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['Adolescents with type 1 diabetes (T1D) often have a less atherogenic-appearing fasting lipid profile than controls, despite increased rates of cardiovascular disease (CVD) as adults. We previously reported an atherogenic lipoprotein subfraction cholesterol distribution associated with insulin resistance (IR) in T1D adults. We sought to determine if T1D youth have more atherogenic profile than controls via a cross-sectional study.', 'Following 3 days of controlled diet and restricted exercise, fasting plasma samples were drawn from 28 T1D youth [50% female, age 15.3 ± 2 yr, body mass index (BMI) 48%ile; diabetes duration 73 ± 52 months, hemoglobin A1c (HbA1c) 8.3 ± 1.4%] and 17 non-diabetic controls (47% female, age: 15.0 ± 2 yr, BMI 49%ile) prior to a hyperinsulinemic euglycemic clamp. Lipoproteins were fractionated by fast protein liquid chromatography (FPLC) and lipoprotein cholesterol distribution determined. Outcome measures were IR assessed by glucose infusion rate (GIR) and FPLC lipoprotein subfraction cholesterol distribution.', 'T1D youth were more IR (GIR 9.1 ± 3.6 vs. 14.7 ± 3.9 mg/kg/min, p < 0.0001) and had more cholesterol distributed as small dense low density lipoprotein-cholesterol (LDL-C) and less as large buoyant high density lipoprotein-cholesterol (HDL-C) than controls (p < 0.05), despite no differences in the fasting lipid panel. T1D girls lacked the typical female less-atherogenic profile, whereas control girls tended to have a shift toward less dense LDL-C and HDL-C vs. control boys. Among T1D, IR but not HbA1c was associated with a more atherogenic lipoprotein profile.'] Is lipoprotein subfraction cholesterol distribution more atherogenic in insulin resistant adolescents with type 1 diabetes? | qiaojin/PubMedQA | 2 | [
-1.6010338068008423,
-1.5968196392059326,
2.1917319297790527
] |
['Low-grade inflammation is involved in adipose tissue (AT) and extracellular matrix (ECM) remodeling and induces deposition of ECM proteins in AT. We have previously shown that MFAP5 (microfibrillar-associated protein 5) expression decreases in AT after weight loss. The aim of this study was to investigate MFAP5 localization in human AT and gene expression in adipocytes and the role of MFAP5 in adipocyte metabolism and inflammation.', 'MFAP5 protein localization and gene expression were studied with immunohistochemistry and quantitative reverse transcriptase PCR (RT-qPCR) in human subcutaneous AT and cultured Simpson-Golabi-Behmel syndrome (SGBS) adipocytes, respectively. The effect of MFAP5 knock-down by siRNA on gene expression and insulin action was examined with RT-qPCR, western blot, and insulin-stimulated glucose uptake. The effect of different cytokines on MFAP5 gene and protein expression was investigated in cultured human SGBS preadipocytes.', 'MFAP5 protein was highly expressed in AT, and gene expression decreased during adipocyte differentiation in SGBS cells. Treatment of preadipocytes with TNFα and TGFβ1 increased MFAP5 gene and protein expression. Furthermore, MFAP5 knock-down decreased the expression of genes involved in inflammation.'] Is mFAP5 related to obesity-associated adipose tissue and extracellular matrix remodeling and inflammation? | qiaojin/PubMedQA | 2 | [
-2.499485492706299,
-1.1238794326782227,
2.7316224575042725
] |
['Laccase isoenzymes (LacI,II,III) produced on wheat bran from Trametes hirsuta were partially purified through anion exchange chromatography. The three isoenzymes had the same MW of 65\xa0kDa, and their main physico-chemical properties were studied. As single isoenzymes, laccases were unable to decolourize dye. Among several mediators evaluated, syringaldehyde was the most effective in dye decolourization (100%). A remarkable increase in dye decolourization was observed when LacI, II, III in mixture or crude enzyme were added to the reaction system, indicating that the laccases acted synergistically.'] Does synergistic action of laccases from Trametes hirsuta Bm2 improve decolourization of indigo carmine? | qiaojin/PubMedQA | 2 | [
-2.472313642501831,
-0.9066590666770935,
2.4832653999328613
] |
['Defective beta cell function during lipid oversupply and type 2 diabetes is associated with dysregulation of lysosomal function and autophagy. Whether this dysregulation represents augmentation or inhibition is unclear because of technical limitations in assaying autophagy. The current aim was to determine the effects of high-fat feeding on true autophagic flux in beta cells in vivo in mice, and to establish the relationship between autophagy, endoplasmic reticulum (ER) stress and apoptosis.', 'Green fluorescent protein-microtubule-associated protein 1 light chain 3 (GFP-LC3) mice were fed chow or high-fat diets for 8-10 weeks and injected with 100 mg kg(-1) day(-1) chloroquine for 5 days, prior to being killed, to block clearance of autophagic markers. Pancreases and livers were fixed and GFP-LC3 aggregates or autophagosomes were detected by fluorescence or electron microscopy, respectively. Independently, islets isolated from chow or high-fat-fed mice were treated for 2 h with chloroquine ex vivo, and immunoblotting was performed for markers of autophagy (LC3 lipidation - LC3II and p62/SQSTM1), ER stress (C/EBP homology protein [CHOP], phosphorylated eukaryotic initiation factor 2α [p-eIFα] and inositol requiring enzyme 1α [p-IRE1α]) and apoptosis (cleaved caspase-3).', 'Numbers of autophagosomes and GFP puncta were increased in beta cells by combined high-fat feeding and chloroquine injection, indicative of enhanced autophagic flux. By contrast, GFP puncta were attenuated in liver under the same conditions. Relative to chow-fed controls, islets isolated from fat-fed mice exhibited higher LC3II levels when treated ex vivo with chloroquine. The combination of high-fat feeding and acute chloroquine treatment induced CHOP, p-eIF2α and caspase-3, but not either treatment alone.'] Does high-fat diet increase autophagic flux in pancreatic beta cells in vivo and ex vivo in mice? | qiaojin/PubMedQA | 2 | [
-2.41135573387146,
-1.3754857778549194,
2.8355977535247803
] |
['To define the DNA methylation landscape of neuroblastoma and its clinicopathological impact.', 'Microarray DNA methylation data were analyzed and associated with functional/regulatory genome annotation data, transcriptional profiles and clinicobiological parameters.', 'DNA methylation changes in neuroblastoma affect not only promoters but also intragenic and intergenic regions at cytosine-phosphate-guanine (CpG) and non-CpG sites, and target functional chromatin domains of development and cancer-related genes such as CCND1. Tumors with diverse clinical risk showed differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation observed essentially in clinically favorable cases was associated with the differentiation status of neuroblastoma and expression of key genes such as ALK.'] Does dNA methylation fingerprint of neuroblastoma reveal new biological and clinical insights? | qiaojin/PubMedQA | 2 | [
-2.6728708744049072,
-0.9442822933197021,
2.7570691108703613
] |
['In adults undergoing gastric bypass surgery, it is routine practice to perform pre-operative testing for Helicobacter pylori infection. Evidence suggests that infection impairs anastomotic healing and contributes to complications. There currently are no data for adolescents undergoing bariatric procedures. Despite few patients with pre-operative symptoms, we noted occasional patients with H. pylori detected after sleeve gastrectomy. We reviewed our experience with our adolescent sleeve gastrectomy cohort to determine the prevalence of H. pylori infection, its predictive factors, and association with outcomes. We hypothesized that H. pylori infection would be associated with pre-operative symptoms, but not surgical outcomes.', 'All patients undergoing sleeve gastrectomy at our hospital were included. We conducted a chart review to determine pre- or post-operative symptoms of gastroesophageal reflux disease GERD or gastritis, operative complications, and long-term anti-reflux therapy after surgery. Pathology reports were reviewed for evidence of gastritis and H. pylori infection.', '78 adolescents had laparoscopic sleeve gastrectomy from January 2010 through July 2014. The prevalence of chronic gastritis was 44.9% (35/78) and 11.4% of those patients had H. pylori (4/35). Only one patient with H. pylori had pre-operative symptoms, and only 25.7% (9/35) of patients with pathology-proven gastritis had symptoms. One staple line leak occurred but this patient did not have H. pylori or gastritis. Mean patient follow-up was 10 (3-26) mos.'] Does prevalence of Chronic Gastritis or Helicobacter pylori Infection in Adolescent Sleeve Gastrectomy Patients Correlate with Symptoms or Surgical Outcomes? | qiaojin/PubMedQA | 2 | [
-2.018571138381958,
-1.3760335445404053,
2.4184980392456055
] |
['Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC).', 'Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7) and keratin 34βE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients.', 'Based on keratin 34βE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34βE12+/K7+, 168 months vs. 34βE12+/K7+, 73 months vs. 34βE12-/K7+, 30 months; p = 0.0004). In multivariate analysis, stage II-IIIA (HR 2.9), 34βE12+/K7+ (HR 1.90) and 34βE12-/K7+ (HR 3.7), were prognostic factors of poor cancer-specific survival (CSS) (p < 0.001). Validation in the Norwegian cohort confirmed that stage II-IIIA (HR 2.3), 34βE12+/K7+ (HR 1.6), and 34βE12-/K7+ (HR 2.0) were prognostic factors of poor CSS (p < 0.05). Multivariate Cox proportional-hazard analysis demonstrated that 34βE12+/K7 + and 34βE12+/K7 + status was significantly associated with poor overall survival (p < 0.05).'] Is keratin 34betaE12/keratin7 expression a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer? | qiaojin/PubMedQA | 2 | [
-1.8241424560546875,
-1.5123211145401,
2.3693182468414307
] |
['Familial glucocorticoid deficiency (FGD) reflects specific failure of adrenocortical glucocorticoid production in response to adrenocorticotropic hormone (ACTH). Most cases are caused by mutations encoding ACTH-receptor components (MC2R, MRAP) or the general steroidogenesis protein (StAR). Recently, nicotinamide nucleotide transhydrogenase (NNT) mutations were found to cause FGD through a postulated mechanism resulting from decreased detoxification of reactive oxygen species (ROS) in adrenocortical cells.', 'In a consanguineous Palestinian family with combined mineralocorticoid and glucocorticoid deficiency, whole-exome sequencing revealed a novel homozygous NNT_c.598 G>A, p.G200S, mutation. Another affected, unrelated Palestinian child was also homozygous for NNT_p.G200S. Haplotype analysis showed this mutation is ancestral; carrier frequency in ethnically matched controls is 1/200. Assessment of patient fibroblasts for ROS production, ATP content and mitochondrial morphology showed that biallelic NNT mutations result in increased levels of ROS, lower ATP content and morphological mitochondrial defects.'] Is combined mineralocorticoid and glucocorticoid deficiency caused by a novel founder nicotinamide nucleotide transhydrogenase mutation that alters mitochondrial morphology and increases oxidative stress? | qiaojin/PubMedQA | 2 | [
-2.3946139812469482,
-1.3679637908935547,
2.8173422813415527
] |
['At present there is still controversy about the relationship between emotional stress and psoriasis lesions. Most of the published literature does not include the broad spectrum of emotional response.', 'The aim of this study was to evaluate the association between skin lesions and emotional state in a large sample of patients with psoriasis.', '823 psoriasis patients were recruited (mean age 45.9 years, 55.7% female) and answered two online questionnaires: lesion severity and current extension were evaluated using a self-administered psoriasis severity index (SAPASI); emotional state was assessed using the positive and negative affect schedule (PANAS). Second order factors were calculated and correlated with the SAPASI.', 'We found positive associations between the extent and severity of skin lesions and the negative and submissive emotions, a negative correlation with dominance emotions and no association with positive emotions.'] Are psoriasis lesions associated with specific types of emotions . Emotional profile in psoriasis? | qiaojin/PubMedQA | 2 | [
-2.5973846912384033,
-0.4846290647983551,
2.1907663345336914
] |
["Little is known about the developing breastfeeding behaviour of newborn infants. This study describes infants' prebreastfeeding behaviour during the second day of life and explores possible associations with infant characteristics.", 'We studied 13 mothers and healthy full-term infants after normal births. At 24-48\xa0hours of life, the newborns were placed in skin-to-skin contact with their mothers for breastfeeding and were video-filmed. The order, frequency and duration of predefined infant prefeeding behaviours and suckling were coded and analysed using computer-based video software.', 'Prefeeding behaviours occurred in the following order: rooting, hand to mouth movements, licking of the nipple and hand to breast to mouth movements. The infants started to suckle at a median of one to two minutes. Rooting was the most common behaviour, observed in 12 infants. The duration of rooting movements during the last minute before breastfeeding was inversely related to neonatal age (p\xa0≤\xa00.001) and positively related to neonatal weight loss (p\xa0=\xa00.02) after birth.'] Are weight loss and low age associated with intensity of rooting behaviours in newborn infants? | qiaojin/PubMedQA | 2 | [
-1.5076998472213745,
-0.300851434469223,
0.9132684469223022
] |
['Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH.', 'Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH.', 'High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated.'] Does hyperbaric oxygen therapy ameliorate acute brain injury after porcine intracerebral hemorrhage at high altitude? | qiaojin/PubMedQA | 2 | [
-2.488598346710205,
-1.187720537185669,
2.6730709075927734
] |
['Cranioplasty encompasses various cranial reconstruction techniques that are used following craniectomy due to stroke or trauma. Despite classical infectious signs, symptoms, and radiologic findings, however, the diagnosis of infection following cranioplasty can be elusive, with the potential to result in definitive treatment delay. We sought to determine if fever or leukocytosis at presentation were indicative of infection, as well as to identify any factors that may limit its applicability.', 'Following institutional review board approval, a retrospective cohort of 239 patients who underwent cranioplasty following craniectomy for stroke or trauma was established from 2001-2011 at a single center (Massachusetts General Hospital). Analysis was then focused on those who developed a surgical site infection, as defined by either frank intra-operative purulence or positive intra-operative cultures, and subsequently underwent operative management.', 'In 27 total cases of surgical site infection, only two had a fever and four had leukocytosis at presentation. This yielded a false-negative rate for fever of 92.6% and for leukocytosis of 85.2%. In regard to infectious etiology, 22 (81.5%) cases generated positive intra-operative cultures, with Propionibacterium acnes being the most common organism isolated. Median interval to infection was 99 days from initial cranioplasty to time of infectious presentation, and average follow-up was 3.4 years.'] Does the Absence of Fever or Leukocytosis Exclude Infection Following Cranioplasty? | qiaojin/PubMedQA | 2 | [
-2.395268678665161,
-1.0799360275268555,
2.65139102935791
] |
['One of the early hallmarks of osteoarthritis (OA) is a progressive degeneration of the articular cartilage. Early diagnosis of OA-associated cartilage alterations would be beneficial for disease prevention and control, and for the development of disease-modifying treatments. However, early diagnosis is still hampered by a lack of quantifiable readouts in preclinical models.', 'In this study, we have shown the potency of contrast-enhanced nanofocus x-ray computed tomography (CE-nanoCT) to be used for virtual 3-dimensional (3D) histopathology in established mouse models for OA, and we compared with standard histopathology.', 'We showed the equivalence of CE-nanoCT images to histopathology for the modified Mankin scoring of the cartilage structure and quality. Additionally, a limited set of 3D cartilage characteristics measured by CE-nanoCT image analysis in a user-independent and semiautomatic manner, that is, average and maximum of the noncalcified cartilage thickness distribution and loss in glycosaminoglycans, was shown to be predictive for the cartilage quality and structure as can be evaluated by histopathological scoring through the use of an empirical model.'] Does contrast-Enhanced Nanofocus X-Ray Computed Tomography allow Virtual Three-Dimensional Histopathology and Morphometric Analysis of Osteoarthritis in Small Animal Models? | qiaojin/PubMedQA | 2 | [
-2.4675614833831787,
-1.233459234237671,
2.804652214050293
] |
['To investigate the application value of empty puparia in species identification of common sarcosaphagous flies.', 'Fifty-five samples of adult flies and their empty puparia were collected. All the samples were identified as 2 families, 6 genera and 8 species by morphological characteristics. The samples were divided into 3 groups according to their time period between eclosion and our analyses: less than 2 years (n = 23), 2-5 years (n = 20), and more than 5 years (n = 12). The mtDNA of each sample was extracted by CTAB method. The purity and concentration of DNA were tested. PCR products were amplified using two sets of primers. Two sequences of CO I gene (sequence I: 498 bp, sequence II : 841 bp) from each sample were compared to the sequences in GenBank using BLAST for species identification.', 'The mtDNA was extracted successfully from all the samples. DNA concentration of adult chest muscle preserved less than or equal to 5 years and empty puparia preserved less than 2 years ranged from 1.0 to 3.0 µg/µl, and the value of A260/A280 ranged from 1.6 to 1.8. The purity and concentration was lower than 1.6 and 1.0 µg/µl, when the adult chest muscle and empty puparia preserved more than 5 years and 2 years, respectively. DNA concentration of the samples significantly decreased with the prolonged preservation time (P < 0.01). Two sequences of CO I gene was amplified in adult chest muscle and empty puparia which preserved less than 2 years. The success rates of amplification decreased with the prolonged preservation time, especially for the sequence II (P < 0.01). The morphological identification of 8 species did not match exactly with the results based on the COI gene, correct species identification occurred in 6 and 7 species out of 8 based on the two sequences, respectively, and their Max ident value exceeded 97%'] Does [ Species Identification of Puparium Samples of Common Sarcosaphagous fly Based on Molecular Marker Analysis ]? | qiaojin/PubMedQA | 2 | [
-0.2580205798149109,
-1.6214390993118286,
1.0189721584320068
] |
['Mechanisms that regulate regeneration of injured livers are complex. YAP, a stem cell associated factor, controls liver growth in healthy adult mice. Increasing nuclear localization of YAP triggers accumulation of reactive-appearing ductular cells (YAP+RDC) with liver progenitor capabilities. The significance of YAP activation, and mechanisms involved, are unknown in diseased livers. We evaluated the hypothesis that YAP is more activated in injured livers that are scarring than in those that are regenerating effectively.', 'Immunohistochemistry and qRT-PCR analysis were used to localize and quantify changes in YAP and RDC in 52 patients with non-alcoholic fatty liver disease (NAFLD) and two mouse models of diet-induced non-alcoholic steatohepatitis (NASH). Results were correlated with liver disease severity, metabolic risk factors, and factors proven to control NAFLD progression.', 'YAP increased in NAFLD where it mainly localized in nuclei of RDC that expressed progenitor markers. Accumulation of YAP+RDC paralleled the severity of hepatocyte injury and accumulation of Sonic hedgehog, but not steatosis or metabolic risk factors. YAP+RDC expressed osteopontin, a Shh-regulated fibrogenic factor. Myofibroblast accumulation, fibrosis, and numbers of YAP+RDC strongly correlated. In murine NASH models, atrophic fibrotic livers contained significantly more YAP+RDC than livers with less severe NASH.'] Does accumulation of duct cells with activated YAP parallel fibrosis progression in non-alcoholic fatty liver disease? | qiaojin/PubMedQA | 2 | [
-2.29321551322937,
-1.2952638864517212,
2.6308486461639404
] |
['Somatic mutations occur at early stages of adenoma and accumulate throughout colorectal cancer progression. The aim of this study was to characterize the mutational landscape of stage II tumors and to search for novel recurrent mutations likely implicated in colorectal cancer tumorigenesis.', 'The exomic DNA of 42 stage II, microsatellite-stable colon tumors and their paired mucosae were sequenced. Other molecular data available in the discovery dataset [gene expression, methylation, and copy number variations (CNV)] were used to further characterize these tumors. Additional datasets comprising 553 colorectal cancer samples were used to validate the discovered mutations.', 'As a result, 4,886 somatic single-nucleotide variants (SNV) were found. Almost all SNVs were private changes, with few mutations shared by more than one tumor, thus revealing tumor-specific mutational landscapes. Nevertheless, these diverse mutations converged into common cellular pathways, such as cell cycle or apoptosis. Among this mutational heterogeneity, variants resulting in early stop codons in the AMER1 (also known as FAM123B or WTX) gene emerged as recurrent mutations in colorectal cancer. Losses of AMER1 by other mechanisms apart from mutations such as methylation and copy number aberrations were also found. Tumors lacking this tumor suppressor gene exhibited a mesenchymal phenotype characterized by inhibition of the canonical Wnt pathway.'] Does exome Sequencing reveal AMER1 as a Frequently Mutated Gene in Colorectal Cancer? | qiaojin/PubMedQA | 2 | [
-2.4133975505828857,
-1.0085304975509644,
2.5416862964630127
] |
['The response rate of first-line fluoropyrimidine-based regimens for metastatic colorectal cancer (mCRC) is generally less than 50\xa0%. The down-regulation of miR-197 in colorectal cancer cells after exposure to 5-fluorouracil might be related to the mechanism of resistance to fluoropyrimidine-based chemotherapy. So we investigated the regulatory mechanism of miR-197 on 5-FU sensitivity.', 'Dual luciferase reporter gene construct and dual luciferase reporter assay were used to identify the target of miR-197. TYMS expression was evaluated by immunohistochemistry staining. 5-Fu resistance of colorectal cancer cell lines was detected by MTS assay. The expression of miR-197 was detected by real time PCR.', 'A luciferase assay and western blot analysis confirmed that miR-197 directly binds to and negatively regulates TYMS expression. Overexpressing miR-197 could increase the sensitivity of colorectal cancer cells to 5-fluorouracil (5-FU). The expression of miR-197 negatively correlated with TYMS expression in cancerous tissues from patients with stage IV colorectal cancer.'] Does microRNA-197 influence 5-fluorouracil resistance via thymidylate synthase in colorectal cancer? | qiaojin/PubMedQA | 2 | [
-2.3117499351501465,
-1.220238447189331,
2.5298573970794678
] |
["More than 1 in 10 infants are born prematurely worldwide, making preterm birth the leading cause of neonatal mortality and morbidity. Chronic maternal stress is increasingly recognized as one of the contributing risk factors for preterm birth, yet its specific role remains largely unknown. Examining the exposure to stressors over a mother's life course might provide more perspective on the role of maternal stress in preterm birth. Our aim was therefore to retrospectively explore the associations between chronic, lifelong stressors and protective factors and spontaneous preterm birth.", 'This study was part of a large case-control study based in Edmonton, Canada, examining gene-environment interactions and preterm birth. Cases were mothers with a spontaneous singleton preterm birth (<37 weeks) without preterm premature rupture of membranes. Controls were mothers with an uncomplicated singleton term birth without a history of preterm birth. Sociodemographic and medical data were collected. A postpartum telephone questionnaire was administered to assess stressors across the lifespan. Both individual and contextual variables that could influence stress response systems were examined. Overall, 622 women were included, of which 223 subjects - 75 cases and 148 controls - completed the stress questionnaire. Univariate and multivariate logistic regression analyses were performed.', 'Multivariate analysis showed that exposure to two or more adverse childhood experiences (ACEs) was associated with a two-fold risk of preterm birth, regardless of maternal age, smoking status, educational status, and history of miscarriage (adjusted OR, 2.09; 95 % CI, 1.10-3.98; P = 0.024). The adjusted odds ratio for the ACE score was 1.18 (95 % CI, 0.99-1.40), suggesting that for every increase in childhood adverse event endorsed, the risk of preterm birth increased by 18 %. Lifetime physical and emotional abuse was also associated with spontaneous preterm birth in our study population (adjusted OR, 1.30; 95 % CI, 1.02-1.65; P = 0.033).'] Are adverse childhood experiences associated with spontaneous preterm birth : a case-control study? | qiaojin/PubMedQA | 2 | [
-1.8282924890518188,
-1.0103578567504883,
1.8662285804748535
] |
['Differentiation of metazoan cells requires execution of different gene expression programs but recent single-cell transcriptome profiling has revealed considerable variation within cells of seeming identical phenotype. This brings into question the relationship between transcriptome states and cell phenotypes. Additionally, single-cell transcriptomics presents unique analysis challenges that need to be addressed to answer this question.', 'We present high quality deep read-depth single-cell RNA sequencing for 91 cells from five mouse tissues and 18 cells from two rat tissues, along with 30 control samples of bulk RNA diluted to single-cell levels. We find that transcriptomes differ globally across tissues with regard to the number of genes expressed, the average expression patterns, and within-cell-type variation patterns. We develop methods to filter genes for reliable quantification and to calibrate biological variation. All cell types include genes with high variability in expression, in a tissue-specific manner. We also find evidence that single-cell variability of neuronal genes in mice is correlated with that in rats consistent with the hypothesis that levels of variation may be conserved.'] Does deep sequencing reveal cell-type-specific patterns of single-cell transcriptome variation? | qiaojin/PubMedQA | 2 | [
-2.5378966331481934,
0.22733424603939056,
1.440108299255371
] |
["The hand hygiene technique that the World Health Organization recommends for cleansing hands with soap and water or alcohol-based handrub consists of 7 poses. We used an automated training system to improve clinicians' hand hygiene technique and test whether this affected hospitalwide hand hygiene compliance.", 'Seven hundred eighty-nine medical and nursing staff volunteered to participate in a self-directed training session using the automated training system. The proportion of successful first attempts was reported for each of the 7 poses. Hand hygiene compliance was collected according to the national requirement and rates for 2011-2014 were used to determine the effect of the training system on compliance.', 'The highest pass rate was for pose 1 (palm to palm) at 77% (606 out of 789), whereas pose 6 (clean thumbs) had the lowest pass rate at 27% (216 out of 789). One hundred volunteers provided feedback to 8 items related to satisfaction with the automated training system and most (86%) expressed a high degree of satisfaction and all reported that this method was time-efficient. There was no significant change in compliance rates after the introduction of the automated training system. Observed compliance during the posttraining period declined but increased to 82% in response to other strategies.'] Does an automated hand hygiene training system improve hand hygiene technique but not compliance? | qiaojin/PubMedQA | 1 | [
-0.564099133014679,
0.6769363284111023,
-0.8482854962348938
] |
['This study investigates the role of Toll-like receptor 2 (TLR2) in the regulation of migratory and invasive mechanisms in rheumatoid arthritis (RA).', 'Invasion, migration, matrix metalloproteinase (MMP)-1, -3 and tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) expression, β-integrin binding, cytoskeletal rearrangement and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation in response to a TLR2-ligand, Pam3CSK4 (1 μg/ml), in ex vivo RA synovial tissue explants, primary RA synovial fibroblasts (RASFC) and microvascular endothelial cells (HMVEC) were assessed by Transwell Matrigel™ invasion chambers, enzyme-linked immunosorbent assay (ELISA), multiplex adhesion binding assay, reverse transcription polymerase chain reaction (RT-PCR), F-actin immunofluorescent staining, matrigel synovial outgrowths, Rac1 pull-down assays/Western blot and zymography. β1-integrin expression in RA/control synovial tissue was assessed by immunohistology. The effect of Pam3CSK4 on cell migration, invasion, MMP-3 and Rac1 activation was examined in the presence or absence of anti-β1-integrin (10 μg/ml) or anti-IgG control (10 μg/ml). The effect of an anti-TLR-2 mAb (OPN301)(1 μg/ml) or immunoglobulin G (IgG) control (1 μg/ml) on RASFC migration and RA synovial tissue MMP activity was assessed by wound assays, ELISA and zymography.', 'Pam3CSK4 significantly induced cell migration, invasion, MMP-1, MMP-3, MMP-2 and MMP-9 expression and induced the MMP-1/TIMP-3 and MMP-3/TIMP-3 ratio in RASFC and explants (p <0.05). β1-integrin expression was significantly higher in RA synovial tissue compared to controls (p <0.05). Pam3CSK4 specifically induced β1-integrin binding in RASFC (p <0.05), with no effect observed for β2-4, β6, αvβ5 or α5β1. Pam3CSK4 increased β1-integrin mRNA expression, Rac1 activation, RASFC outgrowths and altered cytoskeletal dynamic through induction of filopodia formation. Pam3CSK4-regulated cell migration and invasion processes, but not MMP-3, were inhibited in the presence of anti-β1-integrin (p <0.05), with no effect observed for anti-IgG control. Furthermore, anti-β1-integrin inhibited Pam3CSK4-induced Rac1 activation. Finally, blockade of TLR2 with OPN301 significantly decreased spontaneous release of MMP-3, MMP-2 and MMP-9 and increased TIMP-3 secretion from RA synovial explant cultures (p <0.05). Incubation of RASFC with OPN301 RA ex vivo conditioned media inhibited migration and invasion compared to IgG control.'] Does toll-like receptor 2 ( TLR2 ) induce migration and invasive mechanisms in rheumatoid arthritis? | qiaojin/PubMedQA | 2 | [
-2.2183008193969727,
-1.4684593677520752,
2.7405223846435547
] |
['Mesenchymal stem cells (MSCs) can differentiate into chondroblasts, adipocytes, or osteoblasts under appropriate stimulation. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), stimulates growth hormone (GH) secretion, and has both orexigenic and adipogenic effects. This study sought to understand the potential involvement of members of MAPK serine/threonine kinases in the ghrelin-induced growth of rabbit MSCs ( rBMSC).', 'We applied various concentrations of ghrelin to cultured rBMSC and observed the growth rate of the cells by MTT, changes in the phosphorylation state of ERK1/2, JNK and p38, and the expression levels of ALP, Runx2, and Osterix by wetern blot.', 'We found that the growth and osteogenic differentiation of ghrelin-treated rBMSC are promoted primarily by phosphorylated ERK1/2, and that this phosphorylation, as well p38 phosphorylation, is mediated by GHSR.'] Does ghrelin accelerate the growth and osteogenic differentiation of rabbit mesenchymal stem cells through the ERK1/2 pathway? | qiaojin/PubMedQA | 2 | [
-2.50516676902771,
-1.1279187202453613,
2.6719870567321777
] |
['Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease.', 'To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos.', 'Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 μg/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1β, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1β, anti-IL-6, anti- IL-1β+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls.', 'Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1β, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1β andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers.'] Do inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells? | qiaojin/PubMedQA | 2 | [
-2.5775957107543945,
-1.1471874713897705,
2.7708301544189453
] |
['There is considerable controversy about the significance and appropriate treatment of type II endoleaks (T2Ls) after endovascular aneurysm repair (EVAR). We report our long-term experience with T2L management in a large multicenter registry.', 'Between 2000 and 2010, 1736 patients underwent EVAR, and we recorded the incidence of T2L. Primary outcomes were mortality and aneurysm-related mortality (ARM). Secondary outcomes were change in aneurysm sac size, major adverse events, and reintervention.', 'During the follow-up (median of 32.2 months; interquartile range, 14.2-52.8 months), T2L was identified in 474 patients (27.3%). There were no late abdominal aortic aneurysm ruptures attributable to a T2L. Overall mortality (P = .47) and ARM (P = .26) did not differ between patients with and without T2L. Sac growth (median, 5 mm; interquartile range, 2-10 mm) was seen in 213 (44.9%) of the patients with T2L. Of these patients with a T2L and sac growth, 36 (16.9%) had an additional type of endoleak. Of all patients with T2L, 111 (23.4%) received reinterventions, including 39 patients who underwent multiple procedures; 74% of the reinterventions were performed in patients with sac growth. Reinterventions included lumbar embolization in 66 patients (59.5%), placement of additional stents in 48 (43.2%), open surgical revision in 14 (12.6%), and direct sac injection in 22 (19.8%). The reintervention was successful in 35 patients (31.5%). After patients with other types of endoleak were excluded, no difference in overall all-cause mortality (P = .57) or ARM (P = .09) was observed between patients with T2L-associated sac growth who underwent reintervention and those in whom T2L was left untreated.'] Does type II endoleak with or without intervention after endovascular aortic aneurysm repair change aneurysm-related outcomes despite sac growth? | qiaojin/PubMedQA | 2 | [
-1.7746798992156982,
-1.6220698356628418,
2.264129638671875
] |
['It has been reported that the neutrophil-to-lymphocyte ratio (NLR) can be measured relatively easily and can serve as a valuable index for much clinical pathology. The aim of this study was to investigate the association between NLR and hepatic histological findings in patients with nonalcoholic fatty liver disease (NAFLD).', 'A total of 226 consecutive patients with biopsy-proven NAFLD [nonalcoholic steatohepatitis (NASH, n=105), borderline-NASH (n=74), and simple steatosis (n=47)] were enrolled. NASH and fibrosis were diagnosed histologically using the NAFLD Clinical Research Network criteria.', 'Significant differences were found in aspartate aminotransferase (P<0.001), alanine aminotransferase (P<0.001) levels, and white blood cell (P=0.007) and neutrophil counts (P=0.042) between the three groups of patients. In addition, significantly higher BMI (P=0.024), waist circumference (P=0.011), aspartate aminotransferase (P=0.003), alanine aminotransferase (P=0.005), insulin (P=0.008), and homeostasis model assessment-insulin resistance (P=0.009) levels were found in patients with fibrosis (n=133) in comparison with those without fibrosis (n=93). There was no correlation between NLR and glucose, homeostasis model assessment-insulin resistance, lipid parameters, and the NAFLD activity score. Analysis of the NLR in relation to histological findings also showed no association between these parameters.'] Is neutrophil-to-lymphocyte ratio a predictor of liver histology in patients with nonalcoholic fatty liver disease? | qiaojin/PubMedQA | 2 | [
-2.1079766750335693,
-1.4687750339508057,
2.606107234954834
] |
['Metastasectomy can provide durable disease control for selected patients with metastatic melanoma. Vemurafenib is a BRAF kinase inhibitor which has demonstrated significant improvement in disease-specific survival in patients with metastatic melanoma with a BRAF gene mutation. This study examined the efficacy and safety of metastasectomy during treatment with vemurafenib.', 'A retrospective review was performed of all patients receiving vemurafenib at Peter MacCallum Cancer Centre. Patient records were reviewed to identify patients undergoing surgery within 30 days of vemurafenib therapy. Descriptive statistics and survival analysis were performed.', 'Nineteen patients underwent 21 metastasectomies including craniotomy (57%), spinal decompression (14%), small bowel resection (14%), lung resection (9.5%) and neck dissection (4.5%). Indications for surgery were: an isolated residual focus of disease (n\u2009=\u20092); isolated progressive disease in the setting of stability elsewhere (n\u2009=\u20099); and symptomatic disease (n\u2009=\u20098). Grade 2 or higher surgical complications occurred in 19% of cases and there was one peri-operative death. Median post-operative survival was seven months. There was a trend toward improved post-operative survival for patients with longer duration of vemurafenib therapy (P\u2009=\u20090.04) and for those undergoing elective surgery (P\u2009=\u20090.07).'] Is post-operative survival following metastasectomy for patients receiving BRAF inhibitor therapy associated with duration of pre-operative treatment and elective indication? | qiaojin/PubMedQA | 2 | [
-2.1233444213867188,
-1.4845778942108154,
2.6514666080474854
] |
['To investigate the mechanism of immune response in mouse macrophage induced by Pneumococcal heat shock protein 40 (HSP40).', 'After recombinant HSP40 (rHSP40) underwent expression detection and purification, lipopolysaccharide (LPS) was removed from it. Then rHSP40 was used to stimulate bone marrow derived macrophages (BMDMs) derived from C57BL/6 wild-type mice. The mRNA levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1β, IL-23p19, IL-12p40, IL-12p35 and IL-10 in BMDMs were determined by reverse transcription PCR; the expressions of TNF-α, IL-6 and IL-12p40 were measured by ELISA. After stimulated by rHSP40, the levels of TNF-α and IL-6 expressed by wide-type, TLR2-/- and TLR4-/- BMDMs were detected by ELISA. The effects of the pretreatment of mitogen-activated protein kinases (MAPK) inhibitors on the secretion of TNF-α and IL-6 induced by rHSP40 were also evaluated by ELISA in BMDMs. The phosphorylation levels of p38MAPK and c-Jun N-terminal kinase (JNK) were determined by Western blotting.', 'The rHSP40 protein reached a purity of more than 90%. It significantly enhanced the phosphorylation levels of p38MAPK and JNK as well as the expressions of TNF-α and IL-6. The p38MAPK and JNK inhibitors significantly suppressed the expressions of TNF-α and IL-6. The expressions of TNF-α and IL-6 in TLR4-/- BMDMs significantly decreased compared with wide-type BMDMs.'] Does [ Pneumococcal HSP40 induce the immune response in mouse macrophages via p38MAPK and JNK signaling pathways ]? | qiaojin/PubMedQA | 2 | [
-2.2078497409820557,
-1.3475980758666992,
2.6089978218078613
] |
['Isoflurane may be protective in preclinical models of lung injury, but its use in patients with lung injury remains controversial and the mechanism of its protective effects remains unclear. The authors hypothesized that this protection is mediated at the level of alveolar tight junctions and investigated the possibility in a two-hit model of lung injury that mirrors human acute respiratory distress syndrome.', 'Wild-type mice were treated with isoflurane 1\u2009h after exposure to nebulized endotoxin (n = 8) or saline control (n = 9) and then allowed to recover for 24\u2009h before mechanical ventilation (MV; tidal volume, 15\u2009ml/kg, 2\u2009h) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane 1\u2009h after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo.', 'Mice treated with isoflurane following exposure to inhaled endotoxin and before MV exhibited significantly less physiologic lung dysfunction. These effects appeared to be mediated by decreased vascular leak, but not altered inflammatory indices. Mouse lung epithelial cells treated with lipopolysaccharide and cyclic stretch and lungs harvested from mice after treatment with lipopolysaccharide and MV had decreased levels of a key tight junction protein (i.e., zona occludens 1) that was rescued by isoflurane treatment.'] Does isoflurane ameliorate Acute Lung Injury by Preserving Epithelial Tight Junction Integrity? | qiaojin/PubMedQA | 2 | [
-2.5130817890167236,
-1.2827858924865723,
2.831911087036133
] |
['Microsatellite loci were developed as polymorphic markers for the New Zealand endemic Myosotis pygmaea species group (Boraginaceae) for use in species delimitation and population and conservation genetic studies.', 'Illumina MiSeq sequencing was performed on genomic DNA from seedlings of M. drucei. From trimmed paired-end sequences >400 bp, 484 microsatellite loci were identified. Twelve of 48 microsatellite loci tested were found to be polymorphic and consistently scorable when screened on 53 individuals from four populations representing the geographic range of M. drucei. They also amplify in all other species in the M. pygmaea species group, i.e., M. antarctica, M. brevis, M. glauca, and M. pygmaea, as well as 18 other Myosotis species.'] Do microsatellite markers for the New Zealand endemic Myosotis pygmaea species group ( Boraginaceae ) amplify across species? | qiaojin/PubMedQA | 2 | [
-1.6029950380325317,
-0.3317182958126068,
1.1378848552703857
] |
['To evaluate the correlation of epicardial adipose tissue volume (EATV) with the coronary artery lesion and its severity.', 'Inpatients with suspicious stable angina of coronary heart lesion were recruited. For patients with coronary artery lesions in CTA, further coronary angiography (CAG) was performed to evaluate the coronary artery lesion. Gensini scoring system was employed to assess the severity of coronary artery lesions.', 'Patients were classified as coronary heart disease (CHD) group (n = 160). Results showed the mean EATV was 192.57 ± 30.32 cm(3) in CHD group, which was significantly larger than that in control group (138.56 ± 23.18 cm(3); P < 0.01). The coronary artery stenosis was classified as mild, moderate and severe stenosis according to the extent of coronary artery lesions, and results showed marked difference in the EATV among patients with different severities of coronary artery stenosis (P < 0.005). The Gensini score was positively related to EATV (r = 0.285, P = 0.000). The EATV increased with the increase in the number of affected coronary arteries. Multivariate Logistic regression analysis showed EATV was an independent risk factor of CHD after adjusting other confounding factors (OR = 1.023, P = 0.013).'] Is epicardial fat volume correlated with coronary lesion and its severity? | qiaojin/PubMedQA | 2 | [
-1.7675243616104126,
-1.508453130722046,
2.3446877002716064
] |
['Extrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon malignancies in the digestive system which is characterized by a poor prognosis. Aberrations of miRNAs have been shown involved in the progression of this disease. In this study, we evaluated the expression and effects of miR-34a on EHCC.', 'miR-34a expression levels were detected in EHCC tissues, adjacent non-tumor tissues, normal bile duct (NBD) specimens of patients and cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics of EHCC patients were further analyzed. Computational search, functional luciferase assay and western blot were further used to demonstrate the downstream target of miR-34a in CC cells. Immunohistochemistry was carried on to identify the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion and migration assays were further applied to confirm the anti-carcinogenic effects of miR-34a through the downstream target.', 'miR-34a expression was significantly decreased in human EHCC tissues and CC cell lines when compared with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was found correlated with the migration and invasion in EHCC patients. Smad4 was over-expressed in most of the EHCC patients and was further demonstrated as one of the downstream targets of miR-34a, which was involved in the progression of EHCC. Moreover, activation of miR-34a suppressed invasion and migration through TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in vitro.'] Does microRNA-34a inhibit epithelial mesenchymal transition in human cholangiocarcinoma by targeting Smad4 through transforming growth factor-beta/Smad pathway? | qiaojin/PubMedQA | 2 | [
-2.3171300888061523,
-1.3552989959716797,
2.6905508041381836
] |
['Improvement of transduction and augmentation of cytotoxicity are crucial for adenoviruses (Ad)-mediated gene therapy for cancer. Down-regulated expression of type 5 Ad (Ad5) receptors on human tumors hampered Ad-mediated transduction. Furthermore, a role of the p53 pathways in cytotoxicity mediated by replication-competent Ad remained uncharacterized.', 'We constructed replication-competent Ad5 of which the E1 region genes were activated by a transcriptional regulatory region of the midkine or the survivin gene, which is expressed preferentially in human tumors. We also prepared replication-competent Ad5 which were regulated by the same region but had a fiber-knob region derived from serotype 35 (AdF35). We examined the cytotoxicity of these Ad and a possible combinatory use of the replication-competent AdF35 and Ad5 expressing the wild-type p53 gene (Ad5/p53) in esophageal carcinoma cells. Expression levels of molecules involved in cell death, anti-tumor effects in vivo and production of viral progenies were also investigated.', 'Replication-competent AdF35 in general achieved greater cytotoxic effects to esophageal carcinoma cells than the corresponding replication-competent Ad5. Infection with the AdF35 induced cleavages of caspases and increased sub-G1 fractions, but did not activate the autophagy pathway. Transduction with Ad5/p53 in combination with the replication-competent AdF35 further enhanced the cytotoxicity in a synergistic manner. We also demonstrated the combinatory effects in an animal model. Transduction with Ad5/p53 however suppressed production of replication-competent AdF35 progenies, but the combination augmented Ad5/p53-mediated p53 expression levels and the downstream pathways.'] Are cytotoxic effects of replication-competent adenoviruses on human esophageal carcinoma enhanced by forced p53 expression? | qiaojin/PubMedQA | 2 | [
-2.4380719661712646,
-1.1977185010910034,
2.717190742492676
] |
['Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV.', 'We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging-derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest.', 'We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed.'] Is lower white matter microstructure in the superior longitudinal fasciculus associated with increased response time variability in adults with attention-deficit/ hyperactivity disorder? | qiaojin/PubMedQA | 2 | [
-2.417574167251587,
-1.144570231437683,
2.6333892345428467
] |
['Transforming growth factor/Smad family member 3 (TGF)-β/Smad3 signalling is essential for maintaining articular cartilage. A relationship between the genetic variants of TGF-β itself, TGF-β signalling and binding molecules, and osteoarthritis (OA) has been reported. Although variants of candidate genes have become prime targets for genetic analysis, their detailed interplay has not been documented. Our goal was to establish whether single nucleotide polymorphisms (SNPs) of TGF-β1, TGF-βRI, Smad3 and tissue inhibitor of metalloproteinases 3 (TIMP3), and their interactions, are associated with knee OA.', 'We performed a case-control association study and genotyped 518 knee patients with OA and 468 healthy controls. All participants were genotyped for TGF-β1 (rs1800469C/T), TGF-βRI (rs1590A/G), Smad3 (rs12901499A/G and rs6494629T/C), and TIMP3 (rs715572G/A and rs1962223G/C) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis. Multifactor dimensionality reduction (MDR) was used to identify gene-gene interactions.', 'Significant associations were observed for TIMP3 rs715572G/A polymorphisms in knee patients with OA and healthy individuals. The GA heterozygote in TIMP3 (rs715572G/A) was significantly associated with OA (p=0.007). Patient stratification using the Kellgren-Lawrence grading scale showed significant differences in TIMP3 rs715572G/A genotypes between grade 4 knee OA and controls. By MDR analysis, a two-locus model (Smad3 rs6494629T/C and TIMP3 rs715572G/A) of gene-gene interaction was the best for predicting knee OA risk, and its maximum testing accuracy was 57.55% and maximum cross-validation consistency was 10/10.'] Do gene-gene interactions between TGF-β/Smad3 signalling pathway polymorphisms affect susceptibility to knee osteoarthritis? | qiaojin/PubMedQA | 2 | [
-2.2249841690063477,
-1.4286856651306152,
2.6646008491516113
] |
['Clone libraries provide researchers with a powerful resource to study nucleic acid from diverse sources. Metagenomic clone libraries in particular have aided in studies of microbial biodiversity and function, and allowed the mining of novel enzymes. Libraries are often constructed by cloning large inserts into cosmid or fosmid vectors. Recently, there have been reports of GC bias in fosmid metagenomic libraries, and it was speculated to be a result of fragmentation and loss of AT-rich sequences during cloning. However, evidence in the literature suggests that transcriptional activity or gene product toxicity may play a role.', 'To explore possible mechanisms responsible for sequence bias in clone libraries, we constructed a cosmid library from a human microbiome sample and sequenced DNA from different steps during library construction: crude extract DNA, size-selected DNA, and cosmid library DNA. We confirmed a GC bias in the final cosmid library, and we provide evidence that the bias is not due to fragmentation and loss of AT-rich sequences but is likely occurring after DNA is introduced into Escherichia coli. To investigate the influence of strong constitutive transcription, we searched the sequence data for promoters and found that rpoD/σ(70) promoter sequences were underrepresented in the cosmid library. Furthermore, when we examined the genomes of taxa that were differentially abundant in the cosmid library relative to the original sample, we found the bias to be more correlated with the number of rpoD/σ(70) consensus sequences in the genome than with simple GC content.'] Does strong spurious transcription likely contribute to DNA insert bias in typical metagenomic clone libraries? | qiaojin/PubMedQA | 2 | [
-2.136528730392456,
-0.5568221211433411,
1.728844404220581
] |
['Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors.', 'Sixty-two stage II-III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers.', 'We found, using Cox regression models, that the presence of TILs was associated with improved OS (p = 0.034) and RFS (p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma (p = 0.632, 0.416). CD2 expression also was correlated with improved OS (p = 0.021) and RFS (p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma (p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count.'] Are immune biomarkers more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas? | qiaojin/PubMedQA | 2 | [
-1.9763741493225098,
-1.5309066772460938,
2.5340816974639893
] |
['The human activation peptide of factor XIII (AP-FXIII) comprises the first 37 amino acids of the N-terminus and holds the FXIII in an inactive state. FXIII is activated either proteolytically by cleavage of AP-FXIII by thrombin, or non-proteolytically by high calcium concentrations.', 'To investigate the role of AP-FXIII in the expression and stability of FXIII.', 'We cloned 13 FXIII variants with progressive\xa0truncations of AP-FXIII from the N-terminus (delN-FXIII-A), expressed them in mammalian cells, and measured their thermostability, activation, and transglutaminase activity. We also used in silico calculations to analyze the stability of hypothetical delN-FXIII dimers and to identify crucial motifs within AP-FXIII.', 'Variants with deletions longer than the first 10 amino acids and an R11Q point mutant were not expressed as proteins. In silico calculations indicated that the sequence (8) FGGR(12) R plays a substantial role in intersubunit interactions in FXIII-A2 homodimers. In agreement with this prediction, the temperature stability of delN-FXIII variants decreased with increasing length of deletion. These results may suggest a role of the N-terminus of AP-FXIII in dimer stability. Substantial sequence homology was found among activation peptides of vertebrate and even invertebrate (crustacean) FXIII-A orthologs, which further supports our conclusion.'] Is the activation peptide of coagulation factor XIII vital for its expression and stability? | qiaojin/PubMedQA | 2 | [
-2.360556125640869,
-1.0983572006225586,
2.5113048553466797
] |
['The human malaria parasite Plasmodium falciparum has a complex and multi-stage life cycle that requires extensive and precise gene regulation to allow invasion and hijacking of host cells, transmission, and immune escape. To date, the regulatory elements orchestrating these critical parasite processes remain largely unknown. Yet it is becoming increasingly clear that long non-coding RNAs (lncRNAs) could represent a missing regulatory layer across a broad range of organisms.', 'To investigate the regulatory capacity of lncRNA in P. falciparum, we harvested fifteen samples from two time-courses. Our sample set profiled 56 h of P. falciparum blood stage development. We then developed and validated strand-specific, non-polyA-selected RNA sequencing methods, and pursued the first assembly of P. falciparum strand-specific transcript structures from RNA sequencing data. This approach enabled the annotation of over one thousand lncRNA transcript models and their comprehensive global analysis: coding prediction, periodicity, stage-specificity, correlation, GC content, length, location relative to annotated transcripts, and splicing. We validated the complete splicing structure of three lncRNAs with compelling properties. Non-polyA-selected deep sequencing also enabled the prediction of hundreds of intriguing P. falciparum circular RNAs, six of which we validated experimentally.'] Does strand-specific RNA sequencing in Plasmodium falciparum malaria identify developmentally regulated long non-coding RNA and circular RNA? | qiaojin/PubMedQA | 2 | [
-2.2884438037872314,
-0.7747679352760315,
2.167358160018921
] |
['Use of analgesics has been associated with lower risk of ovarian cancer, but, to date, very few studies have explored the association between analgesics and ovarian cancer survival.', 'We examined the relationship between self-reported prediagnostic use of aspirin, ibuprofen, and acetaminophen and overall survival (OS), progression-free survival (PFS), ascites at the time of primary treatment, and persistence of disease after primary treatment among 699 women diagnosed with epithelial ovarian carcinoma. The associations between use of these medications and OS and PFS were estimated using Cox proportional hazards models. We utilized unconditional logistic regression models to estimate associations between medication use and presence of ascites and persistence of disease.', 'Prediagnostic intake of aspirin, both low-dose and regular-dose, ibuprofen, and acetaminophen was not associated with any of the outcomes of interest.'] Is use of common analgesics associated with ovarian cancer survival? | qiaojin/PubMedQA | 2 | [
-2.8577935695648193,
-0.574677586555481,
2.4896159172058105
] |
['Heart rate (HR) parameters are known indicators of cardiovascular complications after cardiac surgery, but there is little evidence of their role in predicting outcome after major vascular surgery. The purpose of this study was to determine whether arrival HR (AHR) and highest intraoperative HR are associated with mortality or major adverse cardiac events (MACEs) after elective vascular surgery in the Vascular Quality Initiative (VQI).', 'Patients undergoing elective lower extremity bypass (LEB), aortofemoral bypass (AFB), and open abdominal aortic aneurysm (AAA) repair in the VQI were analyzed. MACE was defined as any postoperative myocardial infarction, dysrhythmia, or congestive heart failure. Controlled HR was defined as AHR <75 beats/min on operating room arrival. Delta HR (DHR) was defined as highest intraoperative HR - AHR. Procedure-specific MACE models were derived for risk stratification, and generalized estimating equations were used to account for clustering of center effects. HR, beta-blocker exposure, cardiac risk, and their interactions were explored to determine association with MACE or 30-day mortality. A Bonferroni correction with P < .004 was used to declare significance.', 'There were 13,291 patients reviewed (LEB, n = 8155 [62%]; AFB, n = 2629 [18%]; open AAA, n = 2629 [20%]). Rates of any preoperative beta-blocker exposure were as follows: LEB, 66.5% (n = 5412); AFB, 57% (n = 1342); and open AAA, 74.2% (n = 1949). AHR and DHR outcome association was variable across patients and procedures. AHR <75 beats/min was associated with increased postoperative myocardial infarction risk for LEB patients across all risk strata (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.03-1.9; P = .03), whereas AHR <75 beats/min was associated with decreased dysrhythmia risk (OR, 0.42; 95% CI, 0.28-0.63; P = .0001) and 30-day death (OR, 0.50; 95% CI, 0.33-0.77; P = .001) in patients at moderate and high cardiac risk. These HR associations disappeared in controlling for beta-blocker status. For AFB and open AAA repair patients, there was no significant association between AHR and MACE or 30-day mortality, irrespective or cardiac risk or beta-blocker status. DHR and extremes of highest intraoperative HR (>90 or 100 beats/min) were analyzed among all three operations, and no consistent associations with MACE or 30-day mortality were detected.'] Are heart rate variables in the Vascular Quality Initiative reliable predictors of adverse cardiac outcomes or mortality after major elective vascular surgery? | qiaojin/PubMedQA | 2 | [
-1.576772928237915,
-1.6776409149169922,
2.2317419052124023
] |
['Genome-wide association study (GWAS) is a powerful tool to identify novel pharmacogenetic single nucleotide polymorphisms (SNPs). Leukotriene receptor antagonists (LTRAs) are a major class of asthma medications, and genetic factors contribute to variable responses to these drugs. We used GWAS to identify novel SNPs associated with the response to the LTRA, montelukast, in asthmatics.', 'Using genome-wide genotype and phenotypic data available from American Lung Association - Asthma Clinical Research Center (ALA-ACRC) cohorts, we evaluated 8-week change in FEV1 related to montelukast administration in a discovery population of 133 asthmatics. The top 200 SNPs from the discovery GWAS were then tested in 184 additional samples from two independent cohorts.', 'Twenty-eight SNP associations from the discovery GWAS were replicated. Of these, rs6475448 achieved genome-wide significance (combined P = 1.97 x 10-09), and subjects from all four studies who were homozygous for rs6475448 showed increased ΔFEV1 from baseline in response to montelukast.'] Does genome-Wide Association Study identify Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma? | qiaojin/PubMedQA | 2 | [
-2.225407838821411,
-1.1516587734222412,
2.405923366546631
] |
['We hypothesized that lung injury and rib cage fracture quantification would be associated with adverse outcomes.', 'Consecutive admissions to a trauma center with Injury Severity Score ≥ 9, age 18-75, and blunt trauma. CT scans were reviewed to score rib and sternal fractures and lung infiltrates. Sternum and each anterior, lateral, and posterior rib fracture was scored 1 = non-displaced and 2 = displaced. Rib cage fracture score (RCFS) = total rib fracture score + sternal fracture score + thoracic spine Abbreviated Injury Score (AIS). Four lung regions (right upper/middle, right lower, left upper, and left lower lobes) were each scored for % of infiltrate: 0% = 0; ≤ 20% = 1, ≤ 50% = 2, > 50% = 3; total of 4 scores = lung infiltrate score (LIS).', 'Of 599 patients, 193 (32%) had 854 rib fractures. Rib fracture patients had more abdominal injuries (p < 0.001), hemo/pneumothorax (p < 0.001), lung infiltrates (p < 0.001), thoracic spine injuries (p = 0.001), sternal fractures (p = 0.0028) and death or need for mechanical ventilation ≥ 3 days (Death/Vdays ≥ 3) (p < 0.001). Death/Vdays ≥ 3 was independently associated with RCFS (p < 0.001), LIS (p < 0.001), head AIS (p < 0.001) and abdominal AIS (p < 0.001). Of the 193 rib fracture patients, Glasgow Coma Score 3-12 or head AIS ≥ 2 occurred in 43%. A lung infiltrate or hemo/pneumothorax occurred in 55%. Thoracic spine injury occurred in 23%. RCFS was 6.3 ± 4.4 and Death/Vdays ≥ 3 occurred in 31%. Death/Vdays ≥ 3 rates correlated with RCFS values: 19% for 1-3; 24% for 4-6; 42% for 7-12 and 65% for ≥ 13 (p < 0.001). Death/Vdays ≥ 3 was independently associated with RCFS (p = 0.02), LIS (p = 0.001), head AIS (p < 0.001) and abdominal AIS (p < 0.001). Death/Vdays ≥ 3 association was better for RCFS (p = 0.005) than rib fracture score (p = 0.08) or number of fractured ribs (p = 0.80).'] Are trauma patient adverse outcomes independently associated with rib cage fracture burden and severity of lung , head , and abdominal injuries? | qiaojin/PubMedQA | 2 | [
-0.49040499329566956,
-1.848766803741455,
1.3383023738861084
] |
['Increasing evidence has shown that protein tyrosine phosphatases have dominant roles in setting the levels of tyrosine phosphorylation and promoting oncogenic processes. PTP4A3 has been implicated in cancer metastasis but to our knowledge the role of PTP4A3 in upper tract urothelial carcinoma is unknown. The aim of this study was to investigate the association of PTP4A3 with disease characteristics, distant metastasis and prognosis of upper tract urothelial carcinoma.', 'The importance of PTP4A3 was initially examined in paired normal urothelium, noninvasive upper tract urothelial carcinoma, invasive upper tract urothelial carcinoma and nodal metastatic tissue. The PTP4A3 transcript level was assessed in another 20 upper tract urothelial carcinoma samples by real-time reverse transcriptase-polymerase chain reaction. PTP4A3 protein expression was determined by immunohistochemistry using the H-score in 340 upper tract urothelial carcinoma samples. It was further correlated with clinicopathological factors, and disease specific and metastasis-free survival.', 'The expression of PTP4A3 significantly increased from normal urothelium, noninvasive upper tract urothelial carcinoma and invasive upper tract urothelial carcinoma to nodal metastatic tissue (p <0.001). The PTP4A3 transcript level was also markedly up-regulated in higher stage upper tract urothelial carcinoma (p = 0.002). Over expression of PTP4A3 protein was significantly associated with advanced pT status, nodal metastasis, lymphovascular invasion and perineural invasion (each p <0.001) as well as with inferior disease specific and metastasis-free survival on multivariate analysis (each p\xa0<0.0001). In addition, it predicted metastasis in patients with pTa, pT1 and pT2 upper tract urothelial carcinoma.'] Does pTP4A3 Independently predict Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy? | qiaojin/PubMedQA | 2 | [
-2.2137317657470703,
-1.3991549015045166,
2.6428215503692627
] |
['The mucin MUC1, best known for providing an epithelial barrier, is an important protective host factor in both humans and mice during Helicobacter pylori pathogenesis. This study aimed to identify the long-term consequences of MUC1 deficiency on H. pylori pathogenesis and the mechanism by which MUC1 protects against H. pylori gastritis.', 'Wildtype and Muc1(-/-) mice were infected for up to 9\u2005months, and the gastric pathology, immunological response and epigenetic changes assessed. The effects of MUC1 on the inflammasome, a potent inflammatory pathway, were examined in macrophages and H. pylori-infected mice deficient in both MUC1 and inflammasome components.', 'Muc1(-/-) mice began to die 6\u2005months after challenge, indicating Muc1 deficiency made H. pylori a lethal infection. Surprisingly, chimaeric mouse infections revealed MUC1 expression by haematopoietic-derived immune cells limits H. pylori-induced gastritis. Gastritis in infected Muc1(-/-) mice was associated with elevated interleukin (IL)-1β and epigenetic changes in their gastric mucosa similar to those in transgenic mice overexpressing gastric IL-1β, implicating MUC1 regulation of an inflammasome. In support of this, infected Muc1(-/-)Casp1(-/-) mice did not develop severe gastritis. Further, MUC1 regulated Nlrp3 expression via an nuclear factor (NF)-κB-dependent pathway and reduced NF-κB pathway activation via inhibition of IRAK4 phosphorylation. The importance of this regulation was proven using Muc1(-/-)Nlrp3(-/-) mice, which did not develop severe gastritis.'] Does the MUC1 mucin protect against Helicobacter pylori pathogenesis in mice by regulation of the NLRP3 inflammasome? | qiaojin/PubMedQA | 2 | [
-2.414503574371338,
-1.331331491470337,
2.786637306213379
] |
['Fine particulate matter (PM2.5) air pollution and variations in ambient temperature have been linked to increased cardiovascular morbidity and mortality. However, no large-scale study has assessed their effects on directly measured aerobic functional capacity among high-risk patients.', 'Using a cross-sectional observational design, we evaluated the effects of ambient PM2.5 and temperature levels over 7\u2005days on cardiopulmonary exercise test results performed among 2078 patients enrolling into a cardiac rehabilitation programme at the University of Michigan (from January 2003 to August 2011) using multiple linear regression analyses (controlling for age, sex, body mass index).', 'Peak exercise oxygen consumption was significantly decreased by approximately 14.9% per 10 μg/m(3) increase in ambient PM2.5 levels (median 10.7 μg/m(3), IQR 10.1 μg/m(3)) (lag days 6-7). Elevations in PM2.5 were also related to decreases in ventilatory threshold (lag days 5-7) and peak heart rate (lag days 2-3) and increases in peak systolic blood pressure (lag days 4-5). A 10°C increase in temperature (median 10.5°C, IQR 17.5°C) was associated with reductions in peak exercise oxygen consumption (20.6-27.3%) and ventilatory threshold (22.9-29.2%) during all 7 lag days. In models including both factors, the outcome associations with PM2.5 were attenuated whereas the effects of temperature remained significant.'] Do higher fine particulate matter and temperature levels impair exercise capacity in cardiac patients? | qiaojin/PubMedQA | 2 | [
-2.1318535804748535,
-1.1855857372283936,
2.3768062591552734
] |
['To investigate whether Decorin, a matrikine that regulates extracellular matrix (ECM) deposition, can reverse established trabecular meshwork (TM) fibrosis, lower IOP, and reduce progressive retinal ganglion cell (RGC) death in a novel rodent model of TM fibrosis.', 'Adult rats had intracameral (IC) injections of human recombinant (hr) TGF-β over 30 days (30 d; to induce TM fibrosis, raise IOP, and initiate RGC death by 17 d) or PBS (controls) and visually evoked potentials (VEP) were measured at 30 d to evaluate resultant visual pathway dysfunction. In some animals TGF-β injections were stopped at 17 d when TM fibrosis and IOP were consistently raised and either hrDecorin or PBS IC injections were administered between 21 d and 30 d. Intraocular pressure was measured biweekly and eyes were processed for immunohistochemical analysis of ECM deposition to assess TM fibrosis and levels of matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinases (TIMP) to assess fibrolysis. The effect of hrDecorin treatment on RGC survival was also assessed.', 'Transforming growth factor-β injections caused sustained increases in ECM deposition in the TM and raised IOP by 17 d, responses that were associated with 42% RGC loss and a significant decrease in VEP amplitude measured at 30 d. Decorin treatment from 17 d reduced TGF-β-induced TM fibrosis, increased levels of MMP2 and MMP9 and lowered TIMP2 levels, and lowered IOP, preventing progressive RGC loss.'] Does decorin reduce Intraocular Pressure and Retinal Ganglion Cell Loss in Rodents Through Fibrolysis of the Scarred Trabecular Meshwork? | qiaojin/PubMedQA | 2 | [
-2.3163373470306396,
-1.3880890607833862,
2.7317562103271484
] |
['We minimized the influence of image quality variability, as measured by signal strength (SS), on optical coherence tomography (OCT) thickness measurements using the histogram matching (HM) method.', 'We scanned 12 eyes from 12 healthy subjects with the Cirrus HD-OCT device to obtain a series of OCT images with a wide range of SS (maximal range, 1-10) at the same visit. For each eye, the histogram of an image with the highest SS (best image quality) was set as the reference. We applied HM to the images with lower SS by shaping the input histogram into the reference histogram. Retinal nerve fiber layer (RNFL) thickness was automatically measured before and after HM processing (defined as original and HM measurements), and compared to the device output (device measurements). Nonlinear mixed effects models were used to analyze the relationship between RNFL thickness and SS. In addition, the lowest tolerable SSs, which gave the RNFL thickness within the variability margin of manufacturer recommended SS range (6-10), were determined for device, original, and HM measurements.', 'The HM measurements showed less variability across a wide range of image quality than the original and device measurements (slope = 1.17 vs. 4.89 and 1.72 μm/SS, respectively). The lowest tolerable SS was successfully reduced to 4.5 after HM processing.'] Does histogram Matching extend Acceptable Signal Strength Range on Optical Coherence Tomography Images? | qiaojin/PubMedQA | 2 | [
-0.8239969611167908,
-1.5611374378204346,
1.4556597471237183
] |
['Rhabdomyosarcoma (RMS) is a soft tissue sarcoma associated with the skeletal muscle lineage. Of the two predominant subtypes, known as embryonal (eRMS) and alveolar (aRMS), aRMS has the poorer prognosis, with a five-year survival rate of <50%. The majority of aRMS tumors express the fusion protein PAX3-FOXO1. As PAX3-FOXO1 has proven chemically intractable, this study aims to identify targetable proteins that are downstream from or cooperate with PAX3-FOXO1 to support tumorigenesis.', 'Microarray analysis of the transcriptomes of human skeletal muscle myoblasts expressing PAX3-FOXO1 revealed alteration of several Wnt pathway gene members, including secreted frizzled related protein 3 (SFRP3), a secreted Wnt pathway inhibitor. Loss-of-function using shRNAs against SFRP3 was used to interrogate the role of SFRP3 in human aRMS cell lines in vitro and conditional murine xenograft systems in vivo. The combination of SFRP3 genetic suppression and the chemotherapeutic agent vincristine was also examined.', 'In vitro, suppression of SFRP3 inhibited aRMS cell growth, reduced proliferation accompanied by a G1 arrest and induction of p21, and induced apoptosis. In vivo, doxycycline-inducible suppression of SFRP3 reduced aRMS tumor growth and weight by more than three-fold, in addition to increasing myogenic differentiation and β-catenin signaling. The combination of SFRP3 suppression and vincristine was more effective at reducing aRMS cell growth in vitro than either treatment alone, and ablated tumorigenesis in vivo.'] Does secreted Frizzled-Related Protein 3 ( SFRP3 ) be Required for Tumorigenesis of PAX3-FOXO1-Positive Alveolar Rhabdomyosarcoma? | qiaojin/PubMedQA | 2 | [
-2.4010958671569824,
-1.3494329452514648,
2.793667793273926
] |
['Although a previous study reported nerve ending-derived acetylcholine promoted prostate cancer invasion and metastasis by regulating the microenvironment of cancer cells, the present study aims to determine whether there is autocrine cholinergic signaling in prostate epithelial cells that promotes prostate cancer growth and castration resistance.', 'In this study, IHC was performed to detect protein expression in mouse prostate tissue sections and human prostate cancer tissue sections. Subcutaneously and orthotopically xenografted tumor models were established to evaluate the functions of autocrine cholinergic signaling in regulating prostate cancer growth and castration resistance. Western blotting analysis was performed to assess the autocrine cholinergic signaling-induced signaling pathway.', 'We found the expression of choline acetyltransferase (ChAT), the secretion of acetylcholine and the expression of CHRM3 in prostate epithelial cells, supporting the presence of autocrine cholinergic signaling in the prostate epithelium. In addition, we found that CHRM3 was upregulated in clinical prostate cancer tissues compared with adjacent non-cancer tissues. Overexpression of CHRM3 or activation of CHRM3 by carbachol promoted cell proliferation, migration, and castration resistance. On the contrary, blockading CHRM3 by shRNA or treatment with darifenacin inhibited prostate cancer growth and castration resistance both in vitro and in vivo. Furthermore, we found that autocrine cholinergic signaling caused calmodulin/calmodulin-dependent protein kinase kinase (CaM/CaMKK)-mediated phosphorylation of Akt.'] Does autocrine Activation of CHRM3 promote Prostate Cancer Growth and Castration Resistance via CaM/CaMKK-Mediated Phosphorylation of Akt? | qiaojin/PubMedQA | 2 | [
-2.5019004344940186,
-1.2493348121643066,
2.8141820430755615
] |
['Female gender has been reported to be a risk factor for graft loss after liver transplantation for hepatitis C virus (HCV)-related cirrhosis but evidence is limited to retrospective studies.', 'To investigate the impact of recipient gender and donor/recipient gender mismatch on graft outcome.', 'We performed a survival analysis of a cohort of 1530 first adult transplants enrolled consecutively in Italy between 2007 and 2009 and followed prospectively. After excluding possible confounding factors (fulminant hepatitis, human immunodeficiency virus co-infection, non-viremic anti-HCV positive subjects), a total of 1394 transplant recipients (604 HCV-positive and 790 HCV-negative) were included.', 'Five-year graft survival was significantly reduced in HCV-positive patients (64% vs 76%, p=0.0002); Cox analysis identified recipient female gender (HR=1.44, 95% CI 1.03-2.00, p=0.0319), Mayo clinic End stage Liver Disease score (every 10 units, HR=1.25, 95% CI 1.03-1.50; p=0.022), portal thrombosis (HR=2.40, 95% CI 1.20-4.79, p=0.0134) and donor age (every 10 years, HR=1.14, 95% CI 1.05-1.24, p=0.0024) as independent determinants of graft loss. All additional mortality observed among female recipients was attributable to severe HCV recurrence.'] Is recipient female gender a risk factor for graft loss after liver transplantation for chronic hepatitis C : Evidence from the prospective Liver Match cohort? | qiaojin/PubMedQA | 2 | [
-1.8279163837432861,
-1.3303290605545044,
2.2626309394836426
] |
['The spinal curvature in patients with Adolescent Idiopathic Scoliosis (AIS) causes an asymmetry of upper body postural alignment, which might affect postural balance. However, the currently available studies on balance in AIS patients are not consistent. Furthermore, it is not known whether potential deficits are similar between patients with single and double curves. Finally, the effects of a corrective posterior spinal fusion on postural balance have not yet been well established.', 'Postural balance was tested on a force plate, in 26 female subjects with AIS (12-18 years old; preoperative Cobb-angle: 42-71°; single curve n\u2009=\u200918, double curve n\u2009=\u20096) preoperatively, at 3\xa0months and 1\xa0year postoperatively. We also conducted a balance assessment in 18 healthy age-matched female subjects. Subjects were tested during quiet double-leg standing in four conditions (eyes open/closed; foam/solid surface), while standing on one leg, while performing a dynamic balance (weight shifting) task and while performing a reaching task in four directions.', 'AIS subjects did not demonstrate greater COP velocities than controls during the double-leg standing tasks. In the reaching task, however, they achieved smaller COP displacements than healthy controls, except in the anterior direction. AIS patients with double curves had significantly greater COP velocities in all test conditions compared to those with a single curve (p\u2009<\u20090.05). For the AIS group, a slight increase in COP velocities was observed in the foam eyes closed and right leg standing condition at 3\xa0months post surgery. At 1-year post surgery, however, there were no significant differences in any of the outcome measures compared to the pre-surgery assessment, irrespective of the curve type.'] Do adolescent idiopathic scoliosis and spinal fusion substantially impact on postural balance? | qiaojin/PubMedQA | 2 | [
-1.7376025915145874,
-1.4663605690002441,
2.1292366981506348
] |
['Esophageal adenocarcinoma (EAC) incidence increases, maybe due to increasing prevalences of obesity and diabetes. Concurrent hyperinsulinemia might promote carcinogenesis via the insulin-like growth factor-I receptor (IGF-1R). Expression of the IGF-1R was studied in correlation with diabetes and prognostic parameters.', 'Patients with EAC undergoing esophagectomy were prospectively selected. From resected tumors a tissue microarray was constructed. Immunohistochemistry evaluated IGF-1R-expression. Logistic-, cox regression models and survival analyses assessed if diabetes and IGF-1R-expression were associated with prognostic parameters. IGF-1R-expression in normal and Barrett tissues was studied.', 'Absence or low IGF-1R-expression was associated with T3-, grade 3 tumors and R1 resections (P\u2009=\u20090.001, P\u2009=\u20090.025, P\u2009<\u20090.001, respectively). Logistic regression showed that this was associated with R1 resections (HR 0.24, 95%CI 0.11-0.52). Diabetes was not associated with IGF-1R-expression (P\u2009=\u20090.612). Absence or low IGF-1R-expression decreased 5-year overall survival (P\u2009=\u20090.023) univariably, but not multivariably. IGF-1R-expression was present in Barrett tissues, but diminished in high-grade dysplasia.'] Is absence or low IGF-1R-expression in esophageal adenocarcinoma associated with tumor invasiveness and radicality of surgical resection? | qiaojin/PubMedQA | 2 | [
-1.8613438606262207,
-1.5741077661514282,
2.445953369140625
] |
['The evolutionary basis of reproductive success in different environments is of major interest in the study of plant adaptation. Since the reproductive stage is particularly sensitive to drought, genes affecting reproductive success during this stage are key players in the evolution of adaptive mechanisms. We used an ecological genomics approach to investigate the reproductive response of drought-tolerant and sensitive wild barley accessions originating from different habitats in the Levant.', 'We sequenced mRNA extracted from spikelets at the flowering stage in drought-treated and control plants. The barley genome was used for a reference-guided assembly and differential expression analysis. Our approach enabled to detect biological processes affecting grain production under drought stress. We detected novel candidate genes and differentially expressed alleles associated with drought tolerance. Drought associated genes were shown to be more conserved than non-associated genes, and drought-tolerance genes were found to evolve more rapidly than other drought associated genes.'] Does rNA-Seq analysis identify genes associated with differential reproductive success under drought-stress in accessions of wild barley Hordeum spontaneum? | qiaojin/PubMedQA | 2 | [
-2.4925918579101562,
0.3952483832836151,
1.2736868858337402
] |
['The aim of the present study was to investigate whether induction of differentiation by hyperthermia is accompanied by apoptosis and necrosis to further evaluate the benefits of using hyperthermia as a differentiation inducing physical modality.', 'Differentiation was evaluated in K562 erythroleukaemia cells by measuring haemoglobin synthesis and flow cytometric measurement of glycophorin A expression. Apoptosis was measured by Annexin-V-FITC and Propidium Iodide (PI) double staining assay. Apoptosis and necrosis was also evaluated morphologically using staining with acridine orange/ethidium bromide (AO/EtBr) by fluorescence microscopy. Heat shock protein 70 (HSP70) level was measured by ELISA kit.', 'Hyperthermia (43 degrees C) induced differentiation as judged by increased haemoglobin synthesis and glycophorin A expression. No sign of apoptosis or necrosis could be detected at this temperature. Cell viability did not change due to heat treatment, and cellular proliferation was reduced in a dose (heating time) dependent manner. At 45 degrees C, hyperthermia induced apoptosis and necrosis with minimal or no sign of differentiation. HSP70 level was significantly increased at 43 degrees C along with differentiation of leukaemic cells, while at 45 degrees C no significant effect on HSP70 production could be observed.'] Does hyperthermia induce differentiation without apoptosis in permissive temperatures in human erythroleukaemia cells? | qiaojin/PubMedQA | 2 | [
-2.5016891956329346,
-1.2554324865341187,
2.8054678440093994
] |
['Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death. Smoking, diabetes, and pancreatitis are risk factors. It has been shown that the growth of PDAC and pancreatic duct epithelial cells is regulated by beta-adrenoreceptors (beta-ARs). The activity of beta-ARs in the central nervous system is counteracted by gamma-aminobutyric acid (GABA) via GABA B receptor-mediated inhibition of adenylyl cyclase. The aim of the study was to investigate if GABA B R inhibits beta-AR signaling in PDAC and pancreatic duct epithelial cells, thus blocking driving forces of cancer progression, such as cell proliferation and cell migration.', 'Intracellular cAMP was measured by immunoassays, DNA synthesis by BrdU incorporation assays, activation of ERK1/2 by ERK activation assays, and Western blots and metastatic potential by cell migration assays in the human PDAC cell lines PANC-1 and BXPC-3 and immortalized human pancreatic duct epithelial cells HPDE6-C7. The expression of norepinephrine, PKAR IIalpha, and GABA in PDAC microarrays was assessed by immunohistochemistry. RESULTS.: Stimulation of the GABA B R by GABA or baclofen inhibited isoproterenol-induced cAMP signaling below base levels. ERK1/2 activity in response to isoproterenol was blocked by GABA, an effect enhanced by transient overexpression of the GABA B R and abolished by GABA B R knockdown. DNA synthesis and cell migration were stimulated by isoproterenol, responses blocked by GABA and baclofen. Norepinephrine and PKAR IIalpha were overexpressed while GABA was underexpressed in human PDAC tissue arrays.'] Is gABA B receptor a novel drug target for pancreatic cancer? | qiaojin/PubMedQA | 2 | [
-2.4443318843841553,
-1.285774827003479,
2.790977954864502
] |
['This study evaluated the association of a polymorphism in the CD40 gene with BMD and risk of osteopenia or osteoporosis in a population of 602 postmenopausal women. Results showed that women with the TT genotype had lower BMD at femoral neck and spine sites and increased risk of osteopenia or osteoporosis.', 'Recent findings have demonstrated that the CD40/CD40L system, which is of main importance for the immune system, can also be implied in the regulation of bone metabolism. The main objective of the present work has been to clarify whether single nucleotide polymorphisms (SNPs) affecting genes of CD40/CD40L system could be linked with abnormalities in the level of bone mineral density (BMD) in menopausal women.', 'We performed an association study of BMD values with a SNP located at position -1 of the Kozak consensus sequence of CD40 gene (rs1883832; C>T) in a population of 602 postmenopausal women.', 'Women with the TT genotype (8.6% of women) displayed a reduction in femoral neck BMD (FN BMD) and lumbar spine BMD (LS BMD) of 6.2% and of 6.3%, respectively, as compared to women with CC + CT genotype. Logistic regression analysis adjusted for age, weight, and height showed that women with the TT genotype had increased risk for FN (odds ratio: 2.34; 95% CI: 1.12-4.89) and LS (odds ratio: 2.49; 95% CI: 1.19-5.24) osteopenia or osteoporosis.'] Is a C > T polymorphism located at position -1 of the Kozak sequence of CD40 gene associated with low bone mass in Spanish postmenopausal women? | qiaojin/PubMedQA | 2 | [
-1.7906538248062134,
-1.4386063814163208,
2.188227653503418
] |
['Chronic stroke survivors with low hip bone density are particularly prone to fractures. This study shows that fear of falling is independently associated with falls in this population. Thus, fear of falling should not be overlooked in the prevention of fragility fractures in these patients.', 'Chronic stroke survivors with low bone mineral density (BMD) are particularly prone to fragility fractures. The purpose of this study was to identify the determinants of balance, mobility and falls in this sub-group of stroke patients.', 'Thirty-nine chronic stroke survivors with low hip BMD (T-score <-1.0) were studied. Each subject was evaluated for the following: balance, mobility, leg muscle strength, spasticity, and fall-related self-efficacy. Any falls in the past 12 months were also recorded. Multiple regression analysis was used to identify the determinants of balance and mobility performance, whereas logistic regression was used to identify the determinants of falls.', 'Multiple regression analysis revealed that after adjusting for basic demographics, fall-related self-efficacy remained independently associated with balance/mobility performance (R2 = 0.494, P < 0.001). Logistic regression showed that fall-related self-efficacy, but not balance and mobility performance, was a significant determinant of falls (odds ratio: 0.18, P = 0.04).'] Is fall-related self-efficacy , not balance and mobility performance , related to accidental falls in chronic stroke survivors with low bone mineral density? | qiaojin/PubMedQA | 2 | [
-1.3494948148727417,
-0.49012333154678345,
0.986491322517395
] |
['Apoptosis has been implicated in renal ischemic injury, the regulating mechanism of which is still unclear. Signal transducers and activators of transcription (STAT) participate in inflammation, apoptosis, and tumorigenesis. In the in vitro model of renal ischemic injury, we explored the role of the STAT3, a major component of the STAT family, in apoptosis of human proximal tubular epithelial cell (HKC) induced by ATP depletion/recovery.', 'Apoptosis of HKC was induced in an in vitro model of acute renal failure. STAT3 activation was analyzed by Western blotting. RNA interference was used to knock down STAT3 expression. The effect of STAT3 knockdown or STAT3C overexpression on apoptosis was assessed by annexin V binding and propidium iodide uptake.', 'STAT3 was phosphorylated during the course of ATP depletion-induced HKC cell apoptosis. STAT3 knockdown suppressed STAT3 phosphorylation, and promoted apoptosis of HKC subjected to ATP depletion/recovery, while STAT3C overexpression conferred resistance of HKC to ATP depletion-induced apoptosis.'] Does sTAT3 inhibit apoptosis of human renal tubular epithelial cells induced by ATP depletion/recovery? | qiaojin/PubMedQA | 2 | [
-2.440824508666992,
-1.1275043487548828,
2.577272891998291
] |
["To assess the false-positive rate of breast cancer surveillance by magnetic resonance imaging (MRI) in BRCA mutation carriers and the impact of an abnormal mammography or breast MRI on the patients' decision for prophylactic mastectomy.", 'A total of 196 BRCA mutation carriers were included with a median follow-up of 2 years (range 1-9) with annual mammography and MRI. Preference for prophylactic mastectomy was registered at first surveillance after the mutation carriership was revealed.', 'In all, 41% (81 of 196) of the women had at least one positive MRI or mammography. Malignancy was detected in 17 women: 11 at surveillance, 4 at an intended prophylactic mastectomy and 2 had an interval cancer. Imaging by mammography and MRI had a sensitivity of 71% and a specificity of 90%. The probability that a positive MRI result is false positive was 83%. In the group with a prior preference for mastectomy with and without a false-positive imaging, prophylactic mastectomy was carried out in 89% and 66%, respectively (P = 0.06), in the group with prior preference for surveillance these percentages were 15% and 11%, respectively (P = 0.47).'] Is the impact of a false-positive MRI on the choice for mastectomy in BRCA mutation carriers limited? | qiaojin/PubMedQA | 2 | [
-1.0271697044372559,
-1.5521862506866455,
1.5706560611724854
] |
['To evaluate the effect of chronic hypoxia on human spermatogenic parameters and their recovery time.', 'Seminological parameters of six male healthy mountain trekkers were evaluated in normoxia at sea level. After 26 days exposure to altitude (ranging from 2 000 m to 5 600 m, Karakorum Expedition) the same parameters were again evaluated after returning to sea level. These parameters were once again evaluated after 1 month and then again after 6 months.', 'Sperm count was found to be lower immediately after returning to sea level (P = 0.0004) and again after a month (P = 0.0008). Normal levels were reached after 6 months. Spermatic motility (%) shows no reduction immediately after returning to sea level (P = 0.0583), whereas after 1 month this reduction was significant (P = 0.0066). After 6 months there was a recovery to pre-hypoxic exposure values. Abnormal or immature spermatozoa (%) increased immediately after returning to sea level (P = 0.0067) and then again after 1 month (P = 0.0004). After 6 months there was a complete recovery to initial values. The total number of motile sperm in the ejaculate was found to be lower immediately after returning to sea level (P = 0.0024) and then again after 1 month (P = 0.0021). After 6 months there was a recovery to pre-hypoxic exposure values.'] Does evidence that chronic hypoxia cause reversible impairment on male fertility? | qiaojin/PubMedQA | 1 | [
-1.3865150213241577,
0.5369775891304016,
0.015712624415755272
] |
['An inverse association either between depression or impaired functional status and quality of life (QoL) has been reported for cancer patients, but the independent effect of depression or depressive symptoms and of functional impairment on QoL is unclear.', 'We investigated the prevalence of depression or depressive symptoms with the Beck Depression Inventory (BDI), the functional impairment with the ECOG-Performance-Status (ECOG-PS) and the QoL with the EORTC-QLQ-C30 questionnaire in a sample of 175 hospitalised cancer patients prior to the start of chemotherapy.', 'Sixteen of 175 patients (9.1%) screened positive for major depression, 29 (16.6%) had mild to moderate depressive symptoms. In 11 of 15 scales of the EORTC-QLQ-C30 questionnaire depression or depressive symptoms were significantly associated with worse QoL in univariate analysis and in 12 of 15 scales poor ECOG-PS was significantly associated with worse QoL. In multivariate analysis including ECOG-PS and BDI, the effect of depression and/ or depressive symptoms on QoL was persistent in seven scales: global QoL, physical- and role functioning, fatigue, nausea & vomiting, pain, and constipation, that of ECOG-PS in five scales: global QoL, emotional functioning, nausea & vomiting, pain, and appetite loss.'] Do depression and functional impairment independently contribute to decreased quality of life in cancer patients prior to chemotherapy? | qiaojin/PubMedQA | 2 | [
-2.1420557498931885,
-1.0843607187271118,
2.282212257385254
] |
["Intrathecal inflammation has been suggested to play an important role in the pathogenesis of Alzheimer's disease (AD). However, there is little clinical evidence in support of this hypothesis in AD patients. We previously reported that the blood-brain barrier permeability represented by the cerebrospinal fluid/serum albumin ratio correlates with medial temporal lobe atrophy (MTA) in AD. The aim of this study was to elucidate the relationship between intrathecal inflammation and the severity of AD.", 'We investigated the correlations between the cerebrospinal fluid/serum IgG index and the indices of AD severity, including Clinical Dementia Rating and Mini-Mental State Examination, and MTA on magnetic resonance imaging in 42 AD patients. Further, the number of apolipoprotein E isoforms and the blood-brain barrier permeability were also examined for the correlation with the IgG index.', 'The IgG index showed a positive correlation with the severity of MTA but not with the other parameters examined.'] Is cerebrospinal fluid/serum IgG index correlated with medial temporal lobe atrophy in Alzheimer 's disease? | qiaojin/PubMedQA | 2 | [
-2.5174217224121094,
-0.8779522180557251,
2.471437931060791
] |
['To study the effects of homocysteine and copper on type 5 phosphodiesterase (PDE5) expression in cavernosal vascular smooth muscle cells (CVSMCs) and to investigate superoxide (O(2)(.-)) derived from nicotinamide adenine dinucleotide phosphate oxidase as homocysteine and copper generate O(2)(.-), and O(2)(.-) upregulates PDE5 expression.', 'CVSMCs derived from rabbit penis were incubated with homocysteine or copper chloride with or without superoxide dismutase (SOD), catalase, sildenafil citrate, or apocynin (nicotinamide adenine dinucleotide phosphate inhibitor) for 16 h. The expression of PDE5 and of glyceraldehyde-3-phosphate dehydrogenase (internal standard) was assessed using Western blot analysis. In parallel, O(2)(.-) was measured spectrophotometrically.', 'CuCl(2) alone (up to 10 micromol/L) and homocysteine alone (up to 100 micromol/L) had no effect on O(2)(.-) formation in CVSMCs compared to controls. In combination, however, homocysteine and CuCl(2) markedly increased O(2)(.-) formation, an effect blocked by SOD, catalase, apocynin, and sildenafil (1 micromol/L) when co-incubated over the same time course. PDE5 expression was also significantly increased in CVSMCs incubated with homocysteine and CuCl(2), compared to controls. This effect was also negated by 16-h co-incubation with SOD, catalase, apocynin and sildenafil.'] Do homocysteine and copper interact to promote type 5 phosphodiesterase expression in rabbit cavernosal smooth muscle cells? | qiaojin/PubMedQA | 2 | [
-2.220041036605835,
-1.418937087059021,
2.627739191055298
] |
['To evaluate the protective effects of ginger (Gin) and roselle (Ros) against testicular damage and oxidative stress in a cisplatin (CIS)-induced rodent model. Their protective effects against CIS-induced apoptosis in testicular and epididymal sperms is also investigated.', 'Ethanol extracts of Gin or Ros (1 g/kg.day) were given orally to male albino rats for 26 days. This period began 21 days before a single CIS intraperitoneal injection (10 mg/kg body weight).', 'Gin or Ros given orally significantly restored reproductive function. Both tested extracts notably reduced the CIS-induced reproductive toxicity, as evidenced by restoring the testis normal morphology. In Gin and Ros, the attenuation of CIS-induced damage was associated with less apoptotic cell death both in the testicular tissue and in the sperms. CIS-induced alterations of testicular lipid peroxidation were markedly improved by these plant extracts.'] Do herbal extracts counteract cisplatin-mediated cell death in rat testis? | qiaojin/PubMedQA | 2 | [
-2.5738155841827393,
-0.857976496219635,
2.472161054611206
] |
['Galectin-3 (Gal-3) is a 26-kDa lectin known to regulate many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to atherosclerotic plaque progression by enhancing monocyte chemoattraction through macrophage activation.', 'Gal-3 was found to be upregulated in unstable plaque regions of carotid endarterectomy (CEA) specimens compared with stable regions from the same patient (3.2-fold, P<0.05) at the mRNA (n=12) and (2.3-fold, P<0.01) at the protein level (n=9). Analysis of aortic tissue from ApoE-/- mice on a high fat diet (n=14) and wild-type controls (n=9) showed that Gal-3 mRNA and protein levels are elevated by 16.3-fold (P<0.001) and 12.2-fold (P<0.01) and that Gal-3 staining colocalizes with macrophages. In vitro, conditioned media from Gal-3-treated human macrophages induced an up to 6-fold increase in human monocyte chemotaxis (P<0.01, ANOVA), an effect that was reduced by 66 and 60% by Pertussis Toxin (PTX) and the Vaccinia virus protein 35K, respectively. Microarray analysis of human macrophages and subsequent qPCR validation confirmed the upregulation of CC chemokines in response to Gal-3 treatment.'] Is galectin-3 an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction? | qiaojin/PubMedQA | 2 | [
-2.315516233444214,
-1.422703504562378,
2.7994980812072754
] |
['The relationship between subcortical ischemic vascular disease (SIVD) and cognition in normal elderly is unclear, in part because of methodological inconsistencies across studies. To clarify this relationship, the current study investigated a well characterized cognitively normal elderly sample (>or=55 years) with quantitative MRI and psychometrically robust neuropsychological measures within a multivariate model. Converging evidence suggests that SIVD selectively impairs frontal-executive tasks by disrupting frontal-subcortical circuits. We therefore hypothesized that MRI markers of SIVD would be selectively associated with worse executive functioning.', 'We studied 94 participants who were cognitively and functionally normal. Volumetric measures of white matter signal hyperintensity (WMH), subcortical lacunes, hippocampal volume, and cortical gray matter were obtained to predict performance on composite measures of executive functioning and episodic memory.', 'Hierarchical regression demonstrated that after controlling for demographic variables, MMSE, and total intracranial volume, the total number of subcortical lacunes was the only significant predictor, with a greater number of lacunes associated with poorer executive performance. Hippocampal volume best predicted episodic memory performance.'] Are subcortical lacunes associated with executive dysfunction in cognitively normal elderly? | qiaojin/PubMedQA | 2 | [
-2.2800958156585693,
-1.071268081665039,
2.3940515518188477
] |
['Although patients should know the level of training of the physician providing their care in teaching hospitals, many do not.', "The objective of this study is to determine whether the manner by which physicians introduce themselves to patients is associated with patients' misperception of the level of training of their physician.", 'This was an observational study of 100 patient-physician interactions in a teaching emergency department.', 'Residents introduced themselves as a doctor 82% of the time but identified themselves as a resident only 7% of the time. While attending physicians introduced themselves as a "doctor" 64% of the time, only 6% identified themselves as the supervising physician. Patients felt it was very important to know their physicians\' level of training, but most did not.'] Do patients know the level of training of their doctors because doctors do not tell them? | qiaojin/PubMedQA | 1 | [
-0.26945364475250244,
2.173192262649536,
-2.4264075756073
] |
['To assess changes in the Fe and vitamin A status of the population of Nangweshi refugee camp associated with the introduction of maize meal fortification.', 'Pre- and post-intervention study using a longitudinal cohort.', 'Nangweshi refugee camp, Zambia.', 'Two hundred and twelve adolescents (10-19 years), 157 children (6-59 months) and 118 women (20-49 years) were selected at random by household survey in July 2003 and followed up after 12 months.', 'Maize grain was milled and fortified in two custom-designed mills installed at a central location in the camp and a daily ration of 400 g per person was distributed twice monthly to households as part of the routine food aid ration. During the intervention period mean Hb increased in children (0.87 g/dl; P < 0.001) and adolescents (0.24 g/dl; P = 0.043) but did not increase in women. Anaemia decreased in children by 23.4% (P < 0.001) but there was no significant change in adolescents or women. Serum transferrin receptor (log10-transformed) decreased by -0.082 microg/ml (P = 0.036) indicating an improvement in the Fe status of adolescents but there was no significant decrease in the prevalence of deficiency (-8.5%; P = 0.079). In adolescents, serum retinol increased by 0.16 micromol/l (P < 0.001) and vitamin A deficiency decreased by 26.1% (P < 0.001).'] Is maize meal fortification associated with improved vitamin A and iron status in adolescents and reduced childhood anaemia in a food aid-dependent refugee population? | qiaojin/PubMedQA | 2 | [
-1.575558066368103,
-1.0774192810058594,
1.7517166137695312
] |
['Diminished myocardial sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) activity and upregulated phospholamban (PLB) level during cardiac dysfunction, had been reported in many studies.', 'The current study was designed to examine the effects of rAAV-antisense phospholamban (asPLB) gene transfer on cardiac function, SERCA expression and activity, as well as PLB expression and phosphorylation (Pser16-PLB), in a rat myocardial infarction (MI) model.', 'Rat MI model was generated by ligating the left anterior descending coronary artery. Four weeks later, left ventricular ejection fraction (LVEF), left ventricular systolic pressure (LVSP), the maximal rates of increase and decrease in intraventricular pressure (+/-dp/dt(max)) were significantly depressed, and left ventricular end diastolic pressure (LVEDP) was increased. Myocardial PLB was markedly increased while both SERCA activity and Pser16-PLB level were decreased. In rAAV-asPLB transfected rats, rAAV-asPLB, which was injected into the myocardium around the infarction area immediately after the coronary artery ligation, effectively attenuated the depression of cardiac function, significantly inhibited the expression of PLB, restored Pser16-PLB level and enhanced myocardium SERCA activity.'] Does rAAV-asPLB transfer attenuate abnormal sarcoplasmic reticulum Ca2+ -ATPase activity and cardiac dysfunction in rats with myocardial infarction? | qiaojin/PubMedQA | 2 | [
-2.408512830734253,
-1.334932804107666,
2.805354595184326
] |
['Our previous studies have demonstrated that oxidative DNA injury occurs in the brain after intracerebral hemorrhage (ICH). We therefore examined whether edaravone, a free-radical scavenger, could reduce ICH-induced brain injury.', "These experiments used pentobarbital-anesthetized, male Sprague-Dawley rats that received an infusion of either 100 microL autologous whole blood (ICH), FeCl(2), or thrombin into the right basal ganglia. The rats were humanely killed 24 hours later. There were 4 sets of experiments. In the first, the dose-dependent effects of edaravone on ICH-induced brain injury were examined by measuring brain edema and neurologic deficits. In the second set, apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine, which are hallmarks of DNA oxidation, were investigated after treatment for ICH. In the third, the effect of delayed treatment with edaravone on ICH-induced injury was determined, whereas the fourth examined the effects of edaravone on iron- and thrombin-induced brain injury.", "Systemic administration of edaravone immediately or 2 hours after ICH reduced brain water content 24 hours after ICH compared with vehicle (P<0.05). Edaravone treatment immediately or 2 hours after ICH also ameliorated neurologic deficits (P<0.05). Edaravone also attenuated ICH-induced changes in apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine and reduced iron- and thrombin-induced brain injury."] Does edaravone attenuate brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage? | qiaojin/PubMedQA | 2 | [
-2.2608449459075928,
-1.3705929517745972,
2.669693946838379
] |
['Vascular endothelial growth factor (VEGF) is produced by almost all cancer cells and VEGF receptor 1 (R1) (Flt-1) is abundantly expressed on human monocytes. In the present study, we investigated whether VEGF affects the antibody-dependent cell-mediated cytotoxicity (ADCC) of human monocytes mediated by trastuzumab.', 'HER-2-expressing tumor cell lines (MKN-7, TE-4 and SKOV-3) were evaluated for trastuzumab-mediated ADCC of human monocytes in the presence of VEGF(165). The trastuzumab-mediated, monocyte-derived ADCC were treated with the anti-human blocking VEGF R1 or VEGF R2 mAb. VEGF-induced intracellular signaling on monocytes was quantified with ELISA kits.', 'VEGF partially inhibited the ADCC of human monocytes mediated by trastuzumab. The VEGF-induced deficiency of human monocytes for ADCC was completely recovered by the anti-human blocking VEGF R1 mAb, while the anti-VEGF R2 blocking mAb did not have any effect. Furthermore, VEGF treatment enhanced the phospho-Erk 1/2 in human monocytes.'] Does vascular endothelial growth factor partially inhibit the trastuzumab-mediated antibody-dependent cellular cytotoxicity of human monocytes? | qiaojin/PubMedQA | 2 | [
-2.370166540145874,
-1.327315092086792,
2.7384514808654785
] |
['The objective of this study was to determine the effects and potential mechanisms of C-reactive protein (CRP) on cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis.', 'Human THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) were preincubated with acetylated LDL and [3H]-cholesterol to form foam cells, which were then treated with apolipoprotein A-I (apoA-I) or HDL for cholesterol efflux assay. Clinically relevant concentrations of CRP significantly reduced cholesterol efflux from THP-1 and PBMCs to apoA-I or HDL. CRP significantly decreased the expression of ATP-binding membrane cassette transporter A-1 (ABCA1) and ABCG1, whereas it increased superoxide anion production. Furthermore, CRP substantially activated ERK1/2 in THP-1-derived foam-like cells. Reducing superoxide anion by antioxidant seleno-L-methionine or SOD mimetic (MnTBAP) effectively abolished the CRP-induced decrease in cholesterol efflux and the expression of ABCA1 and ABCG1. Inhibiting ERK1/2 activation by its specific inhibitor PD98059 or by a dominant negative mutant of ERK2 could also block CRPs action on THP-1 cells.'] Does c-reactive protein inhibit cholesterol efflux from human macrophage-derived foam cells? | qiaojin/PubMedQA | 2 | [
-2.529743194580078,
-1.1474525928497314,
2.728809356689453
] |
['The liver X receptors (LXRs) regulate a set of genes involved in lipid metabolism and reverse cholesterol transport. We investigated the mechanism by which shear stress regulates LXR in vascular endothelial cells (ECs).', 'Western blot showed that the protein level of LXRalpha and its target ABCA1 in the mouse thoracic aorta was higher than that in the aortic arch. As well, the mRNA level of LXR and its target genes ABCA1, ABCG1, ApoE, and LPL in the thoracic aorta was higher. In vitro, bovine aortic ECs were subjected to a steady laminar flow (12 dyne/cm2). The expressions of LXR and the LXR-mediated transcription were increased by laminar shear stress. Laminar flow increased LXR-ligand binding and the gene expression of sterol 27-hydroxylase (CYP27), which suggests an increased level of LXR ligand in ECs. This effect was attenuated by LXRalpha and CYP27 RNAi. The decrease of LXR in the aorta of PPARgamma+/- mice and that of C57 mice fed with PPARgamma antagonist suggest the involvement of PPARgamma in the LXR induction by flow.'] Does laminar shear stress regulate liver X receptor in vascular endothelial cells? | qiaojin/PubMedQA | 2 | [
-2.4654428958892822,
-1.2636475563049316,
2.745540142059326
] |
['Nonhyperlipidemic postinfarction patients are at high risk for recurrent coronary events by virtue of incident myocardial infarction (MI); however, few studies assess risk beyond incident MI. The aim of this study was to assess such risk as a function of 37 atherosclerosis-associated genetic polymorphisms and 17 blood marker variables.', 'Screening of polymorphisms in nonhyperlipidemic postinfarction patients revealed significant risk only for the 4G/5G insertion/deletion polymorphism in the promoter of the plasminogen-activator inhibitor-1 (PAI-1) gene. Outcome event mapping, an exploratory data analysis tool, was then applied to define a subgroup (182 patients from total study population of 846 nondiabetic patients) exhibiting maximal functional dependence of risk on the PAI-1 polymorphism. Cox multivariable regression analyses within the subgroup adjusted for significant clinical covariates and medication use as a function of the PAI-1 polymorphism and 17 atherosclerosis-associated blood markers revealed significant risk for patients homozygous for the 4G allele (hazard ratio 4.30, 95% CI 1.98 to 9.33, P=0.00023), and lack of significant risk-association with any blood marker.'] Does plasminogen activator inhibitor-1 polymorphism ( 4G/5G ) predict recurrence in nonhyperlipidemic postinfarction patients? | qiaojin/PubMedQA | 2 | [
-2.1654345989227295,
-1.4115813970565796,
2.6137242317199707
] |
['Gammadelta T cells share with natural killer (NK) cells many effector capabilities and cell-surface proteins, including the NKG2 receptor family. A subset of gammadelta T cells that express the variable Vdelta1 region plays a critical role in immune regulation, tumour surveillance and viral infection. Dramatic expansion of Vdelta1 T cells has been observed in HIV disease.', 'To determine if NKG2C expression on Vdelta1 T cells during HIV-1 infection is correlated with CD4 cell count and involved in lysis of CD4 T cells.', 'gammadelta T cells from viraemic HIV-infected patients were examined. Expression of NK cell markers was analyzed by flow cytometry. The cytolytic activity of Vdelta1 T cells was determined by either Cr-release assays or degranulation assays against HLA-E-transfected 721.221 cells or HIV-infected CD4 primary T cells.', 'The expression of C-type lectin NKG2 receptors was sharply modulated on gammadelta T cells in patients with HIV infection. A profound decrease of Vdelta1 T cells bearing inhibitory NKG2A receptors corresponded to a drastic expansion of a distinct population of Vdelta1 T cells expressing a functional activating NKG2C receptor. Engagement of HLA-E, the ligand of both NKG2A and NKG2C, which is specifically induced on HIV-infected CD4 T cells, substantially enhanced the Vdelta1 T cell-mediated cytotoxicity.'] Is nKG2C a major triggering receptor involved in the V [ delta ] 1 T cell-mediated cytotoxicity against HIV-infected CD4 T cells? | qiaojin/PubMedQA | 2 | [
-2.402878522872925,
-1.2548491954803467,
2.7537124156951904
] |
['External beam radiation therapy (EBRT) for rectal cancer unavoidably delivers significant radiation dose to the prostate gland. The effect of this incidental exposure on subsequent prostate cancer diagnosis was investigated using the Surveillance, Epidemiology, and End Results (SEER) cancer registry.', 'Men diagnosed with localized or regional (L/R) rectal cancer from 1988-1997 and treated with EBRT and sphincter-sparing surgery (SSS) were identified. Men treated for L/R rectal cancer with SSS who did not receive EBRT, and men with L/R colon cancer who did not receive EBRT, were studied for comparison. Multiple Primary Standardized Incidence Ratios of observed to expected (O/E) cases of prostate cancer were calculated using SEER*Stat.', 'In all, 1574 men with L/R rectal cancer treated with EBRT and SSS were identified. The median age at diagnosis was 64 and median survival was 76 months. Twenty were subsequently diagnosed with prostate cancer, a number significantly less than expected compared with the general population of similar age and race. The ratio of O/E cases was 0.28 (95% confidence interval [CI], 0.17, 0.43). In contrast, 3114 men diagnosed with rectal cancer undergoing SSS who were not treated with EBRT and 24,578 men diagnosed with colon cancer who were not treated with EBRT were subsequently diagnosed with prostate cancer at rates similar to the general population (O/E of 0.94 and 1.09).'] Is external beam radiation treatment for rectal cancer associated with a decrease in subsequent prostate cancer diagnosis? | qiaojin/PubMedQA | 2 | [
-1.4534467458724976,
-1.4495394229888916,
1.9204823970794678
] |
['To evaluate whether a beta2-adrenergic agonist may reduce acute alveolo-capillary barrier alterations during high-volume ventilation.', 'Experimental study.', 'Animal research laboratory.', 'A total of 48 male Wistar rats.', 'A zone of alveolar flooding was produced by liquid instillation in a distal airway. Proteins in the instilled solution were traced with 99mTc-albumin. 111In, which binds to transferrin, was injected into the systemic circulation. Terbutaline was administered in the instilled solution or intra-peritoneally. Conventional ventilation was applied for 30 min followed by different ventilation strategies for 90 min: conventional ventilation, high-volume ventilation with or without 6 cmH2O PEEP.', 'Protein fluxes across the alveolar and microvascular barriers were evaluated by scintigraphy. High-volume ventilation resulted in immediate leakage of 99mTc-albumin from alveolar spaces and increased pulmonary uptake of systemic 111In-transferrin. Terbutaline in the instilled solution and PEEP lessened alveolar 99mTc-albumin leakage and pulmonary 111In-transferrin uptake due to high-volume ventilation, whereas terbutaline given intra-peritoneally only lessened 111In-transferrin uptake. Terbutaline in the instilled solution also lessened the increase in lung wet-to-dry weight ratio due to high-volume ventilation.'] Does terbutaline lessen protein fluxes across the alveolo-capillary barrier during high-volume ventilation? | qiaojin/PubMedQA | 2 | [
-2.387301206588745,
-1.3332750797271729,
2.7655975818634033
] |
['Genetic variants of upstream transcription factor 1 (USF1) have previously been associated with dyslipidaemias in family studies. Our aim was to further address the role of USF1 in metabolic syndrome and cardiovascular traits at the population level in a large Swedish male cohort (n=2,322) with multiple measurements for risk factors during 32 years of follow-up.', 'Participants, born in 1920-1924, were examined at 50, 60, 70 and 77 years of age. The follow-up period for cardiovascular events was 1970-2002. We genotyped three haplotype tagging polymorphisms capturing the major allelic variants of USF1.', 'SNP rs2774279 was associated with the metabolic syndrome. The minor allele of rs2774279 was less common among individuals with metabolic syndrome than among healthy controls [p=0.0029 when metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III; p=0.0073 when defined according to the International Diabetes Federation (IDF)]. The minor allele of rs2774279 was also associated with lower BMI, lower fasting glucose values and higher HDL-cholesterol concentrations in longitudinal analyses. With SNP rs2073658, a borderline association with metabolic syndrome was observed (p=0.036, IDF), the minor allele being the risk-increasing allele. The minor allele of rs2073658 also associated with higher total and LDL-cholesterol, apolipoprotein B-100 and lipoprotein(a) concentrations in longitudinal analyses. Importantly, these trends with respect to the allelic variants prevailed throughout the follow-up time of three decades.'] Do uSF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study? | qiaojin/PubMedQA | 2 | [
-1.7080527544021606,
-1.2874449491500854,
2.0038886070251465
] |
['Platelets are essential for pulmonary leukocyte recruitment, airway hyperresponsiveness, and bronchial remodeling in animals with allergic inflammation and can be found in bronchoalveolar lavage of sensitized animals. No studies, however, have explored the direct migration of platelets to lungs.', 'To assess whether platelets migrate into lung parenchyma in response to inhaled allergen in ovalbumin-sensitized mice; to assess the role of the FcepsilonRI receptor in this phenomenon; and to evaluate whether platelets from patients with asthma, or from sensitized mice, undergo chemotaxis in vitro in response to relevant antigens.', 'Ovalbumin-sensitized wild-type (WT) mice, or FcRgamma(-/-) mice lacking the FcepsilonRIgamma, were challenged with aerosolized allergen and lungs analyzed by platelet-specific immunohistochemistry. In some experiments, mice were depleted of platelets and cross-transfused with either WT or FcRgamma(-/-) platelets to assess the role of platelet FcRgamma(-/-). Chemotaxis of platelets from patients with asthma or from sensitized mice was studied in vitro.', 'Histology of lungs revealed isolated platelets, migrating out of vessels and localizing underneath the airways after allergen challenge in WT but not in FcRgamma(-/-) mice. Platelets from patients with asthma and from sensitized WT mice, but not from sensitized FcRgamma(-/-) mice, migrated in vitro toward the relevant allergen or an anti-IgE. Platelets from normal mice were found to express FcepsilonRIgamma and platelet-bound IgEs were increased in sensitized mice.'] Does allergen induce the migration of platelets to lung tissue in allergic asthma? | qiaojin/PubMedQA | 2 | [
-2.514286756515503,
-1.2113795280456543,
2.7575955390930176
] |
['The motilin receptor (MTLR) is an important therapeutic target for treatment of hypomotility disorders. The negative outcome in clinical trials with the motilin agonist, ABT-229, indicated that desensitization may limit the therapeutic usefulness of motilides. We therefore compared the mechanisms involved in the intracellular trafficking of the MTLR after stimulation with motilin, erythromycin-A (EM-A) or ABT-229.', 'Desensitization was studied by measuring changes in Ca2+ rises and by receptor binding studies in CHO cells co-expressing the Ca2+ indicator apoaequorin and the MTLR, C-terminally tagged with EGFP. Receptor phosphorylation was studied by immunoprecipitation. MTLR-EGFP trafficking to organelles and translocation of beta-arrestins were visualized by fluorescence microscopy.', 'Agonist-induced desensitization of the MTLR was due to receptor internalization with potencies (p-int50) in the order of: ABT-229 (8.3)>motilin (7.86)>EM-A (4.77) but with no differences in the internalization kinetics (t(1/2): approximately 25 min). The percentage cell surface receptor loss was more profound after exposure to ABT-229 (88+/-1%) than to motilin (63+/-10%) or EM-A (34+/-2%). For motilin and EM-A MTLR phosphorylation probably occurs via G protein-coupled receptor kinases while for ABT-229 phosphorylation was also protein kinase C dependent. All agonists translocated cytosolic beta-arrestin-2 with greater affinity to the plasma membrane than beta-arrestin-1. After internalization the MTLR co-localized with transferrin but not with cathepsin D. After stimulation with motilin and EM-A the t(1/2) for MTLR resensitization was 3h and 1h, respectively but amounted 26h for ABT-229.'] Are differences in motilin receptor desensitization after stimulation with motilin or motilides due to alternative receptor trafficking? | qiaojin/PubMedQA | 2 | [
-2.076965093612671,
-1.4402806758880615,
2.527308940887451
] |
['Recent studies suggest an increasing prevalence of atypical initial symptoms in patients with celiac disease (CD). The aim of this study was to compare the presenting symptoms of CD at 2 comparable referral institutions in South Florida, and in Ankara, Turkey. We retrospectively reviewed the records of patients with an initial diagnosis of CD by small bowel biopsy during the same (1991 to 2001) 10-year period at Cleveland Clinic Florida and University of Ankara, Turkey. A numerical score was assigned to presenting symptom and signs.', 'There were 28 patients in the South Florida group (51% men) and 40 patients in the Turkish group (35% men) (P=NS). The Turkish patients were significantly younger at diagnosis (36+/-2 y vs. US patients 66+/-3 y) (P<0.0001). Typical celiac symptom scores were similar (Turkey 1.1+/-0.2 vs. South Florida 1.3+/-0.3) (P=NS). Atypical symptom scores were significantly higher in the US patients (1.9+/-0.2) versus those from Turkey (1.2+/-0.1) (P<0.01). The Turkish patients were significantly more likely (P<0.01) to present with chronic diarrhea, hypoalbuminemia, and mactocytosis at the time of diagnosis.'] Are a tale of two cities : typical celiac sprue presenting symptoms significantly more common in Turkish than in US Patients? | qiaojin/PubMedQA | 2 | [
-2.1960933208465576,
0.0033789968583732843,
1.3305585384368896
] |
['The goal of this investigation was to correlate particular age-related structural changes (compaction) to the amount of scatter in rabbit lenses and to determine if significant fiber compaction occurred in the nuclear and inner cortical regions.', 'New Zealand White rabbits at 16-20 months old (adult; n = 10) and at 3.5-4 years old (aged; n = 10) were utilized for this study. Immediately after euthanising, scatter was assessed in fresh lenses by low power helium-neon laser scan analysis. Scatter data was analyzed both for whole lenses and regionally, to facilitate correlation with morphometric data. After functional analysis, lenses were fixed and processed for scanning electron microcopy (SEM; right eyes) and light microscopy (LM; left eyes). Morphometric analysis of SEM images was utilized to evaluate compaction of nuclear fibers. Similarly, measurements from LM images were used to assess compaction of inner cortical fibers.', 'Scatter was significantly greater in aged lenses as compared to adult lenses in all regions analyzed, however the difference in the mean was slightly more pronounced in the inner cortical region. The anterior and posterior elliptical angles at 1 mm (inner fetal nucleus) were significantly decreased in aged vs. adult lenses (anterior, p = 0.040; posterior, p = 0.036). However, the average elliptical angles at 2.5 mm (outer fetal nucleus) were not significantly different in adult and aged lenses since all lenses examined had comparable angles to inner fetal fibers of aged lenses, i.e. they were all compacted. In cortical fibers, measures of average cross-sectional fiber area were significantly different at diameters of both 6 and 7 mm as a function of age (p = 0.011 and p = 0.005, respectively). Accordingly, the estimated fiber volume was significantly decreased in aged as compared to adult lenses at both 6 mm diameter (p = 0.016) and 7 mm diameter (p = 0.010).'] Does age-related compaction of lens fibers affect the structure and optical properties of rabbit lenses? | qiaojin/PubMedQA | 2 | [
-1.0847654342651367,
-1.5006979703903198,
1.6629183292388916
] |
['Hypoxia-inducible factor (HIF)-1alpha levels in invasive breast carcinoma have been shown to be an adverse prognostic indicator. Cellular HIF-1alpha activity is regulated by factor-inhibiting hypoxia-inducible factor 1 (FIH-1). In hypoxia, FIH-1 hydroxylation of Asn803 within the C-terminal transactivation domain does not occur and HIF-1alpha forms a fully active transcriptional complex. The present study investigates the role of FIH-1 in invasive breast carcinoma and its correlation with hypoxia.', 'Microarrayed tissue cores from 295 invasive carcinomas were stained for FIH-1, for HIF-1alpha and for carbonic anhydrase 9. FIH-1 expression was correlated with standard clinicopathological parameters and with the expression of the surrogate hypoxic markers HIF-1alpha and carbonic anhydrase 9.', 'FIH-1 was positive in 239/295 (81%) tumours, 42/295 (14%) exclusively in the nucleus and 54/295 (18%) exclusively in the cytoplasm. Exclusive nuclear FIH-1 expression was significantly inversely associated with tumour grade (P = 0.02) and risk of recurrence (P = 0.04), whereas exclusive cytoplasmic FIH-1 was significantly positively associated with tumour grade (P = 0.004) and carbonic anhydrase 9 expression (P = 0.02). Patients with tumours that excluded FIH-1 from the nucleus had a significantly shorter survival compared with those with exclusive nuclear expression (P = 0.02). Cytoplasmic FIH-1 expression was also an independent poor prognostic factor for disease-free survival.'] Is cytoplasmic location of factor-inhibiting hypoxia-inducible factor associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer? | qiaojin/PubMedQA | 2 | [
-2.072517156600952,
-1.5198068618774414,
2.5491456985473633
] |
['The use of punctal plugs in the treatment of dry eyes is well established. Anophthalmic patients have less tears in the anophthalmic socket in comparison to their normal side, due to an absent corneal reflex (Lee & Elsie, 1981a,b). Many of those patients complain of dry eye symptoms, even when they are treated with tear replacement therapy. The authors wished to examine whether they could improve their dry socket complaints with punctal plugs.', 'To evaluate the clinical efficacy and tolerability of punctal plug (Smart Plugs) insertion in anophthalmic patients with symptoms of dry eye.', 'Interventional case series. Fifteen anophthalmic patients with dry eye symptoms, a Schirmer test of less than 3 mm and an open lacrimal passage were examined before and after insertion of punctal plugs. The patients were asked for their subjective evaluation of the treatment and were examined to evaluate the change. Schirmer tests were compared. Bacterial cultures were taken at both visits.', 'Schirmer results of less than 3 mm in the anophthalmic socket were obtained in 75% of patients with dry eyes symptoms; 87% of patients in whom punctal plugs were inserted reported an improvement in dry eye sensation. More than half of the patients demonstrated less discharge (p < or = 0.05). Schirmer tests improved from 1.4 mm to 1.9 mm (p < or = 0.05). Patients with a Schirmer outcome of 2 mm or more tended to have less pathogenic bacterial cultures (p = 0.11).'] Does favorable effects of lacrimal plug in patients with an anophthalmic socket? | qiaojin/PubMedQA | 2 | [
-1.4988106489181519,
-1.5091679096221924,
2.0066003799438477
] |
['This study examined whether alpha lipoic acid (ALA), an antioxidant with anti-apoptotic properties, synthesized in mitochondria of endothelial cells, would inhibit intrinsic apoptotic signaling and microvascular endothelial cell hyperpermeability.', 'Rat lung microvascular endothelial cells were transfected with BAK (BH3) peptide (5 microg/mL) or active caspase-3 (5 microg/mL) and were pretreated with ALA (10 and 100 micromol/L). Hyperpermeability was determined using fluorescein isothiocyanate albumin-flux across the cells grown as monolayer. Reactive oxygen species (ROS) formation was determined using 123 dihydrorhodamine and mitochondrial membrane potential using JC-1. Cytochrome c levels and caspase-3 activity were determined using an enzyme-linked immunosorbent assay and a fluorometric assay, respectively.', 'ALA (100 micromol/L) pretreatment attenuated BAK (BH3)-induced hyperpermeability and ROS formation. ALA restored BAK (BH3)-induced collapse in mitochondrial membrane potential and decreased BAK (BH3)-induced cytochrome c release and caspase-3 activity.'] Does alpha lipoic acid attenuate microvascular endothelial cell hyperpermeability by inhibiting the intrinsic apoptotic signaling? | qiaojin/PubMedQA | 2 | [
-2.4592714309692383,
-1.3127901554107666,
2.8124194145202637
] |
['Profiling mRNA levels of 11 informative genes expressed by circulating immune effector cells identifies cardiac allograft recipients at low risk for current moderate-severe acute cellular rejection (ACR).', 'We conducted a nested case-control study of 104 cardiac allograft recipients to investigate the association of transcriptional profiles of blood samples with either a future rejection episode within 12 weeks of a baseline clinical sample or persistent histologic quiescence for the same time period.', 'The transcription profile yielded a score (0 to 40 scale) of 27.4 +/- 6.3 for future rejectors (n = 39) and 23.9 +/- 7.1 for controls (n = 65) (p = 0.01). In patients who were <or=180 days post-transplant, the gene expression score was 28.4 +/- 4.9 for rejectors (n = 28) and 22.4 +/- 7.5 for controls (n = 48) (p < 0.001). In this period, no samples from patients who went on to reject within 12 weeks had gene expression scores of <20. Differential expression of the gene IL1R2 was significantly associated with future events. Of 33 additional genes profiled, 5 supported corticosteroid-sensitive constituents (IL1R2 and FLT3), whereas 6 supported T-cell activation (PDCD1).'] Are transcriptional signals of T-cell and corticosteroid-sensitive genes associated with future acute cellular rejection in cardiac allografts? | qiaojin/PubMedQA | 2 | [
-1.824410319328308,
-1.4433282613754272,
2.2887203693389893
] |
['Adenovirus serotype 5 has remained the pre-eminent vector in pre-clinical gene therapy applications in cardiac transplantation. Concerns over the potential effects of adenoviral vectors on the later development of cardiac allograft vasculopathy (CAV) are addressed in this study.', 'Hearts (n = 22) harvested from Brown Norway rats were perfused ex vivo with either University of Wisconsin (UW) solution with no virus, Ad-CMV-LacZ or Ad-CMV-Null. Donor hearts were transplanted heterotopically into the abdomen of Lewis rats. All recipients received cyclosporine for the duration of the experiment. Transplanted hearts were recovered for analysis at 120 days. Sections of the heart were stained with elastic-van Gieson stain for morphometric analysis of the vessels to ascertain the degree of vascular luminal occlusion. Hematoxylin-eosin staining facilitated diagnosis of chronic rejection.', 'Seventy-seven percent of transplanted hearts showed signs of chronic rejection with no difference in the proportion of animals between groups (p = 0.797). No difference was noted in the degree of vascular luminal occlusion between the Ad-Null (0.57 +/- 0.22), Ad-LacZ (0.62 +/- 0.19) and UW (0.47 +/- 0.29) groups (p = 0.653).'] Does recombinant adenoviral gene transfer affect cardiac allograft vasculopathy? | qiaojin/PubMedQA | 2 | [
-2.120839834213257,
-1.3726317882537842,
2.576636791229248
] |
['Gene expression profiling distinguishes the absence or presence of moderate to severe grades of acute cellular rejection in cardiac allograft recipients using a 20-gene classifier. We explored the hypothesis that the rejection classifier also differentiates various forms of mild rejection and we performed sub-analyses based on time post-transplant and confirmatory pathology interpretations.', 'A post hoc analysis of 265 CARGO study patients and 714 clinical encounters focused on the correlation of rejection classifier-derived gene expression (GE) scores for blood samples accompanying endomyocardial biopsies. Biopsy grades assigned by a study center pathologist (center) were re-interpreted by three pathologists (panel) in a blinded manner.', "Mean GE scores not only differentiated Grades >or=3A from Grade 0 (p < 0.00001, center or panel), but also from Grades 1A or 2 (p < 0.05, center or panel), based on mild rejection sub-groups defined by the ISHLT 1990 grading system. In contrast, mean GE scores for Grades 1B and >or=3A were indistinguishable, using either center or panel interpretation. Sub-group analyses of encounters from 2 to 6 months or >6 months post-transplant showed similar results for the classifier's ability to discriminate moderate to severe rejection from Grades 1A and 2 mild rejection, but indistinguishable mean GE scores for Grades >or=3A and the Grade 1B sub-group. Of the classifier's 11 informative genes, expression of MIR and WDR40 showed statistically significant increases for both Grade 1B and Grade >or=3A rejection, while expression of PDCD1 or SEMA7A showed similar directional patterns without achieving statistical significance."] Does gene expression profiling distinguish a molecular signature for grade 1B mild acute cellular rejection in cardiac allograft recipients? | qiaojin/PubMedQA | 2 | [
-2.072882890701294,
-1.4170385599136353,
2.539327621459961
] |
['The purpose of this study was to identify which characteristics of a multidimensional sequence containing motor, spatial, and temporal elements would be most salient for motor sequence learning and whether age might differentially affect this learning.', 'Younger (n=11, mean age=26.0 years), middle-aged (n=13, mean age=50.7 years), and older (n=11, mean age=77.5 years) adults who were neurologically intact participated in the study.', 'Participants practiced a sequencing task with repeated motor, spatial, and temporal dimensions for 2 days; on a separate third day, participants completed retention and interference tests designed to assess sequence learning and which elements of the sequence were learned. The mean median response time for each block of responses was used to assess motor sequence learning.', 'Younger and middle-aged adults demonstrated sequence-specific motor learning at retention testing via faster response times for repeated sequences than random sequences; both of these groups showed interference for the motor dimension. In contrast, older adults demonstrated nonspecific learning (ie, similar improvements in response time for both random and repeated sequences). These findings were shown by a lack of difference between random and repeated sequence performance in the older adult group both at retention testing and during interference tests.'] Is multidimensional motor sequence learning impaired in older but not younger or middle-aged adults? | qiaojin/PubMedQA | 2 | [
-2.181041955947876,
-0.012676345184445381,
1.3038208484649658
] |
['In addition to the regulation of blood pressure, alpha2- and beta-adrenoceptor (AR) subtypes play an important role in the modulation of noradrenergic neurotransmission in the human CNS and PNS. Several studies suggest that the alpha2-AR responsiveness in cells and tissues after chronic epinephrine (EPI) or norepinephrine (NE) exposure may vary, depending on the beta-AR activity present there. Recently, we reported that in BE(2)-C human neuroblastoma cells (endogenously expressing alpha2A- and beta2-AR), chronic EPI treatment (300 nM) produced a dramatic beta-adrenoceptor-dependent desensitization of the alpha2A-AR response. The aim of this study is to determine if stable addition of a beta2-AR to a second neuroblastoma cell line (SH-SY5Y), that normally expresses only alpha2A-ARs that are not sensitive to 300 nM EPI exposure, would suddenly render alpha2A-ARs in that cell line sensitive to treatment with the same EPI concentration.', 'These studies employed RT-PCR, receptor binding and inhibition of cAMP accumulation to confirm alpha2-AR subtype expression. Stable clones of SH-SY5Y cells transfected to stably express functional beta2-ARs (SHbeta2AR4) were selected to compare sensitivity of alpha2-AR to EPI in the presence or absence of beta2-ARs.', 'A series of molecular, biochemical and pharmacological studies indicated that the difference between the cell lines could not be attributed to alpha2-AR heterogeneity. We now report that after transfection of functional beta2-AR into SH-SY5Y cells (SHbeta2AR4), chronic treatment with modest levels of EPI desensitizes the alpha2A-AR. This effect results from a beta2-AR dependent down-regulation of native alpha2A-ARs by EPI accompanied by enhanced translocation of GRK2 and GRK3 to the membrane (required for GRK-mediated phosphorylation of agonist-occupied receptors).'] Does the presence of beta2-adrenoceptors sensitize alpha2A-adrenoceptors to desensitization after chronic epinephrine treatment? | qiaojin/PubMedQA | 2 | [
-2.4218852519989014,
-1.2981102466583252,
2.7809674739837646
] |
['Hepatic steatosis is a major risk factor in ischemia-reperfusion (I/R). Adiponectin acts as an antiobesity and anti-inflammatory hormone. Adiponectin activates peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a transcription factor that regulates inflammation in liver disease. Ischemic preconditioning (PC) based on brief periods of I/R protects steatotic livers against subsequent sustained I/R injury, but just how this is achieved is poorly understood. This study explains the role of PPAR-alpha and adiponectin in the vulnerability shown by steatotic livers to I/R and the benefits of PC in this situation. PPAR-alpha and adiponectin levels in nonsteatotic livers undergoing I/R were similar to those found in the sham group. However, reduced PPAR-alpha and increased adiponectin levels, particularly the high molecular weight isoform, were observed in steatotic livers as a consequence of I/R. Our results suggest that mitogen-activated protein kinases (MAPKs) may be positive regulators of adiponectin accumulation in steatotic livers. The addition of adiponectin small interfering RNA (siRNA) before I/R protected steatotic livers against oxidative stress and hepatic injury. The induction of PC before I/R increased PPAR-alpha and reduced adiponectin levels in steatotic livers. PC, which increased PPAR-alpha, as well as PPAR-alpha agonist pretreatment reduced MAPK expression, adiponectin, oxidative stress, and hepatic injury that follows I/R. In addition, the administration of a PPAR-alpha antagonist in preconditioned steatotic livers eliminated the beneficial effects of PC on MAPKs, adiponectin, oxidative stress, and hepatic injury.'] Does activation of peroxisome proliferator-activated receptor-alpha inhibit the injurious effects of adiponectin in rat steatotic liver undergoing ischemia-reperfusion? | qiaojin/PubMedQA | 2 | [
-2.338620901107788,
-1.349373698234558,
2.7253713607788086
] |
['A retrospective study of the postoperative results and patient satisfaction after evisceration with a split-sclera technique.', 'The medical records of 60 patients were reviewed. All patients were operated by evisceration with a split-sclera technique and placement of an orbital implant. The patients were operated by the same surgeon between 1995 and 2003. Multiple-choice questionnaires were sent to the patients, and the patients were also offered a clinical examination.', "Extrusion/exposure of the implant was seen in 3/62 (4.8%) orbits. Migration of the implant was seen in one patient. At the time of the study, 45/60 patients were still alive, 32 of these answered the questionnaire. In a question about the patient's psychological well-being after the operation, 9/32 (28%) answered that they had felt depressed; four of these had had a recent trauma to the eye resulting in the evisceration; 25/32 (78%) patients were pleased or very pleased with the operation. A clinical examination was performed in 31 patients. The motility of the prosthesis and implant was measured and found to be rather poor (mean between 2.5 to 4.1 mm in each direction); however, most patients judged their motility to be good or excellent."] Does patient satisfaction and result after evisceration with a split-sclera technique? | qiaojin/PubMedQA | 2 | [
-1.4309300184249878,
-0.825023353099823,
1.2850863933563232
] |
['c-MYC amplification and overexpression has been correlated with progression and chemotherapy resistance in lung cancer. AVI-4126, a neutral antisense phosphorodiamidate morpholino oligomer (PMO) has been identified to specifically inhibit c-MYC expression in multiple disease models and identified in Phase I clinical studies to be safe and bioavailable in solid tumors. The present study evaluates AVI-4126 on the development of lung metastasis in the LLC1 syngeneic murine tumor model. Further, this is the first study to show in vivo mis-splicing of c-MYC post-AVI-4126 treatment.', 'Subcutaneous administration of AVI-4126 at local tumor site (50 microg/day) for 3 cycles of 5 days a week starting day 1 post-tumor cell implantation showed significantly decreased tumor burden, number of tumorlets formed in the lung in comparison to saline or control PMO treatment groups, although no significant reduction of the subcutaneous tumor was observed. AVI-4126 treated lung had markedly reduced mitotic activity but higher rate of apoptosis compared to the controls. HPLC-based analysis of tumor and lung lysates confirmed the presence of intact PMO. In addition to decrease in c-MYC expression, a moderate reduction in the levels of MMP-9 mRNA, a pro-angiogenic extracellular matrix protein postulated to be involved in extravasation of cells from the localized tumor or implantation into the distant metastatic site was observed in the LLC1 tumor tissue of AVI-4126 treated animals.'] Does c-MYC antisense phosphosphorodiamidate morpholino oligomer inhibit lung metastasis in a murine tumor model? | qiaojin/PubMedQA | 2 | [
-2.326131582260132,
-1.4456895589828491,
2.803415298461914
] |
['The corn smut fungus Ustilago maydis is a well-established model system for molecular phytopathology. In addition, it recently became evident that U. maydis and humans share proteins and cellular processes that are not found in the standard fungal model Saccharomyces cerevisiae. This prompted us to do a comparative analysis of the predicted proteome of U. maydis, S. cerevisiae and humans.', 'At a cut off at 20% identity over protein length, all three organisms share 1738 proteins, whereas both fungi share only 541 conserved proteins. Despite the evolutionary distance between U. maydis and humans, 777 proteins were shared. When applying a more stringent criterion (> or = 20% identity with a homologue in one organism over at least 50 amino acids and > or = 10% less in the other organism), we found 681 proteins for the comparison of U. maydis and humans, whereas the both fungi share only 622 fungal specific proteins. Finally, we found that S. cerevisiae and humans shared 312 proteins. In the U. maydis to H. sapiens homology set 454 proteins are functionally classified and 42 proteins are related to serious human diseases. However, a large portion of 222 proteins are of unknown function.'] Do the fungus Ustilago maydis and humans share disease-related proteins that are not found in Saccharomyces cerevisiae? | qiaojin/PubMedQA | 2 | [
-1.3285726308822632,
-0.24987107515335083,
0.7248175144195557
] |
['NOD2 is an innate immune receptor for the bacterial cell wall component muramyl-dipeptide. Mutations in the leucine-rich repeat region of NOD2, which lead to an impaired recognition of muramyl-dipeptide, have been associated with Crohn disease, a human chronic inflammatory bowel disease. Tissue specific constitutive and inducible expression patterns of NOD2 have been described that result from complex regulatory events for which the molecular mechanisms are not yet fully understood.', "We have identified two novel exons of the NOD2 gene (designated exon 1a and 1b), which are spliced to the canonical exon 2 and constitute the 5' untranslated region of two alternative transcript isoforms (i.e. exon 1a/1b/2 and exon 1a/2). The two novel transcripts are abundantly expressed and seem to comprise the majority of NOD2 transcripts under physiological conditions. We confirm the expression of the previously known canonical first exon (designated exon 1c) of the gene in unstimulated mononuclear cells. The inclusion of the second alternative exon 1b, which harbours three short upstream open reading frames (uORFs), is downregulated upon stimulation with TNF-alpha or under pro-inflammatory conditions in the inflamed intestinal mucosa in vivo. Using the different 5' UTR splice forms fused to a firefly luciferase (LUC) reporter we demonstrate a rapamycin-sensitive inhibitory effect of the uORFs on translation efficacy."] Does functional characterization of two novel 5 ' untranslated exons reveal a complex regulation of NOD2 protein expression? | qiaojin/PubMedQA | 2 | [
-2.46138596534729,
-1.1703211069107056,
2.639601707458496
] |
['The extraembryonic tissues, visceral endoderm (VE) and extraembryonic ectoderm (ExE) are known to be important for the induction of primordial germ cells (PGCs) in mice via activation of the bone morphogenetic protein (BMP) signalling pathway. We investigated whether the VE and ExE have a direct role in the specification of PGCs, or in an earlier event, namely the induction of the PGC precursors in the proximal posterior epiblast cells.', 'We cultured embryonic day (E) 5.75 to E7.0 mouse embryos in an explant-assay with or without extraembryonic tissues. The reconstituted pieces of embryonic and extraembryonic tissues were assessed for the formation of both PGC precursors and specified PGCs. For this, Blimp1:gfp and Stella:gfp transgenic mouse lines were used to distinguish between PGC precursors and specified PGC, respectively. We observed that the VE regulates formation of an appropriate number of PGC precursors between E6.25-E7.25, but it is not essential for the subsequent specification of PGCs from the precursor cells. Furthermore, we show that the ExE has a different role from that of the VE, which is to restrict localization of PGC precursors to the posterior part of the embryo.'] Do proximal visceral endoderm and extraembryonic ectoderm regulate the formation of primordial germ cell precursors? | qiaojin/PubMedQA | 2 | [
-2.5216758251190186,
-1.0390779972076416,
2.683117151260376
] |
['In previous studies, microarray analysis of livers from mice fed diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridine decarboxylate (DDC) for 10 weeks followed by 1 month of drug withdrawal (drug-primed mice) and then 7 days of drug refeeding showed an increase in the expression of numerous genes referred to here as the molecular cellular memory. This memory predisposes the liver to Mallory Denk body formation in response to drug refeeding. In the current study, drug-primed mice were refed DDC with or without a daily dose of S-adenosylmethionine (SAMe; 4 g/kg of body weight). The livers were studied for evidence of oxidative stress and changes in gene expression with microarray analysis. SAMe prevented Mallory Denk body formation in vivo. The molecular cellular memory induced by DDC refeeding lasted for 4 months after drug withdrawal and was not manifest when SAMe was added to the diet in the in vivo experiment. Liver cells from drug-primed mice spontaneously formed Mallory Denk bodies in primary tissue cultures. SAMe prevented Mallory Denk bodies when it was added to the culture medium.'] Does s-adenosylmethionine prevent Mallory Denk body formation in drug-primed mice by inhibiting the epigenetic memory? | qiaojin/PubMedQA | 2 | [
-2.377135992050171,
-1.0518629550933838,
2.483306646347046
] |
['Adiponectin limits the development of liver fibrosis and activates adenosine monophosphate-activated protein kinase (AMPK). AMPK is a sensor of the cellular energy status, but its possible modulation of the fibrogenic properties of hepatic stellate cells (HSCs) has not been established. In this study, we investigated the role of AMPK activation in the biology of activated human HSCs. A time-dependent activation of AMPK was observed in response to a number of stimuli, including globular adiponectin, 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), or metformin. All these compounds significantly inhibited platelet-derived growth factor (PDGF)-stimulated proliferation and migration of human HSCs and reduced the secretion of monocyte chemoattractant protein-1. In addition, AICAR limited the secretion of type I procollagen. Knockdown of AMPK by gene silencing increased the mitogenic effects of PDGF, confirming the negative modulation exerted by this pathway on HSCs. AMPK activation did not reduce PDGF-dependent activation of extracellular signal-regulated kinase (ERK) or Akt at early time points, whereas a marked inhibition was observed 24 hours after addition of PDGF, reflecting a block in cell cycle progression. In contrast, AICAR blocked short-term phosphorylation of ribosomal S6 kinase (p70(S6K)) and 4E binding protein-1 (4EBP1), 2 downstream effectors of the mammalian target of rapamycin (mTOR) pathway, by PDGF. The ability of interleukin-a (IL-1) to activate nuclear factor kappa B (NF-kappaB) was also reduced by AICAR.'] Does adenosine monophosphate-activated protein kinase modulate the activated phenotype of hepatic stellate cells? | qiaojin/PubMedQA | 2 | [
-2.381805658340454,
-1.288496732711792,
2.681678056716919
] |
['Gene therapy using adenovirus vectors may induce acute liver injury. Tissue injury induced by an adenovirus is likely associated with elevated expression of the Cys-X3-Cys chemokine ligand 1 (CX(3)CL1)/fractalkine (FKN) protein at the site of inflammation. However, the extent to which the actions of FKN contribute to liver injury remains unclear. We induced acute liver injury in mice by a hydrodynamics-based injection of adenovirus vector, which was confirmed to depend on the presence of natural killer (NK) cells and NK-dependent interferon-gamma (IFN-gamma). When the transferred adenovirus vector was inserted with the FKN gene, the severity of liver injury increased with much more Cys-X3-Cys chemokine receptor 1 (CX(3)CR1)-positive NK cell recruitment into the liver because of exogenous overproduction of FKN protein. Moreover, when production of endogenous FKN protein was silenced by inserting FKN-small interfering RNA into the adenovirus vector or was neutralized by an FKN-specific antibody, the adenovirus-induced acute severe liver injury was notably prevented with much lower hepatic NK cell infiltration and a significant reduction in the serum levels of IFN-gamma.'] Does therapeutic RNA silencing of Cys-X3-Cys chemokine ligand 1 gene prevent mice from adenovirus vector-induced acute liver injury? | qiaojin/PubMedQA | 2 | [
-2.4926390647888184,
-1.2634243965148926,
2.8229119777679443
] |
['Cardiac amyloidosis (CA) is the most problematic cause of heart failure because medical treatment strategies are not well tolerated. Due to its high mortality, identification of patients at high risk is crucial for treatment strategies such as heart transplantation prior to chemotherapy for amyloid disease.', 'Left ventricular wall thickness (LVT) progression was retrospectively compared with electrocardiographic and echocardiographic parameters for risk prediction in 39 patients with histologically proven cardiac amyloidosis.', 'Seventeen deaths occurred, equivalent to 1- and 3-year survival rates of 62.1% and 55.0%, respectively. LVT progression in deceased patients was 2.02 +/- 0.85 mm/month compared with 0.19 +/- 0.03 mm/month in survivors (p < 0.001). Autologous stem-cell transplantation (n = 22, or 54%) reduced LVT progression as compared with not receiving stem cells (0.21 +/- 0.04 mm/month vs 1.45 +/- 0.57 mm/month, p < 0.005). LVT progression correlated with maximal LVT and absolute LVT increase. Progression of LVT was more rapid in patients with impaired LV ejection fraction (LVEF) than preserved LVEF (2.16 +/- 1.04 mm/month vs 0.30 +/- 0.13 mm/month, p < 0.001). LVT closely correlated with survival, whereas initial, maximum or absolute increase in LVT did not. Further predictors of survival were LVEF, autologous stem-cell transplantation and low voltage, but not diastolic dysfunction. Multivariate analysis identified LVT progression as the strongest independent parameter for survival.'] Does rapid progression of left ventricular wall thickness predict mortality in cardiac light-chain amyloidosis? | qiaojin/PubMedQA | 2 | [
-1.3454182147979736,
-1.6555416584014893,
1.9769634008407593
] |
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