tbuckley/cabot-search huggingface dataset:
THU0470 Work and professional recognition in fibromyalgia patients – a national french web based survey on sick leave in 1870 fibromyalgia female patients
Authors: F Laroche, D Azoulay, J Guérin, J Coste, S Perrot
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fibromyalgia (FM) induces work limitations with an increase of number of days of sick leave 3 to 4 fold higher (1, 2). <h3>Objectives</h3> Our objectives were to analyze work status, to determine risk factors for sick leave and to compare women working to women in sick leave during the past 12 months in a female population with FM. <h3>Methods</h3> 1870 female workers suffering from FM were selected from a large internet-based national survey of 4516 responders (Fibromyalgie-SOS Association website in France in 2014). Women having a FIRST score ≥5/6 were included. <h3>Results</h3> 1870 patients participated to the survey: 955 with full time job, 149 with part time job (related to FM status) and 766 on sick leave (7% 1–3 months, 27.3% 3–12 months and 62% &gt;12 months). Fibromyalgia Impact questionnaire (FIQ) score was slightly lower in the 1104 patients currently working compared to the 766 on sick leave (56 versus 58.7), but not clinically different. 64,5% of the population have been on sick leave during the last 12 months (average duration: 37 mean days for full time job and 122 among those with part time job). Women being in sick leave were older (p&lt;0,0001), single (p=0,0321), had less financial income (p&lt;0,0001), used more antidepressants (p=0,0085) and more anti epileptics (p=0,0102). Recognition of FM by occupational physicians or social security doctors were lower among the workers (p&lt;0.0001). In the 1104 currently working, more than 33% have never been visiting their occupational physician and 44,2% rarely. They reported no support from these doctors (p=0,0011) particularly those having not being on sick leave. Independent criteria of sick leave were transportation time (p=0.0131), work difficulties (p=0.0031), hinders career progress (p=0.0196), sedentary occupation and repetitive work (p=0.0195). <h3>Conclusions</h3> These data on a large fibromyalgia population shows that clinical status and also professional factors may influence work ability and sick leave. The work factors include work difficulties, transportation time, sedentary and repetitive occupation. These results should be taken into account by the work professionals in order to facilitate work capacity in FM patients. <h3>References</h3> Sicras-Mainar A, Rejas J, Navarro R, Blanca M, Morcillo A, Larios R, Velasco S VillarroyaC. Treating patients with fibromyalgia in primary care settings under routine medical practice: a claim database cost and burden of illness study. Arthritis Research &amp; Therapy 2009, 11:R54. White K. Comparing self-reported function and work disability in 100 community cases of fibromyalgia syndrome versus controls in London, Ontario: the London Fibromyalgia Epidemiology Study. Arthritis Rheum. 1999;42:76–83. <h3>Acknowledgements</h3> Fibromyalgia SOS french Association. <h3>Disclosure of Interest</h3> None declared
Abstract CT144: Pediatric phase I trial of the WEE1 inhibitor AZD1775 and irinotecan in patients with refractory solid and CNS malignancies; A Children’s Oncology Group Study (ADVL1312)
Authors: Kristina A. Cole, Joel M. Reid, Xiaowei Liu, Charles G. Minard, John M. Maris, Elizabeth Fox, Brenda J. Weigel
Journal: Cancer Research (2017)

Abstract Background: Inhibition of the WEE1 kinase by AZD1775 potentiates replicative stress induced by oncogenes or chemotherapy, and demonstrated anti-tumor activity in preclinical models of pediatric cancer. A pediatric phase I dose escalation study of AZD1775 in combination with irinotecan was completed within the COG DVL consortium. Methods: Patients age 1-21 years with relapsed/refractory solid or CNS tumors were eligible. Both agents were administered orally once daily on days 1-5 of a 21-day cycle with a step-wise inter-patient dose escalation of both agents. AZD1775 dose levels (DL) were 50 mg/m2 (DL1), 65 mg/m2 (DL 2 and 3), 85 mg/m2 (DL4) and 110 mg/m2 (DL5). Irinotecan, 70 mg/m2 day (DL 1-2), or 90 mg/m2/day (DL3-5), was administered with cefixime for diarrheal prophylaxis. Toxicity was graded according to CTCAE v4.0. Results: Thirty-one eligible patients, median age 14 years (range 5-20) were enrolled; 29 (93%) received prior chemotherapy (median 3 regimens) and 25 (81%) received prior radiation therapy. Sixteen patients had a primary CNS malignancy: malignant glioma (9), ependymoma (4), medulloblastoma (2) and CNS Ewings sarcoma (1). Fifteen patients had extracranial solid tumors: soft tissue sarcoma (6), neuroblastoma (2), carcinoma (4), osteosarcoma (2) and Wilms’ Tumor (1). The most common toxicities were hematologic and gastrointestinal (nausea, vomiting, diarrhea). Two patients experienced dose limiting toxicity, grade 3 diarrhea and dehydration at DL5 (AZD1775 110 mg/m2 and irinotecan 90 mg/m2). Conclusion: This is the first pediatric clinical trial of AZD1775 in combination with chemotherapy. The maximum tolerated dose in children and adolescents with solid tumors was AZD1775 85 mg/m2/day in combination with irinotecan 90 mg/m2/day for five days every 21 days. Accrual is ongoing for a pediatric PK expansion, PD analysis and Phase 2 expansion in patients with neuroblastoma or medulloblastoma / CNS PNET. Clinical trial information: NCT02095132 Citation Format: Kristina A. Cole, Joel M. Reid, Xiaowei Liu, Charles G. Minard, John M. Maris, Elizabeth Fox, Brenda J. Weigel. Pediatric phase I trial of the WEE1 inhibitor AZD1775 and irinotecan in patients with refractory solid and CNS malignancies; A Children’s Oncology Group Study (ADVL1312) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT144. doi:10.1158/1538-7445.AM2017-CT144
Abstract LB-040: Application of clinical whole exome sequencing among larger scale advanced cancer patients in China
Authors: Qiang Xu, Guan Wang, Chun Dai, Cheng Chen, Xiaoman Xu, Haining Wang, Angela Wu, Jiping Wang
Journal: Cancer Research (2017)

Abstract Background: Genomics-guided precision medicine has become a major paradigm shifting effort in cancer care globally to improve the outcome of cancer patients. More and more patients receive individualized cancer treatments based on their tumor-specific characteristics at both gene and genomic levels. Methods: Over 1,000 cancer patients from more than 70 hospitals across 20 provinces in China were recruited into the project. Majority (88%) of these patients are with 4 major tumor types, which are lung, gastric, colorectal, and breast cancer. The whole exome of tumor specimen and case-matched normal samples were sequenced in each patient. Clinical decision roadmap recommendations were provided to each patient and their treating physician based on clinical whole exome sequencing (CWES) and globally available treatment options. The treatment implementation and the outcome of each patient have been followed. Results: Of the 907 prospectively enrolled patients, 80% patients was recommended at least one FDA approved target/immunotherapy drug. 60% patients’ tumors have cancer driver/suppressor gene large segment deletions or amplifications. At the end of December 2016, 98 patients with late stage NSCLC, breast or colorectal cancer had more than 6 months follow up. Ninety five percent of (93) patients received personalized target/immunotherapy recommendations based on CWES, including genomic-matched clinical trials. Thirty percent (29) patients actually received the recommended therapy clinically. Of those 29 patients, 55% (16) patients received the treatments recommended by CWES. And 14 of those 16 patients had stable disease (SD) at the time of this report. 25 patients initially received treatment based on other panel-based recommendations, and 14 of the 25 patients suffered disease progression. Among those 14 patients, 8 patients received recommended treatment based on CWES and achieved SD at a later time. Conclusions: CWES can provide clinical relevant treatment recommendations for most of the advanced cancer patients. Our preliminary observations suggests that CWES might provide a boarder clinical recommendation roadmap for the cancer patients in China. Longer follow-up is needed to evaluate the clinical significance of CWES on long term prognosis. Citation Format: Qiang Xu, Guan Wang, Chun Dai, Cheng Chen, Xiaoman Xu, Haining Wang, Angela Wu, Jiping Wang. Application of clinical whole exome sequencing among larger scale advanced cancer patients in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-040. doi:10.1158/1538-7445.AM2017-LB-040
Abstract 1538: A mouse model that mimics human MEN1 tumor is effective in preclinical neuroendocrine tumor therapeutics
Authors: Chung Wong, Richard Clausen, Laura Tang, Christian Davidson, Evan Vosburgh, Arnold Levine, Eugenia Xu
Journal: Cancer Research (2017)

Abstract Conditional knockout of Men1 in β cells leads to development of pituitary adenomas and pancreatic neuroendocrine tumors (PanNETs) by the age of eight to twelve months. This suggests that other events, like loss of additional mutations, may be required for development of tumors in the absence of MEN1. Since it was reported that mutations in genes of PI3K/mTOR pathway are found in human neuroendocrine tumors, we hypothesized that double deletion of PTEN and MEN1 may accelerate neuroendocrine tumorigenesis. Mice with double deletion of PTEN and MEN1 in β cells were produced by crosses among mice with Cre gene under the control of Rat Insulin promoter (Rip-Cre), floxed allele Men1 (Men1fl/fl), and Pten (Ptenfl/fl). Then mice with the genotype of Men1fl/fl Ptenfl/fl Rip-Cre were monitored for development of tumors. Consistent with our hypothesis, mice with conditional deletion of PTEN and MEN1 leads to fully developed PanNETs and pituitary adenomas by three to four months old, much earlier than that with Men1 deletion alone. These tumors resemble human MEN1 tumors at a histological and molecular level. Activation of phospho-AKT was observed in these tumors and Rapamycin treatments lead to delayed PanNETs and pituitary adenomas for at least two months. This mouse model (Men1fl/fl Ptenfl/fl Rip-Cre) directly supports that PI3K/mTOR pathway plays a critical role in neuroendocrine tumorigenesis, and also provides a platform to study new therapeutic opportunities for PanNETs and neuroendocrine tumors of the pituitary through the targeting of PI3K/mTOR pathway and MEN1 pathway. This model represents an important tool for studying the biology and preclinical therapeutics of human neuroendocrine tumors. Citation Format: Chung Wong, Richard Clausen, Laura Tang, Christian Davidson, Evan Vosburgh, Arnold Levine, Eugenia Xu. A mouse model that mimics human MEN1 tumor is effective in preclinical neuroendocrine tumor therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1538. doi:10.1158/1538-7445.AM2017-1538
Abstract 5599: Soluble PD-L1 as a surrogate biomarker of metastatic progression and resistance to antiangiogenic therapy
Authors: Michalis Mastri, Amanda Tracz, Yuhao Shi, Georg Bjarnason, Tran Nguyen, Brian Rini, John M.L. Ebos
Journal: Cancer Research (2017)

Abstract Immune-checkpoint inhibitors are now approved for the treatment of early- and late-stage cancers. These include agents that block the T-cell regulatory protein programmed cell death 1 (PD-1) from being activated by the PD-1 ligand 1 (PD-L1) expressed on cancer cells. There is an urgent need to identify biomarkers of PD-1 pathway inhibition that would predict patient populations responsive to treatment and/or serve as surrogates for drug activity and resistance. PD-L1 expression on tumors is currently a biomarker candidate, but reliable detection and quantification methodologies have proven challenging to standardize. Recently, a soluble PD-L1 (sPD-L1) fragment was identified that can derive from cell-bound PD-L1. Retrospective clinical examinations of sPD-L1 levels in cancer patients suggest a potential use as a surrogate for disease progression and response to treatment; but few preclinical studies have been performed to test this predictive value. We undertook experiments to evaluate plasma sPD-L1 in mouse tumor models during localized primary tumor growth (after orthotopic cell implantation) and spontaneous metastatic disease progression (after surgical removal of the primary). Mouse syngeneic and human xenograft implantation models included breast, kidney, colon, and melanoma cell systems. Our results show that circulating plasma sPD-L1 can correlate with primary and metastatic progression in a stage and model specific manner. Next, we evaluated sPD-L1 following treatment with neutralizing antibodies to PD-1 and PD-L1 in tumor-free mice and found significant dose-dependent sPD-L1 increases, suggesting systemic changes may have utility as a measurement of target saturation and dosing independent of tumor growth. Finally, with current approvals of PD-1 inhibitors in renal cell carcinoma (RCC) patients previously treated with antiangiogenic agents that block vascular endothelial growth factor (VEGF), we evaluated plasma in mouse models of sunitinib resistance - a VEGF receptor tyrosine kinase inhibitor (RTKI). Our results demonstrate that VEGF pathway resistance yields changes in sPD-L1 and may be useful in predicting response to PD-1 pathway inhibition in the refractory setting. Together, these investigations suggest that circulating sPD-L1 changes during disease progression (both local and disseminated) may serve as a potential predictive biomarker for immune-checkpoint and antiangiogenic therapy. Citation Format: Michalis Mastri, Amanda Tracz, Yuhao Shi, Georg Bjarnason, Tran Nguyen, Brian Rini, John M.L. Ebos. Soluble PD-L1 as a surrogate biomarker of metastatic progression and resistance to antiangiogenic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5599. doi:10.1158/1538-7445.AM2017-5599
Controlling for continuous variables is not futile: What we can learn about number representation despite imperfect control
Authors: Kristy vanMarle
Journal: Behavioral and Brain Sciences (2017)

Abstract Leibovich et al. argue that because it is impossible to isolate numerosity in a stimulus set, attempts to show that number is processed independently of continuous magnitudes are necessarily in vain. I propose that through clever design and manipulation of confounding variables, we can gain deep insight into number representation and its relationship to the representation of other magnitudes.
Abstract 2302: Differences in risk factor-colorectal adenoma associations according to non-steroidal anti-inflammatory drug use
Authors: Sobia Mujtaba, Roberd M. Bostick
Journal: Cancer Research (2017)

Abstract Multiple observational studies and large, randomized controlled trials indicate that non-steroidal anti-inflammatory drugs (NSAIDs) strongly reduce risk for colorectal neoplasms. The strengths of these findings suggest that NSAIDs may so mask various risk factor-colorectal neoplasm associations, that they may be undetectable among NSAID users. Temporal changes and between-population differences in regular NSAID use prevalence may account for some of the inconsistencies in reported findings for risk factor-colorectal neoplasm associations. We investigated whether associations of known colorectal cancer risk factors with colorectal adenoma differed by non-aspirin NSAID use using pooled data from 3 colonoscopy-based case-control studies of incident, sporadic colorectal adenoma conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002. Participants (n=789 cases, 2,035 polyp-free controls) provided risk factor data prior to colonoscopy. The multivariable-adjusted odds ratios (OR) (95% confidence intervals [CI]) for those in the highest relative to the lowest quartiles of exposure, by regular non-aspirin NSAID non-use/use, respectively, were 1.57 (CI 0.96, 2.55) vs. 1.22 (CI 0.40, 3.70) for total fat, 1.37 (CI 0.86, 2.18) vs. 0.78 (CI 0.26, 2.35) for saturated fat, 0.92 (CI 0.67, 1.26) vs. 1.31 (CI 0.62, 2.76) for total calcium, 0.88 (CI 0.64, 1.22) vs. 1.38 (CI 0.65, 2.93) for total fruits and vegetables, 1.05 (CI 0.73, 1.50) vs. 0.73 (CI 0.33, 1.62) for red and processed meats, and 0.84 (CI 0.65, 1.10) vs. 0.97 (CI 0.54,1.75) for physical activity. For current smokers relative to never smokers, the ORs (CIs) among regular non-NSAID users/non-users were 2.88 (CI 2.20, 3.77) vs. 1.64 (CI 0.85, 3.17), respectively, and for those who were obese relative to those who were normal weight, they were 1.65 (CI 1.27, 2.16) vs. 1.20 (CI 0.70, 2.04). The associations of age, height, and intakes of alcohol, dietary fiber, and total folate with adenoma did not substantially differ according to NSAID use. These findings suggest that regular non-aspirin NSAID use may mask, beyond simple confounding, associations of various risk factors with colorectal adenoma, suggesting that differential proportions of regular NSAID users between study populations may explain some inconsistencies in reported risk factor-colorectal neoplasm associations, and support routinely assessing such associations stratified by regular non-aspirin NSAID use. Citation Format: Sobia Mujtaba, Roberd M. Bostick. Differences in risk factor-colorectal adenoma associations according to non-steroidal anti-inflammatory drug use [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2302. doi:10.1158/1538-7445.AM2017-2302
Diffusion of abiraterone use in prostate cancer patients.
Authors: Emerson A. Lim, Xiaobo Zhong, Jason Dennis Wright, Alfred I. Neugut, Antonio Tito Fojo, Jim C. Hu, Joseph M. Unger, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2016)

e18062 Background: Oral anti-cancer therapies are one of the fastest growing categories of prescription medications but diffusion of their use has not been well studied. In 2011 the Food and Drug Administration approved abiraterone acetate (AA), an oral CYP17 androgen synthesis inhibitor, to treat metastatic castrate resistant prostate cancer (mCRPC) after progression on docetaxel (D). In 2012 it was approved for mCRPC patients (pts) without the receipt of prior D. We evaluated the patterns of use of AA over time. Methods: We identified pts with prostate cancer (ICD-9 185) in the Truven Health Analytics MarketScan Dataset from 2009 to 2013. We assessed the cumulative incidence of first AA claim by age, comorbidity status, region, and health insurance type. To model the diffusion of AA over time and to evaluate the influence of social dynamics on its diffusion, we used the classic mixed influence deterministic diffusion model. This model includes constants k1 and k2 that describe influences external and internal to the social system, respectively. The ratio of k2 to k1 describes the extent to which a social process influences diffusion. Patterns of AA use were evaluated in relation to landmark events. To study factors influencing use of AA without prior D, we performed a logistic regression analysis. Results: We identified 388,701 pts with prostate cancer, 3239 (0.83%) of whom received AA. Patients with a comorbidity score ≥ 1 vs. 0 (p < 0.0001) and age ≥ 65 vs. < 65 (p < 0.0001) had higher cumulative incidence rates of AA use. AA was given without prior D in 50% of pts before the FDA approval for this setting. The main predictor of AA use without prior D was later date of use (2013 vs. 2011; OR 5.57 95%CI 4.51-6.87). Patients aged < 65 vs. ≥ 65 (OR 0.63 95%CI 0.53-0.75), and pts with copayments > $40 vs $0-10 (OR 0.79 95%CI 0.65-0.96) were less likely to receive AA without prior D. Social dynamics were a significant influence in AA diffusion with the ratio k2/k1 = 9 (p = 0.02). Conclusions: We found that diffusion of AA use occurred more quickly in older pts and pts with increased comorbidities. Off-label use of AA prior to D occurred in 50% of pts before FDA approval for this setting. Additional studies evaluating patterns of use of oral anti-cancer therapies are needed to ensure optimal use of these drugs.
Abstract 1306: Two distinct regulatory mechanisms underlie estrogen receptor negative breast cancer susceptibility at the 2p23.2 locus
Authors: Carly M. Harro, Gustavo Mendoza-Fandino, Nicholas T. Woods, Xueli Li, Fergus J. Couch, Alvaro N. Monteiro
Journal: Cancer Research (2017)

Abstract Genome Wide Association Studies (GWAS) are designed to identify single nucleotide polymorphisms (SNPs) mapping to genomic regions associated with a particular trait or disease. Currently, 19 genomic loci associated with risk for estrogen receptor negative breast cancer have been identified. However, for most of these loci the mechanisms driving susceptibility have remained elusive. The 2p23.2 locus, defined by SNP rs67073037 (p = 4.76 x 10-9), contains 79 SNPs exhibiting genome-wide significant associations as well as four candidate genes: SPDYA, TRMT61B, WDR43, and FAM179A. Post-GWAS functional analysis revealed two candidate causal regulatory elements: an enhancer-like element defined by SNP rs44017214 located in the first intron of the WDR43 gene; and a segment in the 3’-UTR region of WDR43 defined by SNPs rs11680458 and rs11331880 which are predicted to have allele specific binding of non-coding microRNAs miR-548 and miR-376, respectively. We validated allele specific transcription factor binding to rs44017214 using competitive binding of USF1/USF2 to the risk allele in both MCF10A and CAL51 cell lines in Electrophoretic Mobility Shift Assays (EMSA). Additionally, rs44017214 was removed using CRISPR-cas9, and expression of neighboring genes was evaluated by qRT-PCR. No change in expression was found for any gene in a 2 Mb region surrounding the SNP, with the exception of PLB1. This suggests that the enhancer element in the intron of WDR43 has PLB1 as its target. To assess the miRNA binding site impact on WDR43 expression the pMIR-REPORT Luciferase allele-specific vector was co-transfected with miR-141/200, miR548, or miR-376 in MCF10A cells. The rs1131880 allele C in the WDR43 3’-UTR lead to the suppression of luciferase expression by miR-376 compared to the G allele. This study reveals two independent regulatory mechanisms within the 2p23.2 locus; (i) modulation of enhancer activity by allele specific binding of transcription factors USF1/USF2 to rs4401714, and (ii) decreasing the expression of WDR43 through the formation of a miR-376 binding site at the 3’-UTR of the WDR43 gene. Elucidating the functional significance of these common variants in the novel susceptibility loci 2p23.2 furthers our knowledge of the etiology of estrogen receptor negative breast cancer. Citation Format: Carly M. Harro, Gustavo Mendoza-Fandino, Nicholas T. Woods, Xueli Li, Fergus J. Couch, Alvaro N. Monteiro. Two distinct regulatory mechanisms underlie estrogen receptor negative breast cancer susceptibility at the 2p23.2 locus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1306. doi:10.1158/1538-7445.AM2017-1306