tbuckley/cabot-search huggingface dataset:
Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial Infarction
Authors: Ying Xian, Tracy Y. Wang, Lisa A. McCoy, Mark B. Effron, Timothy D. Henry, Richard G. Bach, Marjorie E. Zettler, Brian A. Baker, Gregg C. Fonarow, Eric D. Peterson
Journal: Circulation (2015)

Background— Aspirin is the most widely used antiplatelet drug postmyocardial infarction, yet its optimal maintenance dose after percutaneous coronary intervention with stenting remains uncertain. Methods and Results— We compared outcomes of 10 213 patients with myocardial infarction who underwent percutaneous coronary intervention and were discharged on dual-antiplatelet therapy at 228 US hospitals in the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Major adverse cardiovascular events and bleeding within 6 months postdischarge were compared between high-dose (325 mg) and low-dose aspirin (81 mg) by using regression models with inverse probability-weighted propensity adjustment. Overall, 6387 patients (63%) received high-dose aspirin at discharge. Major adverse cardiovascular events risk was not significantly different between groups (high versus low: unadjusted 8.2% versus 9.2%; adjusted hazard ratio, 0.99; 95% confidence interval, 0.85–1.17). High-dose aspirin use was associated with greater risk of any Bleeding Academic Research Consortium–defined bleeding events (unadjusted 24.2% versus 22.7%; adjusted odds ratio, 1.19; 95% confidence interval, 1.06–1.33), driven mostly by minor Bleeding Academic Research Consortium type 1 or 2 bleeding events not requiring hospitalization (unadjusted 21.4% versus 19.5%; adjusted odds ratio, 1.19; 95% confidence interval, 1.05–1.34). Bleeding events requiring hospitalization were similar by aspirin dosing groups (unadjusted 2.8% versus 3.2%, adjusted odds ratio, 1.22; 95% confidence interval, 0.87–1.70). Similar associations were observed in landmark analyses accounting for aspirin dosing change over time, and across subgroup analyses by age, sex, baseline aspirin use, and type of ADP receptor inhibitor (clopidogrel versus prasugrel/ticagrelor). Conclusions— Among percutaneous coronary intervention–treated patients with myocardial infarction, high-maintenance-dose aspirin was associated with similar rates of major adverse cardiovascular events, but a greater risk of minor bleeding than those discharged on low-dose aspirin.
Abstract 2526: Modulation of metastatic factors in prostate cancer cells by DAX-1 (NR0B1), an androgen-induced orphan nuclear receptor
Authors: Roxxana Valeria Beltran Valencia, Christina Tzagarakis-Foster
Journal: Cancer Research (2018)

Abstract DAX-1, a member of the nuclear hormone receptor superfamily, has a pivotal role in adrenal and gonadal development. However, recent studies have shown that DAX-1 acts as a transcriptional repressor influencing the progression of many types of cancers. We hypothesize that DAX-1 has key roles in regulating metastatic genes during prostate cancer progression. We found that introducing DAX-1 into prostate cancer cells lacking endogenous expression of DAX-1 leads to a decrease in metastatic rates. Consequently, we analyzed DAX-1 transcriptional regulation over different markers associated with metastasis. Since the androgen receptor is a key regulator of prostate cancer progression, we used CRISPR to knockout DAX-1 expression in hormone-dependent prostate cancer cells, allowing us to understand the role DAX-1 has as a negative regulator of metastatic genes after androgen receptor activation. We have shown that treatment of hormone-dependent prostate cancer cells with a non-aromatizable androgen leads to upregulation of DAX-1 expression. Here we use the same mechanism to induce DAX-1 expression and analyze the effects on metastatic markers. Results have shown that DAX-1 is sufficient to decrease the expression of metastatic markers and inhibit metastatic rates in prostate cancer cells. These results further explain some of the intrinsic mechanisms involved in prostate cancer metastasis and could reveal new therapeutic routes in the treatment of metastatic prostate cancer. Citation Format: Roxxana Valeria Beltran Valencia, Christina Tzagarakis-Foster. Modulation of metastatic factors in prostate cancer cells by DAX-1 (NR0B1), an androgen-induced orphan nuclear receptor [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 2526.
Abstract 5253: Dietary fiber intake and lung cancer risk: A pooled analysis of 1.44 million individuals in 10 cohorts
Authors: Jae Jeong Yang, Danxia Yu, Yong-Bing Xiang, William Blot, Kim Robien, Rashmi Sinha, Yikyung Park, Emily White, Yumie Takata, Mattias Johansson, Wei Zheng, Xiao-Ou Shu
Journal: Cancer Research (2018)

Abstract Background: Dietary fiber has been shown to have various health benefits, including anti-inflammation. However, the role of dietary fiber on lung cancer risk has not been well characterized. In this pooled analysis of 10 prospective cohort studies from the US, Europe, and Asia, we evaluated the association between dietary fiber intake and risk of lung cancer and further, potential effect modifications by tobacco smoking, alcohol drinking, and demographic factors (e.g., sex and race/ethnicity). Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated within each cohort using Cox proportional hazard models with adjustment for major lung cancer risk factors. Risk estimates from each cohort were pooled using random-effects meta-analysis. To reduce potential reverse causation due to preclinical dietary changes, all analyses were conducted excluding the first two years of observation. Results: A total of 18,822 incident lung cancer cases were identified among 1,445,850 participants during mean follow-ups of 9.4 years. After adjustment for lung cancer risk factors (i.e., age, total energy, smoking status, smoking pack-years, gender, race/ethnicity, education, obesity status, diabetes, family history of lung cancer, alcohol consumption, physical activity level, menopausal status in women, and intake of saturated and polyunsaturated fat), dietary fiber intake was inversely associated with lung cancer risk (HR [95% CI] = 0.90 [0.83-0.99] for highest vs. lowest quintile and 0.93 [0.89-0.97] per 10g/day increase). Stratified analyses showed a significant inverse association in men (HRs [95% CIs] per 10g/day increase = 0.92 [0.85-1.00]), women (0.94 [0.90-0.99]), whites (0.92 [0.88-0.95]), smokers (0.92 [0.88-0.97]), and alcohol drinkers (0.89 [0.86-0.94]). However, no significant association was found in Blacks (1.05 [0.92-1.19]), Asians (0.99 [0.85-1.16]), never smokers (0.97 [0.88-1.07]), and never drinkers (0.99 [0.94-1.05]) (P interaction = 0.06 for sex, 0.004 for race, 0.17 for tobacco smoking, and &amp;lt;0.001 for alcohol drinking). Conclusion: Our findings suggest that a high-fiber diet was associated with a lower risk of lung cancer among whites, smokers, and alcohol drinkers. Further research is needed to determine if the association between dietary fiber intake and lung cancer risk reflects a causal relation. Citation Format: Jae Jeong Yang, Danxia Yu, Yong-Bing Xiang, William Blot, Kim Robien, Rashmi Sinha, Yikyung Park, Emily White, Yumie Takata, Mattias Johansson, Wei Zheng, Xiao-Ou Shu. Dietary fiber intake and lung cancer risk: A pooled analysis of 1.44 million individuals in 10 cohorts [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 5253.
Abstract 3683: Reciprocal expressions of TFF-1 and TTF-1 in lung adenocarcinomas
Authors: Daisuke Matsubara, Manabu Soda, Taichiro Yoshimoto, Yusuke Amano, Atsushi Kihara, Yuji Sakuma, Shunsuke Endo, Koichi Hagiwara, Masashi Fukayama, Hiroyuki Mano, Toshiro Niki
Journal: Cancer Research (2018)

Abstract The molecular targeted therapies against EGFR, ALK etc. have improved progression-free survival of patients with lung adenocarcinomas. However, targetable driver mutations have mainly been found in TTF-1-positive terminal respiratory unit (TRU)-type, but have yet been undiscovered in non-TRU type despite the advances in genomics technologies. In order to find the molecular candidate characterizing major subtype of non-TRU type adenocarcinomas, we compared TTF-1-positive/CDH1-positive adenocarcinoma cell lines (“TRU-type” cell lines) (n=11) and TTF-1-negative/CDH1-positive adenocarcinoma cell lines (“non-TRU-type” cell lines) (n=8), and found that TFF-1 (trefoil factor family-1), a gastric mucosal protective factor, was characteristically highly expressed in “non-TRU-type” cell lines. Immunohistochemical analysis of primary lung adenocarcinomas (n=70) revealed that TFF-1 expression was inversely correlated with TTF-1 expression (p=0.0116) and was very rare in primary lung adenocarcinoma cases (5.7%:4/70). So we focused on the non-TRU type adenocarcinomas on the basis of histologic pattern (acinar, solid or mucinous morphology predominant tumors without non-mucinous lepidic growth components) (n=43). Among them, TFF-1 was frequently expressed (62%:27/43), and significantly correlated with the expressions of MUC5AC, HNF4A and CK20 (p&amp;lt;0.0001, p=0.0001, and p=0.0007, respectively), and inversely correlated with TTF-1 expression (p=00039). Next generation sequencing analysis of the 43 cases revealed that KRAS gene mutations and Inactivating mutations and hypermethylation of the TTF-1 gene were frequent in TFF-1 positive cases. The analysis of publicly available data of 442 lung adenocarcinoma cases revealed that high expression of TFF-1 correlated with low expression of TTF-1 and worse prognosis. We confirmed that shRNA against TFF-1 inhibited the cell proliferation and the colony formation, and induced the apoptosis, in the TFF-1 positive “non-TRU-type” cell lines. These results indicate that TFF-1 is not only the marker but also can possibly be the molecular target of a subset of non-TRU-type lung adenocarcinomas. Citation Format: Daisuke Matsubara, Manabu Soda, Taichiro Yoshimoto, Yusuke Amano, Atsushi Kihara, Yuji Sakuma, Shunsuke Endo, Koichi Hagiwara, Masashi Fukayama, Hiroyuki Mano, Toshiro Niki. Reciprocal expressions of TFF-1 and TTF-1 in lung adenocarcinomas [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 3683.
SNIP1 enhances the transactivation activity of the c-Myc oncogene
Authors: Makiko Fujii, Lyudmila Lyakah, Bob Lechleider, Anita B. Roberts
Journal: Cancer Research (2004)

961   SNIP1(Smad nuclear interacting protein 1) is a nuclear protein which was originally cloned and characterized based on its inhibition of the TGF-β signal transduction pathway. SNIP1 is expressed in various tissues and is developmentally regulated. The protein harbors a nuclear localization signal (NLS) and a Forkhead-associated (FHA) domain and interacts with Smad4 via its amino terminal domain. Overexpression of the SNIP1 amino terminal domain is sufficient to inhibit the formation of Smad4/p300 complexes, suppressing multiple gene responses to TGF-β and CBP/p300. Using a yeast two-hybrid screen, we showed that SNIP1 also binds the c-myc oncogene, which is a regulator of several important cellular processes including the control of normal cell growth, differentiation and apoptosis. Myc is known to be activated in various animal and human tumors, and amplification of c-myc has been described in ∼15% of all human tumors. Initial results in mammalian 293 cells show that both overexpressed and endogeneous SNIP1 and c-Myc interact. Although the inhibitory effect of SNIP1 on TGF-β signaling was localized to its N terminal domain, SNIP1 interacts with c-Myc through its C terminal domain which includes the FHA motif, a modular phosphopeptide recognition domain with striking specificity for phosphothreonine (pT)-containing epitopes. These data suggest that SNIP1 might have important roles in carcinogenesis by simultaneously suppressing the TGF-β pathway and amplifying the c-Myc pathway.
Angiotensin II Antagonist Prevents Electrical Remodeling in Atrial Fibrillation
Authors: HidekoNakashima, KoichiroKumagai, HidenoriUrata, NaokiGondo, MunehitoIdeishi, KikuoArakawa
Journal: Circulation (2000)

Background—The blockade of angiotensin II (Ang II) formation has protective effects on cardiovascular tissue; however, the role of Ang II in atrial electrical remodeling is unknown. The purpose of this study was to investigate the effects of candesartan and captopril on atrial electrical remodeling. Methods and Results—In 24 dogs, the atrial effective refractory period (AERP) was measured before, during, and after rapid atrial pacing. Rapid atrial pacing at 800 bpm was maintained for 180 minutes. The infusion of saline (n=8), candesartan (n=5), captopril (n=6), or Ang II (n=5) was initiated 30 minutes before rapid pacing and continued throughout the study. In the saline group, AERP was significantly shortened during rapid atrial pacing (from 149±11 to 132±16 ms, P<0.01). There was no significant difference in AERP shortening between the saline group and the Ang II group. However, in the candesartan and captopril groups, shortening of the AERP after rapid pacing was completely inhibited (from 142±9 to 147±...
Abstract 1627: Custom VariantFlex technology allows rapid design and testing of reference materials for tumor genotyping assays
Authors: Catherine Huang, Ram Santhanam, Dan Brudzewsky, Trevor Brown, Russell Garlick, Bharathi Anekella
Journal: Cancer Research (2018)

Abstract Introduction: Development and validation of tumor genotyping assays requires highly characterized reference materials for effective assessment of accuracy, precision, reproducibility and limits of detection. Highly multiplexed reference materials can facilitate and expedite these studies; however, there is not a single reference material that is appropriate for all assays. Traditional cancer cell line methods or genetic engineering methods can take 6 - 9 months, so more flexible solutions for reference materials are needed. Here we describe the development of VariantFlex technology, which enables a laboratory to configure a reference material to contain the variants of interest at the allele frequency of relevance to their studies in rapid time. Methods: A library of biosynthetic constructs was generated that contains ~140 somatic cancer DNA variants (SNVs, small and large indels and tandem duplications), ~27 RNA fusions, and 6 very large gene region constructs for copy number gains. TaqMan® digital PCR assays were developed to precisely quantify the variant allele fraction, fusion RNA concentration or copy number gain. As an example, biosynthetic constructs bearing multiple SNVs in TP53, PIK3CA and EGFR, large deletions in EGFR, and the structural variants NCOA4-RET and TPR-ALK, were selected from the VariantFlex library and spiked into DNA extracted from the highly characterized GM24385 cell line. The mixture was processed to obtain ctDNA-like profile, encapsulated to provide stability, and then diluted in artificial plasma to generate a customized reference material for liquid biopsy. Results: The ctDNA reference material was quantified by digital PCR and performance was verified on hybrid capture and amplicon based NGS assays. Variant allele frequency as low as 0.125% VAF was accurately targeted (range for 0.125% target was +/- 0.025% by digital PCR). The VariantFlex technology has been validated to work with amplified NGS workflows, hybrid-capture based NGS assays as well as non-NGS assays such as qPCR and array based methods. Conclusions: This study shows how a large library of cancer-related variants can facilitate rapid production of customized reference materials. The flexibility to include exactly the variants of interest, at the critical allele frequencies, and in the most patient-like format will facilitate assay development and validation. Citation Format: Catherine Huang, Ram Santhanam, Dan Brudzewsky, Trevor Brown, Russell Garlick, Bharathi Anekella. Custom VariantFlex technology allows rapid design and testing of reference materials for tumor genotyping assays [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 1627.
A Study of Hydraulics in Simulated Patent Ductus Arteriosus
Authors: Simonrodbard, Robertzaas, Williamcook
Journal: Circulation Research (1955)

A hydraulic model was designed to study the effects of converging streams such as occur in patent ductus arteriosus. The results showed that flow across the fistula was dependent primarily on the resistance at the outlets of the  as against the  circulation. Even very slight differences in resistance could effect very large shunts. When the left ventricular output was great, the loss across the shunt was relatively unimportant. However, when the left ventricular output was low, most of its flow passed across the shunt and the systemic delivery virtually ceased. This situation became much more severe if the systemic resistance was raised even slightly above that of the pulmonic outflow path.
Increased Soluble Form of P-Selectin in Patients With Unstable Angina
Authors: HisaoIkeda, YoshinoriTakajo, KazuyaIchiki, TakafumiUeno, SanaeMaki, TakehikoNoda, KenzoSugi, TsutomuImaizumi
Journal: Circulation (1995)

Background P-selectin in platelets and endothelial cells mediates adhesive interaction with leukocytes to form thrombi. The purpose of the present study was to investigate the plasma levels of P-selectin in patients with unstable angina and in those with stable effort angina of different pathophysiologies. Methods and Results Plasma P-selectin levels were determined by a monoclonal antibody–based enzyme immunoassay on plasma samples taken from 12 patients with unstable angina, 11 patients with stable effort angina, and 15 healthy volunteers. Patients with unstable angina had angina at rest associated with ECG changes. In patients with unstable angina, plasma P-selectin levels within 1 hour (361±90 ng/mL) and at 3 hours (282±56 ng/mL) after angina were significantly (P<.05) higher than those in volunteers (177±31 ng/mL). Plasma P-selectin levels at 5 hours after attack (242±46 ng/mL) did not differ from those in volunteers. Although patients with stable effort angina developed angina with ST-segment depres...
Coal Workers’ Pneumoconiosis–Attributable Years of Potential Life Lost to Life Expectancy and Potential Life Lost Before Age 65 Years — United States, 1999–2016
Authors: Jacek M. Mazurek, John Wood, David J. Blackley, David N. Weissman
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Coal workers' pneumoconiosis (CWP) is a preventable occupational lung disease caused by inhaling coal mine dust that can lead to premature* death (1,2). To assess trends in premature mortality attributed to CWP (3), CDC analyzed underlying† causes of death data from 1999 to 2016, the most recent years for which complete data are available. Years of potential life lost to life expectancy (YPLL) and years of potential life lost before age 65 years (YPLL65)§ were calculated (4). During 1999-2016, a total of 38,358 YPLL (mean per decedent = 8.8 years) and 2,707 YPLL65 (mean per decedent = 7.3 years) were attributed to CWP. The CWP-attributable YPLL decreased from 3,300 in 1999 to 1,813 in 2007 (p<0.05). No significant change in YPLL occurred after 2007. During 1996-2016, however, the mean YPLL per decedent significantly increased from 8.1 to 12.6 per decedent (p<0.001). Overall, CWP-attributable YPLL65 did not change. The mean YPLL65 per decedent decreased from 6.5 in 1999 to 4.3 in 2002 (p<0.05), sharply increased to 8.9 in 2005, and then gradually decreased to 6.5 in 2016 (p<0.001). Increases in YPLL per decedent during 1999-2016 indicate that over time decedents aged ≥25 years with CWP lost more years of life relative to their life expectancies, suggesting increased CWP severity and rapid disease progression. This finding underscores the need for strengthening proven prevention measures to prevent premature CWP-associated mortality.
Abstract 19163: Public Knowledge and Confidence to Use Automated External Defibrillators
Authors: Benjamin Dahan, Patricia Jabre, Julien Bernasconi, Nicole Karam, Florence Dumas, Muriel Tafflet, Eloi Marijon, Xavier Jouven
Journal: Circulation (2016)

Introduction: Automated External Defibrillators (AED) have been placed in highly frequented public areas in order to improve Out-of-Hospital Cardiac Arrest (OHCA) survival. We sought to analyze pub...
Abstract 3782: Transcriptional regulation of MHC Class II in tumor associated plasmacytoid dendritic cells in glioblastoma
Authors: Sreenivasulu Chintala, Brij N. Tewari, Mario Henriquez, Kaleigh Fetcko, Anna Filley, Mahua Dey
Journal: Cancer Research (2018)

Abstract Background: Glioblastoma (GBM), an aggressive grade IV astrocytoma, is the most common primary brain tumor in adults and carry very poor prognosis. One of the hallmark features of GBM is tumor induced dense immunosuppression that renders immunotherapeutic strategies against GBM ineffective. In order to develop successful immunotherapeutic strategies for GBM, it is critical to understand the mechanism of immunosuppression in the tumor microenvironment (TME). In our previous publication, we have shown that plasmacytoid dendritic cells (pDCs) accumulate in TME and preferentially up-regulate MHC-II expression in comparison to myeloid DCs (mDCs). GBM infiltrating pDCs are immunosuppressive in nature and lack the ability to secrete IFN-alpha, and MHC-II upregulation by immunosuppressive pDCs lead to development of tumor tolerance. MHC-II molecules are transcriptionally regulated by the multiprotein complex enhanceosome consisting of a catalytic Class II transactivator (C2ta) in a cell type-dependent mechanism. There are no studies clearly showing differential enhanceosome and C2ta regulation in GBM associated pDC and mDC. In the present study, we investigated the mechanism of differential expression of enhanceosome multiprotein complex in GBM associated pDC and mDC and identify the upstream regulators and downstream effectors. Methods: GL261 cells were intracranially injected (i.c.) in C57BL6 mice and allowed to establish tumors. Tumor and normal brain (n=5), along with cervical lymph nodes (cLN), were collected and processed for isolation of pDC and mDC using flow sorting. Quantitative RT-PCR analysis was used to determine the enhanceosome components. IHC/IF and Western blot analysis were performed to confirm differential expression of enhanceosome components in mouse and human GBM specimens. Cytokine/chemokine protein array and ELISA methods were used to determine the differential expression of cytokines/chemokines in pDC and mDC. Results: We found differential expression of enhanceosome components in tumor associated pDC compared to mDC. Additionally, we found that GBM derived cytokines regulate differential expression of enhanceosome in tumor associated pDC and mDCs. Conclusions: In conclusion results from our studies show that GBM microenvironment regulates differential expression of enhanceosome transcription factors in pDC compared to mDC in a cytokine dependent process. This in turn helps to maintain an immunosuppressive microenvironment for continued tumor growth. Citation Format: Sreenivasulu Chintala, Brij N. Tewari, Mario Henriquez, Kaleigh Fetcko, Anna Filley, Mahua Dey. Transcriptional regulation of MHC Class II in tumor associated plasmacytoid dendritic cells in glioblastoma [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 3782.