tbuckley/cabot-search huggingface dataset:
Abstract 2683: The landscape of chromosomal aberrations in mouse models of breast cancer reveals driver-specific routes to tumor development
Authors: Uri Ben-David, Gavin Ha, Prasidda Khadka, Xin Jin, Lude Franke, Todd R. Golub
Journal: Cancer Research (2016)

Abstract Aneuploidy and large copy number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscape remains largely unexplored because large-scale CNA data have not been generated. Here we used gene expression profiles to infer CNAs in 3,108 samples from 45 mouse models, providing the first comprehensive catalog of chromosomal aberrations in cancer GEMMs. Mining this expansive resource, we found that most chromosomal aberrations accumulated late during breast tumorigenesis, and we observed marked differences in CNA prevalence between mouse mammary tumors initiated with distinct drivers. Some of these aberrations were recurrent and unique to specific GEMMs, suggesting distinct driver-dependent routes to tumor development. Synteny-based comparison of mouse and human tumors narrowed critical regions in CNAs, thereby identifying candidate driver genes that were not obvious from the analysis of either dataset alone. Specifically, we experimentally validated that loss of Stratifin (SFN) promotes HER2-induced tumorigenesis in human cells. These results demonstrate the power of GEMM CNA analysis in the understanding of human cancer pathogenesis. Citation Format: Uri Ben-David, Gavin Ha, Prasidda Khadka, Xin Jin, Lude Franke, Todd R. Golub. The landscape of chromosomal aberrations in mouse models of breast cancer reveals driver-specific routes to tumor development. [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 2683.
Abstract 273: Inhibition of EGFR/STAT3/CEBPD axis reverses cisplatin cross-resistance with paclitaxel in urothelial carcinoma of urinary bladder
Authors: Ju-Ming Wang.
Journal: Cancer Research (2016)

Abstract Cisplatin (CDDP) is frequently used in combination chemotherapy with paclitaxel (PTX) in the treatment of urothelial carcinomas of the urinary bladder (UCUB). The development of CDDP cross-resistance with PTX has been suggested and remains a challenge that hinders successful UCUB treatment. Consequently, elucidating the mechanisms underlying CDDP-induced anticancer drug resistance is imperative, and this knowledge will aid in the development of novel strategies. CEBPD expression was maintained in post-operative chemotherapy patients, and this expression was responsive to CDDP even in CDDP-resistant UCUB cells. Upon CDDP treatment, CEBPD activated ABCB1 and ABCC2. The EGFR/STAT3 pathway contributed to CDDP-induced CEBPD expression in UCUB cells. Treatment with gefitinib and S3I-201 significantly decreased CEBPD expression and enhanced sensitivity of CDDP-resistant NTUB1/P cells to CDDP and PTX. Our results demonstrate the risk of CEBPD activation in CDDP-resistant UCUB cells and suggest a potential therapeutic strategy for treating patients with UCUB and UCUB with CDDP-induced PTX resistance using CDDP in combination with either gefitinib or S3I-201. Citation Format: Ju-Ming Wang. Inhibition of EGFR/STAT3/CEBPD axis reverses cisplatin cross-resistance with paclitaxel in urothelial carcinoma of urinary bladder. [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 273.
Surgeons’ Disclosures of Clinical Adverse Events
Authors: A. Rani Elwy, Kamal M. F. Itani, Barbara G. Bokhour, Nora M. Mueller, Mark E. Glickman, Shibei Zhao, Amy K. Rosen, Dana Lynge, Melissa Perkal, Erica A. Brotschi, Vivian M. Sanchez, Thomas H. Gallagher
Journal: JAMA Surgery (2016)

Surgeons are frequently faced with clinical adverse events owing to the nature of their specialty, yet not all surgeons disclose these events to patients. To sustain open disclosure programs, it is essential to understand how surgeons are disclosing adverse events, factors that are associated with reporting such events, and the effect of disclosure on surgeons.To quantitatively assess surgeons' reports of disclosure of adverse events and aspects of their experiences with the disclosure process.An observational study was conducted from January 1, 2011, to December 31, 2013, involving a 21-item baseline questionnaire administered to 67 of 75 surgeons (89%) representing 12 specialties at 3 Veterans Affairs medical centers. Sixty-two surveys of their communication about adverse events and experiences with disclosing such events were completed by 35 of these 67 surgeons (52%). Data were analyzed using mixed linear random-effects and logistic regression models.Self-reports of disclosure assessed by 8 items from guidelines and pilot research, surgeons' perceptions of the adverse event, reported personal effects from disclosure, and baseline attitudes toward disclosure.Most of the surgeons completing the web-based surveys (41 responses from men and 21 responses from women) used 5 of the 8 recommended disclosure items: explained why the event happened (55 of 60 surveys [92%]), expressed regret for what happened (52 of 60 [87%]), expressed concern for the patient's welfare (57 of 60 [95%]), disclosed the adverse event within 24 hours (58 of 60 [97%]), and discussed steps taken to treat any subsequent problems (59 of 60 [98%]). Fewer surgeons apologized to patients (33 of 60 [55%]), discussed whether the event was preventable (33 of 60 [55%]), or how recurrences could be prevented (19 of 59 [32%]). Surgeons who were less likely to have discussed prevention (33 of 60 [55%]), those who stated the event was very or extremely serious (40 of 61 surveys [66%]), or reported very or somewhat difficult experiences discussing the event (16 of 61 [26%]) were more likely to have been negatively affected by the event. Surgeons with more negative attitudes about disclosure at baseline reported more anxiety about patients' surgical outcomes or events following disclosure (odds ratio, 1.54; 95% CI, 1.16-2.06).Surgeons who reported they were less likely to discuss preventability of the adverse event, or who reported difficult communication experiences, were more negatively affected by disclosure than others. Quality improvement efforts focused on recognizing the association between disclosure and surgeons' well-being may help sustain open disclosure policies.
Impact of an automated system for endocytoscopic diagnosis of small colorectal lesions: an international web-based study
Authors: Yuichi Mori, Shin-ei Kudo, Philip Chiu, Rajvinder Singh, Masashi Misawa, Kunihiko Wakamura, Toyoki Kudo, Takemasa Hayashi, Atsushi Katagiri, Hideyuki Miyachi, Fumio Ishida, Yasuharu Maeda, Haruhiro Inoue, Yukitaka Nimura, Masahiro Oda, Kensaku Mori
Journal: Endoscopy (2016)

<b>Background and study aims:</b> Optical diagnosis of colorectal polyps is expected to improve the cost-effectiveness of colonoscopy, but achieving a high accuracy is difficult for trainees. Computer-aided diagnosis (CAD) is therefore receiving attention as an attractive tool. This study aimed to validate the efficacy of the latest CAD model for endocytoscopy (380-fold ultra-magnifying endoscopy). <b>Patients and methods:</b> This international web-based trial was conducted between August and November 2015. A web-based test comprising one white-light and one endocytoscopic image of 205 small colorectal polyps (≤ 10 mm) from 123 patients was undertaken by both CAD and by endoscopists (three experts and ten non-experts from three countries). Outcome measures were accuracy in identifying neoplastic change in diminutive (≤ 5 mm) and small (≤ 10 mm) polyps, and accuracy in predicting post-polypectomy surveillance intervals according to current guidelines for high confidence optical diagnoses of diminutive polyps. <b>Results:</b> Of the 205 small polyps (147 neoplastic and 58 non-neoplastic), 139 were diminutive. CAD was accurate for 89 % (95 % confidence interval [CI] 83 % – 94 %) of diminutive polyps and 89 % (84 % – 93 %) of small polyps, which was significantly greater than results for the non-experts (73 % [71 % – 76 %], <i>P</i> < 0.001; and 76 % [74 % – 78 %], <i>P</i> < 0.001, respectively) and comparable with the experts' results (90 % [87 % – 93 %], <i>P</i> = 0.703; and 91 % [89 % – 93 %], <i>P</i> = 0.106, respectively). The surveillance interval predicted by CAD provided 98 % (93 % – 100 %) and 96 % (91 % – 99 %) agreement with pathology-directed intervals of the European and American guidelines, respectively. <b>Conclusions:</b> The use of CAD in endocytoscopy can be effective in the management of diminutive/small colorectal polyps. UMIN Clinical Trial Registry: UMIN000018185.
PMO-046 Audit of a new pathway for enteral feeding head and neck radiotherapy patients: Abstract PMO-046 Table 1
Authors: S Sharp, C H Sheth, C Baughan, S Ramkumar, E Walters
Journal: Gut (2012)

<h3>Introduction</h3> It is well recognised that Head and Neck Cancer (HNC) patients often “have problems with eating and drinking and a substantial proportion have to cope with tube feeding”.<sup>1</sup> With no national pathway, many units use gastrostomy tubes however, clinical indication and timing of placement are debated.<sup>2</sup> Due to gastrostomy tube complications, our unit routinely uses nasogastric tubes (NGT). Using data from a previous audit our centre developed a pathway for enteral feeding (EF) HNC radiotherapy (RT) patients<sup>3</sup>. This pathway includes advice on enteral feeding in this patient group, specifically when and who to electively NG feed and guidance on selecting suitable patients for elective day-case NG placement. The pathway was launched in May 2011 and impact on length of stay (LOS) assessed. <h3>Methods</h3> All patients with primary HNC treated with RT from 1st June to 30th September 2011 requiring EF were included in the audit. Details of anthropometry, day of RT NGT passed, LOS, number of NGT9s required and nutrition related readmissions were collected. <h3>Results</h3> 12 patients met the inclusion criteria; one was excluded from analysis as they were receiving long term gastrostomy feeding prior to RT. Details of the remaining 11 patients are detailed in Abstract PMO-046 table 1. Admissions &gt;24 h occurred in two patients. One patient initially refused an NGT, subsequently needing admission for nutritional complications and an NGT. The second patient had laryngeal cancer, a diagnosis that doesn9t normally require EF; therefore NG feeding was commenced due to unexpected late onset nutritional problems. Despite this using the pathway reduced the average LOS further to only 3 days.<sup>3</sup> <h3>Conclusion</h3> Using our enteral feeding pathway and a multidisciplinary approach, elective NGT feeding in HNC RT patients can be safely established using day-case facilities. It is a cost effective nutritional treatment with no significant complications identified. The pathway provides a clear, safe, efficient and effective approach to nutritional care in HNC RT patients. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>National Institute for Clinical Excellence.</b><i>Improving Outcomes for Head &amp; Neck Cancer</i>. London: National Institute for Clinical Excellence, 2004. 2. <b>Nugent,</b><i>et al.</i> Enteral feeding methods for nutritional management in patients with head &amp; neck cancers being treated with radiotherapy &amp;/or chemotherapy. <i>Cochrane Database Syst Rev</i> 2010;<b>17</b>:CD007904. 3. <b>Walters,</b><i>et al.</i> Dietetic service improvement for patients with head &amp; neck cancer receiving radiotherapy treatment. University Hospital Southampton, 2010. (Unpublished).
Consumer-Oriented Approaches to Cost Containment
Authors: Paul B. Ginsburg
Journal: JAMA Internal Medicine (2016)

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The value of neurocognitive testing for acute outcomes after mild traumatic brain injury
Authors: Latha Ganti, Yasamin Daneshvar, Sarah Ayala, Aakash N. Bodhit, Keith R. Peters
Journal: Military Medical Research (2016)

Traditionally, neurocognitive testing is performed weeks to months after head injury and is mostly performed on patients who continue to have symptoms or difficulties. In this study, we sought to determine whether these tests, when administered acutely, could assist in predicting short-term outcomes after acute traumatic brain injury (TBI).This is an IRB-approved prospective study of adult patients who came to the emergency department of our Level-1 trauma center with TBI. Patients were enrolled prospectively after providing written informed consent and underwent three separate neurocognitive tests: the Galveston Orientation Amnesia Test (GOAT) the Rivermead Post-Concussion Survey Questionnaire (RPCSQ) and the Mini Mental Status Examination (MMSE).A lower GOAT score was significantly associated with hospitalization (P = 0.0212) and the development of post-concussion syndrome (P = 0.0081) at late follow-up. A higher RPCSQ score was significantly associated with hospital admission (P = 0.0098), re-admission within 30 days of discharge (P = 0.0431) and evidence of post-concussion syndrome (PCS) at early follow-up (P = 0.0004). A higher MMSE score was significantly associated with not being admitted to the hospital (P = 0.0002) and not returning to the emergency department (ED) within 72 hours of discharge (P = 0.0078). Lower MMSE was also significantly associated with bleeding or a fracture on the brain CT (P = 0.0431).While neurocognitive testing is not commonly performed in the ED in the setting of acute head injury, it is both feasible and appears to have value in predicting hospital admission and PCS. These data are especially important in terms of helping patients understand what to expect, thus, aiding in their recovery.
Principles of practice parameters for the treatment of sleep disordered breathing in the elderly and frail elderly: the consensus of the International Geriatric Sleep Medicine Task Force
Authors: Nikolaus C. Netzer, Sonia Ancoli-Israel, Donald L. Bliwise, Stephany Fulda, Christine Roffe, Fernanda Almeida, Hakki Onen, Fannie Onen, Friedhart Raschke, Miguel Angel Martinez Garcia, Helmut Frohnhofen
Journal: European Respiratory Journal (2016)

Sleep disordered breathing (SDB) is a leading cause of morbidity worldwide. Its prevalence increases with age. Due to the demographic changes in industrial societies, pulmonologists and sleep physicians are confronted with a rapidly growing number of elderly SDB patients. For many physicians, it remains unclear how current guidelines for SDB management apply to elderly and frail elderly patients. The goal of this consensus statement is to provide guidance based on published evidence for SDB treatment in this specific patient group. Clinicians and researchers with expertise in geriatric sleep medicine representing several countries were invited to participate in a task force. A literature search of PubMed from the past 12 years and a systematic review of evidence of studies deemed relevant was performed. Recommendations for treatment management of elderly and frail elderly SDB patients based on published evidence were formulated via discussion and consensus. In the last 12 years, there have been surprisingly few studies examining treatment of SDB in older adults and even fewer in frail older adults. Studies that have been conducted on the management of SDB in the older patient population were rarely stratified for age. Studies in SDB treatment that did include age stratification mainly focused on middle-aged and younger patient groups. Based on the evidence that is available, this consensus statement highlights the treatment forms that can be recommended for elderly SDB patients and encourages treatment of SDB in this large patient group.
Abstract 756: Myo-inositol modulates the tumor microenvironment in a mouse model of lung cancer chemoprevention
Authors: Nese Unver, Kirubel T. Zeleke, Ximing Tang, Samantha Holt, Seyed Javad M. Moghaddam, Hong Wang, Ignacio I. Wistuba, Samir M. Hanash, Edwin J. Ostrin
Journal: Cancer Research (2016)

Abstract Background: Myo-inositol is a nutritional supplement that has been investigated as a chemopreventive agent for lung cancer. We have investigated the effect of myo-inositol in a CC-LR (CCSPCre/LSL-K-rasG12D) mouse lung cancer model. Blood, broncho-alveolar lavage fluid (BALF), and lungs were collected from CC-LR and LR littermate control mice at 14 weeks of age, when mice had a large number of premalignant lesions with only small foci of adenocarcinoma. Methods: Lesion burden and stage was quantified using macroscopically evident lung surface tumor counts as well as histology from paraffin sections. Serial paraffin sections were also used for immunohistochemistry. Plasma was analyzed using high-sensitivity liquid-chromatography coupled tandem mass spectrometry. Cytokine and chemokine concentrations in BALF were quantitated using multiplex immunobead assays. Results: Myo-inositol treated mice (n = 20) had fewer tumors (p &amp;lt; 0.0001) than mice raised on control diet (n = 23). Additionally, lesions were shifted towards lower grade, from adenomas and adenomatous alveolar hyperplasia to bronchial hyperplasia. Several host factors including cytokines and proteins produced by myeloid derived suppressor cells and macrophages were significantly impacted by myo-inositol treatment. In addition to changes in metabolic inflammation derived factors, proteins which are associated with both chronic inflammation and lung tumorigenesis were altered as well. Conclusions: Myo-inositol treatment both reduced tumor burden and lesion grade in a KRAS model of lung cancer. Our findings of a substantial impact of myo-inositol treatment on the host response suggests novel mechanisms for its chemopreventive activitiy. Citation Format: Nese Unver, Kirubel T. Zeleke, Ximing Tang, Samantha Holt, Seyed Javad M. Moghaddam, Hong Wang, Ignacio I. Wistuba, Samir M. Hanash, Edwin J. Ostrin. Myo-inositol modulates the tumor microenvironment in a mouse model of lung cancer chemoprevention. [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 756.
Abstract 979: Identification of a novel long noncoding RNA within the LCK gene locus that regulates prostate cancer cell growth
Authors: Huy Q. Ta, Samuel R. Jackson, Hilary Whitworth, Shriti Bhadel, Daniel Gioeli
Journal: Cancer Research (2016)

Abstract Prostate cancer remains the second most common type of cancer and frequent cause of cancer-related mortality in American men. Even though many patients with metastatic prostate cancer will initially respond to androgen deprivation therapy, virtually all patients will relapse and develop lethal castration-resistant prostate cancer. Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements of many cellular biological processes, and there is increasing evidence demonstrating that dysregulation of lncRNAs is associated with many human cancers, including cancers of the prostate, breast, and lung. We have discovered in a high-throughput RNAi screen identifying regulators of prostate cancer cell growth that knockdown of lymphocyte-specific protein tyrosine kinase (LCK) significantly decreases growth of prostate cancer cells in the presence and absence of androgen. Surprisingly, immunoprecipitation and western blot analyses show that LCK is not expressed at the protein level in prostate cancer cells. Rapid amplification of cDNA ends (RACE) and sequencing have revealed that a previously unannotated lncRNA lies within exon six and the 3’UTR of the LCK gene. While short hairpin RNAs (shRNAs) targeting the carboxy-terminus of the LCK gene decreases cell growth, expression of shRNAs specific for the amino-terminus has no effect on growth. Furthermore, only quantitative polymerase chain reaction (qPCR) primers directed toward the 3’ section of the LCK gene yield detectable levels of transcript. These data provide further validation for the existence of a lncRNA within the LCK gene locus. Remarkably, the lncRNA situated within the LCK gene is dramatically upregulated in response to androgen. Therefore, we have labeled this lncRNA “HULLK” for Hormone-upregulated lncRNA within LCK. Cellular fractionation and qPCR show that HULLK predominantly localizes to the cytoplasm. In addition to the effects on prostate cancer cell growth, we have data that alludes to the increase in transcript levels of several Src family members following depletion of HULLK. Thus, these studies indicate that the LCK gene contains a lncRNA involved in the regulation of prostate cancer cell growth and perhaps transcription. While additional analyses will be required to fully characterize HULLK, our data suggest that it may serve as a novel regulator of prostate cancer proliferation. Citation Format: Huy Q. Ta, Samuel R. Jackson, Hilary Whitworth, Shriti Bhadel, Daniel Gioeli. Identification of a novel long noncoding RNA within the LCK gene locus that regulates prostate cancer cell growth. [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 979.