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['Liver X receptors (LXRs) are important transcriptional regulators of lipid homeostasis and proliferation in several cell types. However, the roles of LXRs in pancreatic beta cells have not been fully established. The aim of this study was to investigate the effects of LXRs on pancreatic beta cell proliferation.', 'Gene expression was analysed using real-time RT-PCR. Transient transfection and reporter gene assays were used to determine the transcriptional activity of LXRs in pancreatic beta cells. Cell viability and proliferation were analysed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), DNA fluorometric, BrdU labelling and [(3)H]thymidine incorporation assays. Cell cycle distribution was investigated by flow cytometry analysis. Adenovirus-based RNA interference was used to knockdown LXRalpha, LXRbeta and p27 in MIN6 cells and mouse islets.', 'We found that both Lxralpha (also known as Nr1h3) and Lxrbeta (also known as Nr1h2) were expressed and transactivated the LXR response element in HIT-T15 and MIN6 cells. Activation of LXRs dose-dependently inhibited pancreatic beta cell viability and proliferation. This was accompanied by beta cell cycle arrest at the G1 phase. Furthermore, LXR activation increased levels of the p27 protein by inhibiting its degradation. Knockdown of p27 reversed these effects of LXR activation on growth inhibition and cell cycle arrest.'] Does activation of liver X receptors inhibit pancreatic islet beta cell proliferation through cell cycle arrest? | qiaojin/PubMedQA | 2 | [
-2.4327003955841064,
-1.274870753288269,
2.719571828842163
] |
['In-stent restenosis, or renarrowing within a coronary stent, is the most ominous complication of percutaneous coronary intervention, caused by vascular smooth muscle cell (VSMC) migration into and proliferation in the intima. Although drug-eluting stents reduce restenosis, they delay the tissue healing of the injured arteries. No promising alternative anti-restenosis treatments are currently on the horizon.', 'In endothelium-denudated mouse carotid arteries, oral morelloflavone-an active ingredient of the Thai medicinal plant Garcinia dulcis-significantly decreased the degree of neointimal hyperplasia, without affecting neointimal cell cycle progression or apoptosis as evaluated by Ki-67 and TUNEL staining, respectively. At the cellular level, morelloflavone robustly inhibited VSMC migration as shown by both scratch wound and invasion assays. In addition, morelloflavone prevented VSMCs from forming lamellipodia, a VSMC migration apparatus. Mechanistically, the inhibition by morelloflavone of VSMC migration was through its negative regulatory effects on several migration-related kinases, including FAK, Src, ERK, and RhoA. Consistently with the animal data, morelloflavone did not affect VSMC cell cycle progression or induce apoptosis.', 'These data suggest that morelloflavone blocks injury-induced neointimal hyperplasia via the inhibition of VSMC migration, without inducing apoptosis or cell cycle arrest.'] Does morelloflavone block injury-induced neointimal formation by inhibiting vascular smooth muscle cell migration? | qiaojin/PubMedQA | 2 | [
-2.511427640914917,
-1.2133187055587769,
2.8541007041931152
] |
['Bladder outlet obstruction with intravesical pressures exceeding 40 cmH(2)O results in a progressive increase in wall thickness, eventually causing low compliance. We investigated whether intravesical pressure induces hypertrophy and/or hyperplasia of human bladder smooth muscle cells (HBSMC) mediated by a muscarinic (M) receptor, and evaluated the relationship between intravesical pressure and M receptor antagonists.', 'HBSMC were exposed to 40 cmH(2)O pressure and/or acetylcholine (10 nM-100 microM) for 24h. Cells exposed to hydrostatic pressure were treated with either 1 microM AF-DX 16 (M(2) antagonist), 1 microM 4-DAMP (M(3) antagonist) or 1 microM atropine (both M(2) and M(3) antagonists). DNA and protein synthesis of HBSMC were measured by (3)H-thymidine and leucine incorporation assays, respectively.', '(3)H-thymidine incorporation increased following exposure to increasing concentrations of acetylcholine (at 100 microM, P<0.05). When cells were exposed to 40 cmH(2)O for 24h, (3)H-thymidine incorporation increased by 31.4%, 33.3% and 39.5% in 1 microM, 10 microM and 100 microM of acetylcholine, respectively. With exposure to 100 microM acetylcholine, a hydrostatic pressure of 40 cm, and both of these together, (3)H-thymidine incorporation increased by 16.7%, 25.9% and 39.4%, respectively, and leucine incorporation increased by 66.5%, 66.5% and 81.8%, respectively (P<0.05). Antimuscarinic agents had no apparent effect on the proliferative rate of cells grown at atmospheric pressure, but there was a dramatic decrease in thymidine and leucine incorporation for cells that were simultaneously exposed to increased hydrostatic pressure, most pronounced when the combined M(2)/M(3) receptor antagonist was applied.'] Does intravesical pressure induce hyperplasia and hypertrophy of human bladder smooth muscle cells mediated by muscarinic receptors? | qiaojin/PubMedQA | 2 | [
-2.0522961616516113,
-1.4919569492340088,
2.5643575191497803
] |
['We investigated the likelihood of finding vesicoureteral reflux (VUR) in patients with urinary tract infections (UTIs), accompanied by fever or dysfunctional elimination syndrome (DES).', "Two hundred consecutive voiding cystourethrograms performed in 1997-2002 for a diagnosis of UTI were reviewed. Fever, DES, and the grade and laterality of VUR were recorded. Patients were stratified into two groups by age to allow for assessment of DES symptoms in the older patient population: <2 years (n=68) and > or =2 years (n=132). Ratios were compared using a two-tailed Fisher's exact test.", 'Of the children> or =2 years old, 64/132 (48%) had VUR. Patients who were non-febrile with DES were less likely than patients who were febrile without DES to have VUR [12/34 (35%) vs 23/34 (68%), P=0.02], whereas the risk of dilating VUR [5/34 (15%) vs 11/34 (32%), P=0.15] and bilateral VUR [4/34 (12%) vs 11/34 (32%), P=0.08] was not statistically different. In febrile patients, the presence of DES was associated with a lower risk of VUR [22/51 (43%) vs 23/34 (68%), P=0.03] and dilating VUR [5/51 (10%) vs 11/34 (32%), P=0.01], but not bilateral VUR [8/51 (16%) vs 11/34 (32%), P=0.11].'] Is dysfunctional elimination syndrome a negative predictor for vesicoureteral reflux? | qiaojin/PubMedQA | 2 | [
-1.243573546409607,
-1.727133870124817,
1.9680118560791016
] |
['To determine whether T-wave axis on the resting electrocardiogram (ECG) is associated with coronary artery calcification (CAC) score, a measurement of coronary atherosclerosis, in older adults.', 'The sample consisted of 2004 adults aged 66 and over participating in the prospective, population-based Age-Gene/Environment Susceptibility-Reykjavik Study. The cohort was divided into gender-stratified quartiles based upon Agatston CAC score derived from computerized tomography. Frontal T-axis deviation from 45 degrees was assessed using surface ECG. Statistical analysis was performed with Tobit regression models adjusted for demographic and cardiovascular risk factors.', 'In the entire study population, T-axis deviation from 45 degrees was significantly associated with increasing CAC score in men (p<0.001) and women (p=0.03). In men without clinically recognized coronary heart disease (CHD), the association with CAC score remained statistically significant (p=0.02). This association was significant among women without CHD once male CAC cut points were used (p=0.05).'] Is abnormal T-wave axis associated with coronary artery calcification in older adults? | qiaojin/PubMedQA | 2 | [
-2.136361837387085,
-1.3377313613891602,
2.5474939346313477
] |
['Deliberate induction of hypercapnic acidosis protects against lung injury after nonseptic lung injury. In contrast, concerns exist regarding the effects of hypercapnic acidosis in the setting of severe pulmonary sepsis. The potential for the effects of hypercapnic acidosis to be neutrophil-mediated remains to be determined. We investigated whether hypercapnic acidosis--induced by adding CO2 to inspired gas--would protect against severe acute lung injury induced by pulmonary Escherichia coli instillation and the role of neutrophils in mediating this effect.', 'Prospective randomized animal study.', 'University Research Laboratory.', 'Adult male Sprague-Dawley rats.', 'In series 1, after induction of anesthesia and tracheostomy placement, animals were randomized to normocapnia (FICO2 0.00, n = 12) or hypercapnic acidosis (FICO2 0.05, n = 12). E. coli (0.5-3.0 x 10(15) colony-forming units) was instilled intratracheally and the animals were ventilated for 6 hrs to allow a severe acute lung injury to evolve. In series 2, animals were randomized to neutrophil depletion or nondepletion before bacterial instillation, in a three-group design: normocapnia alone (Normo + polymorphonuclear neutrophils [PMN], n = 9), normocapnia with neutrophil depletion (Normo - PMN, n = 9), or hypercapnic acidosis with neutrophil depletion (hypercapnic acidosis - PMN, n = 9). After intratracheal E. coli administration these animals were also ventilated for 6 hrs.', 'Hypercapnic acidosis protected against evolving pneumonia-induced acute lung injury, attenuating the increase in airway pressure, and the decrement in lung compliance and arterial PO2. However, hypercapnic acidosis did not reduce histologic injury. Hypercapnic acidosis also protected against evolving pneumonia-induced acute lung injury in the presence of neutrophil depletion, reducing both physiologic and histologic indices of lung injury.'] Does hypercapnic acidosis attenuate severe acute bacterial pneumonia-induced lung injury by a neutrophil-independent mechanism? | qiaojin/PubMedQA | 2 | [
-2.3497955799102783,
-1.376209020614624,
2.748765468597412
] |
['The high prevalence of Attention Deficit/Hyperactivity Disorder (ADHD) and the increased therapeutic use of methylphenidate (MPH) raise some concerns regarding its long-term side effects and safety profile. Considering that MPH effects on brain metabolism are poorly known and that creatine kinase (CK) plays an important role in cell energy homeostasis, we evaluated CK activity in the brain of young and adult rats following acute (one injection) or chronic (28 days) administration of MPH.', 'MPH was acutely or chronically administered to young and adult rats. For acute administration, a single injection of MPH was given to rats on postnatal day (PD) 25 or PD 60, in the young and adult groups, respectively. For chronic administration, MPH injections were given to young rats starting at PD 25 once daily for 28 days (last injection at PD 53). In adult rats, the same regimen was performed starting at PD 60 (last injection at PD 88). CK activity was measured in brain homogenates.', 'Our results showed that MPH acute administration increased the enzyme in prefrontal cortex, hippocampus, striatum and cerebral cortex, but not cerebellum of young and adult rats. Chronic administration of MPH also increased CK activity in these brain regions, as well as the cerebellum, in young and adult rats. The highest dose (10.0 mg/kg) presented more pronouncing effects.'] Does methylphenidate increase creatine kinase activity in the brain of young and adult rats? | qiaojin/PubMedQA | 2 | [
-2.1102454662323,
-1.0910859107971191,
2.302236318588257
] |
['To define inpatient care of obese children with or without an obesity diagnosis.', 'A total of 29,352 inpatient discharges (18,459 unique inpatients) from a tertiary children\'s hospital were analyzed. Body mass index (BMI) was calculated from measured height and weight. "Obesity" was defined as BMI >or=95th percentile by using Centers for Disease Control and Prevention 2000 growth charts. "Diagnosed obesity" was defined by primary, secondary or tertiary International Classification of Diseases, Ninth Revision codes for "obesity" or "overweight." Analyses controlled for multiple inpatient records per individual.', 'A total of 5989 discharges from the hospital (20.4%) were associated with obesity, but only 512 discharges (1.7%) indicated obesity as a diagnosis. An obesity diagnosis identified only 5.5% of inpatient days for obese inpatients. Obese patients with an obesity diagnosis (Ob/Dx) had fewer hospital discharges per person and shorter lengths of stay than obese patients without an obesity diagnosis (Ob/No Dx). Patients with Ob/Dx had higher odds of mental health, endocrine, and musculoskeletal disorders than non-obese inpatients, but Ob/No Dx patients generally did not.'] Does obesity identified by discharge ICD-9 codes underestimate the true prevalence of obesity in hospitalized children? | qiaojin/PubMedQA | 2 | [
-1.0217652320861816,
-0.9231266975402832,
1.0756211280822754
] |
['With improvements in long-term results after liver transplantation, chronic kidney disease (CKD) has become a highly relevant problem. The early measurement of the glomerular filtration rate (GFR) can identify those patients who are at risk of developing CKD years after liver transplantation. The aims of this study were to describe the prevalence of CKD 5 years after liver transplantation, to study the correlation between measured GFR early after transplantation and late renal function and to identify patients at risk of developing late CKD after liver transplantation.', 'A total of 152 patients who were at least 5 years post-liver transplantation were studied. Measured GFR with Chromium EDTA or iohexol clearance was followed-up for 5 years (n 52) and 10 years (n 41).', 'The overall decrease in measured GFR was 36% after 5 years and 42% after 10 years. Eight patients (5%) required renal replacement therapy. GFR levels pretransplantation showed a poor correlation with later renal function (at 5 years). The GFR measured at 3 months and 1 year post-transplantation correlated well with measured GFR at 5 years post-transplantation. Multivariate analysis showed that measured GFR of less than 30 ml at 3 months post-transplantation was significantly associated with CKD at 5 years post-transplantation.'] Is early renal function post-liver transplantation predictive of progressive chronic kidney disease? | qiaojin/PubMedQA | 2 | [
-1.453501582145691,
-1.1349594593048096,
1.6414289474487305
] |
['The aim of this study was to evaluate whether renal scars and vesicoureteral reflux (VUR) are associated with bladder dysfunction in children after first clinical pyelonephritis.', 'Sixty-four children were evaluated with urodynamics and voiding cystourethrography at a median of 8 weeks after their first episode of clinical pyelonephritis. All patients had ultrasonography and dimercaptosuccinic acid (DMSA) scintigraphy during the infection. After 2 years, DMSA scintigraphy was repeated in 58 patients. Re-infections were recorded.', 'Overactive detrusor was found in 27 (42%) patients. There was no significant difference in the incidence of overactive detrusor between boys and girls. The maximal voiding pressure was higher in boys (median 92.5, range 48-191 cmH(2)O) than in girls (median 82, range 37-150 cmH(2)O) (P=0.0117). Thirty-one (48%) patients had renal defects in scintigraphy during the infection. Ultimately, 12 patients (21%) developed renal scars; 11 patients (17%) had VUR. Renal defects in DMSA scintigraphy and the presence of VUR were not associated with overactive detrusor or high voiding pressures.'] Are post-pyelonephritic renal scars associated with high voiding pressures? | qiaojin/PubMedQA | 2 | [
-2.1433558464050293,
-1.2389514446258545,
2.378720760345459
] |
['TG4010 is a recombinant MVA vector expressing the tumor-associated antigen MUC1 and IL2. We explored the effect two schedules of TG4010 on PSA in men with PSA progression.', 'A randomized phase II trial was conducted in 40 patients with PSA progression. Patients had PSA doubling times less than 10 months, with no overt evidence of disease. Patients received either weekly subcutaneous injection (sc) of TG4010 10(8) pfu for 6 weeks, then one injection every 3 weeks or sc injection of TG4010 10(8) pfu every 3 weeks.', 'The primary endpoint of a 50% decrease in PSA values from baseline was not observed. Nevertheless, 13 of 40 patients had a more than two fold improvement in PSA doubling time. Ten patients had their PSA stabilized for over 8 months. Therapy was well tolerated.'] Does mVA-MUC1-IL2 vaccine immunotherapy ( TG4010 ) improve PSA doubling time in patients with prostate cancer with biochemical failure? | qiaojin/PubMedQA | 2 | [
-1.7498054504394531,
-1.5234358310699463,
2.2982237339019775
] |
['High-density short oligonucleotide microarrays are a primary research tool for assessing global gene expression. Background noise on microarrays comprises a significant portion of the measured raw data, which can have serious implications for the interpretation of the generated data if not estimated correctly.', 'We introduce an approach to calculate probe affinity based on sequence composition, incorporating nearest-neighbor (NN) information. Our model uses position-specific dinucleotide information, instead of the original single nucleotide approach, and adds up to 10% to the total variance explained (R2) when compared to the previously published model. We demonstrate that correcting for background noise using this approach enhances the performance of the GCRMA preprocessing algorithm when applied to control datasets, especially for detecting low intensity targets.'] Does background correction using dinucleotide affinities improve the performance of GCRMA? | qiaojin/PubMedQA | 2 | [
-2.0308659076690674,
-0.8032059073448181,
2.026148796081543
] |
['Up to now, the measurement of carbohydrate-deficient transferrin (CDT) has been used in persons with a regular alcohol consumption of >60 g/day; primarily due to aspects of insurance medicine, as its levels have an informative value even at 2 to 3 weeks after the discontinuation of consumption.', 'In the literature concerning % CDT levels in individuals who used chemicals, medical drugs, food supplements and muscle-tissue increasing drugs there is scarce information, therefore these cases in this paper deserve interest.', 'The authors demonstrate the history and laboratory results of three cases. All of them were ethanol abstinent and they had used protein-containing food supplements for one or two months. The measurement of the % CDT showed elevated values.'] Is [ The level of carbohydrate-deficient transferrin highly increased in bodybuilders ]? | qiaojin/PubMedQA | 2 | [
-2.1845614910125732,
-0.24834755063056946,
1.6127110719680786
] |
['Advanced Glycation Endproducts (AGEs), implicated as one of the major causes of diabetic complications, either directly or via receptor mediated actions, trigger downstream events in the conduit vessels, microvascular bed as well as myocardium leading to microvascular and cardiac dysfunction. The aim of this study was to characterise the activity profile of TRC4149, a novel AGE breaker compound, to determine its ability to reduce the burden of AGEs in vitro and in vivo and to evaluate whether the reduced AGE burden could translate into improvement in hemodynamic function in a model of Streptozotocin induced diabetic Spontaneously Hypertensive Rats (SHR).', 'AGEs were prepared in vitro by incubating BSA and lysozyme with glucose or ribose while AGE-LDL was generated by copper catalyzed LDL oxidation. TRC4149 was evaluated using in vitro assays to determine its capacity to reduce the burden of AGEs and to test its antioxidant activity. To study the effect of TRC4149 on hemodynamic function, diabetic SHR implanted with telemetry transmitter were treated with TRC4149 (20 mg/kg i.p., b.i.d.) or vehicle for 14 weeks. Losartan was administered once per week and blood pressure was monitored telemetrically throughout the treatment period. Cardiac indices of systolic and diastolic function were assessed terminally using MacLab system. AGE load in aorta was determined immunohistochemically and VCAM expression was quantitated by real time PCR analysis.', 'TRC4149 was able to break preformed AGEs as well as reduce further AGE accumulation in vitro in a dose dependent manner. It also demonstrated a potent free radical scavenging activity. In diabetic SHR, treatment with TRC4149 retarded the decline in response to losartan over the study period, and also improved cardiac function as evidenced by an improved dP/dtmax/min, left ventricular systolic pressure and decreased left ventricular diastolic pressure as compared to untreated group. AGE load as well as VCAM expression in aorta was also reduced upon treatment.'] Does tRC4149 a novel advanced glycation end product breaker improve hemodynamic status in diabetic spontaneously hypertensive rats? | qiaojin/PubMedQA | 2 | [
-2.359560251235962,
-1.3968135118484497,
2.8105010986328125
] |
['In proliferative diabetic retinopathy (PDR) increased levels of cytokines, inflammatory cells and angiogenic factors are present.These factors increase the expression of cellular adhesion molecules (CAMs)The objective of this study was to investigate the association between the polymorphisms of the ICAM-1 gene (K469E, G241A) and the development of PDR among patients with type 2 diabetes in the Slovenian population (Caucasians).', 'For the purpose, 195 subjects with type 2 diabetes with PDR were compared with 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. We analysed serum ICAM levels in 54 subjects with type 2 diabetes and 25 subjects without diabetes.', 'A significantly higher frequency of the EE genotype of the K469E polymorphism of the ICAM-1 was found in the patients with PDR compared with those without diabetic retinopathy (OR = 2.0, 95% confidence interval [CI] = 1.1-3.5; P = 0.013), whereas the G241A polymorphism of the ICAM-1 gene failed to yield an association with PDR. Moreover, significantly higher sICAM-1 serum levels were demonstrated in diabetics with the EE genotype compared with those with the other (EK + KK) genotypes (918 +/-104 vs. 664 +/-209 microg/L; P = 0.001). The G241A polymorphism of the ICAM-1 gene, on the hand, failed to affect sICAM-1 serum levels in diabetics.'] Is k469E polymorphism of the intracellular adhesion molecule 1 gene associated with proliferative diabetic retinopathy in Caucasians with type 2 diabetes? | qiaojin/PubMedQA | 2 | [
-1.7962360382080078,
-1.5037583112716675,
2.2918548583984375
] |
['Most extracellular virulence factors produced by Bacillus cereus are regulated by the pleiotropic transcriptional activator PlcR. Among strains belonging to the B. cereus group, the plcR gene is always located in the vicinity of genes encoding the YvfTU two-component system. The putative role of YvfTU in the expression of the PlcR regulon was therefore investigated.', 'Expression of the plcR gene was monitored using a transcriptional fusion with a lacZ reporter gene in a yvfTU mutant and in its B. cereus ATCC 14579 parental strain. Two hours after the onset of the stationary phase, a stage at which the PlcR regulon is highly expressed, the plcR expression in the yvfTU mutant was only 50% of that of its parental strain. In addition to the reduced plcR expression in the yvfTU mutant, a few members of the PlcR regulon showed a differential expression, as revealed by transcriptomic and proteomic analyses. The virulence of the yvfTU mutant in a Galleria mellonella insect model was slightly lower than that of the parental strain.'] Is the YvfTU two-component system involved in plcR expression in Bacillus cereus? | qiaojin/PubMedQA | 2 | [
-2.3757710456848145,
-1.0983712673187256,
2.5216400623321533
] |
['To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment.', 'We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified.', 'Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1 +/- 1.4 vs. 33.9 +/- 1.9 cap/mm(2), p<0.01), during post-occlusive reactive hyperemia (29.3 +/- 1.9 vs. 38.2 +/- 2.2 cap/mm(2), p<0.01) and during venous congestion responses (31.4 +/- 1.9 vs. 41.1 +/- 2.3 cap/mm(2), p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1%. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98 +/- 0.05 vs. 1.17 +/- 0.04 mm/s, p<0.05).'] Does treatment of essential hypertension normalize capillary rarefaction? | qiaojin/PubMedQA | 2 | [
-1.9459251165390015,
-1.508141040802002,
2.4548816680908203
] |
['To determine if peripheral blood monocytes from patients with ankylosing spondylitis (AS) differed in protein expression compared to rheumatoid arthritis (RA) and healthy controls (HC).', 'Monocyte protein expression was characterised by 2D gel electrophoresis and by label-free quantitative expression profiling, using nano-ultra performance liquid chromatography coupled to electrospray ionisation mass spectrometry (ESI-MS(E), where (E) refers to low/high collision energy switching). Data sets were analysed using the Waters expression profiling system and Ingenuity pathway analysis (IPA).', 'Two-dimensional gel electrophoresis showed upregulation of proteasomal constituents in AS monocytes, including the beta subunit of proteasome activator (PA)28. Monocyte expression profiling and IPA showed that significant changes in protein expression within the ubiquitin proteasome pathway (UPP) were restricted to AS monocytes. Statistically significant differences in protein expression involving the leucocyte extravasation, vascular endothelial growth factor, integrin and Toll-like receptor signalling pathways were seen in AS and RA monocytes compared to healthy controls. No evidence of upregulation of proteins involved in the endoplasmic reticulum stress response pathway was found in either AS or RA monocytes. Finally, the PA28 complex was shown to increase the generation of human leucocyte antigen (HLA)-B27 antigenic epitopes by the proteasome in vitro.'] Do ankylosing spondylitis monocytes show upregulation of proteins involved in inflammation and the ubiquitin proteasome pathway? | qiaojin/PubMedQA | 2 | [
-2.4087941646575928,
-1.335502028465271,
2.860996723175049
] |
['Chemotherapy-induced diarrhea (CID) is a well recognized side effect of cancer treatment. However, the pathophysiology behind this debilitating side effect remains unclear. Irinotecan causes cholinergic and delayed onset diarrhea in patients, in which beta-glucuronidase produced by gut bacteria is thought to be involved.', 'Diarrhea occurred, as expected, following irinotecan treatment. beta-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp. and Clostridium spp. (all beta-glucuronidase producing) and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (beta-glucuronidase producing, major component of intestinal flora).', 'Rats were treated with 200 mg/kg irinotecan and killed at various time points up to 72 h. Rats were monitored for diarrhea. Sections were stained for beta-glucuronidase expression, and faecal DNA was analysed using real time PCR.'] Are faecal microflora and beta-glucuronidase expression altered in an irinotecan-induced diarrhea model in rats? | qiaojin/PubMedQA | 2 | [
-2.4313485622406006,
-1.277939796447754,
2.763840675354004
] |
['To examine the expression of beta-catenin in colorectal cancer and look for association with other clinico-pathological parameters.', "Tumor samples from 163 cases of colorectal cancer (CRC) who had undergone primary colectomy between May, 1998 and November, 2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density (OSD) and percentage of cells having nuclear localization was counted as nuclear staining density (NSD). Univariate exploration used log-rank test and multivariate survival analysis used Cox's hazard regression model.", "Beta-catenin immunoreactivity was detected in 161 samples (98.8%), of which 131 cases had nuclear staining. High OSD (> or = 75%), detected in 123 cases (75.5%), was significantly associated with earlier clinical staging (P < 0.01), lower nodal status (P = 0.02), non-metastatic status (P < 0.01) and better differentiation (P = 0.02). Multivariate analysis found that high OSD was independently associated with better survival [Cox's hazard ratio 0.51, 95% confidence interval (CI) 0.31-0.83]. Although high NSD (> or = 75%) was correlated with high pre-operative serum CEA (P = 0.03), well differentiation (P < 0.01), and increased staining intensity (P < 0.01), the parameter was not significantly associated with survival."] Does overall expression of beta-catenin outperform its nuclear accumulation in predicting outcomes of colorectal cancers? | qiaojin/PubMedQA | 2 | [
-1.7490423917770386,
-1.557854175567627,
2.3224265575408936
] |
['This study was designed to investigate effect of gradual detorsion on testicular ischemia reperfusion injury.', 'A total of 21 male rats were divided into 3 groups, each containing 7 rats. Torsion was created by rotating the left testis 720 degrees in a clockwise direction. Group 1 underwent sham operation. Group 2 (sudden detorsion) served as a torsion/detorsion group, receiving 2 hours torsion and 2 hours detorsion. In group 3, 360 degrees detorsion was done for 20 minutes after 720 degrees torsion for 2 hours. Then, testis was done full detorsion for 100 minutes. At the end of the experiments (fourth hour), left orchiectomy was performed to measure the tissue levels of malondialdehyde (MDA), superoxide dismutase, and glutathione peroxidase and to perform histologic examination in testes.', 'The MDA levels of testis tissues were significantly increased in the sudden detorsion group as compared with the sham group. We found decrease of the MDA level in gradual detorsion group, but it was not a statistically significant amount. Significant decrease was found in the superoxide dismutase and glutathione peroxidase activities in the sudden detorsion group as compared with the sham and gradual detorsion groups. Histologic examinations were in accordance with the testicular tissue MDA levels.'] Does gradual detorsion of torsioned rat testis attenuate ischemia reperfusion injury? | qiaojin/PubMedQA | 2 | [
-2.1168484687805176,
-1.131184458732605,
2.3113136291503906
] |
['To investigate whether human embryonic stem cells (hESC) committed in culture into hematopoietic/endothelial cell progenitors can be further developed into mature blood and vascular cells following transplantation into chicken embryos.', 'The yolk sac of 42- to 44-hour chicken embryos received yolk sac injections of unfractionated human embryoid body (hEB) cells, CD34-positive hEB cells, or CD34+CD45+ granulocyte colony-stimulating factor-mobilized human peripheral blood hematopoietic stem-progenitor cells. Human cells in the host were detected by flow cytometry and immunohistochemistry.', 'All injected cell populations engrafted chicken hematopoietic organs, as assessed by detection of CD45+ cells in the spleen, bursa of Fabricius, and thymus. CD34+ day -10 hEB cells showed the highest efficiency for producing human CD45+ cells in the hosts and yielded human glycophorin A+ erythroid, CD13+ myeloid, and CD19+ lymphoid cells in the spleen and bursa of Fabricius. Spleen cells from chimeric embryos also contained human colony-forming units-granulocyte macrophage, as assessed in methylcellulose colony-forming assays. Human endothelial cells expressing vascular endothelial-cadherin, von Willebrand factor, CD31, and the receptor for the Ulex europaeus lectin were also observed in the yolk sac vasculature following injection of either unfractionated or CD34+ day -10 hEB cells.'] Do human embryonic stem cell-derived hematoendothelial progenitors engraft chicken embryos? | qiaojin/PubMedQA | 2 | [
-2.543302536010742,
-1.1895473003387451,
2.834867477416992
] |
['The axonal forms of Charcot-Marie-Tooth (CMT2) disease are a clinically and genetically heterogeneous group of disorders. Mitofusin 2 gene (MFN2) mutations are the most common cause of CMT2. Complex phenotypes have been described in association with MFN2 gene mutations, including CMT2 with pyramidal features (hereditary motor and sensory neuropathy [HSMN V]) and CMT2 with optic atrophy (HMSN VI).', 'To report on the clinical, neurophysiologic, and neuropathologic features of an Italian family with a novel MFN2 gene mutation and investigate brain functional parameters using magnetic resonance spectroscopy (MRS).', 'Three family members, a father and his two sons, were affected by peripheral neuropathy, cognitive impairment, and poor nocturnal vision (also optic neuropathy in one case). A member of this family also showed spastic paraparesis. The MFN2 gene sequence was analyzed. A sural nerve biopsy as well as brain (1)H-MRS and (31)P-MRS were evaluated in two patients.', 'Affected family members carried a novel MFN2 missense mutation, namely R104W, located within the critical GTPase domain of the protein which affects a highly conserved amino acid position. Sural nerve biopsies showed a normal mitochondrial network, particularly at the nodes of Ranvier, upon electron microscopy examination. A significant defect of high energy phosphates (HEPs) in the visual cortex was observed at rest by (31)P-MRS in the adult proband, while his son showed a defective recovery of HEPs after stimulation of the visual cortex.'] Does mutated mitofusin 2 present with intrafamilial variability and brain mitochondrial dysfunction? | qiaojin/PubMedQA | 2 | [
-2.4950225353240967,
-1.2817370891571045,
2.8466696739196777
] |
['To investigate the relationship between white matter tract integrity and language and memory performances in patients with temporal lobe epilepsy (TLE).', 'Diffusion tensor imaging (DTI) was performed in 17 patients with TLE and 17 healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for six fiber tracts (uncinate fasciculus [UF], arcuate fasciculus [AF], fornix [FORX], parahippocampal cingulum [PHC], inferior fronto-occipital fasciculus [IFOF], and corticospinal tract [CST]). Neuropsychological measures of memory and language were obtained and correlations were performed to evaluate the relationship between DTI and neuropsychological measures. Hierarchical regression was performed to determine unique contributions of each fiber tract to cognitive performances after controlling for age and hippocampal volume (HV).', 'Increases in MD of the left UF, PHC, and IFOF were associated with poorer verbal memory in TLE, as were bilateral increases in MD of the AF, and decreases in FA of the right AF. Increased MD of the AF and UF, and decreased FA of the AF, UF, and left IFOF were related to naming performances. No correlations were found between DTI measures and nonverbal memory or fluency in TLE. Regression analyses revealed that several fibers, including the AF, UF, and IFOF, independently predicted cognitive performances after controlling for HV.'] Does diffusion tensor imaging correlate of memory and language impairments in temporal lobe epilepsy? | qiaojin/PubMedQA | 2 | [
-2.2791125774383545,
-1.2489501237869263,
2.565488815307617
] |
['To test the hypothesis that surgeon volume would not predict short- and long-term outcomes when evaluated in the setting of technical credentialing.', 'Surgical volume is a known predictor of outcomes; the importance of technical credentialing has not been evaluated.', 'Fifty-three credentialed surgeons operated on 871 patients in the Clinical Outcomes of Surgical Therapy Study (NCT00002575), investigating laparoscopic versus open surgery for colon cancer. Credentialing required that each surgeon document performance of at least 20 laparoscopic colon cases and demonstrate oncologic techniques on a video-recorded case. Surgeons were separated based on volume entered into the trial (low, < or =5 cases (n = 39); medium, 6-10 cases (n = 9); or high, >10 cases (n = 5)) and compared by outcomes.', 'Patients treated by high volume compared with medium or low volume surgeons were older (70, 66, and 68 years; P < 0.001), more often had right-sided tumors (63%, 46%, and 53%; P < 0.001) and had more previous operations (48%, 38% and 45%; P < 0.004), respectively. Mean operative times were shorter (123, 147 and 145 minutes; P < 0.001), distal margins longer (13.4, 12.4 and 11.6 cm; P = 0.005), and lymph node harvest greater (14.8, 12.8, 12.6; P = 0.05) for high versus medium versus low volume surgeons. However, rates of conversion, complications, 5-year survival, and disease-free survival showed no significant differences.'] Does surgeon volume predict outcomes in the setting of technical credentialing : results from a randomized trial in colon cancer? | qiaojin/PubMedQA | 2 | [
-1.7360585927963257,
-0.6630778908729553,
1.5163469314575195
] |
['To clarify the clinicopathologic features and prognosis of renal cell carcinoma (RCC) in young adults. The features of RCC in young adults have been reported, but the results have been conflicting.', 'The data from 619 patients with RCC were analyzed. The patients were divided into 2 groups according to age at diagnosis, </=55 or >55 years of age. The clinicopathologic parameters were compared, and a survival analysis was performed.', 'Younger patients were more likely to have a lower disease stage (P < .001), lower nuclear grade (P = .018), and smaller tumor size (P = .005) and a greater 5-year cancer-specific survival rate (P < .001) than older patients. Young age was a favorable prognostic factor for cancer-specific survival of clear cell RCC (P < .001). On multivariate analysis, young age was independently associated with a longer cancer-specific survival rate of clear cell RCC (P = .003). In addition, the prognostic implication of age differed between low (I or II) and high (III or IV) stage tumors. In low-stage clear cell RCC, young age was significantly associated with prolonged cancer-specific survival on univariate (P < .001) and multivariate (P = .007) analyses, but not in high-stage clear cell RCC (P = .906).'] Is young age independent prognostic factor for cancer-specific survival of low-stage clear cell renal cell carcinoma? | qiaojin/PubMedQA | 2 | [
-1.950844168663025,
-1.3064919710159302,
2.409242630004883
] |
["TNF-alpha and IL-1 have been associated with mucosal inflammation in both Crohn's disease (CD) and ulcerative colitis (UC). Innate immune defects have been associated with CD, specifically CARD15/NOD2. Recently, Toll-like receptor 8 (TLR8) signaling has been shown to enhance generation of both cytokines. Interestingly, TLR8 is located on the X chromosome and inflammatory bowel disease (IBD) has been associated with abnormalities of the X chromosome. The aim was to test whether TLR8 haplotypes are associated with IBD.", 'Subjects (735 CD, 343 UC, 245 controls) were genotyped. Single nucleotide polymorphisms (SNPs) were chosen to tag common Caucasian haplotypes.', 'Both "risk (H4)" and "protective (H1)" TLR8 haplotypes were observed associated with CD in females. Eighteen percent of CD females had H4 compared with 9% of controls (P = 0.02). Fifty-nine percent of CD females had H1 compared with 72% of controls (P = 0.01). H1 was also negatively associated with UC in females (59% of UC, 72% of controls P = 0.03). Diplotype analysis of CD, UC, and all IBD in females revealed that 2 protective haplotypes (H1/H1) had a markedly diminished odds ratio, 0.4-0.5. The presence of a risk haplotype (H4 / not H1) had a significantly increased odds ratio, 2.0-2.2. Thus, the risk for IBD was 4-5 times higher in females with 1 risk haplotype than with the protective/protective diplotype.'] Are high-frequency haplotypes in the X chromosome locus TLR8 associated with both CD and UC in females? | qiaojin/PubMedQA | 2 | [
-1.5085963010787964,
-1.5998873710632324,
2.0438363552093506
] |
['Lesion studies in human and non-human primates have linked several different regions of prefrontal cortex (PFC) with the ability to inhibit inappropriate motor responses. However, recent functional neuroimaging studies have specifically implicated right inferior PFC in response inhibition. Right frontal dominance for inhibitory motor control has become a commonly accepted view, although support for this position has not been consistent. Particularly conspicuous is the lack of data on the importance of the homologous region in the left hemisphere. To investigate whether the left inferior frontal gyrus (IFG) is critical for response inhibition, we used neuropsychological methodology with carefully characterized brain lesions in neurological patients.', 'Twelve individuals with damage in the left IFG and the insula were tested in a Go/NoGo response inhibition task. In alternating blocks, the difficulty of response inhibition was easy (50% NoGo trials) or hard (10% NoGo trials). Controls showed the predicted pattern of faster reaction times and more false alarm errors in the hard condition. Left IFG patients had higher error rates than controls in both conditions, but were more impaired in the hard condition, when a greater degree of inhibitory control was required. In contrast, a patient control group with orbitofrontal cortex lesions showed intact performance.'] Is left inferior frontal gyrus critical for response inhibition? | qiaojin/PubMedQA | 2 | [
-2.55861496925354,
-0.8765897750854492,
2.4470784664154053
] |
['Constitutive activation of signal transducer and activator of transcription 3 (Stat3) signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer.', 'We found that elevated Stat3 phosphorylation in 19 of 100 (19%) bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F) and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC). The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin) and a cell cycle regulating gene (cyclin D1) was associated with the cell growth inhibition and apoptosis.'] Is signal transducer and activator of transcription 3 activation associated with bladder cancer cell growth and survival? | qiaojin/PubMedQA | 2 | [
-2.458313226699829,
-1.1705528497695923,
2.679464340209961
] |
["The functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells (Rh30) and human primary myocytes in culture. Uniformly 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs' cycle, pentose phosphate pathway and pyrimidine biosynthesis.", "The Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs' cycle activity as determined by 13C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells."] Do rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes? | qiaojin/PubMedQA | 2 | [
-2.4256370067596436,
-1.2667744159698486,
2.754237174987793
] |
['Luminal pressure may injure the gut mucosa in obstruction, ileus, or inflammatory bowel disease.', 'We formed Roux-en-Y anastomoses in 19 mice, creating proximal and defunctionalized partially obstructed limbs and a distal limb to vary luminal pressure and flow. We induced mucosal ulcers by serosal acetic acid, and assessed proliferation (proliferating cell nuclear antigen) and ERK (immunoblotting). Parallel studies compared Caco-2 enterocyte migration and proliferation after pressure and/or ERK blockade.', 'At 3 days, anastomoses were probe-patent, proximal and distal limbs contained chyme, and defunctionalized limbs were empty. The proximal and defunctionalized limbs showed increased pressure and slower healing despite increased proliferation, ERK protein, and ERK activation. In vitro, pressure decreased Caco-2 migration across collagen or fibronectin, stimulated proliferation, and activated ERK. However, ERK blockade did not prevent pressure effects.'] Does supraphysiologic extracellular pressure inhibit intestinal epithelial wound healing independently of luminal nutrient flow? | qiaojin/PubMedQA | 2 | [
-2.514732837677002,
-1.3017184734344482,
2.9256744384765625
] |
['Incidence of cholangiocarcinoma is increasing worldwide, yet remaining highly aggressive and with poor prognosis. The mechanisms that drive cholangiocyte transition towards malignant phenotype are obscure. Cholangiocyte benign proliferation is subjected to a self-limiting mechanism based on the autocrine release of endogenous opioid peptides. Despite the presence of both, ligands interact with delta opioid receptor (OR), but not with microOR, with the consequent inhibition of cell growth. We aimed to verify whether cholangiocarcinoma growth is associated with failure of opioidergic regulation of growth control.', 'We evaluated the effects of OR selective agonists on cholangiocarcinoma cell proliferation, migration and apoptosis. Intracellular signals were also characterised.', 'Activation of microOR, but not deltaOR, increases cholangiocarcinoma cell growth. Such an effect is mediated by ERK1/2, PI3K and Ca(2+)-CamKIIalpha cascades, but not by cAMP/PKA and PKCalpha. microOR activation also enhances cholangiocarcinoma cell migration and reduces death by apoptosis. The anti-apoptotic effect of microOR was PI3K dependent.'] Is human cholangiocarcinoma development associated with dysregulation of opioidergic modulation of cholangiocyte growth? | qiaojin/PubMedQA | 2 | [
-2.4813356399536133,
-1.2360656261444092,
2.772118091583252
] |
['To investigate the capacity of young children and adults with normal hearing to discriminate speech on the basis of either relatively slow (temporal envelope, E) or fast (temporal fine structure, TFS) auditory cues.', "Vowel-consonant-vowel nonsense disyllables were processed to preserve either the E or the TFS information in 16 adjacent frequency bands. The band signals were then recombined and resulting stimuli were presented for discrimination to adults or 5-, 6-, and 7-year-old children using an odd-ball paradigm. Discrimination scores (d') and response latencies were measured in each listener. No training was given to listeners.", "Overall, discrimination scores were high (d' >or=1) in all speech-processing conditions, and did not differ across age groups. Overall, and irrespective of age, greater discrimination scores and shorter response latencies were observed for E speech than for TFS speech."] Does discrimination of speech sound based upon temporal envelope versus fine structure cues in 5- to 7-year-old children? | qiaojin/PubMedQA | 1 | [
-1.7829861640930176,
0.4785282015800476,
0.45142054557800293
] |
['Activation of macrophages is central to the implantation of endometriosis (EM). We examined the hypothesis that macrophage depletion by intraperitoneal (IP) injection of liposomal alendronate (LA) could result in EM attenuation in a rat model, thus supporting the notion of the pivotal role of macrophages in EM pathology.', 'In this study, 90 rats were subjected to an EM model and were divided randomly into seven groups: five groups were treated by 4x once-weekly IP injections of LA (0.02, 0.1, 1, 5 or 10 mg/kg) and the other two groups received saline injections (control) or empty liposomes. Sham-operated rats also received empty liposomes. Depletion of circulating monocytes was determined by flow cytometry analyzes of blood specimens. Four weeks after the initial surgery, the number, size and weight of implants were recorded, adhesions were graded, macrophage infiltration was assessed and the peritoneal fluid was analyzed for monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor alpha (TNFalpha).', "Monocyte depletion following IP LA administration resulted in an inhibitory effect on the initiation and growth of EM implants, as expressed by implantation rate, adhesion scoring, implants' size and weight (>0.1 mg/kg LA, P < 0.05). Reduced numbers of infiltrating macrophages were observed in implants of the 1 mg/kg LA group. Peritoneal fluid MCP-1 levels were negatively correlated with LA dose (P < 0.001), whereas no significant correlation could be found for TNFalpha."] Does peritoneal macrophage depletion by liposomal bisphosphonate attenuate endometriosis in the rat model? | qiaojin/PubMedQA | 2 | [
-2.070474863052368,
-1.5281610488891602,
2.616023302078247
] |
['In the glucagon stimulation test (GST) growth hormone (GH) secretion is considered sufficient when at least 1 value is >10 ng/mL. Because GH typically peaks at 90 or 120 minutes, we evaluated whether peak occurrence at other times ("atypical") signifies abnormal GH secretion.', 'A retrospective review of 222 GSTs was conducted to determine these outcomes: 1) frequency of GH deficiency per confirmatory clonidine or arginine stimulation test in typical versus atypical GSTs, and 2) growth velocity standard deviation score (GVSDS) in patients with typical versus atypical GSTs.', 'Of 222 tests, 57 GST results (25.7%) were atypical, and 54 GST results (24.3%) were deficient. Atypical deficient tests had a higher chance than typical deficient tests of predicting GH deficiency per confirmatory test (15/21, 71.4% versus 14/33, 42.4%; P < .05). Patients with deficient atypical GST results and sufficient confirmatory tests (n = 6) had a lower GVSDS than patients with deficient typical GST results (n = 18; -1.58 [-3.2-1.76], versus 0.23 [-1.54-3.95], P = .03). Overall, 75% of atypical deficient GST results were followed by atypical timing in a clonidine test. Three of the 222 tests (1.3%) peaked at 180 minutes.'] Is glucagon stimulation test for childhood growth hormone deficiency : timing of the peak important? | qiaojin/PubMedQA | 2 | [
-1.0597938299179077,
-1.686366319656372,
1.733381748199463
] |
['To investigate the influence of rapid nongenomic effect of androgen on the insulin sensitivity of mature adipocytes and the molecular mechanism thereof.', 'Fetal mice [corrected] preadipocytes of the line 3T3-L1 were cultured to develop into mature adipocytes. 3T3-L1 adipocytes were pretreated with testosterone of the concentration of 10-9 to approximately 10(-5) mol/L for a short-time 0-30 minutes) or a long-time (24 hours). Insulin (Ins) 200 microl at the concentration 100 micromol/L and 2-deoxy [3H] glucose were added to examine the glucose uptake. Phosphorylation and protein expression of Ins receptor (InsR) and its downstream signaling molecules (Akt and GSK3beta) were analyzed by Western blotting.', 'The Ins-stimulated glucose uptake after the pretreatment of testosterone for 30 min and 24 h decreased gradually in response to the increasing of the concentration of testosterone with the nadir both at the testosterone concentration of 10(-5) mol/L (both P < 0.05). The phosphorylation levels of InsR, Akt, and GSK3Pbeta were significantly down-regulated by adding of testosterone at the concentration of 10(-6) mol/L for 3-30 minutes (all P < 0.05) or by adding of testosterone at the concentrations of 10(-7) - 10(-6) mol/L for 24 hours (all P < 0.05). The protein expression levels of InsR, Akt, and GSK3Pbeta, however, were not significantly affected by testosterone treatment.'] Does [ Testosterone impair insulin sensitivity in 3T3-L1 adipocytes and the related nongenomic mechanisms ]? | qiaojin/PubMedQA | 2 | [
-2.0203394889831543,
-1.3606667518615723,
2.3716468811035156
] |
['During pregnancy, variations in maternal-foetal cellular interactions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies.', 'For this cohort study, peripheral blood was collected from allergic (n = 69) and nonallergic (n = 63) pregnant women at 20, 30, 36-week gestation and 6-week postpartum (pp). Cord blood was collected at delivery. Mixed lymphocyte reactions were used to measure maternal cytokine responses [interleukin-6 (IL-6), IL-10, IL-13 and (interferon-gamma) IFN-gamma] at each time point towards foetal mononuclear cells.', 'Maternal cytokine responses during pregnancy (20, 30 and 36 weeks) were suppressed compared to the responses at 6-week pp. The ratio of maternal IFN-gamma/IL-13 and IFN-gamma/IL-10 responses were lower during pregnancy. Allergic mothers had lower IFN-gamma responses at each time-point during pregnancy with the greatest difference in responses observed at 36-week gestation. When allergic and nonallergic women were further stratified by gravidity group, IFN-gamma responses of allergic multigravid mothers were significantly lower than nonallergic multigravid mothers during pregnancy.'] Are pregnancy IFN-gamma responses to foetal alloantigens altered by maternal allergy and gravidity status? | qiaojin/PubMedQA | 2 | [
-2.152963161468506,
-1.0864053964614868,
2.270631790161133
] |
['Various studies have found reduced prevalences of atopic sensitization and atopic diseases in children previously exposed to infections or living conditions with a high microbial burden, such as the farming environment.', 'We sought to determine the relationships of cord blood immunoglobulin E (IgE) with maternal health conditions before and during pregnancy.', 'Pregnant women living in rural areas in five European countries were recruited in the third trimester of pregnancy. Information on maternal health during pregnancy was collected from maternity records and by questionnaires (n = 497). Specific IgE for inhalant and food allergens was assessed in cord blood and peripheral blood samples of the mothers.', 'Inverse associations of cord blood IgE to seasonal allergens with positive maternal records for Toxoplasma gondii (adjusted odds ratio = 0.37 [0.17-0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13-0.96]) were found. The previously described effect of prenatal farm exposure on IgE to seasonal allergens was partly confounded by a positive maternal record for T. gondii. The number of maternal siblings, maternal contact to cats during pregnancy or during her first year of life, predicted a positive maternal record for T. gondii.'] Is specific IgE to allergens in cord blood associated with maternal immunity to Toxoplasma gondii and rubella virus? | qiaojin/PubMedQA | 2 | [
-2.4676458835601807,
-0.966090202331543,
2.55715274810791
] |
['The purpose was to examine human osteoblasts immunohistochemically in order to clarify the significance of the innervation for alveolar bone growth.', 'Unstained sections available from 21 normal human mandibles (foetal gestational ages: 14-22 weeks).', 'Before sectioning in 1980-1990, the mandibular tissue had been fixed in 4% neutral-buffered formaldehyde for 5 days. Tissue blocks were then decalcified in equal parts of 2% citric acid and 20% sodium citrate for 7-15 days, dehydrated, embedded in paraffin, and sagittally cut into 4-mum-thick serial sections and mounted on Superfrost Plus microscope slides. Sections were dried overnight at 40 degrees C. In the present study, paraffin sections were deparaffinized and treated with Tris-EDTA (Merck, Germany), pH 9.0, and immunohistochemically tested with polyclonal rabbit anti-PGP 9.5, and the EnVision +/HRP dual link (K4065; DAKO Denmark A/S, Denmark) method.', 'A pronounced protein gene product (PGP) 9.5 activity was registered in osteoblasts from alveolar bone in all specimens. In all cases, the activity was intense at the top of and labially to the alveolar bone, while less or no activity was observed on the inner lingual aspects of the alveolar processes. Osteoclasts and osteocytes reacted vaguely or negatively.'] Are immunohistochemical PGP 9.5 positivity in human osteoblasts may indicate that compensatory and dysplastic craniofacial growth under control by peripheral nerves? | qiaojin/PubMedQA | 2 | [
-2.4092776775360107,
-1.4164931774139404,
2.909834384918213
] |
['To analyse the effects of short-term treatment with etidronate on the glucocorticoid-induced retardation of bone growth and deterioration of bone structure in the prepubertal rat mandible.', 'Fifty 5-week-old male rats were divided into five groups. Etidronate or vehicle treatment (5 mg/kg/day, daily, subcutaneous injection) was initiated after glucocorticoid administration (30 mg/kg/day, on alternate days, orally) for 6 weeks and was continued for 3 weeks. Then, bone growth was measured using lateral cephalometric analysis. Peripheral quantitative computed tomography was used to determine bone density, bone cross-sectional area and bone strength.', 'Glucocorticoid-treated rats had significantly lower body weight, mandibular length, cortical bone density, bone strength and cross-sectional area in trabecular and cortical bone, but had significantly higher trabecular bone density than untreated rats. No significant difference in mandibular height was observed between the glucocorticoid-treated group and the untreated control group. Etidronate treatment improved the glucocorticoid-induced decrease in bone strength and increased density in trabecular and cortical bone above the untreated control level, but had no significant effects on the reduction in mandibular length.'] Does short-term etidronate treatment prevent glucocorticoid-induced bone debility of the mandible in growing rats? | qiaojin/PubMedQA | 2 | [
-2.2680323123931885,
-1.3424980640411377,
2.700289726257324
] |
['Cordyceps militaris, one of traditional herbal ingredient in oriental medicine, has been known to promote anticancer and immunomodulatory activities in vitro and in vivo. However, the biological mechanism of anticancer activity has been unknown.', 'To investigate the effect of Cordyceps militaris extract on expression of interferon gamma (IFN-gamma) through interlukin-18 (IL-18) induction and its biological mechanism in vitro and in vivo.', 'Mice were administrated orally with solution extracted from Cordyceps militaris. The transcription level of IL-18 and IFN-gamma production were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RAW 264.7 cells were transiently transfected with pCATp1 and pCATp2 for IL-18 promoter functional analysis.', "Cordyceps militaris extracts treatment significantly induced level of IL-18 transcription in mouse brain and liver and enhanced IL-18 transcription level and activated the IFN-gamma production in RAW 264.7 cells. Furthermore, Cordyceps militaris extract led to increase the activity of pCATp1 construct containing the 5' franking region of IL-18 promoter in RAW 264.7 cells."] Does cordyceps militaris induce the IL-18 expression via its promoter activation for IFN-gamma production? | qiaojin/PubMedQA | 2 | [
-2.4191176891326904,
-1.1698516607284546,
2.680654287338257
] |
['Cognitive inflexibility in schizophrenia is treatment-resistant and predictive of poor outcome. This study examined the effect of asenapine, a novel psychopharmacologic agent being developed for schizophrenia and bipolar disorder, on cognitive dysfunction in the rat.', 'The objective of this paper was to establish whether asenapine has a beneficial effect on the performance of rats with ibotenic acid-induced lesion of the medial prefrontal cortex (mPFC) in an intradimensional/extradimensional (ID/ED) test of cognitive flexibility.', 'The effect of subcutaneously administered asenapine (0.75, 7.5, 75 microg/kg) on ID/ED performance of controls or mPFC-lesioned rats was examined using a within-subjects, repeated-measures design. In a second experiment, lesioned and control rats were tested with or without asenapine in a modified version of the task, with multiple set-shifts, before brains were processed for Fos-immunoreactivity in the mPFC.', 'The mPFC lesion-induced deficit in the ID/ED task was stable with repeated testing over more than two months. Asenapine (75 microg/kg s.c., p < 0.05) completely restored the performance of lesioned rats. Experiment 2 replicated both lesion and asenapine effects and demonstrated that it is possible to measure set-shifting multiple times within a test session. Asenapine (75 microg/kg s.c.) was associated with differential activation of the neurons in the anterior mPFC of lesioned animals, but was without effect in controls.'] Does asenapine restore cognitive flexibility in rats with medial prefrontal cortex lesions? | qiaojin/PubMedQA | 2 | [
-2.083024263381958,
-1.3260622024536133,
2.404608726501465
] |
['Stromal cell-derived factor (SDF)-1, a chemokine produced in the bone marrow (BM), is essential for the homing of hematopoietic stem/progenitor cells (HSPCs) to the BM after transplantation. This study examines whether there is a correlation between the in vitro chemotaxis of CD34+ HSPC toward an SDF-1 gradient and in vivo hematopoietic engraftment.', 'Thirty-five patients underwent granulocyte-colony-stimulating factor HSPC collection and autologous transplant with a median dose of 7.7 (range, 3.9-41.5) x 10(6) CD34+ cells per kg body weight. The chemotactic index (CI) of CD34+ cells isolated from leukapheresis products collected from these patients was calculated as the ratio of the percentages of cells migrating toward an SDF-1 gradient to cells migrating to media alone. Expression of the SDF-1 receptor CXCR4 on CD34+ cells was measured by flow cytometry.', 'Spontaneous cell migration (range, 3.1 +/- 0.6 to 26.5 +/- 7.7%) and SDF-1-directed chemotaxis (11.1 +/- 0.7 to 54.9 +/- 8.3%) of CD34+ cells did not correlate with time to neutrophil engraftment, which occurred at a median of 10 days (range, 8-16 days). Nonparametric tests showed a negative correlation (r = -0.434) between CI and CD34+ cell dose such that neutrophil recovery occurred within the same period in patients transplanted with a lower dose of CD34+ cells but having a high CI as in those transplanted with a higher dose of CD34+ cells but having a low CI. Moreover, CI correlated (r = 0.8) with surface CXCR4 expression on CD34+ cells.'] Does cD34+ cell responsiveness to stromal cell-derived factor-1alpha underlies rate of engraftment after peripheral blood stem cell transplantation? | qiaojin/PubMedQA | 2 | [
-1.9705036878585815,
-1.5405833721160889,
2.5203471183776855
] |
['Heart failure (HF) is associated with factors that may contribute to accelerated bone loss and subsequent fractures. Whether it leads to an increased fracture risk is unknown.', 'A population-based cohort of consecutive patients >/=65 years of age with cardiovascular disease presenting to all emergency rooms between 1998 and 2001 in Alberta, Canada (n=16294 patients), was used. The 2041 patients with a new diagnosis of HF were compared with a control group of 14 253 patients with non-HF cardiovascular diagnoses. The primary outcome was any orthopedic fracture requiring hospital admission in the year after the emergency room visit. Patients with HF had a median age of 78 years (interquartile range, 72 to 84 years), and 51.9% were female; control subjects had a median age of 73 years (interquartile range, 68 to 79 years), and 53.2% were female. In the first year after the emergency room visit, 4.6% of the HF cohort (n=93) and 1.0% of patients without HF (n=147) sustained an orthopedic fracture (P<0.001). Hip fractures occurred in 26 HF patients (1.3%) and 18 patients (0.1%) without HF (P<0.001). After multivariable adjustment, HF was independently associated with a greater risk of any orthopedic fracture (adjusted odds ratio, 4.0; 95% CI, 2.9 to 5.3) or hip fracture (adjusted odds ratio, 6.3; 95% CI, 3.4 to 11.8).'] Is heart failure a risk factor for orthopedic fracture : a population-based analysis of 16,294 patients? | qiaojin/PubMedQA | 2 | [
-0.5823938250541687,
-1.5281178951263428,
1.1436858177185059
] |
['Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model.', 'Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159+/-44% of normal (P=0.016), whereas muscle viability and contraction force were reduced to 65+/-13% (P=0.016) and 45+/-34% (P=0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132+/-16% versus 185+/-42%; P=0.011) and muscle viability (74+/-11% versus 57+/-9%; P=0.004) and contraction force (68+/-40% versus 26+/-7%; P=0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion (P=0.027).'] Does basic control of reperfusion effectively protect against reperfusion injury in a realistic rodent model of acute limb ischemia? | qiaojin/PubMedQA | 2 | [
-1.6767266988754272,
-1.5931257009506226,
2.2930002212524414
] |
['RACK1 is a versatile scaffold protein in mammals, regulating diverse developmental processes. Unlike in non-plant organisms where RACK1 is encoded by a single gene, Arabidopsis genome contains three RACK1 homologous genes, designated as RACK1A, RACK1B and RACK1C, respectively. Previous studies indicated that the loss-of-function alleles of RACK1A displayed multiple defects in plant development. However, the functions of RACK1B and RACK1C remain elusive. Further, the relationships between three RACK1 homologous genes are unknown.', "We isolated mutant alleles with loss-of-function mutations in RACK1B and RACK1C, and examined the impact of these mutations on plant development. We found that unlike in RACK1A, loss-of-function mutations in RACK1B or RACK1C do not confer apparent defects in plant development, including rosette leaf production and root development. Analyses of rack1a, rack1b and rack1c double and triple mutants, however, revealed that rack1b and rack1c can enhance the rack1a mutant's developmental defects, and an extreme developmental defect and lethality were observed in rack1a rack1b rack1c triple mutant. Complementation studies indicated that RACK1B and RACK1C are in principle functionally equivalent to RACK1A. Gene expression studies indicated that three RACK1 genes display similar expression patterns but are expressed at different levels. Further, RACK1 genes positively regulate each other's expression."] Do rACK1 genes regulate plant development with unequal genetic redundancy in Arabidopsis? | qiaojin/PubMedQA | 2 | [
-2.044888734817505,
-0.04896905645728111,
1.0752995014190674
] |
['We conducted a pilot study of dose-dense epirubicin/cyclophosphamide (EC) x 6 --> paclitaxel (P) x 6 with pegfilgrastim. A previous dose-dense trial of FEC (5-fluorouracil [5-FU]/EC) x 6 with filgrastim --> by weekly paclitaxel alternating with docetaxel x 18 was not feasible because of pneumonitis (with dose-dense FEC) and pericardial/pleural effusion (taxane phase). Dose-dense EC (without the 5-FU) is not associated with pneumonitis, and dose-dense paclitaxel (alone) is feasible. Primary objective was feasibility.', 'Patients with resectable breast cancer were enrolled, regardless of surgery status, tumor size, or nodal status. Treatment regimen consisted of every-2-week EC (100/600 mg/m2) x 6 --> by 2-weekly P (175 mg/m2) x 6 with pegfilgrastim 6 mg on day 2.', 'Between November 2004 and May 2005, 38 patients were enrolled. The median age was 47 years (range, 30-72 years); 33 of 38 (87%) were treated in the adjuvant setting and 27 of 33 (81%) had involved nodes (range, 1-46); 5 of 38 (13%) were treated pre-operatively; 33 of 38 (87%) completed all chemotherapy as planned; the remaining patients (13%) had treatment modifications for toxicity. Febrile neutropenia occurred in 6 of 38 patients (16 %) and only during EC. There were 12 hospitalizations in 9 of 38 patients (24%) enrolled.'] Is prolonged dose-dense epirubicin and cyclophosphamide followed by paclitaxel in breast cancer feasible? | qiaojin/PubMedQA | 2 | [
-1.4808721542358398,
-1.6894360780715942,
2.133762836456299
] |
['To investigate the effects of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the biological activity of glioblastoma cell line GL15.', 'Glioblastoma GL15 cells were cultured and transfected with LRIG3-EGFP plasmid. The location of LRIG3 in GL15 cells was observed with confocal microscopy. The proliferation and invasiveness of GL15 cells were detected with methyl thiazolyl tetrazolium (MTT) and Transwell methods respectively; the expression of epidermal growth factor receptor (EGFR) and LRIG3 mRNA and protein were detected with reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot respectively.', 'After transfection with the plasmid LRIG-EGFP, LRIG3 fusion protein was found in cytoplasm of GL15 cells and cell proliferative and invasiveness were reduced. The expression of EGFR and LRIG3 varied with the duration of EGF treatment (100 ng/ml): the expression of EGFR decreased while the expression of LRIG3 increased as time prolonged.'] Does [ LRIG3 gene regulate biological activity of GL15 cell line ]? | qiaojin/PubMedQA | 2 | [
-2.375491142272949,
-1.282508373260498,
2.747654676437378
] |
['To investigate the degree of CHD awareness as well as symptom, risk factor, and treatment knowledge in a broad sample of cardiac inpatients, and to examine its sociodemographic, clinical and psychosocial correlates.', '1308 CHD inpatients (351 [27.0%] female), recruited from 11 acute care sites in Ontario, participated in this cross-sectional study. Participants were provided with a survey which included a knowledge questionnaire among other measures, and clinical data were extracted from medical charts.', '855 (68.8%) respondents cited heart disease as the leading cause of death in men, versus only 458 (37.0%) in women. Participants with less than high school education (p<.001), an annual family income less than $50,000CAD (p=.022), low functional capacity (p=.042), who were currently smoking (p=.022), who had no family history of heart disease (p<.001), and who had a perception of low personal control (p=.033) had significantly lower CHD knowledge.'] Does degree and correlate of cardiac knowledge and awareness among cardiac inpatients? | qiaojin/PubMedQA | 2 | [
-1.2684351205825806,
0.20192109048366547,
0.2881186604499817
] |
["Measuring children's dietary behavior is central to evaluating interventions and identifying predictors and outcomes of dietary behaviors. Systematic biases may obscure or inflate associations with self-reported intakes.", "To identify cognitive, behavioral, and social correlates of bias in children's reporting of breakfast items on a self-completion questionnaire.", "Cross-sectional survey. Children completed standardized tests of episodic memory, working memory, and attention, and a questionnaire assessing attitudes toward breakfast. Teachers completed a classroom behavior measure. Associations between measures and children's underreporting of breakfast foods (ie, cereals, bread, milk, fruits, sweet items, and potato chips) on a self-completion questionnaire relative to validated 24-hour recall were examined.", 'Subjects were aged 9 to 11 years (n=678). Data were collected from 111 schools throughout Wales in 2005.', 'A larger percentage of less-healthful breakfast items (ie, sweet snacks and potato chips) than more healthful items (ie, fruit, cereals, bread, and milk) were omitted from questionnaire self-reports. Children from lower socioeconomic status schools omitted more items than those from wealthier schools (Kruskal-Wallis H=12.51, P<0.01), with omissions twice as high for less-healthful items than for more-healthful items within the lowest socioeconomic status schools. Those with positive attitudes (H=23.85, P<0.001), better classroom behavior (H=6.26, P<0.05), and better episodic memory (H=8.42, P<0.05) omitted fewer items than those with negative attitudes, poorer behavior, and poorer episodic memory. Children who ate more items omitted more than those who ate fewer (H=47.65, P<0.001). No differences were observed in terms of attention and working memory.'] Are cognitive , behavioral , and social factors associated with bias in dietary questionnaire self-reports by schoolchildren aged 9 to 11 years? | qiaojin/PubMedQA | 2 | [
-0.24311721324920654,
-0.47479891777038574,
-0.2344958484172821
] |
['Neoplastic transformation originates from a large number of different genetic alterations. Despite this genetic variability, a common phenotype to transformed cells is cellular alkalinization. We have previously shown in human keratinocytes and a cell line in which transformation can be turned on and followed by the inducible expression of the E7 oncogene of human papillomavirus type 16 (HPV16), that intracellular alkalinization is an early and essential physiological event driven by the up-regulation of the Na/(+)H(+) exchanger isoform 1 (NHE1) and is necessary for the development of other transformed phenotypes and the in vivo tumor formation in nude mice.', 'Here, we utilize these model systems to elucidate the dynamic sequence of alterations of the upstream signal transduction systems leading to the transformation-dependent activation of NHE1.', 'We observe that a down-regulation of p38 MAPK activity is a fundamental step in the ability of the oncogene to transform the cell. Further, using pharmacological agents and transient transfections with dominant interfering, constitutively active, phosphorylation negative mutants and siRNA strategy to modify specific upstream signal transduction components that link HPV16 E7 oncogenic signals to up-regulation of the NHE1, we demonstrate that the stimulation of NHE1 activity is driven by an early rise in cellular cAMP resulting in the down-stream inhibition of p38 MAPK via the PKA-dependent phosphorylation of the small G-protein, RhoA, and its subsequent inhibition.'] Does hPV16 E7-dependent transformation activate NHE1 through a PKA-RhoA-induced inhibition of p38alpha? | qiaojin/PubMedQA | 2 | [
-2.553124189376831,
-1.1518791913986206,
2.752319812774658
] |
["Barrett's esophagus is a premalignant condition whereby the normal stratified squamous esophageal epithelium undergoes a transdifferentiation program resulting in a simple columnar epithelium reminiscent of the small intestine. These changes are typically associated with the stratified squamous epithelium chronically exposed to acid and bile salts as a result of gastroesophageal reflux disease (GERD). Despite this well-defined epidemiologic association between acid reflux and Barrett's esophagus, the genetic changes that induce this transdifferentiation process in esophageal keratinocytes have remained undefined.", "To begin to identify the genetic changes responsible for transdifferentiaiton in Barrett's esophagus, we performed a microarray analysis of normal esophageal, Barrett's esophagus and small intestinal biopsy specimens to identify candidate signaling pathways and transcription factors that may be involved. Through this screen we identified the Cdx1 homeodomain transcription factor and the c-myc pathway as possible candidates. Cdx1 and c-myc were then tested for their ability to induce transdifferentiation in immortalized human esophageal keratinocytes using organotypic culturing methods. Analyses of these cultures reveal that c-myc and cdx1 cooperate to induce mucin production and changes in keratin expression that are observed in the epithelium of Barrett's esophagus."] Do cdx1 and c-Myc foster the initiation of transdifferentiation of the normal esophageal squamous epithelium toward Barrett 's esophagus? | qiaojin/PubMedQA | 2 | [
-2.5270392894744873,
-1.2602653503417969,
2.822622060775757
] |
['Bone remodeling relies on the tightly regulated interplay between bone forming osteoblasts and bone digesting osteoclasts. Several studies have now described the molecular mechanisms by which osteoblasts control osteoclastogenesis and bone degradation. It is currently unclear whether osteoclasts can influence bone rebuilding.', 'Using in vitro cell systems, we show here that mature osteoclasts, but not their precursors, secrete chemotactic factors recognized by both mature osteoblasts and their precursors. Several growth factors whose expression is upregulated during osteoclastogenesis were identified by DNA microarrays as candidates mediating osteoblast chemotaxis. Our subsequent functional analyses demonstrate that mature osteoclasts, whose platelet-derived growth factor bb (PDGF-bb) expression is reduced by siRNAs, exhibit a reduced capability of attracting osteoblasts. Conversely, osteoblasts whose platelet-derived growth factor receptor beta (PDGFR-beta) expression is reduced by siRNAs exhibit a lower capability of responding to chemotactic factors secreted by osteoclasts.'] Do osteoclasts control osteoblast chemotaxis via PDGF-BB/PDGF receptor beta signaling? | qiaojin/PubMedQA | 2 | [
-2.6633710861206055,
-0.5591089129447937,
2.2652289867401123
] |
['Despite numerous in vivo evidences that Tumor Necrosis Factor Receptor-Associated Factor 4 (TRAF4) plays a key biological function, how it works at the cellular and molecular level remains elusive.', 'In the present study, we show using immunofluorescence and immuohistochemistry that TRAF4 is a novel player at the tight junctions (TJs). TRAF4 is connected to assembled TJs in confluent epithelial cells, but accumulates in the cytoplasm and/or nucleus when TJs are open in isolated cells or EGTA-treated confluent cells. In vivo, TRAF4 is consistently found at TJs in normal human mammary epithelia as well as in well-differentiated in situ carcinomas. In contrast, TRAF4 is never localized at the plasma membrane of poorly-differentiated invasive carcinomas devoid of correct TJs, but is observed in the cytoplasm and/or nucleus of the cancer cells. Moreover, TRAF4 TJ subcellular localization is remarkably dynamic. Fluorescence recovery after photobleaching (FRAP) experiments show that TRAF4 is highly mobile and shuttles between TJs and the cytoplasm. Finally, we show that intracellular TRAF4 potentiates ERK1/2 phosphorylation in proliferating HeLa cells, an epithelial cell line known to be devoid of TJs.'] Is tumor necrosis factor receptor-associated factor 4 a dynamic tight junction-related shuttle protein involved in epithelium homeostasis? | qiaojin/PubMedQA | 2 | [
-2.427171468734741,
-1.2123134136199951,
2.7416605949401855
] |
['Polyketides are a diverse group of biotechnologically important secondary metabolites that are produced by multi domain enzymes called polyketide synthases (PKS).', 'We have estimated frequencies of type I PKS (PKS I) - a PKS subgroup - in natural environments by using Hidden-Markov-Models of eight domains to screen predicted proteins from six metagenomic shotgun data sets. As the complex PKS I have similarities to other multi-domain enzymes (like those for the fatty acid biosynthesis) we increased the reliability and resolution of the dataset by maximum-likelihood trees. The combined information of these trees was then used to discriminate true PKS I domains from evolutionary related but functionally different ones. We were able to identify numerous novel PKS I proteins, the highest density of which was found in Minnesota farm soil with 136 proteins out of 183,536 predicted genes. We also applied the protocol to UniRef database to improve the annotation of proteins with so far unknown function and identified some new instances of horizontal gene transfer.'] Do a computational screen for type I polyketide synthases in metagenomics shotgun data? | qiaojin/PubMedQA | 2 | [
-2.5224339962005615,
-0.44810038805007935,
2.1076483726501465
] |
['Knowledge and quantification of the microcirculation are very important for estimating the status of an organ. Real-time contrast-enhanced sonography assesses microvascular tissue perfusion. This technique has been proposed as innocuous; however, data from experimental animals (rats) have shown renal interstitial microhemorrhage after the procedure. Therefore, we developed a porcine model to explore potential renal damage that in situ exposure might cause.', 'Kidneys from 8 anesthetized pigs were surgically exposed. An ultrasound contrast agent (sulfur hexafluoride) was infused through the femoral vein in a continuous perfusion. Destructive ultrasonic flashes were applied with a high mechanical index over only 1 kidney (the contralateral kidney was used as a control). Blinded histologic and laboratory analyses were performed to reveal any lesions.', 'Histologic analysis of the kidney samples showed no evidence of renal damage. Biochemical parameters that could represent renal tissue damage and hemoglobin levels did not change after the microbubble-ultrasound interaction.'] Does in situ kidney insonation with microbubble contrast agents cause renal tissue damage in a porcine model? | qiaojin/PubMedQA | 2 | [
-2.533132791519165,
-1.2129619121551514,
2.8607606887817383
] |
['The study aimed at the retrospective evaluation of rhGH treatment results in children with chronic renal failure CRF and short stature treated at Dpt. and Clinic of Pediatrics, Dialysis Unit and Ambulatory in Zabrze, Medical University of Silesia in Katowice. Medical records of 21 children at mean age of 11.0 years (7 girls and 14 boys) were analysed. Eleven children remained on renal replacement therapy. The mean dose of rhGH was 1.1 UI/kg/week). Five children are still on rhGH treatment.', 'Mean growth velocity during rhGH treatment was 15.2 cm/ total period of treatment, 6.98 cm/year. Mean SDS of growth at the beginning of treatment was: -3.25, at the end of treatment: -2.76 (p < 0.02). PTH value 123.6 pg/ml, at the end of treatment 241.29 pg/mL (p < 0.05).'] Does [ Evaluation of growth hormone treatment result in children with chronic renal failure -- one center experience ]? | qiaojin/PubMedQA | 2 | [
-0.6412016153335571,
-1.062536358833313,
0.8635944128036499
] |
['Chromosomal instability is a key feature in hepatocellular carcinoma (HCC). Array comparative genomic hybridization (aCGH) revealed recurring structural aberrations, whereas fluorescence in situ hybridization (FISH) indicated an increasing number of numerical aberrations in dedifferentiating HCC. Therefore, we examined whether there was a correlation between structural and numerical aberrations of chromosomal instability in HCC.', '27 HCC (5 well, 10 moderately, 12 lower differentiated) already cytogenetically characterized by aCGH were analyzed. FISH analysis using probes for chromosomes 1, 3, 7, 8 and 17 revealed 1.46-4.24 signals/nucleus, which correlated with the histological grade (well vs. moderately,p < 0.0003; moderately vs. lower, p < 0.004). The number of chromosomes to each other was stable with exceptions only seen for chromosome 8. Loss of 4q and 13q, respectively, were correlated with the number of aberrations detected by aCGH (p < 0.001, p < 0.005; Mann-Whitney test). Loss of 4q and gain of 8q were correlated with an increasing number of numerical aberrations detected by FISH (p < 0.020, p < 0.031). Loss of 8p was correlated with the number of structural imbalances seen in aCGH (p < 0.048), but not with the number of numerical changes seen in FISH.'] Are losses of chromosome arms 4q , 8p , 13q and gain of 8q correlated with increasing chromosomal instability in hepatocellular carcinoma? | qiaojin/PubMedQA | 2 | [
-1.1634126901626587,
-1.453047275543213,
1.655071496963501
] |
['Aggresomes are juxtanuclear inclusion bodies that have been proposed to represent a general cellular response to misfolded proteins in mammalian cells. Yet, why aggresomes are not a pathological characteristic of protein misfolding diseases is unclear. Here, we investigate if a misfolded protein inevitably forms aggresomes in mammalian cells.', 'We show that a cytoplasmic form of the prion protein may form aggresomes or dispersed aggregates in different cell lines. In contrast to aggresomes, the formation of dispersed aggregates is insensitive to histone deacetylase 6 inhibitors and does not result in cytoskeleton rearrangements. Modulation of expression levels or proteasome inhibitors does not alter the formation of dispersed aggregates.'] Do aggresomes represent a general cellular response to protein misfolding in mammalian cells? | qiaojin/PubMedQA | 2 | [
-2.874695062637329,
0.14824481308460236,
1.7542449235916138
] |
['Thyrotropin-releasing hormone (TRH) is expressed in rodent and human adult pancreata and in mouse pancreas during embryonic development. However, expression of TRH receptors (TRHRs) in the pancreas is controversial. We sought to provide evidence that the TRH/TRHR system might play a role in fetal development.', 'We used quantitative reverse transcription-polymerase chain reaction to measure TRH and TRHR messenger RNA (mRNA). To study the effects of TRHR expression in a pancreatic progenitor population, we expressed TRHRs in human islet-derived precursor cells (hIPCs) by infection with adenoviral vector AdCMVmTRHR. Thyrotropin-releasing hormone receptor signaling was measured as inositol phosphate production and intracellular calcium transients. Thyrotropin-releasing hormone receptor expression was measured by [H]methyl-TRH binding. Apoptosis was monitored by release of cytochrome c from mitochondria.', 'We show that TRH mRNA is expressed in human fetal and adult pancreata, and that TRHR mRNA is expressed in fetal human pancreas but not in adult human pancreas. Thyrotropin-releasing hormone receptors expressed in hIPCs were shown to signal normally. Most importantly, TRH treatment for several days stimulated apoptosis in hIPCs expressing approximately 400,000 TRHRs per cell.'] Do high levels of thyrotropin-releasing hormone receptors activate programmed cell death in human pancreatic precursors? | qiaojin/PubMedQA | 2 | [
-2.4910409450531006,
-1.0212321281433105,
2.5395619869232178
] |
['Self-ratings of olfactory function often correlates poorly with results of objective smell tests. We explored these ratings relative to self-rating of odor annoyance, to odor identification ability, and to mean perceived intensity of odors, and estimated relative genetic and environmental contributions to these traits.', 'A total of 1,311 individual twins from the general population (62% females and 38% males, aged 10-83 years, mean age 29 years) including 191 monozygous and 343 dizygous complete twin pairs from Australia, Denmark, Finland, and the United Kingdom rated their sense of smell and annoyance caused by ambient smells (e.g., smells of foods) using seven categories, and performed odor identification and evaluation task for six scratch-and-sniff odor stimuli.', 'The self-rating of olfactory function correlated with the self-rating of odor annoyance (r = 0.30) but neither correlated with the odor identification score. Quantitative genetic modeling revealed no unambiguously significant genetic contribution to variation in any of the studied traits.'] Do self-ratings of olfactory function reflect odor annoyance rather than olfactory acuity? | qiaojin/PubMedQA | 2 | [
-1.6472135782241821,
-0.1896563619375229,
0.9676006436347961
] |
['Healthy colonic mucosa uses butyrate as the major energy source. In ulcerative colitis (UC) butyrate oxidation has been shown to be disturbed, but it remains unclear whether this is a primary defect. The aim of this study was to measure mucosal butyrate oxidation in UC (involved and noninvolved colon) and in pouchitis and to study the relationship with endoscopic as well as histological disease activity.', 'Butyrate oxidation was measured in 73 UC patients, 22 pouchitis patients, and 112 controls (95 colon, 17 ileum) by incubating biopsies with 1 mM 14C-labeled Na-butyrate and measuring the released 14CO2.', 'Compared with that in normal colon, butyrate oxidation was significantly impaired in endoscopically active but not in quiescent disease or uninvolved colon segments. The severity of the metabolic defect was related to histological disease activity and decreased epithelial cell height. In active pouchitis, butyrate oxidation was significantly decreased compared with that in normal ileum and excluded pouches without inflammation. The histological pouchitis score correlated significantly with butyrate oxidation.'] Is pouchitis , similar to active ulcerative colitis , associated with impaired butyrate oxidation by intestinal mucosa? | qiaojin/PubMedQA | 2 | [
-2.4073989391326904,
-1.2959346771240234,
2.7867074012756348
] |
['This study investigates possible differences in the perception of quality of care at an emergency department, as related to patient background and visit characteristics.', "The study uses a prospective, descriptive survey design with data collected in May 2002 from the emergency department of a Swedish university hospital. It included 200 patients with an average age of 51 yr (range 18-91 yr). The research-based Quality from the Patient's Perspective (QPP) questionnaire, emergency department version, was used for data collection.", 'Several factors, for example, information after procedures, respect and empathy, nutrition, general atmosphere and routines, were rated significantly lower by patients with gastrointestinal symptoms, general surgery patients and patients admitted to a hospital ward, than by patients with other background or visit characteristics.'] Do different patient groups request different emergency care - a survey in a Swedish emergency department? | qiaojin/PubMedQA | 1 | [
-1.6064532995224,
1.359756588935852,
-0.48260781168937683
] |
['The prevalence of chronic hepatitis C infection in U.S. prisons is 12% to 31%. Treatment of this substantial portion of the population has been subject to much controversy, both medically and legally. Studies have demonstrated that treatment of chronic hepatitis C with pegylated interferon (PEG IFN) and ribavirin is a cost-effective measure in the general population; however, no study has addressed whether the same is true of the prison population. The aim of this study was to determine the cost-effectiveness of hepatitis C treatment with PEG IFN and ribavirin in the U.S. prison population. Cost-effectiveness was determined via a decision analysis model employing Markov simulation. The cohort of prisoners had a distribution of genotypes and stages of fibrosis in accordance with prior studies evaluating inmate populations. The probability of transitioning from one health state to another, reinfection rates, in-prison and out-of-prison mortality rates, sustained viral response rates, costs, and quality of life weights were also obtained from the literature. Sensitivity analysis was performed. In a strategy without a pretreatment liver biopsy, treatment was cost-effective for all ages and genotypes. This model was robust to rates of disease progression, mortality rates, reinfection rates, sustained viral response rates, and costs. In a strategy employing a pretreatment liver biopsy, treatment was also cost-saving for prisoners of all ages and genotypes with portal fibrosis, bridging fibrosis, or compensated cirrhosis. Treatment was not cost-effective in patients between the ages of 40 and 49 with no fibrosis and genotype 1.'] Is treating hepatitis C in the prison population cost-saving? | qiaojin/PubMedQA | 2 | [
-2.2629058361053467,
-0.8009374141693115,
2.1492552757263184
] |
['The current method of producing cultured skin substitutes (CSS) is focused on providing treatments for severe skin wounds/burns. We have developed a modified growth method to make them more suitable for in vitro product-testing/toxicity-testing purposes.', 'CSS grown in Petri dishes were either transferred to Franz diffusion cells on day 5 (modified method) or left in the Petri dish (standard method) and maintained in these environments for the remainder of the growth phase. Mitochondrial metabolism (MTT assay) was measured on days 5, 10 and 14 and histology was studied on days 5, 10 and 14. Barrier function for all tissues was evaluated by transferring them to Franz cells (standard method) and measuring transepidermal water loss (TEWL), 3H2O penetration and 14C-niacinamide permeability on days 7, 14 and 21.', 'CSS grown by the standard and modified methods showed comparable cell viability and tissue morphology. Barrier function, however, was markedly improved in CSS grown by the modified method. The average improvement at days 7 and 14 was 1.3-fold for TEWL, 2.1-fold for 3H2O penetration and 6.4-fold for 14C-niacinamide permeability. The barrier function of CSS grown by the modified method was still significantly lower than that of human cadaver skin tested by the same methods.'] Does improved barrier function observed in cultured skin substitute developed under anchored conditions? | qiaojin/PubMedQA | 2 | [
-2.3307576179504395,
-0.9626888036727905,
2.380175828933716
] |
['Receptor tyrosine kinase inhibitors (RTKIs) and mTOR inhibitors are potential novel anticancer therapies for HCC. We hypothesized that combination targeted on distinctive signal pathways would provide synergistic therapeutics.', 'ABT-869, a novel RTKI, and rapamycin were investigated in HCC pre-clinical models.', 'Rapamycin, but not ABT-869, inhibited in vitro growth of Huh7 and SK-HEP-1 HCC cells in a dose dependant manner. However, in subcutaneous Huh7 and SK-HEP-1 xenograft models, either ABT-869 or rapamycin can significantly reduce tumor burden. Combination treatment reduced the tumors to the lowest volume (95+/-20mm(3)), and was significantly better than single agent treatment (p<0.05). Immunohistochemical staining of tumor shows that ABT-869 potently inhibits VEGF in HCC in vivo. In addition, the MAPK signaling pathway has been inhibited by significant inhibition of phosphorylation of p44/42 MAP kinase by ABT-869 in vivo. Rapamycin inhibits phosphorylation of p70 S6 kinase and 4E-BP-1, downstream targets of mTOR, and decreases VEGF. Combination treatment showed synergistic effect on expression levels of p27 in vivo. Dramatic inhibition of neo-angiogenesis by ABT-869 was also demonstrated.'] Is aBT-869 , a multi-targeted tyrosine kinase inhibitor , in combination with rapamycin effective for subcutaneous hepatocellular carcinoma xenograft? | qiaojin/PubMedQA | 2 | [
-2.297025442123413,
-1.359775185585022,
2.685340166091919
] |
['To determine whether intraocular pressure (IOP) elevation alters OPA1 expression and triggers OPA1 release, as well as whether the uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist memantine blocks OPA1 release and subsequent apoptotic cell death in glaucomatous DBA/2J mouse retina.', 'Preglaucomatous DBA/2J mice received memantine (5 mg/kg, intraperitoneal injection, twice daily for 3 months) and IOP in the eyes was measured monthly. RGC loss was counted after FluoroGold labeling. OPA1, Dnm1, Bcl-2, and Bax mRNA were measured by qPCR. OPA1 protein was assessed by immunohistochemistry and Western blot. Apoptotic cell death was assessed by TUNEL staining.', 'Memantine treatment significantly increased RGC survival in glaucomatous DBA/2J mice and increased the 75-kDa OPA1 isoform, but did not alter the 80- and 90-kDa isoforms. The isoforms of OPA1 were significantly increased in the cytosol of the vehicle-treated glaucomatous retinas but were significantly decreased in memantine-treated glaucomatous retinas. OPA1 immunoreactivity was decreased in the photoreceptors of both vehicle- and memantine-treated glaucomatous retinas, but was increased in the outer plexiform layer of only the memantine-treated glaucomatous retinas. Memantine blocked apoptotic cell death in the GCL, increased Bcl-2 gene expression, and decreased Bax gene expression.'] Does memantine block mitochondrial OPA1 and cytochrome c release and subsequent apoptotic cell death in glaucomatous retina? | qiaojin/PubMedQA | 2 | [
-2.365522623062134,
-1.4020510911941528,
2.8050010204315186
] |
['To evaluate whether the extended secretin-stimulated direct endoscopic pancreatic function test (ePFT) technique is superior to the rapid 15 minute secretin-stimulated ePFT in determining pancreatic exocrine function.', 'We conducted a retrospective study of 53 patients with chronic abdominal pain and normal pancreatic imaging. These patients had ePFT testing with the following modified endoscopic collection system. Porcine synthetic or human secretin was intravenously administered 15 minutes before endoscopic duodenal aspiration. The first 10-minute collection was performed in the third portion of the duodenum. A Liguory drainage tube was placed in the third portion of the duodenum. Two additional 10-minute-period collections were obtained via the drainage tube at 30 and 45 minutes after intravenous administration of secretin. All fluid collections were analyzed for bicarbonate (HCO3) concentration.', 'Peak HCO3 concentrations at 15 minutes occurred in 62%, at 30 to 40 minutes in 23%, and at 45 to 55 minutes in 15%. Normal concentrations of HCO3 (> or =80 mEq/L) were seen in 70%, abnormal concentration in 7%, and equivocal concentrations (60-79 mEq/L) in 23% even after 55 minutes of duodenal collections.'] Is pancreatic function testing best determined by the extended endoscopic collection technique? | qiaojin/PubMedQA | 2 | [
-1.8974045515060425,
-1.5734522342681885,
2.5129141807556152
] |
['The antiproliferative mechanisms of flavonoid drugs inpancreatic cancer cells remain unclear. In this study, we evaluated the effects of the flavonoid apigenin on glucose uptake, on the expression of the glucose transporter 1 (GLUT-1), and on the phosphoinositide 3-kinase (PI3K)/Akt pathway in human pancreatic cancer cells.', 'Human pancreatic cancer cells were treated with apigenin and then underwent glucose uptake assays. Real-time reverse transcription-polymerase chain reaction and Western blot analysis were conducted to evaluate GLUT-1 and pAkt expression in CD18 and S2-013 human pancreatic cancer cells after treatment with apigenin or PI3K inhibitors (LY294002 and wortmannin).', 'Apigenin (0-100 microM) significantly inhibited, in a dose-dependent fashion, glucose uptake in CD18 and S2-013 human pancreatic cancer cell lines. Apigenin inhibited both GLUT-1 mRNA and protein expression in a concentration- and time-dependent fashion. The PI3K inhibitors, like apigenin, downregulated both GLUT-1 mRNA and protein expression.'] Does apigenin inhibit the GLUT-1 glucose transporter and the phosphoinositide 3-kinase/Akt pathway in human pancreatic cancer cells? | qiaojin/PubMedQA | 2 | [
-2.453766107559204,
-1.207506537437439,
2.6595444679260254
] |
['The sonic hedgehog (Shh) pathway has an established role in pancreatic cancer (pancreatic adenocarcinoma [PDAC]). We tested whether magnetic resonance imaging measures of vascular volume fraction (VVF) using magnetic iron oxide nanoparticles are sensitive to the antiangiogenic effect of targeted Shh therapies in a PDAC xenograft model.', 'Pancreatic adenocarcinoma xenograft lines were subcutaneously implanted into nude mice (n = 19 samples within 4 groups). Therapies were targeted to 3 loci of the Shh signaling pathway (anti-Shh antibody, cyclopamine, or forskolin). Magnetic resonance imaging (4.7-T Bruker Pharmascan) was performed (after 1 week of intraperitoneal therapy) before and after intravenous injection of MION-47. Vascular volume fraction was quantified as DeltaR2 (from multicontrast T2 sequences) and normalized to an assumed VVF in muscle of 3%. Linear regression compared VVF to histological indices including microvessel density (MVD), viable gland density (VGD), and proliferative index (PI).', 'In response to anti-Hh treatment, tumors showed a decrease in VGD, PI, MVD, and VVF compared with controls (P < 0.001). Vascular volume fraction was compared with histological indicators of response: PI (R2 = 0.88; P < 0.05), VGD (R2 = 0.87; P< 0.05), and MVD (R2 = 0.85; P < 0.05).'] Does magnetic resonance imaging monitor physiological changes with antihedgehog therapy in pancreatic adenocarcinoma xenograft model? | qiaojin/PubMedQA | 2 | [
-2.1996166706085205,
-1.5236330032348633,
2.7498297691345215
] |
['To investigate the feasibility of using calcifications as surrogates for the prostate position during cone-beam computed tomography (CBCT) image-guided radiotherapy.', 'The twice-weekly CBCT images taken during the treatment course of 4 patients were retrospectively studied for the stability of the calcifications. The geometric center of three fiducial markers was used as the reference. The planning CT images of 131 prostate patients recently treated with external beam radiotherapy at our center were reviewed to estimate the calcification occurrence rate. Analysis was conducted using the Varian Eclipse treatment planning system. Two patients were treated using prostate calcifications as the landmark in on-line registration. Both the Varian standard and the low-dose CBCT modes were used for imaging.', 'The calcifications were found to be stable during the treatment course. At the 95% confidence interval, the difference between the distance from an identified calcification to the fiducial markers on CBCT and the distance on the planning CT scans was 0.2 +/- 2.0 mm, 0.8 +/- 2.2 mm, and 0.4 +/- 2.4 mm in the left-right, anteroposterior, and superoinferior direction, respectively. Of the 131 patients, 46 (35%) had well-defined calcifications either inside the prostate or near the borders. Our experience in treating the first 2 patients demonstrated that the calcifications are easily distinguished on low-dose scans and that calcification registration can be precisely performed.'] Are calcifications potential surrogates for prostate localization in image-guided radiotherapy? | qiaojin/PubMedQA | 2 | [
-2.4051170349121094,
-1.2359405755996704,
2.7474422454833984
] |
['(5R)-5-hydroxytriptolide (LLDT-8) displayed immunosuppressive activities both in vitro and in autoimmune disease models. Here, we aim to further clarify the effect of LLDT-8 on the immune responses of human peripheral blood mononuclear cells (PBMC).', 'Cell proliferation of human PBMC from healthy donors was evaluated by [3H]-thymidine uptake. NK cell cytotoxicity was assayed using K562 cells in a [3H] lysis assay. Cytokine production was determined by enzyme-linked immunosorbent assay. The expression of cell surface molecules was detected with flow cytometry. The mRNA expression and the protein phosphorylation levels were detected by RT-PCR and Western immunoblot assay.', 'LLDT-8 at 25 and 50 nM significantly inhibited the PHA- and recall antigens-induced T cell proliferation, and suppressed mixed lymphocyte reaction. LLDT-8 reduced cytokines production (IFN-gamma, IL-2, TNF-alpha) in PHA- and Sac-activated PBMC. LLDT-8 did not alter the increased expression of MHC class I/II and B7.1, but reduced B7.2 by approximately 30%. No effect of LLDT-8 was observed for the expression of T cell activation markers (CD69, CD154). However, LLDT-8 significantly reduced IFN-gamma-expressing T cell percentages and IFN-gamma mRNA transcription in PHA-activated T cells. It also inhibited the phosphorylation levels of JNK and p38. LLDT-8 did not affect NK cytotoxic activity against K562 cells.'] Does ( 5R ) -5-hydroxytriptolide inhibit the immune response of human peripheral blood mononuclear cells? | qiaojin/PubMedQA | 2 | [
-2.304671287536621,
-1.3972549438476562,
2.706810235977173
] |
['Oral epithelial cells may be invaded by a polymicrobial intracellular flora, including pathogens together with commensals. Various oral pathogens can induce the production of interleukin-8, a potent neutrophil chemotractant, in oral epithelial cells. Evidence from the gut suggests that commensal species may modulate inflammatory responses to pathogens. The aim of this study was to examine the interleukin-8 responses of oral epithelial cells to an oral pro-inflammatory species, Fusobacterium nucleatum, in combination with an oral commensal, Streptococcus cristatus.', 'KB, TERT-2, TR146 and SCC15 cells were cocultured with F. nucleatum and S. cristatus, either alone or in combination, at 37 degrees C in 5% CO2 under various conditions. The mRNA expression of interleukin-8 was analyzed by reverse transcription-polymerase chain reaction and protein secretion was measured by enzyme-linked immunosorbent assay.', 'F. nucleatum alone evoked a potent interleukin-8 response, whereas S. cristatus alone did not induce significant interleukin-8 expression in oral epithelial cells. When present together, S. cristatus attenuated the F. nucleatum-induced interleukin-8 production in the four oral epithelial cell lines to varying degrees. The inhibitory effect of S. cristatus was independent of its viability and its co-aggregation with F. nucleatum, was not related to soluble bacterial products and appeared to require bacterial contact with epithelial cells. Similar effects were seen with several other species of oral streptococci.'] Does streptococcus cristatus attenuate Fusobacterium nucleatum-induced interleukin-8 expression in oral epithelial cells? | qiaojin/PubMedQA | 2 | [
-2.4357187747955322,
-1.3359370231628418,
2.852402448654175
] |
['Cardiac resynchronization therapy (CRT) improves cardiac performance and survival in patients with congestive heart failure. Recent observations suggest that diabetes is associated with a worse outcome in these patients. The aim of the study was to investigate the effect of diabetes and insulin treatment on outcome after CRT.', 'Diabetic status and insulin treatment were assessed in 447 patients who underwent CRT (males 80.8%, mean age 65.7 +/- 9.7 years, ejection fraction 29.9 +/- 6.11%). Patients were stratified in three groups according to the presence or absence of diabetes and insulin treatment.', 'Nondiabetic patients were 366 (79.6%), noninsulin-treated diabetic patients 62 (13.9%), insulin-treated diabetic patients 29 (6.5%). The estimated death rate was 5.15 per 100 patients-year in the nondiabetic group, 8.63 in noninsulin-treated diabetics (HR 1.59, P = 0.240), and 15.84 in insulin-treated diabetics (HR 3.05, P = 0.004). Cardiac mortality accounted for 81% of deaths in nondiabetic patients and for 56% of deaths in diabetic patients. Diabetic patients tended to have a worse recovery of left ventricular ejection fraction over time (P = 0.057) and of the distance at 6-minute walking test (6MWT) (P = 0.018).'] Is insulin-treated type 2 diabetes associated with a decreased survival in heart failure patients after cardiac resynchronization therapy? | qiaojin/PubMedQA | 2 | [
-1.228773593902588,
-1.38102388381958,
1.6821123361587524
] |
['Fibrosis and myocyte hypertrophy are classical remodeling parameters in heart failure (HF); however, an intriguing possibility is that myocytes undergo intracellular remodeling which decrease compliance, contributing to diastolic dysfunction. The most obvious candidates are cytoskeletal proteins. The cytoskeletal protein desmin reinforces the sarcomeres, enabling force generation. As a contributor to sarcomere performance, desmin may represent a better appraisal of dysfunction than fibrosis or myocyte hypertrophy.', 'HF was induced in sheep via coronary microembolization. Echocardiography was performed at baseline, 4-, and 12-months in HF. Desmin, fibrosis, and myocyte hypertrophy from infarcted LV posterior and noninfarcted LV anterior walls were measured using Western blot, immunohistochemistry, and digital image analysis. Multivariate regression analysis was performed, providing structure/function mechanisms. *p<0.05.', 'EF decreased from 55% to 24%*. LV end-diastolic area (LVEDA) increased 123%* at month-12. Fibrosis increased only in posterior LV whereas myocyte hypertrophy increased in both LV posterior and LV anterior regions but only at month-12. Desmin content progressively increased 121% at month-4 and 182%* at month-12 in both LV posterior and anterior walls. Multivariate linear regression (beta coefficient standardization) demonstrated that desmin was a much better predictor of EF (beta=-0.38*) and LVEDA (beta=0.58*) than fibrosis or myocyte hypertrophy.'] Is cytoskeletal remodeling of desmin a more accurate measure of cardiac dysfunction than fibrosis or myocyte hypertrophy? | qiaojin/PubMedQA | 2 | [
-1.8930647373199463,
-1.618541955947876,
2.5184268951416016
] |
['In order to know the role of gastric emptying in the mechanism of weight loss and early satiety after a restrictive surgical procedure for treatment of morbid obesity, a consecutive series of patients were scintigraphically investigated before and after laparoscopic adjustable gastric banding.', 'Sixteen patients undergoing laparoscopic adjustable gastric banding underwent preoperatively, and at 6 months postoperatively, a gastric emptying study (solid meal and single isotope). Esophageal retention time, lag phase, peak activity time, gastric emptying rate, fundus emptying rate, and weight loss were recorded. Upper GI symptom assessment was carried out by using a standardized questionnaire. Gastric emptying parameters were correlated with the upper GI symptoms.', 'Gastric band placement showed no significant influence on postoperative gastric emptying rate [median % (interquartile range): 42 (23.3-59) preoperatively vs 38 (31-71) postoperatively and fundus emptying rate: 59(37-91) preoperatively vs 70 (53-89) postoperatively]; however, an increase in early satiety was found. Neither gastric emptying rate nor fundus emptying rate showed a relation with early satiety or weight loss. Furthermore, no correlation was found between early satiety and lag phase, esophageal retention time, start of activity, and peak activity time in proximal stomach.'] Is weight loss after laparoscopic adjustable gastric banding caused by altered gastric emptying? | qiaojin/PubMedQA | 2 | [
-2.3110263347625732,
-1.2695372104644775,
2.667802095413208
] |
['Tumor necrosis factor-alpha has a significant role in renal tubular cell apoptosis during obstruction induced renal injury. While we have previously reported the role of tumor necrosis factor-alpha in extrinsic pathway apoptotic signaling during renal obstruction, to our knowledge its effect on intrinsic pathway signaling and mitochondrial release of cytochrome C has not previously been evaluated.', 'Male Sprague-Dawley rats were anesthetized and underwent unilateral ureteral obstruction vs sham operation. At 24 hours before surgery and every 84 hours thereafter the animals received vehicle or a pegylated form of soluble tumor necrosis factor receptor type 1. The kidneys were harvested 1 week postoperatively. The renal cortex was analyzed for tumor necrosis factor-alpha production (enzyme-linked immunosorbent assay), apoptosis (TUNEL and enzyme-linked immunosorbent assay), Bcl-2, Bcl-x(L), Bax, caspase 8 and truncated Bid expression (Western blot), and mitochondrial cytochrome C release (immunohistochemistry).', 'Renal obstruction induced increased tumor necrosis factor-alpha production, apoptotic renal tubular death, the expression of Bax, caspase 8 and truncated BID, and mitochondrial release of cytochrome C, while simultaneously stimulating decreased Bcl-2 and Bcl-x(L) expression. Treatment with the pegylated form of soluble tumor necrosis factor receptor type 1 significantly decreased obstruction induced tumor necrosis factor-alpha production, apoptosis, Bax, caspase 8, truncated Bid expression and mitochondrial cytochrome C release, and increased Bcl-2 and Bcl-x(L) expression.'] Does tumor necrosis factor-alpha induce intrinsic apoptotic signaling during renal obstruction through truncated bid activation? | qiaojin/PubMedQA | 2 | [
-2.5241854190826416,
-1.2972164154052734,
2.8954098224639893
] |
['The gamma-aminobutyric acid (GABA) system is implicated in the neurobiological actions of ethanol, and pharmacological agents that increase the activity of this system have been proposed as potential treatments for alcohol use disorders. As ethanol has its own GABA mimetic properties, it is critical to determine the mechanism by which GABAergic drugs may reduce the response to ethanol (i.e., via an inhibition or an accentuation of the neurobiological effects of ethanol).', 'In this study, we examined the ability of 3 different types of GABAergic compounds, the GABA reuptake inhibitor NO-711, the GABA(A) receptor agonist muscimol, and the GABA(B) receptor agonist baclofen, to attenuate the locomotor stimulant response to ethanol in FAST mice, which were selectively bred for extreme sensitivity to ethanol-induced locomotor stimulation. To determine whether these compounds produced a specific reduction in stimulation, their effects on ethanol-induced motor incoordination were also examined.', 'NO-711, muscimol, and baclofen were all found to potently attenuate the locomotor stimulant response to ethanol in FAST mice. However, both NO-711 and muscimol markedly increased ethanol-induced ataxia, whereas baclofen did not accentuate this response.'] Is attenuation of the stimulant response to ethanol associated with enhanced ataxia for a GABA , but not a GABA , receptor agonist? | qiaojin/PubMedQA | 2 | [
-2.50862717628479,
-1.0393383502960205,
2.5627646446228027
] |
['Leptin, a profibrogenic cytokine, plays an important role in the development of non-alcoholic steatohepatitis. Leptin also regulates immune responses, including macrophage phagocytic activity. Stellate cells are key elements in liver fibrogenesis, and previously we have demonstrated that phagocytosis of apoptotic bodies by stellate cells is profibrogenic. To study the effects of leptin on the phagocytic activity of hepatic stellate cells, we exposed both LX-2 cells and primary stellate cells to leptin, and we have observed increased phagocytic activity. In stellate cells isolated from Zucker (fa/fa) rats, the rate of phagocytosis was significantly decreased. To investigate the mechanism by which leptin induces phagocytosis, we focused on the role of Rho-guanosine triphosphate (GTP)-ases. We found that leptin induced the PI3K-dependent activation of Rac1, and that nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase activation was also implicated in this process. Leptin also induced RhoA activation and translocation to the phagosomes. Expression of the constitutive active Rac1 and RhoA both increased the phagocytic rate, whereas inhibition of the Rho-dependent kinase decreased the phagocytic activity.'] Does leptin induce phagocytosis of apoptotic bodies by hepatic stellate cells via a Rho guanosine triphosphatase-dependent mechanism? | qiaojin/PubMedQA | 2 | [
-2.5686371326446533,
-0.9952730536460876,
2.5836024284362793
] |
['Thiazolidinedione ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), are used to treat diabetes. PPARgamma is highly expressed in the colon, and exposure to thiazolidinediones has been proposed to affect the risk for colorectal neoplasia. In vitro models suggest that thiazolidinediones have antineoplastic effects, whereas in vivo studies have produced mixed results: Some indicate an increased risk for intestinal tumors. This study examined the association between PPARgamma-targeted therapies and the risk of colonic neoplasia in patients with diabetes.', 'We conducted 3 retrospective case-control studies nested within the cohort of diabetic patients who were cared for within the Kaiser Permanente of Northern California system from 1994 to 2005. Case subjects were those with colonic neoplasia identified at the time of colonoscopy (study 1), sigmoidoscopy (study 2), or at follow-up lower endoscopy (study 3). Controls had no neoplasia identified at the endoscopic examination. A minimum of 1 year of therapy was used to define medication exposure.', 'Fourteen thousand eighty-six patients were included. Among patients undergoing colonoscopy, there was an inverse association between thiazolidinedione exposure and prevalence of neoplasia (adjusted odd ratio [OR], 0.73; 95% confidence interval [CI], 0.57-0.92); however, this was not evident among patients without anemia (adjusted OR, 0.97; 95% CI, 0.64-1.49). Significant associations between any or long-term thiazolidinedione use and colonic neoplasia were not observed among patients undergoing sigmoidoscopy or serial lower endoscopies.'] Is thiazolidinedione therapy associated with increased colonic neoplasia risk in patients with diabetes mellitus? | qiaojin/PubMedQA | 2 | [
-1.7560797929763794,
-1.5474741458892822,
2.287569999694824
] |
['UpToDate and PubMed are popular sources for medical information. Data regarding the efficiency of PubMed and UpToDate in daily medical care are lacking.', 'The purpose of this observational study was to describe the percentage of answers retrieved by these information sources, comparing search results with regard to different medical topics and the time spent searching for an answer.', 'A total of 40 residents and 30 internists in internal medicine working in an academic medical center searched PubMed and UpToDate using an observation portal during daily medical care. The information source used for searching and the time needed to find an answer to the question were recorded by the portal. Information was provided by searchers regarding the topic of the question, the situation that triggered the question, and whether an answer was found.', 'We analyzed 1305 patient-related questions sent to PubMed and/or UpToDate between October 1, 2005 and March 31, 2007 using our portal. A complete answer was found in 594/1125 (53%) questions sent to PubMed or UpToDate. A partial or full answer was obtained in 729/883 (83%) UpToDate searches and 152/242 (63%) PubMed searches (P < .001). UpToDate answered more questions than PubMed on all major medical topics, but a significant difference was detected only when the question was related to etiology (P < .001) or therapy (P = .002). Time to answer was 241 seconds (SD 24) for UpToDate and 291 seconds (SD 7) for PubMed.'] Are answers to questions posed during daily patient care more likely to be answered by UpToDate than PubMed? | qiaojin/PubMedQA | 0 | [
1.5878897905349731,
-0.5995208621025085,
-1.8069459199905396
] |
['Caveolae, lipid-rich microdomains of the sarcolemma, localize and enrich cardiac-protective signaling molecules. Caveolin-3 (Cav-3), the dominant isoform in cardiac myocytes, is a determinant of caveolar formation. We hypothesized that cardiac myocyte-specific overexpression of Cav-3 would enhance the formation of caveolae and augment cardiac protection in vivo.', 'Ischemic preconditioning in vivo increased the formation of caveolae. Adenovirus for Cav-3 increased caveolar formation and phosphorylation of survival kinases in cardiac myocytes. A transgenic mouse with cardiac myocyte-specific overexpression of Cav-3 (Cav-3 OE) showed enhanced formation of caveolae on the sarcolemma. Cav-3 OE mice subjected to ischemia/reperfusion injury had a significantly reduced infarct size relative to transgene-negative mice. Endogenous cardiac protection in Cav-3 OE mice was similar to wild-type mice undergoing ischemic preconditioning; no increased protection was observed in preconditioned Cav-3 OE mice. Cav-3 knockout mice did not show endogenous protection and showed no protection in response to ischemic preconditioning. Cav-3 OE mouse hearts had increased basal Akt and glycogen synthase kinase-3beta phosphorylation comparable to wild-type mice exposed to ischemic preconditioning. Wortmannin, a phosphoinositide 3-kinase inhibitor, attenuated basal phosphorylation of Akt and glycogen synthase kinase-3beta and blocked cardiac protection in Cav-3 OE mice. Cav-3 OE mice had improved functional recovery and reduced apoptosis at 24 hours of reperfusion.'] Does cardiac-specific overexpression of caveolin-3 induce endogenous cardiac protection by mimicking ischemic preconditioning? | qiaojin/PubMedQA | 2 | [
-2.343877077102661,
-1.3624708652496338,
2.7377352714538574
] |
['Inducible nitric oxide synthase (iNOS) is an obligatory mediator of the late phase of ischemic preconditioning, but the mechanisms of its cardioprotective actions are unknown. In addition, it remains unclear whether sustained elevation of iNOS in myocytes provides chronic protection against ischemia/reperfusion injury.', 'Constitutive overexpression of iNOS in transgenic mice (alpha-myosin heavy chain promoter) did not induce contractile dysfunction and did not affect mitochondrial respiration or biogenesis, but it profoundly decreased infarct size in mice subjected to 30 minutes of coronary occlusion and 24 hours of reperfusion. In comparison with wild-type hearts, isolated iNOS-transgenic hearts subjected to ischemia for 30 minutes followed by 40 minutes of reperfusion displayed better contractile recovery, smaller infarct size, and less mitochondrial entrapment of 2-deoxy-[(3)H]-glucose. Reperfusion-induced loss of NAD(+) and mitochondrial release of cytochrome c were attenuated in iNOS-transgenic hearts, indicating reduced mitochondrial permeability transition. The NO donor NOC-22 prevented permeability transition in isolated mitochondria, and mitochondrial permeability transition-induced NAD(+) loss was decreased in wild-type but not iNOS-null mice treated with the NO donor diethylene triamine/NO 24 hours before ischemia and reperfusion ex vivo. iNOS-mediated cardioprotection was not abolished by atractyloside. Reperfusion-induced production of oxygen-derived free radicals (measured by electron paramagnetic resonance spectroscopy) was attenuated in iNOS-transgenic hearts and was increased in wild-type hearts treated with the mitochondrial permeability transition inhibitor cyclosporin A.'] Does cardiac myocyte-specific expression of inducible nitric oxide synthase protect against ischemia/reperfusion injury by preventing mitochondrial permeability transition? | qiaojin/PubMedQA | 2 | [
-2.4332034587860107,
-1.3881282806396484,
2.8552818298339844
] |
['Persistent stimulation of cardiac beta1-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the alpha 2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (ADRB1 and ADRA2C, respectively) on the risk of death/transplant in heart failure patients.', 'Sixteen sequence variations in ADRA2C and 17 sequence variations in ADRB1 were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation.', 'Three polymorphisms in ADRA2C and five polymorphisms in ADRB1 were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18) relative to all other genotype classes.'] Do multiple interactions between the alpha 2C- and beta1-adrenergic receptors influence heart failure survival? | qiaojin/PubMedQA | 2 | [
-2.2310006618499756,
-1.2899760007858276,
2.5306801795959473
] |
['Surgical staging of endometrial carcinoma is practiced to identify the true extent of disease. The impact of para-aortic lymphadenectomy (PALD) on survival is unproven. The purpose of this study was to determine if a staging procedure that includes PALD is associated with improved survival in endometrial carcinoma patients who had been surgically staged.', "Retrospective review of patients' records.", 'Ajou University Hospital, a tertiary care hospital in South Korea.', 'One hundred and sixty patients with endometrial carcinoma.', 'We retrospectively analyzed a total of 160 FIGO stage I-III endometrial carcinoma patients without grossly metastatic para-aortic lymph nodes, who underwent surgery between 1994 and 2007. Exclusion criteria included presurgical radiation, stage IV disease and sarcomas. Two groups were identified: patients who underwent pelvic lymphadenectomy (PLD) and PALD (n=85) versus those who underwent PLD alone (n=75). Survival was analyzed using Kaplan-Meier method and Cox proportional hazards model.', 'Disease-free and overall survival.', "Overall, patients who underwent PALD demonstrated improved 5-year disease-free survival (81.0 vs 91.2%) and overall survival (85.8 vs 96.2%) compared to those who underwent PLD alone (p=0.019 and p=0.039, respectively). After multivariate analysis, patients' age (p=0.028), FIGO stage (p<0.001) and lymphadenectomy (p=0.014) were independent prognostic factors. The type of lymphadenectomy did not affect survival of low-risk patients. In intermediate to high-risk patients, PALD improved disease-free survival and showed a trend toward improvement of overall survival."] Does para-aortic lymphadenectomy improve survival in patients with intermediate to high-risk endometrial carcinoma? | qiaojin/PubMedQA | 2 | [
-1.9219778776168823,
-1.440242886543274,
2.3634910583496094
] |
['Peritoneal adhesions are the most common complication of the abdominal surgery. Normal saline is frequently used to rinse the peritoneal cavity during abdominal surgery, although there is no well-established data describing effect of such procedure on the process of formation of peritoneal adhesions.', 'Effect of 0.9% NaCl solution on viability, oxidative stress, and fibrinolytic activity of human peritoneal mesothelial cells maintained in in vitro culture was evaluated.', 'Exposure of mesothelial cells to 0.9% NaCl induces oxidative stress, derangement of their structure with subsequent increased release of tissue factor (+75%) and plasminogen activator inhibitor-1 (+19%), and simultaneous suppression of tissue plasminogen activator release (-39%). In effect, ration tissue plasminogen activator/plasminogen activator inhibitor-1 was reduced in 0.9% NaCl-treated cells by 50%. Pretreatment of cells with precursor of glutathione synthesis: L-2-oxothiazolidine-4-carboxylic acid prevented these changes.'] Does normal saline induce oxidative stress in peritoneal mesothelial cells? | qiaojin/PubMedQA | 2 | [
-2.48105788230896,
-1.2664388418197632,
2.8449020385742188
] |
['This was a prospective cross-sectional study for people with chronic spinal cord injury (SCI).', 'To (1) evaluate the intensity level and nature of physical activity in community-dwelling individuals living with SCI, and (2) explore the relation between descriptive individual variables (for example, lesion level), secondary complications and participation in physical activity.', 'Urban community setting.', 'A total of 49 subjects with SCI who used a manual wheelchair for primary mode of mobility (mean years since injury, 11.8; mean age, 43.7 years; 67% paraplegia) completed the physical activity recall assessment for people with SCI (PARA-SCI).', 'Approximately 50% of reported physical activity among individuals with SCI is due to activities of daily living. The amount of physical activity was not related to lesion level, age, body mass index or waistline size. Greater heavy-intensity activity was related to lower levels of pain and fatigue and higher levels of self-efficacy, whereas higher amounts of mild-intensity activity and total activity were related to less depressive symptoms.'] Is physical activity related to lower levels of pain , fatigue and depression in individuals with spinal-cord injury : a correlational study? | qiaojin/PubMedQA | 2 | [
-2.3968923091888428,
0.3759065270423889,
1.3045670986175537
] |
['Social avoidance and inhibition in animals is associated with hyperresponsiveness of the glucocorticoid stress-system. In humans, the relation between glucocorticoid stress-reactivity and social avoidance behavior remains largely unexplored. We investigated whether increased cortisol stress-responsiveness is linked to increased social avoidance behavior in patients with social anxiety disorder (SAD).', 'Patients with SAD (n = 18) as well as two control groups of healthy participants (n = 22) and patients with posttraumatic stress disorder (PTSD; n = 17), respectively, performed a social approach-avoidance task (AA-task) in a baseline condition and in a social stress condition (provided by the Trier Social Stress Test). The AA-task is a computerized reaction-time task measuring the speed of manual approach and avoidance responses to visually presented social threat cues (angry faces). Salivary cortisol, blood pressure, and subjective anxiety were assessed throughout the experiment.', 'Patients with SAD showed larger cortisol responses to the social stress test, as compared with healthy and PTSD control subjects. Most crucially, these increased cortisol responses were significantly correlated to the increase in social avoidance behavior measured by the AA-task in the social stress condition in SAD. An additional regression analysis showed that the cortisol responses predicted the stress-induced increase in social avoidance tendencies over and above the effects of blood pressure and subjective anxiety.'] Is hypothalamus-pituitary-adrenal axis hyperresponsiveness associated with increased social avoidance behavior in social phobia? | qiaojin/PubMedQA | 2 | [
-2.6553633213043213,
-0.6482648253440857,
2.3413009643554688
] |
['Tactile defensiveness in children is associated with difficult social relations, emotional dysregulation, and inattention. However, there are no studies of lead exposure and tactile defensiveness in children or animals in spite of the fact that lead exposure is also associated with inattention and emotional dysregulation.', 'In this study we tested whether lead exposure induces tactile defensiveness in rhesus monkeys.', 'We tested 61 monkeys from a 3 (no lead, 1-year lead, 2-year lead) x 2 (succimer chelation or not) factorial experiment for tactile defensiveness at 4 years of age. Lead-treated monkeys had been orally administered lead in a daily milk solution from 8 days of life to either 1 or 2 years of age to produce blood lead levels of 35-40 mg/dL. Succimer chelation therapy or placebo was administered at 1 year of age. We measured tactile defensiveness using six repeated trials of each of three textures as a swipe to the cheek and neck.', 'Lead-exposed monkeys showed higher negative responses to repeated tactile stimulation compared with controls. Blood lead during the first 3 months of life was positively correlated with the negative response on the tactile defensiveness test. There was an interaction of lead exposure x succimer chelation x trials, but it is not clear that succimer chelation was beneficial with respect to tactile defensiveness.'] Does developmental lead exposure induce tactile defensiveness in rhesus monkeys ( Macaca mulatta )? | qiaojin/PubMedQA | 2 | [
-2.412587881088257,
-0.620705783367157,
2.0547378063201904
] |
['Although severe hepatitis and liver tumors occur in a high percentage of A/J male mice naturally infected with Helicobacter hepaticus, these effects have not been observed after injection of adult mice with the bacteria.', 'We tested the hypothesis that perinatal exposure to the bacteria is required for liver tumorigenesis.', 'A/J female mice were infected by intragastric (ig) or intraperitoneal (ip) treatment with 1.5 x 10(8) H. hepaticus before pregnancy. We examined offspring at progressive time intervals, including some kept until natural death in old age. A/J, BALB/c, and C57BL/6 weanling male mice were similarly treated ig with the bacteria and observed for up to 2 years.', 'After ip bacterial infection of A/J females, 41% of their male offspring developed hepatitis and 33% had hepatocellular tumors, including 18% with hepatocellular carcinoma. Treatment by the ig route resulted in a similar incidence of hepatitis in offspring (35%) but fewer total liver tumors (8%) and carcinomas (4%). By contrast, ig instillation of H. hepaticus in weanling A/J, C57BL/6, or BALB/c mice resulted in low incidence of hepatitis (0-20%) and few liver tumors, despite presence of bacteria confirmed in feces.'] Does marked liver tumorigenesis by Helicobacter hepaticus require perinatal exposure? | qiaojin/PubMedQA | 2 | [
-2.3677752017974854,
-0.9481949210166931,
2.3583757877349854
] |
['The decrease of maternal docosahexaenoic (DHA) status during pregnancy has been associated with postpartum depression, especially in women with a low intake of DHA. Since the DHA intake in the Netherlands is low, we investigated whether supplementation of low doses of DHA or DHA plus arachidonic acid (AA) during pregnancy and lactation could prevent depressive symptoms and sleep disturbances in this period.', 'Women were supplemented daily with placebo, DHA (220 mg) or DHA+AA (220 mg each) from week 16 of pregnancy till three months postpartum. Fatty acid analyses were performed in the available plasma samples at 16 and 36 weeks of pregnancy. Depressive symptoms were measured in weeks 16 and 36 of pregnancy and six weeks postpartum using EPDS and within one week postpartum using a blues questionnaire.', '119 women completed the study. The average frequency of fish intake was low, 0.94 times per week, and did not differ between the groups. The supplementation groups did not differ in mean EPDS scores or changes in EPDS scores, nor in incidence or severity of postpartum blues. Red blood cell DHA, AA and DHA/AA ratio did not correlate with EPDS or blues scores. Indices of sleep quality did not differ between the groups.'] Does supplementation of a low dose of DHA or DHA+AA prevent peripartum depressive symptoms in a small population based sample? | qiaojin/PubMedQA | 2 | [
-1.50835120677948,
-0.7301825881004333,
1.2822397947311401
] |
['The development of abdominal aortic aneurysms (AAAs) involves a complex interplay of extracellular matrix degradation, inflammation, and apoptosis. We have previously shown that protein kinase Cdelta (PKCdelta) plays a critical role in vascular smooth muscle cell (vSMC) apoptosis in the setting of oxidative stresses. Here, we show that PKCdelta is also involved in the signaling that draws inflammatory cells to aneurismal tissue.', 'Immunostaining for monocyte chemotactic factor (MCP)-1 and PKCdelta was performed on paraffin-fixed arterial sections. Enzyme-linked immunosorbent assay to detect MCP-1 produced by vSMCs was performed on media from cultured rat A10 cells after cytokine induction with or without the PKCdelta-specific inhibitor rottlerin. Migration of isolated lymphocytes was evaluated in response to media from activated A10 cells.', 'Human AAAs show widespread and elevated expression of PKCdelta that is not seen in normal aortic tissues. Cytokine stimulation of cultured vSMCs induced vigorous production of the key chemotactant MCP-1, the expression of which was PKCdelta dependent. Stimulated vSMCs were capable of inducing the migration of leukocytes, and this effect was also dependent on PKCdelta activity. Staining of human AAA tissue for MCP-1 showed an expression pattern that was identical to that of PKCdelta and smooth muscle specific alpha-actin.'] Does upregulation of protein kinase cdelta in vascular smooth muscle cells promote inflammation in abdominal aortic aneurysm? | qiaojin/PubMedQA | 2 | [
-2.442600965499878,
-1.3134469985961914,
2.7886829376220703
] |
["This study examined whether college students' descriptive norm perceptions of protective behavioral drinking strategies explain variance in use of such strategies, controlling for covariates of students' gender, typical number of drinks, and negative drinking consequences.", 'Derivation (n = 7,960; 55.2% women) and replication (n = 8,534; 54.5% women) samples of undergraduate students completed the Campus Alcohol Survey in classroom settings. Students estimated how frequently other students used each of nine protective behavioral strategies (PBS) and how frequently they themselves used each strategy.', "All items assessing norm perception of PBS (NPPBS) had pattern matrix coefficients exceeding .50 on a single factor, and all contributed to the overall scale reliability (Cronbach's alpha = .81). Hierarchical regression analyses indicated NPPBS explained significant variance in PBS, controlling for covariates, and explained an additional 7% of variance (p < .001). A Gender x Scale (PBS, NPPBS) repeated-measures analysis of variance revealed students believed peers used PBS less frequently than they themselves did (eta(p) (2) = .091, p < .001). Such social distancing was greater in women (omega(effect) (2) = .151, p < .001) than in men (omega(effect) (2) = .001, p < .001)."] Does college students ' norm perception predict reported use of protective behavioral strategies for alcohol consumption? | qiaojin/PubMedQA | 2 | [
-0.7388520240783691,
-0.3969668447971344,
0.2681092917919159
] |
['Vascular access failure is a common cause of morbidity in patients with end-stage renal failure on hemodialysis (HD). Activation of the coagulation system and formation of a thrombus play important roles in recurrent arteriovenous fistula/graft (AVFG) failure. Thrombin in complex with thrombomodulin (TM) activates the anticoagulant protein C and creates activated protein C (APC), which is subsequently inactivated by the protein C inhibitor (PCI). The plasma concentration of the complex between APC and PCI (P-APC-PCI complex) is increased in hypercoagulable states and is therefore a sensitive indicator of the degree of activation of blood coagulation.', 'Thirty-five HD patients dialyzed through a functioning AVFG were studied. The period of patency of AVFGs was recorded. Blood was drawn before and after the HD session for the analysis of the APC-PCI complex, soluble TM concentration and activity, von Willebrand factor antigen and homocysteine.', 'Patients with frequent AVFG failures (n = 8) had a significantly lower level of P-APC-PCI complex (median 0.09 microg/l) than those with less frequent AVFG failures (median 0.18 microg/l; n = 27; p = 0.04). No other significant differences were found between the groups.'] Is low plasma activated protein C-protein C inhibitor complex concentration associated with vascular access failure in hemodialysis patients? | qiaojin/PubMedQA | 2 | [
-2.2966043949127197,
-1.4274113178253174,
2.8060998916625977
] |
["Calcium phosphate (Ca-P), mainly concerning hydroxyapatite (HA), is the main inorganic component of the body's hard tissue. It is acknowledged that Ca-P biomaterial not only has osteoconduction but also can form bone bonding to host bone, making an ideal tissue-engineering scaffold. However, whether Ca-P biomaterial possesses osteoinductivity is still debated. The present study was performed to explore the expression level of osteoblast maker genes in human mesenchymal stem cells (hMSCs) grown on a Ca-P biomaterial.", 'hMSCs were cultured on the HA/tricalcium phosphate-(TCP) double-phase ceramic. After coculture for 5, 10, 15, or 20 days, the cells were digested for isolation of total RNA. Fluorescence quantitative polymerase chain reaction was used to detect the relative mRNA levels of Runx2, collagen type I, osteopontin, and osteocalcin, all of which are the marker genes for osteoblasts. The mg63 cell was recruited as the reference and un-cocultured hMSCs as the negative controls. Alkaline phosphatase (ALP) activity in the cells was also examined after culture for 10 or 20 days.', 'Our results showed that the expression levels of all four genes continued to rise during the first 10 days. Then, both collagen type I and Runx2 decreased. In contrast, osteocalcin mRNA reached its maximum at day 15 and osteopontin mRNA kept increasing throughout the whole experimental period. Additionally, ALP activity increased in a time-dependent manner.'] Do the upregulation of osteoblast marker genes in mesenchymal stem cells prove the osteoinductivity of hydroxyapatite/tricalcium phosphate biomaterial? | qiaojin/PubMedQA | 2 | [
-2.2741849422454834,
-1.2992913722991943,
2.6004230976104736
] |
["The Parkland-Baxter formula is a widely utilized resuscitation guideline for the initial management of fluid deficits in burn victims. Implementation of resuscitation formulas has helped to reduce the incidence of shock and hypovolemic organ failure such as acute renal failure in the setting of burn trauma. However, it has been shown that indiscriminate implementation of these formulas may inappropriately suit individual patient's requirements. In our experience resuscitation by the Parkland formula often forced corrections in order to reach predefined resuscitation goals.", 'Given these findings we felt the need to refine formula based resuscitation strategies.', 'Reviewing a subset of 81 burn admissions we screened for predictive parameters in addition to total body surface area burned (TBSA burned) and body weight influencing resuscitation volume requirements.', 'Using multivariate linear regression analysis (MRA) various parameters were integrated in a stepwise forward mathematical selection procedure resulting in a modified resuscitation formula.', 'A new formula including body weight, TBSA burned, inhalation injury (IHI), high blood alcohol level (BAL) and a compensating factor for advanced age was set up. The new formula was compared to the original Parkland formula. Both were assessed for predictive reliability (PR(+/-20%)). Using this strategy we were able to improve PR(+/-20%) from 28.4% to 51.9%.'] Do new multifactorial burn resuscitation formula offers superior predictive reliability in comparison to established algorithms? | qiaojin/PubMedQA | 2 | [
-2.134699583053589,
-1.2308893203735352,
2.426034450531006
] |
['Breast and intestinal cancers chemoprevention would significantly impact on cancer care. Hence, we assessed the chemopreventive efficacy of the antioxidant lipoic acid (LA) in mice overexpressing a wild-type Her2/neu, as an animal model of breast cancer, and in APCmin mice for intestinal cancer.', 'Mice were randomised at weaning, and were treated with LA for lifetime. Tumour incidence, growth rate and histopathology were analysed on an individual tumour basis.', 'LA efficiently chemoprevented tumour appearance in APCmin mice. Strikingly, though, LA doses, that were chemopreventive in APCmin mice (> or = 300 microg/day), increased breast cancer growth in Her2/neu mice. Even in experimental groups, where LA overall reduced tumour risk (80 microg/day), LA consistently stimulated the growth rate of established breast tumours. Breast and colon tumours incidence was unaffected by LA, indicating no significant impact of LA on tumour initiation and no protection from mutations driving tumour progression.'] Does intestinal tumour chemoprevention with the antioxidant lipoic acid stimulate the growth of breast cancer? | qiaojin/PubMedQA | 2 | [
-2.125260591506958,
-1.3473458290100098,
2.4636144638061523
] |
['We studied the impact of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on inflammation-driven hepatocarcinogenesis.', 'HB-EGF expression was determined by qRT-PCR and immunodetection in hepatocellular adenoma and carcinoma and in mesenchymal (MC) and parenchymal liver cells obtained from different models of inflammation. The functions of HB-EGF in early hepatocarcinogenesis were assessed in co-cultures of unaltered and initiated/premalignant hepatocytes.', 'In human and rat (pre)malignant liver lesions, HB-EGF levels were comparable to that of the surrounding tissue. In inflamed livers HB-EGF was expressed predominantly in MC and was further increased by pro-inflammatory lipopolysaccharide (LPS) or linoleic acid hydroperoxide (LOOH). In culture, DNA-replication occurred rather in initiated/premalignant than unaltered hepatocytes and was further elevated by LOOH- or LPS-stimulated MC-supernatants. The supernatant effects were abrogated by pre-incubation with HB-EGF-neutralizing antisera. HB-EGF itself induced DNA-replication and mitosis preferentially in the initiated/premalignant cells. When transducing hepatocytes with a dominant-negative ErbB1-construct, HB-EGF-induced DNA-replications were blocked completely in unaltered hepatocytes but incompletely in initiated/premalignant cells, which suggests elevated ErbB-mediated signal transduction in first stages of hepatocarcinogenesis.'] Is hB-EGF a paracrine growth stimulator for early tumor prestages in inflammation-associated hepatocarcinogenesis? | qiaojin/PubMedQA | 2 | [
-2.4222328662872314,
-1.3602079153060913,
2.8236937522888184
] |
['To explore the reasons why nursing staff use the subjective "worried" Medical Emergency Team (MET) calling criterion and compare the outcomes of calls activated using the "worried" criterion with those calls activated using "objective" criteria such as vital sign abnormalities.', 'A descriptive study of MET calls in six acute hospitals over a 12 months period. Outcomes for "objective" and "worried" calls were compared.', 'The "worried" criterion was used to activate 29% of 3194 MET calls studied; it was the single most common reason for a MET call. Half (51.7%) of the "worried" calls were related to problems with Airway, Breathing, Circulation or Neurology. \'Breathing\' problems accounted for the largest proportion (35.2%). A low oxygen saturation by pulse oximetry (SpO2) (n=249, 26.9%) and \'respiratory distress\' (n=133, 14.4%) were the most common reasons for a "worried" call. Only 1.1% (10) of calls triggered by the "worried" criteria had cardiac arrest as an outcome compared with 170 calls (7.6%) for "objective" criteria. The proportion of patients who remained in a general ward area after MET calls was higher for the "worried" calls.'] Does analysis of medical emergency team call comparing subjective to `` objective '' call criteria? | qiaojin/PubMedQA | 2 | [
-1.1150379180908203,
-0.4427511990070343,
0.7156939506530762
] |
['This report examines the relationship between pretreatment prostate-specific antigen (PSA) velocity (PSAV) and freedom from biochemical recurrence (FFBR) in men with prostate cancer treated with low-dose-rate prostate brachytherapy (LDRPB).', 'This is a report of 51 men treated with LDRPB between 1997 and 1999.', 'two or more evaluable PSA values >3 months apart and <18 months before treatment. PSAV is calculated using a linear regression equation. All patients had biopsy confirmed, clinically localized prostate cancer. All men were treated with (125)I LDRPB. The prescription dose was 144Gy. Biochemical failure is determined from PSA values over time using the ASTRO Consensus Definition. FFBR is estimated using Kaplan-Meier method. Pretreatment variables analyzed include percentage positive biopsy cores, D(90), risk group, and PSAV. All p values are two-sided.', 'The median followup is 60 months. The median pretreatment PSA is 6.5, 75% of men were Stage T1c, and 88% had Gleason score > or =6; 10% developed evidence of biochemical recurrence at a median of 13 months (range, 6-36). The 6-year estimate of FFBR is 90% for the entire cohort. On univariate analysis, pretreatment PSAV and risk group are associated with FFBR. The 6-year estimate of FFBR in patients with a PSAV <2 ng/mL/yr is 100% vs. 80% (95% confidence interval: 64-96%) when the pretreatment PSAV is > or =2 ng/mL/yr before LDRPB (p = 0.017).'] Is pretreatment prostate-specific antigen velocity associated with freedom from biochemical recurrence of prostate cancer after low-dose-rate prostate brachytherapy alone? | qiaojin/PubMedQA | 2 | [
-0.9180738925933838,
-1.8824214935302734,
1.7803678512573242
] |
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