tbuckley/cabot-search huggingface dataset:
Guideline adherence rates of chemotherapy treatment for breast cancer patients treated in U.S. community oncology practices.
Authors: K. A. Bergstrom, Z. Wang, I. Aksamit, L. Tuscher, T. Lam, B. S. Tom, C. G. Baker, K. B. Whitlock, Z. Ansari-Jaberi, M. Mayo
Journal: Journal of Clinical Oncology (2010)

596 Background: Adherence to national guidelines is a key step to improving the quality of cancer treatment. This study examined guideline adherence rates and cost of chemotherapy treatment for breast cancer patients treated in the adjuvant (Adj) and first-line metastatic (Met) settings in U.S. community oncology practices. Methods: Using a large, U.S. medical oncology clinical database derived from a web-based drug dispensing technology, adult patients with breast cancer treated with Adj and Met chemotherapy were identified from 1/1/09-9/30/09. Regimens utilized were compared to national guidelines. Costs based on Medicare (MC) reimbursement were also compared. Results: A total of 4,616 Adj and 2,828 first-line metastatic regimens were administered by 458 practices across 46 states. Median patient age was 56 and 62 in the Adj and Met groups, respectively. The Adj and Met groups received 135 and 216 different regimens, respectively. The rate of guideline adherence in the Adj group, 83%, was significantly higher than in the Met group, 58% (p<0.001 by chi-test). The top 10 regimens utilized in the Adj group were given to 74.3% of patients, while in the Met group 50.2% were given. Top 5 regimens in each group were appropriate according to guidelines, except trastuzumab in the Met setting. Regimen costs based on MC national reimbursement rates (including antineoplastic and supportive care drugs, CPT and some lab codes) for the top 5 regimens in the Adj and Met settings varied. A standard course of therapy in the Adj setting ranged from $8,350 (AC+Pac every 7 days) to $ 34,691 (TCH+H). Regimen costs in the Met setting ranged from $2,861 (fulvestrant) to $29,149 for Pacl+Bev based on 3 months of therapy. Conclusions: The guideline adherence rate for regimens utilized in the community setting is significantly higher in the Adj setting than in the Met setting. Costs for the top 5 regimens in the Adj and Met settings vary considerably Regimen % Adj Docetaxel (Doc)/cyclophosphamide (C) (TC) 29.7 Doxorubicin (Dox)/C + paclitaxel (Pac) every 14 days (AC+Pac) 11 AC+Pac every 7 days 7.6 Doc/Dox/C (TAC) 6.2 Doc/carboplatin/trastuzumab (H) + H (TCH) 5.9 Met Fulvestrant 8.3 Trastuzumab 7.7 Pac/bevacizumab 7.1 Pac 6.4 Nab-paclitaxel 4 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, McKesson
Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury
Authors: Christopher E. Pedigo, Gloria Michelle Ducasa, Farah Leclercq, Alexis Sloan, Alla Mitrofanova, Tahreem Hashmi, Judith Molina-David, Mengyuan Ge, Mariann I. Lassenius, Carol Forsblom, Markku Lehto, Per-Henrik Groop, Matthias Kretzler, Sean Eddy, Sebastian Martini, Heather Reich, Patricia Wahl, GianMarco Ghiggeri, Christian Faul, George W. Burke, Oliver Kretz, Tobias B. Huber, Armando J. Mendez, Sandra Merscher, Alessia Fornoni
Journal: Journal of Clinical Investigation (2016)

High levels of circulating TNF and its receptors, TNFR1 and TNFR2, predict the progression of diabetic kidney disease (DKD), but their contribution to organ damage in DKD remains largely unknown. Here, we investigated the function of local and systemic TNF in podocyte injury. We cultured human podocytes with sera collected from DKD patients, who displayed elevated TNF levels, and focal segmental glomerulosclerosis (FSGS) patients, whose TNF levels resembled those of healthy patients. Exogenous TNF administration or local TNF expression was equally sufficient to cause free cholesterol-dependent apoptosis in podocytes by acting through a dual mechanism that required a reduction in ATP-binding cassette transporter A1-mediated (ABCA1-mediated) cholesterol efflux and reduced cholesterol esterification by sterol-O-acyltransferase 1 (SOAT1). TNF-induced albuminuria was aggravated in mice with podocyte-specific ABCA1 deficiency and was partially prevented by cholesterol depletion with cyclodextrin. TNF-stimulated free cholesterol-dependent apoptosis in podocytes was mediated by nuclear factor of activated T cells 1 (NFATc1). ABCA1 overexpression or cholesterol depletion was sufficient to reduce albuminuria in mice with podocyte-specific NFATc1 activation. Our data implicate an NFATc1/ABCA1-dependent mechanism in which local TNF is sufficient to cause free cholesterol-dependent podocyte injury irrespective of TNF, TNFR1, or TNFR2 serum levels.
Prevalence and characteristics of prematurely terminated cancer clinical trials.
Authors: Kristian D Stensland, Asma Latif, Ryan Hendricks, Nitin Roper, Russell McBride, Simon J Hall, William K. Oh, Matt D. Galsky
Journal: Journal of Clinical Oncology (2013)

6613 Background: Cancer clinical trials require a substantial investment of patient and financial resources. Trials that are terminated prematurely contribute little to the scientific knowledge base and divert resources from answering other critical questions. To our knowledge, the prevalence of prematurely terminated trials, and reasons for termination, has not been comprehensively assessed. Methods: The ClinicalTrials.gov database was queried to identify all phase II and phase III interventional trials for any neoplasm registered between 9/2005 and 11/2012. The disease type, enrollment status, phase, funding source, and number of study sites were collected for each trial. A ”prematurely terminated” trial was any trial with a status of “terminated,” “withdrawn,” or “suspended.” The reason for termination was collected for each prematurely terminated trial. Results: We identified 11,483 interventional cancer trials, of which 1,326 (11.5%) were terminated prematurely. The reasons for termination are shown in the Table. The proportion of cancelled trials was similar among the various disease types, but was slightly higher in lung cancer (14.4% vs. 11.2%, p = 0.001), and slightly lower in skin cancer (8.2% vs. 11.7%, p = 0.022). The most common reason for premature termination was poor accrual (33.1%) though no reason was provided for 23% of trials. Trials sponsored by industry were more likely to be canceled than those with NIH or “other” sponsorship (13.4% vs. 9.9%, p = 0.001). Single center trials were more likely to be canceled than trials with multiple sites (13.6% vs. 9.4%, p &lt; 0.001). Conclusions: More than one in ten cancer clinical trials is terminated prematurely. Full reporting of the reasons for premature termination is necessary for further evaluation of the cancer clinical trial enterprise and identification of predictors of study early closure. [Table: see text]
Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBPα expression
Authors: Kol Jia Yong, Daniela S. Basseres, Robert S. Welner, Wen Cai Zhang, Henry Yang, Benedict Yan, Meritxell Alberich-Jorda, Junyan Zhang, Lorena Lobo de Figueiredo-Pontes, Chiara Battelli, Christopher J. Hetherington, Min Ye, Hong Zhang, Giorgia Maroni, Karen O’Brien, Maria Cristina Magli, Alain C. Borczuk, Lyuba Varticovski, Olivier Kocher, Pu Zhang, Young-Choon Moon, Nadiya Sydorenko, Liangxian Cao, Thomas W. Davis, Bhavin M. Thakkar, Ross A. Soo, Atsushi Iwama, Bing Lim, Balazs Halmos, Donna Neuberg, Daniel G. Tenen, Elena Levantini
Journal: Science Translational Medicine (2016)

In lung cancers with low expression of C/EBPα, BMI1 expression correlates with worse prognosis but can be targeted with a drug.
Brief Report: Predicting Functional Disability: One‐Year Results From the Scottish Early Rheumatoid Arthritis Inception Cohort
Authors: Caroline Kronisch, David J. McLernon, James Dale, Caron Paterson, Stuart H. Ralston, David M. Reid, Ann Tierney, John Harvie, Neil McKay, Hilary E. Wilson, Robin Munro, Sarah Saunders, Ruth Richmond, Derek Baxter, Mike McMahon, Vinod Kumar, John McLaren, Stefan Siebert, Iain B. McInnes, Duncan Porter, Gary J. Macfarlane, Neil Basu
Journal: Arthritis & Rheumatology (2016)

To identify baseline prognostic indicators of disability at 1 year within a contemporary early inflammatory arthritis inception cohort and then develop a clinically useful tool to support early patient education and decision-making.The Scottish Early Rheumatoid Arthritis (SERA) inception cohort is a multicenter, prospective study of patients with newly presenting RA or undifferentiated arthritis. SERA data were analyzed to determine baseline predictors of disability (defined as a Health Assessment Questionnaire [HAQ] score of ≥1) at 1 year. Clinical and psychosocial baseline exposures were entered into a forward stepwise logistic regression model. The model was externally validated using newly accrued SERA data and subsequently converted into a prediction tool.Of the 578 participants (64.5% female), 36.7% (n = 212) reported functional disability at 1 year. Functional disability was independently predicted by baseline disability (odds ratio [OR] 2.67 [95% confidence interval (95% CI) 1.98, 3.59]), depression (OR 2.52 [95% CI 1.18, 5.37]), anxiety (OR 2.37 [95% CI 1.33, 4.21]), being in paid employment with absenteeism during the last week (OR 1.19 [95% CI 0.63, 2.23]), not being in paid employment (OR 2.36 [95% CI 1.38, 4.03]), and being overweight (OR 1.61 [95% CI 1.04, 2.50]). External validation (using 113 newly acquired patients) evidenced good discriminative performance with a C statistic of 0.74, and the calibration slope showed no evidence of model overfit (P = 0.31).In the context of modern early inflammatory arthritis treatment paradigms, predictors of disability at 1 year appear to be dominated by psychosocial rather than more traditional clinical measures. This indicates the potential benefit of early access to nonpharmacologic interventions targeting key psychosocial factors, such as mental health and work disability.
Ablation of Atrial Fibrillation
Authors: Mark S. Link, Michel Haïssaguerre, Andrea Natale
Journal: Circulation (2016)

Atrial fibrillation (AF) is the most common arrhythmia encountered by cardiologists and is a major cause of morbidity and mortality. Risk factors for AF include age, male sex, genetic predisposition, hypertension, diabetes mellitus, sleep apnea, obesity, excessive alcohol, smoking, hyperthyroidism, pulmonary disease, air pollution, heart failure, and possibly excessive exercise. The management of AF involves decisions about rate versus rhythm control. Asymptomatic patients are generally managed with rate control and anticoagulation. Symptomatic patients will desire rhythm control. Rhythm control options are either antiarrhythmic agents or ablation, with each having its own risks and benefits. Ablation of AF has evolved from a rare and complex procedure to a common electrophysiological technique. Selection of patients to undergo ablation is an important aspect of AF care. Patients with the highest success rates of ablation are those with normal structural hearts and paroxysmal AF, although those with congestive heart failure have the greatest potential benefit of the procedure. Although pulmonary vein isolation of any means/energy source is the approach generally agreed on for those with paroxysmal AF, optimal techniques for the ablation of nonparoxysmal AF are not yet clear. Anticoagulation reduces thromboembolic complications; the newer anticoagulants have eased management for both the patient and the cardiologist. Aggressive management of modifiable risk factors (hypertension, diabetes mellitus, sleep apnea, obesity, excessive alcohol, smoking, hyperthyroidism, pulmonary disease, air pollution, and possibly excessive exercise) after ablation reduces the odds of recurrent AF and is an important element of care.
Abstract 1435: Psychoimmunological effect of depression on cervical carcinoma: Genome-wide long noncoding RNA implications
Authors: Wanjun Dai, Yinhua Yu, Yu Kang
Journal: Cancer Research (2016)

Abstract Objective: Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer death among females in developing countries. Depression is a vital psychological factor for tumor progression. Long noncoding RNAs(LncRNAs) are a novel group of gene regulators and may contribute to the disease development. Herein, the study aims to discover the mechanisms of psychoimmunological effect of depression on cervical carcinoma from the perspective of long noncoding ribonucleic acid. Methods: Six tumor tissues were obtained from Ib-IIa invasive squamous cell cervical carcinoma patients during laproscopic surgeries. They were divided into high-depressed group and low-depressed group according to the scoring system. LncRNA microarray experiments were performed. Expression levels of six lncRNA-mRNA pairs were confirmed by quantitative real-time PCR in other 20 patients’ materials. Results: We found that 1621 lncRNA transcripts are differently expressed between high-depressed and paired low-depressed samples, with 510 up-regulated and 1111 down-regulated (fold-change&amp;gt;2.0). Most of lncRNAs were found trans-regulated by three TFs with most credentiality: BCL11A,MEF2A and TBP. In the KEGG analysis, the most down-regulated mRNA involved was systemic lupus erythematosus (Maximun transcriptional domain coverage: 25.5%). In the LncRNA and mRNA Coexpression, the function of lncRNAs with most differently expressions was predicted in relationship with interleukin-1 receptor activity (Number of lncRNAs annotated: 15). Conclusions: Our study identified that genome-wide LncRNA profiles are significantly altered in cervical carcinoma patients with worse depressed profiles, and the psychoimmunological effect of tumor progression needs further investigation. Keywords: Depression, Cervical Cancer, Immunology, Long-noncoding RNA Citation Format: Wanjun Dai, Yinhua Yu, Yu Kang. Psychoimmunological effect of depression on cervical carcinoma: Genome-wide long noncoding RNA implications. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1435.
Erratum to: Transmission of α-synucleinopathy from olfactory structures deep into the temporal lobe
Authors: Daniel M. Mason, Negin Nouraei, Deepti B. Pant, Kristin M. Miner, Daniel F. Hutchison, Kelvin C. Luk, John F. Stolz, Rehana K. Leak
Journal: Molecular Neurodegeneration (2016)

* C E D Pi “Please download the high-resolution supplemental versions of these files at the link at the end of this article (Additional file 3) or email the corresponding author at leakr@duq.edu for access to the files and zoom in and out of the stitched montages in order to appreciate the density of the pathology, distinguish it from background, and judge the precise anatomical location.” In the Fig. 2 legend, the article [1] should have had the additional line: “For a high-resolution version of this figure, please download the image at the link at the end of this article (Additional file 3) or email the corresponding author at leakr@duq.edu for access to the files.” In the Fig. 3 legend, the article [1] should have had the additional line: “To view the pSer129 pathology in the entorhinal cortex and transentorhinal region in panel c, please
Abstract 1356: Cell-based screening to identify repressors of wild type and mutated telomerase reverse transcriptase gene promoter activity
Authors: Alan Bilsland, Yu Liu, Sharon Burns, David Jenkinson, Jon Roffey, W. Nicol Keith
Journal: Cancer Research (2016)

Abstract Cellular immortality is a near-universal phenotype of cancer cells with the central role played by the multicomponent telomerase complex firmly established. The reactivation of telomerase is found in approximately 85% of all cancers. Furthermore, frequent activating non-coding mutations in the hTERT promoter region have been identified in multiple tumour types. A considerable body of evidence supports the concept of targeting the signal transduction pathways that contribute to telomerase overexpression in cancer cells. We have exploited our knowledge in this area to develop cell-based luciferase reporter gene assays to measure hTERT and hTR gene promoter activity. To this end we undertook high throughput screening in the A2780 human ovarian cancer cell line against both hTR and hTERT promoters. Secondary specificity and cytotoxicity assays reduced the initial hits to a single chemical series of dual inhibitors which strongly suppress both hTR and hTERT promoter activity without primary cytotoxicity, as predicted of telomerase inhibitors. Through a process of Hit to Lead we have further developed the chemical series. Lead compounds are active across a panel of cell lines from distinct histological origins, reduce endogenous hTERT mRNA levels and decrease telomerase catalytic activity at nM concentrations. Furthermore, these compounds repress both wild type and mutant C228T and C250T hTERT promoter activity. In specificity assays no off-target activity has been identified in an expanded promoter screen against a panel of 15 off-target promoter reporters. Citation Format: Alan Bilsland, Yu Liu, Sharon Burns, David Jenkinson, Jon Roffey, W. Nicol Keith. Cell-based screening to identify repressors of wild type and mutated telomerase reverse transcriptase gene promoter activity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1356.
Slowing Down the Progression of Type 2 Diabetes: We Need Fair, Innovative, and Disruptive Action on Environmental and Policy Levels!
Authors: Peter E.H. Schwarz, Henna Riemenschneider
Journal: Diabetes Care (2016)

Over the past decades, we have observed an increase of prevalence of diabetes in many countries along with significant differences in prevalence trends between countries worldwide (1). In Europe and other Western countries, the prevalence rate reaches a plateau or has slowed down on the level of ∼8–10%. In Asia, a continuous rise in prevalence has been monitored, similar to that in Africa, and an explosion of diabetes prevalence can be observed in the Arabic region.

Surprisingly, in each of the countries, there is a significant number of people who do not develop diabetes during their lives despite living unhealthy lifestyles in similar environments—in Europe, an estimated 10% of the population (2). These people might be the secret answer to successful individual diabetes prevention, but we still do not understand the detailed mechanisms of why some people develop diabetes—and why others do not. What we can do is observe individual lifestyle and environment as determinants for the development or prevention of diabetes and the respective risk factors including genetic susceptibility. The interplay between these determinants, influencing the probability of the individual staying healthy or how a person learns or chooses a healthy lifestyle, will define success in diabetes prevention (3). Innovative actions are needed to slow down the progression of type 2 diabetes. The purpose of this article is to offer innovative policy and environmental strategic activities designed to enable sustainable diabetes prevention with scalability on national level.

### Why Do We Need Environmental and Policy Changes in Diabetes Prevention?

Diabetes prevention is a success story, but it generates new challenges. Throughout the past 15 years, a number of randomized controlled trials have sought to test various interventions to prevent diabetes (4). The results are overwhelmingly positive on an individual level, with a significant relative diabetes risk reduction attributed to lifestyle and pharmacological intervention (5 …
Case 11-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, John W. Braasch, Maire A. Duggan
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 54-year-old woman was admitted to the hospital because of a pancreatic mass.She was well until six weeks earlier, when she began to experience persistent nausea and anorexia, with occasional vomiting of ingested food. She became aware of an enlarging mass in the right upper abdominal quadrant that was occasionally painful on movement. Pruritus developed and worsened during the four weeks before admission, and she observed darkening of her urine. There were rare night sweats, without frank chills. A computed tomographic (CT) scan of the abdomen showed a pancreatic mass. An attempted percutaneous biopsy of the . . .
Abstract 463: Immunohistochemical study of TROP-2 protein expression in thyroid lesions
Authors: Zhiming Liao
Journal: Cancer Research (2016)

Abstract Introduction Tumor-associated calcium signal transducer 2 (TROP-2) is a transmembrane glycoprotein overexpressed in various types of epithelial carcinomas from lung, breast, stomach, ovary, cervix, colon and pancreas. A recent immunohistochemical (IHC) study indicated that TROP-2 is also overexpressed in thyroid papillary carcinoma, but the sensitivity is only 82% in formalin-fixed and paraffin-embedded thyroid (FFPE) tissues when a polyclonal anti-TROP-2 antibody was used. A high quality of TROP-2 antibody for IHC applications is needed to improve the sensitivity of the detection of thyroid papillary carcinoma in FFPE tissues. Methodology A rabbit monoclonal antibody (clone SP295) against human TROP-2 protein was developed. Western blot was performed using SK-BR-3 cell lysates to verify the specificity of the TROP-2 antibody. An IHC study of TROP-2 was performed on normal tissue and tumor arrays from the thyroid and other organs. TROP-2 staining intensity was semi-quantitatively scored using a 0-3 scale. The sensitivity and specificity of the TROP-2 IHC assay for detecting papillary carcinoma were determined using 65 cases of thyroid papillary carcinoma, 29 cases of follicular carcinoma, and 31 cases of other thyroid conditions (normal, adenoma, Grave's disease, thyroiditis, Goiter, medullary carcinoma, clear cell carcinoma, squamous cell carcinoma, and undifferentiated carcinoma). Results A single band at 33 kDa was detected by SP295 on a western blot. In normal tissues, TROP-2 is detectable by IHC mostly in squamous epithelia of many normal organs (skin, pharynx, esophagus, and cervix) and cuboidal and columnar epithelium (breast, kidney, liver, uterus, pancreas, prostate and transitional epithelium of the bladder). In thyroid lesions, the TROP-2 positive rate is 100% (65/65) in papillary adenocarcinoma and it is negative in all other thyroid conditions (normal, adenoma, Grave's disease, thyroiditis, Goiter, medullary carcinoma, clear cell carcinoma, squamous cell carcinoma, and undifferentiated carcinoma). The sensitivity and specificity of TROP-2 IHC for detecting papillary carcinoma were both 100% in this study. Conclusions Rabbit monoclonal TROP-2 antibody (clone SP295) is highly sensitive and specific for detecting TROP-2 in FFPE tissues and it can be used to identify thyroid papillary carcinoma. Citation Format: Zhiming Liao. Immunohistochemical study of TROP-2 protein expression in thyroid lesions. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 463.