tbuckley/cabot-search huggingface dataset:
The potential effect of improved provision of rabies post-exposure prophylaxis in Gavi-eligible countries: a modelling study
Authors: Katie Hampson, Francesco Ventura, Rachel Steenson, Rebecca Mancy, Caroline Trotter, Laura Cooper, Bernadette Abela-Ridder, Lea Knopf, Moniek Ringenier, Tenzin Tenzin, Sowath Ly, Arnaud Tarantola, Ronelngar Moyengar, Assandi Oussiguéré, Bassirou Bonfoh, DH Ashwath Narayana, Mysore Kalappa Sudarshan, Matthew Muturi, Athman Mwatondo, Gati Wambura, Soa Fy Andriamandimby, Laurence Baril, Glenn T Edosoa, Abdallah Traoré, Sarah Jayme, Johann Kotzé, Amila Gunesekera, Nakul Chitnis, Jan Hattendorf, Mirjam Laager, Monique Lechenne, Jakob Zinsstag, Joel Changalucha, Zac Mtema, Ahmed Lugelo, Kennedy Lushasi, Onphirul Yurachai, Charlotte Jessica E. Metcalf, Malavika Rajeev, Jesse Blanton, Galileu Barbosa Costa, Nandini Sreenivasan, Ryan Wallace, Deborah Briggs, Louise Taylor, Samuel M. Thumbi, Nguyen Thi Thanh Huong
Journal: The Lancet Infectious Diseases (2018)

Tens of thousands of people die from dog-mediated rabies annually. Deaths can be prevented through post-exposure prophylaxis for people who have been bitten, and the disease eliminated through dog vaccination. Current post-exposure prophylaxis use saves many lives, but availability remains poor in many rabies-endemic countries due to high costs, poor access, and supply.
Abstract 73: Changes in AMSA During Controlled Coronary Perfusion by Extracorporeal Circulation in a Swine Model of Ventricular Fibrillation
Authors: Vesna Borovnik-Lesjak, Kasen Whitehouse, Alvin Baetiong, Jeejabai Radhakrishnan, Christopher L Kaufman, Raúl J Gazmuri
Journal: Circulation (2013)

Background: Previous VF studies in rats showed that 6 min of CPR was needed before an electrical shock could be successful in reestablishing cardiac activity. During this interval the amplitude spectral area (AMSA) - a method of VF waveform analysis - progressively rose reaching a plateau within the same interval required for enabling successful defibrillation. No previous studies have examined AMSA continuously using a model of tightly controlled CPR. Methods: VF was induced and left untreated for 8 min in 16 swine after which extracorporeal circulation (ECC) was maintained for 10 min adjusting its flow to generate a coronary perfusion pressure of 10 mmHg. AMSA was calculated from the VF signal in the frequency domain within 2-48 Hz and analyzed continuously with a 2.1 s timeframe and a Tukey window that moved ahead every 0.5 s. Results: AMSA progressively declined during untreated VF. During ECC, AMSA rose from 6.8±1.9 to 12.4±4.1 mV*Hz (p&lt;0.001). The increase occurred early during ECC and plateaued after 4 to 6 minutes (Figure). Individual experiments showed distinct and varying AMSA patterns during ECC. The average peak AMSA was reached 368 ± 127 s after the start of ECC. Conclusion: The time course of AMSA varied among animals suggesting variability in the time required for the myocardium to reach the optimal conditions for successful defibrillation and highlights the value of continuous monitoring of AMSA during CPR.
Nipple and areola lesions: Dermoscopy and reflectance confocal microscopy features
Authors: Elisa Cinotti, Danila Galluccio, Marco Ardigò, Salvador Gonzalez, Ausila Maria Manganoni, Marina Venturini, Paolo Broganelli, Simone Ribero, Francesca Farnetani, Victor Desmond Mandel, Giovanni Pellacani, Linda Tognetti, Francesco Lacarrubba, Pascale Guitera, Ignazio Stanganelli, Iris Zalaudek, Edith Johanna Arzberger, Philippe Bahadoran, Caterina Longo, Giuseppe Spataro, Jean-Luc Perrot, Pietro Rubegni
Journal: Journal of the American Academy of Dermatology (2018)
CHARACTERIZATION OF HUMAN MONOCLONAL ANTI-BET-V-I ANTIBODIES WHICH AFFECT THE HUMAN IGE-BINDING TO BET-V-I
Authors: S Lebecque, C Dolecek, S Denepoux, J J Pin, V Visco, D Kraft, R Valenta, J Banchereau
Journal: Journal of Allergy and Clinical Immunology (1995)
Mutation landscape in patients with myelofibrosis receiving ruxolitinib or hydroxyurea
Authors: Annalisa Pacilli, Giada Rotunno, Carmela Mannarelli, Tiziana Fanelli, Alessandro Pancrazzi, Elisa Contini, Francesco Mannelli, Francesca Gesullo, Niccolò Bartalucci, Giuditta Corbizi Fattori, Chiara Paoli, Alessandro M. Vannucchi, Paola Guglielmelli
Journal: Blood Cancer Journal (2018)

Abstract Refractoriness to ruxolitinib in patients with myelofibrosis (MF) was associated with clonal evolution; however, whether genetic instability is promoted by ruxolitinib remains unsettled. We evaluated the mutation landscape in 71 MF patients receiving ruxolitinib ( n = 46) and hydroxyurea ( n = 25) and correlated with response. A spleen volume response (SVR) was obtained in 57% and 12%, respectively. Highly heterogenous patterns of mutation acquisition/loss and/or changes of variant allele frequency (VAF) were observed in the 2 patient groups without remarkable differences. In patients receiving ruxolitinib, driver mutation type and high-molecular risk profile (HMR) at baseline did not impact on response rate, while HMR and sole ASXL1 mutations predicted for SVR loss at 3 years. In patients with SVR, a decrease of ≥ 20% of JAK2 V617F VAF predicted for SVR duration. VAF increase of non-driver mutations and clonal progression at follow-up correlated with SVR loss and treatment discontinuation, and clonal progression also predicted for shorter survival. These data indicate that (i) ruxolitinib does not appreciably promote clonal evolution compared with hydroxyurea, (ii) VAF increase of pre-existing and/or (ii) acquisition of new mutations while on treatment correlated with higher rate of discontinuation and/or death, and (iv) reduction of JAK2 V617F VAF associated with SVR duration.
Characteristics and Outcomes of Patients (pts) with Malignancy-Associated Hemophagocytic Lymphohistiocytosis (M-HLH) in Adults: A Single-Center, Prospective Analysis of 36 Pts
Authors: Rita Assi, Prajwal Boddu, Tapan M. Kadia, Zeev E. Estrov, Guillermo Garcia-Manero, Farhad Ravandi, Elias J. Jabbour, Koichi Takahashi, Marina Y. Konopleva, Michael Andreeff, Abdallah Abou Zahr, Courtney D. DiNardo, Gautam Borthakur, Nitin Jain, Naveen Pemmaraju, Musa E. Yilmaz, Nicholas J Short, Jing Ning, Sherry A. Pierce, William G. Wierda, Jorge E. Cortes, Hagop M. Kantarjian, Naval G. Daver
Journal: Blood (2018)
Biomedical Explanations of Psychopathology and Their Implications for Attitudes and Beliefs About Mental Disorders
Authors: Matthew S. Lebowitz, Paul S. Appelbaum
Journal: Annual Review of Clinical Psychology (2018)

Mental disorders are increasingly conceptualized as biomedical diseases, explained as manifestations of genetic and neurobiological abnormalities. Here, we discuss changes in the dominant explanatory accounts of psychopathology that have occurred over time and the driving forces behind these shifts, lay out some real-world evidence for the increasing ascendancy of biomedical explanations, and provide an overview of the types of attitudes and beliefs that may be affected by them. We examine theoretical and conceptual models that are relevant to understanding how biomedical conceptualizations might affect attitudes and beliefs about mental disorders, and we review some empirical evidence that bears on this question. Finally, we examine possible strategies for combatting potential negative effects of biomedical explanations and discuss important conclusions and directions for future research.
Characterization of chronic myeloid leukemia cell lines with acquired drug resistance to 6-mercaptopurine and imatinib
Authors: Xing-Xiang Peng, Zhi Shi, Xiao-Cong Huang, Gary Kruh, Hsiang-Chun Wu, Smitaben Parmar, Ying Zhou, Ioana Abraham, Zhe-Sheng Chen
Journal: Cancer Research (2007)

2315  The development of refractory disease is often associated with the overexpression of multidrug resistance (MDR) proteins, especially in the hematological malignancies, such as chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and non Hodgkin’s lymphomas (NHL). To investigate the mechanisms of cellular resistance to 6-mercaptopurine (6-MP) and imatinib mesylate, we established a 6-MP resistant cell line, K562-MP5, and an imatinib mesylate resistant cell line K562-imatinib, by step wise selection of the CML cell line K562 cells in drug. Drug sensitivity analysis showed that K562-MP5 cells were about 300-fold resistant to 6-MP and cross-resistant to imatinib mesylate, 6-thioguanine (6-TG) and doxorubicin compared to the parental cells. K562-imatinib cells were about 330-fold resistant to imatinib mesylate and cross-resistant to 6-MP, 6-TG and arabinosylcytosine (AraC) compared to the parental cells. Accumulation of [14C]6-MP in K562-MP5 cells was lower than that in K562 cells, and ATP-dependent efflux of [14C]6-MP in K562-MP5 cells was increased compared to the parental K562 cells. Accumulation of [14C]6-MP in K562-imatinib cells was also lower than that in parental cells and ATP-dependent efflux of [14C]6-MP in K562-imatinib cells was increased compared to the parental cells. Immunoblot analysis demonstrated that both K562-MP5 and K562-imatinib cells overexpressed P- glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter that is able to extrude anticancer drugs out from the cells. However, in the present investigation there were no significant differences in the levels of expression of MRP1, MRP4 and MRP5 in parental K562 cells, K562-MP5 cells and K562-imatinib cells detected by western blotting analysis. These results suggest that overexpression of P-gp is involved in 6-MP and imatinib mesylate resistance in K562 cells. To our knowledge, this is the first report that overexpression of P-gp has been observed in a cell line made resistant to a nucleobase anticancer drug.
Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Salivary Duct Carcinoma
Authors: Hideaki Takahashi, Yuichiro Tada, Takashi Saotome, Kohei Akazawa, Hiroya Ojiri, Chihiro Fushimi, Tatsuo Masubuchi, Takashi Matsuki, Kaori Tani, Robert Y. Osamura, Hideaki Hirai, Shuhei Yamada, Daisuke Kawakita, Kouki Miura, Shin-etsu Kamata, Toshitaka Nagao
Journal: Journal of Clinical Oncology (2018)

Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease's rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2-positive SDC.This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437).Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred.Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2-positive SDC, with a manageable toxicity profile.
Atypical Immunophenotype Predicts Worse Prognosis in Adult T-Cell Lymphoma/Leukemia: A Retrospective Study of 63 Caribbean Patients at a New York City Tertiary Center
Authors: Bachar Samra, Edwin Chiu, Bo Lin, Eric Tam, Babak Baseri, Iuliana Shapira, Jason Gonsky, Robert David Lewis, Gurinder Sidhu, Ahmed Sawas, Evelyn O. Taiwo
Journal: Blood (2018)
Left Ventricular Scar and Prognosis in Chronic Chagas Cardiomyopathy
Authors: Gustavo J. Volpe, Henrique T. Moreira, Henrique S. Trad, Katherine C. Wu, Maria Fernanda Braggion-Santos, Marcel K. Santos, Benedito C. Maciel, Antonio Pazin-Filho, José Antonio Marin-Neto, João A.C. Lima, André Schmidt
Journal: Journal of the American College of Cardiology (2018)
Clinical features and outcomes of spitzoid proliferations in children and adolescents
Authors: D.W. Bartenstein, J.M. Fisher, C. Stamoulis, C. Weldon, J.T. Huang, S.E. Gellis, M.G. Liang, B. Schmidt, E.B. Hawryluk
Journal: British Journal of Dermatology (2018)

Spitzoid proliferations range from Spitz naevi to melanomas. There are few studies describing clinical features and outcomes in the paediatric population. To determine the clinical features and outcomes of a large paediatric cohort with histopathologically confirmed Spitz tumours. This was a retrospective cohort study of patients seen at Boston Children's Hospital who were aged < 20 years and had a histopathological diagnosis of spitzoid proliferation from 1 January 1994 to 23 October 2012. In total 595 patients with 622 spitzoid proliferations were identified (median age 7·4 years, interquartile range 4·6–11·7). Overall 512 proliferations (82·3%) were typical, 107 (17·2.%) were atypical and three (0·5%) were melanomas. The median ages at biopsy were 7·4, 7·2 and 17·2 years, respectively, and there was a significant difference in age at biopsy for patients with typical or atypical proliferations vs. melanoma (P < 0·01). Among samples with positive margins (n = 153), 55% (54 of 98) of typical proliferations, 77% (41 of 53) of atypical proliferations and 100% (two of two) of melanomas were re‐excised. Six patients had sentinel lymph node biopsy performed, with three patients demonstrating nodes positive for melanocytic cells. Within a median follow‐up of 4·1 years for the full cohort there were no related deaths. Spitz tumours have strikingly benign outcomes in the paediatric population, although this study is limited by the low number of melanomas and restriction to a single paediatric institution. Aggressive management recommendations should be reconsidered for children and adolescents with banal‐appearing Spitz naevi, based on the clinically indolent behaviour in this cohort.
Incidence of germline BRCA1 and BRCA2 mutations among Filipinos
Authors: F.V.F. Que, D.C. Ang, J.J.L. Andal, M.A. Madrid, R.W. Lo, M.S. Imasa, M.L.D. Enriquez, F.P. Tria Iv, L.K.D. Cabral, R. Dimalibot, R.K. Li
Journal: Annals of Oncology (2018)
Symptoms at diagnosis of (metastatic) pancreatic adenocarcinoma ([m]PAC) in routine practice and frequency variation across Europe
Authors: A. Carrato Mena, D. Melisi, B. Westphalen, Å.B.C. Mellbring, J. Taieb, G. Prager, T. Macarulla Mercadé, N.D. esquermes, A. Ferreras, F. de Jong
Journal: Annals of Oncology (2018)
AB0873 Us rheumatologists have mixed perceptions about managing patients with non-radiographic axial spondyloarthritis and ankylosing spondylitis
Authors: J. Robinson, L. Price
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Non-radiographic axial spondyloarthropathy (nrAxSpA) is a relatively new term used to describe patients who clinically appear to have ankylosing spondylitis (AS) but do not exhibit radiographic sacroilitis. Though several biologics are currently FDA approved for the treatment of AS, there are no agents approved for patients in which there is not radiographic evidence of sacroilitis. With several agents under investigation with the hopes of gaining a line-extension label for nr-axSpA, it is important to understand how the current treating rheumatologists view these two diseases and their current and future plans for spondyloarthropathy management. <h3>Objectives</h3> The study sought to (a) evaluate the differences between AS and nr-axSpA diagnosis and treatment patterns (b) highlight the challenges clinicians face in managing patients with nr-AxSpa and (c) understand rheumatologists' willingness to use biologic agents to treat nr-AxSpa. <h3>Methods</h3> An independent market analytics firm collaborated with US rheumatologists (n=98) to learn about current and anticipated changes to the management of Ankylosing Spondylitis and Non-radiographic Axial Spondylitis. Participants were administered an online survey, lasting approximately 30 min in length and respondents were compensated for their professional time. Following the fieldwork, data were analysed in SPSS, a statistical software, to determine significant differences. <h3>Results</h3> 87% of the surveyed rheumatologists agree that AS and nr-AxSpA are part of a spectrum, and 37% report that they often find it challenging to differentiate between the two conditions. The majority of the respondents report that they treat these conditions in a very similar manner. In fact, 40% agree that distinguishing between the two has no relevance to their treatment decisions. Use of biologics is significantly more pronounced in AS (56% vs. 39%, respectively), largely because there is currently no FDA indicated biologic for nr-AxSpA and because many rheumatologists view nr-AxSpA simply as a less severe precursor to AS, where aggressive treatment with a biologic is not warranted. In order to gain reimbursement for a biologic in patients with nr-AxSpA, rheumatologists frequently classify patients as having AS (as opposed to nr-AxSpA). Although adalimumab is the most frequently prescribed biologic in both conditions, rapid adoption of an IL-17 inhibitor (secukinumab) is occurring in the US market. <h3>Conclusions</h3> There is a need to educate both primary care physicians and rheumatologists about the differences between AS and nr-AxSpA. The official FDA approval of biologic agents in nr-AxSpA is anticipated to lead to more aggressive treatment of these patients earlier in the spectrum. <h3>Reference</h3> [1] RealTime Dynamix<sup>TM</sup>: Anlylosing Spondylitis and Non-radiographic Axial Spondylitis <h3>Disclosure of Interest</h3> None declared
Relationships between lenvatinib plasma concentration and toxicity in Japanese cancer patients
Authors: R.A. Makihara, S.N. Narita, N. Yamamoto, J. Sato, S. Murakami, Y. Goto, S. Kanda, Y. Fujiwara, H. Horinouchi, T. Tsukamoto, H. Hashimoto, Y. Makino, Y. Ohe, M. Yamaguchi
Journal: Annals of Oncology (2018)
Craniospinal irradiation as part of re-irradiation for children with recurrent intracranial ependymoma
Authors: Derek S Tsang, Louise Murray, Vijay Ramaswamy, Michal Zapotocky, Uri Tabori, Ute Bartels, Annie Huang, Peter B Dirks, Michael D Taylor, Cynthia Hawkins, Eric Bouffet, Normand Laperriere
Journal: Neuro-Oncology (2018)

The goal of this study was to evaluate outcomes in children with relapsed, molecularly characterized intracranial ependymoma treated with or without craniospinal irradiation (CSI) as part of a course of repeat radiation therapy (re-RT). This was a retrospective cohort study of 31 children. Patients with distant relapse received CSI as part of re-RT. For patients with locally recurrent ependymoma, those treated before 2012 were re-irradiated with focal re-RT. In 2012, institutional practice changed to offer CSI, followed by boost re-RT to the site of resected or gross disease. Median follow-up was 5.5 years. Of 9 patients with distant relapse after initial RT, 2-year freedom from progression (FFP) and overall survival (OS) were 12.5% and 62.5%, respectively. There were 22 patients with local failure after initial RT. In these patients, use of CSI during re-RT was associated with improvement in 5-year FFP (83.3% with CSI vs 15.2% with focal re-RT only, P = 0.030). In the subgroup of patients with infratentorial primary disease, CSI during re-RT also improved 5-year FFP (100% with CSI, 10.0% with focal re-RT only, P = 0.036). Twenty-three patients had known molecular status; all had posterior fossa group A tumors (n = 17) or tumors with a RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) fusion (n = 6). No patient developed radiation necrosis after fractionated re-RT, though almost all survivors required assistance throughout formal schooling. Five out of 10 long-term survivors have not developed neuroendocrine deficits. Re-irradiation with CSI is a safe and effective treatment for children with locally recurrent ependymoma and improves disease control compared with focal re-irradiation, with the benefit most apparent for those with infratentorial primary tumors.
Selection of house dust mite–allergic patients by molecular diagnosis may enhance success of specific immunotherapy
Authors: Kuan-Wei Chen, Petra Zieglmayer, René Zieglmayer, Patrick Lemell, Friedrich Horak, Carmen Panaitescu Bunu, Rudolf Valenta, Susanne Vrtala
Journal: Journal of Allergy and Clinical Immunology (2018)

House dust mites (HDMs) are one of the most potent and frequent allergen sources worldwide.1 More than 40% of patients with allergy are sensitized to HDM allergens and suffer from allergic symptoms such as rhinoconjunctivitis, atopic dermatitis, and allergic asthma, the most severe form of respiratory allergy.2 The HDM Dermatophagoides pteronyssinus contains several different allergens of which Der p 1, Der p 2, Der p 5, Der p 7, Der p 21, and Der p 23 are the clinically most relevant allergens according to the frequency of IgE sensitization and the ability to induce allergic reactions.
Bioresorbable Silicon Nanomembranes and Iron Catalyst Nanoparticles for Flexible, Transient Electrochemical Dopamine Monitors
Authors: Hyun‐Seung Kim, Seung Min Yang, Tae‐Min Jang, Nuri Oh, Hee‐Soo Kim, Suk‐Won Hwang
Journal: Advanced Healthcare Materials (2018)

Abstract A strategy of materials synthesis, characteristic evaluations, and manufacturing process for a mechanically elastic, biologically safe silicon‐based dopamine detector that is designed to be completely transient, i.e., dissolved in water and/or biofluids, potentially in the brain after a desired period of operation, is introduced. Use of inexpensive, bioresorbable iron (Fe)‐based nanoparticles (NPs) is one of the attractive choices for efficient catalytic oxidation of dopamine as an alternative for noble, nontransient platinum (Pt) nanoparticles, based on extensive studies of synthesized materials and catalytic reactions. Arrays of transient dopamine sensors validate electrochemical functionality to determine physiological levels of dopamine and to selectively sense dopamine in a variety of neurotransmitters, illuminating feasibilities for a higher level of soft, transient electronic implants integrated with other components of overall system.
Fully Human Bcma Targeted Chimeric Antigen Receptor T Cells Administered in a Defined Composition Demonstrate Potency at Low Doses in Advanced Stage High Risk Multiple Myeloma
Authors: Damian J. Green, Margot Pont, Blythe Duke Sather, Andrew J. Cowan, Cameron J. Turtle, Brian G. Till, Anne M Nagengast, Edward N. Libby, Pamela S. Becker, David G. Coffey, Sherilyn A. Tuazon, Brent Wood, Michelle Blake, Melissa Works, Bruce S Thompson, Ted Gooley, Frederick R. Appelbaum, David G. Maloney, Stanley R. Riddell
Journal: Blood (2018)
Endothelial dysfunction and cellular repair in heart failure with preserved ejection fraction: response to a single maximal exercise bout
Authors: Andreas B. Gevaert, Paul J. Beckers, Amaryllis H. Van Craenenbroeck, Katrien Lemmens, Caroline M. Van De Heyning, Hein Heidbuchel, Christiaan J. Vrints, Emeline M. Van Craenenbroeck
Journal: European Journal of Heart Failure (2018)