187 results on '"Zambrano, S"'
Search Results
2. SELNET clinical practice guidelines for bone sarcoma
- Author
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Blay, JY, Palmerini, E., Bollard, J., Aguiar, S., Angel, M., Araya, B., Badilla, R., Bernabeu, D., Campos, F., CHS, Caro-Sánchez, Carvajal Montoya, A., Casavilca-Zambrano, S., Castro-Oliden, V, Chacón, M., Clara-Altamirano, MA, Collini, P., Correa Genoroso, R., Costa, FD, Cuellar, M., dei Tos, AP, Dominguez Malagon, HR, Donati, DM, Dufresne, A., Eriksson, M., Farias-Loza, M., Frezza, AM, Frisoni, T., Garcia-Ortega, DY, Gerderblom, H., Gouin, F., Gómez-Mateo, MC, Gronchi, A., Haro, J., Hindi, N., Huanca, L., Jimenez, N., Karanian, M., Kasper, B., Lopes, A., Lopes David, BB, Lopez-Pousa, A., Lutter, G., Maki, RG, Martinez-Said, H., Martinez-Tlahuel, JL, Mello, CA, Morales Pérez, JM, Moura, DS, Nakagawa, SA, Nascimento, AG, Ortiz-Cruz, EJ, Patel, S., Pfluger, Y., Provenzano, S., Righi, A., Rodriguez, A., Santos, TG, Scotlandi, K., MLG, Silva, Soulé, T., Stacchiotti, S., Valverde, CM, Waisberg, F., Zamora Estrada, E., and Martin-Broto, J.
- Published
- 2022
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3. Current Situation of Congenital Toxoplasmosis in Ecuador
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Serra, G. C. Velásquez, Urgiles, L. I. Piloso, Cabredo, B. P. Guerrero, Caballero, M. J. Chico, Zambrano, S. L. Zambrano, Gutierrez, E. M. Yaguar, and Reyes, C. G. Barrera
- Published
- 2020
4. Decision framework for the integration of RPAS in non-segregated airspace
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Pérez-Castán, J.A., Gómez Comendador, F., Rodríguez-Sanz, A., Arnaldo Valdés, R.M., Águeda, G., Zambrano, S., and Torrecilla, J.
- Published
- 2020
- Full Text
- View/download PDF
5. On the destabilization of a periodically driven three-dimensional torus
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Euzzor, S., Di Garbo, A., Ginoux, J.-M., Zambrano, S., Arecchi, F. T., and Meucci, R.
- Published
- 2021
- Full Text
- View/download PDF
6. Current Situation of Congenital Toxoplasmosis in Ecuador
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Velásquez Serra, G. C., Piloso Urgiles, L. I., Guerrero Cabredo, B. P., Chico Caballero, M. J., Zambrano Zambrano, S. L., Yaguar Gutierrez, E. M., and Barrera Reyes, C. G.
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- 2020
- Full Text
- View/download PDF
7. Exploring phase control with square pulsed perturbations
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Arecchi, F. T., Euzzor, S., Gallas, M. R., Gallas, J. A. C., Meucci, R., Pugliese, E., and Zambrano, S.
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- 2017
- Full Text
- View/download PDF
8. Corrigendum to “SELNET clinical practice guidelines for soft tissue sarcoma and GIST” [Cancer Treat. Rev. 102 (2021) 102312]
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Blay, J.Y., Hindi, N., Bollard, J., Aguiar, S., Jr., Angel, M., Araya, B., Badilla, R., Bernabeu, D., Campos, F., Caro-Sánchez, C.H.S., Carvajal, B., Carvajal Montoya, A., Casavilca-Zambrano, S., Castro-Oliden, V., Chacón, M., Clara, M., Collini, P., Correa Genoroso, R., Costa, F.D., Cuellar, M., dei Tos, A.P., Dominguez Malagon, H.R., Donati, D., Dufresne, A., Eriksson, M., Farias-Loza, M., Fernandez, P., Frezza, A.M., Frisoni, T., Garcia-Ortega, D.Y., Gelderblom, H., Gouin, F., Gómez-Mateo, M.C., Gronchi, A., Haro, J., Huanca, L., Jimenez, N., Karanian, M., Kasper, B., Lopes David, B.B., Lopez-Pousa, A., Lutter, G., Martinez-Said, H., Martinez-Tlahuel, J., Mello, C.A., Morales Pérez, J.M., Moura David, S., Nascimento, A.G., Ortiz-Cruz, E.J., Palmerini, E., Patel, S., Pfluger, Y., Provenzano, S., Righi, A., Rodriguez, A., Salas, R., Santos, T.T.G., Scotlandi, K., Soule, T., Stacchiotti, S., Valverde, C., Waisberg, F., Zamora Estrada, E., and Martin-Broto, J.
- Published
- 2023
- Full Text
- View/download PDF
9. Corrigendum to “SELNET clinical practice guidelines for bone sarcoma” Critical reviews in oncology/hematology, vol. 174 (2022), 1–10
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Blay, J.Y., Palmerini, E., Bollard, J., Aguiar, S., Angel, M., Araya, B., Badilla, R., Bernabeu, D., Campos, F., Chs, Caro-Sánchez, Carvajal Montoya, A., Casavilca-Zambrano, S., Castro-Oliden, 5th, Chacón, M., Clara-Altamirano, M.A., Collini, P., Correa Genoroso, R., Costa, F.D., Cuellar, M., Dei Tos, A.P., Dominguez Malagon, H.R., Donati, D.M., Dufresne, A., Eriksson, M., Farias-Loza, M., Frezza, A.M., Frisoni, T., Garcia-Ortega, D.Y., Gerderblom, H., Gouin, F., Gómez-Mateo, M.C., Gronchi, A., Haro, J., Hindi, N., Huanca, L., Jimenez, N., Karanian, M., Kasper, B., Lopes, A., Lopes David, B.B., Lopez-Pousa, A., Lutter, G., Maki, R.G., Martinez-Said, H., Martinez-Tlahuel, J.L., Mello, C.A., Morales Pérez, J.M., Moura, D.S., Nakagawa, S.A., Nascimento, A.G., Ortiz-Cruz, E.J., Patel, S., Pfluger, Y., Provenzano, S., Righi, A., Rodriguez, A., Santos, T.G., Scotlandi, K., Mlg, Silva, Soulé, T., Stacchiotti, S., Valverde, C.M., Waisberg, F., Zamora Estrada, E., and Martin-Broto, J.
- Published
- 2022
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10. PROGRAMA NACIONAL DE PRESERVACIÓN Y MEJORAMIENTO GENÉTICO DE LA RAZA CRIOLLO LIMONERO EN LA REPÚBLICA BOLIVARIANA DE VENEZUELA
- Author
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Florio - Luis Jazmín, Contreras G.,Zambrano S., Fajardo J.,Fuenmayor A.
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Animal culture ,SF1-1100 ,Genetics ,QH426-470 - Published
- 2011
11. Nucleosome loss facilitates the chemotactic response of macrophages
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De Toma, I., Rossetti, G., Zambrano, S., Bianchi, M. E., and Agresti, A.
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- 2014
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12. Detection of hemorrhage by analyzing shapes of the arterial blood pressure waveforms
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Romero Zambrano, S, Guillame-Bert, M, Dubrawski, A, Clermont, G, and Pinsky, MR
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- 2015
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13. La atención primaria de salud: un programa viable para las comunidades indígenas
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Francisco A. Zambrano S. and César Méndez Lizarazo
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Medicine ,Public aspects of medicine ,RA1-1270 - Published
- 1991
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14. Cancer patients’ experiences with an early palliative care conversation: A qualitative study of an intervention based on the SENS-structure
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Fliedner, MC, Zambrano, S, Lohrmann, C, Schols, JMGA, Halfens, R, and Eychmüller, S
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610 Medicine & health - Published
- 2018
15. Energy constraints in pulsed phase control of chaos
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Meucci, R., Euzzor, S., Zambrano, S., Pugliese, E., Francini, F., and Arecchi, F.T.
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- 2017
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16. Composition and thickness of gold and silver nose decorations from the tomb of the Lady of Cao determined by combining EDXRF-analysis and X-ray transmission measurements/Composicion y espesor de las decoraciones nasales de oro y plata provenientes de la tumba de la Dama de Cao determinados por la combinacion del analisis EDXRF y las medidas de transmision de rayos X
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Cesareo, R., Gigante, G., Fabian, J., Zambrano, S., Franco, R., Fernandez, A., and Bustamante, A.
- Published
- 2014
17. Clinical outcomes of five patients implanted with a cardiac-based Vagus Nerve Stimulator (VNS)
- Author
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Landi, A, Zambrano, S, Trezza, A, Cavandoli, C, and Grioni, D
- Published
- 2017
18. PRELIMINARY RESULTS IN PAEDIATRIC AND YOUNG ADULT PATIENTS TREATED WITH CARDIAC BASED VAGUS NERVE STIMULATION (VNS)
- Author
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Grioni, D, Zambrano, S, Cavandoli, C, and Landi, A
- Published
- 2017
19. Ecotourism: the 'human shield' for wildlife conservation in the Osa Peninsula, Costa Rica.
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Lopez Gutierrez, Beatriz, Almeyda Zambrano, A. M., Mulder, G., Ols, C., Dirzo, R., Almeyda Zambrano, S. L., Quispe Gil, C. A., Cruz Díaz, J.C., Alvarez, D., Valdelomar Leon, V., Villareal, E., Sanchez Espinosa, A., Quiros, A., Stein, T. V., Lewis, K., and Broadbent, E. N.
- Subjects
WILDLIFE conservation ,BIODIVERSITY conservation ,ECOTOURISM ,GOLD mining ,NATURE reserves ,PENINSULAS - Abstract
The sustainability and efficiency of ecotourism regarding biodiversity conservation are under constant scrutiny and often dismissed based on negative effects arising from other types of nature-based tourism. Our study assess the impacts of infrastructure, human activity, and environmental factors on medium-large ground terrestrial species within the Lapa Rios Ecolodge Nature Reserve; results indicate that restoration, preservation, and conservation efforts are responsible for the wide range of species found within their reserve, including increased abundance of highly threatened rodents and ground birds. There is no indication that visitation or tour activities have negative impacts on wildlife; instead, the Ecolodge effectively created a 'human shield' that weakens threats to wildlife arising from hunting, logging, and gold mining. This shield effect ripples across the Osa Peninsula through the socio-economic benefits provided by ecotourism. Our results support a conservation model incorporating private reserves and parks to sustain biodiversity. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
20. High-throughput analysis of NF-κB dynamics in single cells reveals basal nuclear localization of NF-κB and spontaneous activation of oscillations
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Zambrano S, Bianchi M, Agresti A, Zambrano, S, Bianchi, M, and Agresti, A
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inflammation ,NF-kB ,transcription factor - Abstract
NF-kB is a transcription factor that upon activation undergoes cycles of cytoplasmic-to-nuclear and nuclear-to-cytoplasmictransport, giving rise to so called ‘‘oscillations’’. In turn, oscillations tune the transcriptional output. Since a detailedunderstanding of oscillations requires a systems biology approach, we developed a method to acquire and analyze largevolumes of data on NF-kB dynamics in single cells. We measured the time evolution of the nuclear to total ratio of GFP-p65in knock-in mouse embryonic fibroblasts using time-lapse imaging. We automatically produced a precise segmentation ofnucleus and cytoplasm based on an accurate estimation of the signal and image background. Finally, we defined a set ofquantifiers that describe the oscillatory dynamics, which are internally normalized and can be used to compare datarecorded by different labs. Using our method, we analyzed NF-kB dynamics in over 2000 cells exposed to differentconcentrations of TNF- a a. We reproduced known features of the NF-kB system, such as the heterogeneity of the responsein the cell population upon stimulation and we confirmed that a fraction of the responding cells does not oscillate. We alsounveiled important features: the second and third oscillatory peaks were often comparable to the first one, a basal amountof nuclear NF-kB could be detected in unstimulated cells, and at any time a small fraction of unstimulated cells showedspontaneous random activation of the NF-kB system. Our work lays the ground for systematic, high-throughput, andunbiased analysis of the dynamics of transcription factors that can shuttle between the nucleus and other cellcompartments.
- Published
- 2014
21. A simple model of NF-kappaB dynamics reproduces experimental observations
- Author
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Zambrano S, BIANCHI , MARCO EMILIO, Agresti A., Zambrano, S, Bianchi, MARCO EMILIO, and Agresti, A.
- Abstract
The mathematical modeling of the NF-κB oscillations has attracted considerable attention in recent times, but there is a lack of simple models in the literature that can capture the main features of the dynamics of this important transcription factor. For this reason we propose a simple model that summarizes the key steps of the NF-κB pathway. We show that the resulting 5-dimensional dynamical system can reproduce different phenomena observed in experiments. Our model can display smooth and spiky oscillations in the amount of nuclear NF-κB and can reproduce the variety of dynamics observed when different stimulations such as TNF-α and LPS are used. Furthermore we show that the model can be easily extended to reproduce the expression of early, intermediate and late genes upon stimulation. As a final example we show that our simple model can mimic the different transcriptional outputs observed when cells are treated with two different drugs leading to nuclear localization of NF-κB: Leptomycin B and Cycloheximide.
- Published
- 2014
22. Analysis of the spectacular gold and silver from the Moche tomb 'Senora de Cao'
- Author
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Cesareo, R., Franco Jordan, R., Fernandez, A., Bustamante, A., Fabian, J., del Pilar Zambrano, S., Azeredo, S., Lopes, R. T., Ingo, G. M., Riccucci, C., Di Carlo, G., and Gigante, G. E.
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optical microscopy ,in-situ analysis ,depletion gilding ,X-ray fluorescence ,metal artifacts - Abstract
On the north coast of present-day Peru, between the Andes and the Pacific Ocean, approximately between 100 and 600 ad, the Moche civilization prospered. The Moche were very sophisticated artisans and metal smiths, so that they are considered the finest producers of jewels and artifacts of the region. Their metalworking ability was impressively demonstrated by the excavations of the tomb of the 'Lady of Cao' (dated around third-fourth century ad) discovered by Regulo Franco in 2005. Impressive is the beauty of the artifacts, and also the variety of metallurgical solutions, demonstrated by not only the presence of objects composed of gold and silver alloys but also of gilded copper, gilded silver, and tumbaga, a poor gold Cu-Au alloy subject to depletion gilding. About 100 metal artifacts from the tomb of the Lady of Cao, never before analyzed, were studied by using various portable equipments based on following non-destructive and non-invasive methods: energy-dispersive X-ray fluorescence with completely portable equipments; transmission of monenergetic X-rays; radiographic techniques; and optical microscopy. Gold objects and gold areas of nose decorations are characterized by approximately the same composition, that is, Au = (79.5 ± 2.5) %, Ag = (16 ± 3) %, and Cu = (4.5 ± 1.5) %, while silver objects and silver areas of the same nose decorations show completely erratic results, and a systematic high gold concentration. Many gilded copper and tumbaga artifacts were identified and analyzed. Further, soldering gold-silver was specifically studied by radiographs. Additional measurements are needed, particularly because of the suspect that depletion gilding was systematically employed also in the case of some nose decorations.
- Published
- 2016
23. Analysis of the spectacular gold and silver from the Moche tomb ‘Señora de Cao’
- Author
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Gigante, Giovanni Ettore, Cesareo, R., Franco Jordan, R., Fernandez, A., Bustamante A, Fabian, J., Zambrano, S., Azeredo, S., Lopes, R. T., Ingo, G. M., Riccucci, C., Di Carlo, G., and Gigante, G. E.
- Subjects
XRF ,XRF., gold artefact ,gold artefact - Published
- 2016
24. Non‐meningothelial meningeal tumours with meningioangiomatosis‐like pattern of spread.
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Iorgulescu, J. B., Ferris, S., Agarwal, A., Casavilca Zambrano, S., Hill, D. A., Schmidt, R., and Perry, A.
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DIAGNOSIS of brain diseases ,MENINGEAL cancer ,RHABDOMYOSARCOMA ,SARCOMA ,TUMORS - Abstract
The article offers information about Non-meningothelial meningeal tumors with meningioangiomatosis. Topics discussed include perivascular spread of meningothelial and fibroblastic cells results Meningioangiomatosis; talks about biopsy of parieto-occipital mass reveals cellular neoplasm involving the leptomeninges; and mentions morphological and immunohistochemical sarcoma, shows features of rhabdomyosarcoma.
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- 2018
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25. Simulation of the power supply for a flash charging e-BRT system.
- Author
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Rios, M. A., Ramos, G. A., and Zambrano, S.
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- 2015
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26. Load profile for a bus rapid transit flash station of full-electric buses.
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Rios, M. A., Munoz, L. E., Zambrano, S., and Albarracin, A.
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- 2014
- Full Text
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27. Partial Control of a System with Fractal Basin Boundaries.
- Author
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Zambrano, S. and Sanjuán, M. A. F.
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CHAOS theory , *FRACTALS , *ATTRACTORS (Mathematics) , *NOISE , *CONTROL theory (Engineering) - Abstract
In this paper we apply the technique of partial control of a chaotic system to a dynamical system with two attractors with fractal basin boundaries, in presence of environmental noise. This technique allows one to keep the trajectories far from any of the attractors by applying a control that is smaller than the amplitude of environmental noise. We will show that the same geometrical horseshoe-like action that gives rise to the existence of fractal basin boundaries will allow us to detect certain sets for the dynamical system considered, the safe sets, that make this type of control possible. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
28. DETECTING DETERMINISM IN TIME SERIES WITH ORDINAL PATTERNS:: A COMPARATIVE STUDY.
- Author
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AMIGÓ, J. M., ZAMBRANO, S., and SANJUÁN, M. A. F.
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TIME series analysis , *COMPARATIVE studies , *INDEPENDENCE (Mathematics) , *MULTIVARIATE analysis , *NONLINEAR theories , *RANDOM noise theory , *MATHEMATICAL mappings , *PERMUTATIONS - Abstract
Detecting determinism in univariate and multivariate time series is difficult if the underlying process is nonlinear, and the noise level is high. In a previous paper, the authors proposed a method based on observable ordinal patterns. This method exploits the robustness of admissible ordinal patterns against observational noise, and the super-exponential growth of forbidden ordinal patterns with the length of the patterns. The new method compared favorably to the Brock-Dechert-Scheinkman independence test when applied to time series projected from the Hénon attractor and contaminated with Gaussian noise of different variances. In this paper, we extend this comparison to higher fractal dimensions by using noisy orbits on the attractors of the Lorenz map, and the time-delayed Hénon map. Finally, we make an analysis that enlightens the robustness of admissible ordinal patterns in the presence of observational noise. [ABSTRACT FROM AUTHOR]
- Published
- 2010
29. Characteristics of the Last Hospital Stay in Terminal Patients at an Acute Care Hospital in Colombia.
- Author
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Moyano J, Zambrano S, and Mayungo T
- Published
- 2010
- Full Text
- View/download PDF
30. SELNET clinical practice guidelines for soft tissue sarcoma and GIST.
- Author
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Blay, J.Y., Hindi, N., Bollard, J., Aguiar, S., Angel, M., Araya, B., Badilla, R., Bernabeu, D., Campos, F., Caro-Sánchez, C.H.S., Carvajal, B., Carvajal Montoya, A., Casavilca-Zambrano, S., Castro-Oliden, V., Chacón, M., Clara, M., Collini, P., Correa Genoroso, R., Costa, F.D., and Cuellar, M.
- Abstract
• Soft tissue sarcoma (STS) and gastrointestinal tumors (GIST) encompass > 80 different histologic subtypes. • Clinical practice guidelines for STS and GIST still lack in Latin-American countries. • Tailored clinical guidelines are instrumental to improve outcome in sarcoma patients in LatinAmerican countries. • This is the first review establishing STS and GIST guidelines for the purpose of LatinAmerican clinical practices to our knowledge. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
31. Tropical dry forests in Venezuela: assessing status, threats and future prospects.
- Author
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RODRÍGUEZ, J. P., NASSAR, J. M., RODRÍGUEZ-CLARK, K. M., ZAGER, I., PORTILLO-QUINTERO, C. A., CARRASQUEL, F., and ZAMBRANO, S.
- Abstract
Tropical dry forests may be among the world's most threatened ecosystems, but few studies have objectively quantified their status and threats. This study analysed Venezuelan dry forests at multiple scales, assessing status, present threats and the policy context shaping their future. Historical and current dry forest cover at both national and local scales were contrasted, and a set of quantitative risk assessment criteria applied. While dry forests were vulnerable nationally, in northern-central locations they were endangered. Clearing for cattle ranching and for intensive and subsistence agriculture were the principal factors driving dry forest loss at the national scale, while at a local level, urbanization and fire seemed to be the primary threats. The analysis emphasized the separation of risk assessment from the very different task of establishing conservation priorities; high risk areas may not necessarily be the highest priority for investment, and policy makers may become explicitly aware of the spatial scale at which their policies are implemented, as well as how these policies may affect or be affected by the status of ecosystems beyond their area of influence. The main challenge to future dry forest conservation is a paucity of explicit policies for management and use. However, scientifically-based management can support positive dry forest policies in many ways, including identifying locations and protocols for ecological restoration, maintaining seed banks, quantifying baseline conditions, and monitoring genetic diversity and other indicators. [ABSTRACT FROM PUBLISHER]
- Published
- 2009
- Full Text
- View/download PDF
32. Palliative sedation in Latin America: survey on practices and attitudes.
- Author
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Moyano J, Zambrano S, Ceballos C, Santacruz CM, Guerrero C, Moyano, Jairo, Zambrano, Sofia, Ceballos, César, Santacruz, Carlos Miguel, and Guerrero, Carlos
- Abstract
Introduction: Palliative sedation (PS) is the subject of ethical and legal debates worldwide. Statistics of its utilization are available in developed countries; however, in Latin America, these data are scarcely known. The purpose of this research was to determine the practices and attitudes of palliativists in Latin America towards PS.Materials and Methods: Data was collected during the Latin American Congress on Palliative Care in Isla Margarita, Venezuela. A total of 89 professionals participated in this survey.Results: It was found that the use of PS was positively associated with being a physician and being members of a palliative care (PC) group. On the other hand, it was found that being a psychologist and identifying barriers toward PS limited its utilization.Discussion: The findings of this study support the need to establish clinical guidelines for its utilization and to educate other specialists on end-of-life care approaches, and the need to develop PC programs in acute care hospitals in Latin America. [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
- View/download PDF
33. ADAPTIVE PROCEDURE FOR THE PARAMETER ESTIMATION OF A MODEL OF A CO2 CHAOTIC LASER.
- Author
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MARIÑO, I. P., ZAMBRANO, S., SANJUÁN, M. A. F., SALVADORI, F., MEUCCI, R., and ARECCHI, F. T.
- Subjects
- *
LASERS , *TIME measurements , *SYNCHRONIZATION , *NONLINEAR systems , *PARAMETER estimation - Abstract
We have proposed an adaptive procedure in order to estimate unknown parameters of a numerical model of a chaotic CO2 laser, which is observed through a time series that represents the output intensity of the laser. To do that, we consider a coupled system with the same functional form and adjustable parameters. The salient feature of the proposed technique is that accurate parameter estimation and identical synchronization can be jointly achieved by adaptively adjusting the desired parameters of the coupled system. [ABSTRACT FROM AUTHOR]
- Published
- 2007
34. Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production
- Author
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Eleonora Cantoni, Ivan Merelli, Davide Stefanoni, Alessandro Tomelleri, Corrado Campochiaro, Vito Giordano, Maddalena Panigada, Elena M Baldissera, Laura Merlo Pich, Valentina Natoli, Athanasios Ziogas, Jorge Domínguez-Andrés, Giacomo De Luca, Davide Mazza, Samuel Zambrano, Daniela Gnani, Marina Ferrarini, Elisabetta Ferrero, Alessandra Agresti, Barbara Vergani, Biagio Eugenio Leone, Simone Cenci, Angelo Ravelli, Marco Matucci-Cerinic, Angelo D’Alessandro, Leo A B Joosten, Lorenzo Dagna, Mihai G Netea, Raffaella Molteni, Giulio Cavalli, Cantoni, E, Merelli, I, Stefanoni, D, Tomelleri, A, Campochiaro, C, Giordano, V, Panigada, M, Baldissera, E, Merlo Pich, L, Natoli, V, Ziogas, A, Domínguez-Andrés, J, De Luca, G, Mazza, D, Zambrano, S, Gnani, D, Ferrarini, M, Ferrero, E, Agresti, A, Vergani, B, Leone, B, Cenci, S, Ravelli, A, Matucci-Cerinic, M, D'Alessandro, A, Joosten, L, Dagna, L, Netea, M, Molteni, R, and Cavalli, G
- Subjects
IL-6 ,trained immunity ,Rheumatology ,immunometabolism ,Pharmacology (medical) ,monocyte/macrophage ,epigenetic - Abstract
ObjectiveTrained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production.MethodsMonocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes.ResultsGCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production.ConclusionsMyelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production.
- Published
- 2023
35. An online international comparison of palliative care identification in primary care using the Surprise Question
- Author
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Yvonne Engels, B. Leysen, Nicola White, Patrick Stone, Christina Gerlach, Giovanni Ottoboni, Guido Biasco, Sofia C. Zambrano, Victoria Vickerstaff, Rabih Chattat, Carel Veldhoven, Linda J. M. Oostendorp, Maud Maessen, Steffen Eychmüller, Christina Avgerinou, Johan Wens, Christopher Tomlinson, White N., Oostendorp L.J.M., Vickerstaff V., Gerlach C., Engels Y., Maessen M., Tomlinson C., Wens J., Leysen B., Biasco G., Zambrano S., Eychmuller S., Avgerinou C., Chattat R., Ottoboni G., Veldhoven C., and Stone P.
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medicine.medical_specialty ,Palliative care ,Prognosi ,media_common.quotation_subject ,Primary health care ,610 Medicine & health ,Primary care ,survival ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,360 Social problems & social services ,medicine ,Humans ,media_common ,palliative care ,business.industry ,Original Articles ,General Medicine ,Prognosis ,primary health care ,Surprise ,Identification (information) ,Cross-Sectional Studies ,Anesthesiology and Pain Medicine ,Family medicine ,Hospice and Palliative Care Nursing ,Human medicine ,business - Abstract
Background: The Surprise Question (‘Would I be surprised if this patient died within 12 months?’) identifies patients in the last year of life. It is unclear if ‘surprised’ means the same for each clinician, and whether their responses are internally consistent. Aim: To determine the consistency with which the Surprise Question is used. Design: A cross-sectional online study of participants located in Belgium, Germany, Italy, The Netherlands, Switzerland and UK. Participants completed 20 hypothetical patient summaries (‘vignettes’). Primary outcome measure: continuous estimate of probability of death within 12 months (0% [certain survival]–100% [certain death]). A threshold (probability estimate above which Surprise Question responses were consistently ‘no’) and an inconsistency range (range of probability estimates where respondents vacillated between responses) were calculated. Univariable and multivariable linear regression explored differences in consistency. Trial registration: NCT03697213. Setting/participants: Registered General Practitioners (GPs). Of the 307 GPs who started the study, 250 completed 15 or more vignettes. Results: Participants had a consistency threshold of 49.8% (SD 22.7) and inconsistency range of 17% (SD 22.4). Italy had a significantly higher threshold than other countries ( p = 0.002). There was also a difference in threshold levels depending on age of clinician, for every yearly increase, participants had a higher threshold. There was no difference in inconsistency between countries ( p = 0.53). Conclusions: There is variation between clinicians regarding the use of the Surprise Question. Over half of GPs were not internally consistent in their responses to the Surprise Question. Future research with standardised terms and real patients is warranted.
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- 2022
36. MLL4-associated condensates counterbalance Polycomb-mediated nuclear mechanical stress in Kabuki syndrome
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Enrico Domenici, Daniela Intartaglia, Vittoria Poli, Gennaro Oliva, Louis Antonelli, Claudia Testi, Carmine Settembre, Daniela Michelatti, Sven Beyes, Panagiotis Vergyris, Luca Fagnocchi, Alessio Zippo, Alessandra Fasciani, Francesco Corazza, Francesco Gregoretti, Giancarlo Ruocco, Daniele Peroni, Romina Belli, Ivan Conte, Samuel Zambrano, Sarah D'Annunzio, Fasciani, A., D'Annunzio, S., Poli, V., Fagnocchi, L., Beyes, S., Michelatti, D., Corazza, F., Antonelli, L., Gregoretti, F., Oliva, G., Belli, R., Peroni, D., Domenici, E., Zambrano, S., Intartaglia, D., Settembre, C., Conte, I., Testi, C., Vergyris, P., Ruocco, G., and Zippo, A.
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Polycomb-Group Proteins ,Haploinsufficiency ,Mechanotransduction, Cellular ,Mice ,0302 clinical medicine ,Osteogenesis ,Gene expression ,0303 health sciences ,3T3 Cells ,Compartmentalization (psychology) ,Chromatin ,Cell biology ,Experimental models of disease ,Vestibular Diseases ,Kabuki syndrome. MLL4, Brillouin, Mechanobiology ,Chondrogenesis ,Biology ,Osteocytes ,Article ,Cell Line ,Mechanobiology ,03 medical and health sciences ,Chondrocytes ,Genetics ,medicine ,Animals ,Humans ,Abnormalities, Multiple ,Cell Lineage ,Transcription factor ,Loss function ,030304 developmental biology ,Cell Nucleus ,epigenetics ,Mesenchymal stem cell ,Brillouin ,fungi ,Mesenchymal Stem Cells ,Histone-Lysine N-Methyltransferase ,medicine.disease ,Hematologic Diseases ,Gene regulation ,HEK293 Cells ,Gene Expression Regulation ,Face ,Stress, Mechanical ,Kabuki syndrome ,030217 neurology & neurosurgery ,Kabuki syndrome. MLL4 - Abstract
The genetic elements required to tune gene expression are partitioned in active and repressive nuclear condensates. Chromatin compartments include transcriptional clusters whose dynamic establishment and functioning depend on multivalent interactions occurring among transcription factors, cofactors and basal transcriptional machinery. However, how chromatin players contribute to the assembly of transcriptional condensates is poorly understood. By interrogating the effect of KMT2D (also known as MLL4) haploinsufficiency in Kabuki syndrome, we found that mixed lineage leukemia 4 (MLL4) contributes to the assembly of transcriptional condensates through liquid-liquid phase separation. MLL4 loss of function impaired Polycomb-dependent chromatin compartmentalization, altering the nuclear architecture. By releasing the nuclear mechanical stress through inhibition of the mechanosensor ATR, we re-established the mechanosignaling of mesenchymal stem cells and their commitment towards chondrocytes both in vitro and in vivo. This study supports the notion that, in Kabuki syndrome, the haploinsufficiency of MLL4 causes an altered functional partitioning of chromatin, which determines the architecture and mechanical properties of the nucleus.
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- 2020
37. Exploring phase control with square pulsed perturbations
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E. Pugliese, Marcia R. Gallas, Samuel Zambrano, Jason A. C. Gallas, F. T. Arecchi, Stefano Euzzor, R. Meucci, Arecchi, F. T., Euzzor, S., Gallas, M. R., Gallas, J. A. C., Meucci, R., Pugliese, E., and Zambrano, S.
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Physics ,Mathematical analysis ,Chaotic ,General Physics and Astronomy ,Perturbation (astronomy) ,Duffing equation ,01 natural sciences ,010305 fluids & plasmas ,Periodic perturbation ,Linear term ,0103 physical sciences ,General Materials Science ,Physical and Theoretical Chemistry ,010306 general physics ,Phase control - Abstract
We discuss the phase control technique consisting of an applied square pulsed periodic perturbation. We explore the effect of such perturbations to the different terms of the Duffing oscillator. We find that the effect depends sensitively on how the perturbation is applied, indeed, it is specially effective when it modulates the cubic and the linear term and uneffective when applied to the driving term. Our results highlight the highly nontrivial role of the phase when applying a second periodic perturbation to a chaotic system.
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- 2017
38. NF-κB oscillations translate into functionally related patterns of gene expression
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Ilario De Toma, Arianna Piffer, Marco Bianchi, Alessandra Agresti, Samuel Zambrano, Zambrano, S, De Toma, I, Piffer, A, Bianchi, MARCO EMILIO, and Agresti, A.
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0301 basic medicine ,Mouse ,Transcription, Genetic ,QH301-705.5 ,Systems biology ,Science ,synchronous oscillations ,Stimulus (physiology) ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,Chemokine receptor ,Mice ,0302 clinical medicine ,Transcription (biology) ,Gene expression ,medicine ,Animals ,NF-kappaB ,mathematical modelling ,Biology (General) ,Transcription factor ,Genetics ,General Immunology and Microbiology ,General Neuroscience ,Gene Expression Profiling ,NF-kappa B ,General Medicine ,Fibroblasts ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Genomics and Evolutionary Biology ,Gene Expression Regulation ,Cytoplasm ,Medicine ,transcription ,single-cell imaging ,Nucleus ,030217 neurology & neurosurgery ,Research Article ,Computational and Systems Biology ,TNF-alpha - Abstract
Several transcription factors (TFs) oscillate, periodically relocating between the cytoplasm and the nucleus. NF-κB, which plays key roles in inflammation and cancer, displays oscillations whose biological advantage remains unclear. Recent work indicated that NF-κB displays sustained oscillations that can be entrained, that is, reach a persistent synchronized state through small periodic perturbations. We show here that for our GFP-p65 knock-in cells NF-κB behaves as a damped oscillator able to synchronize to a variety of periodic external perturbations with no memory. We imposed synchronous dynamics to prove that transcription of NF-κB-controlled genes also oscillates, but mature transcript levels follow three distinct patterns. Two sets of transcripts accumulate fast or slowly, respectively. Another set, comprising chemokine and chemokine receptor mRNAs, oscillates and resets at each new stimulus, with no memory of the past. We propose that TF oscillatory dynamics is a means of segmenting time to provide renewing opportunity windows for decision. DOI: http://dx.doi.org/10.7554/eLife.09100.001, eLife digest The process of producing useful biological molecules from genes – known as gene expression – is not always simple. Many genes are part of complex circuits, some of which show regular patterns of activity in response to an environmental cue. For example, the expression of some genes is tied to the 24-hour daily cycle of light and dark. Transcription factors are proteins that control gene activation and expression, and some transcription factors periodically move in and out of the cell’s nucleus – the compartment of an animal cell that houses the vast majority of the genetic material. This behavior is known as oscillation. A transcription factor called NF-κB oscillates, changing between an inactive form outside of the nucleus and an active form inside. NF-κB plays important roles in inflammation and cancer, and is activated by cues from outside the cell. Some of the genes that the active form of NF-κB activates then produce molecules that inactivate NF-κB, thus helping to establish the oscillations. The benefits of the oscillations are not clear. However, recent studies suggest that environmental cues can cause small perturbations that gradually adjust the rate at which the oscillations occur, and in doing so, synchronize the oscillations amongst neighboring cells. By using embryo cells from genetically engineered mice, Zambrano et al. investigated how NF-κB oscillations get synchronized. The experiments showed that the activity of the NF-κB protein and the expression of the genes it controls synchronize across neighboring cells whenever the external environmental perturbations come in pulses. However, once the pulsed cues stop, this synchronization is quickly lost. In essence, the cells reset after each environmental cue with no memory of previous episodes of NF-κB activity. Further work revealed that the expression of the genes controlled by NF-κB also cycles and resets with each new environmental cue. However, the products of these genes accumulate in three different ways. Some accumulate quickly; some accumulate at a slow and steady pace; and some oscillate in amount, and this amount resets once the environmental cue has stopped. Each of these classes of gene products can be related to specific cell behaviors that activate sequentially on well-defined time schedules. Overall, Zambrano et al. suggest that the ability of NF-κB to reset its activity with each new environmental cue gives cells the opportunity to pause and adjust course. Zambrano et al. now plan to explore what happens to NF-κB synchronization in different cell types exposed to a collection of inflammatory stimuli. Along the same line, it will be worth exploring NF-κB behavior in cancer cells, where NF-κB activity is often out of control and drives unrestrained cell proliferation. These studies would contribute to a deeper understanding of cancer biology and to the identification of new treatments for the disease. DOI: http://dx.doi.org/10.7554/eLife.09100.002
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- 2016
39. Optimal Phase-Control Strategy for Damped-Driven Duffing Oscillators.
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Meucci, R., Euzzor, S., Pugliese, E., Zambrano, S., Gallas, M. R., and Gallas, J. A. C.
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CHAOS theory , *DUFFING oscillators , *PERTURBATION theory - Abstract
Phase-control techniques of chaos aim to extract periodic behaviors from chaotic systems by applying weak harmonic perturbations with a suitably chosen phase. However, little is known about the best strategy for selecting adequate perturbations to reach desired states. Here we use experimental measures and numerical simulations to assess the benefits of controlling individually the three terms of a Duffing oscillator. Using a real-time analog indicator able to discriminate on-the-fly periodic behaviors from chaos, we reconstruct experimentally the phase versus perturbation strength stability areas when periodic perturbations are applied to different terms governing the oscillator. We verify the system to be more sensitive to perturbations applied to the quadratic term of the double-well Duffing oscillator and to the quartic term of the single-well Duffing oscillator. [ABSTRACT FROM AUTHOR]
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- 2016
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40. SELNET clinical practice guidelines for soft tissue sarcoma and GIST
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Shreyaskumar Patel, Jean-Yves Blay, S. Moura David, Y. Pfluger, K. Scotlandi, M. Angel, M. Chacón, A. Carvajal Montoya, J. Haro, J. Bollard, N. Jimenez, Bernd Kasper, Claudia Haydee Sarai Caro-Sánchez, A. G. Nascimento, T. Soule, S. Casavilca-Zambrano, R. Badilla, Héctor Martínez-Said, F. Campos, M. Farias-Loza, Alberto Righi, A. P. Dei Tos, Armelle Dufresne, E. J. Ortiz-Cruz, Hans Gelderblom, G. Lutter, B. B. Lopes David, J. M. Morales Pérez, C. A. Mello, Daniel Bernabeu, T. T. G. Santos, V. Castro-Oliden, Jorge Luis Martínez-Tlahuel, D. Donati, L. Huanca, M. C. Gómez-Mateo, D.Y. Garcia-Ortega, Paola Collini, M. Clara, P. Fernandez, Emanuela Palmerini, F. Waisberg, E. Zamora Estrada, J. Martin-Broto, Antonio Lopez-Pousa, Mikael Eriksson, A. Rodriguez, François Gouin, Claudia Valverde, S. Provenzano, B. Araya, Nadia Hindi, S. Aguiar, Silvia Stacchiotti, H. R. Dominguez Malagon, M. Cuellar, T. Frisoni, Alessandro Gronchi, R. Correa Genoroso, A.M. Frezza, Marie Karanian, R. Salas, B. Carvajal, F. D. Costa, Blay, J.Y., Hindi, N., Bollard, J., Aguiar, S., Angel, M., Araya, B., Badilla, R., Bernabeu, D., Campos, F., Caro-Sánchez, C.H.S., Carvajal, B., Carvajal Montoya, A., Casavilca-Zambrano, S., Castro-Oliden, V., Chacón, M., Clara, M., Collini, P., Correa Genoroso, R., Costa, F.D., Cuellar, M., dei Tos, A.P., Dominguez Malagon, H.R., Donati, D., Dufresne, A., Eriksson, M., Farias-Loza, M., Fernandez, P., Frezza, A.M., Frisoni, T., Garcia-Ortega, D.Y., Gelderblom, H., Gouin, F., Gómez-Mateo, M.C., Gronchi, A., Haro, J., Huanca, L., Jimenez, N., Karanian, M., Kasper, B., Lopes David, B.B., Lopez-Pousa, A., Lutter, G., Martinez-Said, H., Martinez-Tlahuel, J., Mello, C.A., Morales Pérez, J.M., Moura David, S., Nascimento, A.G., Ortiz-Cruz, E.J., Palmerini, E., Patel, S., Pfluger, Y., Provenzano, S., Righi, A., Rodriguez, A., Salas, R., Santos, T.T.G., Scotlandi, K., Soule, T., Stacchiotti, S., Valverde, C., Waisberg, F., Zamora Estrada, E., and Martin-Broto, J.
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medicine.medical_specialty ,Gastrointestinal Stromal Tumors ,MEDLINE ,Guidelines as Topic ,Soft Tissue Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,neoplasms ,GiST ,business.industry ,SELNET, SOFT TISSUE SARCOMA, GIST, GUIDELINES ,Soft tissue sarcoma ,Sarcoma ,General Medicine ,medicine.disease ,digestive system diseases ,3. Good health ,Clinical Practice ,Latin America ,Oncology ,030220 oncology & carcinogenesis ,Radiology ,business - Abstract
Soft tissue sarcoma (STS) is a heterogeneous group of neoplasms, encompassing >80 different histologic subtypes. Approximately three quarter of sarcoma arise from soft-tissue, about 15% are gastrointestinal stromal tumours (GISTs) and bone sarcoma represent the remaining 10%. The current guidelines will focus on soft-tissue and GIST, excluding Kaposi sarcoma and non-pleomorphic rhabdomyosarcoma
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41. In vitro models of the crosstalk between multiple myeloma and stromal cells recapitulate the mild NF-κB activation observed in vivo.
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Colombo F, Guzzeloni V, Kizilirmak C, Brambilla F, Garcia-Manteiga JM, Tascini AS, Moalli F, Mercalli F, Ponzoni M, Mezzapelle R, Ferrarini M, Ferrero E, Visone R, Rasponi M, Bianchi ME, Zambrano S, and Agresti A
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- Humans, Cell Line, Tumor, Interleukin-1beta metabolism, Tumor Microenvironment, Cell Communication, Stromal Cells metabolism, Stromal Cells pathology, Paracrine Communication, Signal Transduction, Transcription Factor RelA metabolism, Multiple Myeloma metabolism, Multiple Myeloma pathology, Multiple Myeloma genetics, Mesenchymal Stem Cells metabolism, NF-kappa B metabolism, Coculture Techniques
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Multiple myeloma (MM) is linked to chronic NF-κB activity in myeloma cells, but this activity is generally considered a cell-autonomous property of the cancer cells. The precise extent of NF-κB activation and the contributions of the physical microenvironment and of cell-to-cell communications remain largely unknown. By quantitative immunofluorescence, we found that NF-κB is mildly and heterogeneously activated in a fraction of MM cells in human BMs, while only a minority of MM cells shows a strong activation. To gain quantitative insights on NF-κB activation in living MM cells, we combined advanced live imaging of endogenous p65 Venus-knocked-in in MM.1S and HS-5 cell lines to model MM and mesenchymal stromal cells (MSCs), cell co-cultures, microfluidics and custom microbioreactors to mimic the 3D-interactions within the bone marrow (BM) microenvironment. We found that i) reciprocal MM-MSC paracrine crosstalk and cell-to-scaffold interactions shape the inflammatory response in the BM; ii) the pro-inflammatory cytokine IL-1β, abundant in MM patients' plasma, activates MSCs, whose paracrine signals are responsible for strong NF-κB activation in a minority of MM cells; iii) IL-1β, but not TNF-α, activates NF-κB in vivo in BM-engrafted MM cells, while its receptor inhibitor Anakinra reduces the global NF-κB activation. We propose that NF-κB activation in the BM of MM patients is mild, restricted to a minority of cells and modulated by the interplay of restraining physical microenvironmental cues and activating IL-1β-dependent stroma-to-MM crosstalk., (© 2024. The Author(s).)
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- 2024
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42. Treatment Outcomes and Definition Inconsistencies in High-Risk Unilateral Retinoblastoma: Outcomes and Definition Variances in High-Risk Rb.
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Arazi M, Baum A, Casavilca-Zambrano S, Alarcon-Leon S, Diaz-Coronado R, Ahmad A, Mushtaq A, Hussain M, Ushakova T, Yuri S, Vladimir P, Shields CL, Eagle RC Jr, Berry JL, Pike S, Brown B, Roy SR, Huque F, Fabian I, Frenkel S, Eiger-Moscovich M, Pe'er J, Hubbard GB 3rd, Olson TA, Grossniklaus H, Reddy MA, Sagoo MS, Staffieri SE, Elder JE, McKenzie JD, Tanabe M, Kaliki S, and Fabian ID
- Abstract
Purpose: To compare the clinical outcomes of children with unilateral retinoblastoma (Rb) and high-risk histopathology features (HRHF) following upfront enucleation with/without adjuvant chemotherapy, and investigate cases locally considered non-HRHF but converted to a standardized HRHF definition., Design: Retrospective multinational clinical cohort study., Methods: Children with Rb who presented to 21 centers from 12 countries between 2011-2020, and underwent primary enucleation were recruited. Centers retrieved clinical data and were asked to report detailed histopathology findings, as well as indicate cases defined locally as high-risk. For analysis, only unilateral cases with standardized HRHF, defined as retrolaminar optic nerve invasion, massive choroidal invasion, scleral invasion, anterior-segment involvement, and/or combined non-massive choroidal and prelaminar/laminar optic nerve invasion, were included. Main Outcome Measures included orbital tumor recurrence, systemic metastasis, survival and number and outcome of cases converted to standardized HRHF., Results: A total of 600 children presenting to 14 centers in 9 countries were included. Of these, 505 (84.2%) were considered locally as HRHF and received adjuvant chemotherapy. After a median follow-up period of 39.2±1.6 months (range: 0.8-60.0 months), 36 (6.0%) had orbital tumor recurrence, 49 (8.2%) metastasis, and 72 (12.0%) children died. Children not receiving adjuvant chemotherapy were at significantly increased risk of orbital tumor recurrence, metastasis, and death (p ≤0.002). Of the study children, 63/600 (10.5%) were considered locally non-HRHF, but converted to standardized HRHF and included in the analysis. Of these, 6/63 (9.5%) had orbital tumor recurrence, 5/63 (7.9%) metastasis, and 6/63 (9.5%) children died. Isolated minor choroidal invasion with prelaminar/laminar optic nerve invasion was reported in 114 (19.0%) children, but considered locally as HRHF only in 68/114 (59.6%). Of these, 6/114 (5.3%) children developed metastasis and subsequently died, yielding a number needed to treat of 15., Conclusion: Based on this multinational cohort of children with Rb, we recommend the use of adjuvant chemotherapy following upfront enucleation and diagnosis of HRHF. Variation exists worldwide among centers when defining HRHF, resulting in adverse patient outcomes, warranting standardization., Competing Interests: Declaration of competing interest None of the authors has any conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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43. How Many Autistic Children are there in Colombia? A Nationwide Examination of Autism Through Health System Data.
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García-Zambrano S and Pinto-Ocampo RH
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Purpose: Accurate healthcare data is indispensable for monitoring the epidemiology of autism spectrum disorders (ASD) and improving the quality of care for individuals on the spectrum. In Colombia, the Ministry of Health has developed the social protection information system (SISPRO) as a comprehensive registry, drawing data from the healthcare system with close to universal coverage (approximately 95%). This study utilizes data gathered by SISPRO to estimate the prevalence and specific characteristics of autistic children registered between January 2020 and December 2022., Method: A descriptive epidemiological approach was employed, using the International Statistical Classification of Diseases as search terms for ASD within the SISPRO dataset., Results: The study revealed a prevalence of 13.788 cases per 10,000 children in 2022 among aged 4 to 14. Regarding healthcare coverage types in 2022, the majority of autistic children served were under the contributory regime (68.28%), followed by the subsidized regime (25.36%). Geographic analysis indicated a non-uniform distribution of ASD prevalence in Colombia. The regions with the highest GDP, such as Antioquia, Atlántico, Bogotá, Cundinamarca, and Valle del Cauca, exhibited the highest prevalence (M = 17.90; SD = 14.3). In contrast, areas with the lowest GDP, including Amazonas, Guainía, Vaupés, Vichada, and Guaviare, showed the lowest prevalence among children (M = 2.6; SD = 2.5)., Conclusion: The estimation of ASD prevalence in Colombia represents an ongoing initiative to inform public policy actions. During the COVID-19 pandemic, there was a decrease in the number of autistic children served by the healthcare sector; however, the prevalence of ASD changed to higher levels in 2022. These findings contribute to strategies aimed at improving the quality of life for autistic individuals and mitigating the economic burden on their families., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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44. Valproic acid-induced teratogenicity is driven by senescence and prevented by Rapamycin in human spinal cord and animal models.
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Pietrogrande G, Shaker MR, Stednitz SJ, Soheilmoghaddam F, Aguado J, Morrison SD, Zambrano S, Tabassum T, Javed I, Cooper-White J, Davis TP, O'Brien TJ, Scott EK, and Wolvetang EJ
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Valproic acid (VPA) is an effective and widely used anti-seizure medication but is teratogenic when used during pregnancy, affecting brain and spinal cord development for reasons that remain largely unclear. Here we designed a genetic recombinase-based SOX10 reporter system in human pluripotent stem cells that enables tracking and lineage tracing of Neural Crest cells (NCCs) in a human organoid model of the developing neural tube. We found that VPA induces extensive cellular senescence and promotes mesenchymal differentiation of human NCCs. We next show that the clinically approved drug Rapamycin inhibits senescence and restores aberrant NCC differentiation trajectory after VPA exposure in human organoids and in developing zebrafish, highlighting the therapeutic promise of this approach. Finally, we identify the pioneer factor AP1 as a key element of this process. Collectively our data reveal cellular senescence as a central driver of VPA-associated neurodevelopmental teratogenicity and identifies a new pharmacological strategy for prevention. These results exemplify the power of genetically modified human stem cell-derived organoid models for drug discovery., (© 2024. The Author(s).)
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- 2024
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45. Dealing With Temporality in Patients With Life-Limiting Disease: An International Qualitative Study.
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Joshi M, Ásgeirsdóttir GH, Bakan M, Kodba Čeh H, Haugen DRF, Lunder U, Víbora Martín E, Morris B, Rasmussen BH, Romarheim E, Tripodoro V, van der Heide A, Veloso V, Yildiz B, Zambrano S, Strupp J, and Voltz R
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The prospect of death influences people's thoughts about and how they deal with their remaining time. We aimed to understand whether patients with progressive, life-limiting diseases are oriented in the past, present, or future and how they deal with temporality. We conducted 57 in-depth interviews with end-of-life patients in 10 countries using thematic analysis at three levels (i.e., locally in three countries, with codes shared in the three-country subgroup, and in all 10 countries with a codebook that we developed). We found that the patients' thoughts were oriented toward all three time levels (i.e., past, present, and future). Complementing these levels, we identified another, namely, the future after death. Each time level included patients actively and passively dealing with their thoughts. Past themes were remorse and regret , nostalgia , and coming to terms with past choices ; present themes were feeling grateful for being alive , a time for farewells , and living for the day ; future themes were worries about the future , to miss out , hope , ideas about death and dying , and planning the near future ; and future after death themes were not being there , worries about loved ones , and preparations for a future after death . A changed view on lifetime and avoidance of thinking about a certain time level related to several time levels, while desire to die fluctuated between levels and between acting on and feeling about it. Living for the day, worries about the future , and worries about the well-being of loved ones were common themes in all countries., Competing Interests: Declaration of Conflicting InterestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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46. Apoptosis Pathway-Associated Proteins Are Frequently Expressed in Melanoma: A Study of 32 Cases With Focus on Acral Lentiginous Melanoma.
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Ledesma DA, Marques-Piubelli ML, Li-Ning-Tapia E, Hudgens C, Gu J, Lazcano R, Casavilca-Zambrano S, Castillo M, Davies MA, Hwu WJ, Aung PP, Giubellino A, Curry JL, and Torres-Cabala C
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- Humans, Male, Female, Middle Aged, Aged, Proto-Oncogene Proteins B-raf genetics, Adult, Immunohistochemistry, Aged, 80 and over, Skin Neoplasms pathology, Skin Neoplasms genetics, Skin Neoplasms metabolism, Melanoma pathology, Melanoma genetics, Melanoma metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Bcl-2-Like Protein 11 metabolism, Bcl-2-Like Protein 11 genetics, Myeloid Cell Leukemia Sequence 1 Protein metabolism, Myeloid Cell Leukemia Sequence 1 Protein genetics, Apoptosis, Biomarkers, Tumor metabolism, Biomarkers, Tumor analysis
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Abstract: Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and clinical significance in patients with ALM. Thus, we assessed protein expression of BCL2, MCL1, BIM, and BRAF V600E by immunohistochemistry in 32 melanoma samples from White and Hispanic populations, including ALM and non-ALM (NALM). BCL2, MCL1, and BIM were expressed in both ALM and NALM tumors, and no significant differences in expression of any of these proteins were detected between the groups, in our relatively small cohort. There were no significant associations between protein expression and BRAF V600E status, overall survival, or ethnicity. In summary, ALM and NALM demonstrate frequent expressions of apoptosis-related proteins BCL2, MCL1, and BIM. Our findings suggest that patients with melanoma, including ALM, may be potential candidates for apoptosis-directed therapies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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47. Interprofessional interventions and factors that improve end-of-life care in intensive care units: An integratory review.
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Hernández-Zambrano SM, Carrillo-Algarra AJ, Manotas-Solano OE, Ibáñez-Gamboa SE, Mejia-Mendez LM, Martínez-Montoya OH, Fernández-Alcántara M, and Hueso-Montoro C
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Introduction: The changes in health dynamics, caused by the SARS-COVD-2 pandemic and its consequences, generated a greater need to integrate palliative care in the ICU to promote a dignified death., Objective: Identify interprofessional interventions and factors that improve the care of patients at the end of life., Methodology: Integrative review, including experimental, quasi-experimental, observational, analytical, and descriptive studies with correlation of variables, published from 2010 to 2021, identified in COCHRANE, CINAHL, CUIDEN, LILACS, SCIELO, Dialnet, PsychInfo, PubMed, PROQUES, PSYCHOLOGY, JOURNALS, SCIENCEDIRECT, with MeSH/DECS terms: "Critical Care", "IntensiveCare" "Life support care", "Palliative care", "Life Quality", "Right to die". 36,271 were identified, after excluding duplicate title, abstract, year of publication, design, theme, methodological quality, objectives, and content, 31 studies were found., Results: It included 31 articles, 16.7% experimental, 3.3% quasi-experimental, 80% observational, analytical, and descriptive with correlation of variables, 38% published in the United States, 38%, and 19% in Brazil. The pooled sample was 24,779 participants. 32.2% of the studies had level of evidence 1 recommendation (c), and 25.8% level of evidence 2 recommendation (c). This paper synthesises evidence to promote Interprofessional Collaborative Practice in the ICU, improve end-of-life care, and interventions to achieve established therapeutic goals, implement effective care policies, plans, and programmes for critically ill patients and their families; factors that affect palliative care and improve with training and continuing education for health personnel., Conclusion: There are interventions to manage physical and emotional symptoms, training strategies and emotional support aimed at health personnel and family members to improve the quality of death and reduce stays in the ICU. The interdisciplinary team requires training on palliative and end-of-life care to improve care., (Copyright © 2023 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Published by Elsevier España S.L.U. All rights reserved.)
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- 2024
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48. Executive Functions Rehabilitation in Premature Children Using an Adaptive Motion-Interaction Videogame Platform: A Randomized Controlled Trial.
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Cutillo G, Brazzoduro V, Bedogni G, Colombo C, Zambrano S, Rossi S, Zuccotti GV, Daniele I, Lista G, and Scelsa B
- Abstract
Background: Premature children are at increased risk of executive functions (EF) deficits and these difficulties persist into adolescence and adulthood, potentially undermining their development and academic achievements. The aim of the present randomized controlled trial (RCT) is to evaluate the efficacy of the Intendu trainer, an adaptive virtual reality platform, at ameliorating EF in preterm children. Methods: A single-center, RCT was conducted. The intervention group was exposed to game session with the Intendu software in addition to the standard of care in use in our center. The main outcome was the proportion of children with a 10-point increase in the processing speed quotient as measured by WPPSI-III after 4 weeks from the baseline assessment. Results: Forty-seven children born before 36 + 5 weeks were randomized to the experimental ( n = 24) or control arm ( n = 23). Five children were lost to follow-up. Thirteen of 23 children (56%) reached the main outcome in the experimental group and 5 of 19 (26%) in the control group ( P = 0.049, per-protocol analysis) with an absolute benefit increase (ABI) of 30% reconfirmed by the intention-to-treat analysis ( P = 0.022, ABI of 32%). Conclusion: Intendu brain-trainer showed promising short-term results on EF in pre-term children, however, larger studies with longer periods of follow-up are warranted to better investigate the role of this or similar technology in promoting better EF in preterm children.
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- 2024
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49. A preoperative risk score based on early recurrence for estimating outcomes after resection of hepatocellular carcinoma in the non-cirrhotic liver.
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Ruiz E, Honles J, Fernández R, Uribe K, Cerapio JP, Cancino K, Contreras-Mancilla J, Casavilca-Zambrano S, Berrospi F, Pineau P, and Bertani S
- Subjects
- Humans, Male, Female, Risk Assessment, Middle Aged, Aged, Risk Factors, Retrospective Studies, Time Factors, Treatment Outcome, Adult, Machine Learning, Liver Neoplasms surgery, Liver Neoplasms mortality, Liver Neoplasms pathology, Carcinoma, Hepatocellular surgery, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Hepatectomy, Neoplasm Recurrence, Local
- Abstract
Background: Liver resection is the mainstay treatment option for patients with hepatocellular carcinoma in the non-cirrhotic liver (NCL-HCC), but almost half of these patients will experience a recurrence within five years of surgery. Therefore, we aimed to develop a rationale-based risk evaluation tool to assist surgeons in recurrence-related treatment planning for NCL-HCC., Methods: We analyzed single-center data from 263 patients who underwent liver resection for NCL-HCC. Using machine learning modeling, we first determined an optimal cut-off point to discriminate early versus late relapses based on time to recurrence. We then constructed a risk score based on preoperative variables to forecast outcomes according to recurrence-free survival., Results: We computed an optimal cut-off point for early recurrence at 12 months post-surgery. We identified macroscopic vascular invasion, multifocal tumor, and spontaneous tumor rupture as predictor variables of outcomes associated with early recurrence and integrated them into a scoring system. We thus stratified, with high concordance, three groups of patients on a graduated scale of recurrence-related survival., Conclusion: We constructed a preoperative risk score to estimate outcomes after liver resection in NCL-HCC patients. Hence, this score makes it possible to rationally stratify patients based on recurrence risk assessment for better treatment planning., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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50. Real-World Dalbavancin Use for Serious Gram-Positive Infections: Comparing Outcomes Between People Who Use and Do Not Use Drugs.
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Zambrano S, Paras ML, Suzuki J, Pearson JC, Dionne B, Schrager H, Mallada J, Szpak V, Fairbank-Haynes K, Kalter M, Prostko S, and Solomon DA
- Abstract
Background: Dalbavancin has been used off-label to treat invasive bacterial infections in vulnerable populations like people who use drugs (PWUD) because of its broad gram-positive coverage and unique pharmacological properties. This retrospective, multisite study examined clinical outcomes at 90 days in PWUD versus non-PWUD after secondary treatment with dalbavancin for bacteremia, endocarditis, osteomyelitis, septic arthritis, and epidural abscesses., Methods: Patients at 3 teaching hospitals who received dalbavancin for an invasive infection between March 2016 and May 2022 were included. Characteristics of PWUD and non-PWUD, infection highlights, hospital stay and treatment, and outcomes were compared using χ
2 for categorical variables, t test for continuous variables, and nonparametric tests where appropriate., Results: There were a total of 176 patients; 78 were PWUD and 98 were non-PWUD. PWUD were more likely to have a patient-directed discharge (26.9% vs 3.1%; P < .001) and be lost to follow-up (20.5% vs 7.14%; P < .01). Assuming loss to follow-up did not achieve clinical cure, 73.1% of PWUD and 74.5% of non-PWUD achieved clinical cure at 90 days ( P = .08)., Conclusions: Dalbavancin was an effective treatment option for invasive gram-positive infections in our patient population. Despite higher rates of patient-directed discharge and loss to follow-up, PWUD had similar rates of clinical cure at 90 days compared to non-PWUD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)- Published
- 2024
- Full Text
- View/download PDF
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