tbuckley/cabot-search huggingface dataset:
Epidermal growth factor receptor expression is associated with poor outcome in cutaneous squamous cell carcinoma
Authors: J. Cañueto, E. Cardeñoso, J.L. García, Á. Santos-Briz, A. Castellanos-Martín, E. Fernández-López, A. Blanco Gómez, J. Pérez-Losada, C. Román-Curto
Journal: British Journal of Dermatology (2016)

Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans after basal cell carcinoma, and its incidence is dramatically rising. CSCC is rarely problematic, but given its high frequency, the absolute number of complicated cases is also high. It is necessary to identify molecular markers in order to recognize those CSCCs with poor prognosis. There is controversy concerning the role of epidermal growth factor receptor (EGFR) as a marker of prognosis in CSCC. In addition, EGFR‐targeted therapies have emerged in recent years and a better understanding of the role of EGFR in CSCC may be of help for some patients in predicting prognosis and guiding curative management. To evaluate the role of EGFR as a prognostic factor in CSCC. We evaluated clinical and histopathological features, including events of poor clinical evolution, in a series of 94 cases of CSCC. We also analysed EGFR expression by immunohistochemistry, fluorescent in situ hybridization and quantitative polymerase chain reaction. We detected EGFR in 85 cases (90%), with overexpression in 33 cases (35%), and aberrant EGFR expression in the cytoplasm in 50 cases (53%). EGFR overexpression in the primary tumours was associated with lymph node progression, tumour–nodes–metastasis stage progression and proliferation (Ki‐67 staining) in CSCC. EGFR overexpression and poor grade of differentiation were the strongest independent variables defining lymph node metastasis and progression in CSCC in a logistic regression model. We demonstrate that EGFR overexpression has prognostic implications associated with lymph node metastasis and progression in CSCC.
Emergency Department Use and Hospital Admissions Among Patients With End-Stage Renal Disease in the United States
Authors: Brendan P. Lovasik, Rebecca Zhang, Jason M. Hockenberry, Justin D. Schrager, Stephen O. Pastan, Sumit Mohan, Rachel E. Patzer
Journal: JAMA Internal Medicine (2016)

This population epidemiology study uses US Renal Data System data to characterize emergency department (ED) visits, hospitalizations from the ED, and demographic characteristics of patients with end-stage renal disease who used ED services between 2005 and 2011.
A phase 1 study of RX-5902, an oral agent targeting phosphorylated p68, to treat subjects with advanced solid tumors.
Authors: S. Gail Eckhardt, William Larry Gluck, Martin Gutierrez, Christine Peterson, Ely Benaim
Journal: Journal of Clinical Oncology (2015)

TPS2608 Background: RX-5902 is a novel compound that targets phosphorylated p68 RNA helicase (also known as DDX5), a member of the DEAD box family of RNA helicases. Phosphorylated p68 may play a vital role in cell proliferation and tumor/cancer progression. As a single agent, RX-5902 inhibits tumor growth and enhances survival in a variety of in vivo animal xenograft tumor models (e.g., renal, ovarian, pancreatic, melanoma). Methods: This Phase 1, open-label, multicenter study evaluates the efficacy and safety of RX-5902 in subjects with solid tumors. RX-5902 is administered orally once weekly for 3 weeks with 1 week of rest in each 4 week cycle. Dose escalation starts with an accelerated design treating 1 subject per dose followed by a standard 3 + 3 design using a modified Fibonacci sequence after the occurrence of a single Grade 2 or greater adverse event that is considered at related to RX-5902. The primary endpoint is the overall safety profile characterized by the type, frequency, severity, timing of onset, duration and relationship to study therapy of any adverse events, or abnormalities of laboratory tests or electrocardiograms as well as the description of any dose limiting toxicities that occur during Cycle 1, serious adverse events, or adverse events leading to discontinuation of study treatment. Secondary endpoints include pharmacokinetic parameters (e.g., time to maximum observed concentration [Tmax], maximum observed plasma concentration [Cmax], trough concentration [Ctrough], area under the concentration-time curve [AUC]) and Indices of anti-tumor activity (e.g., overall response rate , time to response, duration of response, and progression-free surviva during treatment. Exploratory endpoints are biochemical levels of drug targets in blood and tumor samples. Eligible subjects must have confirmed histologic or cytologic evidence of metastatic or locally advanced solid neoplasm that has failed to respond to standard therapy, progressed despite standard therapy or for which standard therapy does not exist. There is no limit on the number of prior treatment regimens. Clinical trial information: NCT02003092.
Ultrasociality: When institutions make a difference
Authors: Petr Houdek, Julie Novakova, Dan Stastny
Journal: Behavioral and Brain Sciences (2016)

We present arguments that the analogy between humans and social insects is coincidental, rather than based upon real similarities. In their claims, Gowdy & Krall largely omit the role of institutions in the formation of complex societies, warfare, and regulation. They also offer no strong explanation for the expansion of agriculture despite its early detrimental effects except the "mistake hypothesis" (cf. Diamond 1987).
Monitoring of B Cell Subpopulations in Patients with Chronic Graft-Versus-Host Disease May Predict Response to Extracorporeal Photopheresis
Authors: Zoya Kuzmina, Winfried Pickl, Robert Knobler, Michal Kouba, Nina Worel, Georg Stary, Margit Mitterbauer, Peter Kalhs, Hildegard Greinix
Journal: Blood (2008)
223P Efficacy and safety of weekly nab-paclitaxel (nab-P) plus gemcitabine (Gem) in Chinese patients (Pts) with metastatic adenocarcinoma of the pancreas (MPC): A phase II study
Authors: X. Yu, L. Shen, J. Hao, L. Wang, H. Pan, G. Han, J. Xu, Y. Zhang, S. Yang, J. Ying, M. Li, D. Begic, B. Lu, R. Xu
Journal: Annals of Oncology (2015)
Screening for Breast Cancer
Authors: Myron Moskowitz
Journal: JAMA (1977)

<h3>To the Editor.—</h3> Breast self-examination, physical examination, and mammography lack the accuracy necessary to be considered diagnostic tools for breast cancer. They are, however, screening tools that, when aggressively used, will discover many highly curable, small cancers (in situ lobular, in situ ductal, and intraductal cancer with less than 10% microinvasion, 5-mm invasive cancer, or tubular cancer), which we estimate to have a 20-year relative survival rate of 90%. As the article by Lesnick (237:967, 1977) has so eloquently shown, these modalities, as currently practiced in the nonscreen setting, are of very little value in detecting these small cancers in younger women. Contrariwise, our experience at the Breast Cancer Demonstration Project in Cincinnati indicates that of 17 cancers found in self-selected volunteers aged 35 to 44 years, 12 (71%) were minimal. Ten of 17 (58%) were found by mammography alone, and eight of ten found by mammography alone were minimal.
Somatic Engineering of Oncogenic Chromosomal Rearrangements: A Perspective
Authors: Danilo Maddalo, Andrea Ventura
Journal: Cancer Research (2016)

The ability to engineer specific mutations in mice has proven essential to advancing our understanding of the molecular basis of cancer. Chromosomal rearrangements, a common and clinically relevant class of cancer-causing mutations, have however remained difficult to faithfully recapitulate in vivo The development of genetic tools for in vivo somatic genome editing has recently overcome this limitation and led to the generation of more sophisticated and accurate preclinical models of human cancers. Here, we review the potential applications of these new technologies to the study of tumor biology and discuss their advantages over more conventional strategies, their limitations, and the remaining challenges. Cancer Res; 76(17); 4918-23. ©2016 AACR.
Capecitabine/trastuzumab for the first-line treatment of patients with HER2-positive metastatic breast cancer (MBC).
Authors: A. Chan, D. Yamamoto, R. Bell
Journal: Journal of Clinical Oncology (2010)

1139 Background: Preclinical studies demonstrate at least additive effects on tumor growth inhibition and growth delay when trastuzumab (H) is combined with capecitabine (X) in human breast cancer xenograft models, and provide a rationale for the development of XH combination therapy in patients with HER2-positive MBC. Data from the randomized, phase III GBG-26/BIG03-05 study demonstrated that this combination is active in patients with H-pretreated MBC, with no unexpected side effects. Phase II studies have also shown the efficacy of XH therapy in anthracycline-/taxane-pretreated MBC. This review evaluates the available evidence for XH-based therapy in the first-line MBC setting. Methods: We reviewed efficacy and safety data for 335 patients who received XH combination therapy as first-line treatment for HER2-positive MBC in four phase II studies. Wardley et al. randomized patients with HER2-overexpressing, inoperable MBC to H-docetaxel (T) with or without X until disease progression (CHAT study). In another nonrandomized study women with HER2-postive MBC received XH plus oral vinorelbine (N). A further two uncontrolled, single-arm trials in China and Japan assessed XH therapy in patients with HER2-positive MBC. Results: Across studies, median overall response rates (ORR) were 63-77%, and median time to progression (TTP)/progression-free survival (PFS) was 9.2-18.6 months. Median overall survival (OS) of up to 25.6 months was reported (Table). The regimens were generally well tolerated, with manageable adverse event profiles. The most common nonhematological grade 3/4 adverse events were hand-foot syndrome (2-20%) and diarrhea (2-16%). In the CHAT and HXN studies grade 3/4 neutropenia and febrile neutropenia were seen in 54-69% and 8-15% of patients, respectively. Conclusions: These data support the consideration of XH combinations in first-line treatment of metastatic HER2-positive breast cancer. Regimen n ORR, % Median TTP, months OS, months XHT 222 70.5 18.6 Not reached XHN 50 77 12.8* Not reached XH (China) 43 63 NR NR XH (Japan) 20 65 9.2 25.6 * PFS; NR > not reported Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche
ECG Challenge: May 13, 2014
Authors: Philip Podrid
Journal: Circulation (2014)

A 66-year-old man with a history of hypertension and hyperlipidemia presents with substernal chest burning that he felt was gastrointestinal related because it occurred shortly after lunch.However, antacids were without benefit.After 4 to 5 hours, he decided to go to an emergency room.Because of the ECG abnormalities and elevated serum troponin and creatine kinas-MB, he was brought to the cardiac catheterization laboratory.One-vessel disease (right coronary artery) was noted, and a percutaneous coronary intervention was performed.What is the diagnosis?
Social and Economic Factors in Patients With Coronary Disease
Authors: David P. Lux
Journal: JAMA (1992)

To the Editor.  —I am pleasantly surprised to see that the recent findings of the effect of social and economic resources on outcome in coronary  disease, published by Williams et al 1 comes from an institution (Duke University Medical Center) that has furnished my hospital with countless guest lecturers who religiously preach the gospel of the angiographically documented open coronary artery as the final word in postinfarction prognosis, and to explain how the finding of the TIMI-II 2 and SWIFT 3 trials, that postinfarction patients treated conservatively after thrombolysis do as well as individuals catheterized routinely, does not apply to the population treated at Duke. With this evidence that social and economic status affects prognosis in coronary  disease, a clinical trial of intervention seems appropriate.  As no clinical trial has to my knowledge demonstrated increased survival with performing routine angiography on all postthrombolysis patients who do not have
Primary Care as Part of US Health Services Reform
Authors: Alice M. Godfrey
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Starfield and Simpson<sup>1</sup>are to be complimented on their recommendations for strengthening the provision of primary medical services in the United States. However, I would go further and suggest that access to specialist services, except in the case of an emergency, should be only by referral from a primary care provider. Under the reformed health service it would be feasible for everyone to have a primary care provider of record. Only this provider would be granted the discretion to refer a patient for specialist care. In Britain it is unethical for a specialist to see a patient without referral from a general practitioner; penalties could be imposed on specialists accepting patients without referral. This policy would achieve considerable economy by avoiding the costly duplication of services that now occurs and would permit each provider to practice the type of medicine he or she does best. A
Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma
Authors: Kai Qing, Zhen Jin, Wanbin Fu, Wenfang Wang, Zhao Liu, Xiaoyang Li, Zizhen Xu, Junmin Li
Journal: Journal of Hematology & Oncology (2016)

We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235.
Protoporphyrin IX in the skin measured noninvasively predicts photosensitivity in patients with erythropoietic protoporphyria
Authors: I.M. Heerfordt, H.C. Wulf
Journal: British Journal of Dermatology (2016)

Erythropoietic protoporphyria (EPP) is a rare genetic disease that causes severe sensitivity to visible light as a result of protoporphyrin IX (PpIX) accumulation in the skin.To establish a noninvasive method to measure PpIX in the skin of patients with EPP and to investigate how skin PpIX relates to erythrocyte PpIX and photosensitivity.Skin PpIX was measured in 25 patients with EPP by calculating the difference in PpIX fluorescence before and after complete photobleaching of PpIX using controlled illumination. The patients reported symptoms during the illumination and skin erythema was measured before and after illumination. Confirmation of the presence of PpIX was obtained in seven patients by measuring the in vivo fluorescence emission spectrum. This method was used to examine skin PpIX during the hours after an illumination in seven patients.We established a noninvasive method to measure skin PpIX based on measurements of PpIX fluorescence before and after complete PpIX photobleaching. The patients had an average skin PpIX of 2·0 units and skin emission spectra confirmed the presence of skin PpIX (peak emission 632 nm). Skin PpIX was associated with erythrocyte PpIX (P = 0·002, R2 = 0·34), skin erythema (P = 0·001, R2 = 0·47) and symptoms during illumination. Furthermore, skin PpIX increased during the hours after illumination.We have developed a noninvasive method to measure skin PpIX in patients with EPP. Skin PpIX is dependent on erythrocyte PpIX and exposure of the skin to light. This method can be used for objective monitoring of treatment effect.
Real-world treatment patterns and the uptake of biologics in elderly medicare patients with metastatic colon cancer.
Authors: C. Daniel Mullins, Kaloyan A. Bikov, Brian S. Seal, Anna Hung, Nader Hanna
Journal: Journal of Clinical Oncology (2015)

540 Background: Metastatic colon cancer (mCC) patients may receive multiple lines of treatment (Tx1, Tx2, etc.) consisting of one or more cytotoxic (CYT: 5FU/LV, oxaliplatin [OX], irinotecan [IRI]) and biologic (BIO: bevacizumab [BEV], cetuximab [CET], panitumumab [PAN]) drugs. The National Comprehensive Cancer Network (NCCN) provides evidence-based Tx recommendations for each line. The objective of this study was to examine real-world clinical practice patterns between 2002 and 2010. In particular, we compared the most common regimens across Tx lines and how Tx patterns changed over time. We also documented the uptake and use of new BIOs. Methods: We used population-based SEER-Medicare data to determine Tx1, Tx2, and Tx3 regimens of 4,616 mCC patients (the median age at diagnosis was 78) diagnosed in 2003-2009 and followed through 2010. We will use an algorithm previously developed by us to identify regimens. Results: The most common CYT backbone in Tx1 was OX (51% of patients) followed by 5FU/LV (30%). In comparison, IRI was a preferred choice in Tx2 (65%) and Tx3 (31%). In 2003, the most common Tx1 regimens were 5FU/LV- (56%) and IRI-based (35%). 5FU/LV and IRI use decreased to 22% and 9% respectively in 2009, while OX use increased from 7% in 2003 to 63% in 2009. In 2004, the FDA approved BEV for Tx1. BEV’s share increased from 9% in 2004 to 53% in 2005. BEV was used in 9% of Tx2 regimens in 2004 and 46% in 2005. CET was approved in 2004. CET was used in less than 5% of Tx1 regimens in any year up to 2010. CET use in Tx2 increased from 19% to 27% between 2005 and 2007, and declined to 23% in 2010. The FDA approved PAN in September 2006 for treatment after failure of CYT-based regimens, i.e., primarily in Tx3 and beyond. Only 350 (8%) of patients received Tx3, and of these 59 (17%) received PAN without a CYT backbone. One in three Tx3 regimens consisted of biologics only (54% CET, 43% PAN). Conclusions: This study used SEER-Medicare registry data to examine and document real-world clinical practice patterns in treatment of elderly mCC patients between 2003 and 2010. We observed that as new biologic agents were introduced to the market, variations in the combinations and the number of treatment have significantly and rapidly changed.
Bi-layered polyurethane – Extracellular matrix cardiac patch improves ischemic ventricular wall remodeling in a rat model
Authors: Antonio D'Amore, Tomo Yoshizumi, Samuel K. Luketich, Matthew T. Wolf, Xinzhu Gu, Marcello Cammarata, Richard Hoff, Stephen F. Badylak, William R. Wagner
Journal: Biomaterials (2016)
Differences in the Quality of Pediatric Resuscitative Care Across a Spectrum of Emergency Departments
Authors: Marc Auerbach, Travis Whitfill, Marcie Gawel, David Kessler, Barbara Walsh, Sandeep Gangadharan, Melinda Fiedor Hamilton, Brian Schultz, Akira Nishisaki, Khoon-Yen Tay, Megan Lavoie, Jessica Katznelson, Robert Dudas, Janette Baird, Vinay Nadkarni, Linda Brown
Journal: JAMA Pediatrics (2016)

The quality of pediatric resuscitative care delivered across the spectrum of emergency departments (EDs) in the United States is poorly described. In a recent study, more than 4000 EDs completed the Pediatric Readiness Survey (PRS); however, the correlation of PRS scores with the quality of simulated or real patient care has not been described. To measure and compare the quality of resuscitative care delivered to simulated pediatric patients across a spectrum of EDs and to examine the correlation of PRS scores with quality measures. This prospective multicenter cohort study evaluated 58 interprofessional teams in their native pediatric or general ED resuscitation bays caring for a series of 3 simulated critically ill patients (sepsis, seizure, and cardiac arrest). A composite quality score (CQS) was measured as the sum of 4 domains: (1) adherence to sepsis guidelines, (2) adherence to cardiac arrest guidelines, (3) performance on seizure resuscitation, and (4) teamwork. Pediatric Readiness Survey scores and health care professional demographics were collected as independent data. Correlations were explored between CQS and individual domain scores with PRS. Overall, 58 teams from 30 hospitals participated (8 pediatric EDs [PEDs], 22 general EDs [GEDs]). The mean CQS was 71 (95% CI, 68-75); PEDs had a higher mean CQS (82; 95% CI, 79-85) vs GEDs (66; 95% CI, 63-69) and outperformed GEDs in all domains. However, when using generalized estimating equations to estimate CQS controlling for clustering of the data, PED status did not explain a higher CQS (β = 4.28; 95% CI, -4.58 to 13.13) while the log of pediatric patient volume did explain a higher CQS (β = 9.57; 95% CI, 2.64-16.49). The correlation of CQS to PRS was moderate (r = 0.51; P < .001). The correlation was weak for cardiac arrest (r = 0.24; P = .07), weak for sepsis (ρ = 0.45; P < .001) and seizure (ρ = 0.43; P = .001), and strong for teamwork (ρ = 0.71; P < .001). This multicenter study noted significant differences in the quality of simulated pediatric resuscitative care across a spectrum of EDs. The CQS was higher in PEDs compared with GEDs. However, when controlling for pediatric patient volume and other variables in a multivariable model, PED status does not explain a higher CQS while pediatric patient volume does. The correlation of the PRS was moderate for simulation-based measures of quality.
Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration
Authors: Melanie von Schimmelmann, Philip A Feinberg, Josefa M Sullivan, Stacy M Ku, Ana Badimon, Mary Kaye Duff, Zichen Wang, Alexander Lachmann, Scott Dewell, Avi Ma'ayan, Ming-Hu Han, Alexander Tarakhovsky, Anne Schaefer
Journal: Nature Neuroscience (2016)
Financial Relationships With Industry Among National Comprehensive Cancer Network Guideline Authors
Authors: Aaron P. Mitchell, Ethan M. Basch, Stacie B. Dusetzina
Journal: JAMA Oncology (2016)

Financial conflicts of interest (FCOIs) among authors of clinical practice guidelines have the potential to influence treatment recommendations.To quantify FCOIs with industry among authors of the National Comprehensive Cancer Network (NCCN) guidelines.We assessed FCOIs occurring during 2014 among NCCN guideline authors in the United States. All were physician members of the NCCN guideline committees for lung, breast, prostate, and colorectal cancer as of the end of 2014. The data source for FCOIs was Open Payments, which is publically reported by the Centers for Medicare and Medicaid Services. This study was cross-sectional.The proportion of NCCN authors having FCOIs with industry; the average amount received from industry sources per author.Of 125 guideline authors, 108 (86%) had at least 1 reported FCOI. Authors received an average of $10 011 (range, $0-$106 859) in general payments (GPs), which include consulting, meals, lodging, and similar transfers of value, and $236 066 (range $0-$2 756 713) in industry research payments (RPs), including funding associated with clinical trials. Approximately 84% of authors received GPs, while 47% received RPs. Eight (6%) had FCOIs in excess of the $50 000 net and/or $20 000 single-company maximums stipulated by NCCN.Among NCCN guideline authors, FCOIs involving RPs were of greater value, while those involving GPs were more prevalent. Although FCOIs may result from engaging in important scholarship, FCOIs may still influence guideline authors in counterproductive ways. Research is needed to understand how best to manage author FCOIs during guideline creation.
Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration
Authors: Fuqin Fan, Zhixiang He, Lu-Lu Kong, Qinghua Chen, Quan Yuan, Shihao Zhang, Jinjin Ye, Hao Liu, Xiufeng Sun, Jing Geng, Lunzhi Yuan, Lixin Hong, Chen Xiao, Weiji Zhang, Xihuan Sun, Yunzhan Li, Ping Wang, Lihong Huang, Xinrui Wu, Zhiliang Ji, Qiao Wu, Ning-Shao Xia, Nathanael S. Gray, Lanfen Chen, Cai-Hong Yun, Xianming Deng, Dawang Zhou
Journal: Science Translational Medicine (2016)

Manipulation of the Hippo signaling pathway with a reversible and selective small-molecule inhibitor of Hippo kinase MST1/2 provides a therapeutic option for tissue injury and repair.