tbuckley/cabot-search huggingface dataset:
Soluble thrombopoietin receptor (Mpl) and granulocyte colony- stimulating factor receptor directly stimulate proliferation of primitive hematopoietic progenitors of mice in synergy with steel factor or the ligand for Flt3/Flk2
Authors: H Ku, F Hirayama, T Kato, H Miyazaki, M Aritomi, Y Ota, AD D'Andrea, SD Lyman, M Ogawa
Journal: Blood (1996)
<i>Notes from the Field:</i> Unintentional Fentanyl Overdoses Among Persons Who Thought They Were Snorting Cocaine — Fresno, California, January 7, 2019
Authors: Patil Armenian, Jeffrey D. Whitman, Adina Badea, Whitney Johnson, Chelsea Drake, Simranjit Singh Dhillon, Michelle Rivera, Nicklaus Brandehoff, Kara L. Lynch
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

On January 7, 2019, three patients arrived at the Community Regional
X-tra X: An escape to autoimmunity
Authors: Gregory F. Wu
Journal: Journal of Clinical Investigation (2019)

Identifying the factors driving disease disparities between males and females with multiple sclerosis (MS) holds great promise for deciphering immunopathogenic disease mechanisms. In this issue of JCI, Itoh et al. explore the basis for sexual dimorphism in autoimmunity, specifically in MS. Using the experimental autoimmune encephalomyelitis (EAE) model of MS, which recapitulates CD4+ T cell-dependent disease, the authors examined the contribution of Kdm6a, a histone demethylase gene known to escape X inactivation. Conditional knockout in CD4+ T cells revealed Kdm6a involvement with a collection of immunologic processes having the potential to skew immunity toward inflammatory responses. This study concisely shows the value of X chromosome gene expression in T cell regulation of autoimmunity and the relevance of Kdm6a in the pathogenesis of EAE as a model of MS.
Evolving Concepts in the Management of Newly Diagnosed Epithelial Ovarian Cancer
Authors: Charlie Gourley, Michael A. Bookman
Journal: Journal of Clinical Oncology (2019)

Article Tools REVIEW ARTICLES Gynecologic Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.19.00337 Journal of Clinical Oncology - published online before print August 12, 2019 PMID: 31403859 Evolving Concepts in the Management of Newly Diagnosed Epithelial Ovarian Cancer Charlie Gourley, PhD1xCharlie GourleySearch for articles by this author and Michael A. Bookman, MD2xMichael A. BookmanSearch for articles by this author Show More 1University of Edinburgh, Edinburgh, United Kingdom2Kaiser Permanente Northern California, San Francisco, CA https://doi.org/10.1200/JCO.19.00337 First Page Full Text PDF Figures and Tables © 2019 by American Society of Clinical Oncology
Evolving Practice Patterns in the Use of Prophylactic Cranial Irradiation for Extensive-Stage Small Cell Lung Cancer
Authors: Olsi Gjyshi, Ethan B. Ludmir, Todd A. Pezzi, David Boyce-Fappiano, Amy E. Dursteler, Timur Mitin, Steven H. Lin
Journal: JAMA Network Open (2019)

This survey study compares use of prophylactic cranial irradiation in patients with extensive-stage small cell lung cancer before and after the publication of a phase 3 trial that demonstrated no overall survival benefit for this therapy.
Design of biodegradable nanoparticles to modulate phenotypes of antigen-presenting cells for antigen-specific treatment of autoimmune disease
Authors: Eiji Saito, Robert Kuo, Kevin R. Kramer, Nishant Gohel, David A. Giles, Bethany B. Moore, Stephen D. Miller, Lonnie D. Shea
Journal: Biomaterials (2019)
Sex-Related Differences in the Extent of Myocardial Fibrosis in Patients With Aortic Valve Stenosis
Authors: Lionel Tastet, Jacek Kwiecinski, Philippe Pibarot, Romain Capoulade, Russell J. Everett, David E. Newby, Mylène Shen, Ezequiel Guzzetti, Marie Arsenault, Élisabeth Bédard, Éric Larose, Jonathan Beaudoin, Marc Dweck, Marie-Annick Clavel
Journal: JACC. Cardiovascular imaging (2019)
Identification of a protein profile predicting tamoxifen-resistance in breast cancer: employing nanoLC-FTICR to analyze laser microdissected tumor cells
Authors: Arzu Umar, Huyk Kang, Marion Meijer-van Gelder, Theo Luider, John Foekens, Ljiljana Pasa-Tolic
Journal: Cancer Research (2007)

592  The anti-estrogen tamoxifen has been widely used as therapy in breast cancer. However, only half of the patients with recurrent tumors show an objective response (OR) to tamoxifen therapy, while the remaining half continues in progressive disease (PD). Eventually, even responsive tumors become resistant, which is a major cause of death and therefore a problem that needs to be tackled. Identification of proteins that associate with tamoxifen-resistance is a first step towards unraveling the molecular mechanisms involved. This information can be used to better predict therapy response, thereby reducing over-treatment of patients, and to identify new targets for therapy that may lead to tailored treatment strategies.  To identify protein biomarkers indicative of tamoxifen-resistance in breast cancer, a comparative proteomics analysis was performed using nanoscale liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (nanoLC-FTICR MS). Two independently processed datasets (n=27 and n=28) of both OR and PD tumors were subjected to laser capture microdissection (LCM), ~ 4000 tumor cells were collected and subsequently pooled into groups of seven. Tryptic digests were prepared and analyzed in triplicate; ~550 ng of peptides per analysis were separated on a 50 μm x 80 cm reversed phase nanoLC column prior to FTICR MS analysis. Peptide mass and elution time features were matched to information in previously generated accurate mass and time (AMT) tag reference databases to identify peptide sequences and proteins, and the MS peak intensities were used to determine relative peptide abundances.  More than 20,000 unique peptides were identified that corresponded to a total of 2309 non-redundant proteins identified with two or more peptides. From this total, 1713 (74%) proteins that overlapped between the two datasets were used for further statistical analysis. The two datasets were separated into a ‘training’ and ‘validation’ set and analyzed for differential protein abundance between OR and PD groups, using a univariate t-test from BRB array-tools software package, followed by a Wilcoxon rank-sum test. In both datasets, 100 differentially abundant proteins were identified (p  In summary, an 8-protein profile observed to predict tamoxifen-resistance in breast cancer was revealed by ultra-sensitive nanoLC-FTICR technology for comprehensive proteome analyses of LCM cells. This profile may harbor biomarkers that are useful in the clinic.
Placental growth factor regulates the generation of TH17 cells to link angiogenesis with autoimmunity
Authors: Seung-Ah Yoo, Mingyo Kim, Min-Cheol Kang, Jin-Sun Kong, Ki-Myo Kim, Saseong Lee, Bong-Ki Hong, Gi Heon Jeong, Jinhee Lee, Min-Gyeong Shin, Yeon-Gu Kim, Ivana Apicella, Valeria Cicatiello, Sandro De Falco, Chong-Hyeon Yoon, Chul-Soo Cho, Zae Young Ryoo, Seung-Hyo Lee, Wan-Uk Kim
Journal: Nature Immunology (2019)
Why Dax’s Case Still Matters
Authors: Kayhan Parsi, William J. Winslade
Journal: The American Journal of Bioethics (2019)

After nearly 50  years, the case of Dax Cowart still engages ethicists, lawyers, health professionals, students, and the general public. Why? Dax Cowart, who died of cancer on April 28, 2019, at th...
Abstract 19114: Attenuating Mitochondrial ROS Reduces AF in Mice With Persistent Na+ Current
Authors: Uma Avula, Meghana Noonavath, Charlotte Buck, Hasan Garan, Steven Marx, Elaine Wan
Journal: Circulation (2017)

Introduction: Atrial fibrillation (AF) in humans is associated with increased reactive oxygen species (ROS). Using a mouse model of spontaneous and persistent AF, we demonstrated that increased per...
Incremental cost (IC) analysis of skeletal related events (SREs) among elderly men with stage IV metastatic (M1) prostate cancer (PCa).
Authors: Jinani Jayasekera, Ebere Onukwugha, Kaloyan A. Bikov, C. Daniel Mullins, Brian S. Seal, Arif Hussain
Journal: Journal of Clinical Oncology (2013)

e16034 Background: Patients diagnosed with stage IV M1PCa are predisposed to SREs, such as pathologic fracture (PF), spinal cord compression (SCC) and bone surgery (BS). There is limited information in the literature regarding the ICs associated with SREs among stage IV M1 PCa patients. Methods: We analyzed patients aged 66+ yrs diagnosed with incident stage IV M1 PCa between 2000 and 2007 from the linked SEER-Medicare dataset. Five mutually exclusive SRE categories were created: PF only, PF+concurrent surgery (SRG), SCC only, SCC+SRG, and BS only. Patients with multiple SREs were excluded. A propensity score for the incidence of an SRE was estimated using a logistic regression model including baseline demographic and clinical variables, diagnosis year and SEER region. Patients with SREs (cases) were matched to those without SREs (controls), based on the propensity score. The date of SRE of a case was assigned to a matched control, and the 12 month pre- and post-SRE costs were calculated. A difference-in-difference method was used to estimate the ICs (post-pre) for cases vs. controls. The analysis was conducted from a US Medicare perspective. Results: Application of inclusion criteria resulted in 1,131 stage IV M1 PCa patients with SREs. The average age was 78 yrs and 12% were African American. Using the propensity score, 1,031 cases were matched with 1,031 controls and allocated to the following SRE groups: PF+SRG (n=134), PF only (n=143), SCC+SRG (n=40), SCC only (n=538) and BS only (n=176). The average IC per SRE was $30,548 (vs. controls). The most expensive SRE group was SCC+SRG with a total average IC of $62,412, followed by BS only ($37,554), PF+SRG ($35,520), SCC ($28,027), and PF only ($17,839). Inpatient costs were the major driver of ICs followed by physician/non-institutional provider and skilled nursing facility (SNF) costs. Conclusions: The ICs associated with an SRE are significant. The IC of an SRE varies by type of SRE and service category. [Table: see text]
Incidence trends for human papillomavirus-related (HPV-R) and unrelated (HPV-U) head and neck squamous cell carcinomas (HNSCC) in the United States (US)
Authors: A. Chaturvedi, E. Engels, W. Anderson, M. Gillison
Journal: Journal of Clinical Oncology (2007)

6001 Background: HNSCC are etiologically heterogeneous, with one subset primarily attributable to HPV and another to tobacco and alcohol. Methods: Data from SEER9 program registries were used to investigate the potential influence of HPV on incidence and survival of HNSCC in the US from 1973–2003. HNSCCs (N=58,158) were classified by anatomic site as potentially HPV-R (base of tongue; tonsil; oropharynx; N=16,712) or HPV-U (lip; tongue; gum; floor of mouth; palate; other mouth; hypopharynx; ill-defined sites of lip, oral cavity, and pharynx; N=41,446). Joinpoint regression was used to assess incidence trends and life-table methods were used to compare survival for HPV-R and HPV-U HNSCCs. Results: For HPV-R HNSCCs, age-adjusted incidence increased significantly from 1973–2003 (annual percent change [APC] = 0.65), particularly among males (APC=1.02), whites (APC=0.89), and younger ages (APCs for 30–39 = 1.46; 40- 49=1.92; 50–59=0.61, and =60= -0.66). By contrast, HPV-U HNSCC incidence was stable from 1973–1983 and then decreased significantly from 1983–2003 (APC= -2.42). Mean age at diagnosis was younger for HPV-R HNSCC than HPV-U (61.1 vs. 64.5 years; p&lt;0.001), and from 1973- 2003, decreased significantly for HPV-R, but increased for HPV-U. Improvements in overall survival (OS) were observed for HPV-R (all stages) and HPV-U (regional and distant) HNSCC treated by radiotherapy (RT) from 1973–2003, but were more marked for HPV-R HNSCC, e.g. absolute increase in two-year OS for regional disease of 24.4% (vs. 5.8% for HPV-U). OS for HPV-R (local and regional) was significantly better than HPV-U HNSCC if treated by RT, but worse if not so treated. Conclusions: The proportion of HNSCC that is potentially HPV- R increased in the US from 1973–2003, particularly among recent birth cohorts, perhaps due to changing sexual and smoking behaviors. Recent improvements in locoregional control with RT-based therapy may be due in part to a gradual shift in the etiology of the underlying disease. No significant financial relationships to disclose.
Moral rigidity as a proximate facilitator of group cohesion and combativeness
Authors: Antoine Marie
Journal: Behavioral and Brain Sciences (2019)

Abstract De Dreu and Gross's description of the proximate mechanisms conditioning success in intergroup conflict omits humans' deontological morality. Drawing on research on sacralization and moral objectivism, I show how “moral rigidity” may have evolved through partner selection mechanisms to foster coalitions’ cohesion and combativeness in intergroup conflict.
Renal Ewing's sarcoma: A single institute experience of seven patients.
Authors: Sorun Shishak, Sameer Rastogi, Rambha Panday, Dayanand Sharma, Adarsh Barwad, Aditi Aggarwal, Ekta Dhamija, Anshul Gupta, Soorej Balan, Svs Deo, Rimlee Dutta, Parisa Manasa, Santosh Kumar C, Pankaj Kumar
Journal: Journal of Clinical Oncology (2019)

e22538 Background: Renal Ewing’s sarcoma constitutes a rare subset of extraskeletal ewings with aggressive clinical course and dismal outcomes. The purpose of our study was to review our experience in the management of patients with Renal Ewing’s Sarcoma. Methods: We retrospectively analysed patients with Renal Ewing’s Sarcoma who were registered in Sarcoma Medical Oncology Clinic at AIIMS, New Delhi between September 2016 and January 2019. Results: A total of eight patients were registered in the study period, one of which was diagnosed with wilms tumor post nephrectomy and was excluded from our study. Of seven patients included in analysis, five (71.4%) were males. The commonest symptoms were flank pain (57.1%) and hematuria (57.1%). The median age was 28 years (range, 18 to 50 years). The mean Hemoglobin was 10.4 g/dl (range, 6-14 g/dl). The median tumor size was 13 cm (range, 5-25 cm). Four patients (57.1%) were non-metastatic while three (42.9%) had metastases in bone, lung and liver, and peritoneum respectively. Diagnosis was established by an upfront nephrectomy in four patients (57.1%) and biopsy in three patients (42.9%). Translocation for EWSR1 was done in 5 patients of which four (80%) were positive and one patient (20%) were negative. The test was not carried out in two patients due to inadequate tissue sampling. Three patients received neoadjuvant chemotherapy with VAC and the rest (four) received it after surgery. Ifosfamide-etoposide (IE) was added to VAC regimen in first two patients, in one being added post nephrectomy. This patient developed Ifosfamide-induced renal failure resulting in death. Radiotherapy was given in two patients, one pre-operative owing to large inoperable mass, and post operative in the other due to positive margins. At last follow up, three patients (42.9%) are alive and are on chemotherapy after radical nephrectomy. Four patients (57.1%) have died, three due to disease (all metastatic) and one due to chemotoxicity. The median survival was 15 months. Conclusions: Unlike extremity, renal ewings sarcoma more commonly presents in higher age and with advanced disease. Translocation studies are a prerequisite in a suspected case of Renal Ewings Sarcoma, especially due to possibility of discrepancies in pre and post-operative diagnoses. Our institutional protocol does not recommend the use of Ifosfamide in the subset of patients with single kidney, post nephrectomy. Caution must be exercised before instituting the drug and should be given only pre-operatively in absence of renal dysfunction.
High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care
Authors: Jian Li, Olajide E. Olaleye, Xuan Yu, Weiwei Jia, Junling Yang, Chuang Lu, Songqiao Liu, Jingjing Yu, Xiaona Duan, Yaya Wang, Kai Dong, Rongrong He, Chen Cheng, Chuan Li
Journal: Acta Pharmaceutica Sinica B (2019)

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality via modulating the host response, pharmacokinetic herb–drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5′-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.
Tumor suppressor p53 down regulates the expression of hepatocyte nuclear factor 4 α
Authors: Wendy W. Hwang-Verslues, Yutaka Maeda, Gang Wei, Takuya Fukazawa, Mary L. Durbin, Laurie B. Owen-Schaub, Xuan Liu, Frances M. Sladek
Journal: Cancer Research (2006)

2706  Terminal differentiation of a B lymphocyte to an antibody secreting plasma cell requires the activity of the transcriptional repressor protein PRDI-BF1 (Blimp-1). PRDI-BF1 functions by suppressing a complex network of genes involved in maintaining the B cell phenotype and in maintaining cellular proliferation. The human PRDM1 gene, encoding the PRDI-BF1 protein, is highly expressed in bone marrow cells isolated from myeloma patients as well as in established myeloma cell lines. This makes the PRDM1 gene a potential therapeutic target in myeloma patients however little is known about it regulation. Our studies now demonstrate that the PRDM1 gene is regulated primarily at the level of transcription while mRNA stability has a minor role in myeloma cells. Furthermore PRDM1 gene transcription is rapidly induced upon treatment of lymphoma cells with histone deacetylase inhibitors, proteasome inhibitors, or cross-linking of the B cell receptor, suggesting that the promoter is poised for activation in these cells. In vivo genomic footprinting of the PRDM1 promoter reveals protein-DNA interactions occurring at the proximal promoter and in several distal clusters within 2618 base pairs of the transcription initiation point. Most of the in vivo contacts are similar between the expressing myeloma cell lines and the non-expressing lymphoma cell lines consistent with the promoter being poised for activation. However, several of the interactions are unique to either the myeloma or lymphoma cells suggesting that specific activation or repression complexes exist at the promoter. Functional analysis of the PRDM1 promoter using a series of promoter deletion constructs reveals that the proximal promoter region and two distal domains can confer strong transcriptional activation. In vitro characterization of the factors bound within these domains indicates that Sp1 and IRF/Ets proteins interact at these sites. Point mutation of these occupied sites demonstrates that they are functionally active. These studies indicate that the PRDM1 gene utilizes a complex promoter spanning at least 2618 base pairs that is poised for activation in lymphoma cell lines and is transcriptionally activated in myeloma cells.
Abstract 17060: The Effect of Resuscitation Position on Cerebral and Coronary Perfusion Pressure During Mechanical Cardiopulmonary Resuscitation in Porcine Model
Authors: Yong-Joo Park, Taeyun Kim, Sang Do Shin, Kyoung Jun Song, Dayea Jang, Hyun Ho Ryu, Guillaume DeBaty, Keith Lurie
Journal: Circulation (2015)

Objectives: Mechanical compression devices can allow us to select a positon during transport with cardiopulmonary resuscitation (CPR) in a small space (like elevator) to reduce the length of stretcher cart. It is unclear, however, whether resuscitation position is associated with cerebral perfusion pressure (CePP) or coronary perfusion pressure (CoPP). Methods: This is a randomized crossover experimental trial using female farm pigs (n=12) (42 ± 3kg) sedated, intubated, and paralyzed on a tilt table. After surgical preparation, 6 minutes of untreated ventricular fibrillation was induced followed by 3 minutes in 0° supine position as a stabilization period with mechanical CPR device (M) and an impedance threshold device (ITD). Then, 5 minutes of M-CPR+ITD was performed in a position randomly assigned to either head-up tilt at 30°, 45°, or 60°, supine, or head-down tilt at 30°, 45°, or 60° followed by 5 minutes of M-CPR+ITD in crossover position to the other. We measured and compared the CePPs and CoPPs at the positions using ANOVA with Duncan post-hoc test. Results: Baseline hemodynamic parameters among pigs were not different. From head-down to head-up by elevation of angle, mean aortic pressures slightly decreased and intracranial pressure significantly decreased. With 60°, 45°, 30° head-down, 0°(supine), and 30°, 45°, 60° head-up positioning, CePPs increased linearly as follows: 2.4± 3.1, 9.3±3.9, 16.5±5.0, 27.0±2.3, 35.1±1.2, 39.4±12, 39.9±1.5mmHg respectively (p&lt;0.001 by ANOVA and all significant for post-hoc test). CoPPs was peak in head-up 30 °: 12.9± 4.2, 13.3±5.0, 12.8±2.9, 18.1±2.0, 30.3±1.5, 24.1±1.7, 26.5±1.9 mmHg respectively (p&lt;0.001 by ANOVA post-hoc test except between head-down -30° and -65°). Conclusion: Mechanical CPR position was associated with different cerebral perfusion pressure by head-up angles. The head-up 30° showed the peak coronary perfusion pressure.
Strategies to Adjust Positive End-Expiratory Pressure in Patients With ARDS
Authors: Xiaobo Yang, Shiying Yuan
Journal: JAMA (2019)

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