tbuckley/cabot-search huggingface dataset:
Natural History of Myocardial Function in an Adult Human Population
Authors: Kihei Yoneyama, Sirisha Donekal, Bharath A. Venkatesh, Colin O. Wu, Chia-Ying Liu, Marcelo Souto Nacif, Anderson Armstrong, Antoinette S. Gomes, W. Gregory Hundley, Robyn L. McClelland, David A. Bluemke, João A.C. Lima
Journal: JACC. Cardiovascular imaging (2016)
Quantifying the Dynamics of Field Cancerization in Tobacco-Related Head and Neck Cancer: A Multiscale Modeling Approach
Authors: Marc D. Ryser, Walter T. Lee, Neal E. Ready, Kevin Z. Leder, Jasmine Foo
Journal: Cancer Research (2016)

High rates of local recurrence in tobacco-related head and neck squamous cell carcinoma (HNSCC) are commonly attributed to unresected fields of precancerous tissue. Because they are not easily detectable at the time of surgery without additional biopsies, there is a need for noninvasive methods to predict the extent and dynamics of these fields. Here, we developed a spatial stochastic model of tobacco-related HNSCC at the tissue level and calibrated the model using a Bayesian framework and population-level incidence data from the Surveillance, Epidemiology, and End Results (SEER) registry. Probabilistic model analyses were performed to predict the field geometry at time of diagnosis, and model predictions of age-specific recurrence risks were tested against outcome data from SEER. The calibrated models predicted a strong dependence of the local field size on age at diagnosis, with a doubling of the expected field diameter between ages at diagnosis of 50 and 90 years, respectively. Similarly, the probability of harboring multiple, clonally unrelated fields at the time of diagnosis was found to increase substantially with patient age. On the basis of these findings, we hypothesized a higher recurrence risk in older than in younger patients when treated by surgery alone; we successfully tested this hypothesis using age-stratified outcome data. Further clinical studies are needed to validate the model predictions in a patient-specific setting. This work highlights the importance of spatial structure in models of epithelial carcinogenesis and suggests that patient age at diagnosis may be a critical predictor of the size and multiplicity of precancerous lesions. Cancer Res; 76(24); 7078-88. ©2016 AACR.
Ponatinib Is Active Against the CUX1-FGFR1 Fusion Kinase and Against Imatinib Resistance Mutations of the FIP1L1-PDGFRα Fusion Kinase and of KIT,
Authors: Els Lierman, Sanne Smits, Jan Cools, Barbara Dewaele, Maria Debiec-Rychter, Peter Vandenberghe
Journal: Blood (2011)
Multiscale Modeling of Muscular-Skeletal Systems
Authors: Gang Seob Jung, Markus J. Buehler
Journal: Annual Review of Biomedical Engineering (2017)

Multiscale modeling of muscular-skeletal systems-the materials and structures that help organisms support themselves and move-is a rapidly growing field of study that has contributed key elements to the understanding of these systems, especially from a multiscale perspective. The systems, including materials such as bone and muscle, have hierarchical structures ranging from the nano- to the macroscale, and it is difficult to understand their macroscopic behaviors, both physiological and pathological, without knowledge of their hierarchical structures and properties. In this review, we discuss the methods of multiscale modeling. Through a series of case studies about key materials in muscular-skeletal systems, we describe how different methods can bridge the gap between hierarchical structures and their roles in the systems' mechanical properties. In particular, we emphasize the importance of the quality of minerals in bone. Finally, we discuss biomimetic material designs facilitated by additive manufacturing technology.
90Yttrium-Ibritumomab Tiuxetan for Non-Hodgkin Lymphoma: Results after a Median Follow-up of 5 Years in a Single Institution
Authors: Antonella Anastasia, Enrico Morello, Alessandra Tucci, Alessandro Re, Marina Motta, Chiara Pagani, Raffaele Giubbini, Giancarlo Magri, Marta Petullà, Giuseppe Rossi
Journal: Blood (2014)
Patient (PT) participation and disaster (D) agency (AG) coordination for oncology (ONC) PT D preparedness (PREP): Analysis of the Great Southern California Shake Out (GSCSO) drill and implications for regional and national emergency (E) planning (P)
Authors: R. A. Moss, C. Presant, M. Lamb
Journal: Journal of Clinical Oncology (2009)

e17549 Background: PT E PREP is important (Katrina, Los Angeles fires 2007, 2008). MOASC developed the ONC PT E Network (OPEN) (www.open-central.com; Proc ASCO 2006 a6142, 2007 a17003 , and 2008 a6545). On Novermber 13, 2008, 28 organizations and sponsors (US and Cal govt and private) conducted the GSCSO drill with a Richter scale 7.8 earthquake. MOASC tested OPEN as part of GSCSO. Methods: In OPEN, PTs were given wallet cards with E information (diagnosis, stage, treatment, doses). As part of GSCSO, MOASC a) surveyed two practices in two counties to evaluate ONC PT motivation and PREP; and b) surveyed D AG to determine the triage program for ONC PTs who required CT. PTs in two offices pretended the ONC offices had been closed due to the D. They were asked to call the MOASC E line and advise an address to which they would evacuate where MOASC referred PTs to a participating physician for chemotherapy (CT). Results: 36 PTs participated. In office interviews, PTs had concerns about transportation to evacuation locations during the D, how they would find available phone lines during an E, and whether MOASC lines would be responsive in an E. Only 5 PTs (13.9%) contacted the MOASC E line within 24 hours. The 4 most available D AGs were unaware of how to triage ONC PTs requiring CT, and were unaware of MOASC and ASCO resources. They wanted to refer ONC PTs to E rooms which would be unresponsive to PT needs for CT. Conclusions: ONC PTs are not yet motivated for D PREP (concerns regarding current CT have higher priority). Responding AGs are not capable of correctly triaging ONC PTs for CT. Neither PTs nor doctors have a list of D AGs. State ONC societies, ASCO, and ACCC should create regional E phone response lines through state societies, regional E oncologist contacts, and a single national facilitating D response office, as well as coordinate regional and national D AGs so that PTs can be triaged to appropriate resources. National D AGs funded to coordinate responses should be the source of support for this process. Motivating ONC PTs for EP will require reimbursed practice participation. No significant financial relationships to disclose.
E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1
Authors: Guanhua Song, Bingyu Liu, Zhihui Li, Haifeng Wu, Peng Wang, Kai Zhao, Guosheng Jiang, Lei Zhang, Chengjiang Gao
Journal: Nature Immunology (2016)
Human Microbiome <i>Fusobacterium Nucleatum</i> in Esophageal Cancer Tissue Is Associated with Prognosis
Authors: Kensuke Yamamura, Yoshifumi Baba, Shigeki Nakagawa, Kosuke Mima, Keisuke Miyake, Kenichi Nakamura, Hiroshi Sawayama, Koichi Kinoshita, Takatsugu Ishimoto, Masaaki Iwatsuki, Yasuo Sakamoto, Yoichi Yamashita, Naoya Yoshida, Masayuki Watanabe, Hideo Baba
Journal: Clinical Cancer Research (2016)

Fusobacterium nucleatum (F. nucleatum) is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. Although there are several reports of the relationship between F. nucleatum and the clinical outcome in human cancers, its prognostic significance in esophageal cancer remains unclear.We quantified F. nucleatum DNA in 325 resected esophageal cancer specimens by qPCR. Significant pathways in F. nucleatum-positive esophageal cancer tissues were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using microarray data.Esophageal cancer tissues contained significantly more F. nucleatum DNA than matched normal esophageal mucosa (P = 0.021; n = 60). F. nucleatum DNA was detected in 74 of 325 cases (23%). F. nucleatum DNA positivity was significantly associated with tumor stage, but not with sex, age, performance status, tobacco use, alcohol use, histology, tumor location, or preoperative treatment. F. nucleatum DNA positivity was also significantly associated with cancer-specific survival [log-rank P = 0.0039; univariate HR = 2.01; 95% confidence interval (CI), 1.22-3.23; P = 0.0068; multivariate HR = 1.78; 95% CI, 1.06-2.94; P = 0.031]. The top-ranked KEGG pathway in F. nucleatum-positive tissues was "cytokine-cytokine receptor interaction." A significant relationship between F. nucleatum and the chemokine CCL20 was validated by IHC.F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574-81. ©2016 AACR.
Impact of age and medical comorbidity (MC) on adjuvant treatment outcomes for stage III colon cancer (CC): A pooled analysis of individual patient data from four randomized controlled trials.
Authors: Daniel G. Haller, Michael O'Connell, Thomas H. Cartwright, Christopher Twelves, Edward McKenna, Weijing Sun, Wasif M. Saif, Luen F. Lee, Greg Yothers, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2012)

3522 Background: Studies show significantly improved disease-free and overall survival (DFS, OS) for oxaliplatin (Ox)-based vs. leucovorin/5-fluorouracil (LV/5-FU) adjuvant therapy in CC, with conflicting reports of Ox benefit in patients &gt; 70 years old. The impact of MC on Ox benefit has not been assessed. We assessed the impact of age and MC on adjuvant treatment outcomes for stage III CC. Methods: N = 4,819 patients from NSABP C-08, XELOXA, X-ACT, and AVANT were analyzed by Ox therapy (XELOX/FOLFOX) vs. LV/5-FU, MC, and age; patients treated with bevacizumab were excluded. Endpoints were DFS (primary), OS, and safety. MC was assessed (except NSABP C-08) by adapted Charlson Comorbidity and NCI Combined Indices (CCI, NCI): Low (≤ 1) vs. high (&gt; 1). Hazardratios (HR) were estimated by Cox regression analyses. Multivariate Cox regression analyses (MVA) tested for independent effects of age and MC on Ox benefit, controlling for gender, T, and N stage. Results: Patient demographics, MC, and disease characteristics (except lymph nodes examined) were well balanced across groups. Median follow-up was shorter in NSABP C-08 and AVANT (36 and 50 months) vs. XELOXA and X-ACT (83 and 74 months). MVA-confirmed DFS/OS benefit was consistently shown for XELOX/FOLFOX vs. LV/5-FU, regardless of age or MC. Grade 3/4 serious adverse event (AE) rates were comparable across cohorts and CCI scores, and higher in patients aged ≥ 70. Grade 3/4 AEs of interest, including peripheral sensory neuropathy, were comparable across ages and CCI scores, and higher with XELOX/FOLFOX. Conclusions: Ox benefit is modestly attenuated in patients aged ≥ 70; however, significant benefit is observed regardless of age or MC in this analysis. Our results further support XELOX or FOLFOX as standard options for the adjuvant management of stage III CC in all age groups. [Table: see text]
Evaluating and Improving the Cardiovascular Drug Supply for Better Global Health
Authors: Mark D. Huffman
Journal: JAMA Cardiology (2016)

Marie Antignac, PharmD, PhD; Bara Ibrahima Diop, MD; Bernard Do, PharmD, PhD; Roland N’Guetta, MD; Ibrahim Ali Toure, MD; Patrick Zabsonre, MD; Xavier Jouven, MD, PhD
GW26-e2441 Left atrium appendage orifice area and left atrial volume as predictors for the risk of stroke in patients with atrial fibrillation
Authors: Jie-ming Zhu, Rui-min Dong, Zhen-da Zheng, Xu-jing Xie, Jie Qin, Yan-ting Luo, Jin-lai Liu
Journal: Journal of the American College of Cardiology (2015)
Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia.
Journal: Circulation (1994)

BACKGROUND Although coronary thrombosis plays a critical role in the pathogenesis of unstable angina and non-Q-wave myocardial infarction (NQMI), the effects of thrombolytic therapy in these disorders is not clear. Also, the role of routine early coronary arteriography followed by revascularization has not been established. METHODS AND RESULTS Patients (n = 1473) seen within 24 hours of ischemic chest discomfort at rest, considered to represent unstable angina or NQMI, were randomized using a 2 x 2 factorial design to compare (1) TPA versus placebo as initial therapy and (2) an early invasive strategy (early coronary arteriography followed by revascularization when the anatomy was suitable) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients were treated with bed rest, anti-ischemic medications, aspirin, and heparin. The primary end point for the TPA-placebo comparison (death, myocardial infarction, or failure of initial therapy at 6 weeks) occurred in 54.2% of the TPA-treated patients and 55.5% of the placebo-treated patients (P = NS). Fatal and nonfatal myocardial infarction after randomization (reinfarction in NQMI patients) occurred more frequently in TPA-treated patients (7.4%) than in placebo-treated patients (4.9%, P = .04, Kaplan-Meier estimate). Four intracranial hemorrhages occurred in the TPA-treated group versus none in the placebo-treated group (P = .06). The end point for the comparison of the two strategies (death, myocardial infarction, or an unsatisfactory symptom-limited exercise stress test at 6 weeks) occurred in 18.1% of patients assigned to the early conservative strategy and 16.2% of patients assigned to the early invasive strategy (P = NS). In the latter, the average length of initial hospitalization, incidence of rehospitalization within 6 weeks, and days of rehospitalization all were significantly lower. CONCLUSIONS In the overall trial, patients with unstable angina and NQMI were managed with low rates of mortality (2.4%) and myocardial infarction or reinfarction (6.3%) at the time of the 6-week visit. These results can be achieved using either an early conservative or early invasive strategy, the latter resulting in a reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs. The addition of a thrombolytic agent is not beneficial and may be harmful.
Updated Efficacy and Safety Data from the AETHERA Trial of Consolidation with Brentuximab Vedotin after Autologous Stem Cell Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse
Authors: John Sweetenham, Jan Walewski, Auayporn P. Nademanee, Tamas Masszi, Edward Agura, Jerzy Holowiecki, Muneer H. Abidi, Andy I Chen, Patrick Stiff, Simonetta Viviani, Angelo Michele Carella, Dzhelil Osmanov, Veronika Bachanova, Anna Sureda, Dirk Huebner, Emily K Larsen, Naomi N Hunder, Craig H Moskowitz
Journal: Blood (2015)
Very Poor Survival of Patients with AML Who Relapse after Achieving a First Complete Remission: The Eastern Cooperative Oncology Group Experience.
Authors: Jacob M. Rowe, Xiaochun Li, Peter A. Cassileth, Frederick R. Appelbaum, Charles A. Schiffer, Peter H. Wiernik, Mark R. Litzow, Larry D. Cripe, Hillard M. Lazarus, Elisabeth Paietta, Gordon W. Dewald, Howard J. Weinstein, Angela K. Ogden, William G. Woods, Lois Shepherd, James H. Feusner, Clara D. Bloomfield, Martin S. Tallman
Journal: Blood (2005)
Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms
Authors: Lauren M. Postlewait, Cecilia G. Ethun, Mia R. McInnis, Nipun Merchant, Alexander Parikh, Kamran Idrees, Chelsea A. Isom, William Hawkins, Ryan C. Fields, Matthew Strand, Sharon M. Weber, Clifford S. Cho, Ahmed Salem, Robert C. G. Martin, Charles Scoggins, David Bentrem, Hong J. Kim, Jacquelyn Carr, Syed Ahmad, Daniel E. Abbott, Gregory C. Wilson, David A. Kooby, Shishir K. Maithel
Journal: JAMA Surgery (2016)

Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN.To examine the preoperative risk factors for malignancy in resected MCNs and to assess outcomes of MCN-associated adenocarcinoma.Patients who underwent pancreatic resection of MCNs at the 8 academic centers of the Central Pancreas Consortium from January 1, 2000, through December 31, 2014, were retrospectively identified. Preoperative factors of patients with and without malignant tumors were compared. Survival analyses were conducted for patients with adenocarcinoma.Binary logistic regression models were used to determine the association of preoperative factors with the presence of MCN-associated malignancy.A total of 1667 patients underwent resection of pancreatic cystic lesions, and 349 (20.9%) had an MCN (310 women [88.8%]; mean (SD) age, 53.3 [14.7] years). Male sex (odds ratio [OR], 3.72; 95% CI, 1.21-11.44; P = .02), pancreatic head and neck location (OR, 3.93; 95% CI, 1.43-10.81; P = .01), increased radiographic size of the MCN (OR, 1.17; 95% CI, 1.08-1.27; P < .001), presence of a solid component or mural nodule (OR, 4.54; 95% CI, 1.95-10.57; P < .001), and duct dilation (OR, 4.17; 95% CI, 1.63-10.64; P = .003) were independently associated with malignancy. Malignancy was not associated with presence of radiographic septations or preoperative cyst fluid analysis (carcinoembryonic antigen, amylase, or mucin presence). The median serum CA19-9 level for patients with malignant neoplasms was 210 vs 15 U/mL for those without (P = .001). In the 44 patients with adenocarcinoma, 41 (93.2%) had lymph nodes harvested, with nodal metastases in only 14 (34.1%). Median follow-up for patients with adenocarcinoma was 27 months. Adenocarcinoma recurred in 11 patients (25%), with a 64% recurrence-free survival and 59% overall survival at 3 years.Adenocarcinoma or high-grade dysplasia is present in 14.9% of resected pancreatic MCNs for which risks include male sex, pancreatic head and neck location, larger MCN, solid component or mural nodule, and duct dilation. Mucinous cystic neoplasm-associated adenocarcinoma appears to have decreased nodal involvement at the time of resection and increased survival compared with typical pancreatic ductal adenocarcinoma. Indications for resection of MCNs should be revisited.
GW26-e2344 The optimal cutoff point of waist-to-hip ratio for Uyghur population aged over 35 years in Xinjiang
Authors: None Abudukeremu, Shuo Pan, Yining Yang, Xiang Ma, Xiaomei Li, Zhenyan Fu, Ying Huang, Xiang Xie, Fen Liu, Yitong Ma
Journal: Journal of the American College of Cardiology (2015)
Abstract A07: Plinabulin: Evidence for an immune-mediated mechanism of action
Authors: George Kenneth Lloyd, Philipp Mueller, ALfred Zippelius, Lan Huang
Journal: Cancer Research (2016)

Abstract The purpose of this study was to investigate the evidence for an immune-mediated mechanism of action for plinabulin. Plinabulin, a novel compound for use in oncology, is an inhibitor of tubulin polymerization, induces direct tumor cell apoptosis (Nicholson et al, 2006), inhibits angiogenesis and activates the JNK pathway (Singh et al, 2011) and is in Phase 3 trials for NSCLC (Bazhenova, 2015). The methods for the in vitro and in vivo studies performed are described by Martin et al (2014) and Müller et al (2014). Recent data from in vitro studies demonstrate that plinabulin enhances immune responses as (1) it increases dendritic cell maturation as evidenced by elevated levels of CD40, MHCII, CD80 and CD86 and (2) the release of pro-inflammatory cytokines such as IL-1beta, IL-6 and IL12p40. These increases were similar to those observed with LPS. Paclitaxel and etoposide were inactive in these assays. In the MC-38 syngeneic colon tumor model in the C57BL/6 immunocompetent mouse, plinabulin (7.5 mg/kg, IP, BIW) significantly enhanced the therapeutic effect of combined PD-1/CTLA-4 inhibition on tumor volume, with a maximal effect occurring between days 13-20 after initiation of treatment. When tumor weight was measured at necropsy, plinabulin significantly enhanced the effect of both PD-1 inhibition and combined PD-1 + CTLA-4 inhibition. In this regard, evidence has been provided that agents which interfere with tubulin polymerization (e.g. ansamytocin-P3, dolastatin-10), but not microtubule stabilizing agents (e.g. docetaxel, paclitaxel) promote anti-tumor immunity as demonstrated by dendritic cell maturation and enhanced T-cell activation both in vitro and in vivo. In addition, the microtubule depolymerizing agents act synergistically with immune checkpoint inhibitors (Martin et al, 2014, Müller et al, 2014). These data indicate an immune mediated mechanism of action of plinabulin and provide the basis for initiating a clinical trial of plinabulin with the PD-1 mAb Nivolumab in metastatic NSCLC (Yeh et al, 2015). Citation Format: George Kenneth Lloyd, Philipp Mueller, ALfred Zippelius, Lan Huang. Plinabulin: Evidence for an immune-mediated mechanism of action. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A07.
Blockade of Chemotherapy-Induced Thrombocytopenia by Bax Inhibiting Peptides (BIPs) in Mouse Model.
Authors: Jose A. Gomez, Vivian Gama, Tomoyuki Yoshida, Michelle Stapleton, Cathy Paddock, David A. Wilcox, Peter J. Newman, Eimei Sato, Shigemi Matsuyama
Journal: Blood (2007)
Review: Newer and older drugs do not differ for lower urinary tract symptoms due to benign prostatic hyperplasia
Authors: Cara Foldes, Steven E. Canfield
Journal: Annals of Internal Medicine (2016)

Source Citation Brasure M, MacDonald R, Dahm P, et al. Newer medications for lower urinary tract symptoms attributed to benign prostatic hyperplasia: a review. Comparative Effectiveness Review No. 178. Rockville, MD: Agency for Healthcare Research and Quality; May 2016. 27336104
Health service finances are at crunch point, says NHS Providers
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The government cannot expect to “have its cake and eat it” by restricting NHS funding while expecting services to stay at current levels, a senior NHS leader has warned.

Chris Hopson, chief executive of NHS Providers, the body that represents NHS trusts in England, said that the health service had reached a “tipping point” where it was being asked to deliver services “that it simply cannot carry on delivering for the funding available.” He also called for a proper debate with the public about increasing NHS funding and the consequences of continuing under the current financial squeeze.

Hopson’s remarks came after the Guardian reported that the prime minister has told NHS England’s chief executive, Simon Stevens, that the government’s autumn statement would contain no extra money for the NHS.1 Theresa May is reported to have told Stevens that the NHS should focus on making further efficiency savings to plug the £22bn …
Involvement Of S100 Proteins and Hsp90 In The Pathogenesis Of Graft-Versus-Host Disease After Allogeneic Hematopoetic Cell Transplantation
Authors: Katharina Reinhardt, Dirk Föll, Thomas Vogl, Falko Fend, Christian Gille, Tobias Feuchtinger, Peter Lang, Rupert Handgretinger, Wolfgang A. Bethge, Ursula Holzer
Journal: Blood (2013)