tbuckley/cabot-search huggingface dataset:
Using the research on intergroup conflict in nonhuman animals to help inform patterns of human intergroup conflict
Authors: Amanda R. Ridley, Melanie O. Mirville
Journal: Behavioral and Brain Sciences (2019)

There is a large body of research on conflict in nonhuman animal groups that measures the costs and benefits of intergroup conflict, and we suggest that much of this evidence is missing from De Dreu and Gross's interesting article. It is a shame this work has been missed, because it provides evidence for interesting ideas put forward in the article.
The Chromosome 21 Kinase DYRK1A and Its Substrate FOXO1 Constitute a Novel Therapeutic Pathway in B-ALL
Authors: Rahul S. Bhansali, Malini Rammohan, Ji Heon Paul Lee, Sebastien Malinge, Yi-Chien Tsai, Nobuko Hijiya, Beat Bornhauser, Jean-Pierre Bourquin, Corinne Fruit, Thierry Besson, John D. Crispino
Journal: Blood (2018)
Gut-derived GIP activates central Rap1 to impair neural leptin sensitivity during overnutrition
Authors: Kentaro Kaneko, Yukiko Fu, Hsiao-Yun Lin, Elizabeth L. Cordonier, Qianxing Mo, Yong Gao, Ting Yao, Jacqueline Naylor, Victor Howard, Kenji Saito, Pingwen Xu, Siyu S. Chen, Miao-Hsueh Chen, Yong Xu, Kevin W. Williams, Peter Ravn, Makoto Fukuda
Journal: Journal of Clinical Investigation (2019)

Nutrient excess, a major driver of obesity, diminishes hypothalamic responses to exogenously administered leptin, a critical hormone of energy balance. Here, we aimed to identify a physiological signal that arises from excess caloric intake and negatively controls hypothalamic leptin action. We found that deficiency of the gastric inhibitory polypeptide receptor (Gipr) for the gut-derived incretin hormone GIP protected against diet-induced neural leptin resistance. Furthermore, a centrally administered antibody that neutralizes GIPR had remarkable antiobesity effects in diet-induced obese mice, including reduced body weight and adiposity, and a decreased hypothalamic level of SOCS3, an inhibitor of leptin actions. In contrast, centrally administered GIP diminished hypothalamic sensitivity to leptin and increased hypothalamic levels of Socs3. Finally, we show that GIP increased the active form of the small GTPase Rap1 in the brain and that its activation was required for the central actions of GIP. Altogether, our results identify GIPR/Rap1 signaling in the brain as a molecular pathway linking overnutrition to the control of neural leptin actions.
Allelic loss during progression of follicular lymphoma
Authors: Masahide Matsushita, Seisho Takeuchi, Sven De Vos, Thomas M. Grogan, Hiromi Seo, Jonathan W. Said, H. P. Koeffler
Journal: Cancer Research (2004)

1704  Follicular lymphoma (FL) is characterized by a continuous rate of transformation to a high grade lymphoma, usually diffuse large B-cell lymphoma (DLBCL), which results in a dismal prognosis and a poor response to chemotherapy. To expand the understanding of genetic changes in the progression of FL, we performed loss of heterozygosity (LOH) analyses using 36 microsatellite markers on matched lymph nodes before and after progression. Seven cases progressed from FL to DLBCL, and 3 FL cases which remained FL at relapse, were biopsied both at diagnosis and at either recurrence or relapse. LOH was observed in four of the 10 cases (40 %) as the disease progressed (3 of 7 cases of transformed FL and 1 of 3 cases of relapse FL). Frequent allelic loss in > 20 % of the informative cases occurred on chromosome arms 6q (20 %), 9p (25 %), and 12p (22 %). Microsatellite instability was found in one of 7 (14 %) transformed lymphomas. These data suggest that altered tumor suppressor genes exist on 6q, 9p, and 12p that have an important role in the progression of FL. Also, genetic changes accumulated in relapsed FL in the absence of histological changes compared to initial diagnosis.
Sex Differences in Grant Funding
Authors: Reshma Jagsi, Kanakadurga Singer, Eve Kerr
Journal: JAMA (2019)

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Combination of cel ecoxib derivative OSU03012 and EGFR inhibitors enhances cell death in gefitinib/erlotinib-resistant lung cancer cells through induction of ER stress-related apoptosis and suppression of Akt signaling
Authors: Yu-Chieh Wang, Samuel Kulp, Chih-Cheng Yang, Aaron Sargeant, Ya-Ting Yang, Mamoru Yamaguchi, Yoko Kashida, Geen-Dong Chang, Ching-Shih Chen
Journal: Cancer Research (2007)

5419  Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death among men and women in the US. Although recent advances in the treatment of NSCLC have been realized through the development of epidermal growth factor receptor tyrosine kinase (EGFR-TK)-targeted agents, namely gefitinib and erlotinib, resistance to these drugs is common and precludes a substantial anticancer effect. In light of the need to understand and overcome this resistance to EGFR inhibitors, we evaluated the sensitizing activity of OSU03012, a celecoxib derivative developed in our laboratory, in combination with gefitinib or erlotinib in NSCLC cells. As determined by annexin V/PI counterstaining with flow cytometric analysis, 24-h co-treatment of OSU03012 with gefitinib or erlotinib significantly enhances apoptosis in H1155 and H23, but not A549 cells. Immunoblotting shows that the basal level of phospho-Akt is relatively higher in H1155 and H23 cells, and is dose-dependently suppressed by OSU03012 in combination with gefitinib or erlotinib. Transfection of constitutively active Akt partially rescues H1155 cells exposed to the combination treatments. The combination treatment also induces upregulation of GADD153, an ER stress-associated transcriptional factor, accompanied by elevated expression of DR5 gene and activation of extrinsic signaling of apoptosis in H1155 cells. Moreover, RNAi-suppression of GADD153 diminishes the apoptosis elicited by the combination of OSU03012 and gefitinib. The in vivo efficacy of this combination strategy is evidenced by a significant delay of tumor progression in xenograft-bearing mice treated orally with OSU03012 and erlotinib. Upregulation of GADD153 and suppression of phospho-Akt are also detected in the tumors resected from the mice, which correlates well with the in vitro data. Our data suggest that OSU03012 combined with the EGFR inhibitors is a promising approach to clinically treat resistant NSCLC through suppression of Akt signaling and induction of ER stress-associated apoptosis.
RNA sequencing for research and diagnostics in clinical oncology
Authors: Anton Buzdin, Maxim Sorokin, Andrew Garazha, Alexander Glusker, Alex Aleshin, Elena Poddubskaya, Marina Sekacheva, Ella Kim, Nurshat Gaifullin, Alf Giese, Alexander Seryakov, Pavel Rumiantsev, Sergey Moshkovskii, Alexey Moiseev
Journal: Seminars in Cancer Biology (2019)
Hypertension is a modifiable risk factor for osteonecrosis in acute lymphoblastic leukemia
Authors: Laura J. Janke, Sara L. Van Driest, Mary V. Portera, Ravi V. Atreya, Joshua C. Denny, Deqing Pei, Cheng Cheng, Sue C. Kaste, Hiroto Inaba, Sima Jeha, Ching-Hon Pui, Mary V. Relling, Seth E. Karol
Journal: Blood (2019)
Phase I trial of PTK787/ZK222584 (PTK/ZK) in combination with carboplatin (C) and paclitaxel (T) in platinum-sensitive recurrent epithelial ovarian (EOC), fallopian tube (FT), or primary peritoneal (PPC) cancers
Authors: M. M. Juretzka, C. Aghajanian, M. L. Hensley, W. P. Tew, D. Spriggs, J. Konner, A. C. Chiang, S. Pezzulli, M. Kim, P. Sabbatini
Journal: Journal of Clinical Oncology (2007)

5564 Background: Targeting vascular endothelial growth factor (VEGF) in patients (pts) with ovarian cancer achieves objective responses. PTK/ZK is an orally active angiogenesis inhibitor which blocks all known VEGF receptor and platelet-derived growth factor receptor tyrosine kinases. A previous study administered PTK/ZK only on days 3–21 of C and T cycle based on pre-clinical data suggesting PTK/ZK increases T levels (PROC ASCO # 5042, 2005), and recent data supports bid dosing (JCO 18:1–10, 2005). Methods: In this open label, single institution phase I study, pts with platinum sensitive recurrent EOC, FT, or PPC were treated with C and T every 21 days with increasing continuous daily doses of PTK/ZK (250 mg to 1,250mg with bid dosing). Primary endpoints were safety and maximum tolerated dose (MTD). Pharmacokinetic (PK) analysis is planned to describe C and T pharmacokinetics when combined with PTK/ZK. Results: To date, 14 pts with median age 61 (range 45–73) have been enrolled on the first 3 dose levels, including 13 EOC and 1 PPC. All patients were evaluable for toxicity and 8 were evaluable for investigator assessed response. MTD has not been reached. Febrile neutropenia was dose limiting toxicity requiring expansion at levels II and III. PK analysis is ongoing. To date, best responses are: 4 (PR), 3 (SD) and 1 (POD). Other G III toxicity included: C hypersensitivity reaction (1, gr 3), hyperglycemia (4, gr 3), hypertension (1, gr 3), diarrhea (1, gr 3), and elevated liver function tests (1, gr 3). Conclusion: PTK/ZK can be administered continuously in combination with standard doses of C and T using bid dosing. MTD is not yet reached and accrual is ongoing. PK data and MTD will be presented. Supported by Novartis and Bayer Schering Pharma. [Table: see text] No significant financial relationships to disclose.
Targeting HSP90 in pediatric malignancies by the European Consortium "Innovative Therapies for Children with Cancer"
Authors: Arnauld Verschuur, Claudia Lanvers, Monique den Boer, Andre van Kuilenburg, Massimo Serra, Kathy Pritchard-Jones, Jane Renshaw, Torsten Pietsch, Wolfgang Hartmann, Joachim Boos, Paul Workman, Gilles Vassal, Huib Caron
Journal: Cancer Research (2007)

526  On behalf of ITCC Biology and Preclinical Evaluation Committee  Innovative Therapies for Children with Cancer (ITCC) is a European consortium of ± 30 pediatric oncology clinical centres in five European countries for early clinical trials, and a consortium of 9 laboratories for the preclinical evaluation of targeted anti-cancer compounds in childhood cancer models (ITCC Biology).  This ITCC Biology Consortium evaluates novel targeted anti-cancer compounds. Six high risk childhood cancers have been selected representing over 50% of therapy failures in children: neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, acute lymphoblastic leukemia (ALL), medulloblastoma, osteosarcoma. The preclinical evaluation strategy consists of:  1.  Target presence screening (mRNA profiles of ± 100 tumor samples per tumor type and of 95 cell lines (CL) representing the 6 tumor types)  2.  In vitro drug efficacy screening on cell lines  3.  In vivo drug efficacy screening using mouse xenografts  4.  Target validation by siRNA  HSP90 is a chaperone protein and active in the homeostasis of many client proteins: EGFR, ErbB2, BCR/ABL, Flt3, c-Kit and others. 17-AAG is an inhibitor of HSP90 and is currently in early clinical (combination) trials. Recently we performed in vitro incubations with 17-AAG. The 72hrs anti-proliferative effect of 17-AAG (GI50 and LC50) was measured by MTT -assay. A GI50 or IC50 > 1000 nM was considered as resistant to 17-AAG, 200-1000 nM as moderate sensitivity.  >Results:  >45 ceIl lines representing 6 pediatric tumor types were studied. The in vitro drug effects to 17-AAG proved to be predominantly anti-proliferative since the majority of LC50 values for all tumor types exceeded 1000 nM. A high to moderate in vitro growth inhibitory effect to 17-AAG was observed in 11 out of 12 CL in neuroblastoma (GI50 41-851 nM), in 7 out of 8 osteosarcoma CL (GI50 100-505 nM) and 2 out of 5 rhabdomyosarcoma CL (11-31nM). Four out of 8 Ewing sarcoma CL (GI50 29-371 nM) and 5 out of 8 medulloblastoma CL (78-852 nM) were intermediate sensitive. One out of 5 CL of ALL (237 nM) was moderately sensitive.  >Conclusion:  >HSP90 inhibition may be an attractive target in solid pediatric malignancies, although the concentration of 17-AAG required for in vitro growth inhibition is variable. 17-AAG seems not efficacious in ALL. The ITCC-consortium is extending the in vitro testing of 17-AAG into combination studies with conventional cytotoxics and targeted compounds.
Earlier ingestion of peanut after changes to infant feeding guidelines: The EarlyNuts study
Authors: Victoria X. Soriano, Rachel L. Peters, Anne-Louise Ponsonby, Shyamali C. Dharmage, Kirsten P. Perrett, Michael J. Field, Andrew Knox, Dean Tey, Sasha Odoi, Grace Gell, Beatriz Camesella Perez, Katrina J. Allen, Lyle C. Gurrin, Jennifer J. Koplin
Journal: Journal of Allergy and Clinical Immunology (2019)
Covered self-expandable metal stent placement for post-endoscopic sphincterotomy bleeding in a patient with surgically altered anatomy
Authors: Tadahisa Inoue, Mayu Ibusuki, Rena Kitano, Yuji Kobayashi, Kiyoaki Ito, Masashi Yoneda
Journal: Endoscopy (2019)

Although balloon enteroscopy-assisted endoscopic retrograde cholangiography (ERC) is a useful procedure for biliary intervention in patients with surgically altered anatomy, advanced skills are required. Therefore, if post-endoscopic sphincterotomy bleeding occurs during the procedure, endoscopic hemostasis is challenging. Placement of a covered self-expandable metal stent (CSEMS), which has been reported as a useful hemostasis treatment for refractory bleeding after endoscopic sphincterotomy on conventional ERC [1] [2] [3] [4], may be effective even in such a difficult situation. However, to our knowledge, CSEMS placement for such bleeding events has not been reported under balloon enteroscopy-assisted ERC. Here, we report a successful case of hemostasis for post-endoscopic sphincterotomy bleeding by CSEMS placement using balloon enteroscopy in a patient with surgically altered anatomy.
Abstract 9471: Temporal Relationship and Predictive Value of Urinary Acute Kidney Injury Biomarkers After Pediatric Cardiopulmonary Bypass
Authors: Catherine D Krawczeski, Stuart L Goldstein, Jessica G Woo, Yu Wang, Nuntawan Piyaphanee, Qing Ma, Michael R Bennett, Prasad Devarajan
Journal: Circulation (2011)

Introduction Acute kidney injury (AKI) occurs commonly after cardiopulmonary bypass (CPB). Serum creatinine (S Cr ) is an inadequate marker for AKI. Rapidly detectable AKI biomarkers could allow early intervention and improve outcome. We evaluated the temporal pattern and predictive value (alone and in combination) of 4 urinary AKI biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver fatty-acid binding protein (L-FABP) and kidney injury molecule-1 (KIM-1) for CPB associated AKI. Methods Urine samples were obtained prospectively before and at intervals after CPB in 220 patients. AKI was defined as a ≥50% S Cr rise within 48h of CPB. The temporal pattern of biomarker elevation was established and biomarker elevations were correlated with AKI severity and clinical outcomes. Logistic regression was used to assess AKI predictors. Biomarker predictive abilities were evaluated by AUC, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results AKI occurred in 27% of patients. NGAL increased in AKI patients at 2h after CPB and remained elevated at all timepoints (Figure). IL-18 and L-FABP increased at 6h and KIM-1 increased at 12h. Biomarker elevations correlated with disease severity and clinical outcomes, and improved AKI prediction above a clinical model. At 2h addition of NGAL increased the AUC from 0.74 to 0.85 ( p &lt;0.0001). At 6h NGAL, IL-18 and L-FABP each improved the AUC from 0.72 to 0.91, 0.84 and 0.77, respectively (all p &lt;0.05). At 12h, all biomarkers improved the AUC. The added predictive ability of the biomarkers was supported by NRI and IDI. Biomarker combinations further improved AKI prediction. Conclusion Urine NGAL, IL-18, L-FABP and KIM-1 are sequential predictive AKI biomarkers and correlate with clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may be useful in establishing AKI timing and application of appropriately timed therapy.
The effect of gaps in chemotherapy in patients with stage IV colorectal cancer.
Authors: Yvonne Sada, Jessica Davila, Hashem El-Serag, Zhigang Duan
Journal: Journal of Clinical Oncology (2013)

e17501 Background: Chemotherapy (CT) utilization in patients with stage IV colorectal cancer (CRC) has not been well documented in community practice settings. Further, clinical trial data indicate that time gaps during CT for stage IV CRC patients are associated with worse survival. However, the prevalence of CT gaps and their effect on survival in the general population is unclear. Methods: Using national Surveillance, Epidemiology, and End Results-Medicare linked data, stage IV CRC patients diagnosed during 2000-07 were identified. Those who received CT (based on ICD-9 codes) within 3 months after CRC diagnosis were identified. CT duration during the 2 years following CRC diagnosis and frequency of gaps were calculated. A CT gap was defined as &gt;30 days between 2 CT claims. Data on demographics and clinical factors were collected. Multivariable regression was used to identify determinants of CT gaps. Cox proportional hazard models were used to examine the effect of gaps on mortality. Results: 4015 patients with stage IV CRC were identified. Median age was 74 (IQR: 70-79); 51% were male. A CT gap occurred in 2123 patients (53%). Most patients received &lt;3 months of CT (37%), followed by 7-12 months (26%), 3-6 months (21%), &gt;12 months (16%). Nearly 70% of patients who had &gt;3 months of CT had a gap. Among these patients, 41% had 1 gap, 27% had 2 gaps, and 32% had ≥3 gaps. Median number of days per gap was 42 (IQR: 35-75). Multivariate analysis showed that patients who were Asian (OR 1.8, 95% CI: 1.2-2.70), had &gt;12 months CT (5.1, 4.0-6.5), hospitalized during CT (3.9, 3.3-4.6), or had toxicity (1.5, 1.3-1.8) were more likely to have a gap, while patients with comorbidity index ≥2 (0.7, 0.6-0.9) were less likely to have a gap. 1-yr survival was higher in patients with gaps compared to no gaps (89% vs. 60%) after excluding patients who had &lt;3 months of CT. Cox proportional hazard models showed that patients with gaps had a lower risk of mortality (HR 0.58, 0.52-0.64), adjusting for patient and clinical factors. Conclusions: Over half of patients with stage IV CRC had a gap during CT. Contrary to clinical trial data, CT gaps were associated with a survival benefit. Further studies are needed to confirm these findings and to explore patient and provider reasons for stopping CT.
Epidermal mammalian target of rapamycin complex 2 controls lipid synthesis and filaggrin processing in epidermal barrier formation
Authors: Xiaolei Ding, Sebastian Willenborg, Wilhelm Bloch, Sara A. Wickström, Prerana Wagle, Susanne Brodesser, Axel Roers, Alexander Jais, Jens C. Brüning, Michael N. Hall, Markus A. Rüegg, Sabine A. Eming
Journal: Journal of Allergy and Clinical Immunology (2019)
Eligibility of patients with hepatocellular carcinoma for systemic treatment with sorafenib
Authors: L. C. Zimmermann, K. Schuette, J. Borschein, A. Csepregi, P. Malfertheiner
Journal: Journal of Clinical Oncology (2009)

e15673 Background: Sorafenib is the first systemic drug that effects prolonged overall survival in patients with advanced hepatocellular carcinoma (HCC) by almost three months with moderate toxicity. This study aims to evaluate how many patients diagnosed with HCC are candidates for systemic treatment and possibly benefit from it. Methods: All patients diagnosed with HCC in our hospital in between January 2006 and June 2008 were analysed regarding the presence and stage of liver cirrhosis, tumor stage and the treatment applied. Results: In a period of 30 months 182 patients were diagnosed with HCC (female n = 42, male n = 140, median age 66 (16–84)). 169 suffered from liver cirrhosis, 96 in Child A, 46 in Child B and 27 in Child C stage. 36 patients (19.8 %) were diagnosed with uninodular disease, in 17 patients (9.3%) 2 or 3 nodules were detected and 129 (70.9%) patients suffered from multinodular HCC. 79 patients received local ablative therapy or transarterial chemoembolisation, 15 underwent surgical resection, 29 patients were treated with best supportive care and 59 patients were candidates for systemic treatment. Out of these 25 either had no liver cirrhosis or were in stage Child A and 17 were in Child B stage and would therefore fit for therapy with sorafenib (23.1%). 17 pts with advanced disease and Child C cirrhosis did not fit for this treatment. Conclusions: Assuming that patients with advanced HCC and good or moderate liver function are candidates for systemic treatment with sorafenib every fifth patient is likely to benefit from the introduction of this treatment option. [Table: see text]
Behavioural inhibition and valuation of gain/loss are neurally distinct from approach/withdrawal
Authors: Neil McNaughton, Philip J. Corr
Journal: Behavioral and Brain Sciences (2019)

Abstract Gain or omission/termination of loss produces approach; while loss or omission/termination of gain produces withdrawal. Control of approach/withdrawal motivation is distinct from valuation of gain/loss and does not entail learning – making “reward” and “punishment” ambiguous. Approach-withdrawal goal conflict engages a neurally distinct Behavioural Inhibition System, which controls “anxiety” (conflict/passive avoidance) but not “fear” (withdrawal/active avoidance).
Individualised axitinib regimen for patients with metastatic renal cell carcinoma after treatment with checkpoint inhibitors: a multicentre, single-arm, phase 2 study
Authors: Moshe C Ornstein, Sumanta K Pal, Laura S Wood, Jackie M Tomer, Brian P Hobbs, Xuefei S Jia, Kimberly D Allman, Allison Martin, Thomas Olencki, Nancy B Davis, Timothy D Gilligan, Amir Mortazavi, W Kimryn Rathmell, Jorge A Garcia, Brian I Rini
Journal: The Lancet Oncology (2019)