tbuckley/cabot-search huggingface dataset:
Novel Oxidative Phosphorylation Inhibitor IACS-010759 Induces AMPK-Dependent Apoptosis of AML Cells
Authors: Haeun Yang, Yoko Tabe, Kazumasa Sekihara, Kaori Saito, Helen Ma, Vivian Ruvolo, Junichi Imoto, Kazuho Ikeo, Kaoru Mogushi, Masaki Hosoya, Yoshihide Hayashizaki, Yasunari Yamanaka, Takashi Miida, Michael Andreeff, Joseph R Marszalek, Marina Konopleva
Journal: Blood (2017)
β2 adrenergic receptor polymorphisms and COPD exacerbations: a complicated story
Authors: Wassim W Labaki, MeiLan K Han
Journal: Thorax (2019)

Genomics has significantly improved our understanding of chronic obstructive pulmonary disease (COPD) over the past decade. Genome-wide association studies have identified a number of genetic variants associated with lung function and susceptibility to COPD,1 2 and have helped explain why only some smokers develop COPD and why never-smokers can also be affected by the disease. Once COPD is diagnosed, reducing the burden of respiratory exacerbations is a clinical priority because these events are associated with accelerated lung function decline3 and increased mortality.4 However, not all patients with COPD experience exacerbations.5 6 Therefore, identifying individuals at increased risk of exacerbations may help target management and improve outcomes. Beyond the susceptibility to COPD, genomics may also help inform the morbidity of COPD. A previously reported twin study suggests that more than 60% of the risk of severe COPD exacerbations can be attributed to genetic factors.7 Among those, genetic polymorphisms of the β2 adrenergic receptor have been of particular interest.8 9 

Using data from individuals with COPD in the Copenhagen General Population Study (n=5262) and the Copenhagen City Heart Study (n=923), Ingebrigtsen et al tested the association of β2 adrenergic receptor polymorphisms Gly16Arg (rs1042713, c.46G>A) and Gln27Glu (rs1042714, c.79C>G) with incident risk of COPD exacerbations requiring hospitalisation.10 In the Copenhagen General Population Study, compared with 16Gly homozygotes, 16Gly/Arg heterozygotes (HR 1.62, 95% CI 1.30 to 2.03, p=0.00002) and 16Arg homozygotes (HR 1.41, 95% CI …
Comparing the Association Between Insurance and Mortality in Ovarian, Pancreatic, Lung, Colorectal, Prostate, and Breast Cancers
Authors: Alexander P. Cole, Chang Lu, Marieke J. Krimphove, Julie Szymaniak, Maxine Sun, Sean A. Fletcher, Stuart R. Lipsitz, Brandon A. Mahal, Paul L. Nguyen, Toni K. Choueiri, Adam S. Kibel, Adil H. Haider, Quoc-Dien Trinh
Journal: Journal of the National Comprehensive Cancer Network (2019)

Insurance coverage is associated with better cancer outcomes; however, the relative importance of insurance coverage may differ between cancers. This study compared the association between insurance coverage at diagnosis and cancer-specific mortality (CSM; insurance sensitivity) in 6 cancers.Using the SEER cancer registry, data were abstracted for individuals diagnosed with ovarian, pancreatic, lung, colorectal, prostate, or breast cancer in 2007 through 2010. The association between insurance coverage at diagnosis and CSM was modeled using a Fine and Gray competing-risks regression adjusted for demographics. An interaction term combining insurance status and cancer type was used to test whether insurance sensitivity differed between cancers. Separate models were fit for each cancer. To control for lead-time bias and to assess whether insurance sensitivity may be mediated by earlier diagnosis and treatment, additional models were fit adjusting for disease stage and treatment.Lack of insurance was associated with an increased hazard of CSM in all cancers (P<.01). The magnitude of the effect differed significantly between cancers (Pinteraction=.04), ranging from an adjusted hazard ratio of 1.13 (95% CI, 1.01-1.28) in ovarian and 1.19 (95% CI, 1.11-1.29) in pancreatic cancer to 2.19 (95% CI, 2.02-2.37) in breast and 2.98 (95% CI, 2.54-3.49) in prostate cancer. The benefit of insurance was attenuated after adjusting for stage and treatment (eg, screening/early treatment effect), with the largest reductions in prostate, breast, and colorectal cancers.Greater insurance sensitivity was seen in screening-detected malignancies with effective treatments for early-stage disease (eg, prostate, breast, and colorectal cancers). Given that this differential is significantly reduced after adjusting for stage and treatment, our results suggest that a significant portion (but not all) of the benefit of insurance coverage is due to detection and treatment of certain curable early-stage cancers.
Satisfaction of general versus specialized continuity clinic in hematology oncology fellowship training: A survey.
Authors: Sama Imran Ilyas, Martina Cathryn Murphy, Jennifer Michelle Duff, Julia Lee Close
Journal: Journal of Clinical Oncology (2019)

10529 Background: At the University of Florida (UF), oncology fellows participate in two general types of continuity clinic as part of their training. One clinic at the Veterans Hospital (VA) allows them to care for patients in a general clinic setting that encompasses a variety of hematology oncology diagnoses. The other clinic, located at the university site, is disease or system specific (such as breast or GI clinic). Considerable research supports the value of continuity clinic in residency and fellowship training, but the differences in having a general versus specialized clinic for oncology fellows have not been explored. The purpose of this study is to investigate the perceived differences of general versus specialized continuity clinics by recent oncology graduates from UF, and what features of a continuity clinic they feel were most important for an effective and meaningful experience. Methods: An anonymous survey was sent to the last six graduating classes of oncology fellows at UF. The survey contained short demographic questions, followed by five open ended questions pertaining to both continuity clinic experiences. Graduates were asked about their opinions of both the general and specialized clinics during their training at UF. Survey responses were reviewed and coded for common themes. Results: The most common themes that emerged from the surveys were concerning autonomy, supervision, and the diversity of cases and patient population. A majority of respondents felt they had more autonomy and personal responsibility at the VA general clinic, but less direct supervision than at the specialized clinics. They also believed they got a broader exposure of different disease types at the VA general clinic. Surveyed participants also commented on the quality of educational seminars and activities, preceptor expertise and teaching, and ability to observe cutting edge practice and clinical trials. Eleven out of thirty surveys were returned and we anticipate a greater than 50% response for the final poster. Conclusions: Graduated oncology fellows from UF believe that there is a balance that exists between having autonomy and ownership of their patients versus having adequate supervision. Many believe that having “controlled autonomy” and “as much independence as is safe for patients” is key to a meaningful continuity clinic experience during oncology fellowship training.
P13.07 Multi-omics as a tool for elucidating temozolomide resistance in glioblastoma multiforme
Authors: F Fabro, E Tóth, L J M Dekker, T M Luider, T M Pierson, S Leenstra
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma multiforme is the most common and aggressive brain tumor in adults, with an average overall survival of 14 months. Current standard of care consists of tumor resection followed by radiotherapy with concomitant temozolomide and adjuvant temozolomide. However, glioblastoma recurs in all patients. The causes reside in the enhanced invasiveness and resistance to treatment, giving a clear indication that recurrent and resistant glioblastoma biology must be understood better in order to achieve future treatment strategies to benefit the patients. The complex nature of recurrent glioblastoma makes its understanding still a challenging achievement in the field. Nowadays multi-omics approaching is developing further and further and it may be used to unravel, by combining different layers of biological information, a comprehensive view of the changes occurring during the treatment. MATERIAL AND METHODS A discovery set of 13 primary patient-derived glioblastoma stem-like cultures were analysed, comprising selected resistant, induced resistant and with pre-existing resistance conditions. A characterization of transcriptome, proteome and phosphoproteome was performed using RNAseq and liquid chromatography mass spectrometry. Additional 10 paired primary and recurrent tumor tissues were utilized as a validation set. The data obtained was visualised, explored and integrated through TIBCO Spotfire, Ingenuity Pathway Analysis, STRING and COREMINE medical software. RESULTS Genetic regulatory processes such as DNA repair mechanism, mRNA splicing and chromatin assembly were shown to be common over-represented trends in resistant and recurrent glioblastomas as a result of increased genomic instability and stress deriving from acute an repeated temozolomide exposure. Due to the immense heterogeneity of glioblastomas, other proteins and genes here identified as differentially expressed need a further investigation as they also may play an important role in relevant biological processes in a patient-specific way. CONCLUSION This study provides further understanding of glioblastoma biology revealing an association with processes of recurrence and temozolomide resistance, moreover offering potential therapeutic targets for better treatment options for glioblastoma patients.
Endothelin receptor B predicts poor prognosis in epithelial ovarian cancer (EOC) and can be inhibited to increase intratumoral T cells and enhance tumor vaccine therapy
Authors: R. J. Buckanovich, S. Kim, F. Benencia, D. Sasaroli, P. Gimotty, G. Coukos
Journal: Journal of Clinical Oncology (2006)

2524 Background: An inability of T cells to penetrate into tumor islets leads to a poor clinical outcome. We sought to identify tumor endothelial regulators of T cell trafficking. Methods: We used immunohistochemistry-guided laser capture microdissection to isolate and profile of vascular cells from EOC with or without (12 each) intratumoral T cells (ITC). Quantitative PCR (qPCR) and western blot of 60 EOC tumors was used to confirm array results and quantitate expression. Kaplan-Meier curves were generated to estimate survival according to high and low expression of ETRB (as determined by ROC analysis). Cox proportional hazard model was used to estimate the hazard ratio (HR). ETRB peptide antagonist BQ-788 was given QOD for 2 weeks to anti-tumor vaccinated mice with established ovarian tumors. After 8 weeks we used FACS and IHC to assess the presence of tumor-infiltrating T cells. Results: We identified ETRB as upregulated by the tumor vascular cells from tumors lacking ITCs. qPCR showed ETRB mRNA was 5.4 fold increased in ITC(-) vs. ITC(+) tumors. Univariate analyses demonstrated that ETRB expression was an independent prognosticator for both OS and DFS in EOC; the five-year overall survival rate was 70% for low ETRB expression versus &lt;5%for high ETRB expression (p &lt; 0.05, HR 0.35 (95% CI 0.17–0.71)). Bivariate analysis indicated that high ETRB expression predicted suboptimal cytoreduction (p &lt; 0.05). High expression of ETRB strongly correlated with ITC (-). ETRB blockade in a murine tumor vaccine model with peptide BQ-788 restricted tumor growth, reduced ascites, and increased survival compared to control animals. Analysis of BQ-788 treated tumors revealed a 5–15× increase in CD4+ and CD8+ intratumoral T cells. Conclusion: ETRB is an important new biomarker, for EOC patients, that correlates with ITC status and predicts both suboptimal cytoreduction and poor clinical outcome. Antagonism of ETRB in mice can restore an otherwise ineffective anti-tumor immune response. This suggests that ETRB inhibition may be a powerful adjuvant for tumor immunotherapy. No significant financial relationships to disclose.
Predictors of gastrointestinal bleeding in adult ICU patients: a systematic review and meta-analysis
Authors: Anders Granholm, Linan Zeng, Joanna Colleen Dionne, Anders Perner, Søren Marker, Mette Krag, Robert MacLaren, Zhikang Ye, Morten Hylander Møller, Waleed Alhazzani
Journal: Intensive Care Medicine (2019)
Over 100 cases of zero-ischemia robotic/laparoscopic partial nephrectomy: Is global renal ischemia necessary?
Authors: Scott Leslie, Andre Luis de Castro Abreu, Dennis J Lee, Andre K Berger, Alvin Goh, Hamed Ahmadi, Harman Maxim Bruins, Osamu Ukimura, Monish Aron, Mihir Desai, Inderbir S Gill
Journal: Journal of Clinical Oncology (2012)

e15060 Background: We report peri-operative and short-term outcomes of a novel technique of zero-ischemia robotic and laparoscopic partial nephrectomy (PN) for renal masses. Methods: From March 2010 to July 2011, 100 zero-ischemia robotic (n=40) and laparoscopic (n=60) PN were performed at our institution. The technique consists of performing micro-dissection of tertiary or higher-order renal arterial branches to super-selectively devascularize the tumor and surrounding parenchyma. Blood flow continues uninterrupted to the remainder of the kidney. As such, PN is performed without hilar cross-clamping. The procedure was offered to all-comers regardless of the tumor complexity or renovascular anatomy. Results: Median patient age was 59 years, tumor size was 3cm (0.9-13.6), baseline serum creatinine (SCr) was 1 mg/dl (0.5-2.6), and estimated glomerular filtration rate (eGFR) was 73 ml/min per 1.73m2 (24-149). 9 patients had a solitary kidney and 8 patients had multiple ipsilateral tumors. Overall, 70% of tumors were complex: central (43%), completely intra-renal (23%), cT1b &gt;4cm (21%), and hilar (19%). Median (range) RENAL, PADUA and C-Index scores were 8 (4-11), 9 (6-13), 2.2 (0.5 c 13.2), respectively. Warm ischemia time was zero, median operative time was 275 min (126-534), estimated blood loss was 200cc, percent of kidney excised was 20 (5-70) and hospital stay was 4 days (2-20). There were 13 complications in 12 patients, with major complications, Clavien grade ≥3, in 4 patients. Histology confirmed malignancy in 80% of tumors. All surgical margins were negative for cancer. There were no significant difference for median percent change in SCr, 0 mg/dl (-31 to 215), and eGFR, -1 (-74 to 53), at discharge. In 65 patients with more than 2 months (median 219 days) follow up data available, median percent change in SCr and eGFR were 18 (-31 to 154), p&lt;.001 and -18 (-66 t0 53), p&lt;.001, respectively. 1 patient developed pulmonary metastases at 1 year follow up. Conclusions: Zero-ischemia robotic/laparoscopic PN without hilar clamping is feasible and safe. It could be performed even in the setting of complex tumors and various vascular anatomy scenarios. Eliminating global renal ischemia now appears achievable.
World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
Authors: Stephen Kaptoge, Lisa Pennells, Dirk De Bacquer, Marie Therese Cooney, Maryam Kavousi, Gretchen Stevens, Leanne Margaret Riley, Stefan Savin, Taskeen Khan, Servet Altay, Philippe Amouyel, Gerd Assmann, Steven Bell, Yoav Ben-Shlomo, Lisa Berkman, Joline W Beulens, Cecilia Björkelund, Michael Blaha, Dan G Blazer, Thomas Bolton, Ruth Bonita Beaglehole, Hermann Brenner, Eric J Brunner, Edoardo Casiglia, Parinya Chamnan, Yeun-Hyang Choi, Rajiv Chowdry, Sean Coady, Carlos J Crespo, Mary Cushman, Gilles R Dagenais, Ralph B D'Agostino Sr, Makoto Daimon, Karina W Davidson, Gunnar Engström, Ian Ford, John Gallacher, Ron T Gansevoort, Thomas Andrew Gaziano, Simona Giampaoli, Greg Grandits, Sameline Grimsgaard, Diederick E Grobbee, Vilmundur Gudnason, Qi Guo, Hanna Tolonen, Steve Humphries, Hiroyasu Iso, J Wouter Jukema, Jussi Kauhanen, Andre Pascal Kengne, Davood Khalili, Wolfgang Koenig, Daan Kromhout, Harlan Krumholz, TH Lam, Gail Laughlin, Alejandro Marín Ibañez, Tom W Meade, Karel G M Moons, Paul J Nietert, Toshiharu Ninomiya, Børge G Nordestgaard, Christopher O'Donnell, Luigi Palmieri, Anushka Patel, Pablo Perel, Jackie F Price, Rui Providencia, Paul M Ridker, Beatriz Rodriguez, Annika Rosengren, Ronan Roussel, Masaru Sakurai, Veikko Salomaa, Shinichi Sato, Ben Schöttker, Nawar Shara, Jonathan E Shaw, Hee-Choon Shin, Leon A Simons, Eleni Sofianopoulou, Johan Sundström, Henry Völzke, Robert B Wallace, Nicholas J Wareham, Peter Willeit, David Wood, Angela Wood, Dong Zhao, Mark Woodward, Goodarz Danaei, Gregory Roth, Shanthi Mendis, Oyere Onuma, Cherian Varghese, Majid Ezzati, Ian Graham, Rod Jackson, John Danesh, Emanuele Di Angelantonio
Journal: The Lancet Global Health (2019)

To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions.
Predictors of Recurrent Severe Hypoglycemia in Adults With Type 1 Diabetes and Impaired Awareness of Hypoglycemia During the HypoCOMPaSS Study
Authors: Anneliese J.S. Flatt, Stuart A. Little, Jane Speight, Lalantha Leelarathna, Emma Walkinshaw, Horng Kai Tan, Anita Bowes, Alexandra Lubina-Solomon, Elizabeth Holmes-Truscott, Thomas J. Chadwick, Ruth Wood, Timothy J. McDonald, David Kerr, Daniel Flanagan, Augustin Brooks, Simon R. Heller, Mark L. Evans, James A.M. Shaw
Journal: Diabetes Care (2019)

OBJECTIVE The HypoCOMPaSS study was designed to test the hypothesis that successful avoidance of biochemical hypoglycemia without compromising overall glycemic control would restore sufficient hypoglycemia awareness to prevent recurrent severe hypoglycemia in the majority of participants with established type 1 diabetes. Before starting the study, we planned to investigate associations between baseline characteristics and recurrent severe hypoglycemia over 2 years’ follow-up. RESEARCH DESIGN AND METHODS A total of 96 adults with type 1 diabetes and impaired awareness of hypoglycemia participated in a 24-week 2 × 2 factorial randomized controlled trial comparing insulin delivery and glucose monitoring modalities, with the goal of rigorous biochemical hypoglycemia avoidance. The analysis included 71 participants who had experienced severe hypoglycemia in the 12-month prestudy with confirmed absence (complete responder) or presence (incomplete responder) of severe hypoglycemia over 24 months’ follow-up. RESULTS There were 43 (61%) complete responders and 28 (39%) incomplete responders experiencing mean ± SD 1.5 ± 1.0 severe hypoglycemia events/person-year. At 24 months, incomplete responders spent no more time with glucose ≤3 mmol/L (1.4 ± 2.1% vs. 3.0 ± 4.8% for complete responders; P = 0.26), with lower total daily insulin dose (0.45 vs. 0.58 units/24 h; P = 0.01) and greater impairment of hypoglycemia awareness (Clarke score: 3.8 ± 2.2 vs. 2.0 ± 1.9; P = 0.01). Baseline severe hypoglycemia rate (16.9 ± 16.3 vs. 6.4 ± 10.8 events/person-year; P = 0.002) and fear of hypoglycemia were higher in incomplete responders. Peripheral neuropathy was more prevalent in incomplete responders (11 [39%] vs. 2 [4.7%]; P &amp;lt; 0.001) with a trend toward increased autonomic neuropathy. CONCLUSIONS Recurrent severe hypoglycemia was associated with higher preintervention severe hypoglycemia rate, fear of hypoglycemia, and concomitant neuropathy.
P14.44 Survival benefit of lobectomy over gross-total resection without lobectomy in cases of glioblastoma in the noneloquent area: a retrospective study
Authors: T Roh, S Kang, C Hong, J Chang
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Following resection of glioblastoma (GBM), microscopic remnants of the GBM tumor remaining in nearby tissue cause tumor recurrence more often than for other tumors, even after gross-total resection (GTR). Although surgical oncologists traditionally resect some of the surrounding normal tissue, whether further removal of nearby tissue may improve survival in GBM patients is unknown. In this single-center retrospective study, the authors assessed whether lobectomy confers a survival benefit over GTR without lobectomy when treating GBMs in the noneloquent area. MATERIAL AND METHODS The authors selected 40 patients who had undergone GTR of a histopathologically diagnosed isocitrate dehydrogenase (IDH)-wild type GBM in the right frontal or temporal lobe and divided the patients into 2 groups according to whether GTR of the tumor involved lobectomy, defined as a supratotal resection (SupTR group, n = 20) or did not (GTR group, n = 20). Progression-free survival (PFS), overall survival (OS), and Karnofsky Performance Status (KPS) scores were compared between groups (p ≤ 0.05 for statistically significant differences). RESULTS The median postoperative PFS times for each group were as follows: GTR group, 11.5 months (95% CI 8.8–14.2) and SupTR group, 30.7 months (95% CI 4.3–57.1; p = 0.007). The median postoperative OS times for each group were as follows: GTR group, 18.7 months (95% CI 14.3–23.1) and SupTR group, 44.1 months (95% CI 25.1–63.1; p = 0.040). The mean postoperative KPS scores (GTR, 76.5; SupTR, 77.5; p = 0.904) were not significantly different. In multivariate analysis, survival for the SupTR group was significantly longer than that for the GTR group in terms of both PFS (HR 0.230; 95% CI 0.090–0.583; p = 0.002) and OS (HR 0.247; 95% CI 0.086–0.704; p = 0.009). CONCLUSION In cases of completely resectable, noneloquent area GBMs, SupTR provides superior PFS and OS without negatively impacting patient performance.