is known about the long-term consequences of ureteropelvic junction obstruction.', 'Using capillary electrophoresis coupled with mass spectrometry, we analyzed the urinary proteome of 42 patients with ureteropelvic junction obstruction 5 years postoperatively or 5 years following spontaneous resolution.', 'At 5-year followup urinary proteomes were similar between patients with early surgical correction of ureteropelvic junction obstruction and age matched controls. In contrast, urinary proteomes differed significantly between conservatively followed patients and controls. Analyses of the proteomic differences suggested ongoing renal or ureteral remodeling in the conservatively followed patients that was not visible clinically.'] Does urinary proteome analysis at 5-year followup of patients with nonoperated ureteropelvic junction obstruction suggest ongoing kidney remodeling? | qiaojin/PubMedQA | 2 | [
-2.306156873703003,
-1.2102694511413574,
2.5999326705932617
] |
['Methotrexate (MTX) resistance is defined on the basis of the human chorionic gonadotropin (hCG) curve. The aim of this study was to identify low-risk non-metastatic patients with gestational trophoblastic neoplasia (GTN) who can achieve resolution by continuing MTX treatment despite a transient hCG plateau.', 'Before starting chemotherapy, 24 patients with FIGO Stage I GTN underwent transvaginal ultrasonography with power Doppler in order to identify myometrial lesions (areas of increased echogenicity and increased power Doppler signal). Ultrasound response to chemotherapy was defined when myometrial lesions decreased in echogenicity, Doppler signal or size. When ultrasound response occurred, despite chemoresistance defined by hCG values, MTX treatment was continued.', 'MTX was continued in three out of seven chemoresistant patients because ultrasound suggested response to MTX. All three of these patients achieved a complete response, thus nearly halving the MTX-resistance rate.'] Does transvaginal ultrasound predict delayed response to chemotherapy and drug resistance in stage I low-risk trophoblastic neoplasia? | qiaojin/PubMedQA | 2 | [
-2.476243734359741,
-1.2693321704864502,
2.805835723876953
] |
['The aim is to assess the effect of survivin knockdown on the radio- and chemosensitivity of gastric cancer cells in vitro and in nude mice.', 'Survivin messenger RNA and protein were detected by semiquantitative reverse transcription-polymerase chain reaction and Western blot. Survivin and control small hairpin RNA (shRNA) expression constructed vectors were stably transfected into gastric cancer SGC7901 cells. The cells were in turn subjected to irradiation, cisplatin or fluorouracil (5-FU) treatment for colony formation, methyl-thiazolyl-tetrazolium cell viability and flow cytometry assays in vitro. An in vivo nude mouse xenograft assay was performed to assess the effects of Survivin knockdown on regulation of the sensitivity of SGC7901 cells to irradiation, cisplatin or 5-FU treatment.', 'Survivin shRNA markedly inhibited levels of survivin messenger RNA and protein in SGC7901 cells and significantly increased sensitivity of the tumor cells to radiation treatment, ie, the mean lethal and quasi-threshold doses in survivin shRNA-transfected cells were significantly lower than that of the negative control shRNA-transfected and parental cells. The same is true for cisplatin- and 5-FU-treated tumor cells, ie, colony formation and cell viability of the survivin-knocked down SGC7901 cells were reduced, while apoptosis was induced compared with the control cells. Furthermore, the xenograft assay showed survivin knockdown in SGC7901 cells suppressed tumor formation and growth compared with the controls.'] Does survivin knockdown enhance gastric cancer cell sensitivity to radiation and chemotherapy in vitro and in nude mice? | qiaojin/PubMedQA | 2 | [
-2.3728010654449463,
-1.367494821548462,
2.7893905639648438
] |
['Combination of multiple biomarkers representing distinct aspects of tumor biology will have a better prognostic value. This study was to identify prognostic subgroups of colon adenocarcinoma by combined analysis of synuclein-gamma (SNCG), a human homologue of piwi (Hiwi), phosphatase of regenerating liver-3 (PRL-3), arrest-defective protein 1, homolog A (ARD1) and clinicopathologic features in 225 colon adenocarcinoma specimens.', 'Immunohistochemistry for 4 tumor markers was performed in whole tissue sections from 225 colon adenocarcinoma patients with complete clinicopathologic data and up to 10-year follow-up. The immunohistochemical expression patterns were examined individually and in multimarker combinations. Univariate and multivariate analyses were performed to identify independent predictive markers of poor outcome.', 'With the tumor marker positive rate [32.0% (62/225) for SNCG; 76.9% (173/225) for combined SNCG/Hiwi/PRL-3/ARD1] and the detecting accuracy [61.9% (252/407) for SNCG; 82.6% (336/407) for combined SNCG/Hiwi/PRL-3/ARD1] increasing, incremental value of combined SNCG/Hiwi/PRL-3/ARD1 (P < 0.001; hazard ratios (HR), 3.2) to poor outcome was found. Stratified by lymph node, Hiwi alone (P = 0.004; HR, 3.2) led to poor outcome in patients without lymph node metastasis (LN-), and SNCG (P < 0.001; HR, 2.5) had independently poor prognostic value for patients with lymph node metastasis (LN+).'] Does combined phenotype of 4 markers improve prognostic value of patients with colon cancer? | qiaojin/PubMedQA | 2 | [
-1.7133774757385254,
-1.6701993942260742,
2.4078316688537598
] |
['Previously, the authors demonstrated that the lack of the P2X(7) receptor impairs epithelial wound healing and stromal collagen organization in the cornea. The goal here is to characterize specific effects of the P2X(7) receptor on components of the corneal stroma extracellular matrix.', 'Unwounded corneas from P2X(7) knockout mice (P2X(7) (-/-)) and C57BL/6J wild type mice (WT) were fixed and prepared for quantitative and qualitative analysis of protein expression and localization using Real Time PCR and immunohistochemistry. Corneas were stained also with Cuprolinic blue for electron microscopy to quantify proteoglycan sulfation in the stroma.', 'P2X(7) (-/-) mice showed decreased mRNA expression in the major components of the corneal stroma: collagen types I and V and small leucine-rich proteoglycans decorin, keratocan, and lumican. In contrast P2X(7) (-/-) mice showed increased mRNA expression in lysyl oxidase and biglycan. Additionally, we observed increases in syndecan 1, perlecan, and type III collagen. There was a loss of perlecan along the basement membrane and enhanced expression throughout the stroma, in contrast with the decreased localization of other proteoglycans throughout the stroma. In the absence of lyase digestion there was a significantly smaller number of proteoglycan units per 100 nm of collagen fibrils in the P2X(7) (-/-) compared to WT mice. While digestion was more pronounced in the WT group, double digestion with Keratanase I and Chondroitinase ABC removed 88% of the GAG filaments in the WT, compared to 72% of those in the P2X(7) (-/-) mice, indicating that there are more heparan sulfate proteoglycans in the latter.'] Does the P2X ( 7 ) receptor regulate proteoglycan expression in the corneal stroma? | qiaojin/PubMedQA | 2 | [
-2.207602024078369,
-1.416312575340271,
2.6151506900787354
] |
['To investigate the roles of intracellular signaling elicited by Hedgehog (Hh) ligands in corneal maintenance and wound healing.', 'The expression of Hedgehog pathway components in the cornea was assayed by immunohistochemistry, western blot and reverse-transcription polymerase chain reaction (RT-PCR), in wild-type mice and mice that were heterozygous null for the gene encoding the transcription factor, paired box gene 6 (Pax6).\xa0 Corneal epithelial wound healing and cell migration assays were performed after pharmacological upregulation and downregulation of the hedgehog pathway.\xa0 Reporter mice, mosaic for expression of the gene encoding β-galactosidase (LacZ), were crossed to Pax6(+/-) mice, mice heterozygous for the gene encoding GLI-Kruppel family member GLI3, and Pax6(+/-)Gli3(+/-)\xa0double heterozygotes, to assay patterns of cell migration and corneal epithelial organization in vivo.', 'Corneal epithelial wound healing rates increased in response to application of Sonic hedgehog (Shh), but only in mice with wild-type Pax6 dosage.\xa0 Downregulation of Hedgehog signalling inhibited corneal epithelial cell proliferation.\xa0 Pax6(+/-)\xa0corneal epithelia showed increased proliferation in response to exogenous Shh, but not increased migration. Desert hedgehog (Dhh) was shown to be the major endogenous ligand, with Shh detectable only by RT-PCR and only after epithelial wounding. The activity of phosphatidylinositol-3-OH kinase-γ (PI3Kγ) was not required for the increased migration response in response to Shh.\xa0 Nuclear expression of the activator form of the transcription factor Gli3 (which mediates Hh signalling) was reduced in Pax6(+/-) corneal epithelia. Pax6(+/-)Gli3(+/-) double heterozygotes showed highly disrupted patterns of clonal arrangement of cells in the corneal epithelium.'] Does interaction between hedgehog signalling and PAX6 dosage mediate maintenance and regeneration of the corneal epithelium? | qiaojin/PubMedQA | 2 | [
-2.339838743209839,
-1.4054410457611084,
2.758066177368164
] |
['The Caenorhabditis elegans basic helix-loop-helix (bHLH) factor HLH-8, the single Twist ortholog in the nematode genome, plays important roles in mesoderm development, including M lineage patterning and differentiation of vulval and enteric muscles. HLH-8 cooperates with HLH-2, the bHLH E/Daughterless ortholog, to regulate downstream target genes, but it is not known whether HLH-2 is an obligate partner for all HLH-8 functions.', 'Using hlh-2 loss-of-function alleles and RNAi, we discovered that HLH-2 is required in the vulval muscles but not in M patterning or enteric muscle development. Additionally, we found that expressing tethered HLH-8/HLH-8 dimers in hlh-8 null animals rescued M patterning and enteric but not vulval muscle development.'] Do distinct Caenorhabditis elegans HLH-8/twist-containing dimers function in the mesoderm? | qiaojin/PubMedQA | 2 | [
-2.4466519355773926,
-1.0833537578582764,
2.5611371994018555
] |
["Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Based on the associations of programmed death-1 (PD-1) protein encoding gene (PDCD1) with connective tissue diseases and vasculitides, PDCD1 polymorphisms are studied for susceptibility to TA in this study.", 'The study group is made up of TA patients (n=229) fulfilling the 1990 ACR classification criteria and compared to 193 healthy controls (HC). PD-1.3, PD-1.5 and PD-1.6 single nucleotide polymorphisms of PDCD1 gene are genotyped by polymerase chain reaction and restriction analysis (PCR-RFLP).', 'The distribution of PD-1.5 polymorphism in TA patients and HC revealed a similar presence of TT genotype in patients and controls (13.3% vs. 11.4%). PD-1.3 and PD-1.6 were less polymorphic and did not differ between the groups. Rare AA genotype of PD-1.3 (1.4% vs. 1.0%) and AG genotype of PD-1.6 was again similarly (22.4% vs. 19.2%) present in TA and HC.'] Are pDCD1 polymorphisms associated with Takayasu 's arteritis in Turkey? | qiaojin/PubMedQA | 2 | [
-2.2041308879852295,
-1.454277753829956,
2.7031774520874023
] |
['Replication-competent oncolytic viruses have shown great promise as a potential cancer treatment. This study aimed to determine whether a novel vaccinia virus, GLV-1h151, with genetic modifications enhancing cancer specificity and enabling virus detection, is effective against a range of human cancers and is safe when administered in preclinical models.', 'GLV-1h151 was modified with deletion of thymidine kinase enhancing specificity and insertion of the green fluorescent protein (GFP) gene. The virus was tested in several human cancer cell lines for cytotoxicity including breast, lung, pancreatic, and colorectal. Virus replication was assessed via visualization of GFP expression and bioluminescence, and viral plaque assays. Finally, GLV-1h151 was administered systemically or intratumorally in mice with pancreatic cancer xenografts (PANC-1) to assess virus biodistribution, toxicity, and effect on tumor growth.', 'GLV-1h151 effectively infected, replicated in, and killed several cancer cell types. Detection and visualization of virus replication was successful via fluorescence imaging of GFP expression, which was dose dependent. When administered intravenously or intratumorally in vivo, GLV-1h151 regressed tumor growth (P < 0.001) and displayed a good biosafety profile. GLV-1h151 infection and replication in tumors was successfully visualized via GFP and bioluminescence, with virus presence in tumors confirmed histologically.'] Is a novel genetically modified oncolytic vaccinia virus in experimental models effective against a wide range of human cancers? | qiaojin/PubMedQA | 2 | [
-2.314300298690796,
-1.3308088779449463,
2.7330355644226074
] |
['Although it is well known that adenovirus 36 (Ad36) is associated with obesity in humans as well as in animals, the detailed cellular mechanism is unclear.', 'Wild-type (WT) mice and monocyte chemoattractant protein-1 knockout (MCP-1(-/-)) mice were infected with Ad36, and their weights and inflammatory status were measured. Macrophage infiltration was examined in their reproductive fat pads and in a coculture system. The correlation between Ad36 antibody presence and MCP-1 levels was tested in human samples.', 'We have shown that Ad36 infection stimulated an inflammatory state by increasing the level of MCP-1 through the activation of nuclear factor κB, which in turn induced the infiltration of macrophages into adipocytes. This induced inflammation resulted in viral obesity, which caused chronic inflammation and affected lipid metabolism. In contrast to WT mice, MCP-1(-/-) mice were protected from Ad36-induced inflammation and obesity. The MCP-1 levels in Ad36-antibody-positive human group were higher than those in the antibody-negative group.'] Does adenovirus 36 as an obesity agent maintain the obesity state by increasing MCP-1 and inducing inflammation? | qiaojin/PubMedQA | 2 | [
-2.2976338863372803,
-1.2223517894744873,
2.5733184814453125
] |
['Migraine headache is one of the most common neurological disorders, but the pathophysiology contributing to migraine is poorly understood. Intracranial interleukin-6 (IL-6) levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges and contribute to the development of headache.', 'Cutaneous allodynia was measured in rats following stimulation of the dura with IL-6 alone or in combination with the MEK inhibitor, U0126. The number of action potentials and latency to the first action potential peak in response to a ramp current stimulus as well as current threshold were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. These recordings were performed in the presence of IL-6 alone or in combination with U0126. Association between ERK1 and Nav1.7 following IL-6 treatment was also measured by co-immunoprecipitation.', 'Here we report that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia. The MEK inhibitor U0126 blocked IL-6-induced allodynia indicating that IL-6 produced this behavioral effect through the MAP kinase pathway. In trigeminal neurons retrogradely labeled from the dura, IL-6 application decreased the current threshold for action potential firing. In response to a ramp current stimulus, cells treated with IL-6 showed an increase in the numbers of action potentials and a decrease in latency to the first spike, an effect consistent with phosphorylation of the sodium channel Nav1.7. Pretreatment with U0126 reversed hyperexcitability following IL-6 treatment. Moreover, co-immunoprecipitation experiments demonstrated an increased association between ERK1 and Nav1.7 following IL-6 treatment.'] Does sensitization of dural afferents underlie migraine-related behavior following meningeal application of interleukin-6 ( IL-6 )? | qiaojin/PubMedQA | 2 | [
-2.479018449783325,
-1.2856175899505615,
2.7468199729919434
] |
['We have previously found that atorvastatin decreases liver injury markers in patients with nonalcoholic steatohepatitis. However, how atorvastatin treatment ameliorates the disease activity in nonalcoholic steatohepatitis patients remains unknown.', 'We examined here which anthropometric, metabolic and inflammatory variables were improved and related with amelioration of disease activity in atorvastatin-treated nonalcoholic steatohepatitis patients.', 'Forty-two biopsy-proven nonalcoholic steatohepatitis patients with dyslipidemia were enrolled. Patients were treated with atorvastatin (10mg/day) for 12 months.', 'Atorvastatin significantly decreased liver transaminase, γ-glutamyl transpeptidase, low-density lipoprotein-cholesterol, triglycerides, type IV collagen, and tumour necrosis factor-α levels, whilst it increased adiponectin and high-density lipoprotein-cholesterol. Atorvastatin improved nonalcoholic fatty liver disease activity score and increased liver to spleen density ratio. Multiple stepwise regression analysis revealed that γ-glutamyl transpeptidase, tumour necrosis factor-α and liver to spleen density ratio (inversely) were independently associated with nonalcoholic fatty liver disease activity score. Aspartate aminotransferase, low-density lipoprotein-cholesterol and nonalcoholic fatty liver disease activity score were independent determinants of decreased liver to spleen density ratio.'] Does atorvastatin improve disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property? | qiaojin/PubMedQA | 2 | [
-2.3866071701049805,
-1.3896570205688477,
2.8323981761932373
] |
['Macrophages mediate the epithelial response to Helicobacter pylori and are involved in the development of gastritis. Sonic Hedgehog (Shh) regulates gastric epithelial differentiation and function, but little is known about its immunoregulatory role in the stomach. We investigated whether gastric Shh acts as a macrophage chemoattractant during the innate immune response to H pylori infection.', 'Mice with parietal cell-specific deletion of Shh (PC-Shh(KO)) and control mice were infected with H pylori. Levels of gastric Shh, cytokines, and chemokines were assayed by quantitative reverse-transcriptase polymerase chain reaction or by a Luminex-based multiplex assay 2, 7, or 180 days after infection. Circulating concentrations of Shh were measured by enzyme-linked immunosorbent assay. Bone marrow chimera experiments were performed with mice that have myeloid cell-specific deletion of the Hedgehog signal transduction protein Smoothened (LysMCre/Smo(KO)). Macrophage recruitment was measured in gastric tissue and peripheral blood by fluorescence-activated cell sorting analysis.', 'Control mice infected with H pylori for 6 months developed an inflammatory response characterized by infiltration of CD4(+) T cells and increased levels of interferon gamma and interleukin 1β in the stomach. PC-Shh(KO) mice did not develop gastritis, even after 6 months of infection with H pylori. Control mice had increased concentrations of Shh, accompanied by the recruitment of CD11b(+)F4/80(+)Ly6C(high) macrophages 2 days after infection. Control mice that received bone marrow transplants from control mice had an influx of macrophages to the gastric mucosa in response to H pylori infection; this was not observed in H pylori-infected control mice that received bone marrow transplants from LysMCre/Smo(KO) mice.'] Does gastric Sonic Hedgehog act as a macrophage chemoattractant during the immune response to Helicobacter pylori? | qiaojin/PubMedQA | 2 | [
-2.387723922729492,
-1.3417115211486816,
2.795903205871582
] |
['Changes in brain derived neurotrophic factor (BDNF) expression have been associated with mood disorders and cognitive dysfunction. Transgenic models that overexpress or underexpress BDNF demonstrate similar deficits in cognition and mood. We explored the hypothesis that BDNF expression is controlled by balancing the activity of BDNF promoter IV (BP4) with a negative regulatory region containing a polymorphism associated with cognitive dysfunction and mood disorders.', 'We used comparative genomics, transgenic mouse production, and magnetofection of primary neurons with luciferase reporters and signal transduction agonist treatments to identify novel polymorphic cis-regulatory regions that control BP4 activity.', "We show that BP4 is active in the hippocampus, the cortex, and the amygdala and responds strongly to stimuli such as potassium chloride, lithium chloride, and protein kinase C agonists. We also identified a highly conserved sequence 21 kilobase 5' of BP4 that we called BE5.2, which contains rs12273363, a polymorphism associated with decreased BDNF expression, mood disorders, and cognitive decline. BE5.2 modulated the ability of BP4 to respond to different stimuli. Intriguingly, the rarer disease associated allele, BE5.2(C), acted as a significantly stronger repressor of BP4 activity than the more common BE5.2(T) allele."] Does a polymorphism associated with depressive disorders differentially regulate brain derived neurotrophic factor promoter IV activity? | qiaojin/PubMedQA | 2 | [
-2.375742197036743,
-1.031264066696167,
2.443801164627075
] |
['Human and animal studies suggest that testosterone may have antidepressant effects. In this study, we sought to investigate the molecular mechanisms underlying the antidepressant effects of testosterone within the hippocampus, an area that is fundamental in the etiology of depression.', 'The effects of testosterone replacements in gonadectomized adult male rats were investigated using the sucrose preference and forced swim tests. We explored possible effects of testosterone on hippocampal neurogenesis and gene expression of stress-related molecules. Through the use of viral vectors, we pursued the antidepressant molecular mechanism(s) of testosterone in mediating anhedonia and manipulated extracellular signal-regulated kinase 2 (ERK2) expression in the dentate gyrus in gonadectomized rats with testosterone replacements.', 'Testosterone had antidepressant effects, likely mediated by aromatization to estrogen metabolites, in the sucrose preference and forced swim tests despite having no effects on hippocampal cell proliferation or survival. We found a testosterone-dependent regulation of hippocampal ERK2 expression. Functionally, reducing ERK2 activity within the dentate gyrus induced anhedonia in gonadectomized rats receiving testosterone supplementation, whereas the overexpression of ERK2 rescued this behavior in gonadectomized rats.'] Does extracellular signal-regulated kinase 2 signaling in the hippocampal dentate gyrus mediate the antidepressant effects of testosterone? | qiaojin/PubMedQA | 2 | [
-2.686586618423462,
-0.8252666592597961,
2.4693171977996826
] |
["Murray's law describes the optimal branching anatomy of vascular bifurcations. If Murray's law is obeyed, shear stress is constant over the bifurcation. Associations between Murray's law and intravascular ultrasound (IVUS) assessed plaque composition near coronary bifurcations have not been investigated previously.", "In 253 patients plaque components (fibrous, fibro-fatty, necrotic core, and dense calcium) were identified by IVUS in segments proximal and distal to the bifurcation of a coronary side branch. The ratio of mother to daughter vessels was calculated according to Murray's law (Murray ratio) with a high Murray ratio indicating low shear stress. Analysis of variance was used to detect independent associations of Murray ratio and plaque composition.", 'Patients with a high Murray ratio exhibited a higher relative amount of dense calcium and a lower amount of fibrous and fibro-fatty tissue than those with a low Murray ratio. After adjustment for age, sex, cardiovascular risk factors or concomitant medications, the Murray ratio remained significantly associated with fibrous volume distal (F-ratio 4.90, P=0.028) to the bifurcation, fibro-fatty volume distal (F-ratio 4.76, P=0.030) to the bifurcation, and dense calcium volume proximal (F-ratio 5.93, P=0.016) and distal (F-ratio 5.16, P=0.024) to the bifurcation.'] Is deviation from Murray 's law associated with a higher degree of calcification in coronary bifurcations? | qiaojin/PubMedQA | 2 | [
-2.196842670440674,
-1.1201376914978027,
2.4411749839782715
] |
['Red blood cell transfusion is done primarily as a means to improve oxygen delivery (DO₂). Current transfusion guidelines are based solely on hemoglobin levels, regardless of actual DO₂ need. As central venous oxygen saturation (ScvO₂) may reflect imbalances in DO₂ and consumption (VO₂) the aim of this study was to investigate the value of ScvO₂ as an indicator of oxygen balance in isovolemic anemia.', 'After splenectomy, anesthetized Vietnamese mini pigs (n\u2009=\u200913, weight range: 18-30\u2009kg) underwent controlled bleeding in five stages (T₀-T₅). During each stage approximately 10% of the estimated starting total blood volume was removed and immediately replaced with an equal volume of colloid. Hemodynamic measurements and blood gas analysis were then performed.', 'Each stage of bleeding resulted in a significant fall in hemoglobin, T₀ : 125 (113-134) to T(5) : 49 (43-55) g/l [T₀ : 7.7 (6.9-8.2) to T₅ : 3.0 (2.6-3.4) mmol/l]. The O₂-extraction (VO₂/DO₂) increased significantly only from T₃ : 35 (21-40) %, P\u2009<\u20090.05. The change of ScvO₂ showed a similar pattern and dropped below the physiological threshold of 70% at T₄ : 68 (61-76) %. At this point, hemoglobin was below the recommended transfusion trigger value, 59 (53-67) g/l [3.6 (3.3-4.1) mmol/l]. There was a strong significant association between ScvO₂<\u200970%) and VO₂/DO₂ >\u200930%): r\u2009=\u2009-0.71, r² \u2009=\u20090.50, P\u2009<\u20090.001.'] Is central venous oxygen saturation a good indicator of altered oxygen balance in isovolemic anemia? | qiaojin/PubMedQA | 2 | [
-1.5395156145095825,
-1.7214555740356445,
2.226111650466919
] |
['The aim of this study was to describe anesthetic management and perioperative complications in patients undergoing pulmonary vein isolation for the treatment of atrial fibrillation under general anesthesia using high-frequency jet ventilation. The authors also identified variables associated with longer ablation times in this patient cohort.', 'A retrospective observational study.', 'The electrophysiology laboratory in a major university hospital.', 'One hundred eighty-eight consecutive patients undergoing pulmonary vein isolation under general anesthesia with high-frequency jet ventilation.', 'High-frequency jet ventilation was used as the primary mode of ventilation under general anesthesia.', 'High-frequency jet ventilation was performed successfully throughout the ablation procedure in 175 cases of the study cohort. The remaining 13 patients had to be converted to conventional positive-pressure ventilation because of high PaCO(2) or low PaO(2) on arterial blood gas measurements. Variables associated with a shorter ablation time included a higher ejection fraction (p = 0.04) and case volume performed by each electrophysiologist in the study group (p = 0.001).'] Do anesthetic management of patients undergoing pulmonary vein isolation for treatment of atrial fibrillation using high-frequency jet ventilation? | qiaojin/PubMedQA | 2 | [
-2.467406988143921,
-0.6305248141288757,
2.21612811088562
] |
['Studies suggest that altered immune activation, manifested by an imbalance in anti- and pro-inflammatory cytokine levels, exists in a subgroup of irritable bowel syndrome (IBS) patients. However, similar studies have not been conducted in Latin populations. The objective of this study was to measure serum levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α in subjects fulfilling symptom criteria for IBS and controls.', 'Volunteers (n=178) from a university population in Mexico City, participated in the study. Of the sample, 34.8% met Rome II criteria for IBS and 65.2% were designated as controls. Serum cytokines were measured by enzyme-linked immunoabsorbent assay. Analysis of covariance models were used to test main effects between gender, IBS symptoms, and bowel habit subtype to explain the cytokine serum levels. Statistical models were tested using body mass index as a covariate.', 'IL-10 levels were significantly lower in IBS vs. controls (mean (95% confidence interval): 15.6 (14.8, 16.3) vs. 18.6 (17.9, 19.4)\u2009pg/ml, P<0.001), while TNF-α levels were higher in IBS (20.9 (19.1, 23.0) vs. 17.9 (16.7, 19.3)\u2009pg/ml, P=0.010). IBS and female gender were independent predictors for IL-10 (P<0.05). In contrast, female gender was an independent predictor for TNF-α. In addition, women with IBS-D had the lowest IL-10 (P<0.001) and highest TNF-α (P=0.021) vs. other subtypes.'] Is lower serum IL-10 an independent predictor of IBS among volunteers in Mexico? | qiaojin/PubMedQA | 2 | [
-1.2988812923431396,
-1.586118459701538,
1.8125578165054321
] |
['To determine optimal timing of assessing postradiation radiographic response on magnetic resonance imaging (MRI) scans in pediatric patients with diffuse intrinsic pontine glioma (DIPG).', 'Patients were treated on a prospective study at the National Cancer Institute (Protocol #06-C-0219) evaluating the effects of radiotherapy (RT). Standard RT was administered in standard fractionation over 6 weeks. Postradiation MRI scans were performed at 2 and 6-8 weeks.', 'Eleven patients with DIPG were evaluated. Median age was 6 years (range, 4-13 years). Patients were treated with external-beam RT to 55.8 Gy (n = 10) or 54 Gy (n = 1), with a gross tumor volume to planning target volume expansion of 1.8-2.0 cm. All patients received prescribed dose and underwent posttreatment MRI scans at 2 and 6-8 weeks. Pretreatment imaging revealed compression of fourth ventricle (n = 11); basilar artery encasement (n = 9); tumor extension outside the pons (n = 11); and tumor hemorrhage (n = 2). At the 2-week scan, basilar artery encasement improved in 7 of 9 patients, and extent of tumor was reduced in 5 of 11 patients. Fourth ventricle compression improved in 6 of 11 patients but worsened in 3 of 11 patients. Presumed necrosis was observed in 5 of 11 patients at 2 weeks and in 1 additional patient at 6-8 weeks. There was no significant difference in mean anteroposterior and transverse diameters of tumor between the 2- and 6-8-week time points. Six of 11 patients had increasing ventricular size, with no evidence of obstruction.'] Does role of early postradiation magnetic resonance imaging scan in children with diffuse intrinsic pontine glioma? | qiaojin/PubMedQA | 2 | [
-1.8303083181381226,
-1.561604619026184,
2.470973253250122
] |
['The transport of endoplasmic reticulum (ER)-derived COPII vesicles toward the ER-Golgi intermediate compartment (ERGIC) requires cytoplasmic dynein and is dependent on microtubules. p150(Glued), a subunit of dynactin, has been implicated in the transport of COPII vesicles via its interaction with COPII coat components Sec23 and Sec24. However, whether and how COPII vesicle tether, TRAPP (Transport protein particle), plays a role in the interaction between COPII vesicles and microtubules is currently unknown.', 'We address the functional relationship between COPII tether TRAPP and dynactin. Overexpressed TRAPP subunits interfered with microtubule architecture by competing p150(Glued) away from the MTOC. TRAPP subunit TRAPPC9 bound directly to p150(Glued) via the same carboxyl terminal domain of p150(Glued) that binds Sec23 and Sec24. TRAPPC9 also inhibited the interaction between p150(Glued) and Sec23/Sec24 both in vitro and in vivo, suggesting that TRAPPC9 serves to uncouple p150(Glued) from the COPII coat, and to relay the vesicle-dynactin interaction at the target membrane.'] Does tRAPPC9 mediate the interaction between p150 and COPII vesicles at the target membrane? | qiaojin/PubMedQA | 2 | [
-2.3284895420074463,
-0.834435760974884,
2.211808919906616
] |
['Low admission Norton scale scores (ANSS) are usually associated with high risk of pressure ulcer. The aim of this study was to determine whether low ANSS are also associated with long-term mortality following rehabilitation in older adults.', 'A cross-sectional retrospective study.', 'Consecutive older adults admitted during 2009 for rehabilitation following stroke (n\u2009=\u2009110), hip arthroplasty (n\u2009=\u2009201), and hospital-associated deconditioning (n\u2009=\u200996).', 'Patients were followed until January, 2011. Long-term mortality rates, i.e. within one year or more, were compared between patients with low (≤\u200914) ANSS and patients with high (≥\u200915) ANSS.', 'The final cohort included 407 patients (67.8% females; mean age 82.2 years). Overall, 193 (47.4%) patients had low ANSS. Patients were followed for a mean period of 524 days. Overall, 66 (16.2%) patients died during this time. Patients who died had significantly lower mean ANSS compared with those who survived (13.9 vs 14.9; p\u2009=\u20090.001). Cumulative survival rates were significantly lower among patients with low ANSS compared with patients with high ANSS (p\u2009=\u20090.004). Regression analysis showed that ANSS were independently associated with mortality (p\u2009=\u20090.02), regardless of rehabilitation cause, age, gender, and chronic co-morbidities.'] Are admission Norton scale scores associated with long-term mortality following rehabilitation in older adults? | qiaojin/PubMedQA | 2 | [
-0.9011515378952026,
-1.2206670045852661,
1.1134971380233765
] |
['AIM. This study was designed to examine whether the class I and class IIa histone deacetylase (HDAC) inhibitors, sodium butyrate and sodium valproate alter the expression of human NCOR1 and/or NCOR2 genes coding for N-CoR (nuclear receptor corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone receptors), respectively.', 'Human leukemia HL-60 cells were treated for 24 h with 0.5 and 1 mM sodium butyrate, 1 to 3 mM sodium valproate, 1 mcM all-trans retinoic acid (ATRA) or cotreated with 1 mcM ATRA and 0.5 mM sodium butyrate. The acetylation of histones H3 and H4 was analysed by western blotting. The levels of NCOR1 and NCOR2 mRNA were determined by quantitative real-time PCR. Expression of NCF2 gene coding for the NADPH oxidase subunit p67phox was evaluated as a marker of myeloid differentiation. Results. Both butyrate and valproate increased the acetylation of histone H3 at Lys9 and/or Lys14 as well as histone H4 at Lys12. Both HDAC inhibitors caused a significant increase in NCF2 mRNA levels without affecting NCOR1 or NCOR2 mRNA levels. Similarly, ATRA alone or in combination with butyrate induced NCF2 gene expression without any significant influence on the expression of NCOR1 or NCOR2 genes.'] Do hDAC inhibitors sodium butyrate and sodium valproate affect human ncor1 and ncor2 gene expression in HL-60 cells? | qiaojin/PubMedQA | 2 | [
-2.3644587993621826,
-1.3390395641326904,
2.7456552982330322
] |
['The Eustachian valve (EV) is an embryonic structure redirecting the blood flow from the inferior vena cava through the foramen ovale. It may persist in adults as a floating membrane in the right atrium. A large EV can be associated with thrombosis, embolization, bacterial endocarditis, etc. The prevalence of EV in the normal population is unknown.', 'to assess the prevalence and size of EV in unselected patients examined by transoesophageal echo. Methods. 1100 consecutive patients were examined for various reasons by a single operator and interpreter. Routine check was made for the presence of EV in the right atrium. Only patients with a mobile EV and not with a simple rigid rim were counted. Three measurements of the EV length at the level of the aortic valve (i.e. 90°C) were made off-line and the longest distance considered. If the EV was not visualized and recorded as a straight line because of its chaotic movement, the picture of the valve was segmented into several separated valve portions and the sum taken as the true length.', '46 patients (24 males) with EV were identified out of total 1100 pts examined. The average length of the EV was 23.6 ± 9.7 mm (7-47 mm, median 23 mm).'] Do the prevalence of eustachian valve on transoesophageal echo examination? | qiaojin/PubMedQA | 2 | [
-1.2751294374465942,
-1.5509577989578247,
1.8665404319763184
] |
['Functional cartilage tissue engineering aims to generate grafts with a functional surface, similar to that of authentic cartilage. Bioreactors that stimulate cell-scaffold constructs by simulating natural joint movements hold great potential to generate cartilage with adequate surface properties. In this study two methods based on atomic force microscopy (AFM) were applied to obtain information about the quality of engineered graft surfaces. For better understanding of the molecule-function relationships, AFM was complemented with immunohistochemistry.', 'Bovine chondrocytes were seeded into polyurethane scaffolds and subjected to dynamic compression, applied by a ceramic ball, for 1h daily [loading group 1 (LG1)]. In loading group 2 (LG2), the ball additionally oscillated over the scaffold, generating sliding surface motion. After 3 weeks, the surfaces of the engineered constructs were analyzed by friction force and indentation-type AFM (IT-AFM). Results were complemented and compared to immunohistochemical analyses.', 'The loading type significantly influenced the mechanical and histological outcomes. Constructs of LG2 exhibited lowest friction coefficient and highest micro- and nanostiffness. Collagen type II and aggrecan staining were readily observed in all constructs and appeared to reach deeper areas in loaded (LG1, LG2) compared to unloaded scaffolds. Lubricin was specifically detected at the top surface of LG2.'] Does sliding motion modulate stiffness and friction coefficient at the surface of tissue engineered cartilage? | qiaojin/PubMedQA | 2 | [
-2.504765033721924,
-1.1657743453979492,
2.829176664352417
] |
['Gene therapy of the heart has been attempted in a number of clinical trials with the injection of naked DNA, although quantitative information on myocellular transfection rates is not available. The present study aimed to quantify the efficacy of electropulsing protocols that differ in pulse duration and number to stimulate transfection of cardiomyocytes and to determine the impact on myocardial integrity.', 'Reporter plasmid for constitutive expression of green fluorescent protein (GFP) was injected into the left ventricle of beating hearts of adult, male Lewis rats. Four electrotransfer protocols consisting of repeated long pulses (8\u2009×\u200920\u2009ms), trains of short pulses (eight trains of either 60 or 80\u2009×\u2009100\u2009µs) or their combination were compared with control procedures concerning the degree of GFP expression and the effect on infiltration, fibrosis and apoptosis.', 'All tested protocols produced GFP expression at the site of plasmid injection. Continuous pulses were most effective and increased the number of GFP-positive cardiomyocytes by more than 300-fold compared to plasmid injection alone (p\u2009<\u20090.05). Concomitantly, the incidence of macrophage infiltration, fibrosis and cell death was increased. Trains of short pulses reduced macrophage infiltration and fibrosis by four- and two-fold, respectively, although they were 20-fold less efficient in stimulating cardiomyocyte transfection. GFP expression co-related to delivered electric energy, infiltration and fibrosis, although not apoptosis.'] Do electric pulses augment reporter gene expression in the beating heart? | qiaojin/PubMedQA | 2 | [
-2.1582438945770264,
-1.4733105897903442,
2.6263442039489746
] |
['Oxidative stress has been shown to play an important role in cancer progression. In lung cancer, increasing expression of caveolin-1 (Cav-1) has been found in both primary and metastatic carcinomas and may be critical in the regulation of the oxidative status of cancer cells.', 'Using molecular and pharmacological manipulations, the role of Cav-1 in regulating cellular oxidative status in lung cancer cells was investigated. The level of Cav-1 was determined by western blot analysis and reactive oxygen species (ROS) were detected by specific fluorescence probes.', 'The treatment of lung cancer H460 cells with hydrogen peroxide (H(2)O(2)) significantly up-regulated ROS inside the cells and contributed to cell apoptosis. While cells stably transfected with Cav-1 overexpressing plasmids (H460/Cav-1) exhibited decreased ROS signal and attenuated cell death rate, shRNACav-1 transfected (H460/shCav-1) cells showed enhanced ROS signal and increased cell damage. The use of specific superoxide anion and the hydrogen peroxide detecting assays and hydroxyl radical inhibition assay indicated that the variable oxidative stress found in these cells was mainly due to the alteration of the cellular hydroxyl radical level.'] Does caveolin-1 attenuate hydrogen peroxide-induced oxidative damage to lung carcinoma cells? | qiaojin/PubMedQA | 2 | [
-2.563054323196411,
-1.1337730884552002,
2.741354465484619
] |
['C-reactive protein (CRP) has been associated with the development of many carcinomas, but the significance of CRP remains unclear for metastatic gastric cancer (MGC).', 'Sixty one patients who received S-1 plus cisplatin for MGC were retrospectively identified and categorized into two groups depending on the serum CRP level before chemotherapy.', 'Overall survival was significantly shorter in the CRP≥1.0 group than in the CRP<1.0 group (median, 292 days versus 451 days; p=0.0004). Moreover, progression-free survival was significantly shorter in the CRP≥1.0 group than in the CRP<1.0 group (median, 115 days versus 188 days; p=0.0010). In a multivariate analysis, serum CRP level before chemotherapy was an independent prognostic factor for MGC (hazard ratio 4.20 [95% CI, 1.66 to 10.64] p=0.002).'] Is c-reactive protein a potential prognostic factor for metastatic gastric cancer? | qiaojin/PubMedQA | 2 | [
-1.5114737749099731,
-1.5223495960235596,
2.0898847579956055
] |
['Inhibition of signal transduction pathways has been successfully introduced into cancer treatment. The dual phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 has antitumor activity in vitro against solid tumors. Here, we examined the activity of NVP-BEZ235 in acute lymphoblastic leukemia (ALL) cells and the best modalities for combination approaches.', 'ALL cell lines (SEM, RS4;11, Jurkat and MOLT4) were treated with NVP-BEZ235 alone, or in combination with cytarabine (AraC), doxorubicin (Doxo) or dexamethasone (Dexa).', 'NVP-BEZ235 potently inhibited the proliferation and metabolic activity of ALL cells. Antiproliferative effects were associated with G(0)/G(1) arrest and reduced levels of cyclin-dependent kinase 4 (CDK4) and cyclin D3. Inhibition of PI3K and mTOR activity was detected at 10 and 100 nM. NVP-BEZ235 combined with AraC, Doxo or Dexa synergistically enhanced the cytotoxicity compared to single-drug treatment, even in glucocorticoid-resistant cells.'] Does the dual kinase inhibitor NVP-BEZ235 in combination with cytotoxic drugs exert anti-proliferative activity towards acute lymphoblastic leukemia cells? | qiaojin/PubMedQA | 2 | [
-2.3941941261291504,
-1.3398487567901611,
2.7440686225891113
] |
['Cyclin G1 deficiency is associated with reduced incidence of carcinogen-induced hepatocellular carcinoma (HCC), but its function in HCC progression remains obscure. We report a critical role of cyclin G1 in HCC metastasis. Elevated expression of cyclin G1 was detected in HCCs (60.6%), and its expression levels were even higher in portal vein tumor thrombus. Clinicopathological analysis revealed a close correlation of cyclin G1 expression with distant metastasis and poor prognosis of HCC. Forced expression of cyclin G1 promoted epithelial-mesenchymal transition (EMT) and metastasis of HCC cells in vitro and in vivo. Cyclin G1 overexpression enhanced Akt activation through interaction with p85 (regulatory subunit of phosphoinositide 3-kinase [PI3K]), which led to subsequent phosphorylation of glycogen synthase kinase-3β (GSK-3β) and stabilization of Snail, a critical EMT mediator. These results suggest that elevated cyclin G1 facilitates HCC metastasis by promoting EMT via PI3K/Akt/GSK-3β/Snail-dependent pathway. Consistently, we have observed a significant correlation between cyclin G1 expression and p-Akt levels in a cohort of HCC patients, and found that combination of these two parameters is a more powerful predictor of poor prognosis.'] Does cyclin G1-mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitate liver cancer progression? | qiaojin/PubMedQA | 2 | [
-2.381240129470825,
-1.339362382888794,
2.757244348526001
] |
['We evaluated the in vitro activity of a merochlorin A, a novel compound with a unique carbon skeleton, against a spectrum of clinically relevant bacterial pathogens and against previously characterized clinical and laboratory Staphylococcus aureus isolates with resistance to numerous antibiotics.', 'Merochlorin A was isolated and purified from a marine-derived actinomycete strain CNH189. Susceptibility testing for merochlorin A was performed against previously characterized human pathogens using broth microdilution and agar dilution methods. Cytotoxicity was assayed in tissue culture assays at 24 and 72 hours against human HeLa and mouse sarcoma L929 cell lines.', 'The structure of as new antibiotic, merochlorin A, was assigned by comprehensive spectroscopic analysis. Merochlorin A demonstrated in vitro activity against Gram-positive bacteria, including Clostridium dificile, but not against Gram negative bacteria. In S. aureus, susceptibility was not affected by ribosomal mutations conferring linezolid resistance, mutations in dlt or mprF conferring resistance to daptomycin, accessory gene regulator knockout mutations, or the development of the vancomycin-intermediate resistant phenotype. Merochlorin A demonstrated rapid bactericidal activity against MRSA. Activity was lost in the presence of 20% serum.'] Does novel bacterial metabolite merochlorin A demonstrate in vitro activity against multi-drug resistant methicillin-resistant Staphylococcus aureus? | qiaojin/PubMedQA | 2 | [
-2.5312232971191406,
-1.207863211631775,
2.846069812774658
] |
['Evidence links dietary sodium to hypertension and cardiovascular disease (CVD), but investigation of its influence on cardiovascular function is limited.', 'We examined the relation between habitual dietary sodium and coronary flow reserve (CFR), which is a measure of overall coronary vasodilator capacity and microvascular function. We hypothesized that increased sodium consumption is associated with lower CFR.', 'Habitual daily sodium intake for the previous 12 mo was measured in 286 male middle-aged twins (133 monozygotic and dizygotic pairs and 20 unpaired twins) by using the Willett food-frequency questionnaire. CFR was measured by positron emission tomography [N(13)]-ammonia, with quantitation of myocardial blood flow at rest and after adenosine stress. Mixed-effects regression analysis was used to assess the association between dietary sodium and CFR.', 'An increase in dietary sodium of 1000 mg/d was associated with a 10.0% lower CFR (95% CI: -17.0%, -2.5%) after adjustment for demographic, lifestyle, nutritional, and CVD risk factors (P = 0.01). Across quintiles of sodium consumption, dietary sodium was inversely associated with CFR (P-trend = 0.03), with the top quintile (>1456 mg/d) having a 20% lower CFR than the bottom quintile (<732 mg /d). This association also persisted within pairs: a 1000-mg/d difference in dietary sodium between brothers was associated with a 10.3% difference in CFR after adjustment for potential confounders (P = 0.02).'] Is habitual dietary sodium intake inversely associated with coronary flow reserve in middle-aged male twins? | qiaojin/PubMedQA | 2 | [
-1.6723757982254028,
-1.5641841888427734,
2.20782208442688
] |
['The effect of hormone replacement therapy (HRT) in postmenopausal women on the development of peripheral atherosclerosis remains in question. The goal of this study was to analyze the use of HRT in a large population of postmenopausal women and to determine its association with the prevalence of peripheral arterial disease (PAD).', 'A prospective database of patients who underwent voluntary vascular screening was used. Identification of patients as postmenopausal, and their use of HRT, was based on patient questionnaires. PAD was defined to be present if either lower extremity ankle-brachial index was ≤0.9.', 'Analysis was performed on data from 847,982 postmenopausal women; 433,178 (51.1%) reported having used HRT. HRT subjects were slightly older than patients who had not used HRT (64.5 years vs. 63.6 years). Caucasian women were significantly more likely to have used HRT than non-Caucasian women (52.4% vs. 47.6%). HRT subjects were significantly more likely to have smoked cigarettes (42.8% vs. 40.6%), to have hypertension (47.9% vs. 45.1%), and to have hypercholesterolemia (55% vs. 51.5%) than women who had not used HRT (all P < 0.001). However, HRT subjects were significantly less likely to have diabetes mellitus (8.6% vs. 10.2%, P < 0.001). Despite the increased prevalence of several atherosclerotic risk factors among women who used HRT, they were significantly less likely to have PAD (3.3% vs. 4.1%, P < 0.001). Multivariate analysis adjusting for age, race, and medical comorbidities that predispose toward the development of atherosclerosis confirmed that HRT was independently associated with a decreased risk of PAD (odds ratio: 0.8, 95% confidence interval: 0.78-0.82). In subsets of postmenopausal women with known atherosclerotic risk factors, the significant effect of HRT on the prevalence of PAD was maintained; in women with either a smoking history, hypertension, hypercholesterolemia, diabetes, or age of ≥70 years, the odds ratio of HRT use with regard to PAD remained approximately 0.8.'] Is hormone replacement therapy associated with a decreased prevalence of peripheral arterial disease in postmenopausal women? | qiaojin/PubMedQA | 2 | [
-1.6852203607559204,
-1.4111782312393188,
2.0394692420959473
] |
['The outcome of patients undergoing surgical or interventional therapy is unfavourably influenced by severe systemic inflammation. We assessed the impact of a systemic inflammatory response syndrome (SIRS) on the outcome after transcatheter aortic valve implantation (TAVI).', 'One hundred and fifty-two high-risk patients (mean age: 80.5 ± 6.5 years, mean logistic EuroSCORE: 30.4 ± 8.1%) with symptomatic severe aortic stenosis underwent TAVI. Proinflammatory cytokines [interleukin-6 (IL-6) and interleukin-8 (IL-8)], and acute phase reactants [C-reactive protein (CRP) and procalcitonin (PCT)] were measured at baseline and 1, 4, 24, 48, 72 h, and 7 days after TAVI. Sixty-one of 152 patients developed SIRS during the first 48 h after TAVI. Systemic inflammatory response syndrome patients were characterized by leucocytosis ≥12 × 10(9)/L (83.6 vs. 12.1%; P < 0.001), hyperventilation (80.3 vs. 35.2%; P < 0.001), tachycardia (37.7 vs. 9.9%; P < 0.001), and fever (31.1 vs. 3.3%; P < 0.001) compared with patients without SIRS. Furthermore, the occurrence of SIRS was characterized by a significantly elevated release of IL-6 and IL-8 with subsequent increase in the leucocyte count, CRP, and PCT. Major vascular complications [odds ratio (OR) 5.1, 95% confidence interval (CI): 1.3-19.6; P = 0.018] and the number of ventricular pacing runs (OR 1.7, 95% CI: 1.1-2.8; P = 0.025) were independent predictors of SIRS. The occurrence of SIRS was related to 30-day and 1-year mortality (18.0 vs. 1.1% and 52.5 vs. 9.9%, respectively; P < 0.001) and independently predicted 1-year mortality risk (hazard ratio: 4.3, 95% CI: 1.9-9.9; P < 0.001).'] Does systemic inflammatory response syndrome predict increased mortality in patients after transcatheter aortic valve implantation? | qiaojin/PubMedQA | 2 | [
-1.946980595588684,
-1.581475019454956,
2.5582852363586426
] |
['In the brain, the enzyme catalase by reacting with H(2)O(2) forms Compound I (catalase-H(2)O(2) system), which is the main system of central ethanol metabolism to acetaldehyde. Previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. Manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice. However, the role of H(2)O(2) in the behavioral effects caused by ethanol has not been clearly addressed. The present study investigated the effects of ebselen, an H(2)O(2) scavenger, on ethanol-induced locomotion.', 'Swiss RjOrl mice were pre-treated with ebselen (0-50mg/kg) intraperitoneally (IP) prior to administration of ethanol (0-3.75g/kg; IP). In another experiment, animals were pre-treated with ebselen (0 or 25mg/kg; IP) before caffeine (15mg/kg; IP), amphetamine (2mg/kg; IP) or cocaine (10mg/kg; IP) administration. Following these treatments, animals were placed in an open field to measure their locomotor activity. Additionally, we evaluated the effect of ebselen on the H(2)O(2)-mediated inactivation of brain catalase activity by 3-amino-1,2,4-triazole (AT).', 'Ebselen selectively prevented ethanol-induced locomotor stimulation without altering the baseline activity or the locomotor stimulating effects caused by caffeine, amphetamine and cocaine. Ebselen reduced the ability of AT to inhibit brain catalase activity.'] Does the H2O2 scavenger ebselen decrease ethanol-induced locomotor stimulation in mice? | qiaojin/PubMedQA | 2 | [
-2.3509833812713623,
-1.1914341449737549,
2.558737277984619
] |
['The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier.', 'Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice.', 'In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal and submucosal layers correlating with changes in proinflammatory cytokine profiles and a progressive transition from acute to chronic inflammation of the colon. Tissue-associated bacteria levels peaked at day 21 post-DSS and declined thereafter, correlating with recruitment of innate immune cells and development of the adaptive immune response. Histological parameters, immune cell infiltration and cytokine biomarkers of inflammation were indistinguishable between Nod2 and WT littermates following DSS, however, Nod2 KO mice demonstrated significantly higher tissue-associated bacterial levels in the colon. DSS damage and Nod2 genotype independently regulated the community structure of the colon microbiota.'] Do host genetics and environmental factors regulate ecological succession of the mouse colon tissue-associated microbiota? | qiaojin/PubMedQA | 2 | [
-2.6905734539031982,
-0.8911685943603516,
2.6981711387634277
] |
['The aim of this study was to determine (1) the effect of various scan delays on pixel intensity measurements and (2) the diagnostic accuracy of occlusal caries detection.', '72 non-cavitated extracted human permanent molar teeth with sound and carious occlusal surfaces were radiographed using the DIGORA® storage phosphor plates (SPPs) (Soredex Corporation, Helsinki, Finland). Plates were scanned immediately and 10 min, 30 min, 60 min and 120 min after exposure. Three different plates were used for each scan delay. An aluminium (Al) wedge was used to evaluate the change in mean grey values (MGVs) for scan delays. Diagnostic accuracy for occlusal caries detection was performed by scoring all the digital images. The true presence of caries was determined by stereomicroscopy. Comparison of MGVs of the Al wedge for immediate and delayed scans was made using repeated measures analysis of variance (ANOVA) and Tukey-Kramer tests. The accuracy was expressed as the area under the receiver operating characteristics curves (A(z)). A(z)s were compared using two-way ANOVA and t-tests. Kappa was used to measure inter and intraobserver agreement.', 'The mean A(z)s of immediately scanned plates were higher than the A(z)s of plates scanned with four different delays (p < 0.05). The A(z) of immediately scanned images was significantly higher than the A(z)s of images with 60 min and 120 min scan delays (p < 0.05) but not for 10 min and 30 min delays (p > 0.05). MGVs of immediately scanned plates were significantly higher than the plates scanned with four different delays (p < 0.05). Agreement decreased with increasing scan delays.'] Does the effect of delayed scanning of storage phosphor plate on occlusal caries detection? | qiaojin/PubMedQA | 2 | [
-1.2224414348602295,
-1.6478891372680664,
1.948904275894165
] |
['The etiology of Condylar hyperplasia (CH) of human temporomandibular joint (TMJ) remains largely unknown. Our previous study has demonstrated that enriched insulin-like growth factor-1(IGF-1) was expressed in the proliferation and hypertrophic layers of CH cartilage. Accordingly, this study was aimed to investigate whether IGF-1 regulates CH chondrocytes proliferation in condylar cartilage overgrowth and explore the molecular mechanism of IGF-1 involved in.', 'Chondrocytes were isolated from 6 CH and 3 normal cartilage (NC) specimens and cultured in alginate beads or monolayer, treated with IGF-1 or specific inhibitors such as 7-[trans-3-[(azetidin-1-yl)methyl]cyclobutyl]-5-(3-benzyloxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (NVP-AEW541), U0126, and LY294002. Thereafter, cellular proliferation capacity was evaluated by Cell Viability Analyzer (alginate beads culture) or 3-(4,5-dimethylthiazo(-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (monolayer culture). Gene expression levels of IGF-1, IGF-1 receptor (IGF-1R), collagen type II, type X and those genes associated with proliferation were evaluated by realtime PCR. Protein levels of IGF-1 and IGF-1R synthesized by CH chondrocytes were accessed by enzyme-linked immunosorbent assay (ELISA) and western blotting.', 'CH chondrocytes enhanced cellular proliferation capacity and expressed significantly higher levels of messenger RNA (mRNA) and protein expressions of IGF-1 and IGF-1R, as compared with NC chondrocytes. Furthermore, enriched IGF-1 enhanced CH chondrocytes proliferation, up-regulated the expressions of specific genes associated with cellular proliferation and elevated the gene expression of collagen type II A1 (COL2A1). Besides, IGF-1-mediated CH chondrocytes proliferation mainly depended on the mitogen-activated protein kinase (MAPK)-ERK pathway.'] Does insulin-like growth factor-1 boost the developing process of condylar hyperplasia by stimulating chondrocytes proliferation? | qiaojin/PubMedQA | 2 | [
-2.3834891319274902,
-1.352290391921997,
2.7907235622406006
] |
["What's known on the subject? and What does the study add? Positive surgical margins (PSMs) after radical prostatectomy are common, although their impact on the risk of disease recurrence is unknown. We examined the impact of PSMs on the risk of 'significant' biochemical recurrence stratified by their risk of occult metastatic disease. We find that only in intermediate-risk disease does the presence of a PSM have a significant impact on the risk of recurrence, and this represents a failure of technique. By contrast, for high- and low-risk disease, the risk of recurrence is driven by intrinsic tumour biology, and the presence of a PSM has little impact on outcome.", 'To determine the impact of surgical margin status on the risk of significant biochemical recurrence (prostate-specific antigen [PSA] doubling time <3, <6 or <9 months) after prostatectomy.', 'Patients undergoing radical prostatectomy with complete clinical and pathological data and detailed PSA follow-up were identified from two prospectively recorded databases. Patients were stratified according to their risk of occult systemic disease (low risk: PSA < 10 ng/dL, pT2 stage and Gleason score ≤6; intermediate risk: PSA 10-20 ng/dL, pT2 stage and/or Gleason score 7; high: PSA > 20 ng/dL or pT3-4 stage or Gleason score 8-10) and the impact of a positive surgical margin (PSM) within each stratum determined by univariable and multivariable analysis.', 'Of 1514 patients identified, 276 (18.2%), 761 (50.3%) and 477 (31.5%) were classified as having low-, intermediate- and high-risk disease respectively. A total of 370 (24.4%) patients had a PSM and with a median follow-up of 22.2 months, and 165 (7%) patients had a biochemical recurrence. Sufficient PSA data was available to calculate PSA doubling times in 151/165 patients (91.5%). The PSM rate rose significantly, from 11% in low-risk to 43% in high-risk disease (P < 0.001), with similar positive associations noted with tumour grade, stage and serum PSA (P < 0.001). Patients with low-risk disease had essentially identical risks of significant biochemical recurrence over the study period, regardless of surgical margin status. By contrast, in patients with both intermediate- and high-risk disease, a PSM was a strong predictor of significant biochemical recurrence on univariable analysis. On multivariable analysis, howver, PSM predicted significant disease recurrence in intermediate-risk disease only.'] Are positive surgical margins a risk factor for significant biochemical recurrence only in intermediate-risk disease? | qiaojin/PubMedQA | 2 | [
-1.587234616279602,
-1.4554734230041504,
2.076845645904541
] |
['Idiopathic and inflammation-dependent fibrotic diseases such systemic sclerosis (SSc) impose a major burden on modern societies. Understanding endogenous mechanisms, which counteract fibrosis, may yield new therapeutic approaches. Lipoxins are highly potent lipid mediators, which have recently been found to be decreased in SSc.', 'To determine the potential role of 12/15-lipoxygenase (12/15-LO), the key enzyme for the synthesis of lipoxins, in fibrosis.', 'Two mouse models for experimental dermal fibrosis (bleomycin-induced dermal fibrosis and tight-skin 1 mouse model) together with bone marrow transfers were used in wildtype and 12/15-LO(-/-) mice to elucidate the role of this enzyme during dermal fibrosis. Primary dermal fibroblasts of wildtype and 12/15-LO(-/-) mice, and 12/15-LO-derived eicosanoids, were used to identify underlying molecular mechanisms', 'In both models, 12/15-LO(-/-) mice exhibited a significant exacerbation of the fibrotic tissue response. Bone marrow transfer experiments disclosed a predominant role of mesenchymal cell-derived 12/15-LO in these antifibrotic effects. Indeed, 12/15-LO(-/-) fibroblasts showed an enhanced activation of the mitogen-activated protein-kinase pathway and an increased col 1a2 mRNA expression in response to stimulation with transforming growth factor β (TGFβ), whereas 12/15-LO-derived eicosanoids blocked these TGFβ-induced effects.'] Does the 12/15-lipoxygenase pathway counteract fibroblast activation and experimental fibrosis? | qiaojin/PubMedQA | 2 | [
-2.4238345623016357,
-1.2655836343765259,
2.6929399967193604
] |
['Reverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis (RA) patients is impaired when compared to healthy controls.', "HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Assays of cholesterol efflux, HDL's antioxidant function and paraoxanase-1 (PON-1) activity were performed as described previously. Plasma myeloperoxidase (MPO) activity was assessed by a commercially available assay.", "Mean cholesterol efflux capacity of HDL was not significantly different between RA patients (40.2% ± 11.1%) and controls (39.5% ± 8.9%); p=0.75. However, HDL from RA patients with high disease activity measured by a disease activity score using 28 joint count (DAS28>5.1), had significantly decreased ability to promote cholesterol efflux compared to HDL from patients with very low disease activity/clinical remission (DAS28<2.6). Significant correlations were noted between cholesterol efflux and the DAS28 (r=-0.39, p=0.01) and erythrocyte sedimentation rate, (r=-0.41, p=0.0009). Higher plasma MPO activity was associated with worse HDL function (r=0.41/p=0.009 (antioxidant capacity); r=0.35, p=0.03 (efflux)). HDL's ability to promote cholesterol efflux was modestly but significantly correlated with its antioxidant function (r=-0.34, p=0.03)."] Is cholesterol efflux by high density lipoproteins impaired in patients with active rheumatoid arthritis? | qiaojin/PubMedQA | 2 | [
-1.5245683193206787,
-1.6749670505523682,
2.108729124069214
] |
['When performing cholecystectomy after gastrectomy, we often encounter problems, such as adhesions, nutritional insufficiency, and bowel reconstruction. The purpose of this study was to identify the factors related to surgical outcome of these associated procedures, with emphasis on the use of a laparoscopic approach.', 'We retrospectively analyzed data from 58 patients who had a history of cholecystectomy after gastrectomy. Differences between subgroups with respect to operation time, length of postoperative hospital stay, and complications were analyzed. To identify the factors related with outcomes of cholecystectomy after gastrectomy, we performed multivariable analysis with the following variables: common bile duct (CBD) exploration, laparoscopic surgery, gender, acute cholecystitis, history of stomach cancer, age, body mass index, period of surgery, and interval between cholecystectomy and gastrectomy.', 'We found one case (2.9%) of open conversion. The CBD exploration was the most significant independent factor (adjusted odds ratio (OR), 45.15; 95% confidence interval (CI), 4.53-450.55) related to longer operation time. Acute cholecystitis also was a significant independent factor (adjusted OR, 14.66; 95% CI, 1.46-147.4). The laparoscopic approach was not related to operation time but was related to a shorter hospital stay (adjusted OR, 0.057; 95% CI, 0.004-0.74). Acute cholecystitis was independently related to the occurrence of complications (adjusted OR, 27.68; 95% CI, 1.15-666.24); however, CBD exploration and laparoscopic surgery were not. A lower BMI also was an independent predictor of the occurrence of complications (adjusted OR, 0.41; 95% CI, 0.2-0.87).'] Is multivariable analysis of cholecystectomy after gastrectomy : laparoscopy a feasible initial approach even in the presence of common bile duct stones or acute cholecystitis? | qiaojin/PubMedQA | 2 | [
-1.8714655637741089,
-1.4504698514938354,
2.3848283290863037
] |
['Persistent allergic rhinitis (PER) has a moderate impact on the sense of smell, but no controlled study has reported the effect of antihistamines on the loss of smell in patients with PER.', 'Patients with PER and subjective loss of the sense of smell (n = 27) were included in this pilot randomised, double-blind, placebo-controlled study. Nasal symptoms, nasal endoscopy, skin prick test, acoustic rhinometry, peak nasal inspiratory flow, nasal nitric oxide (nNO), and olfactometry (Barcelona Smell Test-24; BAST-24) were performed and evaluated in all PER patients at baseline and after 7 and 30 days of treatment with levocetirizine 5 mg or placebo.', 'The study population was randomized into two homogeneous groups: levocetirizine (n = 14) and placebo groups (n = 13). The evolution of symptoms reflected the therapeutic effect of levocetirizine treatment on rhinorrhea, nasal itching, eye itching, sneezing, and the total symptoms score after 7 and 30 days. Significant improvement in loss of smell by a visual analog scale (VAS) was observed after 7 days of levocetirizine treatment (7.2 ± 4.3; p < 0.05) compared to placebo (-9.4 ± 6.2). Improvement in smell identification by BAST-24 was strongly correlated (r = 0.72; p < 0.05) with smell improvement by VAS after 30 days. After 7 days of treatment with levocetirizine, the nNO values decreased (-494 ± 188) compared to placebo (155 ± 284 ppb; p < 0.05).'] Is the loss of smell in persistent allergic rhinitis improved by levocetirizine due to reduction of nasal inflammation but not nasal congestion ( the CIRANO study )? | qiaojin/PubMedQA | 2 | [
-1.9526699781417847,
-1.5283198356628418,
2.4552090167999268
] |
['It is well known that port-wine stains of the upper part of the face may herald abnormalities of the brain or eye in the form of Sturge-Weber syndrome. This study focuses on other extracutaneous anomalies in patients with nevi flammei of the head and neck, giving rise to functional complications.', 'A retrospective study was performed on patients with port-wine stains involving the head and neck area. Records were reviewed for demographic parameters, extent of the lesion, clinical complications, diagnostic measures, previous treatments, ultimate therapeutic approach, and outcome.', 'Nine patients, mean age 50.4 years, with port-wine stains and clinical symptoms due to extracutaneous involvement, were admitted and treated from 2006 to 2009. Major clinical features included macrocheilia in three cases, gingival bleeding in two, dysphonia with globus sensation, painful parotideal swelling with recurrent otitis, painful lingual swelling, recurrent epistaxis, and nasal obstruction in one case each. Cases with lower lip hypertrophy were treated by conventional surgical approaches. Recurrent epistaxis and nasal obstruction due to affected inferior turbinate were treated by Nd:YAG laser therapy, and globus sensation and dysphonia by speech therapy. Patients with gingival affection and recurrent otitis were treated by local ear care.'] Are port-wine stains more than skin-deep ! Expanding the spectrum of extracutaneous manifestations of nevi flammei of the head and neck? | qiaojin/PubMedQA | 2 | [
-2.4400322437286377,
-1.244394063949585,
2.755764961242676
] |
['A-to-I RNA editing is found in all phyla of animals and contributes to transcript diversity that may have profound impacts on behavior and physiology. Many transcripts of genes involved in axonal conductance, synaptic transmission and modulation are the targets of A-to-I RNA editing. There are a number of methods to measure the extent of A-to-I RNA editing, but they are generally costly and time consuming. One way to determine the frequency of A-to-I RNA editing is the peak height ratio method, which compares the size of peaks on electropherograms that represent unedited and edited sites.', 'Sequencing of 4 editing sites of the Dα6 nicotinic acetylcholine receptor subunit with an antisense primer (which uses T/C peaks to measure unedited and edited sites, respectively) showed very accurate and precise measurements of A-to-I RNA editing. The accuracy and precision were excellent for all editing sites, including those edited with high or low frequencies. The frequency of A-to-I RNA editing was comparable to the editing frequency as measured by clone counting from the same sample. Sequencing these same sites with the sense primer (which uses A/G peaks) yielded inaccurate and imprecise measurements.'] Does antisense sequencing improve the accuracy and precision of A-to-I editing measurements using the peak height ratio method? | qiaojin/PubMedQA | 2 | [
-1.6737443208694458,
-1.0930211544036865,
1.7159863710403442
] |
['We investigated the roles of neuronal-derived nitric oxide (NO) in the modulation of spontaneous activity of mouse detrusor smooth muscle.', 'Detrusor smooth muscle strips were isolated from nNOS gene knock-out (nNOS(-/-) ) mice and their wild type siblings (nNOS(+/+) ). The properties of smooth muscle cells were assessed using intracellular electrophysiology and Ca(2+) imaging by laser-scanning confocal microscopy. The effects of an nNOS inhibitor, 7-nitro indazole (7-NI) on electrically evoked contractility were assessed using nNOS(+/+) mouse detrusor strips.', 'In spontaneously active cells, the frequency of spontaneous action potentials (sAPs) and whole cell Ca(2+) flashes in nNOS(-/-) preparations was lower than that in the nNOS(+/+) preparations. The frequency of sAPs was enhanced by a nitric oxide donor, diethylamine NONOate sodium salt (NONOate; 100\u2009µM), both when used alone and when the cGMP pathway was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 10\u2009µM). 7-NI (100\u2009µM) significantly suppressed the electrically evoked contraction of mouse detrusor strips.'] Does neuronal-derived nitric oxide modulate the activity of mouse detrusor smooth muscle? | qiaojin/PubMedQA | 2 | [
-2.2695982456207275,
-1.3892263174057007,
2.7089786529541016
] |
['Loss of clinical attachment and alveolar bone destruction are major symptoms of periodontitis, caused by not only the destructive effect of periodontopathic bacteria but also the overactive response of the host immune system against periodontal pathogens. The details of the participation of the immune system in the onset and progression of periodontitis are unclear. In this study, we attempted to determine whether the host immune system, and in particular the formation of immune complexes, is involved in the periodontal destruction.', 'We applied ovalbumin or lipopolysaccharide (LPS) as antigens and their specific immunoglobulin G (IgG) antibodies purified from rat serum to rat gingival sulcus alternately. Loss of attachment, alveolar bone destruction and the numbers of inflammatory cells infiltrating the periodontal tissue and osteoclasts on the alveolar bone surface were investigated histometrically. The formation of immune complex was confirmed by immunohistological staining of complement C1qB.', 'Loss of attachment and the presence of C1qB were observed histopathologically in both experimental groups. The group that had been treated with LPS and anti-LPS IgG showed greater loss of attachment. The number of inflammatory cells in the periodontal tissue was increased in both experimental groups, while osteoclasts at the alveolar bone crest were observed only in the group that had been treated with LPS and anti-LPS IgG.'] Is the formation of immune complexes involved in the acute phase of periodontal destruction in rats? | qiaojin/PubMedQA | 2 | [
-2.5466361045837402,
-1.1687239408493042,
2.8149633407592773
] |
['We have recently found that Wnt-5a regulates the synaptic structure and function in hippocampal neurons. This ligand is expressed in the hippocampus, stimulates dendritic spine morphogenesis and increases glutamatergic neurotransmission. Moreover, we have also shown that Wnt-5a induces the clustering of PSD-95.', 'To explore the role of Wnt-5a in the formation of synaptic contacts.', 'Primary rat hippocampal neurons were exposed to a formylated hexapeptide (Foxy-5) derived from the sequence of Wnt-5a to study synapse formation and function.', 'In short-term experiments, Wnt-5a only induced the clustering of PSD-95 but had no effect on the density of presynaptic puncta, while in long-term experiments, it induced both pre- and postsynaptic protein clustering and the number of synaptic contacts, in agreement with electrophysiological studies. In long-term experiments, Foxy-5 increased miniature excitatory postsynaptic current amplitude and frequency.'] Is wnt-5a a synaptogenic factor with neuroprotective properties against Aβ toxicity? | qiaojin/PubMedQA | 2 | [
-2.5161678791046143,
-1.127095103263855,
2.635596990585327
] |
['Thrombin activatable fibrinolysis inhibitor (TAFI) has been reported to be involved in the pathogenesis and progression of inflammatory bowel disease (IBD). Activated TAFI (TAFIa) attenuates fibrinolysis by cleaving C-terminal lysine residues thus down-regulating plasminogen activation. To date, no reports on TAFIa in IBD have been published.', "Plasma levels of TAFIa were measured using a functional assay in 55 consecutive patients with ulcerative colitis (UC) and 50 with Crohn's disease (CD). Associations of TAFIa with disease activity, hemostatic variables and inflammatory markers were assessed.", 'Plasma TAFIa was higher in CD patients than in those with UC. The disease activity correlated positively with TAFIa levels in the UC group, but not in the CD group. In UC patients, there were positive correlations of TAFIa with white blood cells, C-reactive protein and fibrinogen and an inverse correlation with albumin. In the CD group, a positive correlation was shown for C-reactive protein, fibrinogen and platelet count, while a negative correlation was noted for albumin.'] Is activated thrombin activatable fibrinolysis inhibitor ( TAFIa ) associated with inflammatory markers in inflammatory bowel diseases TAFIa level in patients with IBD? | qiaojin/PubMedQA | 2 | [
-2.2689313888549805,
-1.3773291110992432,
2.6304619312286377
] |
['To compare the biological, technical and aesthetic outcomes of single implant-supported all-ceramic versus metal-ceramic crowns.', 'Thirty-six patients with premolar agenesis were randomly treated with 38 all-ceramic (AC) and 37 metal-ceramic (MC) implant-supported single-tooth restorations. A quasi-randomisation of consecutively included restorations in patients with one or more implants was used, i.e. a combination of parallel group (for 13 patients with one restoration) and split-mouth (for 23 patients with ≥2 restorations). All patients were recalled for baseline and 1-year followup examinations. Biological and technical outcomes, including complications, were clinically and radiographically registered. The Copenhagen Index Score and visual analogue scale (VAS) score were used to assess professional and patient-reported aesthetic outcomes, respectively, by blinded assessors.', 'One-year after loading, no patient dropped out and no implant failed, though one MC restoration had to be remade. The marginal bone loss was not significantly different between AC and MC restorations (AC: mean 0.08 mm, SD 0.25; MC: mean 0.10 mm, SD 0.17). Seven out of 10 inflammatory reactions were registered at AC restorations. Two technical complications, one loss of retention and one chipping of veneering porcelain were recorded at two metal-ceramic crowns. The marginal adaptation of the all-ceramic crowns was significantly less optimal than the metal-ceramic crowns (P = 0.014). The professional-reported colour match of all-ceramic crowns was significantly better than metal-ceramic crowns (P = 0.031), but other aesthetic parameters as well as the VAS scores demonstrated no statistically significant difference between AC and MC restorations.'] Do a 1-year randomised controlled trial comparing zirconia versus metal-ceramic implant supported single-tooth restorations? | qiaojin/PubMedQA | 2 | [
-1.4931894540786743,
-1.6734952926635742,
2.1860039234161377
] |
['This study was carried out to identify the occurrence, type, location, and severity of dental injuries (DIs), as well as predictors for DIs, in pediatric patients with facial fractures.', 'This study examined the files of patients aged 16 years or less who had sustained facial fractures during a 12-year period. The outcome variable was DI. The explanatory variables included gender, age, trauma mechanism, and type of facial fracture. Data analysis was carried out with the χ(2) test and logistic regression analysis.', 'A total of 200 patients, 119 (59.5%) of whom were boys, met the inclusion criteria. The mean age was 12.6 years. A total of 45 patients (22.5%) had DIs. Crown fracture, the most common type of DI, occurred in 59.9% of all DIs. The most common location of crown fractures was in the premolars (37.4% of all crown fractures). Multiple DIs occurred in 71.1% of those with DIs and severe DI in 66.7%. DIs were significantly associated with motor vehicle collision (MVC) (P = .02) and mandibular fracture (P = .03).'] Are dental injuries in pediatric patients with facial fractures frequent and severe? | qiaojin/PubMedQA | 2 | [
-1.730950951576233,
-0.9061371088027954,
1.6768152713775635
] |
['Epigenetic changes in DNA methylation have recently been demonstrated to be involved in effector T-cell polarization, resulting in differential secretion of T(H)1 and T(H)2 cytokines. However, the contribution to the development of a chronic inflammatory phenotype remains still unclear.', 'We sought to investigate changes in DNA methylation in marker genes of T-cell subsets during allergen sensitization/challenge and their influence on the development of an allergic airway inflammatory response.', 'The relationship between changes in DNA methylation and phenotype development were examined in a well-established model of experimental asthma. DNA methylation was investigated at genomic loci associated with T(H)1 (IFNG promoter) or T(H)2 (conserved noncoding sequence 1 [CNS1]) cytokine production by using bisulfite pyrosequencing.', 'Analysis of CD4(+) T cells revealed a significant increase in DNA methylation at the IFNG promoter after allergen sensitization/challenge, which correlated with decreased IFN-γ cytokine expression, whereas only minor changes were observed at the CNS1 locus. Furthermore, the increase in DNA methylation at the IFNG promoter could be reversed with a DNA methyltransferase (DNMT) inhibitor in\xa0vitro and in\xa0vivo with beneficial effects on sensitization status and allergic phenotype. The specific importance of the DNA methylation status in CD4(+) T cells could be confirmed by using adoptive transfer experiments.'] Does dNA methylation of TH1/TH2 cytokine genes affect sensitization and progress of experimental asthma? | qiaojin/PubMedQA | 2 | [
-2.5064895153045654,
-1.1777549982070923,
2.7434098720550537
] |
['IL-9-secreting (T(H)9) T cells are thought to represent a distinct T-cell subset. However, evidence for their functionality in disease is uncertain.', 'To define a functional phenotype for T(H)9-driven pathology in vivo.', 'We used fluorescence-activated cell sorting to identify circulating T(H)9 cells in atopic and nonatopic subjects. In mice we utilized a model of allergic airways disease induced by house dust mite to determine T(H)9 cell function in vivo and the role of activin A in T(H)9 generation.', 'Allergic patients have elevated T(H)9 cell numbers in comparison to nonatopic donors, which correlates with elevated IgE levels. In a murine model, allergen challenge with house dust mite leads to rapid T(H)9 differentiation and proliferation, with much faster kinetics than for T(H)2 cell differentiation, resulting in the specific recruitment and activation of mast cells. The TGF-β superfamily member activin A replicates the function of TGF-β1 in driving the in vitro generation of T(H)9 cells. Importantly, the in vivo inhibition of T(H)9 differentiation induced by allergen was achieved only when activin A and TGF-β were blocked in conjunction but not alone, resulting in reduced airway hyperreactivity and collagen deposition. Conversely, adoptive transfer of T(H)9 cells results in enhanced pathology.'] Do activin A and TGF-β promote T ( H ) 9 cell-mediated pulmonary allergic pathology? | qiaojin/PubMedQA | 2 | [
-2.658607006072998,
-1.037517786026001,
2.701908588409424
] |
['The mechanisms underlying the effects of estrogen on endometrial cancer remain undefined. Although the classical mechanism of the action of estrogen involves binding to the estrogen receptors α and β, and transduction of the signal into the cell, G protein-coupled receptor (GPR) 30 has been shown to mediate nongenomic estrogen signaling. The goal of this study was to determine the role of GPR30 signal in the basic process such as invasion and carcinogenesis of endometrial cancer.', 'We downregulated the expression of GPR30 in endometrial cancer cell line RL95-2 by transfection with shGPR30-pGFP-V-RS, a GPR30 antisense expression vector. The cells were then subjected to an MTT assay and a Transwell(®) migration assay. And an animal model was also used to investigate the influence of downregulation of GPR30 on oncogenesis.', 'Downregulation of GPR30 led to reduced growth and invasion by cells treated with 17β-estradiol. And the capacity of transfected RL95-2 cells to promote tumorigenesis was weakened in vivo.'] Does estrogenic transmembrane receptor of GPR30 mediate invasion and carcinogenesis by endometrial cancer cell line RL95-2? | qiaojin/PubMedQA | 2 | [
-2.545480489730835,
-1.0700924396514893,
2.6472742557525635
] |
['The purpose of this study was to determine whether, in surgical infants requiring parenteral nutrition (PN), septicaemia due to enterococci or Gram-negative bacilli occurs later than septicaemia due to coagulase-negative staphylococci (CNS).', "We retrospectively studied 112 consecutive surgical infants (corrected gestational age up to 3 months) receiving PN for at least 5 days for congenital or acquired intestinal anomalies over a 2-year period (July 2007-June 2009). Data collected included diagnosis, duration of PN, episodes of septicaemia (defined as growth of bacteria from blood culture), and organisms cultured. We compared the time to first occurrence of septicaemia due to CNS with the times to first occurrence of septicaemia due to enterococci, Gram-negative bacilli, or other micro-organisms, using Kruskal-Wallis nonparametric ANOVA test and Dunn's multiple comparisons test. Data are given as median (range).", '31 patients (28%) had a total of 65 episodes of septicaemia. Septicaemia due to CNS was most common, occurring in 22% of patients, after 17 days (1-239) of PN. Septicaemia due to enteric organisms was less common and occurred significantly later, at 59 (24-103) days for enterococci (p<0.01), and at 55 (30-106) days for Gram-negative bacilli (p<0.05).'] Is septicaemia due to enteric organisms a later event in surgical infants requiring parenteral nutrition? | qiaojin/PubMedQA | 2 | [
-1.5994623899459839,
-1.2033634185791016,
1.9585705995559692
] |
['This study investigated a potential interaction between the triallelic polymorphism of the serotonin transporter gene (SLC6A4) promoter and the experience of childhood trauma on the number of problem eating behaviors.', 'The study sample was comprised of 439 (64.7% female) Caucasian college students (mean age = 22.49, SD = 6.12). Participants completed questionnaires that assessed eating problems and experience of trauma in childhood (ages 0-12) and donated cheek cells for 5-HTTLPR and rs25531 genotyping.', 'Women carrying a lower expressing allele (i.e., L(G) or S) who were exposed to higher levels of childhood trauma reported significantly higher mean numbers of eating problems (gender × genotype × trauma interaction, p = .006).'] Is association between the serotonin transporter triallelic genotype and eating problems moderated by the experience of childhood trauma in women? | qiaojin/PubMedQA | 2 | [
-2.265744209289551,
-0.8580959439277649,
2.2619056701660156
] |
['Toll-like receptors (TLRs) are expressed by a variety of cells, including intestinal epithelia. However, the full spectrum of regulators modulating innate responses via TLRs has not been delineated. Tribbles (Trib) have been identified as a highly conserved family of kinase-like proteins. We sought to clarify the role of Trib2 in the TLR signaling pathway.', 'Trib2 mRNA and protein levels were analyzed by quantitative polymerase chain reaction (PCR) and western blot, respectively. Immunohistochemical staining was used to determine the expression of Trib2 in human tissue. Involvement of Trib2 in nuclear factor kappa B (NF-κB) pathways was assessed in epithelial cells by NF-κB reporter assay. Proteins that interacted with Trib2 were identified by mass spectrometry and confirmed by immunoprecipitation. The domain essential for Trib2 function was mapped using truncated constructs.', 'Trib2 expression is decreased in active inflamed tissue from patients with inflammatory bowel disease (IBD). Trib2 is expressed in human and mouse colonic epithelium as well as immune cells, and its expression in epithelium is inducible in a ligand-dependent manner by TLR5 ligand stimulation. Trib2 inhibits TLR5-mediated activation of NF-κB downstream of TRAF6. Trib2 selectively modulates mitogen-activated protein kinase (MAPK) pathways p38 and Jun N-terminal kinase (JNK) but not p44/p42 (ERK1/2). NF-κB2 (p100) was identified as a Trib2 binding partner in regulating the TLR5 signaling pathway that leads to inhibition of NF-κB activity. Residues 158-177 in the Trib2 kinase-like domain are required for Trib2 function.'] Is tribbles 2 ( Trib2 ) a novel regulator of toll-like receptor 5 signaling? | qiaojin/PubMedQA | 2 | [
-2.26735258102417,
-1.2228492498397827,
2.5166759490966797
] |
['We had shown that dienogest (DNG) + testosterone undecanoate (TU) induced complete sperm suppression in rats when administered together every 45 days. On the other hand, individual drugs given alone in a similar fashion failed to achieve the same result.', 'The present study was therefore undertaken to determine the reason for such a differential sperm suppression and to correlate it with the expression of steroidogenic enzyme genes in the rat testis.', 'Administration of DNG (40 mg/kg body weight [bw]) + TU (25 mg/kg bw) every 45 days for a duration of 90 days induced spermatogenic arrest, leading to a significant reduction in testicular weight and number of precursor germ cells. Flow cytometric analysis further confirmed the same result, leading to a significant shift in the distribution of haploid cells. Measurement of testosterone (serum and intratesticular) was significantly low. Complete sperm suppression coincided with significant down-regulation in the expression of upstream steroidogenic enzyme genes represented serially by cytochrome P450 side-chain cleavage, P450 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein (StAR) in the testis. On the other hand, rats administered with either DNG or TU alone demonstrated incomplete sperm suppression in which the expression of all the above genes remained characteristically nonuniform.'] Is complete sperm suppression induced by dienogest plus testosterone undecanoate associated with down-regulation in the expression of upstream steroidogenic enzyme genes in rat testis? | qiaojin/PubMedQA | 2 | [
-2.454263925552368,
-1.2693524360656738,
2.7662696838378906
] |
['Recent studies suggest that tumor microenvironment (stroma) is important in carcinogenesis and progression. We sought to integrate global genomic structural and expressional alterations in prostate cancer epithelium and stroma and their association with clinicopathologic features.', 'We conducted a genome-wide LOH/allelic imbalance (AI) scan of DNA from epithelium and stroma of 116 prostate cancers. LOH/AI hot or cold spots were defined as the markers with significantly higher or lower LOH/AI frequencies compared with the average frequency for markers along the same chromosome. These data were then integrated with publicly available transcriptome data sets and our experimentally derived data. Immunohistochemistry on an independent series was used for validation.', 'Overall, we identified 43 LOH/AI hot/cold spots, 17 in epithelium and stroma (P < 0.001), 18 only in epithelium (P < 0.001), and eight only in stroma (P < 0.001). Hierarchical clustering of expression data supervised by genes within LOH/AI hot/cold spots in both epithelium and stroma accurately separated samples into normal epithelium, primary cancer, and metastatic cancer groups, which could not be achieved with data from only epithelium. Importantly, our experimental expression data of the genes within the LOH/AI hot/cold spots in stroma accurately clustered normal stroma from cancer stroma. We also identified 15 LOH/AI markers that were associated with Gleason score, which were validated functionally in each compartment by transcriptome data. Independent immunohistochemical validation of STIM2 within a stromal significant LOH marker (identified as associated with Gleason grade) confirmed its downregulation in the transition from moderate to high Gleason grade.'] Does integrated analysis reveal critical genomic regions in prostate tumor microenvironment associated with clinicopathologic phenotypes? | qiaojin/PubMedQA | 2 | [
-2.1548452377319336,
-1.3266770839691162,
2.544050931930542
] |
['To determine the prevalence and clinical significance of carotid sinus syndrome (CSS) and vasovagal syncope (VVS), the two common types of Neurally Mediated Syncope (NMS), in a cohort of older patients with unexplained falls.', 'Patients presenting with unexplained and accidental falls were identified from 200 consecutive admissions of falls in patients aged 65 years and older admitted to the Rapid Assessment Medical Unit (RAMU) in a teaching hospital. A sample of unexplained and accidental fallers underwent carotid sinus massage (CSM) and tilt table testing (TTT) as per a standardised protocol. Baseline characteristics, clinical variables and the prevalence of NMS were compared between the two groups.', 'Falls were unexplained in 26% of patients. The prevalence of NMS was 24% (5/21) among patients with unexplained falls who underwent assessment for NMS, whereas it was nil (0/17) in patients with accidental falls (P=0.050). The prevalence of previous falls was significantly higher in patients with unexplained falls (P=0.0025), but all other baseline characteristics were similar between the two groups.'] Does the prevalence of Neurally Mediated Syncope in older patients presenting with unexplained fall? | qiaojin/PubMedQA | 2 | [
-1.8940273523330688,
-0.7422744631767273,
1.6463220119476318
] |
['Compensatory trunk movements during gait, such as a Duchenne limp, are observed frequently in subjects with osteoarthritis of the hip, yet angular trunk movements are seldom included in clinical gait assessments. Hence, the objective of this study was to quantify compensatory trunk movements during gait in subjects with hip osteoarthritis, outside a gait laboratory, using a body-fixed-sensor based gait analysis. Frontal plane angular movements of the pelvis and thorax and spatiotemporal parameters of persons who showed a Duchenne limp during gait were compared to healthy subjects and persons without a Duchenne limp.', 'A Body-fixed-sensor based gait analysis approach was used. Two body-fixed sensors were positioned at the dorsal side of the pelvis and on the upper thorax. Peak-to-peak frontal plane range of motion (ROM) and spatiotemporal parameters (walking speed, step length and cadence) of persons with a Duchenne limp during gait were compared to healthy subjects and persons without a Duchenne limp. Participants were instructed to walk at a self-selected low, preferred and high speed along a hospital corridor. Generalized estimating equations (GEE) analyses were used to assess group differences between persons with a Duchenne limp, without a Duchenne limp and healthy subjects.', 'Persons with a Duchenne limp showed a significantly larger thoracic ROM during walking compared to healthy subjects and to persons without a Duchenne limp. In both groups of persons with hip osteoarthritis, pelvic ROM was lower than in healthy subjects. This difference however only reached significance in persons without a Duchenne limp. The ratio of thoracic ROM relative to pelvic ROM revealed distinct differences in trunk movement patterns. Persons with hip osteoarthritis walked at a significantly lower speed compared to healthy subjects. No differences in step length and cadence were found between patients and healthy subjects, after correction for differences in walking speed.'] Do subjects with hip osteoarthritis show distinctive patterns of trunk movements during gait-a body-fixed-sensor based analysis? | qiaojin/PubMedQA | 2 | [
-1.8419550657272339,
-0.9463759064674377,
1.8840444087982178
] |
['Nicotinic acid (NA) treatment has been associated with benefits in atherosclerosis that are usually attributed to effects on plasma lipoproteins. The NA receptor GPR109A is expressed in monocytes and macrophages, suggesting a possible additional role for NA in modulating function of these immune cells. We hypothesize that NA has the potential to act directly on monocytes to alter mediators of inflammation that may contribute to its antiatherogenic effects in vivo.', 'In human monocytes activated by Toll-like receptor (TLR)-4 agonist lipopolysaccharide, NA reduced secretion of proinflammatory mediators: TNF-α (by 49.2±4.5%); interleukin-6 (by 56.2±2.8%), and monocyte chemoattractant protein-1 (by 43.2±3.1%) (P<0.01). In TLR2 agonist, heat-killed Listeria monocytogenes-activated human monocytes, NA reduced secretion of TNF-α (by 48.6±7.1%), interleukin-6 (by 60.9±1.6%), and monocyte chemoattractant protein-1 (by 59.3±5.3%) (P<0.01; n=7). Knockdown of GPR109A by siRNA resulted in a loss of this anti-inflammatory effect in THP-1 monocytes. However, inhibition of prostaglandin D2 receptor by MK0524 or COX2 by NS398 did not alter the anti-inflammatory effects of NA observed in activated human monocytes. Preincubation of THP-1 monocytes with NA 0.1 mmol/L reduced phosphorylated IKKβ by 42±2% (P<0.001) IKB-α by 54±14% (P<0.01). Accumulation of nuclear p65 NF-κB in response to lipopolysaccharide treatment was also profoundly inhibited, by 89±1.3% (n=4; P<0.01). NA potently inhibited monocyte adhesion to activated HUVEC, and VCAM, mediated by the integrin, very late antigen 4. Monocyte chemotaxis was also significantly reduced (by 45.7±1.2%; P<0.001).'] Are anti-inflammatory effects of nicotinic acid in human monocytes mediated by GPR109A dependent mechanisms? | qiaojin/PubMedQA | 2 | [
-2.1665022373199463,
-1.4152448177337646,
2.5957930088043213
] |
['Transforming growth factor-β1 (TGF-β1) is a profibrotic cytokine that plays a major role in vascular biology, and is known to regulate the phenotype and activity of various vascular cell populations. Because most fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), are associated with vascular remodeling, and as endothelial progenitor cells (EPCs) may be involved in this process, we investigated the impact of TGF-β1 modulation of EPC angiogenic properties.', 'TGF-β1 plasma levels were determined in 64 patients with IPF and compared with those in controls. The effect of TGF-β1 on angiogenesis was studied in vivo in a Matrigel plug model and in vitro on endothelial colony-forming cells (ECFCs). We studied the effects of inhibiting the expression of the three main receptors of TGF-β1 in ECFCs by using short interfering RNA.', 'Total TGF-β1 plasma levels were significantly increased in patients with IPF as compared with controls (P < 0.0001). TGF-β1 had proangiogenic effects in vivo by increasing hemoglobin content and blood vessel formation in Matrigel plugs implanted in C57/Bl6 mice, and in vitro by enhancing ECFC viability and migration. The effects were abolished by silencing the three main TGF-β1 receptors.'] Does the profibrotic cytokine transforming growth factor-β1 increase endothelial progenitor cell angiogenic properties? | qiaojin/PubMedQA | 2 | [
-2.426983118057251,
-1.2345221042633057,
2.671994686126709
] |
['We investigated axonal plasticity in the bilateral motor cortices and the long term therapeutic effect of Niaspan on axonal remodeling after stroke in type-1 diabetic (T1DM) rats.', 'T1DM was induced in young adult male Wistar rats via injection of streptozotocin. T1DM rats were subjected to 2h transient middle cerebral artery occlusion (MCAo) and were treated with 40 mg/kg Niaspan or saline starting 24 h after MCAo and daily for 28 days. Anterograde tracing using biotinylated dextran amine (BDA) injected into the contralateral motor cortex was performed to assess axonal sprouting in the ipsilateral motor cortex area. Functional outcome, SMI-31 (a pan-axonal microfilament marker), Bielschowsky silver and synaptophysin expression were measured. In vitro studies using primary cortical neuron (PCN) cultures and in vivo BDA injection into the brain to anterogradely label axons and terminals were employed.', 'Niaspan treatment of stroke in T1DM-MCAo rats significantly improved functional outcome after stroke and increased SMI-31, Bielschowsky silver and synaptophysin expression in the ischemic brain compared to saline treated T1DM-MCAo rats (p<0.05). Using BDA to anterograde label axons and terminals, Niaspan treatment significantly increased axonal density in ipsilateral motor cortex in T1DM-MCAo rats (p<0.05, n=7/group). Niacin treatment of PCN significantly increased Ang1 expression under high glucose condition. Niacin and Ang1 significantly increased neurite outgrowth, and anti-Ang1 antibody marginally attenuated Niacin induced neurite outgrowth (p=0.06, n=6/group) in cultured PCN under high glucose condition.'] Does niaspan increase axonal remodeling after stroke in type 1 diabetes rats? | qiaojin/PubMedQA | 2 | [
-2.193058490753174,
-1.4708696603775024,
2.6606369018554688
] |
["Circadian mechanisms play an important role in the regulation of sleep. A circadian clock-controlled gene, Tef, has been suggested to be associated with depressive symptoms, restless legs syndrome, and slow wave sleep in patients with sleep disorders. The present study sought to explore the association between Tef and sleep disturbances in patients with Parkinson's disease (PD).", 'Three hundred and ninety-two unrelated patients with PD were recruited for this study. All of them completed the PD Sleep Scale (PDSS) and other clinical and demographic assessments. rs738499, a single nucleotide polymorphism of the Tef gene, was genotyped by polymerase chain reaction-restriction fragment length polymorphism.', 'Mean total PDSS scores were 111.5 (standard deviation [SD] 23.0) in the TT genotype and 122.2 (SD 18.2) in the TG+GG genotypes (P<0.01). Significant differences were found between genotypes (TT vs TG+GG) for 14 item scores (all P<0.05). Total and item scores displayed negative associations with the TT genotype (all P<0.05) except Item 2 (P=0.178). Linear regression adjusted for gender, duration, depression and disease severity showed that the polymorphism could explain 0.9% of the variance in PDSS scores.'] Is tef polymorphism associated with sleep disturbances in patients with Parkinson 's disease? | qiaojin/PubMedQA | 2 | [
-1.7293345928192139,
-1.2243602275848389,
2.032991409301758
] |
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