tbuckley/cabot-search huggingface dataset:
Abstract P2-05-37: In-situ hybridization of microRNA and support vector machines–based prognostic classifiers for breast cancer
Authors: Z Cao, L Yao, X Hu, Z Zhang, Z Shao
Journal: Cancer Research (2017)

Abstract Purpose: We plan to use a tissue microarray-based microRNA(miRNA) detection by in situ hybridization with LNA probe and support vector machine on base of data mining to construct the Prognostic model for breast cancer and triple negative breast cancer (TNBC). Methods: Combining the BreastMark miRNA database and papers published, we chose candidate miRNAs. Then a tissue microarray-based miRNA detection in situ hybridization with LNA probe was used to detect miRNA expression in 445 breast cancer tissue. Univariate analysis with Kaplan-Meier identified independent prognostic factors, 445 patients was divided into the training set and validation set (70% VS 30%) by software R(version 3.2.3), then support vector machine on base of data mining was used to construct the Prognostic model for breast cancer and triple negative breast cancer via software R and predict.svm(e1071). Results: 15 miRNAs were detected from 445 breast cancer tissue and univariate analysis with Kaplan-Meier identified significant prognostic miRNAs: miR-361-5p, miR-301a, miR-223, miR-421, miR-454, miR-493 were the independent prognostic factors for DFS. By using data mining technique, we combined clinical factors(stage, tumor size, lymphnode status, molecular subtype) and miRNAs mentioned above to establish the personalized predictive mathematical models SVM-BC and SVM-TNBC. In the training set and validation set of SVM-BC model, the AUC value of ROC curve for DFS were 0.86,0.83. The total accuracy,sensitivity,specificity of SVM-BC model for DFS were 94%,73%,99% and 84%,57%,92% in the training set and validation set. The SVM-BC model can divide breast cancer patients into high-risk and low-risk groups, and 5-year survival rates for low-risk patients were higher than that for high-risk patients(96.8% VS 39.3%, p&amp;lt;0.001). In the training set and validation set of SVM-TNBC model, the AUC value of ROC curve for DFS were 0.84,0.86. The total accuracy,sensitivity,specificity of SVM-TNBC model for DFS were 90%,71%,97% and 84%,55%,94% in the training set and validation set. The SVM-TNBC model can divide breast cancer patients into high-risk and low-risk groups, and 5-year survival rates for low-risk patients were higher than that for high-risk patients(93.9 % VS 23.5%, p &amp;lt;0.001). Conclusion: The Prognostic model basing of tissue microarray-based miRNA detection in situ hybridization with LNA probe and support vector machine for prognosis can effectively predict the prognosis of breast cancer and TNBC. Citation Format: Cao Z, Yao L, Hu X, Zhang Z, Shao Z. In-situ hybridization of microRNA and support vector machines–based prognostic classifiers for breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-37.
Hsp90 inhibition destabilizes Ezh2 protein in alloreactive T cells and reduces graft-versus-host disease in mice
Authors: Qingrong Huang, Shan He, Yuanyuan Tian, Yuting Gu, Pan Chen, Changhong Li, Jiefang Huang, Yongnian Liu, Hongshuang Yu, Min Jin, Shaoyan Hu, Qing Tong, Anqi Ma, Jian Jin, Elizabeth Hexner, Henry Fung, Ran Reshef, Yi Zhang, Yanyun Zhang
Journal: Blood (2017)
Abstract P6-16-07: Analysing the factors affecting survival of breast cancer patients with leptomeningeal metastasis
Authors: A Niwinska, H Rudnicka, M Kunkiel, A Jagiello-Gruszfeld, Z Nowecki
Journal: Cancer Research (2017)

Abstract AIM: To assess those factors which affect survival in three groups of breast cancer patients with leptomieningeal metastasis (LM) treated at the Warsaw Cancer Center in Poland. Subject groups were: 187 patients consecutively referred during 2003-2015 (group A), 69 patients with LM as the first/only site of dissemination of the disease (group B) and 27 patients who survived for more than 1 year (group C). Methods: Univariate and Cox multivariate analysis were performed using the following variables: age, Karnofsky Performance Status (KPS), biological subtype of breast cancer (ER/PR+HER2- vs. HER2+ vs. ER-PR-HER2-), systemic intravenous/oral treatment, intrathecal treatment, radiation therapy and the number of treatment methods. Results. Median survival of patients in group A was 17 weeks, in group B 18 weeks (p=0.72) and in group C 19.2 months. In group A, factors positively affecting survival were: KPS =&amp;gt; (p=0.01), older age (p=0.003), biological subtype ER/PR+HER2- (p=0.003), systemic intravenous/oral treatment (p=0.0001), intrathecal treatment (p=0.001) and radiation therapy (p=0.001). In the group B, the most important factors affecting survival were a KPS=&amp;gt; 70 (p=0.001), biological subtype ER/PR+HER2- (p=0.04), systemic therapy (p=0.001) and intrathecal therapy (p=0.001). For group C, older patients (p=0.01) with ER/PR+HER2- breast cancer (p=0.05, HR 0.18) and after systemic intravenous/oral treatment (p=0.02) had higher a probability of survival after 1 year. Conclusions: Those breast cancer LM patients who were older, having high KPS, with luminal breast cancer and treated with systemic inravenous/oral therapy had a higher probability of survival than the rest of the group. Based on the presented data, the role of intrathecal therapy could not be exactly defined. Citation Format: Niwinska A, Rudnicka H, Kunkiel M, Jagiello-Gruszfeld A, Nowecki Z. Analysing the factors affecting survival of breast cancer patients with leptomeningeal metastasis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-07.
Abstract P113: Protein Tyrosine Phosphatase-Like A Is a Unique Regulator for Myogenesis
Authors: Xi Lin, Xiangsheng Yang, Qi Li, Yanlin Ma, Xia Lin, Jiang Chang
Journal: Circulation Research (2011)

Background: Protein tyrosine phosphatase-like A (PTPLa) is highly expressed in skeletal and cardiac muscle. Therefore, it has been implicated to play a role in skeletal myogenesis and cardiogenesis. Mutations in PTPLa correlated with arrhythmogenic right ventricular dysplasia in humans and congenital centronuclear myopathy with severe hypotonia in dogs. However, the molecular mechanisms of PTPLa in myogenesis are unknown. Method and results: Mouse myoblast C2C12 cells were used to generate PTPLa deficient and PTPLa overexpression cell lines and the cells were cultured in proliferating and differentiating media, respectively, to study regulatory role of PTPLa in cell proliferation and differentiation. We demonstrated that PTPLa was required for myoblast growth and differentiation. The cells lacking PTPLa remained immature and failed to differentiate into mature myotubes along with repressed MyoG expression. To define the role of MyoG in PTPLa-mediated myoblast differentiation, myoblast cell line lacking MyoG expression was generated. Two cell lines, the PTPLa-deficient and MyoG-deficient myoblasts were used to demonstrate that PTPLa-mediated myoblast differentiation was through MyoG regulation. Meanwhile, the impeded cell growth with an obvious S-phase arrest was observed in PTPLa-deficient myoblasts. Further study demonstrated that the upregulation of cyclin D1 and cyclin E2 complexes along with a compromised Cdk1 activity contributed to the mutant cell S-phase arrest and eventually led to the retarded cell growth. Finally, the transcriptional regulation of PTPLa gene was explored. We identified that PTPLa was a new target gene of serum response factor (SRF). Skeletal- and cardiac-specific SRF knockouts resulted in significant decreases in PTPLa expression, suggesting a conserved transcriptional regulation of PTPLa gene in mice. Conclusion: PTPLa is a unique pro-myogenic factor regulated by SRF. It regulates myoblast proliferation and differentiation through MyoG and cell cycling signaling pathway.
Identifying Educational Needs of the Multidisciplinary Cancer Team in the Treatment of Metastatic Breast Cancer
Authors: Priya Wanchoo, Chris Larrison, Carol Rosenberg, Naomi Ko, Cynthia Cantril, Naomi Moeller, Ruchit Parikh, Ana-Marija Djordjevic
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Rapid advancements in the field of metastatic breast cancer (mBC) add to the complexity of managing patients with this disease. An educational needs assessment of multidisciplinary mBC clinicians was executed to identify practice performance gaps and recommend educational strategies aimed at closing these gaps. Methods: To ensure a collection of reliable data for assessment, a systematic process was used to design, develop, and validate the tools that were used. This grounded theory approach included assessment and confirmation by clinical experts and validation testing within the target audiences. A mixed-methods approach was used to identify practice performance gaps in care, using both qualitative in-depth interviews and quantitative surveying. The quantitative survey assessment consisted of 2 main sections: the Clinician Change Readiness Inventory tool and a Clinical Knowledge and Practice Assessment. Results: The study included 42 clinicians in the interview phase and 186 clinicians in the survey phase from 36 different states. Five key practice performance gaps were identified: (1) selecting optimal treatment, (2) personalizing therapy, (3) monitoring mBC, (4) engaging in effective communication, and (5) balancing patient access and time. Most of the gaps overlap and are related to the integral role communication plays in management decision-making in mBC. Conclusions: Awareness of the key practice performance gaps is critical to inform improvements in quality care.
Mutational profiling of acute lymphoblastic leukemia with testicular relapse
Authors: Ling-Wen Ding, Qiao-Yang Sun, Anand Mayakonda, Kar-Tong Tan, Wenwen Chien, De-Chen Lin, Yan-Yi Jiang, Liang Xu, Manoj Garg, Zhen-Tang Lao, Michael Lill, Henry Yang, Allen Eng Juh Yeoh, H. Phillip Koeffler
Journal: Journal of Hematology & Oncology (2017)

Relapsed acute lymphoblastic leukemia (ALL) is the leading cause of deaths of childhood cancer. Although relapse usually happens in the bone marrow, extramedullary relapse occasionally occurs including either the central nervous system or testis (<1-2%). We selected two pediatric ALL patients who experienced testicular relapse and interrogated their leukemic cells with exome sequencing. The sequencing results and clonality analyses suggest that relapse of patient D483 directly evolved from the leukemic clone at diagnosis which survived chemotherapy. In contrast, relapse leukemia cells (both bone marrow and testis) of patient D727 were likely derived from a common ancestral clone, and testicular relapse likely arose independently from the bone marrow relapsed leukemia. Our findings decipher the mutational spectra and shed light on the clonal evolution of two cases of pediatric ALL with testicular relapse. Presence of CREBBP/NT5C2 mutations suggests that a personalized therapeutic approach should be applied to these two patients.
The risk of injury associated with body checking among Pee Wee ice hockey players: an evaluation of Hockey Canada’s national body checking policy change
Authors: Amanda M Black, Brent E Hagel, Luz Palacios-Derflingher, Kathryn J Schneider, Carolyn A Emery
Journal: British Journal of Sports Medicine (2017)

Background In 2013, Hockey Canada introduced an evidence-informed policy change delaying the earliest age of introduction to body checking in ice hockey until Bantam (ages 13–14) nationwide. Objective To determine if the risk of injury, including concussions, changes for Pee Wee (11–12 years) ice hockey players in the season following a national policy change disallowing body checking. Methods In a historical cohort study, Pee Wee players were recruited from teams in all divisions of play in 2011–2012 prior to the rule change and in 2013–2014 following the change. Baseline information, injury and exposure data for both cohorts were collected using validated injury surveillance. Results Pee Wee players were recruited from 59 teams in Calgary, Alberta (n=883) in 2011–2012 and from 73 teams in 2013–2014 (n=618). There were 163 game-related injuries (incidence rate (IR)=4.37/1000 game-hours) and 104 concussions (IR=2.79/1000 game-hours) in Alberta prior to the rule change, and 48 injuries (IR=2.16/1000 game-hours) and 25 concussions (IR=1.12/1000 game-hours) after the rule change. Based on multivariable Poisson regression with exposure hours as an offset, the adjusted incidence rate ratio associated with the national policy change disallowing body checking was 0.50 for all game-related injuries (95% CI 0.33 to 0.75) and 0.36 for concussion specifically (95% CI 0.22 to 0.58). Conclusions Introduction of the 2013 national body checking policy change disallowing body checking in Pee Wee resulted in a 50% relative reduction in injury rate and a 64% reduction in concussion rate in 11-year-old and 12-year-old hockey players in Alberta.
siRNA-mediated inhibition of SREBP cleavage-activating protein reduces dyslipidemia in spontaneously dysmetabolic rhesus monkeys
Authors: Beth Ann Murphy, Marija Tadin-Strapps, Kristian Jensen, Robin Mogg, Andy Liaw, Kithsiri Herath, Gowri Bhat, David G. McLaren, Stephen F. Previs, Shirly Pinto
Journal: Metabolism (2017)
Disclosure of Disabilities by Medical Students
Authors: Kurt R. Herzer
Journal: JAMA (2017)

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Genome Wide SNP Analysis Reveals Frequent Cryptic Clonal Chromosomal Aberrations Including Uniparental Disomy (UPD) in Waldenstrom's Macroglobulinemia.
Authors: Stephanie Poulain, Christophe Roumier, Meyling Cheok, Sylvie Zoutina, Agnes Daudignon, Olivier Nibourel, Valérie Soenen, Jean Luc Lai, Jose Fernandez, Claude Preudhomme, Patrick Duthilleul, Pierre Morel, Xavier Leleu
Journal: Blood (2009)
Oxaliplatin, Fludarabine, Cytarabine, and Rituximab Combination Therapy Induces High Response Rates in Agressive Chronic Lymphocytic Leukemia (CLL) and Richter's Syndrome (RS).
Authors: Apostolia-Maria Tsimberidou, William Wierda, William Plunkett, Susan O'Brien, Thomas J. Kipps, Jeffrey Alan Jones, Susan Smith, Annette Jalayer, Hagop M. Kantarjian, Michael Keating
Journal: Blood (2009)
Association Between Ratio of Fresh Frozen Plasma to Red Blood Cells During Massive Transfusion and Survival Among Patients Without Traumatic Injury
Authors: Tomaz Mesar, Andreas Larentzakis, Walter Dzik, Yuchiao Chang, George Velmahos, Daniel Dante Yeh
Journal: JAMA Surgery (2017)

Hemostatic resuscitation has been shown to be beneficial for patients with trauma, but there is little evidence that it is equally beneficial for bleeding patients without trauma. The practice of a high transfusion ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) has spread to other surgical and medical fields.To identify whether ratio-based resuscitation in patients without trauma is associated with improved survival.This study is a retrospective review of all massive transfusions provided in an urban academic hospital from January 1, 2009, through December 31, 2012. Massive transfusion was defined as the transfusion of at least 10 U of RBCs in the first 24 hours after a patient's admission to the operating room, emergency department, or intensive care unit. All patients who received massive transfusions within the study period and survived more than 30 minutes after hospital arrival were counted (n=865). Patients were grouped into those with trauma and those without trauma. Sources of data included the Research Patient Data Registry, patients' medical records, and blood bank records. All data collection occurred between April 26, 2013, and April 26, 2015. Data analysis took place from April 27, 2015, and June 22, 2016.Examination of FFP:RBC transfusion ratios for patients without trauma.There were 865 massive transfusion events that occurred within 4 years, transfusing 16 569 U of RBCs, 13 933 U of FFP, 5228 U of cryoprecipitate, and 22 635 U of platelets. Most of these transfusions were received by patients without trauma (767 [88.7%]), by men (582 [67.3%]), and for intraoperative bleeding (544 [62.9%]). The FFP:RBC ratios of survivors and nonsurvivors were nearly identical: the ratio for survivors was 1:1.5 (interquartile range [IQR], 1:1.1-1:2.2) and for nonsurvivors was 1:1.4 (IQR, 1:1.1-1:1.9; P = .43). Among the 767 patients without trauma, there was no difference in the adjusted odds ratio (aOR) for 30-day mortality when comparing the high FFP:RBC ratio vs the low FFP:RBC ratio subgroups (aOR, 1.10; 95% CI, 0.72-1.70; P = .65). In vascular surgery, the aOR for death favored the high FFP:RBC ratio subgroup (aOR, 0.16; 95% CI, 0.03-0.79; P = .02). However, in general surgery and medicine, the aOR for death favored the low FFP:RBC ratio subgroup; general surgery: aOR, 4.27 (95% CI, 1.28-14.22; P = .02); medicine: aOR, 8.48 (95% CI, 1.50-47.75; P = .02).High FFP:RBC transfusion ratios are applied mostly to patients without trauma, who account for nearly 90% of all massive transfusion events. Thirty-day survival was not significantly different in patients who received a high FFP:RBC ratio compared with those who received a low ratio.
Caspase vinyl sulfone small molecule inhibitors prevent axonal degeneration in human neurons and reverse cognitive impairment in Caspase-6-overexpressing mice
Authors: Prateep Pakavathkumar, Anastasia Noël, Clotilde Lecrux, Agne Tubeleviciute-Aydin, Edith Hamel, Jan-Eric Ahlfors, Andrea C. LeBlanc
Journal: Molecular Neurodegeneration (2017)

The activation of the aspartate-specific cysteinyl protease, Caspase-6, is proposed as an early pathogenic event of Alzheimer disease (AD) and Huntington's disease. Caspase-6 inhibitors could be useful against these neurodegenerative diseases but most Caspase-6 inhibitors have been exclusively studied in vitro or show acute liver toxicity in humans. Here, we assessed vinyl sulfone small molecule peptide caspase inhibitors for potential use in vivo. The IC50 of NWL vinyl sulfone small molecule caspase inhibitors were determined on Caspase-1 to 10, and Caspase-6-transfected human colon carcinoma HCT116 cells. Inhibition of Caspase-6-mediated axonal degeneration was assessed in serum-deprived or amyloid precursor protein-transfected primary human CNS neurons. Cellular toxicity was measured by phase contrast microscopy, mitochondrial and lactate dehydrogenase colorimetric activity assays, or flow cytometry. Caspase inhibition was measured by fluorogenic activity assays, fluorescence microscopy, and western blot analyses. The effect of inhibitors on age-dependent cognitive deficits in Caspase-6 transgenic mice was assessed by the novel object recognition task. Liquid chromatography coupled to tandem mass spectrometry assessed the blood-brain barrier permeability of inhibitors in Caspase-6 mice. Vinyl sulfone NWL-117 caspase inhibitor has a higher selectivity against Caspase-6, −4, −8, −9, and −10 whereas NWL-154 has higher selectivity against Caspase-6, −8, and −10. The half-maximal inhibitory concentrations (IC50) of NWL-117 and NWL-154 is 192 nM and 100 nM against Caspase-6 in vitro, and 4.82 μM and 3.63 μM in Caspase-6-transfected HCT116 cells, respectively. NWL inhibitors are not toxic to HCT116 cells or to human primary neurons. NWL-117 and NWL-154 inhibit serum deprivation-induced Caspase-6 activity and prevent amyloid precursor protein-mediated neurite degeneration in human primary CNS neurons. NWL-117 crosses the blood brain barrier and reverses age-dependent episodic memory deficits in Caspase-6 mice. NWL peptidic vinyl methyl sulfone inhibitors are potent, non-toxic, blood-brain barrier permeable, and irreversible caspase inhibitors with neuroprotective effects in HCT116 cells, in primary human CNS neurons, and in Caspase-6 mice. These results highlight the therapeutic potential of vinyl sulfone inhibitors as caspase inhibitors against neurodegenerative diseases and sanction additional work to improve their selectivity against different caspases.
Impact of the Next-Generation Sequencing Panel on Treatment Choice in Patients with Myelodysplastic Syndrome
Authors: Ana Alfonso Pierola, Guillermo Montalban-Bravo, Ali N. Chamseddine, Koichi Takahashi, Feng Wang, Song Xingzhi, Elias J. Jabbour, Tapan M. Kadia, Farhad Ravandi, Jorge E. Cortes, Courtney D. DiNardo, Naval G. Daver, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos E Bueso-Ramos, Keyur Patel, Andrew Futreal, Sherry Pierce, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2016)
New Approaches to the Regulation of Erythropoiesis and Hematoglobin Synthesis in β-Hemoglobinopathies: Studies with the Immunomodulatory Drug CC-4047.
Authors: Laure A. Moutouh de Parseval, Dominique Verhelle, Emilia Glezer, Helen Brady, Laura G. Corral, Christopher L. Morris, George Muller, Kyle Chan
Journal: Blood (2006)
Regulatory T Cells Do Not Affect Human Hematopoietic Stem Cell Engraftment and Prevent T Cell Alloreactivity Against CD34+ Cells: A Preclinical Study.
Authors: Dolores Mahmud, Sandeep Chunduri, Nadim Mahmud, Lennert Van Den Dries, John J. Maciejewski, Damiano Rondelli
Journal: Blood (2007)
Expansion of CD38+ Activated B Cells in Circulation as a Manifestation of Early Onset EBV Associated Post-Transplant Lymphoproliferative Disease.
Authors: Sridhar Chaganti, Sandeep Nagra, Mark Cook, Premini Mahendra, Charles Craddock, Husam Osman, Andrew Hislop, Sylvie Freeman, Fiona Clark
Journal: Blood (2007)