tbuckley/cabot-search huggingface dataset:
Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography
Authors: John J. Mahmarian, Craig Pratt, M. K. Cocanougher, M. S. Verani
Journal: Annals of Internal Medicine (1991)

The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia (52% versus 35%, respectively; p = 0.01). The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia. The prognostic significance of quantified perfusion defects detected by SPECT remains to be assessed.
Response and progression on midostaurin in advanced systemic mastocytosis: KIT D816V and other molecular markers
Authors: Mohamad Jawhar, Juliana Schwaab, Nicole Naumann, Hans-Peter Horny, Karl Sotlar, Torsten Haferlach, Georgia Metzgeroth, Alice Fabarius, Peter Valent, Wolf-Karsten Hofmann, Nicholas C. P. Cross, Manja Meggendorfer, Andreas Reiter
Journal: Blood (2017)
Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis
Authors: Benjamin J. Andreone, Brian Wai Chow, Aleksandra Tata, Baptiste Lacoste, Ayal Ben-Zvi, Kevin Bullock, Amy A. Deik, David D. Ginty, Clary B. Clish, Chenghua Gu
Journal: Neuron (2017)
How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials
Authors: F. Bonnetain, C. Borg, R.R. Adams, J.A. Ajani, A. Benson, H. Bleiberg, B. Chibaudel, E. Diaz-Rubio, J.Y. Douillard, C.S. Fuchs, B.J. Giantonio, R. Goldberg, V. Heinemann, M. Koopman, R. Labianca, A.K. Larsen, T. Maughan, E. Mitchell, M. Peeters, C.J.A. Punt, H.J. Schmoll, C. Tournigand, A. de Gramont
Journal: Annals of Oncology (2017)
Disease Modification in Acute Decompensated Heart Failure
Authors: Paul J Hauptman
Journal: New England Journal of Medicine (2017)

For patients with heart failure, hospitalization is associated with a downward clinical trajectory that accelerates with each subsequent admission. The risk of adverse events after hospitalization may be increased for patients who do not have reductions in levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) between hospital admission and discharge.1 In addition, among patients who present with decompensation, troponin levels that are even slightly above the upper limit of the normal range (not attributable to an acute coronary syndrome) are associated with worse outcomes.2 In part on the basis of these observations, it has been suggested that early . . .
Chronic periodontitis and implant dentistry
Authors: Michael M. Smith, Ellie T. Knight, Latfiya Al‐Harthi, Jonathan W. Leichter
Journal: Periodontology 2000 (2017)

Abstract Dental implants are regularly placed in patients with a history of periodontitis, even though peri‐implant tissues are susceptible to the same host‐modulated plaque‐induced factors that initiate and sustain periodontitis. This article endeavors to clarify the evidence regarding the history of periodontitis as a risk factor for implant success and survival, and the role of supportive periodontal therapy in maintaining implants for individuals with a history of periodontitis.
Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP-treated patients with diffuse large B-cell lymphoma
Authors: Y Kusano, M Yokoyama, Y Terui, N Nishimura, Y Mishima, K Ueda, N Tsuyama, Y Hirofumi, A Takahashi, N Inoue, K Takeuchi, K Hatake
Journal: Blood Cancer Journal (2017)

Abstract The absolute peripheral blood lymphocyte count at diagnosis is known to be a strong prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but it remains unclear as to which peripheral blood lymphocyte population is reflective of DLBCL prognosis. In this cohort, 355 patients with DLBCL treated with R-CHOP from 2006 to 2013 were analyzed. The low absolute CD4+ T-cell count (ACD4C) at diagnosis negatively correlated with the overall response rate and the complete response rate significantly ( P &lt;0.00001). An ACD4C&lt;343 × 10 6 /l had a significant negative impact on the 5-year progression-free survival and the overall survival as compared with an ACD4C⩾343 × 10 6 /l (73.7% (95% confidence interval (CI)=66.7–79.5) versus 50.3% (95% CI=39.0–60.6), P &lt;0.00001 and 83.3% (95% CI=77.1–88.0) versus 59.0% (95% CI=47.9–68.5), P &lt;0.00000001, respectively). Multivariate analysis revealed that the ACD4C was an independent prognostic marker (hazard ratio=2.2 (95% CI=1.3–3.7), P &lt;0.01). In conclusion, a low ACD4C at diagnosis served as an independent poor prognostic marker in patients with DLBCL.
Response by Motovska et al to Letter Regarding Article, “Prasugrel Versus Ticagrelor in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: Multicenter Randomized PRAGUE-18 Study”
Authors: Zuzana Motovska, Ota Hlinomaz, Petr Kala
Journal: Circulation (2017)
Neuroendocrine differentiation in carcinoma of the prostate: An institutional review.
Authors: David Perez, Estefania Linares, Elena Almagro, Blanca Cantos, Miriam Mendez, Constanza Maximiano, Fernando Franco, Judit Rubio, Magda Palka, Virginia Calvo, Patricia Ramirez, Clara Salas, Joaquin Carballido, Mariano Provencio
Journal: Journal of Clinical Oncology (2014)

e16109 Background: Prostate carcinoma (PC) achieves the healing in early stages with radiotherapy or radical prostatectomy. Despite this, there are patients with advanced stages, either at the time of diagnosis or after a recurrence. The androgen deprivation is the base of advanced disease treatment, being the possibility that the tumor evolves to an androgen refractory phenotype, mainly due to tumor cell mutations or hormonal receptor alterations, as well as the possibility of coexistence of a neuroendocrine component among adenocarcinoma cells. In the present study, we reviewed the patients with a neuroendocrine differentiation in PC diagnosed in our Hospital. Methods: Retrospective study of 450 PC diagnosed in Hospital Puerta de Hierro, in Madrid (Spain) during 2010 and 2013. We included the variables: forms of neuroendocrine differentiation in PC, response to treatment, and evolution. Results: Three patients with a mean age of 67 (58-78) were diagnosed of a neuroendocrine differentiation in PC: two of them with a focal neuroendocrine differentiation in conventional prostatic adenocarcinoma, and the third one with a small cell neuroendocrine carcinoma. 100% of them showed a positive immunohistochemical profile for synaptophysin and chromogranin A, being negative for PSA. The two first cases were treated with a GnRH analogue and chemotherapy based on platinum – etoposide doublet, while the third one was only treated with a platinum doublet. Two of them died because of a neuroendocrine disease progression, but the third case is still alive after six cycles of chemotherapy and GnRh analogues, with a slight response to the therapies and with an overall survival of 11 months. Conclusions: It is always necessary to consider the possibility of neuroendocrine differentiation in the PC, mainly when there is a rapid progression to first-line hormone therapy. The study of the endocrine differentiation as a mechanism of resistance should be continued as well as intrinsic genetic factors associated with androgens should. Moreover, the collaboration between pathologists, urologists and clinical oncologists is the basis of understanding the different pathologies, particularly when patient evolution is not as expected.
P16 and cyclin D1 (CYD1) as prognostic markers in hypopharyngeal (HSC) and oropharyngeal squamous cell carcinoma (OSC).
Authors: Siok Hoon Ang, Benjamin Haaland, Minn Minn Myint Thu, Sai Sakktee Krishna, Wallace Chen, Siok Gek Jacqueline Hwang, Puay Hoon Tan, Wai Meng David Tai, Eng Huat Tan, Wan-Teck Lim, Mei-Kim Ang
Journal: Journal of Clinical Oncology (2012)

5580 Background: In head and neck cancer (HNC), dysregulation of cell cycle proteins p16 and CYD1 are common. Variable associations of p16 over- and under- expression and CYD1 overexpression with overall survival (OS) have been described in different HNC sites. We evaluated the relationship of p16 and CYD1 expression with clinical characteristics and OS in OSC and HSC. Methods: p16 and CYD1 expression was evaluated by immunohistochemistry in 77 HSC and 103 OSC patients (pts) and recorded as p16N (0% tumor cells stained), p16L (5-69%) and p16H (≥70%), CYD1-(&lt;10%) and CYD1+ (≥10%). OS between groups was evaluated by Kaplan-Meier method and compared by log rank test. Hazard ratio (HR) for death was estimated using multivariable Cox models. Results: Pts were predominantly Chinese (83.6% v 85.4%) with locally advanced HNC (91.4% v 92.2%). Compared to OSC, HSC pts were older (median age 67 v 61 yrs), more likely male (89.3% v 74.0%), current or ex-smokers (83.3% v 63.6%) with higher comorbidity-age combined risk score (ageCCI), less likely p16H (6.5% v 30.1%)(all p&lt;0.001) and had similar CYD+. p16H pts were younger (median age 58 (p16H) v 65 (p16L) v 66 (p16N) yrs, p=0.002), more likely non-smoker (51.4% v 23.4% v 13% p&lt;0.001) with lowest ageCCI (p&lt;0.001). Clinical characteristics did not differ by CYD1 status. At median f/u of 50mths, median OS was 33 mths. Median OS was poor in HSC compared to OSC (23.9 v 72.1, p&lt;0.001). Multivariate analysis showed associations of N2/N3 disease (HR 1.57, p=0.036), ageCCI (HR 1.22 per 1 pt increase, p&lt;0.001), p16 (p16H: ref; p16L: HR 2.34, p=0.045; p16N: HR 2.74, p=0.013) and CYD1+ (HR 1.94, p=0.015) with death, independent of gender, smoking and site. Association of p16 with OS was seen mainly in OSC (median OS p16H: not reached (NR), p16L: 62, p16N: 22 mths, p&lt;0.001) compared with median OS (HSC) (27 v 28 v 21, p=0.609). Similarly the association of CYD1 with OS was mainly in OSC (median OS CYD1-: NR v 23 mths, p&lt;0.001 v HSC: 25 v 25 mths, p=0.19). Conclusions: In OSC, p16 expression correlates with OS, with p16N associated with worst OS. CYD1 has an independent association with OS. Poorer OS in HSC may be due to adverse clinical characteristics. Assessment of p16 and CYD1 status in HSC did not predict for OS.
Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075 Suggests Combination Therapeutic Strategies
Authors: Mai H. Bui, Xiaoyu Lin, Daniel H. Albert, Leiming Li, Lloyd T. Lam, Emily J. Faivre, Scott E. Warder, Xiaoli Huang, Denise Wilcox, Cherrie K. Donawho, George S. Sheppard, Le Wang, Steve Fidanze, John K. Pratt, Dachun Liu, Lisa Hasvold, Tamar Uziel, Xin Lu, Fred Kohlhapp, Guowei Fang, Steven W. Elmore, Saul H. Rosenberg, Keith F. McDaniel, Warren M. Kati, Yu Shen
Journal: Cancer Research (2017)

Abstract ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models, representing a variety of hematologic malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell-cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo combination studies uncovered surprising benefits of low doses of ABBV-075 coupled with bortezomib and azacitidine treatment, despite the lack of in vitro synergy between ABBV-075 and these agents. The in vitro/in vivo activities of ABBV-075 described here may serve as a useful reference to guide the development of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res; 77(11); 2976–89. ©2017 AACR.
DC - SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis
Authors: Yu Zhang, Qianshi Zhang, Mengyang Zhang, Menglang Yuan, Zhaohui Wang, Jingbo Zhang, Xu Zhou, Yinan Zhang, Fang Lin, Heya NA, Shuangyi Ren, Yunfei Zuo
Journal: Molecular Cancer (2017)

Profiling evidences of selectin demonstrate that they play an crucial role in cancer progression and metastasis. However, DC-SIGNR as a family member of selectin participates in gastric cancer liver metastasis remains unknown. The serum level of DC-SIGNR was evaluated in gastric cancer patients by ELISA. Manipulation DC-SIGNR expression in BGC823 and SGC7901 cell lines was mediated by lentivirus. Investigation the biological effects of DC-SIGNR were verified by MTT, wounding and transwell in vitro and experiments on animals to confirm gastric cancer liver metastasis by IVIS. Insights of the mechanism were employed microarray and bioinformatic analysis. Further to confirm the results were conducted by qRT-PCR, western blot and by flow cytometry. DC-SIGNR serum level was significantly increased in gastric cancer patients compared with healthy group. Additionally, DC-SIGNR level was associated with an advanced pathological stage in gastric cancer patients. DC-SIGNR knockdown inhibited the proliferation, migration and invasion of gastric cancer cells in vitro and suppressed the liver metastasis in vivo. While, DC-SIGNR overexpression promoted cell proliferation, migration and invasion. In mechanism, HNRNPKP2 as a lncRNA was upregulated after DC-SIGNR knockdown. Importantly, STAT5A promoted HNRNPKP2 expression after knockdown DC-SIGNR. Furthermore after HNRNPKP2 depletion, the downstream target gene CXCR4 was downregulated. DC-SIGNR promoted gastric cancer liver metastasis mediated with HNRNPKP2 which expression was regulated by STAT5A. And HNRNPKP2 decreased the expression of downstream target gene CXCR4. These findings indicated potential therapeutic candidates for gastric cancer liver metastasis.
Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure
Authors: Milton Packer, Christopher O’Connor, John J.V. McMurray, Janet Wittes, William T. Abraham, Stefan D. Anker, Kenneth Dickstein, Gerasimos Filippatos, Richard Holcomb, Henry Krum, Aldo P. Maggioni, Alexandre Mebazaa, W. Frank Peacock, Mark C. Petrie, Piotr Ponikowski, Frank Ruschitzka, Dirk J. van Veldhuisen, Lisa S. Kowarski, Mark Schactman, Johannes Holzmeister
Journal: New England Journal of Medicine (2017)

In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis.
Abstract #1868: Epstein Barr virus upregulates MDR1 gene expression in breast tumors
Authors: Sajal Ghosh, Douglas Faller, Teresa Mills
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Although EBV infection is ubiquitous among human population and causes self-limiting infectious mononucleosis in young adolescents, it is strongly associated with several human malignancies such as Burkitt\#8217;s lymphoma (BL), Hodgkin\#8217;s disease (HD), nasopharyngeal carcinoma (NPC), posttransplantation lymphoproliferative disease (PTLD) and some sporadic cancers of breast and gastrointestinal tract. In these diseases EBV maintains a state of latency by restricting expression of about 90% of it genes and thus evades immune surveillance. Only eleven EBV gene products are expressed in these malignancies. The precise role of these latent gene products in EBV pathogenesis is not well understood. However, latent membrane protein 1 (LMP1) and non-coding small RNA (EBERs) have been implicated in the genesis of EBV-associated tumors. A recent study demonstrated that EBV infection of an estrogen receptor negative breast cancer cell line MDA-MB-231 activates expression of multidrug resistant protein MDR1. This observation suggests expansion of the harmful repertoire of EBV in EBV-associated tumors. Because of the significance of MDR phenotype in cancer patients, we initiated investigation on the mechanism of MDR1 expression in EBV infected mammary cell lines. We tested the effect of expression of various latent EBV gene products on MDR1 expression in estrogen receptor positive MCF-7 cells. We generated MCF-7 cell derivatives that stably expressed LMP1, EBERs or another latent gene product, BamH1 A rightward transcript (BART). We analyzed total RNA preparations from these cells by reverse transcription and real time PCR analysis for the expression of MDR1 and MDR related protein (MRP). Our data indicated that expression of non-coding RNA EBER activated MDR1 expression in this cell line. Analysis of the sensitivity of the cells that stably expressed EBER, to chemotherapeutic drug paclitaxel showed that such expression also made the MCF-7 cells resistant to paclitaxel. Our studies warrant that the effect of EBER and other latent EBV gene products are tested on multiple estrogen receptor-positive and -negative breast cancer cell lines as well as for their ability to induce drug resistance in animal models of tumorigenesis. These studies will be highly beneficial to formulate new therapeutic avenues for EBV-associated cancers of the breast and other organs that acquire MDR phenotype.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1868.
Stroke in systemic lupus erythematosus: a Swedish population-based cohort study
Authors: Elizabeth V Arkema, Elisabet Svenungsson, Mia Von Euler, Christopher Sjöwall, Julia F Simard
Journal: Annals of the Rheumatic Diseases (2017)

To study the occurrence of ischaemic and haemorrhagic stroke in systemic lupus erythematosus (SLE) compared with the general population by age, sex and time since SLE diagnosis METHODS: Adults with incident SLE were identified from the Swedish National Patient Register (NPR, n=3390) and general population comparators from the Total Population Register were matched on age, sex and county (n=16730). Individuals were followed prospectively until first of death, December 2013, emigration or incident stroke (identified from the NPR, Cause of Death Register and the Stroke Register). Incidence rates, rate differences and HR were estimated comparing SLE with non-SLE. Estimates were stratified by sex, age and time since diagnosis.We observed 126 strokes in SLE and 304 in the general population. Individuals with SLE had a twofold increased rate of ischaemic stroke compared with the general population (HR 2.2; 95% CI 1.7 to 2.8). The HR for intracerebral haemorrhage was 1.4 (95% CI 0.7 to 2.8). There was effect modification by sex and age, with the highest HRs for females and individuals <50 years old. The HR for ischaemic stroke was highest in the first year of follow-up (3.7; 95% CI 2.1 to 6.5).The relative risk of ischaemic stroke in SLE was more than doubled compared with the general population, and importantly, the highest relative risks were observed within the first year after SLE diagnosis. Thus, the first encounter with patients presents an opportunity for rheumatologists to screen for risk factors and intervene.
Assessing treatment efficacy in the subset of responders in a randomized clinical trial
Authors: E.L. Korn, M. Othus, T. Chen, B. Freidlin
Journal: Annals of Oncology (2017)

Durability of response is a clinically relevant dimension of the treatment effect in randomized clinical trials; it is often measured by comparing among the responders the duration of response between the treatment arms. However, since the comparison groups are defined by response (a post-randomization event), it is subject to analysis-by-responder bias, especially if the proportion of responders differs between the arms.Two simple methods are developed that use tumor shrinkage measurements in order to lessen analysis-by-responder bias by generating more comparable patient subsets in the control and experimental arms of the trial. These subsets are then used to estimate between-arm differences in response duration. In the subtraction method, responding patients with the least tumor shrinkage in the treatment arm with more responders are removed from the patient subset for that arm. In the addition method, non-responding patients with the most tumor shrinkage in the treatment arm with fewer responders are added to the patient subset for that arm. In both methods, the numbers of patients subtracted or added are such that the proportion of patients in the modified patient subset is the same as the proportion of responders in the other treatment arm.The methods are demonstrated on a hypothetical dataset where they are shown to eliminate analysis-by-responder bias, and on two published analyses of randomized trials that compared the duration of response between the treatment arms.The proposed methods can lessen the analysis-by-responder bias. These methods to compare duration of response between treatment arms may provide a useful exploratory analysis to measure treatment efficacy among responders.
Evaluation of Amyloid Protective Factors and Alzheimer Disease Neurodegeneration Protective Factors in Elderly Individuals
Authors: Prashanthi Vemuri, David S. Knopman, Timothy G. Lesnick, Scott A. Przybelski, Michelle M. Mielke, Jonathan Graff-Radford, Melissa E. Murray, Rosebud O. Roberts, Maria Vassilaki, Val J. Lowe, Mary M. Machulda, David T. Jones, Ronald C. Petersen, Clifford R. Jack
Journal: JAMA Neurology (2017)

While amyloid and neurodegeneration are viewed together as Alzheimer disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern neurodegeneration may be considerably different. Protection from these ADP factors may be important for aging without significant ADP.