tbuckley/cabot-search huggingface dataset:
BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas
Authors: Aleksandra Olow, Sabine Mueller, Xiaodong Yang, Rintaro Hashizume, Justin Meyerowitz, William Weiss, Adam C. Resnick, Angela J. Waanders, Lukas J.A. Stalpers, Mitchel S. Berger, Nalin Gupta, C. David James, Claudia K. Petritsch, Daphne A. Haas-Kogan
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Alteration of the BRAF/MEK/MAPK pathway is the hallmark of pediatric low-grade gliomas (PLGGs), and mTOR activation has been documented in the majority of these tumors. We investigated combinations of MEK1/2, BRAFV600E and mTOR inhibitors in gliomas carrying specific genetic alterations of the MAPK pathway. Experimental Design: We used human glioma lines containing BRAFV600E (adult high-grade: AM-38, DBTRG, PLGG: BT40), or wild-type BRAF (pediatric high-grade: SF188, SF9427, SF8628) and isogenic systems of KIAA1549:BRAF-expressing NIH/3T3 cells and BRAFV600E-expressing murine brain cells. Signaling inhibitors included everolimus (mTOR), PLX4720 (BRAFV600E), and AZD6244 (MEK1/2). Proliferation was determined using ATP-based assays. In vivo inhibitor activities were assessed in the BT40 PLGG xenograft model. Results: In BRAFV600E cells, the three possible doublet combinations of AZD6244, everolimus, and PLX4720 exhibited significantly greater effects on cell viability. In BRAFWT cells, everolimus + AZD6244 was superior compared with respective monotherapies. Similar results were found using isogenic murine cells. In KIAA1549:BRAF cells, MEK1/2 inhibition reduced cell viability and S-phase content, effects that were modestly augmented by mTOR inhibition. In vivo experiments in the BRAFV600E pediatric xenograft model BT40 showed the greatest survival advantage in mice treated with AZD6244 + PLX4720 (P &amp;lt; 0.01). Conclusions: In BRAFV600E tumors, combination of AZD6244 + PLX4720 is superior to monotherapy and to other combinatorial approaches. In BRAFWT pediatric gliomas, everolimus + AZD6244 is superior to either agent alone. KIAA1549:BRAF-expressing tumors display marked sensitivity to MEK1/2 inhibition. Application of these results to PLGG treatment must be exercised with caution because the dearth of PLGG models necessitated only a single patient-derived PLGG (BT40) in this study. Clin Cancer Res; 22(21); 5312–21. ©2016 AACR.
Intramural Duodenal Hematoma and Acute Pancreatitis
Authors: Z.  Bodnár, C.  Várvölgyi
Journal: Endoscopy (2003)

We read with great interest the paper by T. L. Dugernier et al. entitled ”Duodenal air dissection secondary to intramural hematoma in necrotizing pancreatitis” [1]. We agree with the authors about the conservative approach to management of intramural duodenal hematoma, especially when the origin is nontraumatic. In addition, we would also emphasize the role of nasojejunal feeding in the case of necrotizing pancreatitis. We have also reported the successful nonsurgical treatment of intramural duodenal hematoma complicating acute necrotizing pancreatitis [2]. Although complete bowel obstruction may prevent the insertion of the jejunal feeding tube, sometimes, even in the case of near-total duodenal obstruction, it is feasible to traverse the narrowed segment allowing utilization of the beneficial effects of enteral nutrition [3] in the presence of serious, life-threatening conditions.
Bariatric Surgery: A Potential Treatment for Type 2 Diabetes in Youth
Authors: Amy S. Shah, David D’Alessio, Martha E. Ford-Adams, Ashish P. Desai, Thomas H. Inge
Journal: Diabetes Care (2016)

Type 2 diabetes, once referred to as “adult-onset” diabetes, has now emerged as a formidable threat to the health of obese adolescents. Although there is growing evidence regarding the epidemiology of type 2 diabetes in youth and its multisystem health consequences, treatment options have lagged and progression of disease occurs even with aggressive medical therapy. Increasing interest in the application of bariatric surgery for adolescents with type 2 diabetes has evolved in part because of the evidence demonstrating improvement or remission in many adults with diabetes after surgery. Here, we review the burden of type 2 diabetes in youth including its associated complications, discuss the outcomes and complications of bariatric surgery in adolescents with diabetes, and conclude with recommendations for future research and options for refinement of the use of bariatric surgery in this patient population.
A Simple Method for the Preparation of Potent Chicken Anti-Rous Sarcoma Virus Serum
Authors: Mary Alexander Fink, Frank J. Rauscher
Journal: JNCI Journal of the National Cancer Institute (1961)

A method is described for the immunization of chickens with either formalin or heat-killed Rous sarcoma virus incorporated in Freund's complete adjuvant. Serums from immunized birds were titrated for neutralizing antibody in chick embryos prior to and after a subsequent injection of viable virus. More than half the birds, all of which had a high antibody content after vaccination, survived the challenge inoculation, and a high concentration of antibody persisted up to a year.
Progress Toward Poliomyelitis Eradication — Pakistan, January 2015–September 2016
Authors: Christopher H. Hsu, Abdirahman Mahamud, Rana Muhammad Safdar, Jamal Ahmed, Jaume Jorba, Salmaan Sharif, Noha Farag, Maureen Martinez, Rudolph H. Tangermann, Derek Ehrhardt
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Pakistan, Afghanistan, and Nigeria remain the only countries where endemic wild poliovirus type 1 (WPV1) transmission continues. This report describes the activities, challenges, and progress toward polio eradication in Pakistan during January 2015-September 2016 and updates previous reports (1,2). In 2015, a total of 54 WPV1 cases were reported in Pakistan, an 82% decrease from 2014. In 2016, 15 WPV1 cases had been reported as of November 1, representing a 61% decrease compared with the 38 cases reported during the same period in 2015 (Figure 1). Among the 15 WPV1 cases reported in 2016, children aged <36 months accounted for 13 cases; four of those children had received only a single dose of oral poliovirus vaccine (OPV). Seven of the 15 WPV1 cases occurred in the province of Khyber Pakhtunkhwa (KP), five in Sindh, two in the Federally Administered Tribal Areas (FATA), and one in Balochistan (3). During January-September 2016, WPV1 was detected in 9% (36 of 384) of environmental samples collected, compared with 19% (69 of 354) of samples collected during the same period in 2015. Rigorous implementation of the 2015-2016 National Emergency Action Plan (NEAP) (4), coordinated by the National Emergency Operations Center (EOC), has resulted in a substantial decrease in overall WPV1 circulation compared with the previous year. However, detection of WPV1 cases in high-risk areas and the detection of WPV1 in environmental samples from geographic areas where no polio cases are identified highlight the need to continue to improve the quality of supplemental immunization activities (SIAs),* immunization campaigns focused on vaccinating children with OPV outside of routine immunization services, and surveillance for acute flaccid paralysis (AFP). Continuation and refinement of successful program strategies, as outlined in the new 2016-2017 NEAP (5), with particular focus on identifying children missed by vaccination, community-based vaccination, and rapid response to virus identification are needed to stop WPV transmission.
Characterisation of Human CD83 Expression on Immune Cells and Their Targeting with CD83 Antibodies to Prevent Graft Versus Host Disease in Allogeneic Haematopoietic Cell Transplantation
Authors: Derek NJ Hart, Xinsheng Ju, Zehra Elgundi, Nirupama Verma, Pablo Silveira, Phillip Fromm, Renz Alingcastre, Blake Hsu, David J Munster, Therese Seldon, Yonghua Sheng, Martina Jones, Trent Munro, Stephen Mahler, Ross Barnard, Ai Vu, Tsun Ho Lo, Kifah Shahin, Stephen Robert Larsen, Kenneth Bradstock, Georgina Clark
Journal: Blood (2015)
Abstract A01: ER stress disrupts circadian rhythms via miR-211
Authors: Yiwen Bu, John Alan Diehl
Journal: Cancer Research (2016)

Abstract The Endoplasmic Reticulum, ER, senses both intracellular and extracellular stimuli that perturb the folding and maturation of secretory proteins that transit the ER. In the context of neoplastic growth, oncogenes such as c-Myc, H-Ras and BRAF trigger ER stress and activate the Unfolded Protein Response (UPR), a cell adaptive signaling pathway composed of three primary signal transducers, PERK, IRE-1 and ATF6. Bmal1 and Clock form a core heterodimeric transcription complex regulates both central and peripheral circadian rhythms. There are multiple lines of evidence suggesting that deregulation of circadian rhythms contribute to neoplastic cell growth, altered cellular metabolism and tumorigenesis. Analogously, UPR signaling contributes to tumor cell survival and tumor growth under conditions of micro-environmental and metabolic stress. However, whether UPR interactively regulates stress with the circadian clock is largely unknown. Herein, we describe the molecular mechanisms whereby UPR signaling integrates with the circadian clock. We provide evidence that ER stress-dependent activation of PERK alters circadian oscillations via micro-RNA 211-dependent suppression of BMAL1 and Clock. We provide evidence that the mechanism of regulation of BMAL1 versus clock is distinct, reflecting novel ability of miR-211 to function in both the nucleus and cytoplasm. We provide additional support for this model through using a mouse model to interrogate the role of PERK signaling in a liver specific response to ER stress. With regard to the impact of PERK signaling and circadian clock disruption in cancer, we assessed PERK-miR-211 signaling in c-Myc and MLL-AF9 driven malignancy. Here, expression of either c-Myc or MLL-AF9 expression was directly associated with activation of PERK-miR-211 and loss of both BMAL1 and Clock expression. We also found that Myc driven human Burkitt's lymphoma has PERK hyperactivation, higher miR-211 expression, and loss of circadian oscillations. As the Bmal1 promoter is hypermethylated in multiple lymphoma cancer cell lines, we hypothesize that this is likely to reflect the action of nuclear miR-211. Consistently, anti-miR211 partially released Bmal1 repression and Inhibition PERK or suppression miR-211 rescued circadian rhythms in lymphoma cells thereby affecting their survival and proliferation. Our data suggested a model where ER stress disrupts peripheral circadian rhythms via PERK-miR211-Bmal1/Clock pathway. Targeting activated ER stress or abnormal miR-211 expression to rescue circadian rhythms could be a new potential therapy for Myc- (perhaps also other oncogenes) driven hematological malignancy. Citation Format: Yiwen Bu, John Alan Diehl. ER stress disrupts circadian rhythms via miR-211. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A01.
Relapse of psychiatric patients in foster care
Authors: M W Linn, C J Klett, E M Caffey
Journal: American Journal of Psychiatry (1982)

The authors examined factors related to relapse of psychiatric patients within 1 year of placement in a foster home. They collected data on 210 male patients who had been hospitalized in VA medical centers who were discharged to foster homes in five states. Slightly fewer schizophrenic than nonschizophrenic patients relapsed, but age, length of hospitalization, number of previous hospitalizations, marital status, education, and income did not predict relapse. There was a suggestion that relapsed schizophrenic patients may be characterized before hospital discharge by hyperactivity, undermedication or drug noncompliance, and fewer social skills.
Abstract IA15: Rarer, yet both interesting and relevant: Other ovarian cancers.
Authors: David G. Huntsman
Journal: Clinical Cancer Research (2016)

Abstract Although high grade serous ovarian carcinoma is justifiably the focus of most research and clinical attention, other histotypes represent significant clinical challenges. An overview of advances in our understanding of germ cell, sex cord-stromal and non-serous cancers will be presented. Specific attention will be placed on granulosa cell tumor and small cell hypercalcemic ovarian cancer where molecular features have both redefined those diseases and offered hope for more rational treatment plans. Citation Format: David G. Huntsman. Rarer, yet both interesting and relevant: Other ovarian cancers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA15.
GENO-03PROGNOSTIC SIGNIFICANCE OF GENETIC ALTERATIONS FROM COMPREHENSIVE ANALYSIS IN LOWER-GRADE GLIOMAS
Authors: Kosuke Aoki, Hiromichi Suzuki, Hideo Nakamura, Kazuya Motomura, Fumiharu Ohka, Masahiro Mizoguchi, Yasutomo Momii, Yoshihiro Muragaki, Reiko Watanabe, Ichiro Ito, Satoru Miyano, Toshihiko Wakabayashi, Seishi Ogawa, Atsushi Natsume
Journal: Neuro-Oncology (2015)

BACKGROUND: Lower-grade gliomas (WHO grade II and III gliomas, including astrocytomas, oligodendrogliomas, and oligoastrocytomas) are usually less aggressive but infiltrative neoplasms, and the optimal treatment is still controversial. Studies have confirmed that lower-grade gliomas could be classified into three genetic subtypes based on IDH1/2 mutation and 1p/19q co-deletion: Type-I tumors (IDH1/2 mutated tumor with 1p/19q co-deletion), Type-II tumors (IDH1/2 mutated tumor without 1p/19q co-deletion) and Type-III tumors (IDH1/2 wild-type tumor). We sought to delineate subtype-specific prognostic values of genetic alterations. METHODS: We analyzed genetic alterations detected by exome/targeted sequencing as well as SNP-array karyotyping obtained from clinically well-annotated 700 cases with lower-grade gliomas. We performed univariate and multivariate Cox hazard proportional analyses for overall survival; multivariate models were adjusted for age ≥ 60, sex, histologic subtype, WHO grade, cohorts (Japan or The Cancer Genome Atlas) and extent of resection. RESULTS: In multivariate Cox regression model, we revealed that several genetic alterations had subtype-specific prognostic significance: chromosome 13q deletion and NOTCH1 mutation in Type-I tumors, CDK4 focal amplification, PIK3R1 mutation, chromosome 20p amplification, and chromosome 9p deletion in Type-II tumors, and chromosome 7p amplification and CDKN2A/2B homozygous deletion in Type-III tumors. High risk group which consisted of patients with at least one of these genetic alterations showed poorer prognosis than low risk group which consisted of patients without them in all genetic subtypes; Hazard Ratio (95% Confidence Interval): 2.88(1.60-5.17), 3.01(1.86-4.86) and 2.40(1.40-4.12) in Type I-III tumors respectively. Most of these mutations and focal copy number variations are components of three major signaling pathways frequently affected in glioblastomas, suggesting deregulation of these pathways is a core requirement of tumor malignancy in lower-grade gliomas. CONCLUSIONS: Several genetic alterations had subtype-specific prognostic significance in lower-grade gliomas and classification based on these genetic alteration would improve patient management.
The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation–Positive Non–Small Cell Lung Cancer: Status in 2016
Authors: Daniel S.W. Tan, Sue S. Yom, Ming S. Tsao, Harvey I. Pass, Karen Kelly, Nir Peled, Rex C. Yung, Ignacio I. Wistuba, Yasushi Yatabe, Michael Unger, Philip C. Mack, Murry W. Wynes, Tetsuya Mitsudomi, Walter Weder, David Yankelevitz, Roy S. Herbst, David R. Gandara, David P. Carbone, Paul A. Bunn, Tony S.K. Mok, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2016)
Standardized Best Practices and Individual Craft-Based Medicine
Authors: Lara Goitein, Brent James
Journal: JAMA Internal Medicine (2016)

Standardization of medical care through protocols, order sets, and other tools is increasingly a part of efforts to improve quality. The authors, a physician beginning a new position as director of a community hospital quality program and the chief quality officer of a health care system and director of a course in health care delivery improvement, discuss the benefits and risks of standardization in health care. Recommendations for responsible standardization are presented.
Pharmacotherapy of four men with paruresis
Authors: J A Hatterer, J M Gorman, A J Fyer, R B Campeas, F R Schneier, E Hollander, L A Papp, M R Liebowitz
Journal: American Journal of Psychiatry (1990)

Four men with paruresis received trials of atenolol or phenelzine or both. Atenolol was effective in one patient. Three patients had a poor response to phenelzine, and they all experienced troublesome side effects.
Treatment of stage I Wilms' tumor.
Authors: D M Green
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.6.1530 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7751904 Treatment of stage I Wilms' tumor. D M GreenxD M GreenSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.6.1530 PDF "Treatment of stage I Wilms' tumor.." Journal of Clinical Oncology, 13(6), p. 1530© 1995 by American Society of Clinical Oncology
A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa
Journal: New England Journal of Medicine (2015)

In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast.We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies.A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies.In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).
A Comparative Analysis of Molar Sodium Lactate and Other Agents in the Treatment of Induced Hyperkalemia in Nephrectomized Dogs
Authors: SIDNEY GREENSTEIN, WARREN P. GOLDBURGH, SANTIAGO V. GUZMAN, SAMUEL BELLET
Journal: Circulation Research (1960)

Molar sodium lactate, sodium bicarbonate, sodium chloride, glucose insulin, and calcium chloride were used in the treatment of induced hyperkalemia in nephrectomized dogs. The effect of these agents on the electrocardiogram and on potassium partition was studied. Molar sodium lactate appeared to be the agent of choice in the treatment of the hyperkalemic state under these experimental conditions.
Tumor-Damaging Capacity of Plant Materials. III. Plants Used as Pesticides
Authors: Morris Belkin, Dorothea B. Fitzgerald
Journal: JNCI Journal of the National Cancer Institute (1953)

Journal Article Tumor-Damaging Capacity of Plant Materials. III. Plants Used as Pesticides Get access Morris Belkin, Morris Belkin Search for other works by this author on: Oxford Academic PubMed Google Scholar Dorothea B. Fitzgerald Dorothea B. Fitzgerald Laboratory of Chemical Pharmacology, National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 4, February 1953, Pages 889–893, https://doi.org/10.1093/jnci/13.4.889 Published: 01 February 1953 Article history Received: 30 September 1952 Published: 01 February 1953
Decision-Making For Patients With Resectable Breast Cancer: Individualized Decisions For and By Patients and Their Physicians
Authors: Charles L. Loprinzi, Peter M. Ravdin
Journal: Journal of the National Comprehensive Cancer Network (2003)

Decisions regarding the use of adjuvant cytotoxic and hormonal therapies for women with breast cancer ideally should be made jointly by the patient and oncologist. For patients to be adequately involved in this decision-making process, they must be provided with appropriate education regarding the potential benefits and risks of adjuvant therapies. The recommended steps for doing this are: 1) understand baseline prognosis with locoregional therapy (surgery, radiation, or both) alone for the individual patient at hand; 2) determine the estimated benefit afforded by adjuvant therapy options for the individual patient; 3) estimate the risk of side effects of adjuvant therapy options; 4) convey the above information to the individual patient; 5) facilitate the individual patient's decision regarding adjuvant systemic therapy; and 6) support the patient's decision. Two computer-based tools (Numeracy and Adjuvant!) are available to facilitate this process.
DNA End Resection: Facts and Mechanisms
Authors: Ting Liu, Jun Huang
Journal: Genomics Proteomics & Bioinformatics (2016)

Abstract DNA double-strand breaks (DSBs), which arise following exposure to a number of endogenous and exogenous agents, can be repaired by either the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways in eukaryotic cells. A vital step in HR repair is DNA end resection, which generates a long 3′ single-stranded DNA (ssDNA) tail that can invade the homologous DNA strand. The generation of 3′ ssDNA is not only essential for HR repair, but also promotes activation of the ataxia telangiectasia and Rad3-related protein (ATR). Multiple factors, including the MRN/X complex, C-terminal-binding protein interacting protein (CtIP)/Sae2, exonuclease 1 (EXO1), Bloom syndrome protein (BLM)/Sgs1, DNA2 nuclease/helicase, and several chromatin remodelers, cooperate to complete the process of end resection. Here we review the basic machinery involved in DNA end resection in eukaryotic cells.