tbuckley/cabot-search huggingface dataset:
Suicide risk among cancer survivors: Head and neck versus other cancers.
Authors: Nosayaba Osazuwa-Peters, Matthew C Simpson, Longwen Zhao, Eric Adjei Boakye, Stephanie I Olomukoro, Mark A Varvares
Journal: Journal of Clinical Oncology (2018)

146 Background: While head and neck cancer (HNC) only accounts for 4% of new cancer cases in the United States, incidence of HNC-associated suicide may be significantly higher due to quality of life issues associated with HNC survivorship. This study estimated incidence of HNC-associated suicide versus other common cancers, and quantified suicide rate among HNC survivors compared with non-HNC. Methods: We queried the Surveillance, Epidemiology and End Results 18 database from 2000-2014 for all cancer deaths confirmed as suicide. Mortality rates from suicide was estimated for the 21 most common cancers in the United States, including HNC. Negative binomial regression estimated mortality rate ratios (MRRs) and 95% confidence intervals (CIs), between HNC and the other 20 other cancers combined, and as individual sites. Models were stratified by sex (when applicable), controlling for race, marital status, age, year and stage of diagnosis. Results: There were 4,769 suicides observed among 4,613,123 cancer survivors from 2000-2014, yielding an incidence rate of 23.6 suicides per 100,000 person-years. Combined, all other cancers had a 45% decreased suicide ratio compared to HNC for both males (MRR = 0.55, 95% CI 0.48, 0.64) and females (MRR = 0.55, 95% CI 0.37, 0.81). For specific cancer sites, only pancreatic cancer had a higher mortality rate due to suicide than HNC (86.4 suicides per 100,000 person-years, versus 63.4 suicides per 100,000 person-years). Stratified by gender, only male pancreatic cancer survivors had a significantly higher suicide MRR compared with HNC (MRR = 1.54, 95% CI 1.23, 1.90). For females, all cancer sites (including pancreas) had either significantly or insignificantly lower suicide MRR compared with HNC. Conclusions: Risk of suicide is significantly higher among HNC survivors compared to all other cancers, except pancreatic cancer. Our findings confirm that HNC survivors are prime candidates for lifelong psychosocial surveillance.
Direct Comparison of the 0/1h and 0/3h Algorithms for Early Rule-Out of Acute Myocardial Infarction
Authors: Patrick Badertscher, Jasper Boeddinghaus, Raphael Twerenbold, Thomas Nestelberger, Karin Wildi, Desiree Wussler, Jonas Schwarz, Christian Puelacher, Maria Rubini Giménez, Nikola Kozhuharov, Jeanne du Fay de Lavallaz, Sara Elisa Cerminara, Eliska Potlukova, Katharina Rentsch, Òscar Miró, Beatriz López, F. Javier Martin-Sanchez, Beata Morawiec, Piotr Muzyk, Dagmar I. Keller, Tobias Reichlin, Christian Mueller, Zaid Sabti, Ivo Strebel, Samyut Shrestha, Dayana Flores, Michael Freese, Claudia Stelzig, Caroline Kulangara, Kathrin Meissner, Nicolas Schaerli, Deborah Mueller, Ana Yufera Sanchez, Lorraine Sazgary, Stella Marbot, Carolina Fuenzalida, Sofia Calderón, Esther Rodriguez Adrada, Damian Kawecki, Ewa Nowalany-Kozielska, Jiri Parenica, Eva Ganovská, Arnold von Eckardstein, Jens Lohrmann, Wanda Kloos, Stefan Osswald, Andreas Buser, Roland Bingisser, Nicolas Geigy
Journal: Circulation (2018)
Letter by Sniecinski et al Regarding Article, “Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement: Insights from the National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry”
Authors: Roman M. Sniecinski, G. Burkhard Mackensen, Miklos D. Kertai
Journal: Circulation (2018)
Integrative analysis of gene expression profiles reveals specific signaling pathways associated with pancreatic duct adenocarcinoma
Authors: Jun Li, Wenle Tan, Linna Peng, Jialiang Zhang, Xudong Huang, Qionghua Cui, Jian Zheng, Wen Tan, Chen Wu, Dongxin Lin
Journal: Cancer Communications (2018)

Pancreatic duct adenocarcinoma (PDAC) remains a major health problem because conventional cancer treatments are relatively ineffective against it. Microarray studies have linked many genes to pancreatic cancer, but the available data have not been extensively mined for potential insights into PDAC. This study attempted to identify PDAC-associated genes and signaling pathways based on six microarray-based profiles of gene expression in pancreatic cancer deposited in the gene expression omnibus database.Pathway network methods were used to analyze core pathways in six publicly available pancreatic cancer gene (GSE71989, GSE15471, GSE16515, GSE32676, GSE41368 and GSE28735) expression profiles. Genes potentially linked to PDAC were assessed for potential impact on survival time based on data in The Cancer Genome Atlas and International Cancer Genome Consortium databases, and the expression of one candidate gene (CKS2) and its association with survival was examined in 102 patients with PDAC from our hospital. Effects of CKS2 knockdown were explored in the PDAC cell lines BxPC-3 and CFPAC-1.The KEGG signaling pathway called "pathway in cancer" may play an important role in pancreatic cancer development and progression. Five genes (BIRC5, CKS2, ITGA3, ITGA6 and RALA) in this pathway were significantly associated with survival time in patients with PDAC. CKS2 was overexpressed in PDAC samples from our hospital, and higher CKS2 expression in these patients was associated with shorter survival time. CKS2 knockdown substantially inhibited PDAC cell proliferation in vitro.Analysis integrating existing microarray datasets allowed identification of the "pathway in cancer" as an important signaling pathway in PDAC. This integrative approach may be powerful for identifying genes and pathways involved in cancer.
FGFR1-Activated Translation of WNT Pathway Components with Structured 5′ UTRs Is Vulnerable to Inhibition of EIF4A-Dependent Translation Initiation
Authors: Tuan M. Nguyen, Elena B. Kabotyanski, Yongchao Dou, Lucas C. Reineke, Peng Zhang, Xiang H.-F. Zhang, Anna Malovannaya, Sung Yun Jung, Qianxing Mo, Kevin P. Roarty, Yiwen Chen, Bing Zhang, Joel R. Neilson, Richard E. Lloyd, Charles M. Perou, Matthew J. Ellis, Jeffrey M. Rosen
Journal: Cancer Research (2018)

Cooperativity between WNT and FGF signaling is well documented in embryonic development and cancer progression, but the molecular mechanisms underlying this cross-talk remain elusive. In this study, we interrogated the dynamics of RNA levels, ribosome occupancy, and protein expression as a function of inducible FGF signaling in mouse mammary glands with constitutive WNT hyperactivation. Multiomics correlation analysis revealed a substantial discrepancy between RNA and ribosome occupancy levels versus protein levels. However, this discrepancy decreased as cells became premalignant and dynamically responded to FGF signaling, implicating the importance of stringent gene regulation in nontransformed cells. Analysis of individual genes demonstrated that acute FGF hyperactivation increased translation of many stem cell self-renewal regulators, including WNT signaling components, and decreased translation of genes regulating cellular senescence. WNT pathway components translationally upregulated by FGF signaling had long and structured 5' UTRs with a high frequency of polypurine sequences, several of which harbored (CGG)
Clinicians and Health Care Price Transparency—Buyers vs Sellers?
Authors: Anna D. Sinaiko
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Modulation of T cell and macrophage tumor infiltration by the TLR9 agonist lefitolimod in a murine model of colorectal cancer.
Authors: Manuel Schmidt, Detlef Oswald, Barbara Volz, Burghardt Wittig, Kerstin Kapp
Journal: Journal of Clinical Oncology (2018)

687 Background: The use of TLR9 agonists for immunotherapeutic approaches is supported by preclinical and ongoing clinical studies. Lefitolimod, a covalently-closed dumbbell-shaped DNA construct, is an immune surveillance reactivator which broadly activates cells of the innate and adaptive immune system. The conversion of non-immunogenic (cold) tumors into immunogenic (hot) tumors, characterized by their T-cell infiltration, is a pre-requisite for response to immunotherapies. By its mode-of-action lefitolimod likely provides the necessary signals for activation of immune cells and their differentiation into anti-tumor effector cells as well as their recruitment to the tumor microenvironment (TME). Methods: To support the further clinical development of lefitolimod in mCRC, the syngeneic colon carcinoma model CT26 was used to evaluate anti-tumoral efficacy of lefitolimod and its modulation of the TME. The phenotype of T cells and macrophages present within tumor-infiltrating immune cells were analyzed by flow cytometry. Their localization within the tumor was investigated by immunohistochemistry. Results: Intratumoral injection of single-agent lefitolimod in the CT26 model resulted in reduced tumor growth. This was accompanied by an increased infiltration of T cells, in particular CD8 + T cells, into the tumor center. The CD8 + T cells were activated and showed an up-regulation of the cytolytic effector Granzyme B. Correspondingly, the ratio of activated CD8 + T cells with cytolytic function to regulatory T cells was increased by lefitolimod. Moreover, lefitolimod led to the recruitment of macrophages into the tumor and, importantly, an increase of M1 macrophages and a decrease of M2 macrophages inside the TME. Conclusions: Lefitolimod treatment resulted in modulation of the TME towards an increase of effector cells with anti-tumoral functions like cytotoxic CD8 + T cells and M1-type macrophages as well as a decrease of pro-tumoral M2-type macrophages. Therefore, lefitolimod provides the essential requirements for clinical response to immunotherapeutic drugs like checkpoint inhibitors. This predestines lefitolimod as combination partner in immuno-oncological trials.
Abstract 10344: Impact of Non-alcoholic Fatty Liver on Vulnerable Plaques Evaluated by MDCT Angiography
Authors: Kazuhiro Osawa, Toru Miyoshi, Nobuhiro Nishii, Kazufumi Nakamura, Kunihisa Kohno, Hiroshi Morita, Hiroshi Ito
Journal: Circulation (2013)

Background: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity, type 2 diabetes mellitus (DM) and dyslipidemia and overlaps risk factors of CAD. Moreover, NAFLD has been ...
Identifying specific risk factors for the development of atrial fibrillation on ibrutinib.
Authors: Robert Lentz, Nausheen Akhter
Journal: Journal of Clinical Oncology (2018)

128 Background: Ibrutinib is a tyrosine kinase inhibitor that has proven benefit in B-cell malignancies. Previous studies have shown that the overall incidence of atrial fibrillation (AF) while on ibrutinib is 6-16%. We investigated specific risk factors for the development of AF while on ibrutinib in an open-label single center study. Methods: We conducted a retrospective study of patients treated with ibrutinib between July 2012 and August 2017. ECGs were manually reviewed to document AF. Patients with existing AF or valvular heart disease were excluded. Patients were followed for incident AF until the end of the medical record, death, or August 2017. The presence or absence of AF risk factors and duration of ibrutinib treatment were documented. Statistical analysis used chi-square tests for categorical variables and t-tests for continuous variables. Results: 161 patients were included in the analysis. Mean age was 65.5 years, 70.8% were men, and 60.9% had CLL (13.0% Waldenstrom macroglobulinemia, 10.6% mantle cell lymphoma, and 15.5% other). After a mean follow up of 686 days, the incidence of AF was 9.9%. Combined systolic or diastolic heart failure (HF) was statistically associated with incident AF (p = 0.00454). Ibrutinib treatment length (p =0.09698), age (p = 0.08181), obesity, (p = 0.30800), coronary artery disease (CAD, p = 0.16422), hypertension (HTN, p = 0.65447), diabetes mellitus (DM, p = 0.58836), and male sex (p = 0.30800) were not associated with incident AF (Table 1). Of those with heart failure, 29.4% developed incident AF. Conclusions: In this large retrospective open-label cohort study, the incidence of AF on ibrutinib was higher in patients with heart failure. Duration of ibrutinib treatment was not associated with incident AF. Ibrutinib should be used with caution in patients with heart failure and these patients should be closely monitored for incident AF. [Table: see text]
Abstract 11996: The Impact of Left Ventricular Diastolic Dysfunction on Instantaneous Wave-Free Ratio in Intermediate Coronary Stenosis
Authors: Tonre Ri, Hiroyuki Arashi, Junichi Yamaguchi, Eiji Shibahashi, Ryosuke Itani, Kensuke Shimazaki, Hisao Otsuki, Shintaro Haruki, Masashi Nakao, Kazuho Kamishima, Kentaro Jujo, Yuichiro Minami, Nobuhisa Hagiwara
Journal: Circulation (2015)

Background: Instantaneous wave-free ratio (iFR) is a new vasodilator-free index of the functional severity of coronary stenosis and reported to have a similar feature to coronary flow reserve (CFR) that is considered to reflect not only resistances of an epicardial stenosis but also microvascular resistances in myocardium. Previous studies reported that CFR was impaired in patients with left ventricular (LV) diastolic dysfunction which is thought to have an impact on microvascular circulation. However, there was no report examining the impact of LV diastolic dysfunction on iFR. Accordingly, the purpose of this study was to assess the relationship between iFR and LV diastolic dysfunction in comparison with fractional flow reserve (FFR). Method and Results: We examined consecutive 76 patients (with 107 stenosis) whose iFR, FFR and E/e’ were measured simultaneously. Patients with hemodialysis or left ventricular hypertrophy (defined as left ventricular mass index more than 116g/m2 (male) or 96g/m2 (female) in echocardiography) were excluded. LV diastolic dysfunction in the present study was defined as E/e’ more than 15. The mean age of patients with LV diastolic dysfunction (n=18, mean E/e’=19.3 ± 6.3) was higher than patients without LV diastolic dysfunction (n=58, mean E/e’= 10.1 ± 6.2). Other patients’ characteristics are shown in table 1. The mean iFR values in patients with LV diastolic dysfunction was significantly lower than that in patients without LV diastolic dysfunction, despite no significant differences were observed in the mean FFR values and % diameter stenosis (Table 2). iFR showed negative correlation with E/e’ (r=0.31, p=0.0012) (Figure 1), whereas, there was no correlation between FFR and E/e’ (data not shown). Conclusion: Our present results suggested that LV diastolic dysfunction affect the iFR values, but not FFR, in intermediate coronary stenosis. In patients with LV dysfunction, iFR may overestimate the severity of coronary stenosis.
Influence of the ethnical groups and kinship in the dissemination of the HBV infection in brazilian families of oriental and occidental origin: validation of a mathematical model
Authors: Flair José Carrilho, S. K. O Nita, L. C. da Silva, R. A. Cardoso, L. E. P Fonseca, Antônio Atílio Laudanna, Venâncio Avancini Ferreira Alves, Luiz Carlos da Costa Gayotto
Journal: Hepatology (1996)
Current landscape and future of dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in cancer; lessons learned from clinical trials with melanoma and non-small cell lung cancer (NSCLC)
Authors: Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R. Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Journal: Journal for ImmunoTherapy of Cancer (2018)

Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens. Preliminary trials assessing combination therapy with anti-PD-1/PD-L1 plus anti-CTLA-4 immune-checkpoint inhibitors have documented considerable advantages in survival indices over single-agent immunotherapy. The therapeutic potential of combinatorial approaches is highlighted by the recent FDA approval of nivolumab plus ipilimumab for patients with advanced melanoma. Presently, dual-immune checkpoint inhibition with anti-programmed death receptor-1/programmed cell death receptor- ligand-1 (anti-PD-1/PD-L1) plus anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) monoclonal antibodies (MoAbs) is being evaluated for a wide range of tumor histologies. Furthermore, several ongoing clinical trials are investigating combination checkpoint inhibition in association with traditional treatment modalities such as chemotherapy, surgery, and radiation. In this review, we summarize the current landscape of combination therapy with anti-PD-1/PD-L1 plus anti-CTLA-4 MoAbs for patients with melanoma and non-small cell lung cancer (NSCLC). We present a synopsis of the prospects for expanding the indications of dual immune-checkpoint inhibition therapy to a more diverse set of tumor histologies.
Trajectories of Antidepressant Use before and after the Loss of a Family Member: Evidence from the Finnish Public Sector Study
Authors: Helena Honkaniemi, Mikael Rostila, Maarit Kauppi, Pekka Virtanen, Liudmila Lipiäinen, Jaana Pentti, Mika Kivimäki, Jussi Vahtera
Journal: Psychotherapy and Psychosomatics (2018)

Trajectories of Antidepressant Use before and after the Loss of a Family Member : Evidence from the Finnish Public Sector Study
New strategies in achieving antiangiogenic effect: Multiplex inhibitors suppressing compensatory activations of RTKs
Authors: Yuanyuan Shan, Binghe Wang, Jie Zhang
Journal: Medicinal Research Reviews (2018)

Abstract Pathological angiogenesis plays a crucial role in malignant neoplasia. Vascular normalization has been confirmed as a promising strategy to promote chemotherapy efficacy. However, compensatory activation of alternative angiogenic receptor tyrosine kinases (RTKs) reduces vascular normalization and induces resistance. Moreover, complexity and heterogeneity of angiogenesis make it difficult to treat with single‐target agents. Accordingly, it has been proposed that multiplex inhibition of RTKs could enhance treatment efficacy and overcome resistance on the basis of the vascular normalization concept. Meanwhile, it is feasible to develop multiplex inhibitors against VEGFR‐2/Tie‐2/EphB4 because of their highly conserved ATP‐binding pockets. These inhibitors possess the properties of not only stabilizing the vascular normalization “time window” but also preventing the occurrence of resistance. This novel strategy has yielded promising results in the discovery of antiangiogenic agents. This review highlights the recent progress on the development of such angiogenesis inhibitors.
Publisher Correction: N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications
Authors: Yang Wang, Yue Li, Minghui Yue, Jun Wang, Sandeep Kumar, Robert J. Wechsler-Reya, Zhaolei Zhang, Yuya Ogawa, Manolis Kellis, Gregg Duester, Jing Crystal Zhao
Journal: Nature Neuroscience (2018)
Cardiovascular Disease in Survivors of Childhood Cancer: Insights Into Epidemiology, Pathophysiology, and Prevention
Authors: Saro H. Armenian, Gregory T. Armstrong, Gregory Aune, Eric J. Chow, Matthew J. Ehrhardt, Bonnie Ky, Javid Moslehi, Daniel A. Mulrooney, Paul C. Nathan, Thomas D. Ryan, Helena J. van der Pal, Elvira C. van Dalen, Leontien C.M. Kremer
Journal: Journal of Clinical Oncology (2018)

Cardiovascular disease (CVD), which includes cardiomyopathy/heart failure, coronary artery disease, stroke, pericardial disease, arrhythmias, and valvular and vascular dysfunction, is a major concern for long-term survivors of childhood cancer. There is clear evidence of increased risk of CVD largely attributable to treatment exposures at a young age, most notably anthracycline chemotherapy and chest-directed radiation therapy, and compounded by traditional cardiovascular risk factors accrued during decades after treatment exposure. Preclinical studies are limited; thus, it is a high priority to understand the pathophysiology of CVD as a result of anticancer treatments, taking into consideration the growing and developing heart. Recently developed personalized risk prediction models can provide decision support before initiation of anticancer therapy or facilitate implementation of screening strategies in at-risk survivors of cancer. Although consensus-based screening guidelines exist for the application of blood and imaging biomarkers of CVD, the most appropriate timing and frequency of these measures in survivors of childhood cancer are not yet fully elucidated. Longitudinal studies are needed to characterize the prognostic importance of subclinical markers of cardiovascular injury on long-term CVD risk. A number of prevention trials across the survivorship spectrum are under way, which include primary prevention (before or during cancer treatment), secondary prevention (after completion of treatment), and integrated approaches to manage modifiable cardiovascular risk factors. Ongoing multidisciplinary collaborations between the oncology, cardiology, primary care, and other subspecialty communities are essential to reduce therapeutic exposures and improve surveillance, prevention, and treatment of CVD in this high-risk population.