tbuckley/cabot-search huggingface dataset:
NIMG-101. EVALUATING THE VALIDITY OF EVIDENCE-BASED AANS/CNS GUIDELINES FOR POST-OPERATIVE TIMING OF IMAGING IN PATIENTS WITH NON-FUNCTIONAL PITUITARY ADENOMAS: A PRELIMINARY STUDY IN A COHORT OF PATIENTS
Authors: Mateo Ziu, Jeffrey Traylor, Pratima Kumar, Steven Taylor, Mrinalini Kulkarni-Date
Journal: Neuro-Oncology (2017)

Non-Functional Pituitary Adenomas (NFPA) are the most common pituitary tumors. Due to lack of hormonal hypersecretion imaging is the main follow-up modality, especially after surgical treatment. Recent evidence-based guidelines recommend the first post-operative MRI be performed no earlier than 3 months to provide the most meaningful information for extend of resection and for cost effectiveness. We retrospectively reviewed 28 cases of NFPA treated surgically in our institution that were designated to receive their first post-operative imaging at 3 months with the aim to identify factors that led to earlier imaging and whether late imaging was related to unexpected events. Twenty-eight patients underwent surgical treatment for NFPA. Twenty-seven underwent transsphenoidal resection and one open craniotomy. Seventeen (60%) were male and 11 (40%) female. Size of tumor ranged from 11mm to 50mm by the largest diameter. MRI of the pituitary gland was performed at or after 3 months post-surgery in all, but 6 patients (21%) who received it on post-operative day 1. Thirteen patients (46%) received CT of head within 1 – 30 days post-operatively (mostly for complains of headache). CT of head did not show any significant abnormality. All patients, but 4 were noticed to have no residual tumor on MRI after 3 months post-operatively. For 6 patients that received MRI on post-operative day 1, we found difficult to determine the amount of residual tumor when compared to MRI at 3 months. One patient underwent exploration transsphenoidal surgery for questionable rhinorrhea. The majority of the patients in our cohort received their first imaging after 3 months post-operatively as recommended by the AANS/CNS guidelines. No unexpected events were noticed. The timing of the MRI did not change treatment plans. We conclude that following evidence-based guidelines for the first post-operative imaging is safe and certainly more cost effective.
P1.15-004 An Open-Label, Multitumor Phase II Basket Study of Olaparib and Durvalumab (MEDIOLA): Results in Patients with Relapsed SCLC
Authors: M. Krebs, K. Ross, S. Kim, M. De Jonge, F. Barlesi, S. Postel-Vinay, S. Domchek, J. Lee, H. Angell, K. Bui, S. Chang, C. Gresty, P. Herbolsheimer, J. Delord
Journal: Journal of Thoracic Oncology (2017)
Políticas de vacinação contra o virus da varicela-zoster e estrategias de vigilância na Europa
Authors: A Pinot de Moira, A Nardone
Journal: Eurosurveillance (2005)

Na Europa, incluir a vacinacao contra o virus da varicela-zoster (VVZ) no calendario vacinal infantil e uma opcao cada vez mais frequente. O estudo seguinte e parte da analise sobre o VVZ realizada no quadro da Rede europeia de vigilância serologica 2 (ESEN 2), e descreve as politicas actuais de vacinacao passiva, as estrategias actuais e as estrategias propostas de vacinacao activa e os sistemas de vigilância das doencas devidas ao virus de varicela zoster nos paises participantes da Rede. Um questionario foi elaborado e enviado a 23 paises participantes. Actualmente, 14 entre 20 paises participantes tinham comercializada uma vacina contra o VVZ. A Alemanha e o unico pais que incluiu a vacina anti VVZ no calendario de vacinacao infantil de rotina. Outros tres paises recomendam a vacinacao infantil contra o VVZ e cinco projetam de incluir esta vacina no calendario vacinal infantil. Por enquanto, entre os oito paises que tem introduzido essa vacina nas criancas ou que vao faze-lo, so seis tem uma declaracao obrigatoria de casos de varicela, e so dois paises tem dados de vigilância de cuidados primarios para o herpes-zoster.
Abstract 12215: Objective Stratification of Six-Month Mortality Risk among Patients Referred to Hospice
Authors: Benjamin D Horne, Joseph B Muhlestein, Heidi T May, Brianna S Ronnow, Tami L Bair, Donald L Lappé
Journal: Circulation (2016)

Introduction: The Intermountain Mortality Risk Scores (IMRS) are a suite of sex-specific mortality risk stratification tools created from the complete blood count (CBC), basic metabolic profile (BMP), and age. Patients referred to hospice should have probable 6-month mortality, but this is currently estimated based on clinical gestalt. Hypothesis: Use of an objective clinical decision tool like IMRS may improve estimation of 6-month mortality risk for evaluation of patient referral to hospice. Methods: Subjects were Intermountain Healthcare patients who were referred to hospice (females: n=1,753, males: n=1,522) from 2009-2014. Baseline CBC and BMP laboratory data from the time of initial referral to hospice were used to compute the previously-derived IMRS scores. Cox regression and Kaplan-Meier survival curves were used for statistical analyses to evaluate six-month all-cause mortality risk. Results: Females averaged 77.2±14.2 years of age, and males were 74.4±14.6 years. Six-month survival was 37% in females and 33% in males; stratified into IMRS deciles, survival was 44.9% in decile 1 and 27.8% in decile 10 for females, while in males survival was 39.5% and 25.2%, respectively. Females had hazard ratio (HR)=1.72 (95% CI=1.34, 2.18; p&lt;0.001) for decile 10 vs. 1, and males had HR=1.57 (95% CI=1.18, 2.09; p=0.002). Stratified by previously-established IMRS thresholds (Figure), 12%, 38%, and 50% of females were grouped into low-, intermediate-, and high-risk groups, respectively, and 10%, 31%, 59% of males were in those groups. Conclusions: About one third of hospice patients did not die within 6 months, suggesting that additional objective evidence is needed to guide referral. IMRS, an evidence-based clinical decision tool derived in a large healthcare population, significantly stratified mortality risk in hospice patients. An electronically-deliverable stratification tool, IMRS may be useful in evaluation of patient risk prior to hospice referral.
P3.08-004 Phase I/II Trial of Nab-Paclitaxel or Paclitaxel Plus Carboplatin with Concurrent Radiation for Inoperable Stage IIIA/B NSCLC
Authors: A. Laine, P. Iyengar, K. Westover, A. Christie, I. Smith, S. Shakeel, A. Attia, L. Villaruz, D. Gerber, Y. Chen, D. Spigel, M. Socinski, H. Choy
Journal: Journal of Thoracic Oncology (2017)
GENE-07. EPIGENETIC PATHWAYS CONTROLLING HOTAIR EXPRESSION IN GLIOBLASTOMA
Authors: Sze Kiat Tan, Chiara Pastori, Marie Maloof, Nagi Ayad
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) is the most common and aggressive malignant adult brain tumor. Long noncoding RNAs (lncRNAs) have emerged as new players in the cancer paradigm, demonstrating potential roles in both oncogenic and tumor-suppressive pathways. Utilizing single molecule sequencing, we have previously demonstrated that hundreds of lncRNAs, including HOTAIR, are strongly dysregulated in GBM and HOTAIR is critical in GBM cells proliferation. Histone deacetylase inhibitors (HDACi) are small molecules that interfere with histone tail modification, thus altering chromatin structure and epigenetic pathways. However, the mechanistic into HDAC dependent control of HOTAIR expression has remained elusive. We hypothesized that BRD4 that binds to HOTAIR promoter and Gli2 acetylation status could provide insight into regulation of HOTAIR transcription by HDACs. The HOTAIR expression after treatment of HDACi on 2 patient-derived xenografts GBM cells (PDX-10 and PDX-22) were measured via qRT-PCR and the levels of proteins were investigated via Western blot analysis. shRNA constructs targeting individual HDACs (1–7) were used to knockdown HDAC and chromatin immunoprecipitation was performed to assess the protein binding on HOTAIR. From the epigenetic drug library screening, Tricostatin A, NSC-3852, BML-281, Apicidin, M-344, Scriptaid, Oxamflatin and Vorinostat (SAHA) reduced HOTAIR levels more than 50%. HDACi treatments resulted in a dose-dependent decrease in HOTAIR expression in both newly diagnosed and recurrent GBM cells. Both BRD4 RNA and protein levels were also reduced. Furthermore, HDACi treatment resulted in an increase in acetylation and BRD4 binding at HOTAIR gene bodies but a decrease in HOTAIR promoter region. We found that the acetylation of Gli2 after HDACi treatment also prevents its usual occupancy at HOTAIR promoter and subsequent BRD4 recruitment. Importantly, our results unravel a previously unappreciated mechanism through which HDAC inhibition modulate a key regulatory step in GBM cells growth by reducing the recruitment of BRD4 and Gli2 to the HOTAIR promoter.
Abstract 16425: Slow Ca2+ Sparks De-synchronize Ca2+ Release in Failing Cardiomyocytes: Evidence for Altered Ryanodine Receptor Distribution?
Authors: William Louch, Johan Hake, Halvor K Mørk, Karina Hougen, Biljana Skrbic, Glenn T Lines, Theis Tønnessen, Ivar Sjaastad, Ole M Sejersted
Journal: Circulation (2012)

In heart failure, cardiomyocytes exhibit slowing of the rising phase of the Ca2+ transient which contributes to the impaired contractility observed in this condition. We investigated the underlying...
Formação em epidemiologia das doenças transmissíveis na Europa do Norte
Authors: P Aavitsland, S Andresen
Journal: Eurosurveillance (2001)

Os cinco paises nordicos (Dinamarca, Finlândia, Islândia, Noruega e Suecia) tem uma grande tradicao de colaboracao na epidemiologia e controlo das doencas transmissiveis. Os epidemiologistas estatais e os directores dos programas de vacinacao reunem-se regularmente para discutirem desafios comuns e trocarem experiencias sobre a vigilância e controlo das doencas transmissiveis.
PATH-05. ALDH1A3, THE CRITICAL ALDEHYDE DEHYDROGENASE ISOFORM, DETERMINES GLIOMA STEM-LIKE CELL MESENCHYMAL IDENTITY AND POOR CLINICAL OUTCOME
Authors: Guanzhang Li, Wei Zhang
Journal: Neuro-Oncology (2017)

Mesenchymal (MES) transdifferentiation in glioma stem cells (GSCs) is associated with advanced malignancy and poor outcome in glioblastoma (GBM) patients. Identification of key regulator is therefore critical for developing GSCs-targeted therapy. Aldehyde dehydrogenase (ALDH) is thought to be a novel marker of GSCs. Our study is designed to elucidate the mechanisms by which ALDH1A3 regulated in GSCs. Aldefluor assays and qRT-PCR were performed to identify the major activity isoform of ALDH in GSCs. qRT-PCR, western blot and immunofluorescence were used to validate the vital role of ALDH1A3 in driving MES transformation. Then, we manipulated ALDH1A3 expression followed by transwell, neurosphere formation assays，glycolytic assays and orthotopic xenograft models to explore its functions. The prognostic value of ALDH1A3 was estimated by Kaplan-Meier survival analysis and COX regression analysis. We found that ALDH1A3 was a major contributor to ALDH activity and highly enriched in MES GSCs. ALDH1A3 silencing attenuated MES identity and reduced clonogenicity and tumorigenicity in vitro and vivo. By contrast, ALDH1A3 overexpression led to the opposite effect. Also, ALDH1A3 was an independent prognostic factor for GBM patients. A novel molecular classification scheme centered on ALDH1A3 could predict clinical prognosis accurately in GBMs. ALDH1A3 played a critical role in the maintenance of ALDH activity and MES identity in GSCs. ALDH1A3 expression was identified as an independent survival predictor and can be used to establish a novel molecular classification scheme. Inhibition of ALDH1A3 might be a potential therapeutic strategy to improve the prognosis of GBM patients.
P1.01-024 Plasma Circulating cfDNA as a Potential Biomarker in Clinical Management of NSCLC: Experience of Tata Memorial Hospital, India
Authors: A. Choughule, K. Prabhash, V. Naronha, V. Patil, A. Joshi, V. Hariniv, R. Prasad
Journal: Journal of Thoracic Oncology (2017)
Interruption de la transmission de la rougeole à Gipuzkoa, Pays basque espagnol
Authors: G Cilla, M Basterretxea, J Artieda, D Vicente, E Pérez-Trallero
Journal: Eurosurveillance (2004)

La vaccination contre la rougeole a ete introduite en 1978 a Gipuzkoa (Pays basque espagnol) puis remplacee en 1981 par le vaccin trivalent rougeole, oreillons, rubeole (ROR) pour les enfants de 12 a 15 mois. Une deuxieme dose du vaccin ROR a ete mise en place en 1992. La population a reagi favorablement a la nouvelle vaccination en deux doses et une couverture vaccinale elevee a ete atteinte (95% et 91% respectivement pour les premiere et seconde doses pour la periode 1993-2002). La circulation du virus de la rougeole a ete interrompue dans la seconde moitie des annees 1990 : aucun cas de rougeole autochtone n'a ete declare entre 1998 et 2003, seuls des cas importes ont ete confirmes pendant cette periode. Ces donnees suggerent que le programme de vaccination contre la rougeole est efficace. Neanmoins, il importe de maintenir des taux de couverture vaccinale eleves (g95%) pour les deux doses afin d'eviter des epidemies de rougeole dues a une re-introduction du virus.
STEM-23. DEVELOPMENT OF NEW THERAPIES FOR GLIOBLASTOMA MULTIFORME TARGETING NONSELECTIVE CATION CHANNELS
Authors: Ryoichi Iwata, Kohei Ofune, Mikio Hayashi, Kunikazu Yoshimura, Masahiro Nonaka, Hiroko Matsuda, Akio Asai
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme are refractory diseases and it is necessary to develop new therapies. Ion channels are membrane proteins that permeate ions and are involved in proliferation, metastasis and invasion in cancer. To date, functional analysis of ion channels in glioma cancer stem cells (GSCs) has not been done much.However, there is limited evidence regarding the ion channels in glioma cancer stem cells. Ion channels in GSCs are identified and the anti-tumor effect by inhibitors against them is verified. Cancer stem cell lines were established from patients with Glioblastoma multiforme. The whole current of cancer stem cells was measured using patch clamp technique, and electrophysiological properties and pharmacological properties were analyzed. We analyzed the effects of ion channel inhibitors on proliferation, cell death and invasion of cancer stem cells. Nonselective cationic current was observed in GSCs. This current was blocked in a concentration dependent manner by lanthanum which is a trivalent cation. Lanthanum inhibited the growth and invasion of GSCs. It is suggested that lanthanum inhibits cell proliferation and invasion by blocking nonselective cation channel current of GSCs.
Tendência da SIDA na Europa: decréscimo no Ocidente, aumento no Oriente
Authors: F F Hamers, A M Downs, J Alix, J B Brunet
Journal: Eurosurveillance (1997)

Foram notificados, em 1996, 24 920 casos de SIDA na Regiao Europeia da OMS, o que perfaz um total acumulado de 185 808 casos, incluindo 6969 (4%) de casos pediatricos (<13 anos)(1). Pela primeira vez, desde o inicio da epidemia, o numero anual de casos notificados diminuiu (5% entre 1995 e 1996, apos uma subida de 1% em 1995).
Patients’ views were sidelined as STPs were launched, says Healthwatch England
Authors: Tom Moberly
Journal: BMJ (2017)

Public engagement with NHS changes went into “paralysis” when plans for sustainability and transformation partnerships (STPs) were launched in December 2015, the deputy director of Healthwatch England has said.

Neil Tester said that communications between NHS bosses and the public went into “lockdown” and a “period of stasis” at a local level as plans for STPs were rolled out. The head of the organisation set up to represent NHS patients’ views was speaking at an event at the King’s Fund on 7 November.

Tester spoke …
Un'epidemia di malattia dei legionari tra i visitatori di una fiera in Belgio nel 1999
Authors: K De Schrijver, E van Bouwel, L Mortelmans, P van Rossom, T De Beukelaer, C Vael, K Dirven, H Goossens, M Leven, O Ronveaux
Journal: Eurosurveillance (2000)

Nel novembre 1999 sono stati identificati 93 casi di malattia dei legionari (43 confermati, 12 presunti e 38 possibili/clinici) in un'epidemia associata a una fiera a Kapellen, Belgio. Cinque casi sono morti. L'indagine epidemiologica ha mostrato che il tempo passato alla fiera e l'esposizione a particolari aree del tendone erano associate con la malattia. Attraverso il test della Polymerase chain reaction si e dimostrato che una vasca con idromassaggio e una fontana erano contaminati da legionella.
Hepatocyte nuclear factor 1A deficiency causes hemolytic anemia in mice by altering erythrocyte sphingolipid homeostasis
Authors: Karin von Wnuck Lipinski, Sarah Weske, Petra Keul, Susann Peters, Hideo A. Baba, Gerd Heusch, Markus H. Gräler, Bodo Levkau
Journal: Blood (2017)
Vigilancia del síndrome hemolítico-urémico en niños menores de 15 años en Francia en 1998
Authors: S Haeghebaert, V Vaillant, B Decludt, P. A.D. Grimont
Journal: Eurosurveillance (2000)

Los datos de la red nacional de unidades de nefrologia pediatrica en Francia sugieren que la incidencia del sindrome hemolitico-uremico (SHU) en 1998 fue de 0,7 casos por 100.000 ninos menores de 15 anos y que los casos ocurren esporadicamente. Seis de los 85 casos declarados en 1998 fueron importados, lo que pone de manifiesto la necesidad de implantar sistemas de alerta precoz del SHU tanto nacionales como internacionales. La proporcion de casos con serologia positiva ha disminuido desde la implantacion de este sistema de vigilancia en 1996. Esto sugiere que nuevos serogrupos de Escherichia coli, no detectables mediante las pruebas de diagnostico serologico utilizadas en la actualidad, podrian ser la causa de algunos casos de SHU.
IMMU-25. ENHANCED T CELLS TUMOR RECOGNITION USING DENDRITIC CELLS PULSED WITH CHIMERIC RNAs ENCODING FULL-LENGTH LAMP-1 FUSION CONSTRUCTS
Authors: Changlin Yang, Anjelika Dechkovskaia, Jeffrey Drake, Fernanda Guimaraes, Paul Kubilis, Jianping Huang, Duane Mitchell
Journal: Neuro-Oncology (2017)

Human CMV antigens have been proposed as novel targets for immunotherapy in glioblastoma (GBM). We previously demonstrated in a pilot randomized and blinded clinical trial, that vaccination of patients with newly-diagnosed GBM with autologous dendritic cells (DC) pulsed with RNA encoding the CMV antigen pp65 led to the expansion of pp65-specific T cell responses and was associated with prolonged survival (Mitchell, Batich et al., Nature 2015). A short targeting peptide from the lysosomal associated membrane protein 1 (LAMP-1) was expressed as a fusion construct with pp65 to enhance antigen-processing and presentation in RNA-pulsed DCs. In this study, we compared the use of a full-length LAMP fusion RNA construct (flLAMP-pp65, provided by Immunomic Technologies, Inc.) with the used short peptide chimeric antigen (shLAMP-pp65). DCs from HLA-A2+ or B7+, CMV seropositive (n=7) were pulsed with flLAMP-pp65 or shLAMP-pp65 RNA and used to stimulate autologous lymphocytes in vitro. Activation of CMV-specific T cells was evaluated by tetramer expansion, cytokine secretion, flow cytometric phenotyping, and recognition of HLA-matched GBM tumor cells expressing CMV pp65. DCs pulsed with full-length LAMP-1-pp65 chimeric RNAs demonstrated enhanced CMV-specific T cells as assessed by tetramer expansion in 7 out of 7 evaluated subjects, comparable induction of effector memory and central memory T cells, and increased IFNgamma secretion in recognition of pp65-expressing GBM tumor cells. Our results demonstrated potential superiority in the expansion of CMV-specific T cells and recognition of CMV pp65-expressing GBM tumor cells in vitro with use of the full-length LAMP-1 pp65 chimeric RNA pulsed DCs. A multi-institutional, blinded, randomized, and placebo-controlled phase 2 clinical trial is underway at our center utilizing flLAMP-pp65 RNA pulsed DCs, shLAMP-pp65 RNA pulsed DCs, and unpulsed PBMCs as a control vaccine.
STEM-22. Single-cell mass cytometry of human glioblastoma reveals phenotypic heterogeneity and distinct cell cycle and epigenetic states among glioma stem cells
Authors: Erin Simonds, Geraldine Cayanan, Joshua Park, Sean Bendall, Garry Nolan, William Weiss
Journal: Neuro-Oncology (2017)

Human glioblastoma (GBM) tumors harbor a subpopulation of glioma stem cells (GSCs) with the unique capacity to re-establish tumors as xenografts. While GSCs were recently shown to be the predominant cycling population in oligodendroglioma (Tirosh et al. Nature 2016), this relationship has not yet been rigorously examined in GBM biopsies. A variety of surface and intracellular proteins are proposed to mark GSCs, although concordance among these markers is unclear. We hypothesize that the GSC compartment contains distinct subpopulations, including cycling GSCs, that can be distinguished with highly multiplexed single-cell approaches. We used CyTOF mass cytometry to perform simultaneous single-cell measurements of 36 protein targets on dissociated human GBM pre-treatment biopsies (n = 8). The antibody panel included markers of cell cycle and intracellular signaling, as well as 15 previously reported markers of GSCs: A2B5, Bmi1, c-Myc, CD15, CD44, CD49f, CD133, EGFR, FOXM1, L1CAM, Musashi-1, nestin, Olig2, podoplanin, and Sox2. Clustering, dimensionality reduction, and correlation analyses were performed to compare subpopulations of tumor cells and quantify the degree of GSC marker co-expression. The 16 previously published GSC markers exhibited complex overlapping patterns of expression. Cells expressing GSC-associated transcription factors (i.e. Sox2, POU3F2) were common in tumors, but only a subset of those cells co-expressed GSC-associated surface markers (i.e. CD133, podoplanin). Markers of G2/M cell cycle state (i.e. Cyclin B1) or global Polycomb-mediated epigenetic silencing (i.e. H3K27me3) were associated with different subsets of the GSC compartment. Single-cell phenotyping by mass cytometry produced rich phenotypic profiles of the GSC compartment in human GBM biopsies. Subpopulations of GSCs co-exist in GBM and exhibit distinct epigenetic and cell cycle states. Improved surface immunophenotypes and functional understanding of these primitive cells will aid targeting them with small molecule and/or immunotherapeutic approaches.
Retrospective analysis of 77 patients with ovarian cancer undergoing genetic testing for BRCA1 and BRCA2 mutations
Authors: K. Tavella, A. Villanucci, L. Vannini, V. Rossi, B. Fantechi, G. Capone, A.L. Putignano, F. Gensini, B. Porfirio, G. Amunni, T. Mazzei, E. Mini, L. Papi
Journal: Annals of Oncology (2017)
P1.03-026 Interim Results of a Phase I Study of Nivolumab plus Nab-Paclitaxel/Carboplatin in Patients with NSCLC
Authors: J.W. Goldman, D. Waterhouse, B. George, P. O'Dwyer, T. Chen, N. Trunova, K. Kelly
Journal: Journal of Thoracic Oncology (2017)
Autoinflammatory phenotypes in Aicardi-Goutières syndrome with interferon upregulation and serological autoimmune features
Authors: Yuji Sugawara, Kohsuke Imai, Ayako Kashimada, Kengo Moriyama, Shimpei Baba, Ryuta Nishikomori, Mizuho Motegi, Yasuo Takeuchi, Tomohiro Morio
Journal: Journal of Allergy and Clinical Immunology (2017)
Prevención de la infección por rubéola congénita en la Región europea de la OMS: objetivo 2010
Authors: J. S. Spika, F X Hanon, S Wassilak, R G Pebody, N Emiroglu
Journal: Eurosurveillance (2004)

La Oficina regional para Europa de la Organizacion Mundial de la Salud (OMS) acaba de publicar un plan estrategico y las guias de vigilancia para el sarampion y la infeccion por rubeola congenita. La estrategia da prioridad a las actividades de control del sarampion pero fomenta la introduccion de la vacuna contra la rubeola cuando la cobertura antisarampion alcanza g90%, si bien muchos paises de Europa occidental con cobertura vacunal antisarampion ya estan utilizando la triple virica (MMR). Las mujeres de estos paises pueden estar en una situacion de riesgo especialmente elevado de tener un nino con el sindrome de rubeola congenita. La OMS pretende mejorar la vigilancia de la rubeola y del sindrome de la rubeola congenita, como un medio de obtener mejor informacion acerca de la carga de estas enfermedades e involucrar a los responsables de politicas en la necesidad de apoyar las estrategias de la Region europea de la OMS en materia de rubeola.