tbuckley/cabot-search huggingface dataset:
Subjective sleep problems and objective circadian disruption: Impact on outcomes in patients with metastatic colorectal cancer (MCC).
Authors: Oxana Palesh, Ayhan Ulusakarya, Georg A. Bjarnason, Francis Levi, Pasquale F Innominato
Journal: Journal of Clinical Oncology (2015)

e14584 Background: Both subjective sleep problems (S) and circadian disruption (C) have been shown to be independently associated with shorter overall survival (OS), shorter progression-free survival (PFS) and lower objective response (OR) rate in MCC patients (Lévi F., Chronobiol Int, 2014; Innominato P., Sleep Med, 2015). Although sleep and circadian functions are interconnected, the disruption of both (S + C) on patients’ outcomes has yet to be evaluated. Methods: Sleep problems were assessed using self-report sleep item from the EORTC QLQ-C30 questionnaire. Circadian function was evaluated with wrist actigraphy, using the robust I < O parameter. Previously validated cut off values were used. A multivariate Cox regression hazard model was built to predict OS or PFS, whereas a multivariate binary logistic regression was used for predicting OR. Results: Data were available for 237 MCC patients (median age: 60.2 years; Female: 37.6%; Performance Status = 0: 60%) before starting chemotherapy. Sleep problems and circadian disruption were positively correlated (p = 0.006). Patients with no disruption had significantly better outcomes as compared to the other groups. Specifically, patients with C alone or C+S displayed the worst outcomes, followed by those with S alone. Sleep and/or circadian disruption were associated with shorter OS and PFS and lower OR rate, independent of other prognostic factors. Conclusions: Large proportion of MCC patients experience both sleep and circadian disruption. Circadian disruption is sufficient, regardless of sleep, to worsen prognosis, whereas sleep problems are associated with poor outcomes only in patients without circadian disruption. These preliminary results suggest that personalized pharmacological and/or behavioral interventions specifically impacting sleep and/or circadian functions could improve patients’ outcomes. Median OS (months) HR Median PFS (months) HR OR rate OR None (N=47; 19.8%) 28.3 1 13.3 1 55.3 1 Sleep problems alone (N=60; 25.3%) 16.4 1.47 8.8 1.25 43.3 0.64 Circadian disruption alone (N=35; 14.8%) 11.8 2.42 8.6 1.70 28.6 0.34 Both (N=95; 40.1%) 12.0 2.65 5.7 1.96 29.5 0.32 Multivariate p 0.0001 0.001 0.012
Protection of prostate cancer cells from GSK-3β-induced oxidative stress by Il-8 through activating the mTOR signaling pathway.
Authors: Yi Sun, Lu Yang, Qiang Wei
Journal: Journal of Clinical Oncology (2019)

311 Background: Both oxidative stress and inflammation play important roles in prostate cancer cell apoptosis or proliferation. However, the mechanisms underlying these processes remain unclear. Thus, we chose IL-8 as the bridge between inflammation and cancer cell oxidative stress-induced death and confirmed its connection with mTOR and GSK-3beta. Methods: We overexpressed GSK-3beta and observed the effect of GSK-3beta on reactive oxygen species (ROS) and cell death induced by oxidative stress. Then, IL-8 was upregulated or downregulated to determine its impact on preventing cells from damage by GSK-3beta-induced oxidative stress. In addition, we confirmed the role of mTOR in this process through its overexpression or knockdown. Real-time PCR, Western blotting, transcription, Cell Counting Kit 8, flow cytometry and other techniques were used. Results: IL-8 promotes prostate cancer cell proliferation and decreases apoptosis, while GSK-3beta induces cell death by oxidative stress through the activation of the caspase-3 signaling pathway by increasing ROS. In addition, mTOR can also decrease the activation of the caspase-3 signaling pathway by inhibiting GSK--3beta and thus decreasing ROS production. Moreover, the inhibitory effect of IL-8 on GSK-3beta occurs through the regulation of mTOR. Conclusions: The results of this study highlight the importance of GSK-3beta, which increases the production of ROS and then induces oxidative stress in tumor cells, while IL-8 and mTOR attenuate the oxidative stress to protect prostate cancer cells through the inhibitor GSK-3beta.
Attitudes towards highly pathogenic avian influenza (HPAI) and biosecurity mitigation practices in rural Vietnam: a cross-sectional survey
Authors: Mairead G Whelan, Quynh Ba Le, David C Hall
Journal: The Lancet Global Health (2019)

BackgroundAn outbreak of highly pathogenic avian influenza (HPAI) between 2004 and 2006 resulted in the culling of 45 million birds, and has jeopardised sustainable agricultural production in southeast Asia. HPAI is highly virulent, and small-scale farms present a high-risk environment for disease transmission between animals and humans. The purpose of this study was to investigate how attitudes towards HPAI influence biosecurity mitigation behaviours such as water source management and sanitation on small-scale farms in Vietnam.MethodsWe used a participatory approach that included representation from farmers, government, academia, and industry. We collected cross-sectional data on demographics, farm level production, and attitudes and preferences with respect to HPAI and mitigation strategies in north and south Vietnam (Thai Binh and An Giang Provinces, respectively). A stratified randomised selection of 600 small-scale mixed livestock, crop, and fish farmers were interviewed using questionnaires and in-person interviews. We calculated participant numbers using standard epidemiological sample size formulae with α=0·05. The study was approved by Canadian and Vietnamese ethics boards and participants provided verbal informed consent. Logit regression analysis was used to examine the relation between factors influencing HPAI attitudes and behaviours. Further correlation analysis is under investigation, including Pearson correlation and principal component analysis.FindingsPreliminary results show that half the farmers (51%, n=306) did not treat their water according to UN Food and Agriculture Organization guidelines, and fewer than 7% (n=40) said they would report a suspected HPAI case because of the cost and inconvenience of doing so. However, those farmers who expressed concern about HPAI were more likely to practise mitigation behaviours (p=0·034).InterpretationThese preliminary analyses indicate that biosecurity guidelines may not be consistent with management styles of small-scale farms in Vietnam, but also indicate cause for concern for controlling HPAI on such farms. These results should be of interest to public health and policy authorities addressing HPAI mitigation. Our results may not be generalisable to all small-scale farmers in Vietnam because water sources and farming strategies vary across communes.FundingGrand Challenges Canada (Grant Number 0231-01 Stars in Global Health Round 4) and IDRC, Ottawa.
Mutations and Copy Number Changes Predict Progression from Smoldering Myeloma to Symptomatic Myeloma in the Era of Novel IMWG Criteria
Authors: Eileen M Boyle, Cody Ashby, Ruslana G. Tytarenko, Yan Wang, Michael A Bauer, Shayu Deshpande, Sarah K Johnson, Carolina D. Schinke, Sharmilan Thanendrarajan, Frits van Rhee, Christopher Wardell, Niels Weinhold, Thierry Facon, Charles Dumontet, Gareth Morgan, Faith E. Davies, Brian A Walker
Journal: Blood (2018)
Evaluation of Pre-Collection Factors and Collection Efficiency Leads to Strong Correlation between Predicted and Actual Peripheral Blood Stem Cell Collection Yields in Multiple Myeloma Patients: A Single Institution Experience
Authors: FEI FEI, Daniel Peavey, Mariam Youssef, Sondra Dunn, Terry Slover, Nick Boshell, Marisa B. Marques, Luciano J Costa, X. Long Zheng, Lance Williams
Journal: Blood (2018)
Abstract P111: A Mendelian Randomization Study of Alcohol Intake and Ischemic Stroke in a Han Chinese Population
Authors: Mengyao Shi, Yonghong Zhang, Changwei Li, Aili Wang, Tan Xu, Xiao Sun, Xiaoqing Bu, Jing Chen, Tanika N Kelly, Jiang He
Journal: Circulation (2019)

Introduction: Observational studies have reported inconsistent relationships between alcohol intake and ischemic stroke risk. The ALDH2 gene encodes an enzyme critical for alcohol metabolism and can serve as an unconfounded proxy for alcohol intake. The current study examined the association between the ALDH2 gene and ischemic stroke among 11,753 Chinese participants. Hypothesis: This study hypothesized that carriers of the ALDH2 variant tend to drink less alcohol and thus have lower risk for ischemic stroke. Methods: The discovery stage included 999 ischemic stroke cases and 1,001 controls with no history of atherosclerotic disease. The ALDH2 gene was sequenced using the SOLiD 4hq platform. Variants with minor allele count (MAC) &gt;10 were each tested for association with stroke using logistic regression models. Interactions between alcohol intake and ALDH2 variants were also tested. Aggregate analysis of rare variants (MAC &lt;20) used the sequence kernel association test. Variants with P&lt;1х10 -4 were replicated among 4,724 ischemic stroke cases and 5,029 controls from the China Stroke Project. Results: An interaction of alcohol drinking with the ALDH2 rs671 variant, which encodes an inactive aldehyde dehydrogenase isozyme that limits tolerability to alcohol, on ischemic stroke risk was identified using the 2 degree of freedom test (P=2.77х10 -5 , 3.66х10 -11 , and 1.01х10 -15 in discovery, replication and joint analyses, respectively). Among drinkers, each copy of the variant allele conferred decreased odds of ischemic stroke, with odds ratios (95% CI) of 0.38 (0.25, 0.60), 0.79 (0.69, 0.91), and 0.74 (0.65, 0.85) in discovery, replication and joint analyses, respectively. While no association between the variant allele and stroke was observed among non-drinkers in the discovery stage [odds ratio (95% CI): 1.00 (0.82, 1.23)], the protective relation persisted among non-drinkers in the replication and joint analyses [odds ratios (95% confidence interval): 0.77 (0.71, 0.84) and 0.80 (0.74, 0.87), respectively]. This inconsistency may have resulted from disparate frequencies of former drinkers included in the non-drinking groups. No additional variants were identified. Conclusions: This large-scale genomic study implicates increased alcohol intake as an etiologically relevant risk factor for ischemic stroke.
Outcomes for Patients with Pre-Existing Diabetes or Hypertension Treated with Copanlisib from the CHRONOS-1 Study in Patients with Relapsed or Refractory Indolent B-Cell Lymphoma
Authors: Pier Luigi Zinzani, Armando Santoro, Luigina Mollica, Sirpa Leppä, George A Follows, Georg Lenz, Won Seog Kim, Arnon Nagler, Panayiotis Panayiotidis, Judit Demeter, Franck Morschhauser, Liana Rodrigues, John Reeves, Florian Hiemeyer, Ashok Miriyala, Jose Garcia-Vargas, Barrett H. Childs, Martin H. Dreyling
Journal: Blood (2018)
Transplantation after Viability Testing of Discarded Livers with Normothermic Machine Perfusion (NMP): The Vittal (VIability Testing and Transplantation of mArginal Livers) Trial 90-Day Outcomes
Authors: H Mergental, R W Laing, A J Kirkham, Perera Tpr., Y Boteon, J Attard, D Barton, M Wilkhu, S Curbishley, D A Neil, S G Hubscher, L Wallace, P Muiesan, J Isaac, K Roberts, M Abradelo, H Cilliers, J Bion, P J Friend, C Yap, S C Afford, D F Mirza
Journal: Hepatology (2018)
Quantifying the Severity of Pharyngeal Airflow Obstruction Using Polysomnography
Authors: D. Mann, A. Azarbarzin, S. Mariani, A. Franciosini, A. Camassa, L. Taranto-Montemurro, L. Messineo, S. Redline, D. White, A. Wellman, P. Terrill, S. Sands
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Expectations of cure among patients with advanced genitourinary cancer treated with immunotherapy.
Authors: Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Errol James Philip, Joann Hsu, Nazli Dizman, Ulka N. Vaishampayan, Tanya B. Dorff, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2019)

591 Background: Over the past 15 years, considerable progress has been made in systemic therapy options for genitourinary (GU) cancers. In diseases such as metastatic renal cell carcinoma (RCC) and urothelial cancer (UC), immunotherapeutic strategies such as programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition have elicited durable responses, albeit in a minority of patients. We examined expectations for clinical outcome with immunotherapy among patients with advanced GU cancers. Methods: A survey study was conducted in patients with advanced GU cancers initiating PD-1/PD-L1 inhibitors from October 2017 to September 2018. Patients were screened prior to initiation of immunotherapy for their expectation of cure (divided into 4 quartiles), symptoms of anxiety and depression (PROMIS-A and PROMIS-D), and quality of life (QOL; FACT-G). For purposes of the survey, cure was equated to a durable complete response. Differences in frequency of anxiety, depression and QOL were compared amongst subsets of patients divided by expectation of cure. Results: Among 60 patients, median age was 67, 72% were male and 81% were married. Types of cancer included RCC (69%), UC (19%) and prostate cancer (12%). The majority were in the 1 st or 2 nd line of therapy (40% and 31%, respectively). Despite extensive counseling from GU medical oncologists, 23% of patients thought that cure was “very likely”, defined as in the range of 76-100%. Approximately 70% of patients estimated cure in the range of 0-25%, in line with clinical counseling. These patients had higher rates of anxiety (P = 0.01), depression (P = 0.002) and poorer QOL (P = 0.003) compared to patients who felt cure was very likely. Conclusions: A considerable proportion of patients with advanced GU malignancies harbor unrealistic expectations around the potential benefit of immunotherapy. Although a first instinct may be to remedy these expectations, it is important to bear in mind that these patients had better emotional well-being and QOL. We will validate these findings and assess these parameters longitudinally in an upcoming SWOG trial for patients with mRCC receiving upfront immunotherapy.
Predicting vital retroperitoneal residual tumors of metastatic testicular tumor patients after chemotherapy using radiomics.
Authors: Tim Nestler, Bettina Baeßler, Daniel Pinto dos Santos, David J. K. P. Pfister, David Maintz, Axel Heidenreich
Journal: Journal of Clinical Oncology (2019)

527 Background: About 50% of patients undergoing post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) are overtreated due to missing markers or valid prediction scores prior surgery. The potential of radiomics and machine learning applied on computed tomography (CT) imaging to predict the presence of viable tumor or teratoma in retroperitoneal lymph node metastases from germ cell tumor (GCT) patients prior to pcRPLND has not been explored. Therefore, we applied radiomics and machine learning to CT images of GCT patients prior to pcRPLND. Methods: Metastasized GCT patients who were treated with chemotherapy and received a contrast-enhanced CT prior to pcRPLND possessing complete clinical data were included in the study. Only lymph nodes which were identified in the CT images and correlated with the pathological findings (benign: necrosis / fibrosis vs. viable: viable tumor/ teratoma) were included. Lymph nodes identified in the CT images, were semiautomatically segmented and 93 radiographic features were analyzed. A linear support vector machine (SVM) algorithm was applied to analyze reproducible radiomics features. Additionally, a continuous reduction of the features analyzed was performed using Random Forest algorithms, as well as consecutive correlation and receiver operating curve analyzes. Results: Forty-two patients fulfilled the inclusion criteria and were included in the study. Total in these patients 96 lymph nodes were segmented on CT. Histologically, 41 lymph nodes were classified as viable tumors and 55 as benign. To train the SVM, 67 lymph nodes were randomly selected. Of the 93 radiomic features analyzed, 51 features were reproducible. Applying the trained algorithm to the remaining 29 lymph nodes resulted in a classification accuracy of 82% with a diagnostic sensitivity of 81% and a specificity of 83%. After multistep feature reduction, the three most important predictors for viable tumor achieved a sensitivity of 66% and a specificity of 78% when combined in a multivariate model. Conclusions: The applied radiomics model, solely based on CT images achieved a good sensitivity and specificity in predicting viable metastases.
A pilot study of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy (CT) with paclitaxel, capecitabine and mimomycin C for squamous cell anal carcinoma (SCAC).
Authors: Sergey Gordeev, Arsen Rasulov, Vera Gorbunova, Sergey Tkachev, Nataliya Besova, Mikhail Fedyanin, Valeriya Glebovskaya
Journal: Journal of Clinical Oncology (2015)

e14501 Background: The goals of this study were to assess the feasibility and toxicity of a regimen of IMRT and CT with paclitaxel, capecitabine and mitomycin C in the treatment of patients with SCAC. A secondary objective was to assess complete clinical response at 6 months after treatment. Methods: Between November 2013 and August 2014 twenty patients received IMRT and concurrent CT at our institution for localized SCAC. Radiotherapy (RT) was delivered with a simultaneous integrated boost technique, with dose based on the T stage. The planned dose to the primary tumor and pelvis were 52-58 Gy and 42-46 Gy, respectively. The concurrent CT regimen consisted of paclitaxel 45 mg/m2 on days 3,10,17,24,31, capecitabine 625 mg/m2 bid on treatment days and mitomycin C 10 g/m2 on day 1. Follow-up examinations were performed after 3 and 6 months and included digital rectal examination, pelvic MRI, abdominal ultrasound, rectoscopy and serum SCC-ag. Results: The median age was 53.5 years (range 34-67). 17 (85%) patients were female. The percentage of patients with T1, T2, T3, and T4 disease were 3(15%), 7(35%), 5(25%), and 5(25%), respectively. The percentage of patients with N0, N1, N2, and N3 disease were 4(20%), 5(25%), 7(35%), and 4(20%), respectively. Nine patients (45%) completed RT in full accordance with the study protocol, 9(45%) patients had minor treatment alterations (treatment break < 5 days, capecitabine break < 7 days, cancellation of 1 paclitaxel administration) and 2 (10%) patients had major treatment alterations. Grade 3-4 toxicity occurred in 12(60%) patients: 6(30%) skin, 4(20%) diarrhoea, 4(20%) leucopenia, 4(20%) proctitis. All patients completed 6 months follow-up examination. 18(90%) patients had complete response. One patient had incomplete response and underwent salvage APR. One patient had incomplete response and developed distant metastases. Conclusions: IMRT and concurrent CT with paclitaxel, capecitabine and mitomycin C for SCAC is feasible and has acceptable toxicity profile. It could lead to improved chance of complete response and further study with randomization and larger number of patients is warranted.
Liposomal mitomycin C prodrug (Promitil) compared to mitomycin C in chemoradiotherapy in preclinical models of colorectal cancer.
Authors: Xi Tian, Minh Nguyen, Patricia Ohana, Alberto A. Gabizon, Andrew Wang
Journal: Journal of Clinical Oncology (2015)

e13525 Background: Mitomycin C (MMC) is a potent radiosensitizer and a well-established agent in chemoradiotherapy (CRT) for anal cancer and localized bladder cancer. However, its use is often limited by toxicity. Promitil is a pegylated liposomal formulation of a MMC lipid-based prodrug (MLP), activated by thiolytic cleavage, that has shown a significantly improved toxicity profile in preclinical and phase I clinical investigations. We hypothesized that Promitil can improve the therapeutic index of CRT. In this study, Promitil was compared to MMC in CRT using mouse xenograft models of colorectal cancer. Methods: Promitil was provided by LipoMedix Pharmaceuticals. To evaluate Promitil efficacy as a radiosensitizer, it was compared in vitro with MMC using colorectal cancer cell lines (HT-29 and SW480) and in vivo using mouse xenograft subcutaneous tumor models. In addition, any potential toxicity resulting from the combination of CRT, including skin toxicity and hematologic toxicity, were examined. Results: Similar to previous studies, Promitil was less cytotoxic than MMC in vitro. Promitil is as effective as MMC as radiosensitizer of both HT-29 and SW480 cells in vitro, supporting its efficacy as a radiosensitizer. In vivo studies demonstrated that Promitil-based CRT regimens delayed tumor growth significantly more than corresponding treatment with MMC with or without 5-Fluorouracil (5FU). In mice bearing HT-29 tumor xenografts, the addition of 5FU to Promitil further enhanced the tumor growth inhibitory effect of CRT. Promitil did not cause any toxic deaths, and body weight loss in the treated mice was limited and reversible. In addition, there was less hair toxicity in mice treated with Promitil despite using 2.5 fold higher MMC equivalents. Conclusions: Promitil enhances radiosensitivity of colorectal cancer cells over MMC with or without 5FU in vivo, without incurring in toxicity. Promitil may act synergistically with irradiation. Our findings support clinical investigations utilizing Promitil in CRT.
Abstract P002: Seven-Year Changes in Cardiovascular Health in Older Adults: The Cardiovascular Health Study
Authors: Mamadou D Tounkara, Kristine MaWhinney, Kirsten Evans, Emily Startup, Alexa Ehlert, Emarie Covey, Jordan Westra, Natalie J Blades, Mandip S Dhamoon, Hector M Gonzalez, Fumiaki Imamura, Elzbieta Kuzma, David J Llewellyn, M Lelinneth B Novilla, Monica Scrobotovici, W T Longstreth, Evan L Thacker
Journal: Circulation (2019)

Objective: The AHA Life’s Simple 7 (LS7) defines cardiovascular health with smoking, physical activity, diet quality, body mass index (BMI), blood pressure, total cholesterol, and blood glucose. We examined changes in LS7 score and its components in older adults over seven years of follow-up. Methods: We analyzed 2,234 adults aged 65+ in the Cardiovascular Health Study who had all LS7 components measured at baseline (1989) and seven years later (1996). We scored each component as ideal (2), intermediate (1), or poor (0). LS7 score was the sum of components, ranging from 0 (worst) to 14 (best), then categorized as ideal (10-14), intermediate (5-9), or poor (0-4). Results: Mean LS7 score at baseline was 8.71, declining by 0.24 points (95% CI: 0.17, 0.31) to 8.47 seven years later. At baseline, LS7 score was ideal in 35% of participants, intermediate in 63%, and poor in 1.7%. Seven years later, the distribution shifted down, with 31% scoring ideal, 67% scoring intermediate, and 2.0% scoring poor. Of those scoring ideal at baseline, 57% (95% CI: 53%, 60%) maintained ideal scores seven years later (Figure, Panel A). Of those scoring intermediate at baseline (Panel B), 18% (95% CI: 16%, 20%) improved to ideal. Of those scoring poor at baseline (Panel C), 76% (95% CI: 63%, 90%) improved to intermediate, but none improved to ideal. For components, maintenance of baseline ideal status was 95% for smoking, 86% for glucose, 80% for BMI, 77% for cholesterol, and 55% for physical activity, but only 35% for blood pressure and 7% for diet (Panel A). Decline of baseline intermediate status to poor was 33% for blood pressure and 24% for diet (Panel B). Improvement of baseline poor status to intermediate or ideal was &gt;50% for cholesterol and physical activity and &gt;40% for smoking and diet (Panel C). Conclusions: While cardiovascular health declined on average in an aging population, some older adults improved their cardiovascular health as they aged. Declines in diet quality and blood pressure control contributed to overall declines in cardiovascular health.