tbuckley/cabot-search huggingface dataset:
Abstract LB-310: hnRNPM drives cell-state specific alternative splicing during EMT through combinatorial regulation with other RNA binding proteins
Authors: Samuel E. Harvey, Chonghui Cheng
Journal: Cancer Research (2018)

Abstract The epithelial-mesenchymal transition (EMT) is a fundamental developmental program that is abnormally activated in cancer cells, resulting in therapeutic resistance and metastasis. Dramatic changes in alternative splicing occur during EMT, however the master regulators of this critical regulatory layer are poorly understood. We previously identified the ubiquitously expressed RNA binding protein hnRNPM as a causal driver of EMT and breast cancer metastasis whereby hnRNPM drives alternative exon skipping of the cancer stem cell marker CD44 in a mesenchymal-cell-state restricted manner. However, the scope of hnRNPM-mediated regulation of the EMT post-transcriptional landscape and the mechanisms by which hnRNPM functions in a cell-state specific fashion remain uncertain. By integrating breast epithelial and mesenchymal hnRNPM-depletion RNA-sequencing datasets coupled with individual nucleotide crosslinking and immunoprecipitation of hnRNPM, we identified cell-state specific hnRNPM target RNAs undergoing alternative splicing. hnRNPM cell-state specific targets enrich for distinct gene ontology terms where epithelial targets are enriched in genes critical for the cell cycle while mesenchymal targets cluster in pathways associated with cell migration and EMT. Strikingly, we found hnRNPM regulates splicing to oppose EMT in the epithelial state but then promotes EMT in the mesenchymal state. This unexpected regulatory switch where hnRNPM maintains the cell-cycle in epithelial cells while driving cell migration and metastasis in mesenchymal cells suggests a dual role for hnRNPM in sustaining epithelial and mesenchymal-type breast cancers. Motif analysis and regulon overlap of cell-state specific hnRNPM targets identify ESRP1 and other RNA binding proteins as putative mediators of hnRNPM cell-state specific activity during EMT. Together, this study extends our functional understanding of how hnRNPM regulates the EMT post-transcriptional program and functions in different subtypes of breast cancer. Citation Format: Samuel E. Harvey, Chonghui Cheng. hnRNPM drives cell-state specific alternative splicing during EMT through combinatorial regulation with other RNA binding proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-310.
Accurate Assessment of Patient Effective Radiation Dose and Associated Detriment Risk From Radiofrequency Catheter Ablation Procedures
Authors: KostasPerisinakis, JohnDamilakis, NicholasTheocharopoulos, EmmanouelManios, PanayiotisVardas, NicholasGourtsoyiannis
Journal: Circulation (2001)

Background—Radiofrequency (RF) cardiac catheter ablation procedures may require extended fluoroscopic exposure resulting in elevated radiation risk. The aim of the present study was to accurately establish RF ablation radiation risk levels and to provide means for accurate patient risk estimation from studies performed in any electrophysiology laboratory. Methods and Results—Fluoroscopy required during cardiac ablation was classified into 4 types identified by beam orientation and irradiated tissue: (1) posteroanterior exposure during catheter advancing from the groin to the heart, (2) posteroanterior heart exposure, (3) left anterior oblique heart exposure, and (4) right anterior oblique heart exposure. The duration of each exposure was monitored in 24 patients undergoing RF cardiac ablation. Dose per minute of fluoroscopy was measured at 15 organs/tissues for each projection with the use of anthropomorphic phantom and thermoluminescence dosimetry. The effective dose rate was 219, 144, 136, and 112 μGy/m...
Abstract 12630: Implementation of Modified Early Warning Score (MEWS) Reduces in Hospital Mortality and Hospital Length of Stay
Authors: KevinStiver, NandiniSharma, StanleyLemeshow, NkechinyereIjioma, SheilaChucta, RuchikaHusa
Journal: Circulation (2014)

Background: Most in-hospital adverse events are often preceded by warning signs of clinical instability. These early signs typically involve subtle changes in multiple parameters rather than a dramatic change in an isolated value and are frequently overlooked by healthcare providers. MEWS is a weighted score based on 5 basic bedside parameters: systolic blood pressure, heart rate, respiratory rate, temperature, and level of consciousness. It has been developed in an attempt to assist healthcare providers with the early detection of patients with potential for clinical deterioration. Objective: To examine the impact of proactive MEWS based rounding and intervention on in-hospital mortality and hospital length of stay (LOS). Methods: This study was conducted in three urban university hospitals following implementation of a MEWS-based algorithm for early intervention in March 2013. Inpatient nurses were trained to observe patients MEWS at four hour intervals. For MEWS of 4, nurses were encouraged to call the...
Abstract 119: Cardiac Transcription Factor EB Sumoylation Deficiency Exacerbates Age-associated Reduction In Autophagy
Authors: HengMa, LeZhang, LuYu, YanLi
Journal: Circulation Research (2014)

Background: Aging-dependent decline of autophagy contributes to cardiac dysfunction and ischemic intolerance. Transcription factor EB (TFEB) is a master transcriptional regulator of the autophagy-lysosome pathway. The present study aimed to characterize the role of TFEB in the autophagic decrease with aging. Methods and Results: We analyzed age-associated autophagic changes in male C57BL/6 young (4-6 mo) and aged (22-24 mo) mice. The results demonstrated that TFEB expressed predominantly as a SUMOylated form in cardiomyocyte nuclei and this SUMOylation of TFEB declined in aged heart associated with autophagy reduction. Interestingly, SUMOylation of TFEB was unaffected by rapamycin. Rapamycin induced translocation of TFEB into nucleus but lower level of nuclear TFEB in aged hearts than that seen in young hearts (P<0.05). SUMO1 downregulation by adeno-associated-virus-mediated small hairpin RNA (rAAV9-shSUMO1) significantly reduced nuclear TFEB levels (P<0.05), depressed cardiac autophagy and accelerated ca...
Prevalence of Chronic Obstructive Pulmonary Disease in China
Authors: Nanshan Zhong, Chen Wang, Wanzhen Yao, Ping Chen, Jian Kang, Shaoguang Huang, Baoyuan Chen, Changzheng Wang, Diantao Ni, Yumin Zhou, Shengming Liu, Xiaoping Wang, Dali Wang, Jiachun Lu, Jingping Zheng, Pixin Ran
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The prevalence of chronic obstructive pulmonary disease (COPD) in China is largely unknown.To obtain the COPD prevalence in China through a large-population, spirometry-based, cross-sectional survey of COPD.Urban and rural population-based cluster samples were randomly selected from seven provinces/cities. All residents 40 years of age or older in the selected clusters were interviewed with a standardized questionnaire revised from the international BOLD (Burden of Obstructive Lung Diseases) study. Spirometry was performed on all eligible participants. Patients with airflow limitation (FEV(1)/FVC < 0.70) were further examined by post-bronchodilator spirometry, chest radiograph, and electrocardiogram. Post-bronchodilator FEV(1)/FVC of less than 70% was defined as the diagnostic criterion of COPD.Among 25,627 sampling subjects, 20,245 participants completed the questionnaire and spirometry (response rate, 79.0%). The overall prevalence of COPD was 8.2% (men, 12.4%; women, 5.1%). The prevalence of COPD was significantly higher in rural residents, elderly patients, smokers, in those with lower body mass index, less education, and poor ventilation in the kitchen, in those who were exposed to occupational dusts or biomass fuels, and in those with pulmonary problems in childhood and family history of pulmonary diseases. Among the patients who had COPD, 35.3% were asymptomatic; only 35.1% reported lifetime diagnosis of bronchitis, emphysema, or other COPD; and only 6.5% have been tested with spirometry.COPD is prevalent in individuals 40 years of age or older in China.
Upregulation of Soluble Vascular Endothelial Growth Factor Receptor 1 Contributes to Angiogenesis Defects in the Placenta of α2B-Adrenoceptor–Deficient Mice
Authors: VerenaMuthig, RalfGilsbach, MiriamHaubold, MelaniePhilipp, TomiIvacevic, ManfredGessler, LutzHein
Journal: Circulation Research (2007)

α2-adrenoceptors are essential presynaptic regulators of norepinephrine release from sympathetic nerves. Previous studies in mice with targeted deletions in the 3 α2-adrenoceptor genes have indicated that these receptors are essential for embryonic development. In the present study, we searched for the α2-adrenoceptor subtype(s) involved in placental development and its molecular mechanism using mice carrying targeted deletions in α2-adrenoceptor genes. Congenic α2B-adrenoceptor–deficient mice (Adra2b−/−) developed a defect in fetal and maternal vessel formation in the placenta labyrinth at embryonic day 10.5. This defect was accompanied by reduced endothelial cell proliferation and decreased extracellular signal-regulated kinase 1/2 phosphorylation levels in Adra2b−/− as compared with Adra2b+/+ placentae. Microarray analysis of wild-type and mutant placentae (maternal genotype Adra2b+/−) revealed 179 genes, which were significantly up- or downregulated >1.5-fold in α2B-deficient placentae. The type 1 rec...
Abstract 12803: Long-term Outcomes After Surgical Pulmonary Arterioplasty: Analysis of Re-intervention Rates and Patient-specific Risk Factors
Authors: Nicole M Cresalia, Aimee K Armstrong, Jennifer C Hirsch-Romano, Mark Norris, Sunkyung Yu, Albert P Rocchini, Jeffrey D Zampi
Journal: Circulation (2015)

Introduction: Branch pulmonary artery stenosis (PAS) is common in congenital heart disease. Surgical patch arterioplasty is a conventional therapy, however, limited data exist on long-term outcomes. Hypothesis: We examined the incidence of and risk factors for re-intervention after surgical arterioplasty for PAS. We assessed the hypothesis that certain characteristics are associated with increased need for re-intervention. Methods: This retrospective cohort study included patients with two-ventricle physiology who underwent patch arterioplasty for PAS at a single high-volume center from 2004-2013. Freedom from surgical or percutaneous re-intervention for recurrent PAS was estimated. Univariate and multivariable Cox regression were performed to determine risk factors for re-intervention. Results: Among 116 patients undergoing patch arterioplasty at a median age of 1.2 years, hospital discharge survival was 95%. Of the survivors, 97 (88%) had a median follow-up of 3.6 years (range 15 days to 11 years). PAS re-intervention occurred in 31/97 (32%) at a median time to re-intervention of 1.6 years (range 7 days to 9.3 years). Freedom from re-intervention is shown in Figure 1. In univariate analysis, age less than 30 days at time of arterioplasty, congenital PAS (versus acquired), and bilateral PAS were significantly associated with re-intervention. In multivariate analysis, neonatal age (adjusted hazard ratio [AHR 4.4], p=0.004) and bilateral PAS (AHR 3.3, p=0.003) remained independently associated with re-intervention. Conclusions: We present the largest cohort study with the longest follow-up time evaluating outcomes after surgical pulmonary arterioplasty for PAS to date. Re-intervention for recurrent PAS following patch arterioplasty is common. In conclusion, patients at highest risk for re-intervention, such as neonates and patients with bilateral PAS, may benefit from frequent monitoring or novel approaches to repair.
Neurological Symptoms in US Government Personnel in Cuba
Authors: Jon Stone, Stoyan Popkirov, Alan J. Carson
Journal: JAMA (2018)

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Abstract 4166: Hair follicles as a minimally invasive resource of epithelial cells in mouse studies of ionizing radiation
Authors: Hanus Slavik, Martin Mistrik, Pavlina Duskova, Tomas Furst, Josef Srovnal, Marian Hajduch
Journal: Cancer Research (2018)

Abstract Introduction Hair follicles are relatively accessible as a biological material allowing repeatable and minimally invasive sampling of predominantly epithelial cells for biomarker studies. The utility of such a material is promising for example in murine experiments, where repeated sampling would require multiple biopsies. As a proof of concept, the ionizing irradiation response in murine follicular cells was chosen as a suitable and common external factor for studying cellular senescence, apoptotic pathways, neoplastic transformation, tumor development and response to cancer therapy. Methods and material Hair follicles were collected from 30 healthy C57Bl/6 mice into the RNA later for RT-qPCR and into the 4% formaldehyde for immunofluorescence with specially developed vacuum collector. Follicles were collected before X-ray irradiation and 30 min, 3 h, 6 h and 24 h after irradiation. Each group of 10 mice obtained one dose (2, 6 or 10 Gy). RNA was extracted from the samples using miRNeasy mini kit (Qiagen) and two-tube RT-qPCR was performed for SESN1, p21, MDM2 and HPRT gene expression analysis. Immunofluorescence was done for γ-H2AX and quantitatively evaluated by in-house developed software routine. Results Total RNA extracted from one pluck was usually less than 35 ng but it had good quality (RIN ≥ 7.5) even after the storage at room temperature. We determined p21 as the best marker for the uniformity and specific dynamic respond for each of the doses. The strongest responds were found after 30 min with 2 Gy (average fold change FCav = 3,24). In case of higher doses, longer remaining p21 overexpression was detected. For instance, FCav = 2,29 even after 24h at dose 10 Gy. Our data were corroborated by immunofluorescence for direct marker of ionizing radiation induced DNA damage γ-H2AX, where 1-3 hair follicles proved to be efficient for microscopic analyses. Strong γ-H2AX signal was detectable within 3h after irradiation followed by rapid decrease within the next 24h. Conclusion Collected murine hair follicles proved to be a feasible alternative material for molecular analyses which in logistic aspects outreaches phlebotomies or skin biopsies because of repeatable, minimally invasive and accurate sampling and non-laborious processing. Dedication This work was financially supported by grants IGA_LF_2017_013, EATRIS-CZ, TACR TE02000058 and VG20102014001. Citation Format: Hanus Slavik, Martin Mistrik, Pavlina Duskova, Tomas Furst, Josef Srovnal, Marian Hajduch. Hair follicles as a minimally invasive resource of epithelial cells in mouse studies of ionizing radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4166.
Nutrition and oral health in sport: time for action
Authors: Ian Needleman, Paul Ashley, Tom Fairbrother, Peter Fine, Julie Gallagher, Daniel Kings, Ronald John Maughan, Anna Katarina Melin, Michael Naylor
Journal: British Journal of Sports Medicine (2018)

Elite athletes have poor oral health, common negative self-reported performance effects and a lifelong burden for disease management.1–3 One central determinant of oral health is nutrition and in particular the consumption of dietary sugars, acidic food and drinks and eating behaviours. However, nutrition is also clearly of major importance in managing and improving athlete performance. Therefore, this call to action is to recommend strategies to prevent or mitigate the risk from nutrition to the short-term health and performance of athletes and to the long-term oral health of all active individuals. The target audience includes athletes, health professionals (nutritionists and dieticians, sport and exercise medicine practitioners, dental professionals), scientists in related fields, sport policy organisations and industry.

Given that the mechanisms by which carbohydrate-containing or acidic supplements can affect oral health are well established, it is important to develop mitigation strategies to reduce the risk of possible adverse oral effects while maintaining the performance benefits. Based on best evidence for effectiveness,4 …
Erythropoiesis and chronic kidney disease–related anemia: From physiology to new therapeutic advancements
Authors: Valeria Cernaro, Giuseppe Coppolino, Luca Visconti, Laura Rivoli, Antonio Lacquaniti, Domenico Santoro, Antoine Buemi, Saverio Loddo, Michele Buemi
Journal: Medicinal Research Reviews (2018)

Abstract Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia‐inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in‐depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis‐stimulating agents.
Abstract 5892: miR-217 sensitizes chronic myelogenous leukemia cells to tyrosine kinase inhibitors by targeting pro-oncogenic anterior gradient 2
Authors: Bin Pan, Xiangmin Wang, Kailin Xu, Takayuki Ikezoe
Journal: Cancer Research (2018)

Abstract BCR-ABL1 independent mechanisms had been indicated to mediate drug resistance to tyrosine kinase inhibitors (TKIs) in patients with chronic myelogenous leukemia (CML). In this study, we observed increased level of pro-oncogenic anterior gradient 2 (AGR2) in TKIs-resistant CML cells. Silencing of AGR2 in dasatinib-resistant K562 (K562DR) cells led to restored sensitivity to dasatinib both in vitro and in vivo. Exposure to dasatinib induced up-regulation of AGR2 in K562 cells, which indicated a probable treatment related drug resistance. We further investigated the potential interaction between microRNA (miRNA) and AGR2 in K562DR cells, and found that down-regulation of miR-217 was associated with over-expression of AGR2 in K562DR cells. Luciferase reporter assay identified that miR-217 negatively regulated expression of AGR2 through binding 3'-untranslated region (3'-UTR) of AGR2. Forced expression of miR-217 led to decreased expression of AGR2 as well as compromised TKIs-resistant potential of K562DR cells. Similarly, over-expression of miR-217 re-sensitized K562DR cells to dasatinib-treatment in a murine xenograft transplantation model. Taken together, TKIs-treatment induced drug-resistance is correlated with decrease of miR-217 and up-regulation of AGR2. miR-217/AGR2 interaction might be a potential therapeutic target in treating CML patients with TKIs-resistant. Citation Format: Bin Pan, Xiangmin Wang, Kailin Xu, Takayuki Ikezoe. miR-217 sensitizes chronic myelogenous leukemia cells to tyrosine kinase inhibitors by targeting pro-oncogenic anterior gradient 2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5892.
Prediction of Occult Lymph Node Metastasis Using Tumor-to-Blood Standardized Uptake Ratio and Metabolic Parameters in Clinical N0 Lung Adenocarcinoma
Authors: Ming-li Ouyang, Kun Tang, Man-man Xu, Jie Lin, Tian-cheng Li, Xiang-wu Zheng
Journal: Clinical Nuclear Medicine (2018)

We aimed to investigate whether the tumor-to-blood SUV ratio (SUR) and metabolic parameters of F-FDG uptake could predict occult lymph node metastasis (OLM) in clinically node-negative (cN0) lung adenocarcinoma. We retrospectively reviewed 157 patients with cN0 lung adenocarcinoma who underwent both preoperative F-FDG PET/CT and surgical resection with the systematic lymph node dissection. The SUVmax, SUVmean, MTV, and total lesion glycolysis (TLG) of the primary tumor was measured on the PET/CT workstation. SURmax, SURmean, and TLGsur were derived from each of them divided by descending aorta SUVmean. These PET parameters and clinicopathological variables were analyzed for OLM. In our study, OLM was detected in 31 (19.7%) of 157 patients. Significantly higher values of tumor size, SUVmax, SUVmean, MTV, TLGsuv, SURmax, SURmean, and TLGsur were found in patients with OLM. In receiver operating characteristic curve analysis, the optimal cutoff values of the above parameters were 29.50, 4.38, 2.45, 6.37, 44.13, 5.30, 1.86, and 28.24, respectively. The multivariate analysis showed that TLGsur (odds ratio, 1.024; P = 0.002) was the most potent associated factor for the prediction of OLM in cN0 lung adenocarcinoma. TLGsur showed the most powerful predictive performance than the other PET parameters for the prediction of OLM in cN0 lung adenocarcinoma. This normalized volumetric parameter would be helpful in selection of sublobar resection or aggressive tailored treatments in patients with cN0 lung adenocarcinoma.