Sanofi (Mexico)

Preclinical antibody discovery relies on progressive screening and down-selection of candidate antibodies from large immune repertoires, yet this critical process is poorly represented in existing public databases. Here we introduce KyDab (Kymouse Antibody Database), a well-curated database of antibody discovery selection data generated using standardized workflows on the Kymouse humanized mouse platform. The current release includes 11 Kymouse platform mice immunisation studies covering 51 immunogens, more than 120,000 paired heavy-light chain sequences, and binding measurements for a selected subset of experimentally characterized clones. By capturing full-funnel selection data with consistent metadata and both positive and negative experimental outcomes, KyDab provides a valuable data resource for the development and evaluation of artificial intelligence models for antibody discovery. KyDab is accessible https://kydab.naturalantibody.com, and the database will be continuously updated as new datasets become available.

Abstract Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function. In addition to adaptive T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses by producing cytokines like Interleukin-5 (IL-5) and IL-13. Although it has been reported that RAG expression modulates the function of innate natural killer (NK) cells, whether other innate immune cells such as ILC2s are affected by RAG remains unclear. We find that in RAG-deficient mice, ILC2 populations expand and produce increased IL-5 and IL-13 at steady state and contribute to increased inflammation in atopic dermatitis (AD)-like disease. Further, we show that RAG modulates ILC2 function in a cell-intrinsic manner independent of the absence or presence of adaptive T and B lymphocytes. Lastly, employing multiomic single cell analyses of RAG1 lineage-traced cells, we identify key transcriptional and epigenomic ILC2 functional programs that are suppressed by a history of RAG expression. Collectively, our data reveal a novel role for RAG in modulating innate type 2 immunity through suppression of ILC2s.

Hypertension guidelines recommend the use of single-pill combinations (SPCs) of antihypertensive drugs to improve treatment persistence and blood pressure control. This study aimed to investigate the long-term effects of ramipril/amlodipine (R/A) SPC versus free equivalent dose combinations (FEC) on cardiovascular outcomes and treatment persistence. This retrospective, observational study analysed the database of the Hungarian National Health Insurance Fund. The study included patients with hypertension aged at least 18 years who were initiated on R/A SPC or FEC of different dose combinations (R/A 5/5, 5/10, 10/5 and 10/10 mg) between 2012 and 2018, with follow-up for up to 60 months. Imbalances in baseline characteristics were reduced with propensity score-based sub-classification. All analyses were performed with Cox proportional hazard model and propensity score sub-classification to adjust the imbalances in baseline characteristics. Drug persistence and MACEs were the primary and secondary endpoints, respectively. Overall, 104 882 patients with SPC and 68 324 patients with FEC-treated hypertension were included. The R/A 5/5 mg combination represented the largest proportion (62%). The nonpersistence rate was significantly lower with SPC than with FEC from month 1 to month 24 in the R/A 5/5 mg combination ( P < 0.001) and during the entire observation period in the remaining combinations. The MACE rate was significantly reduced with all R/A SPCs versus FECs. No effects on age and sex on both endpoints were noted. This study further supports the beneficial effects of the use of SPC on 60-month persistence and MACEs in hypertension.

Influenza and respiratory syncytial virus (RSV) are responsible for substantial morbidity and mortality in older adults, and can lead to cardiorespiratory sequelae. Older adults hospitalized and then discharged to skilled nursing facilities (SNFs) may be particularly susceptible to these adverse cardiorespiratory outcomes. In this national cohort of over 5 million SNF stays following a hospitalization, cardiorespiratory rehospitalization rates increased by approximately 1% for every 5% increase in circulating influenza A(H3N2), influenza B, and RSV, but decreased by 1% for every 5% increase in circulating influenza A(H1N1pdm09). Interventions to reduce respiratory virus transmission among SNF residents are critical for cardiorespiratory health.

Objetivo: el síndrome coronario agudo es una importante causa de morbimortalidad en Colombia, con una alta carga en calidad de vida, muertes, impacto social y costos para el sistema. El control subóptimo de las dislipidemias tiene múltiples causas, entre ellas el uso inadecuado de las estatinas, la inercia terapéutica, la baja difusión y la adopción de las guías y protocolos de manejo, adicional a las barreras de acceso a la atención y a los medicamentos, y la falta de trazabilidad en la atención a partir del evento isquémico agudo. El proyecto “Ruta de atención y manejo de los lípidos en el paciente con síndrome coronario agudo” busca identificar las brechas en la atención clínica y el manejo de la dislipidemia en los pacientes con síndrome coronario agudo en Colombia, y plantear soluciones para cerrarlas. Materiales y método: se realizaron 178 encuestas a profesionales médicos en instituciones de todo el país, para conocer las pautas de manejo de los pacientes con dislipidemia en el paciente con síndrome coronario agudo. Un panel de 17 expertos analizó los resultados y definió las brechas entre la práctica clínica, la evidencia disponible y el manejo recomendado, y planteó recomendaciones para cerrarlas. Resultados y Conclusiones: este artículo muestra las principales brechas detectadas en el manejo de la dislipidemia en pacientes con síndrome coronario agudo en Colombia, y emite recomendaciones de manejo de la dislipidemia, coherentes con las necesidades y características del Sistema de Salud colombiano.

Objective: Acute coronary syndrome (ACS) is an important cause of morbidity and mortality in Colombia, imposing a heavy burden in terms of quality of life, deaths, social impact, and costs to the system.Suboptimal control of dyslipidemia, associated with inadequate statin use, therapeutic inertia, and a low rate of dissemination and adoption of the management protocols and guidelines are clinical and healthcare-related factors that contribute to this situation.This is compounded by barriers that hinder access to care and medications, and the lack of care traceability after the acute ischemic event.The "Care Pathway and Lipid Management in Patients with Acute Coronary Syndrome" project seeks to identify gaps in clinical care and the management of dyslipidemia in patients with ACS in Colombia and propose solutions to bridge those gaps.Materials and method: To gain insights into the management of dyslipidemia in patients with ACS, 178 surveys were sent to medical professionals working in different institutions throughout the country.A panel of 17 experts analyzed the results, identified gaps in terms of clinical practice, available evidence, and recommended management, and proposed recommendations to bridge those gaps.Results and conclusions: This paper describes the main gaps related to the management of dyslipidemia in patients with ACS in Colombia and offers recommendations according to the needs and characteristics of the Colombian health system.