Reducing energy usage in resource-intensive Java-based scientific applications via micro-benchmark based code refactorings

In-silico research has grown considerably. Today's scientific code involves long-running computer simulations and hence powerful computing infrastructures are needed. Traditionally, research in high-performance computing has focused on executing code as fast as possible, while energy has been recently recognized as another goal to consider. Yet, energy-driven research has mostly focused on the hardware and middleware layers, but few efforts target the application level, where many energy-aware optimizations are possible. We revisit a catalog of Java primitives commonly used in OO scientific programming, or micro-benchmarks, to identify energy-friendly versions of the same primitive. We then apply the micro-benchmarks to classical scientific application kernels and machine learning algorithms for both single-thread and multi-thread implementations on a server. Energy usage reductions at the micro-benchmark level are substantial, while for applications obtained reductions range from 3.90% to 99.18%.Fil: Longo, Mathias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto Superior de Ingeniería del Software. Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto Superior de Ingeniería del Software; Argentina. University of Southern California; Estados UnidosFil: Rodriguez, Ana Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto Superior de Ingeniería del Software. Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto Superior de Ingeniería del Software; ArgentinaFil: Mateos Diaz, Cristian Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto Superior de Ingeniería del Software. Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto Superior de Ingeniería del Software; ArgentinaFil: Zunino Suarez, Alejandro Octavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto Superior de Ingeniería del Software. Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto Superior de Ingeniería del Software; Argentin

Development of poly-N-isopropylacrylamide surfaces for the selection of swine sperm

The reproductive efficiency of pig farms is directly correlated with the fertility of the boars. The aim of this work was to develop polymeric materials that can be used as a platform to select a subpopulation of sperm with better cell physiological parameters. Polymeric hydrogels composed of Poly-N-isopropylacrylamide with different positive charges given by copolymerization with (3-acrylamidopropyl) trimethylammonium chloride (APTA, 5-10-15%), were synthesized. Subsequently, the interaction between the sperm cells and the polymeric surfaces was analyzed in TALP medium. Release of the spermatozoa from the polymeric surfaces was induced by changing to Ca2+ free media. Sperm motility, cell viability, plasma membrane and acrosome integrity were evaluated. The results indicated that a higher percentage of swine sperm attached to PNIPAM co-15% APTA hydrogels (62.86±3.33%). Ninety seven percent (97.19±1.45 %) of the sperm released from the PNIPAM co-15%APTA surfaces were viable (p<0.05 vs unbound population and raw semen), with acceptable motility (58.89±1.28%) and with intact plasma and acrosomal membranes (69±1.2% and 98.5±0.65% respectively). These results indicate that hydrogels can be used to select boar sperm with high viability and mobility for use in assisted reproductive techniques.Fil: Morilla, Gricelda Dolinda. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Liaudat, Ana Cecilia. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Blois, Damián Andrés. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Capella, Virginia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Rivarola, Claudia Rosana. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; ArgentinaFil: Barbero, César Alfredo. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; ArgentinaFil: Bosch, Pablo. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Rodriguez, Nancy. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentin

Transfer of extracellular vesicle-microRNA controls germinal center reaction and antibody production

Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer of a very restricted set of T-cell EV-microRNAs (mmu-miR20-a-5p, mmu-miR-25-3p, and mmu-miR-155-3p) to the B cell. Transferred EV-microRNAs target key genes that control B-cell function, including pro-apoptotic BIM and the cell cycle regulator PTEN. EV-microRNAs transferred during T-B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B-cell responses via the transfer of EV-microRNAs of T-cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune-related and inflammatory disorders.This manuscript was funded by grants SAF2017-82886-R (FS-M) from the Spanish Ministry of Economy and Competitiveness; CAM (S2017/BMD-3671-INFLAMUNE-CM) from the Comunidad de Madrid (FS-M); CIBERCV (CB16/11/00272), BIOIMID PIE13/041 from the Instituto de Salud Carlos III and from the Fundación La MaratóTV3(grant122/C/2015). The current research has received funding from “la Caixa” Foundation under the project code HR17-00016. VGY is supported by the AECC foundation. A.R.R. is supported by CNIC funding. This project was funded by the Spanish Ministerio de Ciencia, Innovacion y Universidades SAF2016-75511-R, and La Caixa Health Research Program HR17-00247 grant to A.R.R. Grants from Ramón Areces Foundation “Ciencias de la Vida y de la Salud” (XIX Concurso-2018) and from Ayuda Fundación BBVA y Equipo de Investigación Científica (BIOMEDICINA-2018) (to FSM). The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Soluble factors from Lactobacillus reuteri CRL1098 have anti-inflammatory effects in acute lung injury induced by lipopolysaccharide in mice

We have previously demonstrated that Lactobacillus reuteri CRL1098 soluble factors were able to reduce TNF-a production by human peripheral blood mononuclear cells. The aims of this study were to determine whether L. reuteri CRL1098 soluble factors were able to modulate in vitro the inflammatory response triggered by LPS in murine macrophages, to gain insight into the molecular mechanisms involved in the immunoregulatory effect, and to evaluate in vivo its capacity to exert antiinflammatory actions in acute lung injury induced by LPS in mice. In vitro assays demonstrated that L. reuteri CRL1098 soluble factors significantly reduced the production of pro-inflammatory mediators (NO, COX-2, and Hsp70) and proinflammatory cytokines (TNF-a, and IL-6) caused by the stimulation of macrophages with LPS. NF-kB and PI3K inhibition by L. reuteri CRL1098 soluble factors contributed to these inhibitory effects. Inhibition of PI3K/Akt pathway and the diminished expression of CD14 could be involved in the immunoregulatory effect. In addition, our in vivo data proved that the PS induced secretion of the pro-inflammatory cytokines, inflammatory cells recruitment to the airways and inflammatory lung tissue damage were reduced in L. reuteri CRL1098 soluble factors treated mice, providing a new way to reduce excessive pulmonary inflammation.Fil: Griet, Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Zelaya, María Hortensia del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Mateos, Melina Valeria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); ArgentinaFil: Juarez, Guillermo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); ArgentinaFil: Font, Graciela Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); ArgentinaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); ArgentinaFil: Rodriguez, Ana Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); Argentin

O Movimento Negro do ABC Paulista: diálogos sobre a prevenção das DST/aids

OBJECTIVE: To present the integration possibility evaluation (between the agendas of the black movement with the themes of health, particularly in relation to prevention of STD/AIDS). METHODS: We used the qualitative instrument called the Delphi Panel, given its flexibility to consultations with stakeholders with different power resources. 135 were registered entities of the black movement: 41 of them agreed to participate in the panel of questions. The project was extended to seven cities in the ABC region, bringing together 655,886 inhabitants (browns and blacks), who represent 32.8% of the total population of the region. RESULTS: The group of 41 participating (grass-roots organizations) proposed to act in actions of prevention of STD/AIDS directly (by adding them to their daily activities) or indirectly (through actions of social control) and assessed the need to understand socio-history of the greater vulnerability of the black population, not only in relation to the prevention of STD/AIDS, but also of health as a whole and the totality of life: "[...] the history of black dehumanization is a denial of the condition to be human, which exposes blacks to any disease. The information is unreliable, if coming this way. Blacks must be seen as a whole. CONCLUSIONS: The racism is understood as something that precedes any other, it has an impact on the access to health and has been reflected in the greater vulnerability of black men and women to HIV infection. The elements of affirmation of racial identity contribute to promoting the health of black people. Joint actions between health services and social movements provide conditions to strengthen a policy of confronting STD/AIDS among black women and black men, all Brazilians.OBJETIVO: Apresentar a avaliação realizada sobre as possibilidades de integração entre as agendas do movimento negro e a prevenção das DST/aids. METODOLOGIA: Utilizou-se o instrumento qualitativo chamado de Panel Delphi, dada a sua flexibilidade de consultas. Foram cadastradas 135 entidades do movimento negro, tendo 41 delas aceitado a proposta de participar do painel de questões. O projeto foi extensivo aos sete municípios da região do ABC paulista, sendo que 32,8% do total da população da região é composta de pretos e pardos. RESULTADOS: O grupo de 41 entidades participantes propôs-se a atuar em ações de prevenção das DST/aids diretamente (agregando-as às suas atividades cotidianas), ou indiretamente (através de ações de controle social) e avaliou a necessidade de um entendimento sócio-histórico da vulnerabilidade da população negra, em relação não somente à prevenção de DTS/aids, mas também da saúde como um todo e da totalidade da vida: "[...] a história do negro é de desumanização, negação da condição de ser humano, que expõe os negros a qualquer doença. A informação fica sem credibilidade vinda dessa maneira. O negro precisa ser visto como ser pleno." (1.10.1). CONCLUSÕES: O racismo vivenciado tem impacto nas condições de acesso à saúde e tem se refletido na maior vulnerabilidade de homens e mulheres negros para a infecção de HIV. Os elementos de afirmação da identidade racial contribuem para a promoção da saúde da população negra. Ações conjuntas entre os serviços de saúde e o movimento social possibilitam condições de fortalecimento de uma política de enfrentamento das DST/aids entre as negras e os negros brasileiros

ctDNA analysis reveals different molecular patterns upon disease progression in patients treated with osimertinib

Background: Several clinical trials have demonstrated the efficacy and safety of osimertinib in advanced nonsmall-cell lung cancer (NSCLC). However, there is significant unexplained variability in treatment outcome. Methods: Observational prospective cohort of 22 pre-treated patients with stage IV NSCLC harboring the epidermal growth factor receptor (EGFR) p.T790M resistance mutation and who were treated with osimertinib. Three hundred and twenty-six serial plasma samples were collected and analyzed by digital PCR (dPCR) and next-generation sequencing (NGS). Results: The median progression-free survival (PFS), since the start of osimertinib, was 8.9 [interquartile range (IQR): 4.6–18.0] months. The median treatment durations of sequential gefitinib + osimertinib, afatinib + osimertinib and erlotinib + osimertinib treatments were 30.1, 24.6 and 21.1 months, respectively. The p.T790M mutation was detected in 19 (86%) pre-treatment blood samples. Undetectable levels of the original EGFR-sensitizing mutation after 3 months of treatment were associated with superior PFS (HR: 0.2, 95% CI: 0.05–0.7). Likewise, re-emergence of the original EGFR mutation, alone or together with the p.T790M mutation was significantly associated with shorter PFS (HR: 8.8, 95% CI: 1.1–70.7 and HR: 5.9, 95% CI: 1.2–27.9, respectively). Blood-based monitoring revealed three molecular patterns upon progression to osimertinib: sensitizing+/T790M+/C797S+, sensitizing+/T790M+/C797S–, and sensitizing+/T790M–/ C797S–. Median time to progression in patients showing the triplet pattern (sensitizing+/T790M+/C797S+) was 12.27 months compared with 4.87 months in patients in whom only the original EGFR sensitizing was detected, and 2.17 months in patients showing the duplet pattern (sensitizing+/T790M+). Finally, we found that mutations in exon 545 of the PIK3CA gene were the most frequent alteration detected upon disease progression in patients without acquired EGFR-resistance mutations. Conclusions: Different molecular patterns identified by plasma genotyping may be of prognostic significance, suggesting that the use of liquid biopsy is a valuable approach for tumor monitoring.post-print468 K

Evaluación de la producción e inocuidad en frutilla cultivadas con manejo agroecológico

La Inocuidad alimentaria se define como “todas las medidas encaminadas a garantizar que los alimentos no causarán daño al consumidor si se preparan y/o ingieren según el uso al que están destinados” (OMS, 2007). Entre las acciones para contribuir a la inocuidad, la agroecología aporta a producir alimentos saludables de una manera más sostenible. La agroecología a través de herramientas como la implantación de cultivos de servicio y el uso de bioinsumos es útil para nutrir, recuperar y reactivar la vida del suelo, fortalecer la fertilidad de las plantas, y estimular la protección de los cultivos contra el ataque de insectos y enfermedades (Starobinsky y col. 2021).Estación Experimental Agropecuaria SaltaFil: Carmona, Pedro. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentina.Fil: Torres, Nancy. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentina.Fil: Sánchez, Virginia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentina.Fil: Orosco, Silvia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentina.Fil: Del Castillo, Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta. Agencia de Extensión Rural Cafayate; Argentina.Fil: Arce, Ana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta. Agencia de Extensión Rural Rosario de Lerma; Argentina.Fil: Lunad Rocha, Jimena. IInstituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentina.Fil: Chávez, Mónica. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentina.Fil: Rodríguez, Susana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta. Agencia de Extensión Rural Rosario de Lerma; Argentina..Fil: Navamuel, Virginia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta. Agencia de Extensión Rural Rosario de Lerma; Argentina

Crosstalk Between LXR and Caveolin-1 Signaling Supports Cholesterol Efflux and Anti-Inflammatory Pathways in Macrophages

© 2021 Ramírez, Torrecilla-Parra, Pardo-Marqués, de-Frutos, Pérez-García, Tabraue, de la Rosa, Martín-Rodriguez, Díaz-Sarmiento, Nuñez, Orizaola, Través, Camps, Boscá and Castrillo.Macrophages are immune cells that play crucial roles in host defense against pathogens by triggering their exceptional phagocytic and inflammatory functions. Macrophages that reside in healthy tissues also accomplish important tasks to preserve organ homeostasis, including lipid uptake/efflux or apoptotic-cell clearance. Both homeostatic and inflammatory functions of macrophages require the precise stability of lipid-rich microdomains located at the cell membrane for the initiation of downstream signaling cascades. Caveolin-1 (Cav-1) is the main protein responsible for the biogenesis of caveolae and plays an important role in vascular inflammation and atherosclerosis. The Liver X receptors (LXRs) are key transcription factors for cholesterol efflux and inflammatory gene responses in macrophages. Although the role of Cav-1 in cellular cholesterol homeostasis and vascular inflammation has been reported, the connection between LXR transcriptional activity and Cav-1 expression and function in macrophages has not been investigated. Here, using gain and loss of function approaches, we demonstrate that LXR-dependent transcriptional pathways modulate Cav-1 expression and compartmentation within the membrane during macrophage activation. As a result, Cav-1 participates in LXR-dependent cholesterol efflux and the control of inflammatory responses. Together, our data show modulation of the LXR-Cav-1 axis could be exploited to control exacerbated inflammation and cholesterol overload in the macrophage during the pathogenesis of lipid and immune disorders, such as atherosclerosis.We thank MINECO FPI predoctoral fellowship granted to MCO (BES-2015-075339). Experimental work was supported by grants from Ministerio de Ciencia, Investigación y Universidades, y Fondo Europeo de Desarrollo Regional (FEDER) Grant REF: PID2019-104284RB-I00/AEI/10.13039/501100011033 (to AC) and support from Networks of Excellence from MINECO (Nuclear Receptors in Cancer, Metabolism and Inflammation [NuRCaMeIn] SAF2017-90604-REDT to AC. Ministerio de Economía, Industria y Competitividad, Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación (SAF2017-82436-R, RTC2017-6283-1), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional (to LB). Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación Proyectos de I+D+i Retos Investigación 2018 (RTI2018-095061-B-I00); TALENTO Grant from Madrid Government, Spain (2017-T1/BMD-5333); Consejería de Ciencia, Universidades e Innovación Comunidad de Madrid, Spain (PEJD-2018-POST/BMD-8900 and PEDJ-2018-AI/BDM-9724) to CMR

Factores Pedagógicos que Favorecen el Éxito Escolar en Estudiantes de Enseñanza Postobligatoria

El foco del presente estudio ha sido el éxito escolar: la continuidad, la permanencia en el sistema educativo, lo cual implica transitar de forma adecuada por sus diversas etapas y modalidades formativas. En particular, hemos buscado conocer qué factores pedagógicos -vinculados a los procesos de enseñanza-aprendizaje y a la relación profesor/a-alumno/a- constituyen condiciones favorables para el éxito y la continuidad escolar de chicas y de chicos de enseñanza secundaria postobligatoria (Bachillerato y Ciclos Formativos). Hemos tratado de visibilizar el éxito escolar de chicos y de chicas en la educación secundaria, de analizar las experiencias y las trayectorias de estudiantes que, más allá del periodo obligatorio, dan continuidad a su vida escolar con éxito académico, de prestar atención a las diferencias entre estudiantes de Bachillerato y Ciclos Formativos y, por último, de analizar de forma diferenciada la experiencia de las chicas y de los chicos, indagando en los elementos de la construcción de la subjetividad en ambos sexos. Para ello, hemos trabajado con una muestra intencional de 26 estudiantes (12 chicas y 14 chicos), 16 de Bachillerato y 10 de Ciclos Formativos, seleccionados por sus docentes, en 12 centros urbanos y semiurbanos de Málaga, Sevilla, Granada, Cádiz y Almería. Los datos han sido recogidos a través de entrevistas semiestructuradas, con el apoyo de la técnica de foto-lenguaje y un cuestionario de contexto.Fundación Centro de Estudios Andaluces - [PRY031/11

Natalizumab-immunogenicity evaluation in patients with infusion related events or disease exacerbations

IntroductionNatalizumab is a biologic drug for relapsing-remitting multiple sclerosis that may induce the generation of anti-drug antibodies in some patients. Anti-natalizumab antibodies (ANA) increase the risk of adverse events and reduce efficacy, being useful biomarkers for monitoring treatment response.MethodsRetrospective observational study including MS patients treated with natalizumab that experienced infusion-related events (IRE) or disease exacerbations (DE). ANA were tested by Elisa including a screening and a confirmation assay. Patients were further classified as transient (one positive result) or persistent (two or more positive results) ANA.ResultsA total of 1251 MS patients were included and 153 (12.3%) had ANA with at least one single point determination, which were more frequent among patients with IRE compared to those with DE (21,6% vs.10.8%) during the first six infusions. Two or more determinations ANA were performed in 184 patients, being 31.5% permanently positive and 7.1% transiently positive. Interestingly, 26.1% of patients that experienced DE had persistent ANA, while 2.6% were transient. In contrast, 43% of patients with IRE had persistent ANA, and 9.3% had transient antibodies. Patients with persistent antibodies had more frequently high levels at the first sampling compared to patients with transient ANA.ConclusionReal-world evidence shows that the presence of ANA is behind an important percentage of patients treated with natalizumab that experience IRE, as well as DE but in a lower degree. These findings support the need to systematically evaluate ANA towards a personalized management of these patients to avoid undesired complications