tbuckley/cabot-search huggingface dataset:
ETIOLOGY OF YELLOW FEVER
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1919)

By injecting into guinea pigs the blood of yellow fever cases occurring in Guayaquil a group of symptoms and lesions closely resembling those observed in human yellow fever were induced in a limited number of instances. Of 74 guinea pigs inoculated with specimens of blood from 27 cases of yellow fever, 8, representing 6 cases, came down with the symptoms; namely, a marked rise of temperature after a period of incubation averaging 3 to 6 days, with simultaneous suffusion of the capillaries, particularly of the conjunctivaes and soles, then preliminary hyperleucocytosis followed by progressive leucopenia, the early appearance of albumin and casts in the urine, which gradually diminishes in volume as the disease progresses. The fever lasts only a few days, rapidly dropping first to the normal and then usually to subnormal. At this period jaundice manifests itself in varying degrees of intensity, first in the scleras, then in the skin and the urine. Hemorrhages from the nasal or gingival mucosa or anus have been observed to occur during this period. Autopsies reveal deep jaundice throughout the entire tissue. The liver is fatty and yellow, the kidney hyperemic, and often swollen and hemorrhagic. Hemorrhagic spots were almost always found in the lungs and gastrointestinal mucosa. Guinea pigs are usually rather sensitive to the infection, though many appeared to be somewhat resistant and some even refractory. The injection of the yellow fever blood into ringtail monkeys, rabbits, cats, guatusas, weasels, and sloths among the mammalians, and pigeons, ground-doves, bluebirds, mantas, blackbirds, parrakeets, reedbirds, blancos, and toucans among the birds, gave negative results. In the blood, liver, and kidneys of the guinea pigs experimentally infected with the blood of yellow fever patients a minute organism was demonstrated which closely resembles in morphology the causative agent of infectious jaundice (Leptospira icterohamorrhagiae). The leptospira transmitted from yellow fever cases to guinea pigs was found to induce similar symptoms and lesions upon further passage into normal guinea pigs. The leptospira obtained from cases of yellow fever has been givern the provisional name of Leptospira icteroides.
Pilot Study with Lenalidomide in Patients with POEMS Syndrome
Authors: Andrea Nozza, Fabrizia Terenghi, Rita Mazza, Eduardo Nobile Orazio, Fausto Adami, Giampaolo Merlini, Chiara Briani, Giovanni Palladini, Mariella Grasso, Sara Gandolfi, Carmelo Carlo-Stella, Armando Santoro
Journal: Blood (2011)
Characterization of IMiDs (Immunomodulating Agents) Induced “Flare Reaction” in Patients with Chronic Lymphocytic Leukemia (CLL) and Correlation with Changes in Serum Cytokine Levels.
Authors: Laurie DiMiceli, Kena C. Miller, Michael Rickert, Paul Wallace, Patricia Marshall, Dawn DePaolo, Swaminathan Padmanabhan, Beverly Landrigan, Asher A. Chanan-Khan
Journal: Blood (2005)
IL1RL1 Variants rs1041973 and rs873022 are Associated With Allergy Markers and Soluble ST2 Production in a Brazilian Population
Authors: Gerson Almeida Queiroz, Ryan Santos Costa, Valdirene Leao Carneiro, Talita Santos Jesus, Neuza Maria Alcântara-Neves, Anaque Oliveira Pires, Héllen Freitas Fonseca, Mauricio Lima Barreto, Camila Alexandrina Figueiredo
Journal: Journal of Allergy and Clinical Immunology (2017)
Results of a Clinical Study of Pevonedistat (Pev), a First-in-Class NEDD8-Activating Enzyme (NAE) Inhibitor, Combined with Azacitidine (Aza) in Older Patients (Pts) with Acute Myeloid Leukemia (AML)
Authors: Ronan T Swords, Steven Coutre, Michael B. Maris, Joshua F. Zeidner, James M. Foran, Jose C. Cruz, Harry P. Erba, Jesus G. Berdeja, Wayne Tam, Saran Vardhanabhuti, Iwona Dobler, Hélène M. Faessel, Ajeeta B. Dash, Farhad Sedarati, Bruce J. Dezube, Michael R. Savona
Journal: Blood (2016)
Final results of weekly paclitaxel and carboplatin plus bevacizumab as first-line treatment of triple-negative breast cancer. A multicenter phase I-II trial by the Hellenic Oncology Research Group
Authors: M. Nikolaou, E. Saloustros, A. Polyzos, C. Christophyllakis, N. Kentepozidis, L. Vamvakas, K. Kalbakis, S. Agelaki, V. Georgoulias, D. Mavroudis
Journal: Annals of Oncology (2016)
32P Heterogeneity analysis of DW MRI as a biomarker for prediction of overall survival and 6 month PFS in GBM patients
Authors: D. Beigi, A. Fathi Kazerooni, M. Safari, A. Ameri, B. Moini, M. Shojaee Moghdam, H. Salighehrad
Journal: Annals of Oncology (2016)
Randomized phase II study of gemcitabine (G), cisplatin (C) with or without veliparib (V) (arms A, B) and a phase II single-arm study of single-agent veliparib (arm C) in patients with <i>BRCA or PALB2</i>-mutated pancreas adenocarcinoma (PC).
Authors: Eileen Mary O'Reilly, Maeve Aine Lowery, Kenneth H. Yu, Marinela Capanu, Zsofia Kinga Stadler, Andrew S. Epstein, Talia Golan, Amiel Segal, Michal Segal, Erin E. Salo-Mullen, Laura H. Tang, Ellen Hollywood, Mary Ellen Moynahan, Kinh G Do, Malcolm J. Moore, Hedy Lee Kindler, Robert J. Mayer, Alice P. Chen, David Paul Kelsen
Journal: Journal of Clinical Oncology (2013)

TPS4144 Background: Germline mutations in BRCA1, 2 predispose to PC (Lal, G. Cancer Res, 2000). 5-8% PC have BRCA 1,2 mutations; higher in Ashkenazi Jewish (10-15%). Pre-clinical data demonstrates that platinums and poly-ADP ribose polymerase inhibitors (PARPi) have activity in BRCA-mutated PC models. Early clinical data supporting (Lowery, M. Oncol, 2011). We are evaluating the role of platinum agents and PARPi, veliparib (ABT-888), in BRCA or PALB2-mutated PC. Methods: Arm A, B: Includes non-randomized phase to optimize V dose combined with G, C (Arm A). Subsequently randomized phase II study will evaluate G, C +/- V. Primary endpoint: RECIST 1.1 response rate (RR) G, C, V (Arm A) and G, C (Arm B). Secondary endpoints: Progression-free survival, safety, disease-control rate, overall survival and correlatives involving pre, post biopsies to evaluate mechanisms of sensitivity, resistance to platinums, PARPi. Arm C: Evaluates single-agent V in previously-treated PC. Primary and secondary endpoints similar. Eligibility: BRCA, PALB2-mutated, measurable, stage III/IV PC; Untreated (Arm A, B), ≤ 2 lines therapy (Arm C); ECOG 0-1 (Arm A, B), ECOG 0-2 (Arm C). Treatment Plan: Arm A, B: V PO BID d1-12 (Arm A), q 3 weeks, G 600mg/m 2 IV, C 25mg/m 2 IV, both d3, 10, q 3 weeks (Arm A, B). Arm C: V 400mg PO BID d1-28 q 4 weeks. Biostatistics: Arms A, B: Simon’s 2-stage minimax design per arm. Unacceptable RR 10%, promising 30%, type I, II errors 10%. N= 16 stage I, +N= 9 (stage II). If ≥ 5/25, then promising. If both arms promising, option to add N= 10, allows distinction between RR 20% and 40%, 83% power. Arm C: Simon’s 2-stage, single-arm, uninteresting RR 10%, promising if ≥ 28%. N= 15 stage I, +N= 18 (stage II). Promising RR ≥ 6/33. Total N 47- 95. Contingency for slow accrual. Progress to Date: Accrual: Arm A (non-randomized): 13 screened, N= 5 enrolled. Arm C: 9 screened, N= 4 enrolled. Israeli, Canadian, other U.S. sites opening 2013. Funding and acknowledgements: National Cancer Institute, Lustgarten Foundation. NCT01585805. Clinical trial information: NCT01585805.
Role Of Hormone Signaling In Eosinophilic Esophagitis: 17-Beta Estradiol Attenuation Of IL-13 Induced Barrier Dysfunction In Esophageal Epithelium
Authors: Justin C. Wheeler, David Wu, Marc E. Rothenberg, Vincent A. Mukkada, Simon P. Hogan
Journal: Journal of Allergy and Clinical Immunology (2017)
Phase I trial of bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines
Authors: K. Possinger, W. Schippinger, P. Kiewe, W. Lange, J. Preiss, N. Niederle, P. Brossart, J. Papke, W. Freier, H. van de Velde, P. Schmid
Journal: Journal of Clinical Oncology (2005)

755 Background: The ubiquitin-proteasome pathway plays an essential role in intracellular degradation of key regulatory proteins that can affect cell cycle, angiogenesis, adhesion and apoptosis. Bortezomib (VELCADE, PS-341) is a first-in class selective inhibitor of the 26S proteasome. The oral fluoropyrimidine capecitabine (Xeloda) has shown substantial activity in taxane and/or anthracycline pretreated patients with metastatic breast cancer. This phase I trial was initiated to determine the maximum tolerated doses (MTD), efficacy and tolerability of combined treatment with capecitabine and bortezomib in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines. Methods: Patients were treated with bortezomib (1.0–1.3 mg/m2; days 1, 4, 8 & 11) and capecitabine (1500–2500 mg/m2, days 1–14) in 3-weeks intervals. Dose limiting toxicity (DLT) was defined as grade (G) 4 platelets, any G platelets with bleeding, G4 ANC >4 days, febrile neutropenia, any >G2 non-hematologic toxicity except alopecia, nausea or emesis, or any ≥ G2 toxicity persisting over day 35. Results: To date, 13 patients (median age 58 years; median number of metastatic sites 3; visceral metastases 85%; prior anthracycline therapy 100%; prior taxane therapy 85%) have been enrolled at 3 different dose levels (1.0 & 1500 (n=3), 1.0 & 2000 (n=6), 1.3 & 2000 (n=4)). Dose-limiting mucositis occurred in 1 patient at dose level 2. No further DLT has been reported so far, and the MTD has not been reached. Hematologic and non-hematological toxicities were generally mild to moderate. No grade 4 toxicity has occurred so far. To date, grade 3 toxicity has only been reported with mucositis in 1 patient. Most common side effects were myelosuppression, nausea, mucositis and asthenia. Preliminary data indicate efficacy in anthracycline and taxane pretreated patients Conclusions: Combination of 1 mg/m2 bortezomib in combination with 1500 mg/m2 and 2000 mg/m2 has been well tolerated. Enrollment is ongoing at the 1.3 & 2000 dose level. Updated data will presented at the meeting. Preliminary data suggest good tolerability of the combination. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Pharmaceutical Research & Development, Millennium Johnson & Johnson Pharmaceutical Research & Development, Millennium Johnson & Johnson Pharmaceutical Research & Development, Roche
Wnt3/RhoA/ROCK Signaling Pathway Is Involved in VLA6-Dependent Adhesion-Mediated Drug Resistance of Multiple Myeloma.
Authors: Masayoshi Kobune, Yutaka Kawano, Rishu Takimoto, Takuya Matsunaga, Junji Kato, Hirofumi Hamada, Yoshiro Niitsu
Journal: Blood (2007)
Oxaliplatin Induced Immune Thrombocytopenia in Patients with Oxaliplatin Hypersensitivity: Implications for Desensitization
Authors: Katherine Larabee Tuttle, Marlene Garcia-Neuer, Nathan T. Connell, David I. Hong, Mariana C. Castells, Paige G. Wickner
Journal: Journal of Allergy and Clinical Immunology (2017)
Quality Evaluation of Allergen Immunotherapy Guidelines Worldwide Using AGREE-II
Authors: Desiree E.S. Larenas Linnemann, Dario Antolin-Amerigo, Alla Nakonechna, Ignacio Davila-Gonzalez, Maximiliano Gomez, Michael Levin, Claudio Parisi, Jose Antonio Ortega Martell, Jorge A. Luna-Pech, Bettina Wedi, Ludger Klimek, Nelson A. Rosario, Oliver Pfaar
Journal: Journal of Allergy and Clinical Immunology (2017)
Characterization of hunter-gatherer networks and implications for cumulative culture
Authors: A. B. Migliano, A. E. Page, J. Gómez-Gardeñes, G. D. Salali, S. Viguier, M. Dyble, J. Thompson, Nikhill Chaudhary, D. Smith, J. Strods, R. Mace, M. G. Thomas, V. Latora, L. Vinicius
Journal: Nature Human Behaviour (2017)
151O Preclinical characterization of alofanib, a novel allosteric FGFR2 inhibitor
Authors: H. Tsimafeyeu, E. Stepanova, D. Khochenkov, G. Murillo, N. Lapina, E. Gavrilova, M. Byakhov, S. Tjulandin
Journal: Annals of Oncology (2016)
Hemostasis in Newly Diagnosed Multiple Myeloma Patients before and after Induction Therapy
Authors: Evdokia S. Urnova, Larisa P. Mendeleeva, Olga S. Pokrovskaya, Marina A. Gracheva, Eduard G. Gemdzhian, Larisa A. Kuzmina, Ivan D. Tarandovsky, Maiia V. Firsova, Mariya V. Nareiko, Elena A. Seregina, Anna N. Balandina, Fazoil I. Ataullakhanov, Sergei A. Vasil'ev, Valeri G. Savchenko
Journal: Blood (2015)
Potential consequences of the immigration ban on the scientific community
Authors: Hossein Ardehali
Journal: Journal of Clinical Investigation (2017)

On January 27, 2017, President Trump signed an executive order banning the citizens of 7 countries from obtaining US entry visas for the next 90 days. Since the announcement, the news media have devoted a large portion of their coverage to the ban and its political ramifications. There have been arguments made by both sides that the ban will make our country safer, while others have argued that this executive order will result in the weakening of our country and bolstering of our enemies. As a physician-scientist who was born in Iran and immigrated to the US, I will stay away from the politics of this executive order; rather, I want to discuss the impact of the immigration ban on scientific discourse, education, and research programs, and how it may influence the dissemination of knowledge to physicians and scientists in low- and middle-income countries. I will use my own experience as an example of how the educational and scientific systems in this country benefit those who strive to learn in a free and intellectually stimulating environment.
Determination of IDH1 Mutational Burden and Clearance Via Next-Generation Sequencing in Patients with IDH1 Mutation-Positive Hematologic Malignancies Receiving AG-120, a First-in-Class Inhibitor of Mutant IDH1
Authors: Courtney D DiNardo, Stéphane de Botton, Eytan M Stein, Gail J. Roboz, Ronan T Swords, Daniel A Pollyea, Amir T. Fathi, Robert Collins, Jessica K Altman, Ian W. Flinn, Gabriel N Mannis, Alice S. Mims, James M. Foran, Arnaud Pigneux, Gabrielle T Prince, Geoffrey L Uy, Martin S. Tallman, Hagop M. Kantarjian, Hua Liu, Eyal C Attar, Jennifer Sacolick, Katharine Yen, Jonathan B Hurov, Sung Choe, Bin Wu, Richard M. Stone
Journal: Blood (2016)
Elevated pretreatment serum activin A and progression-free and overall survival in trastuzumab-treated metastatic breast cancer.
Authors: Lindsey Zubritsky, Kim Leitzel, Suhail M. Ali, Wolfgang Köstler, Eva-Maria Fuchs, Luis Costa, Robert D. Knight, Abderrahmane Laadem, Matthew L. Sherman, Allan Lipton
Journal: Journal of Clinical Oncology (2012)

38 Background: About half of HER2-positive metastatic breast cancer patients will respond tofirst-line trastuzumab-containing therapy, but most will progress within a year. Trastuzumab resistance remains a vexing clinical problem, and better predictive and prognostic biomarkers are needed. Activin A is a TGF-B superfamily member and regulates cell proliferation, apoptosis, differentiation, and immune response. Methods: Serum activin A was measured using ELISA (R&amp;D Systems, Minneapolis, MN) in 60 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) serum activin A analyses. Results: Pretreatment serum activin A levels averaged 2376 pg/ml, and had a median of 629 pg/ml and 25 th and 75 th quartile values of 406 and 1791 pg/ml, respectively. Patients who were hormone receptor negative had significantly higher activin A levels (median 1287 vs 450 pg/ml, p=0.002). Higher serum activin A was significant on a continuous basis for predicting reduced PFS to first-line trastuzumab-containing therapy (p&lt;0.003), and for predicting shorter OS (p&lt;0.0001). When analyzed using a dichotomous (median) cutpoint, the elevated serum activin A cohort had a significantly reduced PFS (HR 2.79, p &lt;0. 002) (median 6.6 mo vs. 31.1 mo) and OS (HR 5.24, p &lt;0.0001) (median 19.6 mo vs. median not reached). In multivariate analysis for PFS with other covariates (age, line of therapy, CA 15-3, and hormone receptor status), activin A was the only significant covariate (p=0.021). In multivariate analysis for OS, activin A (p=0.002) and CA 15-3 (p=0.03) remained significant as prognostic factors. Conclusions: Elevated pretreatment serum activin A predicts reduced PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Activin A deserves further study as an adverse biomarker, and to select patients most likely to respond to activin A-targeted therapy.
Bendamustine Is Highly Effective for Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphoma (B-NHL) and Mantle Cell Lymphoma (MCL): Final Results of a Japanese Multicenter Phase II Study.
Authors: Michinori Ogura, Toshiki Uchida, Kiyoshi Ando, Ken Ohmachi, Kuniaki Itoh, Nobuko Kubota, Kenichi Ishizawa, Joji Yamamoto, Takashi Watanabe, Naokuni Uike, IIseung Choi, Yasuhito Terui, Kensuke Usuki, Hirokazu Nagai, Nobuhiko Uoshima, Kensei Tobinai
Journal: Blood (2009)
Costs associated with chemotherapy-related complications in the treatment of metastatic breast cancer in a real-world setting.
Authors: A. Guerin, D. Lalla, D. Latremouille-Viau, A. P. Yu, E. Q. Wu, M. Brammer, S. A. Hurvitz
Journal: Journal of Clinical Oncology (2011)

602 Background: The objective of this retrospective study was to estimate the incremental medical costs of chemotherapy-related complications in patients with metastatic breast cancer (mBC). Methods: The PharMetrics Integrated Database (2004-2009) was used to identify mBC patients treated with a given regimen for ≥30 days (i.e., an episode of treatment). Selected treatment regimens contained agents commonly used to treat mBC such as trastuzumab, lapatinib, paclitaxel, and docetaxel. The regimen was established reviewing medical and pharmacy claims within 4 weeks after the episode start. An episode start was the first date of the agent(s) and continued until an episode ending event defined as 1) a discontinuation (i.e., gap ≥45 days) of therapy, or 2) a partial change in an existing regimen (e.g., addition/removal of one agent), or 3) the complete replacement of a regimen (switch of therapy). Costs incurred during episodes of treatment during which patients received a diagnosis for anemia, leukopenia, infections, and neutropenia were compared to costs incurred during episodes of treatment without a diagnosis for the complication. Incremental costs and p-values associated with each complication were estimated using regression models adjusted for demographics, resource use, cancer treatments, and comorbidities. Results: 1,551 women (mean age=57 ± 12) representing 3157 episodes of treatment were selected. Incremental monthly total costs were estimated at $3,201 for anemia, $2,605 for infections, $3,718 for leukopenia, and $3,453 for neutropenia. Conclusions: Chemotherapy-related complications in mBC patients are associated with a substantial economic burden. Therapies decreasing the frequency and severity of these complications can impact clinical and economic outcomes. Complication (No. of episodes of treatment with complication) Adjusted monthly incremental costs: Episodes with vs. without complication (2009 USD) Anemia (N=1600) Infection (N=606) Leukopenia (N=782) Neutropenia (N=551) Cost components Pharmacy 2,412* -54 3,233* 2,584* Inpatient admission 747* 2,334* 657* 1,003* Emergency department 26 106* −8 6 Outpatient 114* 212* 45 26 Total costs 3,201* 2,605* 3,718* 3,453* * P < 0.05.
STMC-27. NOVEL LYSINE DEMETHYLASE KDM1A INHIBITORS INDUCE DIFFERENTIATION AND APOPTOSIS OF GLIOMA STEM CELLS VIA UNFOLDED PROTEIN RESPONSE PATHWAY
Authors: Gangadhara Reddy Sareddy, Suryavathi Viswanadhapalli, Prathibha Surapaneni, Takayoshi Suzuki, Andrew Brenner, Ratna Vadlamudi
Journal: Neuro-Oncology (2016)

Glioma Stem Cells (GSCs) play a central role in glioblastoma (GBM) development and chemo/radiation resistance, and their elimination is critical for the development of efficient therapeutic strategies. Recently, we demonstrated that lysine-specific histone demethylase 1A (KDM1A/LSD1) is overexpressed in GBM. In the present study, we determined whether KDM1A modulates GSCs stemness and differentiation and tested the utility of two novel KDM1A specific inhibitors (NCL-1 and NCD-38) to promote differentiation and apoptosis of GSCs. The efficacy of KDM1A targeting drugs was tested on purified GSCs isolated from established and patient-derived GBMs using both in vitro assays and in vivo orthotopic preclinical models. Our results suggested that KDM1A is highly expressed in GSCs and knock down of KDM1A using shRNA reduced GSCs stemness and induced the differentiation. Pharmacological inhibition of KDM1A using NCL-1 and NCD-38 significantly reduced the proliferation, neurosphere formation and induced apoptosis of GSCs with little effect on differentiated cells and KDM1A-knockout cells. In preclinical studies using orthotopic models, NCL-1 and NCD-38 significantly reduced GSC-driven tumor progression and improved mice survival. RNA sequencing analysis showed that KDM1A inhibitors modulate several pathways related to stemness, differentiation and apoptosis. Mechanistic studies showed that KDM1A inhibition induced activation of the unfolded protein response (UPR) pathway. Western blot analysis demonstrated increased expression of BiP, cleaved ATF-6, p-PERK and CHOP. Further immunohistochemical analysis demonstrated increase in expression of UPR components in tumor sections. Chromatin immunoprecipitation assays revealed significant enrichment of H3K4-me2 at the promoters of the UPR genes ATF3 and DDIT3 in GSC following treatment with KDM1A inhibitors. More importantly, in vivo studies demonstrated that KDM1A inhibitors NCL-1 and NCD-38 are safe without any significant toxicity. These results strongly suggest that selective targeting of KDM1A using NCL-1 and NCD-38 is a promising therapeutic strategy for elimination of GSCs.