sot_question
stringlengths
42
9.8k
ds_name
stringclasses
8 values
pred_label
int64
0
2
logits
listlengths
3
3
['At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs) death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis.Apoptosis occurs in not only neuron but also in NPCs and neuroblast. When growth and survival signals such as EGF or LIF are removed, apoptosis is activated as well as the induction of differentiation. To investigate the regulation of cell death during developmental stage, it is essential to investigate the regulation of apoptosis of NPCs.', 'Neural progenitor cells were cultured from E14 embryonic brains of Sprague-Dawley rats. For in vivo VPA animal model, pregnant rats were treated with VPA (400 mg/kg S.C.) diluted with normal saline at E12. To analyze the cell death, we performed PI staining and PARP and caspase-3 cleavage assay. Expression level of proteins was investigated by Western blot and immunocytochemical assays. The level of mRNA expression was investigated by RT-PCR. Interaction of Bcl-XL gene promoter and NF-κB p65 was investigated by ChIP assay.', 'In this study, FACS analysis, PI staining and PARP and caspase-3 cleavage assay showed that VPA protects cultured NPCs from cell death after growth factor withdrawal both in basal and staurosporine- or hydrogen peroxide-stimulated conditions. The protective effect of prenatally injected VPA was also observed in E16 embryonic brain. Treatment of VPA decreased the level of IκBα and increased the nuclear translocation of NF-κB, which subsequently enhanced expression of anti-apoptotic protein Bcl-XL.'] Does valproic acid inhibit neural progenitor cell death by activation of NF-κB signaling pathway and up-regulation of Bcl-XL?
qiaojin/PubMedQA
2
[ -2.3668315410614014, -1.3053569793701172, 2.734708309173584 ]
['Systolic strain rate (SR) has been shown to correlate with the transmural extent of myocardial infarction (MI). Ischemic postconditioning (PC) decreases MI size. We aimed to determine whether SR may predict the reduction of left ventricular (LV) remodeling induced by PC in a murine model of ischemia-reperfusion.', 'C57BL6 mice underwent 60 minutes of left coronary artery occlusion followed by reperfusion. PC consisted of 3 cycles of 1 minute of reperfusion and 1 minute of ischemia performed immediately after reperfusion. After 24 hours of reperfusion, a first subset of mice was euthanized for determination of infarct size. An additional subset of mice underwent 3 months of reperfusion. Echocardiography and SR were serially assessed at baseline, 3 days, and 1, 2, 3 months after reperfusion. PC decreased the infarct size and increased SR values within infarcted segments as soon as 24 hours after reperfusion as compared with controls (14 ± 1 versus 6 ± 1 s(-1), P<0.001). Systolic SR was correlated with MI size assessed by the area of infarction/area at risk (r=-0.88, P<0.001). At 3 months, PC improved LV ejection fraction (55 ± 4 versus 45 ± 3%; P<0.05) and decreased LV dimensions as compared with controls. Strain rate at day 3 correlated with LV ejection fraction (0.75; P<0.001), end-systolic (r=-0.75; P=0.001), and end-diastolic volumes (r=-0.70; P<0.001) at month 3.'] Does strain-rate imaging predict the attenuation of left ventricular remodeling induced by ischemic postconditioning after myocardial infarction in mice?
qiaojin/PubMedQA
2
[ -0.8711791038513184, -1.8350625038146973, 1.6673574447631836 ]
['Little is known about the association between self-weighing frequency and weight gain prevention, particularly in worksite populations.', 'The degree to which self-weighing frequency predicted 2-year body weight change in working adults was examined.', 'The association between self-weighing frequency (monthly or less, weekly, daily, or more) and 24-month weight change was analyzed in a prospective cohort analysis (n\u2009=\u20091,222) as part of the larger HealthWorks trial.', 'There was a significant interaction between follow-up self-weighing frequency and baseline body mass index. The difference in weight change ranged from -4.4\u2009±\u20090.8\xa0kg weight loss among obese daily self-weighers to 2.1\u2009±\u20090.4\xa0kg weight gain for participants at a healthy weight who reported monthly self-weighing.'] Is self-weighing frequency associated with weight gain prevention over 2 years among working adults?
qiaojin/PubMedQA
2
[ -0.23111769556999207, -0.9299766421318054, 0.30329829454421997 ]
['To identify prognostic factors associated with functional outcome at 13 months in a sample of stroke rehabilitation patients. Specifically, we hypothesized that cognitive functioning early after stroke would predict long-term functional outcome independently of other factors.', '163 stroke rehabilitation patients underwent a structured neuropsychological examination 2-3 weeks after hospital admittance, and their functional status was subsequently evaluated 13 months later with the modified Rankin Scale (mRS) as outcome measure. Three predictive models were built using linear regression analyses: a biological model (sociodemographics, apolipoprotein E genotype, prestroke vascular factors, lesion characteristics and neurological stroke-related impairment); a functional model (pre- and early post-stroke cognitive functioning, personal and instrumental activities of daily living, ADL, and depressive symptoms), and a combined model (including significant variables, with p value <0.05, from the biological and functional models).', 'A combined model of 4 variables best predicted long-term functional outcome with explained variance of 49%: neurological impairment (National Institute of Health Stroke Scale; β = 0.402, p < 0.001), age (β = 0.233, p = 0.001), post-stroke cognitive functioning (Repeatable Battery of Neuropsychological Status, RBANS; β = -0.248, p = 0.001) and prestroke personal ADL (Barthel Index; β = -0.217, p = 0.002). Further linear regression analyses of which RBANS indexes and subtests best predicted long-term functional outcome showed that Coding (β = -0.484, p < 0.001) and Figure Copy (β = -0.233, p = 0.002) raw scores at baseline explained 42% of the variance in mRS scores at follow-up.'] Does early post-stroke cognition in stroke rehabilitation patients predict functional outcome at 13 months?
qiaojin/PubMedQA
2
[ -1.566651463508606, -1.354383111000061, 1.9889261722564697 ]
['Postoperative pancreatic fistula (PF) is still regarded as a major complication in pancreatic surgery. In the present study, we evaluated the risk of PF in a large study population of patients with neuroendocrine pancreatic tumors (NPT), pancreatic cancer (PC), and chronic pancreatitis (CP).', 'Patients who underwent pancreatic surgery between 1989 and 2008 at our institution were retrospectively evaluated. Patients were analyzed regarding age, gender, BMI, alcohol, smoking, preoperative diabetes, reason for operation, operative procedure, and PF. Three different grades of PF (grades A, B, C) were defined.', '133 patients with NPT, 212 patients with PC, 52 patients with CP, and 76 patients with other reasons were evaluated. Patients with a NPT had a significant higher risk of developing a PF than patients with PC, CP, or other reasons (p = 0.0001). Enucleation of the tumor was associated with the highest rate of PF (p = 0.001). In a multivariate analysis, BMI >26, and preoperative diabetes were associated with a higher rate of PF (p = 0.042 and p = 0.02, respectively).'] Are neuroendocrine pancreatic tumors risk factors for pancreatic fistula after pancreatic surgery?
qiaojin/PubMedQA
2
[ -1.5746923685073853, -1.0876638889312744, 1.6674178838729858 ]
['Increasing the size of medical school classes has resulted in the use of community hospitals for emergency medicine (EM) clerkships. While differences in clinical experience are expected, it is unclear if they are significant. The authors set out to investigate whether or not clinical site affects student performance on a standard written exam as a measure of medical knowledge.', 'This was a retrospective analysis of data from 2005 to 2009 for a mandatory fourth-year EM clerkship at one institution that uses academic (EM residency), hybrid (residency training site but not EM), and community (no residency programs) hospitals as clerkship sites. Multiple variable linear regression was used to examine the relationship between clerkship site and end of clerkship written exam score. Additional covariates included were the time of year the rotation was completed (by 3- or 4-month tertiles) and whether the student matched in EM. As test scores increased over the study period, a time factor was also included to account for this trend. A p-value of <0.05 was required for variable retention in the model.', 'A total of 718 students completed the clerkship and had complete data for analysis. Thirty-five students matched in EM. A total of 311 rotated at academic sites, 304 at hybrid sites, and 103 at community sites. After adjusting for covariates, clinical site was not a significant predictor of exam score (F(2,691) = 0.42, p = 0.65). Factors associated with higher test score were student match in EM (beta coefficient = 3.4, 95% confidence interval [CI] = 1.0 to 5.7) and rotation in July through September (beta coefficient = 1.8, 95% CI = 0.5 to 3.0, against a reference of January through April). No significant interaction terms or confounders were identified.'] Does clinical teaching site affect test performance in an emergency medicine clerkship?
qiaojin/PubMedQA
0
[ 0.21802005171775818, -1.1358591318130493, 0.015715500339865685 ]
['A potential independent association was recently demonstrated between high red blood cell distribution width (RDW) and the risk of all-cause mortality in patients with cardiovascular disease, although the mechanism remains unclear. However, there have been no reports on the relationship between RDW and mortality in acute kidney injury (AKI) patients treated with continuous renal replacement therapy (CRRT). In this study, we assessed whether RDW was associated with mortality in AKI patients on CRRT treatment in the intensive care unit (ICU).', 'We enrolled 470 patients with AKI who were treated with CRRT at the Yonsei University Medical Center ICU from August 2007 to September 2009 in this study. We performed a retrospective analysis of demographic, biochemical parameters and patient outcomes. Following CRRT treatment, 28-day all-cause mortality was evaluated.', 'At the initiation of CRRT treatment, RDW level was significantly correlated with white blood cell count, hemoglobin (Hb) and total cholesterol. Patients with high RDW levels exhibited significantly higher 28-day mortality rates than patients with low RDW levels (P < 0.01). Baseline RDW level, Sequential Organ Failure Assessment (SOFA) score, low mean arterial pressure (MAP) and low cholesterol levels were independent risk factors for mortality. In multivariate Cox proportional hazard analyses, RDW at CRRT initiation was an independent predictor for 28-day all-cause mortality after adjusting for age, gender, MAP, Hb, albumin, total cholesterol, C-reactive protein and SOFA score.'] Is red blood cell distribution width an independent predictor of mortality in acute kidney injury patients treated with continuous renal replacement therapy?
qiaojin/PubMedQA
2
[ -2.04768967628479, -1.2905073165893555, 2.456991195678711 ]
['Cardiovascular diseases are the most important cause of death in patients with impaired kidney function. Left ventricular hypertrophy (LVH), cardiac interstitial fibrosis and cardiovascular calcifications are characteristic of chronic renal insufficiency (CRI). Periostin is a fibrogenesis- and calcification-related matricellular protein re-expressed in adult tissues undergoing remodelling in response to pathological stimuli. The role of periostin in CRI-induced LVH is unknown.', 'Rats were 5/6-nephrectomized (NX), and after 15 weeks of disease progression high-calcium, high-phosphate or paricalcitol treatment was given for 12 weeks. Cardiac tissue and blood samples were taken to study periostin gene expression and to determine factors contributing to its reactivation, respectively. Left ventricular (LV) periostin expression was also examined in response to angiotensin II or arginine(8)-vasopressin (AVP)-induced pressure overload and in spontaneously hypertensive rats.', 'CRI resulted in a 6.5-fold increase in LV periostin messenger RNA (mRNA) levels. Positive extracellular immunostaining for periostin was detected in areas of infiltrated inflammatory cells and fibrotic lesions. There was a significant correlation between LV periostin mRNA levels and plasma biomarkers of impaired kidney function, LVH, fibrogenesis-related proteins osteopontin and osteoactivin, and anti-calcific matrix Gla protein. Moreover, LV periostin gene expression in CRI correlated positively with systolic blood pressure (BP) and was activated rapidly in response to angiotensin II or AVP infusions.'] Is left ventricular periostin gene expression associated with fibrogenesis in experimental renal insufficiency?
qiaojin/PubMedQA
2
[ -2.4190690517425537, -1.3310267925262451, 2.827033042907715 ]
['To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response.', 'Multicenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed.', '174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to every week. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them.'] Is adalimumab effective in long-term real life clinical practice in both luminal and perianal Crohn 's disease . The Madrid experience?
qiaojin/PubMedQA
2
[ -2.029188871383667, -1.1715412139892578, 2.2970142364501953 ]
['Etonogestrel (ENG) implant is an effective method of contraception. The implant is designed to provide contraceptive efficacy for 3 years with a relatively quick return of fertility upon its removal. Menstrual irregularities are not uncommon on long-acting progestins and can often be the factor for discontinuation or removal. A retrospective chart analysis was done on 58 patients who chose to be on the ENG implant. Age ranged from 12 to 24 years. The cycle ranged from 1 to 17 months. The mean length of use of the implant was 10.9 months. Over the 20-month period, 13 ENG implants were removed because of menstrual bleeding problems.', 'We conducted a chart review of the adolescent patients who received the ENG implant in our adolescent clinic. An analysis was done based on symptoms experienced by patients who were on the ENG implant and their management, which in some cases resulted in its removal.', 'The data is presented on adolescent and young adult patients who receive their reproductive care in the Adolescent Medicine Clinic at the University of Kentucky, Lexington, KY, USA.'] Do menstrual bleeding patterns in adolescents using etonogestrel ( ENG ) implant?
qiaojin/PubMedQA
2
[ -2.3564298152923584, -0.7271270751953125, 2.212484359741211 ]
['Twenty-one excised femurs were studied using (1) a high-resolution digital X-ray device to estimate three textural parameters, (2) dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD), and (3) mechanical tests to failure. Textural parameters significantly correlated with BMD (p < 0.05) and bone strength (p < 0.05). Combining texture parameters and BMD significantly improved the fracture load prediction from adjusted r(2)\u2009= 0.74 to adjusted r(2)\u2009=0.82 (p < 0.05).', 'The purpose of this study is to determine if the combination of bone texture parameters using a new high-resolution X-ray device and BMD measurement by DXA provided a better prediction of femoral failure load than BMD evaluation alone.', 'The proximal ends of 21 excised femurs were studied using (1) a high-resolution digital X-ray device (BMA, D3A Medical Systems) to estimate three textural parameters: fractal parameter Hmean, co-occurrence, and run-length matrices, (2) DXA to measure BMD, and (3) mechanical tests to failure in a side-impact configuration. Regions of interest in the femoral neck, intertrochanteric region, and greater trochanter were selected for DXA and bone texture analysis. Every specimen was scanned twice with repositioning before mechanical testing to assess reproducibility using intraclass correlation coefficient (ICC) with 95% confidence interval. The prediction of femoral failure load was evaluated using multiple regression analysis.', 'Thirteen femoral neck and 8 intertrochanteric fractures were observed with a mean failure load of 2,612 N (SD, 1,382 N). Fractal parameter Hmean, co-occurrence, and run-length matrices each significantly correlated with site-matched BMD (p < 0.05) and bone strength (p < 0.05). The ICC of the textural parameters varied between 0.65 and 0.90. Combining bone texture parameters and BMD significantly improved the fracture load prediction from adjusted r(2)\u2009=0.74 to adjusted r(2)\u2009= 0.82 (p < 0.05).'] Does combination of texture analysis and bone mineral density improve the prediction of fracture load in human femurs?
qiaojin/PubMedQA
2
[ -1.56916081905365, -1.5433911085128784, 2.145540714263916 ]
['Gene transcription is regulated by DNA transcriptional regulatory elements, promoters and enhancers that are located outside the coding regions. Here, we examine the characteristic 3-base periodicity of the coding sequences and analyse its correlation with the genome-wide transcriptional profile of yeast.', 'The analysis of coding sequences by a new class of indices proposed here identified two different sources of 3-base periodicity: the codon frequency and the codon sequence. In exponentially growing yeast cells, the codon-frequency component of periodicity accounts for 71.9% of the variability of the cellular mRNA by a strong association with the density of elongating mRNA polymerase II complexes. The mRNA abundance explains most of the correlation between the codon-frequency component of periodicity and protein levels. Furthermore, pyrimidine-ending codons of the four-fold degenerate small amino acids alanine, glycine and valine are associated with genes with double the transcription rate of those associated with purine-ending codons.'] Are the 3-base periodicity and codon usage of coding sequences correlated with gene expression at the level of transcription elongation?
qiaojin/PubMedQA
2
[ -2.3737800121307373, -0.34452423453330994, 1.7986935377120972 ]
['In the human brain, there are at least as many astrocytes as neurons. Astrocytes are known to modulate neuronal function in several ways. Thus, they may also contribute to cerebral insulin actions. Therefore, we examined whether primary human astrocytes are insulin-responsive and whether their metabolic functions are affected by the hormone.', 'Commercially available Normal Human Astrocytes were grown in the recommended medium. Major players in the insulin signaling pathway were detected by real-time RT-PCR and Western blotting. Phosphorylation events were detected by phospho-specific antibodies. Glucose uptake and glycogen synthesis were assessed using radio-labeled glucose. Glycogen content was assessed by histochemistry. Lactate levels were measured enzymatically. Cell proliferation was assessed by WST-1 assay.', 'We detected expression of key proteins for insulin signaling, such as insulin receptor β-subunit, insulin receptor substrat-1, Akt/protein kinase B and glycogen synthase kinase 3, in human astrocytes. Akt was phosphorylated and PI-3 kinase activity increased following insulin stimulation in a dose-dependent manner. Neither increased glucose uptake nor lactate secretion after insulin stimulation could be evidenced in this cell type. However, we found increased insulin-dependent glucose incorporation into glycogen. Furthermore, cell numbers increased dose-dependently upon insulin treatment.'] Does insulin promote glycogen storage and cell proliferation in primary human astrocytes?
qiaojin/PubMedQA
2
[ -2.642172336578369, -0.6113068461418152, 2.3181235790252686 ]
['Lower extremity (LE) arterial trauma and its treatment may lead to extremity compartment syndrome (ECS). In that setting, the decision to perform fasciotomies is multifactoral and is not well delineated. We evaluated the outcomes of patients with surgically treated LE arterial injury who underwent early or delayed fasciotomies.', 'The National Trauma Data Bank (NTDB) was retrospectively reviewed for patients who had LE arterial trauma and underwent both open vascular repair and fasciotomies. Exclusion criteria were additional non-LE vascular trauma, head or spinal cord injuries, crush injuries, burn injuries, and declaration of death on arrival. Patients were divided into those who had fasciotomies performed within 8h (early group) or >8h after open vascular repair (late group). Comparative analyses of demographics, injury characteristics, complications, and outcomes were performed.', 'Of the 1469 patient admissions with lower extremity arterial trauma that met inclusion criteria there were 612 patients (41.7%) who underwent fasciotomies. There were 543 and 69 patients in the early and late fasciotomy groups, respectively. There was no significant difference in age, injury severity, mechanism of injury, associated injuries, and type of vascular repair between the groups. A higher rate of iliac artery injury was observed in the late fasciotomy group (23.2% vs. 5.9%, P<.001). Patients in the early fasciotomy group had lower amputation rate (8.5% vs. 24.6%, P<.001), lower infection rate (6.6% vs. 14.5%, P = .028) and shorter total hospital stay (18.5 ± 20.7 days vs. 24.2 ± 14.7 days, P = .007) than those in the late fasciotomy group. On multivariable analysis, early fasciotomy was associated with a 4-fold lower risk of amputation (Odds Ratio 0.26, 95% CI 0.14-0.50, P<.0001) and 23% shorter hospital LOS (Means Ratio 0.77, 95% CI 0.64-0.94, P = .01).'] Is early fasciotomy in patients with extremity vascular injury associated with decreased risk of adverse limb outcomes : a review of the National Trauma Data Bank?
qiaojin/PubMedQA
2
[ -1.761768102645874, -1.4615495204925537, 2.2510194778442383 ]
['To describe changes of anti-Müllerian hormone (AMH) and inhibin B during low-dose gonadotropin ovulation induction (OI) treatment in women with polycystic ovary syndrome (PCOS), and thus disturbed selection of the dominant follicle.', 'Observational study.', 'A referral fertility clinic.', 'Women with PCOS (n = 48) and normo-ovulatory women (n = 23).', 'Serum AMH, inhibin B, FSH, and E(2) concentrations were measured at start of stimulation, on the day of follicle selection, and at administration of hCG during OI cycles and were compared with concentration measured during the normal menstrual cycle.', 'Development of a single dominant follicle was observed in 92% of all OI cycles, reflected by similar E(2) concentrations compared with those in spontaneous cycles. AMH concentrations were constant during low-dose ovarian stimulation. Inhibin B concentrations remained elevated in patients with PCOS, suggesting prolonged survival of small antral follicles, whereas in controls inhibin B concentrations declined during the late follicular phase.'] Are serum anti-Müllerian hormone and inhibin B concentrations useful predictors of ovarian response during ovulation induction treatment with recombinant follicle-stimulating hormone in women with polycystic ovary syndrome?
qiaojin/PubMedQA
2
[ -2.544606924057007, -1.0727801322937012, 2.671868085861206 ]
['Sodium nitroprusside-enhanced cardiopulmonary resuscitation consists of active compression-decompression, an impedance threshold device, abdominal binding, and large intravenous doses of sodium nitroprusside. We hypothesize that sodium nitroprusside-enhanced cardiopulmonary resuscitation will significantly increase carotid blood flow and return of spontaneous circulation compared to standard cardiopulmonary resuscitation after prolonged ventricular fibrillation and pulseless electrical activity cardiac arrest.', 'Prospective randomized animal study.', 'Hennepin County Medical Center Animal Laboratory.', 'Forty Yorkshire female farm-bred pigs weighing 32 ± 2 kg.', 'In protocol A, 24 isoflurane-anesthetized pigs underwent 15 mins of untreated ventricular fibrillation and were subsequently randomized to receive standard cardiopulmonary resuscitation (n = 6), active compression-decompression cardiopulmonary resuscitation + impedance threshold device (n = 6), or sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 12) for up to 15 mins. First defibrillation was attempted at minute 6 of cardiopulmonary resuscitation. In protocol B, a separate group of 16 pigs underwent 10 mins of untreated ventricular fibrillation followed by 3 mins of chest compression only cardiopulmonary resuscitation followed by countershock-induced pulseless electrical activity, after which animals were randomized to standard cardiopulmonary resuscitation (n = 8) or sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 8).', 'The primary end point was carotid blood flow during cardiopulmonary resuscitation and return of spontaneous circulation. Secondary end points included end-tidal CO2 as well as coronary and cerebral perfusion pressure. After prolonged untreated ventricular fibrillation, sodium nitroprusside-enhanced cardiopulmonary resuscitation demonstrated superior rates of return of spontaneous circulation when compared to standard cardiopulmonary resuscitation and active compression-decompression cardiopulmonary resuscitation + impedance threshold device (12 of 12, 0 of 6, and 0 of 6 respectively, p < .01). In animals with pulseless electrical activity, sodium nitroprusside-enhanced cardiopulmonary resuscitation increased return of spontaneous circulation rates when compared to standard cardiopulmonary resuscitation. In both groups, carotid blood flow, coronary perfusion pressure, cerebral perfusion pressure, and end-tidal CO2 were increased with sodium nitroprusside-enhanced cardiopulmonary resuscitation.'] Does sodium nitroprusside-enhanced cardiopulmonary resuscitation improve resuscitation rates after prolonged untreated cardiac arrest in two porcine models?
qiaojin/PubMedQA
2
[ -2.0739564895629883, -1.4738467931747437, 2.5675339698791504 ]
['To investigate whether human umbilical cord blood mesenchymal stem cells, a novel source of progenitors with multilineage potential: 1) decrease traumatic brain injury sequelae and restore brain function; 2) are able to survive and home to the lesioned region; and 3) induce relevant changes in the environment in which they are infused.', 'Prospective experimental study.', 'Research laboratory.', 'Male C57Bl/6 mice.', 'Mice were subjected to controlled cortical impact/sham brain injury. At 24 hrs postinjury, human umbilical cord blood mesenchymal stem cells (150,000/5 μL) or phosphate-buffered saline (control group) were infused intracerebroventricularly contralateral to the injured side. Immunosuppression was achieved by cyclosporine A (10 mg/kg intraperitoneally).', 'After controlled cortical impact, human umbilical cord blood mesenchymal stem cell transplantation induced an early and long-lasting improvement in sensorimotor functions assessed by neuroscore and beam walk tests. One month postinjury, human umbilical cord blood mesenchymal stem cell mice showed attenuated learning dysfunction at the Morris water maze and reduced contusion volume compared with controls. Hoechst positive human umbilical cord blood mesenchymal stem cells homed to lesioned tissue as early as 1 wk after injury in 67% of mice and survived in the injured brain up to 5 wks. By 3 days postinjury, cell infusion significantly increased brain-derived neurotrophic factor concentration into the lesioned tissue, restoring its expression close to the levels observed in sham operated mice. By 7 days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a nonphagocytic activation of microglia/macrophages as shown by a selective rise (260%) in CD11b staining (a marker of microglia/macrophage activation/recruitment) associated with a decrease (58%) in CD68 (a marker of active phagocytosis). Thirty-five days postinjury, controlled cortical impact human umbilical cord blood mesenchymal stem cell mice showed a decrease of glial fibrillary acidic protein positivity in the scar region compared with control mice.'] Do human umbilical cord blood mesenchymal stem cells protect mice brain after trauma?
qiaojin/PubMedQA
2
[ -2.359205961227417, -1.4061936140060425, 2.803898811340332 ]
['Microbial manipulations in early life can affect gut development and inflammatory status of the neonate. The maternal diet during pregnancy and lactation also influences the health of the offspring, but the impact of maternal high-fat (HF) feeding along with modulations of the gut microbiota on body weight, fat deposition and gut function in the offspring has been poorly studied.', 'Rat dams were given access to either an HF or a standard low-fat diet during the last 2 weeks of pregnancy and during lactation and effects on body weight and gastrointestinal function were investigated in the 14-day-old offspring. To elucidate whether bacterial administration to the dam could modulate any effects of the diets in the rat pups, another group of dams were given Escherichia coli in their drinking water.', 'Maternal HF feeding resulted in increased body and fat pad weights in the offspring, along with increased levels of the acute-phase protein, haptoglobin and decreased protein content and disaccharidase activities in the small intestine. The addition of E. coli further accentuated these responses in the young rats, which, in addition to higher body weights and increased fat deposition, also showed an increased intestinal permeability and elevated levels of haptoglobin.'] Are effects of a high-fat diet during pregnancy and lactation modulated by E. coli in rat offspring?
qiaojin/PubMedQA
2
[ -2.8695027828216553, 0.0922856479883194, 1.8465518951416016 ]
['Not all health care workers (HCWs) are at the same risk for tuberculin skin test (TST) conversion, indicating latent tuberculosis (TB) infection.', 'To identify risk factors for TST conversion among HCWs.', 'A retrospective cohort study conducted at a tertiary university medical centre included every HCW who had had a negative two-step TST at work entry and at least one consecutive TST in the period 2005-2009 (mean follow-up period 55 months). Binomic logistic regression analysis was used to identify risk factors for TST conversion. Potential risk factors such as age, health care profession, patient exposure profile, workplace division and history of bacille Calmette-Guérin vaccination were entered in the model.', 'A total of 450 subjects met the inclusion criteria, of whom 93 had TST conversion. The highest annual rates of TST conversion occurred in workers who worked as housekeeping staff (6.9%). Older age, a work environment with high patient turnover and employment in maintenance departments were significant risk factors (adjusted odds ratios 2.05, 5.2 and 8.4 respectively).'] Do housekeeping health care workers have the highest risk for tuberculin skin test conversion?
qiaojin/PubMedQA
2
[ -1.8268158435821533, -0.3212439715862274, 1.2315552234649658 ]
['Positive outward remodeling of pre-existing collateral arteries into functional conductance arteries, arteriogenesis, is a major endogenous rescue mechanism to prevent cardiovascular ischemia. Collateral arterial growth is accompanied by expression of kinin precursor. However, the role of kinin signaling via the kinin receptors (B1R and B2R) in arteriogenesis is unclear.', 'The purpose of this study was to elucidate the functional role and mechanism of bradykinin receptor signaling in arteriogenesis.', 'Bradykinin receptors positively affected arteriogenesis, with the contribution of B1R being more pronounced than B2R. In mice, arteriogenesis upon femoral artery occlusion was significantly reduced in B1R mutant mice as evidenced by reduced microspheres and laser Doppler flow perfusion measurements. Transplantation of wild-type bone marrow cells into irradiated B1R mutant mice restored arteriogenesis, whereas bone marrow chimeric mice generated by reconstituting wild-type mice with B1R mutant bone marrow showed reduced arteriogenesis after femoral artery occlusion. In the rat brain 3-vessel occlusion arteriogenesis model, pharmacological blockade of B1R inhibited arteriogenesis and stimulation of B1R enhanced arteriogenesis. In the rat, femoral artery ligation combined with arterial venous shunt model resulted in flow-driven arteriogenesis, and treatment with B1R antagonist R715 decreased vascular remodeling and leukocyte invasion (monocytes) into the perivascular tissue. In monocyte migration assays, in vitro B1R agonists enhanced migration of monocytes.'] Is arteriogenesis modulated by bradykinin receptor signaling?
qiaojin/PubMedQA
2
[ -2.4930412769317627, -1.3083889484405518, 2.817946195602417 ]
['In this study, we tested the antitumor activity of the dual phosphoinositide 3-kinase (PI3K)/mTOR inhibitor BEZ235 against gastric cancer in vitro and in vivo.', "Gastric cancer cell lines (N87, MKN45, and MKN28) were incubated with BEZ235 and assessed for cell viability, cell cycle, and PI3K/mTOR target inhibition. In vivo, athymic nude mice were inoculated with N87, MKN28, or MKN45 cells and treated daily with BEZ235. 3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake was measured via small animal positron emission tomography (PET).", 'In vitro, BEZ235 dose dependently decreased the cell viability of gastric cancer cell lines. The antiproliferative activity of BEZ235 was linked to a G(1) cell-cycle arrest. In vivo, BEZ235 treatment resulted in PI3K/mTOR target inhibition as shown by dephosphorylation of AKT and S6 protein in all xenograft models. However, BEZ235 treatment only inhibited tumor growth of N87 xenografts, whereas no antitumor effect was observed in the MKN28 and MKN45 xenograft models. Sensitivity to BEZ235 in vivo correlated with downregulation of the proliferation marker thymidine kinase 1. Accordingly, [(18)F]FLT uptake was only significantly reduced in the BEZ235-sensitive N87 xenograft model as measured by PET.'] Does gastric cancer growth control by BEZ235 in vivo correlate with PI3K/mTOR target inhibition but with [ 18F ] FLT uptake?
qiaojin/PubMedQA
2
[ -2.2190170288085938, -1.4561498165130615, 2.6645877361297607 ]
['• To identify additional factors that might improve the diagnosis of ureteric stones using ultrasonography (US) as the primary diagnostic method.', '• We performed a retrospective study of 228 patients who underwent rigid ureterorenoscopy (URS) for obstructive ureteric stones. • Patient age, sex, body mass index (BMI) and stone location and size were recorded. • All patients underwent US for stone detection before surgery. • If no cause of the flank pain was found by US, computer tomography (CT) was performed to confirm the absence of ureteric stones.', '• In 57 (25%), 15 (6.6%) and 156 (68.4%) patients a stone was localized on the proximal, mid- and distal ureter, respectively. • In 96 (42.1%), 122 (53.5%) and 10 (4.4%) patients the stone measured 0-5, 6-10 and >10 mm, respectively. • The mean (range) BMI of the patients was 24.7 (17.3-37.2) kg/m(2). • The overall stone detection rate using US was 86.4% overall, and 96.4% in adults ≤ 35 years. In 72/197 patients (36.5%) the stones found using US measured ≤ 5 mm and in 24/31 patients (77.4%) the stones found using CT measured ≤ 5 mm. • Age (P= 0.008), stone size (P < 0.001) and BMI (P= 0.013) were factors that independently affected ureteric stone diagnosis using US.'] Is in young adults with a low body mass index ultrasonography sufficient as a diagnostic tool for ureteric stones?
qiaojin/PubMedQA
2
[ 0.1346316635608673, -1.7321981191635132, 0.6661179065704346 ]
['Diabetes is a risk factor for female sexual dysfunction (FSD). FSD has several etiologies, including a vasculogenic component that could be exacerbated in diabetes. The internal pudendal artery supplies blood to the vagina and clitoris and diabetes-associated functional abnormalities in this vascular bed may contribute to FSD.', 'The Goto-Kakizaki (GK) rat is a non-obese model of type 2 diabetes with elevated endothelin-1 (ET-1) activity. We hypothesize that female GK rats have diminished sexual responses and that the internal pudendal arteries demonstrate increased ET-1 constrictor sensitivity.', 'Female Wistar and GK rats were used. Apomorphine (APO)-mediated genital vasocongestive arousal (GVA) was measured. Functional contraction (ET-1 and phenylephrine) and relaxation (acetylcholine, ACh) in the presence or absence of the ETA receptor antagonist (ETA R; atrasentan) or Rho-kinase inhibitor (Y-27632) were assessed in the internal pudendal and mesenteric arteries. Protein expression of ET-1 and RhoA/Rho-kinase signaling pathway was determined in the internal pudendal and mesenteric arteries.', 'APO-mediated GVAs; contraction and relaxation of internal pudendal and mesenteric arteries; ET-1/RhoA/Rho-kinase protein expression.', 'GK rats demonstrated no APO-induced GVAs. Internal pudendal arteries, but not mesenteric arteries, from GK rats exhibited greater contractile sensitivity to ET-1 compared with Wistar arteries. ETA R blockade reduced ET-1-mediated constriction in GK internal pudendal and mesenteric arteries. Rho-kinase inhibition reduced ET-1-mediated constriction of GK internal pudendal but not mesenteric arteries; however, it had no effect on arteries from Wistar rats. RhoA protein expression was elevated in GK internal pudendal arteries. At the highest concentrations, ACh-mediated relaxation was greater in the GK internal pudendal artery; however, no difference was observed in the mesenteric artery.'] Do internal pudendal artery from type 2 diabetic female rats demonstrate elevated endothelin-1-mediated constriction?
qiaojin/PubMedQA
2
[ -2.4342548847198486, -1.314538836479187, 2.775094509124756 ]
['\u2002 The data on the beneficial effect of ursodeoxycholic acid (UDCA) in non-alcoholic steatohepatitis (NASH) are controversial. The difference of opinion is connected with UDCA dosage to be used. Therefore, we evaluated the dose-dependent efficacy of UDCA in experimental NASH.', '\u2002 Male Wistar rats were fed the methionine- and choline-deficient (MCD) diet for 10\u2003weeks. Rats were administrated UDCA (10, 20, 40 and 80\u2003mg/kg bodyweight intragastrically) after 6\u2003weeks of the MCD diet.', '\u2002 Animals fed the MCD diet developed severe steatohepatitis. Treatment with UDCA dose-dependently decreased liver damage, but only high-dose UDCA (80\u2003mg/kg) significantly diminished ultrastructural changes in addition to preventing steatosis, ballooning and inflammatory changes in the liver. The activities of serum marker enzymes and the content of liver triglyceride and blood glucose were increased in MCD diet-fed rats, but decreased in all the UDCA-treated groups. Serum insulin concentration was decreased whereas the quantitative insulin sensitivity check index did not changed in MCD diet-fed groups. Serum tumor necrosis factor-α content was strongly increased after MCD diet and normalized in the UDCA-treated rats, with the most pronounced effect in the highest dose groups, 40 and 80\u2003mg/kg. The contents of endogenous ethanol in blood and intestinal mucus were increased in MCD diet-fed rats which were significantly lowered by UDCA (40 and 80\u2003mg/kg per day).'] Does ursodeoxycholic acid dose-dependently improve liver injury in rats fed a methionine- and choline-deficient diet?
qiaojin/PubMedQA
2
[ -1.8716379404067993, -1.4864565134048462, 2.3418898582458496 ]
['Macrophage migration inhibitory factor (MIF) has been proposed to play a detrimental role in stroke. We recently showed that MIF promotes neuronal death and aggravates neurological deficits during the first week after experimental stroke, in mice. Since MIF regulates tissue inflammation, we studied the putative role of MIF in post-stroke inflammation.', 'We subjected C57BL/6 mice, Mif-/- (MIF-KO) or Mif+/+ (WT), to a transient occlusion of the right middle cerebral artery (tMCAo) or sham-surgery. We studied MIF expression, GFAP expression and the number of CD74-positive cells in the ischemic brain hemisphere 7 days after tMCAo using primarily immunohistochemistry. We determined IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12, KC/CXCL-1 and TNF-α protein levels in the brain (48 h after surgery) and serum (48 h and 7 days after surgery) by a multiplex immunoassay.', 'We observed that MIF accumulates in neurons and astrocytes of the peri-infarct region, as well as in microglia/macrophages of the infarct core up to 7 days after stroke. Among the inflammatory mediators analyzed, we found a significant increase in cerebral IL-12 and KC levels after tMCAo, in comparison to sham-surgery. Importantly, the deletion of Mif did not significantly affect the levels of the cytokines evaluated, in the brain or serum. Moreover, the spleen weight 48 h and 7 days subsequent to tMCAo was similar in WT and MIF-KO mice. Finally, the extent of GFAP immunoreactivity and the number of MIF receptor (CD74)-positive cells within the ischemic brain hemisphere did not differ significantly between WT and MIF-KO mice subjected to tMCAo.'] Does lack of macrophage migration inhibitory factor in mice affect hallmarks of the inflammatory/immune response during the first week after stroke?
qiaojin/PubMedQA
2
[ -2.300236940383911, -1.302865743637085, 2.6564571857452393 ]
['Chromosomal aneuploidy, that is to say the gain or loss of chromosomes, is the most common abnormality in cancer. While certain aberrations, most commonly translocations, are known to be strongly associated with specific cancers and contribute to their formation, most aberrations appear to be non-specific and arbitrary, and do not have a clear effect. The understanding of chromosomal aneuploidy and its role in tumorigenesis is a fundamental open problem in cancer biology.', 'We report on a systematic study of the characteristics of chromosomal aberrations in cancers, using over 15,000 karyotypes and 62 cancer classes in the Mitelman Database. Remarkably, we discovered a very high co-occurrence rate of chromosome gains with other chromosome gains, and of losses with losses. Gains and losses rarely show significant co-occurrence. This finding was consistent across cancer classes and was confirmed on an independent comparative genomic hybridization dataset of cancer samples. The results of our analysis are available for further investigation via an accompanying website.'] Does large-scale analysis of chromosomal aberrations in cancer karyotypes reveal two distinct paths to aneuploidy?
qiaojin/PubMedQA
2
[ -2.4934628009796143, -0.20437230169773102, 1.8485302925109863 ]
['Chromosome 3p21 is an important locus harboring critical tumor suppressor genes (TSGs) implicated in the pathogenesis of multiple tumors including esophageal carcinoma (EC). Aberrant promoter methylation is a fundamental mechanism of inactivation of TSGs in cancer. RASSF1A, a candidate tumor suppressor gene, recently cloned from the lung tumor locus at 3p21.3, is frequently inactivated by hypermethylation of its promoter region in a number of malignancies. We undertook this study to investigate the methylation status of RASSF1A and its significance in esophageal squamous cell carcinoma (ESCC).', 'Real-time RT-PCR and real-time methylation-specific PCR (real-time MSP) were used to detect RASSF1A expression and the methylation status of the RASSF1A promoter, respectively, in 124 primary ESCC tissues.', 'Hypermethylation, partial methylation and unmethylation of the promoter region of RASSF1A were detected in 56 (45.2%), 23 (18.6%) and 45 (36.2%) of 124 ESCC samples, respectively. Unmethylation of the promoter region of RASSF1A was detected in 119 (96%) of the 124 corresponding noncancerous tissues. Five (4.0%) of 124 noncancerous tissues showed partial methylation. The presence of hypermethylation was statistically associated with loss of RASSF1A mRNA expression in primary ESCC (p <0.05). There were statistically significant correlations between the presence of hypermethylation and regional lymph node involvement (p=0.000), histological differentiation (p=0.009) and tumor stage (p=0.000).'] Is hypermethylation-modulated downregulation of RASSF1A expression associated with the progression of esophageal cancer?
qiaojin/PubMedQA
2
[ -1.9116047620773315, -1.461793303489685, 2.386345624923706 ]
['To compare 12-year (1997-2008) trends in the distribution of Body Mass Index (BMI) status and physical fitness test performances among 8- to 9-year-old Greek children living in rural and urban areas.', 'Population data derived from 11 national school-based health surveys conducted from 1997 to 2008. Anthropometric measurements and physical fitness test performances (ie, multistage shuttle run, vertical jump, small ball throw, and 30-meter sprint) from 725,163 children were analyzed. Distribution between rural and urban areas was based on the Hellenic National Statistics Service (HNSS) criteria.', 'Trend analysis showed an increase in the prevalence of obesity in children living in urban areas from 7.2% in 1997 to 11.3% in 2008 for girls (P < .001) and from 8.1% to 12.4% (P < .001) for boys. In rural areas, obesity increased from 7% in 1997 to 13% in 2008 for girls (P < .001), and from 8.2% to 14.1% (P < .001) for boys. The annual rate of obesity increase was 40%-50% higher in children from rural areas. Nevertheless, rural children presented better performances in all of the physical fitness tests examined. Specifically, mean values of aerobic performance decreased from 3.58 ± 1.9 stages in 1997 to 3.02 ± 2.1 stages in 2007 for boys (P < .001), and from 2.97 ± 1.5 stages to 2.53 ± 1.7 stages (P < .001) for girls in urban areas, whereas in rural areas, the correspondent values were not significantly different between 1997 and 2007.'] Are greek children living in rural areas heavier but fitter compared to their urban counterparts : a comparative , time-series ( 1997-2008 ) analysis?
qiaojin/PubMedQA
1
[ 0.3124362826347351, 0.5002747774124146, -1.3673136234283447 ]
['In the United States, the obese population has increased markedly over the last four decades, and this trend continues. High patient weight places additional stress on TKA components, which may lead to increased polyethylene wear, osteolysis, radiolucencies, and clinical failure. Metal-backed tibial components and all-polyethylene tibial components in the general population have comparable osteolysis and failure, but it is unclear whether these components yield similar osteolysis and failure in obese patients.', 'We therefore determined the (1) function, (2) occurrence of osteolysis, and (3) complications in a cohort of obese patients receiving all-polyethylene tibial components.', 'Between September 17, 1996, and December 19, 2002, we implanted all-polyethylene tibial components in 90 obese patients (125 knees); 24 patients (33 knees) died and 13 patients (17 knees) were lost to followup, leaving 53 patients (59%) with 75 knees. All surgeries were cruciate-retaining, tricompartmental TKAs. We evaluated patients with Knee Society Scores and serial radiographs. Minimum followup was 7 years (mean, 10.4 years; range, 7-14 years).', 'At latest followup, mean Knee Society Score was 92 points. There were five tibial radiolucencies, all less than 1 mm and characterized as nonprogressive. We observed minimal, nonprogressive osteolysis in one knee. One patient required reoperation after a traumatic event. There were no implant-related failures and no implants at risk of failure.'] Are all-polyethylene tibial components in obese patients associated with low failure at midterm followup?
qiaojin/PubMedQA
2
[ -1.8841389417648315, -1.3294024467468262, 2.2454957962036133 ]
['Accurate diagnosis of melanocytic lesions is essential for the adequate clinical management of patients. Thus, thorough reporting of histopathologic parameters, especially in the initial biopsies, is a critical component of both diagnosis and staging.', 'To review current data on histopathologic prognostic factors for melanoma, with special emphasis on their use and applicability to clinical practice. Special attention is focused on the criteria highlighted by the new 2009 version of The American Joint Committee on Cancer (AJCC) system of melanoma staging and classification.', 'Published peer-reviewed literature and personal experience of the authors.'] Do an update on reporting histopathologic prognostic factors in melanoma?
qiaojin/PubMedQA
2
[ -3.003018856048584, -0.1944808065891266, 2.379230260848999 ]
['To use structured clinical data from public health nurse (PHN) documentation to describe client risk, to describe family home visiting interventions, including tailoring, and to assess the associations between client risk and intervention tailoring.', 'Retrospective cohort design. A cohort of 486 family home visiting clients who received at least 3 visits from PHNs in a local Midwest public health agency (2000-2005).', 'Omaha System variables documenting assessments, interventions, and outcomes. A risk index was created to identify low- and high-risk clients. Descriptive and inferential methods were used to describe interventions, and to assess intervention tailoring between groups.', 'Routine PHN family home visiting practice.', 'The risk index meaningfully discriminated between groups. PHNs provided more visits and interventions to clients in the high-risk group, with variations in problem, category, and target by group, demonstrating that PHNs tailored interventions to address specific client needs.'] Do public health nurses tailor interventions for families at risk?
qiaojin/PubMedQA
2
[ -2.639214277267456, 0.6998688578605652, 1.173497200012207 ]
['Dermatological teaching has traditionally stressed that complete skin examination is essential in the assessment of patients with potential skin disease.', 'To determine whether complete skin examination results in increased diagnoses of skin malignancies that would not have been discovered otherwise.', "New patients (n = 483) attending a dermatology clinic in a university teaching hospital and private dermatology practice had a complete skin examination, as is our normal practice. These patients were seen over a 9-month period (January-September 2009). All patients were examined by the same consultant dermatologist. Data were collected on patients' sex, age, presenting complaint and findings on complete skin examination.", "Two nodular malignant melanomas with mean Breslow thickness of 0·6 mm (0·4%) and one melanoma in situ were identified at sites distant from the patient's presenting complaint. Sixteen patients (3·3%) had a basal cell carcinoma that would not have been discovered if the presenting lesion alone had been examined. Thirty-three patients (6·8%) had actinic keratoses or squamous cell carcinoma in situ and nine (1·9%) had dysplastic naevi. A further 21 patients (4·3%) had a suspicious lesion biopsied or excised with subsequent benign histology. Seventy-three patients (15·1%) had other benign dermatological diagnoses requiring treatment or investigation."] Is complete skin examination essential in the assessment of dermatology patients : findings from 483 patients?
qiaojin/PubMedQA
2
[ -1.718744158744812, -0.8406047821044922, 1.5953105688095093 ]
['This study was designed to evaluate the phenolic content and antioxidant activity of ethanolic extracts from T. catappa leaves obtained by different intervals of sonication.', 'Three commonly used methods were followed to evaluate phenolic content and four in vitro methods like 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging assay, ferric reducing antioxidant potency (FRAP), and total antioxidant capacity assays for measuring the antioxidant activities. Antioxidant values of these assays were expressed in terms of milligrams vitamin C equivalent (VCE) antioxidant activities.', 'This study showed that extract obtained with 40 minutes of sonication possessed significant (P < 0.05) polyphenolic contents compared to 20 and 60 minutes sonication and control (24 hour maceration). Moreover, sonication of T. catappa leaf above 40 minutes was found to be unsuitable for extracting out phenolic contents. Even the results of antioxidant assays showed that 40 minutes of the sonicated extract exhibited significant (P < 0.05) VCE values compared to extracts obtained at different intervals of sonication and control.'] Does influence of sonication on the phenolic content and antioxidant activity of Terminalia catappa L. leave?
qiaojin/PubMedQA
2
[ -2.143066644668579, -1.1993142366409302, 2.4809398651123047 ]
['To investigate comorbidities that predict cardiac mortality and re-hospitalization in chronic heart failure (CHF) patients.', "Five hundred eighty patients (mean age 63 ± 13 years, 373 male, 207 female, mean ejection fraction (EF) 26 ± 9%) with mild, moderate or severe CHF [NYHA class II-IV] were included in this prospective observational study. We evaluated all comorbidities such as history of ischemic stroke, coronary artery disease, peripheral arterial disease, chronic obstructive lung disease, hypertension, diabetes mellitus and chronic kidney disease in CHF patients who were hospitalized due to decompensated heart failure in Kocaeli University, Faculty of Medicine's Hospital between January 2003 and July 2009. Cox regression and Kaplan-Meier survival analyses were used to establish predictors of unfavorable outcomes.", 'Of 580 patients 207 (36%) patients died due to cardiovascular reasons. In multivariable Cox regression analysis age (HR-1.06, 95% CI 1.04-1.08, p<0.001), NYHA functional class (HR-3.20 95% CI, 1.90-5.41, p<0.001), history of ischemic stroke (HR-2.48, 95% CI 1.14-5.37, p=0.022), high-sensitive C-reactive protein (HR-1.09, 95% CI, 1.04-1.15, p=0.001), brain natriuretic peptide (HR-1.00, 95% CI 1.00-1.00, p=0.01) and hemoglobin (HR-0.90, 95% CI 0.81-0.99, p=0.038) were independent predictors of cardiac death in the present study. History of ischemic stroke was demonstrated as an important comorbidity that predicts cardiovascular mortality beyond other co-morbidities in CHF patients. NYHA functional class (HR-2.85, 95% CI 1.80-4.65, p<0.001), left ventricular EF [(HR-0.98, 95% CI 0.95-0.99, p=0.039) and ischemic stroke history (HR-2.41, 95% CI 1.15-5.05, p=0.019) were independent predictors for recurrence hospitalization. The stroke history was only predictor showing recurrent hospitalization at least in one year among the other comorbid conditions, which were evaluated during study.'] Does ischemic stroke history predict increased cardiovascular mortality in chronic heart failure?
qiaojin/PubMedQA
2
[ -1.617024302482605, -1.4612793922424316, 2.146782636642456 ]
['Vascular and valvular calcifications are a common finding in chronic kidney disease (CKD) patients and are associated with increased morbidity and mortality. We investigated the hypothesis that calcification of the cardiac valves is a marker of coronary artery calcification (CAC) and thoracic aorta calcification (AoC) in hemodialysis (CKD-5) patients.', 'This was a cross-sectional study of 145 maintenance CKD stage 5 (CKD-5) patients. All patients underwent electron beam tomography for quantification of CAC and AoC score via the Agatston score. The presence of calcification of the cardiac valves was assessed by standard bi-dimensional echocardiography.', 'Eighty-four of the study patients (58%) had echocardiographic evidence of valvular calcification. A significant and graded association between valvular calcification and CAC as well as AoC was detected. Patients with 1 or 2 calcified valves had a significantly greater likelihood of having a CAC score >1,000 (odds ratio [OR] = 5.94; 95% confidence interval [95% CI], 1.91-18.44; p=0.002; and OR=3.27; 95%CI, 1.36-7.88; p=0.007, respectively). Similarly, the presence of 1 or 2 calcified valves was associated with an eightfold and threefold increased probability of an AoC score greater than the third quartile, respectively.'] Is cardiac valve calcification a marker of vascular disease in prevalent hemodialysis patients?
qiaojin/PubMedQA
2
[ -1.7070976495742798, -1.5492584705352783, 2.299044609069824 ]
['To study the expression and localization of Aven in rat and human testis from azoospermic patients with different etiologies and its regulation by estrogens.', 'Experimental study.', 'University research center and private IVF clinic.', 'Six men with obstructive azoospermia, five with hypospermatogenesis, and six with Sertoli cell-only syndrome; male Wistar rats.', 'Testicular biopsies and rat seminiferous tubules (SeT) cultured in the presence or absence of 17β-estradiol (E(2)).', 'Testicular cell localization of Aven protein was analyzed by immunohistochemistry. Expression levels of Aven in testicular biopsies and cultured SeT, in the presence or absence of 17β-estradiol, were determined by quantitative reverse transcription-polymerase chain reaction and Western blot.', 'Aven is expressed in Sertoli cells, spermatocytes, and spermatogonia of both rat and human testis. Aven is underexpressed in the testis of men with nonobstructive azoospermia, and its expression levels correlate with severity of spermatogenic status. Aven expression is regulated by E(2) in rat SeT cultured ex\xa0vivo.'] Is apoptosis-inhibitor Aven downregulated in defective spermatogenesis and a novel estrogen target gene in mammalian testis?
qiaojin/PubMedQA
2
[ -2.5465333461761475, -1.2441771030426025, 2.8299975395202637 ]
['To identify regional alterations of white matter integrity associated with apathy in Alzheimer disease (AD).', 'Cross-sectional study.', 'University Dementia Clinic.', 'Fifty-one very mild or mild probable AD subjects.', 'Volumetric magnetic resonance imaging with diffusion tensor imaging.', 'Volume of interest analyses were performed to compare regional fractional anisotropy (FA) between apathy and apathy-free group, and to test linear relationship between regional FA and apathy severity. Apathy was assessed by the Neuropsychiatric Inventory.', 'Apathy group showed significantly lower FA values than apathy-free group in the left anterior cingulum (A-C), regardless of concomitant depression and psychotropic medications. Left A-C FA values also had significant linear relationship with apathy-composite scores as a measure of apathy severity, even after controlling gray matter density of the ipsilateral anterior cingulate cortex.'] Is microstructural alteration of the anterior cingulum associated with apathy in Alzheimer disease?
qiaojin/PubMedQA
2
[ -2.6520166397094727, -0.9575721621513367, 2.7233998775482178 ]
['Previous studies have shown that patients with bipolar disorder (BD) tend to have altered immune system function. Several studies have reported that changes in interferon-gamma (IFN-γ) may play an important role in the development of BD.', 'To investigate the relationship between IFN-γ and BD, 156 patients with BD and 175 control subjects were genotyped for the IFN-γ +874A/T single nucleotide polymorphism.', 'We detected significant differences in the genotype distributions and allele frequencies of the IFN-γ +874A/T single nucleotide polymorphism (rs2430561) between patients with BD and normal controls. The T allele was found to be significantly more common among patients with BD than in controls. Additionally, significant differences in scores on the Young Mania Rating Scale (YMRS) were found between the three genotypes of this polymorphism.'] Does the T allele of the interferon-gamma +874A/T polymorphism is associate with bipolar disorder?
qiaojin/PubMedQA
2
[ -1.803985357284546, -0.7736344933509827, 1.6489360332489014 ]
['Lymphocyte homeostasis is dependent on the γc cytokines. We hypothesised that sepsis in humans is associated with differential gene expression of the γc cytokines and their associated apoptosis mediators.', 'The study population consisted of a total of 60 patients with severe sepsis, 15 with gram negative bacteraemia, 10 healthy controls and 60 patients undergoing elective lung resection surgery. Pneumonia was diagnosed by CDC NNIC criteria. Gene expression in peripheral blood leukocytes (PBLs) of interleukin (IL)-2, 7, 15 and interferon (IFN)-γ, Bax, Bim, Bcl-2 was determined by qRT-PCR and IL-2 and IL-7 serum protein levels by ELISA. Gene expression of IL-2, 7 and IFN-γ was measured in peripheral blood leukocytes (PBL), cultured in the presence of lipopolysaccharide (LPS) and CD3 binding antibody (CD3ab)', 'IL-2 gene expression was lower in the bacteraemia group compared with controls, and lower still in the sepsis group (P < 0.0001). IL-7 gene expression was similar in controls and bacteraemia, but lower in sepsis (P < 0.0001). IL-15 gene expression was similar in the three groups. Bcl-2 gene expression was less (P < 0.0001) and Bim gene expression was greater (P = 0.0003) in severe sepsis compared to bacteraemic and healthy controls. Bax gene expression was similar in the three groups.In lung resection surgery patients, post-operative pneumonia was associated with a perioperative decrease in IL-2 mRNA (P < 0.0001) and IL-7 mRNA (P = 0.003). IL-2 protein levels were reduced in sepsis and bacteraemia compared to controls (P = 0.02) but similar in pneumonia and non-pneumonia groups. IL-7 protein levels were similar in all groups.In cultured PBLs, IFN-γ gene expression was decreased in response to LPS and increased in response to CD3ab with sepsis: IL-7 gene expression increased in response to LPS in controls and to CD3ab with sepsis; Bcl-2 gene expression decreased in response to combined CD3ab and IL-2 with sepsis.'] Is post-operative infection and sepsis in humans associated with deficient gene expression of γc cytokines and their apoptosis mediators?
qiaojin/PubMedQA
2
[ -1.8753889799118042, -1.5790159702301025, 2.3821945190429688 ]
['Granulocyte colony stimulating factor (GCSF) is protective in animal models of various neurodegenerative diseases. We investigated whether pegfilgrastim, GCSF with sustained action, is protective in a mouse model of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease with manifestations of upper and lower motoneuron death and muscle atrophy accompanied by inflammation in the CNS and periphery.', 'Human mutant G93A superoxide dismutase (SOD1) ALS mice were treated with pegfilgrastim starting at the presymptomatic stage and continued until the end stage. After long-term pegfilgrastim treatment, the inflammation status was defined in the spinal cord and peripheral tissues including hematopoietic organs and muscle. The effect of GCSF on spinal cord neuron survival and microglia, bone marrow and spleen monocyte activation was assessed in vitro.', 'Long-term pegfilgrastim treatment prolonged mutant SOD1 mice survival and attenuated both astro- and microgliosis in the spinal cord. Pegfilgrastim in SOD1 mice modulated the inflammatory cell populations in the bone marrow and spleen and reduced the production of pro-inflammatory cytokine in monocytes and microglia. The mobilization of hematopoietic stem cells into the circulation was restored back to basal level after long-term pegfilgrastim treatment in SOD1 mice while the storage of Ly6C expressing monocytes in the bone marrow and spleen remained elevated. After pegfilgrastim treatment, an increased proportion of these cells in the degenerative muscle was detected at the end stage of ALS.'] Does granulocyte colony stimulating factor attenuate inflammation in a mouse model of amyotrophic lateral sclerosis?
qiaojin/PubMedQA
2
[ -2.462500810623169, -1.3377684354782104, 2.824831008911133 ]
['There are many possible predisposing factors for Achilles tendon disorders suggested in the literature but their pathogenetic relevance is not proven in most cases. The asymmetric mechanical load distribution within the Achilles tendon during locomotion is frequently addressed as a major risk factor for Achilles tendon disorders. The spatial orientation of the subtalar joint axis (STA) may influence the Achilles tendon loading possibly leading to overload injuries. Hypothesis There is a significant difference between the orientation of the STA in subjects with and without Achilles tendon pathologies.', '614 subtalar joint axes determined in 307 long-distance runners with and without Achilles tendon disorders were included. Achilles tendon disorders were defined as any Achilles tendon-related pain during or following running, existing for more than 2 weeks in the past. Motion analysis of the foot was performed using an ultrasonic pulse-echo-based measurement system. The orientation of the STA was expressed by two angles.', 'The mean inclination angle was 42 ± 16° and the mean deviation angle was 11 ± 2 3°. There was a significant difference (p=0.002) between the mean deviation angle measured in subjects with Achilles tendon pathologies (18 ± 23°) and those without (10 ± 23°).'] Is spatial orientation of the subtalar joint axis different in subjects with and without Achilles tendon disorders?
qiaojin/PubMedQA
2
[ -0.5273134708404541, -1.3723220825195312, 0.9621279239654541 ]
['South Asians have a high burden of type 2 diabetes and vascular complications. Vascular inflammation is considered central in the pathophysiology of atherosclerosis, and the complement system is thought to play an important role. Mannose-Binding Lectin (MBL), which activates the lectin pathway of complement activation, has been introduced as a risk marker of vascular damage. The present study explores the association of MBL levels, genotype and cardiovascular events in type 2 diabetic South Asians.', 'We conducted a prospective observational study. A cohort consisting of 168 type 2 diabetic South Asians was followed for a median duration of 7.66 years. At baseline, MBL levels and genotype were determined. The association with future cardiovascular events was assessed by Cox proportional hazard regression.', 'During follow-up, 31 cardiovascular events occurred in 22 subjects (11 men, 11 women). The O/O genotype was significantly associated with the occurrence of cardiovascular events (hazard ratio 3.42, 95%CI 1.24-9.49, P = 0.018). However, log MBL levels were not associated with the occurrence of cardiovascular events (hazard ratio 0.93, 95% CI 0.50-1.73).'] Is low Mannose-Binding Lectin ( MBL ) genotype associated with future cardiovascular events in type 2 diabetic South Asians . A prospective cohort study?
qiaojin/PubMedQA
2
[ -1.8780173063278198, -1.1871380805969238, 2.1601333618164062 ]
['Non-gastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) constitute a heterogeneous group of tumors with poor prognosis. Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor-1 (FGFR-1), in close interplay with platelet-derived growth factor-B (PDGF-B) and vascular endothelial growth factor receptor-3 (VEGFR-3), are strongly involved in angiogenesis. This study investigates the prognostic impact of FGF2 and FGFR-1 and explores the impact of their co-expression with PDGF-B and VEGFR-3 in widely resected tumors from non-GIST STS patients.', 'Tumor samples from 108 non-GIST STS patients were obtained and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expressions of FGF-2, FGFR-1, PDGF-B and VEGFR-3.', 'In the multivariate analysis, high expression of FGF2 (P = 0.024, HR = 2.2, 95% CI 1.1-4.4) and the co-expressions of FGF2 & PDGF-B (overall; P = 0.007, intermediate; P = 0.013, HR = 3.6, 95% CI = 1.3-9.7, high; P = 0.002, HR = 6.0, 95% CI = 2.0-18.1) and FGF2 & VEGFR-3 (overall; P = 0.050, intermediate; P = 0.058, HR = 2.0, 95% CI = 0.98-4.1, high; P = 0.028, HR = 2.6, 95% CI = 1.1-6.0) were significant independent prognostic indicators of poor disease-specific survival.'] Does fibroblast growth factor 2 orchestrate angiogenic networking in non-GIST STS patients?
qiaojin/PubMedQA
2
[ -1.7277264595031738, -1.5542492866516113, 2.2899231910705566 ]
['Microbial translocation may contribute to the immunopathogenesis in HIV infection. We investigated if microbial translocation and inflammation were associated with innate and adaptive immune responses in adults with HIV.', 'This was an observational cohort study. Sera from HIV-infected and HIV-uninfected individuals were analyzed for microbial translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody, and anti-α-galactosyl antibodies) and inflammatory markers (high sensitivity C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor receptor II, and IL-10) with enzyme-linked immunosorbent assays. Peripheral blood mononuclear cells (PBMC) from HIV-infected persons and healthy controls (primed with single-stranded HIV-1-derived RNA) were stimulated with LPS, and cytokine production was measured. Finally, HIV-infected patients were immunized with Prevnar 7vPnC±CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial translocation and inflammation on immunization were analyzed in a predictive regression model. We included 96 HIV-infected individuals, 76 on highly active antiretroviral therapy (HAART), 20 HAART-naive, and 50 healthy controls. Microbial translocation and inflammatory markers were higher among HIV-infected persons than controls. Cytokine levels following LPS stimulation were increased in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons. Further, RNA-priming of PBMCs from controls acted synergistically with LPS to augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine responses among HAART-naive, but not among HAART-treated HIV-infected individuals.'] Is endotoxemia associated with altered innate and adaptive immune responses in untreated HIV-1 infected individuals?
qiaojin/PubMedQA
2
[ -2.301006317138672, -1.4269051551818848, 2.7687668800354004 ]
['We investigated the effects of voluntary wheel running as model for intervention on the development of contextual fear and hyperarousal in a mouse model of post-traumatic stress disorder (PTSD). Physical exercise in general has been associated with improved hippocampus-dependent memory performance both in animals and humans. However, studies that have tried to link physical exercise and contextual conditioning in an animal model of PTSD, revealed mixed findings.', 'Here we tested contextual fear conditioning, generalized fear response, acoustic startle response and emotionality in C57BL/6NCrl mice which had free access to a running wheel for 28 days, compared with control animals which did not run and mice which did not receive a shock during the conditioning phase.', 'We found no significant effects of voluntary running on the above-mentioned variables, except for enhanced anxiety levels in the Dark-Light-Box and O-Maze tests of running mice.'] Does voluntary exercise ameliorate context memory and hyperarousal in a mouse model for post-traumatic stress disorder ( PTSD )?
qiaojin/PubMedQA
2
[ -2.77809739112854, -0.11444012075662613, 1.9317039251327515 ]
['The purpose of this study was to investigate the heart rate variability (HRV) profile in obese women displaying the metabolically healthy but obese (MHO) phenotype.', 'We studied 47 obese, sedentary postmenopausal women. Subjects were classified as MHO or at risk based on insulin resistance as assessed with the homeostatic model assessment (HOMA) index. Subjects were divided into tertiles according to HOMA values. Subjects in the lower tertile were categorised as MHO while subjects in the upper 2 tertiles represented at risk subjects. Outcome measures were heart rate variability factors (RR intervals, SDNN, LF, HF, pNN50, RMSSD), body temperature, body composition (DEXA) and a lipid profile as well as glucose and insulin.', 'MHO individuals had significantly lower resting heart rate, body temperature, lean body mass as well as fasting insulin and HOMA levels compared to at risk subjects (p < 0.05). In addition, RR intervals, SDNN and LF were significantly higher in MHO individuals (p < 0.05). Moreover, stepwise regression analysis showed that SDNN was an independent predictor of the variation in HOMA in our cohort.'] Does the metabolically healthy but obese postmenopausal woman present a favourable heart rate variability profile?
qiaojin/PubMedQA
2
[ -1.9145328998565674, -0.8754045367240906, 1.8913779258728027 ]
['Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast are distinct morphological entities with different biological features and clinical behaviour. In the present study, the authors compare the axillary-lymph-node (ALN) status of patients with grade-matched ILC (no=426) and IDC (no=820). The pattern of nodal metastatic deposits (nodular, sinusoidal and diffuse) and the proportion of involved nodes were also analysed in a selected group of 246 tumours, which were associated with a single positive ALN.', 'Compared with grade-matched IDC, ILC was associated with a higher nodal stage (13.1% vs 4.5% of ILC and IDC were stage 3), higher absolute number of positive nodes and higher ratio of positive nodes (0.46±0.30 and 0.33±0.23 in ILC and IDC respectively). These differences were maintained in the different size subgroups. The most common metastatic morphological pattern was nodular in both types of carcinomas. A sinusoidal pattern was more frequent in IDC, and the diffuse pattern was more frequent in ILC. Despite these differences, ILC and grade-matched IDC exhibited similar rates of regional recurrences (RR) and breast-cancer survival.'] Are lymph-node metastases in invasive lobular carcinoma different from those in ductal carcinoma of the breast?
qiaojin/PubMedQA
2
[ -2.278343915939331, -1.245900273323059, 2.5655770301818848 ]
['We have previously shown that the allergic sensitization to ovalbumin does not represent a superantigen-like immune response. In gene-targeted mice (ΔD-iD) with a single modified Diversity gene segment (D(H)) of the immunoglobulin heavy chain, enriched for charged amino acids, the asthma phenotype in a murine model was markedly alleviated compared to wild-type animals.', 'We now sought to determine whether the confinement to a single D(H) gene segment alone leads to a reduced allergic phenotype.', 'We examined another gene-targeted mouse strain (ΔD-DFL) with a single D(H) gene segment which encodes for neutral amino acids, thus reflecting the preferential repertoire in wild-type mice. Mice were sensitized intraperitoneally to ovalbumin.', 'Despite the constraint to a single D(H) gene segment, ΔD-DFL mice mounted high total and allergen-specific IgG(1) and IgE serum levels after sensitization to ovalbumin. The affinity constants of allergen-specific IgG(1) antibodies did not differ between ΔD-DFL and wild type. Following challenge with aerosolized allergen, a marked local T(H)2 cytokine response and an eosinophilic airway inflammation developed. Quantitative histology revealed increased mucus production and intense goblet cell metaplasia which were identical to those in wild type. Moreover, ΔD-DFL mice developed an airway hyperreactivity to methacholine and to the specific allergen, which both did not differ from those in wild-type animals.'] Is a single DH gene segment sufficient for the establishment of an asthma phenotype in a murine model of allergic airway inflammation?
qiaojin/PubMedQA
2
[ -2.4626710414886475, -1.305345058441162, 2.792961597442627 ]
['The effect of Tualang honey on wound healing in bacterial contaminated full-thickness burn wounds was evaluated in 36 male Sprague Dawley rats.', 'The rats were randomly divided into three groups (n = 12/group). Three full-thickness burn wounds were created on each rat. Each group of rats was inoculated with a different organism in the burn wounds: Group A was inoculated with Pseudomonas aeruginosa, Group B was inoculated with Klebsiella pneumoniae and Group C was inoculated with Acinetobacter baumannii. One wound on each rat was dressed with either Tualang honey, Chitosan gel or Hydrofibre silver. Each wound size was measured on day 3, 6, 9, 12, 15, 18 and 21 of the study.', 'The mean wound size of the Tualang honey-treated wounds was not statistically different than that of the Chitosan gel or Hydrofibre silver-treated wounds when the wounds were compared throughout the entire experiment (P > 0.05). However, comparing the mean wound size on day 21 alone revealed that the Tualang honey-treated wounds were smaller in comparison to that of the Chitosan gel and Hydrofibre silver-treated groups.'] Do evaluations of bacterial contaminated full thickness burn wound healing in Sprague Dawley rats Treated with Tualang honey?
qiaojin/PubMedQA
2
[ -0.40291303396224976, -0.618668258190155, 0.14491084218025208 ]
['About 35% of individuals with type 2 diabetes develop persistent albuminuria, lose renal function, and are at increased risk for microvascular complications like diabetic nephropathy. Recent genome-wide association studies have identified the uromodulin locus (UMOD), encoding the most common protein in human urine to be associated with hypertension and also with chronic kidney disease (CKD). In the present study we examined the association of the common variant of the uromodulin (UMOD) gene with type 2 diabetic nephropathy and kidney function.', 'UMOD variant rs13333226 was genotyped in a case-control material including 4888 unrelated type 2 diabetic individuals (n = 880 with and n = 4008 without nephropathy) from Sweden (Scania Diabetes Registry) using the ABI Real time TaqMan allelic discrimination assay.', 'The G allele of rs13333226 was associated with a decreased risk of nephropathy [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69-0.91, P = 0.001] after correction for confounding factors like age, sex, body mass index (BMI), blood pressure, kidney function, smoking and duration of diabetes. The same allele was also associated with a better kidney function [estimated glomerular filtration rate (eGFR), β = 0.117, P < 0.0001] and lower systolic blood pressure (β = -0.048, P = 0.013) in the overall study cohort.'] Is uromodulin gene variant associated with type 2 diabetic nephropathy?
qiaojin/PubMedQA
2
[ -2.055988073348999, -1.4754507541656494, 2.6074342727661133 ]
['We assessed the clinical profile of patients with acute coronary syndrome (ACS) and nonobstructive coronary artery disease (CAD) in a real world setting, focusing on pattern of care and on prognosis.', 'Each nonobstructive CAD (<50% stenosis in any epicardial coronary artery) patient was matched with an obstructive CAD patient; adjusted estimates of prescription of guideline-recommended drugs at discharge and of long-term prognosis were evaluated.', 'Among 2995 consecutive ACS patients who underwent coronary angiography, 125 (4.2%) had nonobstructive CAD. Nonobstructive CAD patients had significantly lower odds of receiving aspirin [odds ratio (OR) 0.31, 95% confidence interval (CI): 0.14-0.68], thienopyridines (OR 0.01, 95% CI: 0.00-0.07), statins (OR 0.31, 95% CI: 0.17-0.58), beta-blockers (OR 0.32, 95% CI: 0.17-0.63) and angiotensin converting enzyme-inhibitors /angiotensin receptor blockers (OR 0.36, 95% CI: 0.17-0.91) compared with matched patients. During a 3-year follow-up, nonobstructive CAD patients had significantly fewer cardiovascular deaths and myocardial infarctions but numerically more episodes of unstable angina.'] Are patients with acute coronary syndrome and nonobstructive coronary artery disease in the real world markedly undertreated?
qiaojin/PubMedQA
2
[ -2.0547454357147217, -1.3032201528549194, 2.3930530548095703 ]
['Obesity has been implicated in the etiology of postmenopausal breast cancer (PBC). We hypothesized that altered secretion of visfatin may underlie this association. We thus investigated the association of serum visfatin with PBC risk, taking into account known risk factors including adipokines and anthropometric and metabolic parameters.', "In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control women matched on age and time of diagnosis between 2003 and 2010 at Army Share Fund Hospital, Veterans' Hospital (NIMTS). Levels of serum visfatin, adiponectin, leptin, metabolic parameters, carcinoembryonic antigen, and CA 15-3 were determined.", 'The mean serum visfatin level was significantly higher in case than in control participants (P < 0.001). Women in the highest quartile of visfatin concentration presented significantly higher odds for PBC, adjusting for age, date of diagnosis, education, body mass index, waist circumference, years with menstruation, parity/age at first full-term pregnancy, breast-feeding, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, homeostasis model assessment score, and serum leptin and adiponectin concentrations (odds ratio, 7.93; 95% CI, 2.52-24.9). In case participants, the visfatin level correlated significantly with the tumor marker CA 15-3 (P = 0.03) but not with metabolic and anthropometric variables (P > 0.05).'] Are elevated serum visfatin/nicotinamide phosphoribosyl-transferase levels associated with risk of postmenopausal breast cancer independently from adiponectin , leptin , and anthropometric and metabolic parameters?
qiaojin/PubMedQA
2
[ -2.097721815109253, -1.4259531497955322, 2.501640796661377 ]
["Barrett esophagus (BE) is a premalignant condition that develops due to prolonged gastroesophageal reflux disease (GERD). In some but not all cases, BE progresses to Barrett-associated adenocarcinoma. p27 is a tumor-suppressor protein that regulates the cell's division cycle and appears to be frequently inactivated in Barrett-associated adenocarcinoma due to increased degradation or cytoplasmic mislocalization. Reduced or mislocalized p27 would remove it from its nuclear targets and result in increased proliferation. Although bile acid and hydrochloric acid (HCl) are linked to the pathogenesis of BE, not every patient with BE has a history of GERD. Eosinophilic esophagitis mimics GERD, but eosinophil granule proteins, known to mediate inflammation, have not been linked to BE. It was unknown whether mediators of esophagitis affect p27 expression and/or localization in normal esophageal cells. We assessed the effects of bile acid, HCl, and eosinophil granule proteins on p27 protein expression, localization, and its ability to regulate cell proliferation.", 'Human esophageal epithelial (HET-1A) cells were incubated with chenodeoxycholic acid (CDC), HCl, and eosinophil granule proteins (major basic protein, MBP; and eosinophil peroxidase, EPO). Cell viability analysis, immunoblot, immunofluorescence microscopy, and flow cytometric analysis were performed.', 'Exposure of HET-1A cells to CDC, HCl, MBP, and EPO did not affect total p27 levels. CDC, HCl, MBP, and EPO caused mislocalization of p27 from the nucleus to the cytoplasm. Flow cytometry showed that CDC exposure also increased HET-1A cell proliferation.'] Do inflammatory mediators of esophagitis alter p27 Kip1 expression in esophageal epithelial cells?
qiaojin/PubMedQA
2
[ -2.5397818088531494, -1.2664507627487183, 2.8869237899780273 ]
['Few data are available to guide programmatic solutions to the overlapping problems of undernutrition and HIV infection. We evaluated the impact of food assistance on patient outcomes in a comprehensive HIV program in central Haiti in a prospective observational cohort study.', 'Adults with HIV infection were eligible for monthly food rations if they had any one of: tuberculosis, body mass index (BMI) <18.5kg/m2, CD4 cell count <350/mm3 (in the prior 3 months) or severe socio-economic conditions. A total of 600 individuals (300 eligible and 300 ineligible for food assistance) were interviewed before rations were distributed, at 6 months and at 12 months. Data collected included demographics, BMI and food insecurity score (range 0 - 20).', 'At 6- and 12-month time-points, 488 and 340 subjects were eligible for analysis. Multivariable analysis demonstrated that at 6 months, food security significantly improved in those who received food assistance versus who did not (-3.55 vs -0.16; P < 0.0001); BMI decreased significantly less in the food assistance group than in the non-food group (-0.20 vs -0.66; P = 0.020). At 12 months, food assistance was associated with improved food security (-3.49 vs -1.89, P = 0.011) and BMI (0.22 vs -0.67, P = 0.036). Food assistance was associated with improved adherence to monthly clinic visits at both 6 (P < 0.001) and 12 months (P = 0.033).'] Is food assistance associated with improved body mass index , food security and attendance at clinic in an HIV program in central Haiti : a prospective observational cohort study?
qiaojin/PubMedQA
2
[ -0.8637430667877197, -1.1846297979354858, 1.1409567594528198 ]
['Recent studies in budding yeast have shown that antisense transcription occurs at many loci. However, the functional role of antisense transcripts has been demonstrated only in a few cases and it has been suggested that most antisense transcripts may result from promiscuous bi-directional transcription in a dense genome.', "Here, we use strand-specific RNA sequencing to study anti-sense transcription in Saccharomyces cerevisiae. We detect 1,103 putative antisense transcripts expressed in mid-log phase growth, ranging from 39 short transcripts covering only the 3' UTR of sense genes to 145 long transcripts covering the entire sense open reading frame. Many of these antisense transcripts overlap sense genes that are repressed in mid-log phase and are important in stationary phase, stress response, or meiosis. We validate the differential regulation of 67 antisense transcripts and their sense targets in relevant conditions, including nutrient limitation and environmental stresses. Moreover, we show that several antisense transcripts and, in some cases, their differential expression have been conserved across five species of yeast spanning 150 million years of evolution. Divergence in the regulation of antisense transcripts to two respiratory genes coincides with the evolution of respiro-fermentation."] Does strand-specific RNA sequencing reveal extensive regulated long antisense transcripts that are conserved across yeast species?
qiaojin/PubMedQA
2
[ -2.411649465560913, -0.24123811721801758, 1.7206907272338867 ]
['All four Francisella tularensis subspecies possess gene clusters with potential to express type IV pili (Tfp). These clusters include putative pilin genes, as well as pilB, pilC and pilQ, required for secretion and assembly of Tfp. A hallmark of Tfp is the ability to retract the pilus upon surface contact, a property mediated by the ATPase PilT. Interestingly, out of the two major human pathogenic subspecies only the highly virulent type A strains have a functional pilT gene.', 'In a previous study, we were able to show that one pilin gene, pilA, was essential for virulence of a type B strain in a mouse infection model. In this work we have examined the role of several Tfp genes in the virulence of the pathogenic type A strain SCHU S4. pilA, pilC, pilQ, and pilT were mutated by in-frame deletion mutagenesis. Interestingly, when mice were infected with a mixture of each mutant strain and the wild-type strain, the pilA, pilC and pilQ mutants were out-competed, while the pilT mutant was equally competitive as the wild-type.'] Is the type IV pilin , PilA , required for full virulence of Francisella tularensis subspecies tularensis?
qiaojin/PubMedQA
2
[ -2.3027102947235107, 0.21584202349185944, 1.1579456329345703 ]
['T cell migration is essential for immune responses and inflammation. Activation of the T-cell receptor (TCR) triggers a migration stop signal to facilitate interaction with antigen-presenting cells and cell retention at inflammatory sites, but the mechanisms responsible for this effect are not known.', 'Migrating T cells are polarized with a lamellipodium at the front and uropod at the rear. Here we show that transient TCR activation induces prolonged inhibition of T-cell migration. TCR pre-activation leads to cells with multiple lamellipodia and lacking a uropod even after removal of the TCR signal. A similar phenotype is induced by expression of constitutively active Rac1, and TCR signaling activates Rac1. TCR signaling acts via Rac to reduce phosphorylation of ezrin/radixin/moesin proteins, which are required for uropod formation, and to increase stathmin phosphorylation, which regulates microtubule stability. T cell polarity and migration is partially restored by inhibiting Rac or by expressing constitutively active moesin.'] Does rac activation by the T-cell receptor inhibit T cell migration?
qiaojin/PubMedQA
2
[ -2.608666181564331, -0.8610970973968506, 2.504326820373535 ]
['Traumatic brain injury (TBI) results in neurological dysfunction and death through primary or secondary mechanisms. Here, we evaluated the effect of osmotic pump delivery of granulocyte colony-stimulating factor (G-CSF) on the histopathology and motor function recovery of rats after experimental TBI.', "Sprague-Dawley rats were used as experimental model by fluid percussion device to cause brain injury on the motor cortex area. The rats were simultaneously subjected to TBI and were implanted of min-osmotic pump containing recombinant human G-CSF (300 μg/700 μl) via intraperitoneal injection. Motor function was assessed by rotarod test. 5-bromo-2'-deoxyuridine (BrdU) was used to label the proliferating cells and their differentiation was evaluated by histology and immunohistochemistry.", 'The G-CSF group showed significantly better motor function recovery than the control group, and the effect lasted up to 14 days after TBI. Moreover, the G-CSF group exhibited a greater increase in the number of BrdU-positive cells compared with the control group. The G-CSF group also had a significantly higher number of DCX-positive cells in the ipsilateral subventricular zone (SVZ) than the control group.'] Does granulocyte colony-stimulating factor enhance cellular proliferation and motor function recovery on rats subjected to traumatic brain injury?
qiaojin/PubMedQA
2
[ -2.412306070327759, -1.279136061668396, 2.7368195056915283 ]
['Head injury frequently results in increased intracranial pressure and brain edema. Investigators have demonstrated that ischemic injury causes an increase in cerebrospinal fluid (CSF) levels of antidiuretic hormone (ADH); increased CSF ADH levels exacerbate cerebral edema, and inhibition of the ADH system with specific ADH antagonists reduces cerebral edema. The current study was designed to test the hypothesis that elevated levels of ADH are present in the CSF of subjects with head injury.', 'Ventricular CSF and blood samples were taken from 11 subjects with head injury and 12 subjects with no known head trauma or injury. ADH levels were analyzed using radioimmunoassay. Severity of increased intracranial pressure (ICP) was rated in head-injured subjects using a four-point ordinal scale, based on which treatments were necessary to reduce ICP.', 'Subjects with head injury had higher CSF (3.2 versus 1.2 pg/ml; P<0.02) and plasma (4.1 versus 1.4 pg/ml; P<0.02) levels of ADH than did control subjects. In head-injured subjects, CSF ADH levels positively correlated with severity of ICP.'] Is increased intracranial pressure associated with elevated cerebrospinal fluid ADH levels in closed-head injury?
qiaojin/PubMedQA
2
[ -2.1838278770446777, -1.0732336044311523, 2.304189682006836 ]
['Bacteria have a central, although poorly understood, role in inflammatory bowel disease (IBD). Host-bacteria interactions primarily take place in the gastrointestinal tract, but cells may also encounter translocated bacteria in the bloodstream. IBD is associated with activated, circulating Toll-like receptor (TLR)2 and TLR4-expressing B cells suggesting that blood-borne microbial TLR ligands modulate B cell responses.', "Serum levels of lipopolysaccharide (LPS)/endotoxin and high mobility group box 1 (HMGB1), an endogenous TLR ligand, were quantified in Crohn's disease (CD) and ulcerative colitis (UC). Responses of purified B cells to LPS and HMGB1 were correlated with levels of systemic TLR ligands and clinical parameters of disease.", 'While IBD patients have increased levels of blood LPS, the net effect of endotoxemia has unexpected characteristics illustrating that LPS has both pro- and antiinflammatory roles through TLR4+ B cells. Experimental treatment of B cells demonstrates that the antiinflammatory effect of LPS is due to its hypo-acylation of lipid A suggesting an increased prevalence of systemic, hypo-acylated LPS in CD. In contrast, high levels of LPS are associated with disease activity in UC. HMGB1 activates B cells through TLR2 and CD36. Serum levels of HMGB1 correlate with spontaneous IL-8 production by B cells suggesting that blood-borne TLR2 ligands increase B-cell activation in vivo.'] Do systemic Toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease?
qiaojin/PubMedQA
2
[ -2.5034353733062744, -1.2292985916137695, 2.7959463596343994 ]
['Calcitonin gene-related peptide (CGRP), a sensory neuropeptide, affects osteoblast proliferation and bone formation. However, the mechanisms are not fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that stimulates the migration of monocytes and plays important roles in regulating bone remolding during fracture repair. In this study, we investigated the effects of CGRP on proliferation and MCP-1 expression in cultured rat osteoblasts.', 'Primary rat osteoblasts were isolated from fetal rats calvariae. Cells were exposed to gradient concentrations (10(-9) to 10(-7) mol/L) of CGRP. Protein and mRNA levels of MCP-1 were quantified by Western blotting and semiquantitative reverse transcription-polymerase chain reaction, respectively. The protein level of MCP-1 was investigated and compared in cell culture media by enzyme linked immunosorbent assay (ELISA). Phospho-extracellular signal-regulated kinase (ERK) expression was detected by Western blotting. Cell proliferative activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and BrdU assay. The effects of MAPK/ERK kinase (MEK)-inhibitor U0126 on CGRP-induced MCP-1 expression in primary rat osteoblasts were examined.', 'CGRP effectively enhanced primary rat osteoblast proliferation and led to significant increases in the expression of MCP-1 mRNA and protein in time- and dose-dependent manners. CGRP activated the ERK pathway. Pretreatment of cultured rat osteoblasts with MEK inhibitor U0126 resulted in dose-dependent inhibitions of CGRP-induced MCP-1 mRNA and protein levels. Thus, CGRP promoted cell proliferation and stimulated MCP-1 expression in cultured rat osteoblasts.'] Does calcitonin gene-related peptide induce proliferation and monocyte chemoattractant protein-1 expression via extracellular signal-regulated kinase activation in rat osteoblasts?
qiaojin/PubMedQA
2
[ -2.3932178020477295, -1.2964715957641602, 2.739365577697754 ]
['Temporary vascular in- and outflow occlusion is an effective technique for bleeding control during liver resection. However, occlusion can result in ischemia/reperfusion (I/R) injury to the liver. The aim of this study in a porcine model was to investigate the effect of in- and outflow occlusion of part of the liver on the metabolism of the normally perfused parenchyma of the same liver measured by microdialysis.', 'Eight pigs underwent laparotomy. A microdialysis catheter was inserted into in the left and right part of the liver, respectively. Microdialysis samples were collected every 30 min. Occlusion of the left part of the liver was achieved for 60 min, followed by 5 h of reperfusion. Samples were analyzed for glucose, lactate, pyruvate and glycerol. Blood samples were drawn to determine standard liver and biochemical parameters.', 'Comparing the ischemic part of the liver with the normally perfused part, significant differences in the levels of lactate, pyruvate and glycerol were found. During reperfusion, similar and continuous decreases below baseline levels were observed for lactate and pyruvate in both the ischemic and normally perfused part of the liver. No significant changes in liver parameters or blood glucose levels were seen.'] Is partial liver ischemia followed by metabolic changes in the normally perfused part of the liver during reperfusion?
qiaojin/PubMedQA
2
[ -2.420699119567871, -1.1891181468963623, 2.73968505859375 ]
['Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined.', 'We sought to determine whether atopic status modulates ozone response phenotypes in human subjects.', 'Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations.', 'All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significantly change in any group with ozone. All groups had similar levels of hyaluronic acid at baseline, with increased levels after ozone exposure in atopic and atopic asthmatic subjects.'] Do atopic asthmatic subjects but not atopic subjects without asthma have enhanced inflammatory response to ozone?
qiaojin/PubMedQA
2
[ -2.4241325855255127, -0.8482262492179871, 2.2229034900665283 ]
['Nicotinic acetylcholine receptor α1 (nAChRα1) was recently identified as a functional cell receptor for urokinase, a potent atherogenic molecule. Here, we test the hypothesis that nAChRα1 plays a role in the pathogenesis of atherosclerosis.', 'Apolipoprotein E-deficient mice were initially fed a Western diet for 8 wks. Plasmid DNA encoding scramble RNA (pscr) or siRNA (psir2) for nAChRα1 was injected into the mice (n=16) using an aortic hydrodynamic gene transfer protocol. Four mice from each group were sacrificed 7 days after the DNA injection to confirm the nAChRα1 gene silencing. The remaining mice continued on a Western diet for an additional 16 wks.', 'The nAChRα1 was up-regulated in aortic atherosclerotic lesions. A 78% knockdown of the nAChRα1 gene resulted in remarkably less severe aortic plaque growth and neovascularization at 16 wks (both P<0.05). In addition, significantly fewer macrophages (60% less) and myofibroblasts (80% less) presented in the atherosclerotic lesion of the psir2-treated mice. The protective mechanisms of the nAChRα1 knockdown may involve up-regulating interferon-γ/Y box protein-1 activity and down-regulating transforming growth factor-β expression.'] Does in vivo knockdown of nicotinic acetylcholine receptor α1 diminish aortic atherosclerosis?
qiaojin/PubMedQA
2
[ -2.2516934871673584, -1.4656853675842285, 2.694772720336914 ]
['Adult bone marrow mononuclear cells (BMMNCs) can restore cardiac function following myocardial necrosis. Protocols used to date have administered cells relatively late after ischaemia/reperfusion injury, but there is the opportunity with elective procedures to infuse cells shortly after restoration of blood flow, for example after angioplasty. Our aim was therefore to try and quantify protection from myocardial injury by early infusion of BMMNCs in a rat ischaemia reperfusion (I/R) model.', 'Male Wistar rats underwent 25 min of ischaemia followed by 2 h reperfusion of the left anterior descending coronary artery. Ten million BMMNCs were injected i.v. at reperfusion. We found BMMNCs caused a significant reduction in infarct size at 2 h when assessed by staining the area at risk with p-nitro blue tetrazolium (42% reduction, P<0.01). Apoptosis and necrosis of isolated cardiomyocytes was significantly reduced in the area at risk. Functional assessment at 7 days using echocardiography and left ventricular catheterisation showed improved systolic and diastolic function in the BMMNC treatment group (LVEF: BMMNC 71 ± 3% vs. PBS 48 ± 4%, P<0.0001). In functional studies BMMNC injected animals showed increased activation of Akt, inhibition of GSK-3β, amelioration of p38 MAP kinase phosphorylation and NF-κB activity compared to control myocardium. Inhibition of PI3K with LY294002 abolished all beneficial effects of BMMNC treatment. Proteomic analysis also demonstrated that BMMNC treatment induced alterations in proteins within known cardioprotective pathways, e.g., heat shock proteins, stress-70 protein as well as the chaperone protein 14-3-3 epsilon.'] Do bone marrow mononuclear cells reduce myocardial reperfusion injury by activating the PI3K/Akt survival pathway?
qiaojin/PubMedQA
2
[ -2.3305423259735107, -1.4625383615493774, 2.8309226036071777 ]
['To determine the time-course changes of cell-free plasma DNA (cfDNA) following heavy exercise.', 'cfDNA concentration, C-reactive protein levels (hs-CRP), uric acid concentration (UA), creatine kinase activity (CK) were measured before and post-exercise (immediately post, 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 24h).', 'cfDNA increased (15-fold) 30-min post-exercise and normalized thereafter. hs-CRP increased (56%, p<0.001) 1h post-exercise, remained elevated throughout recovery (52-142%, p<0.0001), and peaked (200% rise, p<0.0001) at 24h post-exercise. UA and CK increased (p<0.05), immediately post-exercise, remained elevated throughout recovery (p<0.0001), and peaked (p<0.0001) at 24h of post-exercise recovery.'] Is time of sampling crucial for measurement of cell-free plasma DNA following acute aseptic inflammation induced by exercise?
qiaojin/PubMedQA
2
[ -1.794854760169983, -1.013218879699707, 1.9848520755767822 ]
['Leptin, a cytokine-like protein, plays an important role in the regulation of body weight through inhibition of food intake and stimulation of energy expenditure. Leptin circulates in blood and acts on the brain, which sends downstream signals to regulate body weight. Leptin therapy has been successful in treating leptin deficient obese patients. However, high levels of leptin have been observed in more common forms of obesity indicating a state of leptin resistance which limits the application of leptin in the treatment of obesity. If the central effect of leptin could be by-passed and genes which respond to leptin treatment could be regulated directly, new therapeutic targets for the treatment of obesity may be possible. The purpose of this study was to identify genes and subsequent pathways correlated with leptin-mediated weight loss.', 'WE UTILIZED MICROARRAY TECHNOLOGY TO COMPARE HEPATIC GENE EXPRESSION CHANGES AFTER TWO TYPES OF LEPTIN ADMINISTRATION: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We identified 214 genes that correlate with leptin mediated weight loss. Several biological processes such as mitochondrial metabolic pathways, lipid metabolic and catabolic processes, lipid biosynthetic processes, carboxylic acid metabolic processes, iron ion binding and glutathione S-transferases were downregulated after leptin administration. In contrast, genes involved in the immune system inflammatory response and lysosomal activity were found to be upregulated. Among the cellular compartments mitochondrion (32 genes), endoplasmic reticulum (22 genes) and vacuole (8 genes) were significantly over represented.'] Does hepatic gene expression profiling reveal key pathways involved in leptin-mediated weight loss in ob/ob mice?
qiaojin/PubMedQA
2
[ -2.480614423751831, -1.1544709205627441, 2.706760883331299 ]
['inhibitors of apoptosis proteins (IAPs) have been shown to contribute to resistance of neoplastic cells to chemotherapy and to biologic antineoplastic agents. Consequently, new agents are being developed targeting this family of proteins. In a panel of bladder cancer cell lines, we evaluated a Smac mimetic that antagonizes several IAPs for its suitability for bladder cancer therapy. Experimental design: A panel of seven bladder cancer cell lines were evaluated for sensitivity to the Smac mimetic compound-A alone, TRAIL alone, chemotherapy alone, compound-A plus TRAIL, and compound-A plus chemotherapy by DNA fragmentation analysis. IAP levels and caspase activation were examined by western blotting. Release of caspase-3 from X-linked inhibitor of apoptosis protein (XIAP), the most effective IAP, was assessed by immunoprecipitation and western blotting. Finally, siRNA knockdown of XIAP was correlated with the sensitivity of cells to apoptosis induced by compound-A plus TRAIL by DNA fragmentation and western blotting.', 'single-agent compound-A had little effect, but compound-A augmented TRAIL- and chemotherapy-induced apoptosis. Immunoblotting showed that combination treatment with compound-A and TRAIL resulted in cleavage of procaspase-3 and procaspase-7, activation of which irreversibly commits cells to apoptosis. Immunoprecipitation of XIAP showed displacement of active caspase-3 fragments from XIAP, supporting the proposed mechanism of action. Furthermore, siRNA-mediated silencing of XIAP similarly sensitized these cells to apoptosis.', 'a panel of seven bladder cancer cell lines were evaluated for sensitivity to the Smac mimetic compound-Alone, TRAIL alone, Chemotherapy alone, compound-A plus TRAIL and compound-A plus chemotherapy by DNA fragmentation analysis. IAP levels and caspase activation were examined by western blotting. Release of caspase-3 from X-linked inhibitor of apoptosis protein (XIAP), the most effective IAP, was assessed by immunoprecipitation and western blotting. Finally siRNA knockdown of XIAP was correlated with the sensitivity of cells to apoptosis induced by compound-A plus TRAIL by DNA fragmentation and western blotting.'] Does smac mimetic reverse resistance to TRAIL and chemotherapy in human urothelial cancer cells?
qiaojin/PubMedQA
2
[ -2.363057851791382, -1.387373685836792, 2.803633213043213 ]
['The CACNA1C gene (alpha-1C subunit of the L-type voltage-gated calcium channel) has been identified as a risk gene for bipolar disorder and schizophrenia, but the mechanism of association has not been explored.', 'To identify the neural system mechanism that explains the genetic association between the CACNA1C gene and psychiatric illness using neuroimaging and human brain expression.', 'We used blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure brain activation in circuitries related to bipolar disorder and schizophrenia by comparing CACNA1C genotype groups among healthy subjects. We tested the effect of genotype on messenger RNA (mRNA) levels of CACNA1C in postmortem human brain. A case-control analysis was used to determine the association of CACNA1C genotype with schizophrenia.', 'National Institutes of Health Clinical Center.', 'Healthy men and women of white race/ethnicity participated in the fMRI study. Postmortem samples from normal human brains were used for the brain expression study. Patients with schizophrenia and healthy subjects were used in the case-control analysis.', 'BOLD fMRI, mRNA levels in postmortem brain samples, and genetic association with schizophrenia.', 'The risk-associated single-nucleotide polymorphism (SNP rs1006737) in CACNA1C predicted increased hippocampal activity during emotional processing (P = .001 uncorrected, P((false recovery rate [FDR])) = .05, z = 3.20) and increased prefrontal activity during executive cognition (P = 2.8e-05 uncorrected, P(FDR) = .01, z = 4.03). The risk-associated SNP also predicted increased expression of CACNA1C mRNA in human brain (P = .002). CACNA1C was associated with schizophrenia in our case-control sample (odds ratio, 1.77; P = .03).'] Does genetic variation in CACNA1C affect brain circuitries related to mental illness?
qiaojin/PubMedQA
2
[ -2.1663825511932373, -1.2676231861114502, 2.458932399749756 ]
['Several lines of evidence suggest that the dopaminergic nervous system contributes to methamphetamine (METH) dependence, and there is increasing evidence of antagonistic interactions between dopamine and adenosine receptors. We therefore hypothesized that variations in the A2A adenosine receptor (ADORA2A) gene modify genetic susceptibility to METH dependence/psychosis.', 'We first analyzed variations in the exons and exon-intron boundaries of the ADORA2A gene in METH dependent/psychotic patients. Then an association analysis between these single nucleotide polymorphisms and METH dependence/psychosis was performed using a total of 171 METH dependent/psychotic patients and 229 controls.', 'We found 6 variations, of which one single nucleotide polymorphism (SNP) was novel. Significant associations were observed between the allelic and genotypic frequencies of the Exon2+751 (rs5751876) SNP and METH dependence/psychosis. These associations were observed especially in females. In the clinical feature analyses, significant associations were observed between the SNP and the patient subgroup using METH alone (i.e., without concomitant use of other substances of abuse).'] Is the adenosine A2A receptor associated with methamphetamine dependence/psychosis in the Japanese population?
qiaojin/PubMedQA
2
[ -2.3858320713043213, -1.1353882551193237, 2.523426055908203 ]
['To assess the prevalence of defective homologous recombination (HR)-based DNA repair in sporadic primary breast cancers, examine the clincopathologic features that correlate with defective HR and the relationship with neoadjuvant chemotherapy response.', 'We examined a cohort of 68 patients with sporadic primary breast cancer who received neoadjuvant anthracylcine-based chemotherapy, with core biopsies taken 24 hours after the first cycle of chemotherapy. We assessed RAD51 focus formation, a marker of HR competence, by immunofluorescence in postchemotherapy biopsies along with geminin as a marker of proliferative cells. We assessed the RAD51 score as the proportion of proliferative cells with RAD51 foci.', 'A low RAD51 score was present in 26% of cases (15/57, 95% CI: 15%-40%). Low RAD51 score correlated with high histologic grade (P = 0.031) and high baseline Ki67 (P = 0.005). Low RAD51 score was more frequent in triple-negative breast cancers than in ER- and/or HER2-positive breast cancer (67% vs. 19% respectively; P = 0.0036). Low RAD51 score was strongly predictive of pathologic complete response (pathCR) to chemotherapy, with 33% low RAD51 score cancers achieving pathCR compared with 3% of other cancers (P = 0.011).'] Does a marker of homologous recombination predict pathologic complete response to neoadjuvant chemotherapy in primary breast cancer?
qiaojin/PubMedQA
2
[ -1.9490097761154175, -1.455397605895996, 2.4049899578094482 ]
['Bevacizumab, a monoclonal antibody (mAb) targeting vascular endothelial growth factor (VEGF), has produced promising results when combined with chemotherapy in the treatment of advanced colorectal cancer (CRC). The aim of the present study was to define the immunological profile of metastatic CRC patients at baseline and following chemotherapy with either irinotecan/5-fluorouracil/leucovorin (IFL) alone or IFL in combination with.bevacizumab (B-IFL).', 'Peripheral blood mononuclear cells (PBMCs) obtained from healthy donors (HD) (n\u2009=\u200920) and patients (n\u2009=\u200940) were tested for T-cell proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and cytokine production following stimulation with anti-CD3 mAb.', 'PBMCs obtained from CRC patients prior to treatment exhibited lower auto-MLR responses and low production of IL-2, IFN-γ, IL-12 and IL-18 cytokines, whereas IL-4 and IL-10 cytokines were increased as compared to HD (p\u2009<\u20090.001, for all parameters) following in vitro stimulation with anti-CD3 mAb. During treatment, and in particular in week 12 of evaluation, IL-2 (p\u2009<\u20090.001 for both IFL and B-IFL groups), IFN-γ (p\u2009<\u20090.001 for IFL and p\u2009=\u20090.001 for B-IFL), IL-12 (p\u2009<\u20090.001 for both IFL and B-IFL) and IL-18 (p\u2009<\u20090.001 for both IFL and B-IFL) production, as well as auto-MLR responses increased (p\u2009<\u20090.001 for both IFL and B-IFL), whereas IL-4 (p\u2009<\u20090.001 for IFL and p\u2009=\u20090.001 for B-IFL) and IL-10 [p\u2009<\u20090.001 for IFL and p\u2009=\u20090.067 (non-significant) for B-IFL] production decreased over baseline in the two treatment groups, yet their respective values never reached those of HD. Moreover, IL-2, IFN-γ production, and auto-MLR were higher in the B-IFL over the IFL treatment group (p\u2009<\u20090.001, p\u2009<\u20090.04, p\u2009<\u20090.001, respectively).'] Does combined treatment with bevacizumab and standard chemotherapy restore abnormal immune parameters in advanced colorectal cancer patients?
qiaojin/PubMedQA
2
[ -2.0939066410064697, -1.5200293064117432, 2.6494486331939697 ]
['We observed that a number of patients presenting to our clinic with diverticular fistulation were taking nicorandil for angina. Recognised side effects of nicorandil include gastrointestinal and genital ulceration. The aim of our study was to determine whether nicorandil is an aetiological agent in diverticular fistulation.', 'We conducted a case-control study of patients with diverticular disease related enteric fistulae. Two patient groups were identified: a study group of patients with diverticular fistulae, and a control group with uncomplicated diverticular disease. The proportion of patients who had ever used nicorandil was compared between the two groups.', 'A total of 153 case notes were analysed, 69 patients with fistulae and 84 control patients with uncomplicated diverticular disease. Female to male ratio in both groups was 2:1. The mean age was 71 years in the fistula group and 69 years in the control diverticular disease group (P = ns). Of those with colonic fistulae, 16% were taking nicorandil compared with 2% of the control group (odds ratio 7.8; 95% confidence interval 1.5-39.1; P = 0.008). There was no significant difference in rates of ischaemic heart disease between fistula and control groups.'] Is diverticular fistulation associated with nicorandil usage?
qiaojin/PubMedQA
2
[ -1.6686832904815674, -1.3345005512237549, 1.9958136081695557 ]
['Previous literature has shown that the frontal N30 is increased during movement of the hand contralateral to median nerve stimulation. This finding was a result of non-dominant left hand movement in right-handed participants. It is unclear however if the effect depends upon non-dominant hand movement or if this is a generalized phenomenon across the upper-limbs. This study tests the effect of dominant and non-dominant hand movement upon contralateral frontal and parietal somatosensory evoked potentials (SEPs) and further tests if this relationship persists in left hand dominant participants. Median nerve SEPs were elicited from the wrist contralateral to movement in both right hand and left hand dominant participants alternating the movement hand in separate blocks. Participants were required to volitionally squeeze (~20% of a maximal voluntary contraction) a pressure-sensitive bulb every ~3 seconds with the hand contralateral to median nerve stimulation. SEPs were continuously collected during the task and individual traces were grouped into time bins relative to movement according to the timing of components of the Bereitschaftspotential. SEPs were then averaged and quantified from both FCZ and CP3/4 scalp electrode sites during both the squeeze task and at rest.', 'The N30 is facilitated during non-dominant hand movement in both right and left hand dominant individuals. There was no effect for dominant hand movement in either group.'] Does non-dominant hand movement facilitate the frontal N30 somatosensory evoked potential?
qiaojin/PubMedQA
2
[ -2.4652678966522217, -0.9094113111495972, 2.4455819129943848 ]
['The accumulation of protease resistant conformers of the prion protein (PrP(res)) is a key pathological feature of prion diseases. Polyanions, including RNA and glycosaminoglycans have been identified as factors that contribute to the propagation, transmission and pathogenesis of prion disease. Recent studies have suggested that the contribution of these cofactors to prion propagation may be species specific.', 'In this study a cell-free assay was used to investigate the molecular basis of polyanion stimulated PrP(res) formation using brain tissue or cell line derived murine PrP. Enzymatic depletion of endogenous nucleic acids or heparan sulphate (HS) from the PrP(C) substrate was found to specifically prevent PrP(res) formation seeded by mouse derived PrP(Sc). Modification of the negative charge afforded by the sulphation of glycosaminoglycans increased the ability of a familial PrP mutant to act as a substrate for PrP(res) formation, while having no effect on PrP(res) formed by wildtype PrP. This difference may be due to the observed differences in the binding of wild type and mutant PrP for glycosaminoglycans.'] Does glycosaminoglycan sulphation affect the seeded misfolding of a mutant prion protein?
qiaojin/PubMedQA
2
[ -2.6256797313690186, -0.9086896181106567, 2.6061577796936035 ]
['Inhibition of mammalian target of rapamycin (mTOR) represents an attractive target for anticancer therapy, but its role in suppression of colorectal cancer (CRC) cell growth by cyclooxygenase-2 (COX-2) inhibitors is unclear. Here, we analyzed the effect of indomethacin (Indo, a nonselective COX-2 inhibitor) and nimesulide (Nim, a selective COX-2 inhibitor) on mTOR signaling in CRC cells in vitro and in vivo to determine the dependence of this effect on COX-2.', 'Human CRC cell lines with varying COX-2 expression levels were treated with Indo and Nim. Western blot test was performed to detect mTOR-related components (mTOR, p70s6\xa0K, and 4EBP1), and cell viability, cell cycle, and apoptosis were assessed. HCT116 and SW1116 cells were injected into athymic nude mice to establish a CRC xenograft model. After treatment with Nim, tumor volume, mTOR signaling, and apoptosis were evaluated in this model. HT29 and SW1116 cells were also treated with Nim after transfection with COX-2-specific small interfering RNA (siRNA) to assess dependence of COX-2 on mTOR signaling under drug treatment.', 'Both Indo and Nim reduced mTOR signaling activity in CRC cells that differ in their COX-2 expression in vitro and in vivo. Additionally, Indo and Nim could reduce the mTOR signaling activity after COX-2 silencing in CRC cells.'] Is mTOR signaling involved in indomethacin and nimesulide suppression of colorectal cancer cell growth via a COX-2 independent pathway?
qiaojin/PubMedQA
2
[ -2.394352674484253, -1.2880563735961914, 2.728637218475342 ]
['FOXC2 has been implicated in cancer progression through its induction of epithelial-to-mesenchymal transition. We analyzed the clinical significance of FOXC2 in esophageal cancer cases, in which early distant metastasis or invasion to nearby organs is an obstacle to treatment.', 'Quantitative reverse transcriptase-polymerase chain reaction was used to evaluate FOXC2 mRNA expression in 70 esophageal cancer cases to determine the clinicopathologic significance of FOXC2 expression. Furthermore, we examined associations between FOXC2 expression and matrix metalloproteinases 2 (MMP2) and matrix metalloproteinases 9 (MMP9). We also performed in vitro invasion and migration assays for FOXC2-suppressed esophageal cancer cells.', 'In clinicopathologic analysis, the high-FOXC2 expression group showed a higher incidence of advanced tumor stage, lymph node metastasis, and lymphatic invasion than the low-FOXC2 expression group (P\xa0<\xa00.05). In particular, tumor stage exhibited the most remarkable difference (P\xa0<\xa00.0001). Expression of MMP2 and MMP9 was far higher in the high-FOXC2 expression group. Furthermore, the high-FOXC2 expression group had a significantly poorer prognosis than did the low expression group (P\xa0=\xa00.006). Multivariate analysis indicated that high FOXC2 expression was an independent prognostic factor for survival. Suppression of FOXC2 expression altered the invasive and the migratory ability of esophageal cancer cells in vitro.'] Is fOXC2 a novel prognostic factor in human esophageal squamous cell carcinoma?
qiaojin/PubMedQA
2
[ -2.151195764541626, -1.35727059841156, 2.504767417907715 ]
['Typically, neurosurgery is performed several weeks after diagnostic imaging. In the majority of cases, histopathology confirms the diagnosis of neoplasia. In a small number of cases, a different diagnosis is established or histopathology is nondiagnostic. The frequency with which these outcomes occur has not been established.', 'To determine the frequency and outcome of disappearing brain lesions within a group of patients undergoing surgery for suspected brain tumor.', 'Over the past decade, 982 patients were managed in the intraoperative magnetic resonance imaging unit at the University of Calgary, Calgary, Alberta, Canada. These patients have been prospectively evaluated.', 'In 652 patients, a brain tumor was suspected. In 6 of the 652 patients, histopathology indicated a nontumor diagnosis. In 5 patients, intraoperative images, acquired after induction of anesthesia, showed complete or nearly complete resolution of the suspected tumor identified on diagnostic magnetic resonance imaging acquired 6 ± 4 (mean ± SD) weeks previously. Anesthesia was reversed, and the surgical procedure aborted. The lesions have not progressed with 6 ± 2 years of follow-up.'] Does identification of disappearing brain lesions with intraoperative magnetic resonance imaging prevent surgery?
qiaojin/PubMedQA
2
[ -2.385974645614624, -0.6304340958595276, 2.0687918663024902 ]
['To investigate if granulocyte-macrophage colony stimulating factor (GM-CSF) gene-modified dendritic cells (DC) enhance antitumor immunity in vitro.', 'Mice were injected with chemokine ligand 3 (CCL3) via the tail vein. Fresh B220(-)CD11c(+) cells were sorted from the peripheral blood mononuclear cells (PBMCs) and cultured into DCs by cytokines.DCs were transfected with AdGM-CSF gene at different ratios of multiplicity of infection (MOI) to determine the optimal gene transfection conditions, and the expression of GM-CSF was detected after transfection. The variation of GM-CSF gene-modifiedDCs were analyzed by morphological examination, phenotype analysis, and mixed lymphocyte reaction (MLR).DCs were loaded with gastric cancer antigen obtained by freezing and thawing method. The killing effect of DCs vaccine-stimulated T lymphocytes on gastric cancer cells was assessed by MTT assay. INF-gamma production was determined with the INF-gamma ELISA kit.', 'B220(-)CD11c(+) cells increased obviously after CCL3 injection. The ELISA results showed that after GM-CSF gene modification, DCs could produce high level of GM-CSF. When DCs were transfected with AdGM-CSF gene at MOI equal to 100, the GM-CSF level in culture supernatants reached saturation [(130.00 +/- 12.61) pg/ml]. After GM-CSF gene-modification, DCs tend to be more maturated as detected by morphological observation and phenotype analysis. At the same time, the capacity of activating the proliferation of allogeneic T lymphocytes was enhanced greatly. T lymphocytes stimulated by DCs transfected with GM-CSF gene showed a specific killing effect on gastric carcinoma cells and produced high level of INF-gamma [(1245.00 +/- 13.75) pg/ml].'] Does [ GM-CSF gene-modified dendritic cell vaccine enhance antitumor immunity in vitro ]?
qiaojin/PubMedQA
2
[ -2.1054279804229736, -1.5287644863128662, 2.6834094524383545 ]
['It has been shown that many women with polycystic ovary syndrome (PCOS) are 25-hydroxyvitamin D (25OHD) insufficient. Both statin treatment and vitamin D supplementation have been shown to improve biochemical hyperandrogenemia, insulin resistance, and markers of inflammation in patients with PCOS, raising the possibility that some of the statin effects are mediated through vitamin D.', 'We conducted this randomized, double-blind placebo controlled study to assess the effect of atorvastatin on serum 25OHD concentrations in patients with PCOS. Forty medication-naive patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. After completing the initial 3 months of atorvastatin or placebo, both groups of patients participated in a 3-month extension study with metformin 1500 mg daily. We measured changes in 25OHD concentrations by use of tandem mass spectrometry.', 'Mean (SD) baseline 25OHD concentrations were comparable between the 2 groups [45.9 (2.4) vs 44.8 (1.8) nmol/L; P = 0.7]. There was a significant increase in 25OHD concentrations with atorvastatin [45.9 (2.4) vs 60.8 (3.5) nmol/L] compared with placebo [44.8 (1.8) vs 41.8 (3.2) nmol/L; P = 0.02]. Three-month treatment with metformin maintained the improvement of 25OHD with atorvastatin compared to baseline [45.9 (2.4) vs 61.8 (3.5), P ≤ 0.01). There were no significant changes in 25OHD concentrations in the placebo group after 12 weeks of metformin.'] Does atorvastatin increase 25-hydroxy vitamin D concentrations in patients with polycystic ovary syndrome?
qiaojin/PubMedQA
2
[ -1.4378089904785156, -1.6912894248962402, 2.056976795196533 ]
['The purpose of this study was to investigate the association between atrial fibrillation (AF) and pericardial fat.', 'Pericardial fat is visceral adipose tissue that possesses inflammatory properties. Inflammation and obesity are associated with AF, but the relationship between AF and pericardial fat is unknown.', 'Pericardial fat volume was measured using computed tomography in 273 patients: 76 patients in sinus rhythm, 126 patients with paroxysmal AF, and 71 patients with persistent AF.', 'Patients with AF had significantly more pericardial fat compared with patients in sinus rhythm (101.6 +/- 44.1 ml vs. 76.1 +/- 36.3 ml, p < 0.001). Pericardial fat volume was significantly larger in paroxysmal AF compared with the sinus rhythm group (93.9 +/- 39.1 ml vs. 76.1 +/- 36.3 ml, p = 0.02). Persistent AF patients had a significantly larger pericardial fat volume compared with paroxysmal AF (115.4 +/- 49.3 ml vs. 93.9 +/- 39.1 ml, p = 0.001). Pericardial fat volume was associated with paroxysmal AF (odds ratio: 1.11; 95% confidence interval: 1.01 to 1.23, p = 0.04) and persistent AF (odds ratio: 1.18, 95% confidence interval: 1.05 to 1.33, p = 0.004), and this association was completely independent of age, hypertension, sex, left atrial enlargement, valvular heart disease, left ventricular ejection fraction, diabetes mellitus, and body mass index.'] Is pericardial fat independently associated with human atrial fibrillation?
qiaojin/PubMedQA
2
[ -1.7375895977020264, -1.4566543102264404, 2.1997148990631104 ]
['Early, empiric, broad-spectrum antibiotics followed by de-escalation to pathogen-specific therapy is the standard of care for ventilator-associated pneumonia (VAP). In our surgical intensive care unit (SICU), imipenem-cilastatin (I-C) in combination with tobramycin (TOB) or levofloxacin (LEV) has been used until quantitative bronchoalveolar lavage results are finalized, at which time de-escalation occurs to pathogen-specific agents. With this practice, however, alterations in antimicrobial resistance remain a concern. Our hypothesis was that this strict regimen does not alter antimicrobial susceptibility of common gram-negative VAP pathogens in our SICU.', 'After Institutional Review Board approval, a retrospective review of SICU-specific antibiograms was performed for the sensitivities of common gram-negative VAP pathogens. Time periods were defined as early (January-June 2005) and late (July-December 2006). Chart review of empiric and de-escalation antibiotic usage was obtained. Data were collated, and statistical significance was assessed with the chi-square test using the on-line Simple Interactive Statistical Analysis tool.', 'Imipenem-cilastatin was used 198 times for empiric VAP coverage (811 patient-days), whereas TOB and LEV were given a total of 149 (564 patient-days) and 61 (320 patient-days) times, respectively. Collectively, the susceptibility of gram-negative organisms to I-C did not change (early 91.4%; late 97%; p\u2009=\u20090.33). Individually, non-significant trends to greater sensitivity to I-C were noted for both Pseudomonas aeruginosa (early 85.7%; late 90.9%; p\u2009=\u20090.73) and Acinetobacter baumannii (early 80%; late 100%; p\u2009=\u20090.13). Further, both TOB (early 77.1%; late 70.0%; p\u2009=\u20090.49) and LEV (early 74.3%; late 70.0%; p\u2009=\u20090.67) were found to maintain their susceptibility profiles. The frequency of resistant gram-positive VAPs was unchanged during the study period. Our de-escalation compliance (by 96\u2009h) was 78% for I-C, 77.2% for TOB, and 59% for LEV. When infections requiring I-C were removed from the analysis, de-escalation compliance was improved to 92%.'] Does empiric , broad-spectrum antibiotic therapy with an aggressive de-escalation strategy induce gram-negative pathogen resistance in ventilator-associated pneumonia?
qiaojin/PubMedQA
2
[ -1.980739951133728, -1.5821727514266968, 2.575672149658203 ]
['To study short- and intermediate-term global renal function in patients undergoing a single percutaneous radiofrequency ablation (pRFA) for a solitary renal parenchymal tumor.', 'We reviewed the records of 62 patients who underwent a single pRFA for solitary renal parenchymal tumor. We used the abbreviated Modified Diet for Renal Disease equation to calculate baseline, 1-month, and 1-year glomerular filtration rate (GFR). We defined normal as >60, moderately diminished as 45-60, and severely diminished GFR as <45 cc/minute/1.73 m². We used the Wilcoxon paired rank sum method to compare 1-month and 1-year GFR to baseline. We fit a linear regression model to test the association of lesion size to GFR controlling for lesion location and baseline GFR.', 'There was no difference in GFR from baseline at 1 month or 1 year (55 vs. 58 cc/minute/1.73 m², p=0.24 and 55 vs. 57 cc/minute/1.73 m², p=0.8, respectively). Tumor size did not affect GFR at 1 month or 1 year after controlling for lesion location and baseline GFR.'] Does percutaneous radiofrequency ablation affect glomerular filtration rate?
qiaojin/PubMedQA
2
[ -1.2434669733047485, -1.6591697931289673, 1.915568232536316 ]
['Chronic infection with hepatitis C virus (HCV) is often associated with elevated hepatic iron levels. Excess iron is known to promote oxidative stress and exacerbate liver disease. Nevertheless, biochemical studies in subgenomic HCV replicon systems showed that iron can also suppress the expression of viral RNA and proteins by inhibiting the enzymatic activity of the RNA polymerase NS5B. To explore the physiological relevance of this response, we evaluated the effects of iron during infection of permissive Huh7.5.1 hepatoma cells with HCV.', 'We utilized Fe-SIH (iron complexed with salicylaldehyde isonicotinoyl hydrazone), a cell permeable and highly efficient iron donor.', 'Treatments of infected cells with Fe-SIH drastically reduced the expression of viral proteins (core and NS3) and RNA, in a dose-dependent manner. The inhibition was dramatic when Fe-SIH was administered simultaneously with the HCV inoculum or early afterwards, while pre-treatment of cells with Fe-SIH before infection failed to elicit antiviral responses. Iron chelation with SIH did not significantly alter the expression of viral proteins.'] Does iron inhibit replication of infectious hepatitis C virus in permissive Huh7.5.1 cells?
qiaojin/PubMedQA
2
[ -2.543886423110962, -1.215406060218811, 2.7886159420013428 ]
[': Bacillus Calmette-Guérin (BCG) infection causes hepatic injury following granuloma formation and secretion of cytokines which renders mice highly sensitive to endotoxin-mediated hepatotoxicity. Tumor necrosis factor (TNF) is required for granuloma formation and is one of the most important cytokines in liver injury. TNF inhibitors are effective therapies for inflammatory diseases. However, clinical use of non-selective TNF inhibitors is associated with an increased risk of infections. This work investigates the differential roles of soluble TNF (solTNF) and membrane TNF (memTNF) in BCG infection, BCG/LPS- and D-GALN/LPS-induced liver injury.', 'We have used both genetic and pharmacologic approaches and analyzed liver injury, TLR4, cytokine and iNOS activation induced by BCG, BCG/LPS and D-GALN/LPS.', 'BCG infection-induced liver injury is seen in wild-type mice but not in TNF(-/-), memTNF knock-in (KI), and sTNFR1-Fc transgenic mice. Severity of BCG-induced liver injury is correlated with BCG-granuloma number and hepatic expression of TLR4 and iNOS. In addition, protection from liver damage caused by BCG/LPS or D-GALN/LPS administration was observed in TNF(-/-), memTNF KI and sTNFR1-Fc transgenic mice. To extend the genetic findings, we then evaluated whether selective pharmacological inhibition of solTNF by dominant-negative (DN)-TNF neutralization and non-selective inhibition of solTNF and memTNF by anti-TNF antibodies and etanercept (TNFR2-IgG1) can protect the mice from liver injury. Both selective and non-selective inhibition of solTNF protected mice from BCG/LPS and D-GALN/LPS-induced liver damage.'] Is soluble TNF , but not membrane TNF , critical in LPS-induced hepatitis?
qiaojin/PubMedQA
2
[ -2.457573175430298, -1.3443737030029297, 2.845852851867676 ]
['To examine the association between uric acid (UA) level during the first 20 weeks of pregnancy and the development of gestational diabetes mellitus (GDM) and preeclampsia in the second half of pregnancy.', 'The study population included registered births (n = 5507) between 2001 and 2007 in a tertiary medical center. The UA levels during the first 20 weeks of pregnancy were sorted by UA ≤ 2.4 mEq/L; UA = 2.5-4.0 mEq/L, UA = 4.1-5.5 mEq/L, and UA > 5.5 mEq/L. The linear-by-linear chi-square test and ROC curves were used to determine the association between UA level during the first 20 weeks and pregnancy complications. Multivariate analyses were performed to demonstrate whether UA level is an independent factor for the prevalence of preeclampsia and GDM.', 'Significant linear association was documented between UA level in the first 20 weeks and the prevalence of GDM and mild preeclampsia. The lowest and the highest prevalence of GDM were found in the UA ≤ 2.4 mEq/L group (6.3%) and in the UA > 5.5 mEq/L group (10.5%) (p < 0.001), respectively. Mild preeclampsia was diagnosed in 2.1% of the patients from the UA ≤ 2.4 mEq/L group, 3.3% from the UA = 2.5-4.0 mEq/L group, 5.3% from the UA = 4.1-5.5 mEq/L group, and 4.5% from the UA > 5.5 mEq/L group (p < 0.001). Three multiple logistic regression models controlling for maternal age showed that UA level is an independent risk factor for both GDM and mild preeclampsia.'] Is high uric acid level during the first 20 weeks of pregnancy associated with higher risk for gestational diabetes mellitus and mild preeclampsia?
qiaojin/PubMedQA
2
[ -0.4718262851238251, -1.7197179794311523, 1.1603419780731201 ]
['We aimed to characterize the lasting effect of moderate caloric restriction during early pregnancy on offspring energy homeostasis, by focusing on the effects on food intake and body weight as well as on the insulin and leptin systems.', 'Male and female offspring of 20% caloric restricted dams (from 1 to 12 days of pregnancy) (CR) and from control dams were studied. These animals were fed after weaning with a normal-fat (NF) diet until the age of 4 months, and then moved to a high-fat (HF) diet. Blood parameters were measured under fed and 14-h fasting conditions at different ages (2, 4 and 5 months). Food preferences were also assessed in adult animals.', 'Accumulated caloric intake from weaning to the age of 5 months was higher in CR animals compared with their controls, and this resulted in higher body weight in adulthood in males, but not in females. Both male and female CR animals already showed higher insulin levels at the age of 2 months, under fed conditions, and higher HOMA-IR from the age of 4 months, compared with their controls. CR male animals, but not females, displayed higher preference for fat-rich food than their controls in adulthood and higher circulating leptin levels when they were under HF diet.'] Is sexual dimorphism in the lasting effects of moderate caloric restriction during gestation on energy homeostasis in rats related with fetal programming of insulin and leptin resistance?
qiaojin/PubMedQA
2
[ -2.6560137271881104, 0.7256837487220764, 0.9928154945373535 ]
['After stent-related vascular injury, an inflammatory response triggers the mobilization of bone marrow-derived stem cells, including both endothelial and smooth muscle progenitors, leading to re-endothelialization as well as restenosis. It has been postulated that neutrophil-released matrix metalloproteinase-9 (MMP-9) induces stem cell mobilization.', 'To elucidate the mechanistic link between inflammation and stem cell mobilization after coronary stenting.', 'In 31 patients undergoing coronary stenting, we serially measured activated Mac-1 on the surface of neutrophils and active MMP-9 levels in the coronary sinus blood plasma, and the number of circulating CD34-positive cells in the peripheral blood.', 'After bare-metal stent implantation (n=21), significant increases in the numbers of CD34-positive cells (maximum on post-procedure day 7, P<0.001), activated Mac-1 (at 48 h, P<0.001), and active MMP-9 levels (at 24h, P<0.001) were observed. However, these changes were absent after sirolimus-eluting stent implantation (n=10). In overall patients, the numbers of CD34-positive cells on day 7 (R=0.58, P<0.01) and activated Mac-1 at 48 h (R=0.58, P<0.01) were both correlated with active MMP-9 levels at 24h. Stimulation of activated Mac-1 on the surface of isolated human neutrophils produced active MMP-9 release in vitro.'] Is activation of matrix metalloproteinase-9 associated with mobilization of bone marrow-derived cells after coronary stent implantation?
qiaojin/PubMedQA
2
[ -2.1399919986724854, -1.4351840019226074, 2.5647482872009277 ]
['To evaluate the relationship between dynamic mechanical loading, as indicated by external knee adduction moment (KAM) measures during walking, and measures of articular cartilage morphology and subchondral bone size in people with medial knee osteoarthritis (OA).', '180 individuals with radiographic medial tibiofemoral OA participated. Peak KAM and KAM angular impulse were measured by walking gait analysis. Tibial cartilage volume and plateau bone area, and tibiofemoral cartilage defects were determined from magnetic resonance imaging using validated methods.', 'Both peak KAM (coefficient=0.42, 95% confidence interval (CI) 0.04-0.79, P=0.03) and KAM impulse (coefficient=1.79, 95% CI 0.80-2.78, P<0.001) were positively associated with the severity of medial tibiofemoral cartilage defects. KAM impulse was also associated with the prevalence of medial tibiofemoral cartilage defects (odds ratio 4.78, 95% CI 1.10-20.76, P=0.04). Peak KAM (B=0.05, 95% CI 0.01-0.09, P=0.02) and KAM impulse (B=0.16, 95% CI 0.06-0.25, P=0.002) were positively associated with medial:lateral tibial plateau bone area, and KAM impulse was also associated with medial tibial plateau bone area (B=133.7, 95% CI 4.0-263.3, P=0.04). There was no significant association between KAM measures and tibial cartilage volume.'] Is dynamic knee loading related to cartilage defects and tibial plateau bone area in medial knee osteoarthritis?
qiaojin/PubMedQA
2
[ -1.702767014503479, -1.4899176359176636, 2.2198054790496826 ]
['The role of inflammation in osteoarthritis (OA) pathogenesis is unclear, and the associations between inflammatory cytokines and cartilage loss have not been reported. We determined the associations between serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), knee radiographic OA (ROA) and cartilage loss over 2.9 years in older adults.', 'A total of 172 randomly selected subjects (mean 63 years, range 52-78, 47% female) were studied at baseline and approximately 3 (range 2.6-3.3) years later. IL-6 and TNF-α were assessed by radioimmunoassay. T1-weighted fat-suppressed magnetic resonance imaging of the right knee was performed at baseline and follow-up to determine knee cartilage volume. Knee ROA of both knees was assessed at baseline.', 'At baseline, quartiles of IL-6 and TNF-α were associated with increased prevalence of medial tibiofemoral joint space narrowing (OARSI grade ≥ 1) in multivariate analyses [odds ratio (OR): 1.42 and 1.47 per quartile, respectively, both P<0.05]. Longitudinally, baseline IL-6 predicted loss of both medial and lateral tibial cartilage volume (β: -1.19% and -1.35% per annum per quartile, P<0.05 and P<0.01, respectively), independently of TNF-α. Change in IL-6 was associated with increased loss of medial and lateral tibial cartilage volume (β: -1.18% and -1.06% per annum per quartile, both P<0.05) and change in TNF-α was also negatively associated with change in medial cartilage volume (β: -1.27% per annum per quartile, P<0.05).'] Are circulating levels of IL-6 and TNF-α associated with knee radiographic osteoarthritis and knee cartilage loss in older adults?
qiaojin/PubMedQA
2
[ -1.779467225074768, -1.6074323654174805, 2.381307363510132 ]
['Human exposure to inorganic arsenic (iAs), a potent oxidative stressor, causes various dermal disorders, including hyperkeratosis and skin cancer. Nuclear factor-erythroid 2-related factor 1 (NRF1, also called NFE2L1) plays a critical role in regulating the expression of many antioxidant response element (ARE)-dependent genes.', 'We investigated the role of NRF1 in arsenic-induced antioxidant response and cytotoxicity in human keratinocytes.', 'In cultured human keratinocyte HaCaT cells, inorganic arsenite (iAs3+) enhanced the protein accumulation of long isoforms (120-140 kDa) of NRF1 in a dose- and time-dependent fashion. These isoforms accumulated mainly in the nuclei of HaCaT cells. Selective deficiency of NRF1 by lentiviral short-hairpin RNAs in HaCaT cells [NRF1-knockdown (KD)] led to decreased expression of γ-glutamate cysteine ligase catalytic subunit (GCLC) and regulatory subunit (GCLM) and a reduced level of intracellular glutathione. In response to acute iAs3+ exposure, induction of some ARE-dependent genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), GCLC, and GCLM, was significantly attenuated in NRF1-KD cells. However, the iAs3-induced expression of heme oxygenase 1 (HMOX-1) was unaltered by silencing NRF1, suggesting that HMOX-1 is not regulated by NRF1. In addition, the lack of NRF1 in HaCaT cells did not disturb iAs3+-induced NRF2 accumulation but noticeably decreased Kelch-like ECH-associated protein 1 (KEAP1) levels under basal and iAs3+-exposed conditions, suggesting a potential interaction between NRF1 and KEAP1. Consistent with the critical role of NRF1 in the transcriptional regulation of some ARE-bearing genes, knockdown of NRF1 significantly increased iAs3+-induced cytotoxicity and apoptosis.'] Do long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human keratinocytes?
qiaojin/PubMedQA
2
[ -2.4748904705047607, -1.2401454448699951, 2.749817371368408 ]
['The purpose of the study was to analyze the incidence of intra-abdominal infectious complications after the application of a fibrinogen sealant to the duodenojejunal anastomosis in simultaneous pancreas-kidney transplants (SPK) with enteric drainage.', 'Results of 68 SPKs with enteric drainage were prospectively assessed. A fibrinogen and thrombin sheet was applied to the duodenojejunal anastomosis in 34 patients, who were compared to a control group of 34 patients. The incidence and severity of intra-abdominal infectious complications and the 1-year patient and grafts survival were analyzed.', 'Eighteen patients experienced intra-abdominal infectious complications. Grade 1a complications occurred in the study group, whereas surgery was required only in patients from the control group: complications grade 3a (15%) and complications grade 3b (18%) (p\xa0=\xa00.003 vs. study group, respectively). The overall rate of anastomotic leakage (complications grade 2b and 3b) was 10%, all of which occurred in the control group. The length of hospital stay was higher in the control group was 34.6\xa0±\xa011.3\xa0days vs. 22.8\xa0±\xa011.1\xa0days (p\xa0=\xa00.03). There were no significant differences in 1-year patient and graft survival between groups.'] Does human fibrinogen patches application reduce intra-abdominal infectious complications in pancreas transplant with enteric drainage?
qiaojin/PubMedQA
2
[ -1.7782377004623413, -1.4562463760375977, 2.243668556213379 ]
['During visual system development, multiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum. This information is required for the topographic mapping of retinal ganglion cell axons on the tectum. Meis1 is a TALE-class homeodomain transcription factor known to specify anterior-posterior identity in the hindbrain, but its role in visual system patterning has not been investigated.', 'meis1 is expressed in both the presumptive retina and tectum. An analysis of retinal patterning reveals that Meis1 is required to correctly specify both dorsal-ventral and nasal-temporal identity in the zebrafish retina. Meis1-knockdown results in a loss of smad1 expression and an upregulation in follistatin expression, thereby causing lower levels of Bmp signalling and a partial ventralization of the retina. Additionally, Meis1-deficient embryos exhibit ectopic Fgf signalling in the developing retina and a corresponding loss of temporal identity. Meis1 also positively regulates ephrin gene expression in the tectum. Consistent with these patterning phenotypes, a knockdown of Meis1 ultimately results in retinotectal mapping defects.'] Does meis1 specify positional information in the retina and tectum to organize the zebrafish visual system?
qiaojin/PubMedQA
2
[ -2.4772286415100098, -0.9770824313163757, 2.507655143737793 ]
['We previously showed that elevating hepatic nitric oxide (NO) levels reduced net hepatic glucose uptake (NHGU) in the presence of portal glucose delivery, hyperglycemia, and hyperinsulinemia. The aim of the present study was to determine the role of a downstream signal, soluble guanylate cyclase (sGC), in the regulation of NHGU by NO.', 'Studies were performed on 42-h-fasted conscious dogs fitted with vascular catheters. At 0 min, somatostatin was given peripherally along with 4× basal insulin and basal glucagon intraportally. Glucose was delivered at a variable rate via a leg vein to double the blood glucose level and hepatic glucose load throughout the study. From 90 to 270 min, an intraportal infusion of the sGC inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) was given in -sGC (n = 10) and -sGC/+NO (n = 6), whereas saline was given in saline infusion (SAL) (n = 10). The -sGC/+NO group also received intraportal SIN-1 (NO donor) to elevate hepatic NO from 180 to 270 min.', 'In the presence of 4× basal insulin, basal glucagon, and hyperglycemia (2× basal ), inhibition of sGC in the liver enhanced NHGU (mg/kg/min; 210-270 min) by ∼55% (2.9 ± 0.2 in SAL vs. 4.6 ± 0.5 in -sGC). Further elevating hepatic NO failed to reduce NHGU (4.5 ± 0.7 in -sGC/+NO). Net hepatic carbon retention (i.e., glycogen synthesis; mg glucose equivalents/kg/min) increased to 3.8 ± 0.2 in -sGC and 3.8 ± 0.4 in -sGC/+NO vs. 2.4 ± 0.2 in SAL (P < 0.05).'] Is a soluble guanylate cyclase-dependent mechanism involved in the regulation of net hepatic glucose uptake by nitric oxide in vivo?
qiaojin/PubMedQA
2
[ -1.9209414720535278, -1.5816600322723389, 2.4973626136779785 ]
['Our aim was to evaluate visualization methods for specific tasks performed with personal healthcare e-record systems for lay adults and older patients. We investigated common visualization methods for data entry and follow-up of personal and clinical information for self-control of blood coagulation functions.', 'Twenty-five old (72.2 +/- 5.5 years) and 25 young (30.4 +/- 4.9 years) participants completed tasks based on common scenarios, on experimental Web sites with hidden tracking programs. Functional parameters (time, accuracy), subjective parameters (preference, satisfaction), and physiological parameters (heart rate, skin temperature, sweat, respiratory rate, and muscle tension) monitored with miniature sensors were used.', 'Total time for data entry and information follow-up were significantly longer for older compared with younger participants, with no significant differences in accuracy (errors), in stress-related physiological parameters, in preferences, or in satisfaction between age group. The Menu display was the significantly preferred configuration for data entry in both age groups, based on functional, physiological, and subjective criteria (p < 0.05, Duncan test). The Calendar configuration was significantly preferred for mixed tasks of follow-up and information retrieval, in both age groups, based on functional, physiological, and subjective criteria (p < 0.05, Duncan test).'] Do evaluation of data display for patient-oriented electronic record of anticoagulant therapy?
qiaojin/PubMedQA
2
[ -1.95246160030365, -1.008885145187378, 2.0394253730773926 ]
['Alterations in interrelated endocrine axes may be related to the pathogenesis of mild cognitive impairment (MCI) and dementia.', 'Salivary cortisol before and after a 0.5-mg dexamethasone test, and serum levels of thyroid-stimulating hormone, total thyroxine (T(4)), free T(4), total triiodothyronine (TT(3)), estradiol, testosterone and insulin-like growth factor 1 were measured in 43 MCI cases and 26 healthy controls. All participants underwent a comprehensive neuropsychological test battery covering the cognitive domains of speed/attention, memory, visuospatial functions, language and executive functions.', 'The MCI group did not differ in basal levels of endocrine markers compared to controls. Among those with MCI, TT(3) levels were inversely associated with cognitive performance across all domains. After stratifying MCI cases according to TT(3) levels, those with relatively high TT(3) levels showed impairment in memory as well as in visuospatial and executive functions. Those with TT(3) levels at or below the lower boundary of the normal range performed comparably to healthy controls. Other endocrine markers were not related to cognitive performance.'] Are thyroid hormones associated with poorer cognition in mild cognitive impairment?
qiaojin/PubMedQA
2
[ -2.4411871433258057, -1.1444742679595947, 2.644766330718994 ]
['To determine levels of Peptidyl arginine deiminase 2 (PAD2) and its product protein-bound citrulline in cadaver eyes that suffered from normal tension glaucoma (NTG) compared to primary open angle glaucoma (POAG), and controls.', 'Western analysis, ELISA, and immunohistochemical analysis were performed with human tissues.', 'We report over expression of PAD2 and higher levels of its product protein-bound citrulline in the optic nerve of normal tension glaucoma patients (NTG).'] Is peptidylarginine deiminase type 2 over expressed in the glaucomatous optic nerve?
qiaojin/PubMedQA
2
[ -2.5491089820861816, -1.135223388671875, 2.8156371116638184 ]
['Peroxisome proliferator-activated receptor (PPAR)γ agonists attenuate atherosclerosis and abdominal aortic aneurysms (AAAs). PPARγ, a nuclear receptor, is expressed on many cell types including smooth muscle cells (SMCs).', 'To determine whether a PPARγ agonist reduces angiotensin II (Ang II)-induced atherosclerosis and AAAs via interaction with SMC-specific PPARγ.', 'Low-density lipoprotein receptor (LDLR)(-/-) mice with SMC-specific PPARγ deficiency were developed using PPARγ floxed (PPARγ(f/f)) and SM22 Cre(+) mice. PPARγ(f/f) littermates were generated that did not express Cre (Cre(0/0)) or were hemizygous for Cre (Cre(+/0)). To assess the contribution of SMC-specific PPARγ in ligand-mediated attenuation of Ang II-induced atherosclerosis and AAAs, both male and female Cre(0/0) and Cre(+/0) mice were fed a fat-enriched diet with or without the PPARγ agonist pioglitazone (Pio) (20 mg/kg per day) for 5 weeks. After 1 week of feeding modified diets, mice were infused with Ang II (1000 ng/kg per minute) for 4 weeks. SMC-specific PPARγ deficiency or Pio administration had no effect on plasma cholesterol concentrations. Pio administration attenuated Ang II-increased systolic blood pressure equivalently in both Cre(0/0) and Cre(+/0) groups. SMC-specific PPARγ deficiency increased atherosclerosis in male mice. Pio administration reduced atherosclerosis in only the Cre(0/0) mice, but not in mice with SMC-specific PPARγ deficiency. SMC-specific PPARγ deficiency or Pio administration had no effect on Ang II-induced AAA development. Pio also did not attenuate Ang II-induced monocyte chemoattractant protein-1 production in PPARγ-deficient SMCs.'] Do pioglitazone-induced reductions in atherosclerosis occur via smooth muscle cell-specific interaction with PPAR { gamma }?
qiaojin/PubMedQA
2
[ -2.098567485809326, -1.5020915269851685, 2.5523552894592285 ]
['Nona-D-arginine (D9R) amide suppressed interleukin 1β production during Pseudomonas aeruginosa corneal infection. The purpose of this study was to determine the cellular disposition of D9R and its effect on other inflammatory mediators induced by infection.', 'Mouse eyes received 5 μL of either phosphate-buffered saline (PBS, pH 7.4) or 100-μM D9R hourly for 5 hours (total of 6 drops per eye) immediately after corneal wounding and infection with 1 × 10 colony-forming units (CFUs) of P. aeruginosa strain PAO1. At 6, 12, and 24 hours postinfection, eyes were scored on a scale of 0 (normal eye) to +4 (corneal perforation). After scoring, mice were killed and eyes enucleated. Whole eyes were used for determining viable CFUs per eye. Corneas were excised for quantitation of tumor necrosis factor α, interferon γ, interleukin 10, and granulocyte-macrophage colony-stimulating factor. The fate of D9R in cells was determined using a labeled peptide.', 'Eyes treated with D9R had significantly lower disease scores (P ≤ 0.001) and fewer CFUs (P ≤ 0.01) than those in PBS-treated eyes. No corneal cytokines were detected in any D9R-treated eyes. In contrast, beginning at 12 hours postinfection, increasing amounts of tumor necrosis factor alpha, interleukin 10, and granulocyte-macrophage colony-stimulating factor were detectible in corneas of PBS-treated eyes. Within 60 minutes, D9R accumulated in the cell nucleus and nucleolus and remained for over 24 hours.'] Does nona-D-arginine amide suppress corneal cytokines in Pseudomonas aeruginosa keratitis?
qiaojin/PubMedQA
2
[ -2.1181042194366455, -1.5196001529693604, 2.648508071899414 ]
['Relapsing polychondritis (RP) is a rare and severe disease which may lead to destruction of elastic cartilages. Until now, no reliable biomarker of disease activity in RP has been available. This study was designed to measure serum levels of cartilage biomarkers during both active and inactive phases of the disease.', 'Serum levels of cartilage oligomeric matrix protein (COMP), chondroitin sulfate 846 epitope (CS846) of proteoglycan aggrecan and collagen type II collagenase cleavage neoepitope (C2C) were measured retrospectively in 21 subjects with RP. The Wilcoxon matched-pairs signed-rank test was used for statistical comparisons of biomarker levels in active and inactive phases of RP.', 'Only the serum level of COMP was significantly increased during disease flares. Steroids did not alter the serum cartilage-related biomarker levels. However, during the active phase, C2C levels were significantly higher in steroid treated patients compared with non-steroid treated patients.'] Is serum cartilage oligomeric matrix protein ( COMP ) level a marker of disease activity in relapsing polychondritis?
qiaojin/PubMedQA
2
[ -2.3560783863067627, -1.352485179901123, 2.7891740798950195 ]