tbuckley/cabot-search huggingface dataset:
Impact of Medicaid reimbursement and eligibility policies on receipt of cancer screening.
Authors: Michael T. Halpern, Melissa A. Romaire, Susan G. Haber, Florence K. Tangka, Susan A. Sabatino, David H. Howard
Journal: Journal of Clinical Oncology (2013)

6514 Background: State Medicaid programs cover receipt of cancer screening services. However, coverage of cancer screening tests does not guarantee access to these services. Medicaid beneficiaries are less likely to be screened for cancer and more likely to present with advanced stage cancers. State-specific variations in Medicaid program eligibility requirements and reimbursements for medical services may affect cancer screening rates among Medicaid enrollees. This study examined how eligibility and reimbursement policies affected receipt of breast, cervical, colorectal, and prostate cancer screening. Methods: We examined 2007 Medicaid data for individuals age 21-64 enrolled in fee-for-service Medicaid for at least 4 months from 46 states and the District of Columbia. We examined the association of state-specific Medicaid cancer screening test and office visit reimbursements, income and financial asset eligibility requirements, physician copayments, and frequency of Medicaid eligibility renewal on receipt of cancer screening. Analyses used multivariate logistic regressions with generalized estimating equations to control for correlation between beneficiaries within a state. Results: Increased Medicaid screening test reimbursements were significantly associated with small increases in receipt of colonoscopy, mammograms, and PSA tests. Increased reimbursements for office visits were associated with increased receipt of colonoscopy, FOBT, Pap tests, and mammograms. Greater asset thresholds for Medicaid eligibility increased the likelihood of all screening tests except FOBT. Beneficiaries in states requiring more frequent (&lt;12 month) renewal of Medicaid eligibility were more likely to receive FOBT, PSA, or mammograms, but less likely to receive Pap tests. Conclusions: Increasing Medicaid reimbursement rates and asset policies was generally associated with increases in cancer screening. As proposed Medicaid eligibility expansions will almost certainly increase the number of enrollees in this program, it is crucial to provide adequate reimbursements and develop eligibility policies to promote cancer screening and thereby increase early cancer detection among this underserved population.
Abstract 17097: A Novel Brain Injury Biomarker Correlates With Cyanosis in Infants With Congenital Heart Disease
Authors: Lindsey McPhillips, Kaie Ojamaa, Cristina Sison, Dorota Gruber, Dipak Kholwadwala
Journal: Circulation (2016)

Introduction:  Cyanotic heart lesions are a complex subset of congenital heart disease (CHD) in which patients are persistently desaturated until surgical repair/palliation.   Hypothesis:  We hypothesized there will be a direct relationship between degree of preoperative desaturation and presence of systemic inflammation, as well as evidence of brain injury in children less than one year of age. We further hypothesized that preoperative desaturation with augmented systemic inflammation will predict a more complex postoperative course.   Methods:  Fifty patients with CHD were enrolled in this study and classified as cyanotic (O 2  ≤90%) or acyanotic (O 2 >90%) based on SpO 2 . Serum was obtained within 2 weeks of the cardiac surgery and the following inflammatory mediators were analyzed using commercially available ELISA kits: macrophage migration inhibitory factor, IL-6, IL-8, TNF-α, IL-12p70, IL-10, IL-1β, and INF-γ; and a novel biomarker of axonal injury, phosphorylated high-molecular weight neurofilament (pNF-H). Postoperative variables included inotrope score, duration of mechanical ventilation and length of stay.   Results:  A total of 22 cyanotic and 28 acyanotic patients were enrolled with a median age of 9.5 days (range 2-303 days) and 99.5 days (range 1-274 days), respectively; and a mean ± SD SpO 2  of 78 ± 18% and 97 ± 3% (p   Conclusions:  Cyanotic patients with CHD were exposed to higher serum concentrations of inflammatory mediators in the preoperative period compared to acyanotic patients, and showed evidence of brain injury. The severity of preoperative desaturation was a significant predictor of greater postoperative medical intervention.
Abstract 20132: Carbon Nanotube Fibers Facilitate Ventriculoatrial Conduction
Authors: Mark McCauley, Flavia Vitale, Colin C Young, Matteo Pasquali, Mehdi Razavi
Journal: Circulation (2016)

Introduction: Physiologic atrioventricular (A-V) conduction occurs through the atrioventricular node (AVN), and pathologic conduction may occur through accessory pathways (AP). We have previously s...
Abstract 16130: Early Invasive Assessment of the Coronary Microcirculation Predicts Subsequent Acute Rejection After Heart Transplantation
Authors: Kozo Okada, Yasuhiro Honda, Helen Luikart, Paul G. Yock, Peter J. Fitzgerald, Alan C. Yeung, Hannah A. Valantine, Kiran K. Khush, William F. Fearon
Journal: Circulation (2016)

Background: Acute rejection plays an important role in the development of cardiac allograft vasculopathy (CAV) and long-term mortality after heart transplantation; therefore, more emphasis should b...
SPOP mutation drives prostate neoplasia without stabilizing oncogenic transcription factor ERG
Authors: Jonathan Shoag, Deli Liu, Mirjam Blattner, Andrea Sboner, Kyung Park, Lesa Deonarine, Brian D. Robinson, Juan Miguel Mosquera, Yu Chen, Mark A. Rubin, Christopher E. Barbieri
Journal: Journal of Clinical Investigation (2017)

Nearly 50% of prostate cancers harbor gene fusions that lead to overexpression of the transcription factor ERG, while a mutually exclusive 10% of prostate cancers harbor recurrent mutations in the gene encoding the E3 ubiquitin ligase SPOP. Recent reports suggest that SPOP acts as a ubiquitin ligase for ERG and propose that ERG stabilization is the oncogenic effector of SPOP mutation. Here, we used human prostate cancer samples and showed that the vast majority of human SPOP-mutant cancers do not express ERG. Comparison of SPOP-mutant and ERG-fusion organoid models showed evidence of divergent, rather than common, transcriptional programs. Furthermore, expression of prostate cancer-associated SPOP mutations in genetically engineered mouse models of SPOP-mutant prostate cancer did not result in the expression of ERG protein in histologically normal prostate glands, high-grade prostatic intraepithelial neoplasia, invasive adenocarcinoma, or prostate organoids. In summary, we found no evidence that ERG is an effector of SPOP mutation in human prostate cancer or mouse models.
Differential regulation and localization of β-catenin and cell cycle regulating proteins in Barrett’s esophageal carcinoma: The possible essential signaling factors in the development of esophageal adenocarcinoma
Authors: Aminul Islam, Allan P. Weston, Sharad Mathur, Rachel Cherian, Sushanta K. Banerjee
Journal: Cancer Research (2004)

814   With a view to investigate the role of β-catenin and some cell cycle regulatory proteins like cyclin-B1, Cdc-2, pCdc-2 and pCdc-25C, immunohistochemical localization of β-catenin, Cdc-2 and PCNA were carried out with concomitant detection of β-catenin, cyclin-B1, Cdc-2, pCdc-2 and pCdc-25C by Western blot technique in normal Barrett’s esophagus (BE), low grade dysplasia (LGD), high grade dysplasia (HGD) and esophageal adenocarcinoma (EA) samples. Immunohistochemical detection of β-catenin, Cdc2 and PCNA showed grade specific and tissue specific expressions in relation to the patterns of disease progression. In normal BE, LGD and HGD, β-catenin was mainly noted to be localized in the plasma membrane and cytoplasm; nuclear expression appeared to be insignificant. In adenocarcinoma samples the intensities of β–catenin expression in both membrane and cytoplasm appeared very insignificant. The expression of receptors of β-catenin (TCF-3) appeared almost same in all the samples in both WB and immunohistochemistry. Cdc-2 was noted to be mainly localized in the cytoplasm and is pronounced in the HGD and EA samples. PCNA exhibited tissue specific as well as grade specific expression. Western blot analyses also presented less expression of β-catenin in HGD and almost no expression in EA samples. Cyclin-B1 exhibited more or less similar expressions in all the samples except slightly less expression in LGD. pCdc-2 expression was more or less uniform in all the samples except comparatively less expression in HGD. pCdc-25C expression was relatively low in normal BE and LGD but comparatively higher expression was noted in HGD and EA samples. Less expression of β-catenin in the nucleus of different samples led us to propose its down regulation in the nucleus and alternative mode of function in inducing esophageal carcinoma, it might have indirect role in the trans-activation of different genes to potentiate cell proliferation. In conclusion, these studies suggest a possible role of β-catenin signaling network along with different cell cycle regulating factors in the sequential development of Barrett’s esophageal cancer.
Programa Europeu de Formação em Epidemiologia de Intervenção
Authors: A Moren, Mike Rowland, F van Loock, J Giesecke
Journal: Eurosurveillance (1996)

O Programa Europeu de Formacao em Epidemiologia de Intervencao (PEFEI) faculta experiencia pratica em epidemiologia das doencas infecciosas. O PEFEI tem por objectivo a criacao de uma rede de profissionais dispersos pela Europa, treinados para uma abordagem padrao em epidemioliogia de intervencao, incluindo trabalho de campo, vigilância, investigacao aplicada, comunicacao e utilizacao de informacao epidemiologica como base para a accao de saude publica. O PEFEI e financiado atraves de um subsidio da Direccao Geral V da Comissao das Comunidades Europeias.
Expressed Gene Fusions as Frequent Drivers of Poor Outcomes in Hormone Receptor–Positive Breast Cancer
Authors: Karina J. Matissek, Maristela L. Onozato, Sheng Sun, Zongli Zheng, Andrew Schultz, Jesse Lee, Kristofer Patel, Piiha-Lotta Jerevall, Srinivas Vinod Saladi, Allison Macleay, Mehrad Tavallai, Tanja Badovinac-Crnjevic, Carlos Barrios, Nuran Beşe, Arlene Chan, Yanin Chavarri-Guerra, Marcio Debiasi, Elif Demirdögen, Ünal Egeli, Sahsuvar Gökgöz, Henry Gomez, Pedro Liedke, Ismet Tasdelen, Sahsine Tolunay, Gustavo Werutsky, Jessica St. Louis, Nora Horick, Dianne M. Finkelstein, Long Phi Le, Aditya Bardia, Paul E. Goss, Dennis C. Sgroi, A. John Iafrate, Leif W. Ellisen
Journal: Cancer Discovery (2017)

Abstract We sought to uncover genetic drivers of hormone receptor–positive (HR+) breast cancer, using a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes, including PIK3CA, AKT3, RAF1, and ESR1, in 14% (24/173) of unselected patients with advanced HR+ breast cancer. FISH confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors. Expression of novel kinase fusions in nontransformed cells deregulates phosphoprotein signaling, cell proliferation, and survival in three-dimensional culture, whereas expression in HR+ breast cancer models modulates estrogen-dependent growth and confers hormonal therapy resistance in vitro and in vivo. Strikingly, shorter overall survival was observed in patients with rearrangement-positive versus rearrangement-negative tumors. Correspondingly, fusions were uncommon (&amp;lt;5%) among 300 patients presenting with primary HR+ breast cancer. Collectively, our findings identify expressed gene fusions as frequent and potentially actionable drivers in HR+ breast cancer. Significance: By using a powerful clinical molecular diagnostic assay, we identified expressed intergenic fusions as frequent contributors to treatment resistance and poor survival in advanced HR+ breast cancer. The prevalence and biological and prognostic significance of these alterations suggests that their detection may alter clinical management and bring to light new therapeutic opportunities. Cancer Discov; 8(3); 336–53. ©2017 AACR. See related commentary by Natrajan et al., p. 272. See related article by Liu et al., p. 354. This article is highlighted in the In This Issue feature, p. 253
Abstract 18392: Mir-101a and Tgf-β Are Mutually Inhibitory: Escape of Tgf-β From Mir-101a Inhibition Promotes Cardiac Fibrosis
Authors: Yue ZHou, Arthur M Richards, Peipei Wang
Journal: Circulation (2016)

MiR-101a is a potent cancer suppressor. Its down-regulation promotes cancer cell proliferation and migration. Conversely miR-101a upregulation inhibits liver and lung fibrosis. Its role in cardiac fibrosis is unknown. We hypothesized miR-101a functions as an endogenous TGF-β signaling inhibitor and that escape from such inhibition leads to cardiac fibrosis. Cardiac fibroblasts (FB) were isolated from adult rat hearts, transfected with miR-101a mimic or inhibitor and then treated with TGF-β, Balfilomycin (Baf) or Rapamycin (Rap). Cell proliferation assay CCK8 and myofibroblast marker α-SMA were measured. LC3, p62 and mTOR signaling were assessed by Western blot. Apoptosis was assessed by MUSE cell analyzer with 7-AAD and Annexin V staining. Left coronary artery ligation (MI) was performed. Hearts were collected and underwent picro-sirius staining and stem-loop qPCR.   Result:  TGF-β caused downregulation of miR-101a in FB and concurrent fibrosis as indicated by increased CCK8, α-SMA expression and gel contraction. Interestingly, autophagy was reduced as indicated by falls in LC3 II/I ratio and apoptosis was also reduced. Transfection with miR-101a mimic had opposite effects to TGF-β and miR-101a inhibitor had similar effects. Autophagy flux test, with additional Baf treatment, indicated that TGF-β reduced, while miR-101a augmented, autophagosome formation and degradation. MiR-101 overexpression was associated reduced phosphorylation of p70s6p and 4EBP1, suggesting modulation of mTOR signaling and its downstream effectors. Modulation of autophagy by Rap or Baf respectively accelerated or reversed miR-101a-induced inhibition of FB proliferation. TGF-β-induced FB proliferation was completely blocked by miR-101a. MiR-101a was reduced in the infarct and border zone but unaltered in the remote zone 7 days after MI. This change was correlated with fibrosis (scare formation in the infarct zone) in different zones.   Conclusion:  miR-101a is an endogenous TGF- β inhibitor. Escape of TGF- β from the inhibitory effects of miR-101a lead to cardiac fibrosis. Underlying mechanisms may relate to direction of FB fate through regulation of autophagy and apoptosis. MiR-101a is a promising therapeutic target for treatment of cardiac fibrosis.
Abstract 11275: ST-Segment Elevation in Lead aVR Strongly Predicts In-hospital Mortality in Patients With Type A Acute Aortic Dissection
Authors: Masami Kosuge, Keiji Uchida, Norihisa Karube, Toshiaki Ebina, Kiyoshi Hibi, Noriaki Iwahashi, Nobuhiko Maejima, Yasushi Matsuzawa, Munetaka Masuda, Kazuo Kimura
Journal: Circulation (2016)

Introduction: Early identification of high-risk patients is crucial for appropriate management in type A acute aortic dissection (AAD). ECG is useful for this purpose because it is readily available and rapidly interpretable at presentation. Hypothesis: In type A AAD, ischemic ST-T change at presentation is associated with poor outcomes. ST-segment elevation in lead aVR (ST↑aVR) is an ECG marker of severe acute myocardial ischemia, and therefore, may provide important prognostic information. Methods: We studied the relation of ECG findings to clinical features on admission and in-hospital death in 294 patients who were admitted within 12 h from symptom onset and underwent urgent surgery for type A AAD. Patients with bundle branch block or left ventricular hypertrophy were excluded. Patients were divided into the 3 groups according to admission ECG findings: no significant ST-T changes (n=99, G-A); the absence (n=151, G-B) or the presence (n=44, G-C) of ST↑aVR ≥0.5 mm with ST-T changes in other leads. Hemoglobin (Hb), creatinine (Cr), D-dimer, and cardiac-specific troponin were measured on admission. Results: There were no differences in age, sex, time to admission or Hb level in the 3 groups. In G-A, G-B, and G-C, systolic blood pressure was 130±23, 131±33, and 88±27 mmHg (p&lt;0.01); heart rate was 70±14, 72±19, and 94±23 bpm (p&lt;0.01); the levels of Cr were 0.9±0.6, 1.0±0.7, and 1.3±1.0 mg/dl (p=0.01); D-dimer was 26±43, 33±40, 62±50 μg/ml (p=0.02), the rates of positive-troponin were 3%, 14%, and 41% (p&lt;0.01); shock were 2%, 21%, and 71% (p&lt;0.01); cardiac tamponade was 3%, 19%, and 64% (p&lt;0.01); moderate/severe aortic regurgitation was 4%, 28%, and 43% (p&lt;0.01); coronary ostial involvement was 3%, 10%, and 32% (p&lt;0.01); concomitant coronary artery bypass surgery was 2%, 7%, and 14% (p=0.03); in-hospital death was 1%, 6%, and 36% (p&lt;0.01), respectively. Multivariate analysis showed that as compared with G-A, odds ratio (95%CI) for in-hospital death associated with G-B and G-C were 1.90 (0.68-4.08; p=0.19), and 34.4 (8.01-73.2; p&lt;0.01), respectively. Conclusions: In patients with type A AAD, ST↑aVR on admission ECG strongly predicts in-hospital death. Our findings suggest that ST↑aVR is a simple but reliable tool for an early identification of high-risk patients.
Abstract P117: Mexican Reg <u>i</u> stry of Risk Factors for Cerebrovascular Disease: The “RISK” (RIESGO) Study, a Mexican Approach
Authors: Luis Espinosa, Beatriz L Rodríguez, Gerardo E Pozas, Carlos Cantu-Brito, Carolina León, Dolores Flores, Inma Castilla-Cortázar, Jose J Góngora, Socorro Vargas
Journal: Circulation (2017)

Background: The RIESGO (RISK) study was established to investigate associations between lifestyle, risk factors and cerebrovascular diseases in 300 attendees to the annual meeting of the Mexican Academy of Neurology. In these analyses we describe traditional and several new risk factors for Cerebrovascular Disease on the RIESGO participants as well as a novel way to create a cohort. Methods: The RIESGO study employed a sample of the Mexican Congress of neurology attendees and intends to follow them prospectively. All attendees were invited to participate (n=1300). A survey on lifestyle questions, and clinical evaluations were conducted at the congress site, non-parametric descriptive statistics were used. Results: 300 attendees (68.8% physicians) participated in RIESGO, 18-83 years old mean 47.1(DE=13.9) and 59% were men. In the RIESGO study, self-reported Diabetes (DM) was 6.8% compared to 20.1% using Glycated Hemoglobin (HbA1c) for diagnosis (&gt;6.5%) and 40% of those with self-reported DM had elevated HbA1c. Also remarkable is the 20.3% major and minor electrocardiographic abnormalities. Systolic and diastolic hypertension was observed in 14.1% and 4.1% respectively, vs 18.4% for self-reported hypertension. Obesity and overweight was observed 66.2% based on BMI &gt; 25kg/m2. Active and former smoking rates were 14.3% and 24.4% respectively, active exercise (&gt;150min/week) was reported in 48.5% and high alcohol consumption (&gt;25 12Oz Beer or equivalent/30days) was 19.9%. The subclinical outcomes were: intima-media thickness (≥0.8mm) found in 2.3%, carotid plaque in 6% and ventricular hypertrophy (Sokolow) in 1.8%. We also explored other new risk factors associated with stroke, and found a high heart rate at rest (&gt;70 beats per minute) in 35%, ventricular premature beats 1.1%, prolonged QTc 0.6% and 0% in men and women respectively, finally on the perceived stress scale 97% “never” or “almost never” felt stressed and only 2.3% felt “fairly often stressed”. We will also discuss the association of traditional vs newer risk factors with subclinical outcomes. Conclusions: These findings indicate a high prevalence and poor awareness and control of major cardiovascular disease risk factors and subclinical outcomes, despite the fact that RIESGO participants have a substantially higher education level and health information than the general Mexican population. These findings reflect the alarming public health problems that diabetes and cardiovascular diseases represent in the Mexican population, even among the most educated individuals. Recurrent attendance at the annual meeting is a novel and convenient way to establish a low cost follow-up study.
Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Authors: Zobair M. Younossi, Rohit Loomba, Mary E. Rinella, Elisabetta Bugianesi, Giulio Marchesini, Brent A. Neuschwander‐Tetri, Lawrence Serfaty, Francesco Negro, Stephen H. Caldwell, Vlad Ratziu, Kathleen E. Corey, Scott L. Friedman, Manal F. Abdelmalek, Stephen A. Harrison, Arun J. Sanyal, Joel E. Lavine, Philippe Mathurin, Michael R. Charlton, Naga P. Chalasani, Quentin M. Anstee, Kris V. Kowdley, Jacob George, Zachary D. Goodman, Keith Lindor
Journal: Hepatology (2017)

Nonalcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long-term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long-term outcomes, and patient-reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies.Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. (Hepatology 2018;68:361-371).