Coronary Artery Embolism and Myocardial Infarction, case report.

Coronary embolism (CE) is a rare cause of non-atherosclerotic acute coronary syndrome (ACS). The clinical presentation is similar to ACS, and the diagnosis is supported by Shibata criteria. Atrial fibrillation is the main reported etiology in CE cases. Management includes percutaneous intervention with thromboaspiration and anticoagulation. The following case is a description of a patient with acute chest pain and recently diagnosed atrial fibrillation (AF) with a rapid ventricular response, is described. A thrombotic lesion in the distal right coronary artery (RCA) of embolic origin, was documented. Successful mechanical thromboaspiration was performed; intravascular ultrasound (IVUS) showed no thrombus, dissection, or atherosclerotic plaque. CE is an underdiagnosed cause of ACS; diagnosis relies on Shibata criteria, and patients experience worse outcomes in follow-up.

Resource competition predicts assembly of gut bacterial communities in vitro.

Microbial community dynamics arise through interspecies interactions, including resource competition, cross-feeding and pH modulation. The individual contributions of these mechanisms to community structure are challenging to untangle. Here we develop a framework to estimate multispecies niche overlaps by combining metabolomics data of individual species, growth measurements in spent media and mathematical models. We applied our framework to an in vitro model system comprising 15 human gut commensals in complex media and showed that a simple model of resource competition accounted for most pairwise interactions. Next, we built a coarse-grained consumer-resource model by grouping metabolomic features depleted by the same set of species and showed that this model predicted the composition of 2-member to 15-member communities with reasonable accuracy. Furthermore, we found that incorporation of cross-feeding and pH-mediated interactions improved model predictions of species coexistence. Our theoretical model and experimental framework can be applied to characterize interspecies interactions in bacterial communities in vitro.

[The current state of renal sympathetic denervation in hypertension]. / Estado actual de la denervación renal simpática en el tratamiento de la hipertensión.

This review provides an overview of the efficacy and safety of renal sympathetic denervation as a therapeutic approach for resistant hypertension. While the initial enthusiasm was sparked by the results of early clinical trials, it was dampened by the findings of the Symplicity HTN-3 study. However, recent advances in catheter technology and more refined patient selection criteria have yielded more promising results. Subsequent studies, such as SPYRAL HTN-OFF MED and RADIANCE II, demonstrated significant reductions in blood pressure, even in patients with mild to moderate hypertension. Despite the lack of robust data on major clinical outcomes, investigations into the time in therapeutic range for patients undergoing renal sympathetic denervation suggested potential cardiovascular benefits. Nevertheless, further research is needed to thoroughly understand the long-term impact, assess cost-effectiveness, and accurately identify which patient subgroups may derive the greatest benefits from this therapy.

Esta revisión brinda una síntesis de la eficacia y la seguridad de la denervación simpática renal como enfoque terapéutico para la hipertensión resistente. A pesar del entusiasmo inicial generado por los resultados de los primeros ensayos clínicos, la eficacia de esta terapia se vio comprometida por los hallazgos negativos del estudio Symplicity HTN-3. Sin embargo, recientes avances en la tecnología de catéteres y una refinada selección de los pacientes han proporcionado resultados más prometedores. Estudios posteriores, como SPYRAL HTN-OFF MED y RADIANCE II, demostraron reducciones significativas en la presión arterial, incluso en pacientes con hipertensión de leve a moderada. A pesar de la falta de datos sólidos sobre desenlaces clínicos importantes, las investigaciones sobre el tiempo en rango terapéutico de los pacientes sometidos a denervación simpática renal sugirieron posibles beneficios cardiovasculares. No obstante, se requiere una mayor investigación para comprender a fondo el impacto a largo plazo, evaluar la relación costo-efectividad y determinar con precisión qué subgrupos de pacientes podrían obtener los mayores beneficios de esta terapia.

Diagnosis and clinical management of thrombotic thrombocytopenic purpura (TTP): a consensus statement from the TTP Catalan group.

Thrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an extremely serious condition and, therefore, timely and appropriate treatment is critical to prevent life-threatening complications.Over the past 25 years, significant advances in the understanding of the pathophysiology of immune TTP have led to the development of readily available techniques for measuring ADAMTS13 levels, as well as new drugs that are particularly effective in the acute phase and in preventing relapses. These developments have improved the course of the disease.Given the complexity of the disease and its various clinical and laboratory manifestations, early diagnosis and treatment can be challenging.To address this challenge, a group of experienced professionals from the Catalan TTP group have developed this consensus statement to standardize terminology, diagnosis, treatment and follow up for immune TTP, based on currently available scientific evidence in the field. This guidance document aims to provide healthcare professionals with a comprehensive tool to make more accurate and timely diagnosis of TTP and improve patient outcomes.

Desenlaces maternos y neonatales en gestantes con cardiopatía con evaluación única vs. evaluación semiestructurada por un equipo cardio-obstétrico / Maternal and neonatal outcomes in pregnant women with heart disease with single evaluation vs. semi-structured evaluation by a cardio-obstetric team

Resumen Introducción: Las enfermedades cardiovasculares en las gestantes son desafiantes, con alta morbimortalidad materna y perinatal, por lo que se recomienda un equipo cardio-obstétrico para su atención. Aun así, pocos datos evalúan el impacto de estos equipos. Por lo tanto, el presente estudio tiene como objetivo comparar los resultados obstétricos, maternos y neonatales del seguimiento semiestructurado (SSE) en una clínica cardio-obstétrica con respecto a un seguimiento usual o seguimiento no estructurado (SNE) en gestantes con enfermedad cardiaca. Métodos: Se realizó un registro prospectivo de gestantes con cardiopatías. Se compararon las pacientes con SSE por un equipo cardio-obstétrico, contra aquellas con evaluación única o SNE. Se calculó el riesgo de eventos según la clasificación de la Organización Mundial de la Salud modificado (OMSm) y la escala del Cardiac Disease in Pregnancy Study II (CARPREG-II) y se evaluaron los desenlaces cardiacos, obstétricos y neonatales. Resultados: Se evaluaron 168 pacientes, 37 con SSE y 131 con evaluación única (SNE). Los principales diagnósticos fueron cardiopatía congénita, arritmias y valvulopatías. La media del CARPREG-II en pacientes de SNE fue 2.48 (DE: 2.3) y en pacientes de SSE fue 3.37 (DE: 2.45; p = 0.041). La media de la OMSm en pacientes de SNE fue 2.1 (DE: 1.6) y con SSE fue 2.65 (DE: 0.95; p = 0.0052). No hubo diferencias significativas en los desenlaces cardiacos primarios (13.8% en SNE vs. 5.4% en SSE; p = 0.134), cardiacos secundarios (5.3 en SNE vs. 2.7 en SSE; p = 0.410), obstétricos (10% en SNE vs. 16.2% en SSE; p = 0.253) y neonatales (35.9% en SNE y 40.5% en SSE; p = 0.486) a pesar de que las pacientes con SSE tenían un riesgo mayor que las pacientes con SNE según las escalas de la OMSm y el CARPREG-II. Conclusiones: En gestantes con cardiopatía, un SSE comparado con un SNE por un equipo cardio-obstétrico no mostró diferencias estadísticamente significativas en los desenlaces cardiovasculares, obstétricos y neonatales, a pesar de que las pacientes con SSE tenían un riesgo significativamente más alto de desenlaces adversos por las escalas de la OMSm y el CARPREG-II. Esto sugiere que el SSE logra al menos equiparar los desenlaces a pesar del mayor riesgo de eventos adversos que tenían las pacientes de este grupo.

Abstract Introduction: Cardiovascular diseases in pregnant women are challenging, with high maternal and perinatal morbidity and mortality, so a cardio-obstetric team is recommended for their care. Even so, little data evaluates the impact of these teams. Therefore, the present study aims to compare the obstetric, maternal, and neonatal outcomes of semi-structured follow-up (SSF) in a Cardio-obstetric clinic concerning regular or unstructured follow-up (USF) in pregnant women with heart disease. Methods: A prospective registry of pregnant women with heart disease was carried out. Patients with SSF by a cardio-obstetric team were compared with those with single evaluation or USF. The risk of events was calculated according to the modified World Health Organization (mWHO) classification and the CARPREG-II scale, and cardiac, obstetric, and neonatal outcomes were evaluated. Results: One hundred sixty-eight patients were evaluated, 37 with SSF and 131 with single evaluation (USF). The primary diagnoses were congenital heart disease, arrhythmias, and valve disease. The average CARPREG-II in USF patients was 2.48 (SD 2.3); in SSF patients, it was 3.37 (SD 2.45; p = 0.041). The average of the mWHO in patients with USF was 2.1 (SD 1.6), and with SSF, it was 2.65 (SD 0.95; p = 0.0052). There were no significant differences in primary cardiac outcomes (13.8% in USF vs. 5.4% in SSF; p = 0.134), secondary cardiac (5.3% in USF vs. 2.7% in SSF; p = 0.410), obstetric (10% in USF vs. 16.2% in SSF; p = 0.253) and neonatal (35.9% in USF and 40.5% in SSF; p = 0.486) even though patients with SSF had a higher risk than patients with USF according to the mWHO and CARPREG-II scales. Conclusions: In pregnant women with heart disease, an SSF compared with a USF by a cardio-obstetric team did not show statistically significant differences in cardiovascular, obstetric, and neonatal outcomes. However, patients with SSF had a significantly higher risk of adverse outcomes due to the mWHO and CARPREG-II scales. This result suggests that the SSF achieves at least equal outcomes despite the higher risk of adverse events that patients in this group had.

Maternal and neonatal outcomes in pregnant women with heart disease with single evaluation vs. semi-structured evaluation by a cardio-obstetric team.

INTRODUCTION: Cardiovascular diseases in pregnant women are challenging, with high maternal and perinatal morbidity and mortality, so a cardio-obstetric team is recommended for their care. Even so, little data evaluates the impact of these teams. Therefore, the present study aims to compare the obstetric, maternal, and neonatal outcomes of semi-structured follow-up (SSF) in a Cardio-obstetric clinic concerning regular or unstructured follow-up (USF) in pregnant women with heart disease. METHODS: A prospective registry of pregnant women with heart disease was carried out. Patients with SSF by a cardio-obstetric team were compared with those with single evaluation or USF. The risk of events was calculated according to the modified World Health Organization (mWHO) classification and the CARPREG-II scale, and cardiac, obstetric, and neonatal outcomes were evaluated. RESULTS: One hundred sixty-eight patients were evaluated, 37 with SSF and 131 with single evaluation (USF). The primary diagnoses were congenital heart disease, arrhythmias, and valve disease. The average CARPREG-II in USF patients was 2.48 (SD 2.3); in SSF patients, it was 3.37 (SD 2.45; p = 0.041). The average of the mWHO in patients with USF was 2.1 (SD 1.6), and with SSF, it was 2.65 (SD 0.95; p = 0.0052). There were no significant differences in primary cardiac outcomes (13.8% in USF vs. 5.4% in SSF; p = 0.134), secondary cardiac (5.3% in USF vs. 2.7% in SSF; p = 0.410), obstetric (10% in USF vs. 16.2% in SSF; p = 0.253) and neonatal (35.9% in USF and 40.5% in SSF; p = 0.486) even though patients with SSF had a higher risk than patients with USF according to the mWHO and CARPREG-II scales. CONCLUSIONS: In pregnant women with heart disease, an SSF compared with a USF by a cardio-obstetric team did not show statistically significant differences in cardiovascular, obstetric, and neonatal outcomes. However, patients with SSF had a significantly higher risk of adverse outcomes due to the mWHO and CARPREG-II scales. This result suggests that the SSF achieves at least equal outcomes despite the higher risk of adverse events that patients in this group had.

INTRODUCCIÓN: Las enfermedades cardiovasculares en las gestantes son desafiantes, con alta morbimortalidad materna y perinatal, por lo que se recomienda un equipo cardio-obstétrico para su atención. Aun así, pocos datos evalúan el impacto de estos equipos. Por lo tanto, el presente estudio tiene como objetivo comparar los resultados obstétricos, maternos y neonatales del seguimiento semiestructurado (SSE) en una clínica cardio-obstétrica con respecto a un seguimiento usual o seguimiento no estructurado (SNE) en gestantes con enfermedad cardiaca. MÉTODOS: Se realizó un registro prospectivo de gestantes con cardiopatías. Se compararon las pacientes con SSE por un equipo cardio-obstétrico, contra aquellas con evaluación única o SNE. Se calculó el riesgo de eventos según la clasificación de la Organización Mundial de la Salud modificado (OMSm) y la escala del Cardiac Disease in Pregnancy Study II (CARPREG-II) y se evaluaron los desenlaces cardiacos, obstétricos y neonatales. RESULTADOS: Se evaluaron 168 pacientes, 37 con SSE y 131 con evaluación única (SNE). Los principales diagnósticos fueron cardiopatía congénita, arritmias y valvulopatías. La media del CARPREG-II en pacientes de SNE fue 2.48 (DE: 2.3) y en pacientes de SSE fue 3.37 (DE: 2.45; p = 0.041). La media de la OMSm en pacientes de SNE fue 2.1 (DE: 1.6) y con SSE fue 2.65 (DE: 0.95; p = 0.0052). No hubo diferencias significativas en los desenlaces cardiacos primarios (13.8% en SNE vs. 5.4% en SSE; p = 0.134), cardiacos secundarios (5.3 en SNE vs. 2.7 en SSE; p = 0.410), obstétricos (10% en SNE vs. 16.2% en SSE; p = 0.253) y neonatales (35.9% en SNE y 40.5% en SSE; p = 0.486) a pesar de que las pacientes con SSE tenían un riesgo mayor que las pacientes con SNE según las escalas de la OMSm y el CARPREG-II. CONCLUSIONES: En gestantes con cardiopatía, un SSE comparado con un SNE por un equipo cardio-obstétrico no mostró diferencias estadísticamente significativas en los desenlaces cardiovasculares, obstétricos y neonatales, a pesar de que las pacientes con SSE tenían un riesgo significativamente más alto de desenlaces adversos por las escalas de la OMSm y el CARPREG-II. Esto sugiere que el SSE logra al menos equiparar los desenlaces a pesar del mayor riesgo de eventos adversos que tenían las pacientes de este grupo.

Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators.

Glial-origin brain tumors, including glioblastomas (GBM), have one of the worst prognoses due to their rapid and fatal progression. From an oncological point of view, advances in complete surgical resection fail to eliminate the entire tumor and the remaining cells allow a rapid recurrence, which does not respond to traditional therapeutic treatments. Here, we have reviewed new immunotherapy strategies in association with the knowledge of the immune micro-environment. To understand the best lines for the future, we address the advances in the design of neoantigen vaccines and possible new immune modulators. Recently, the efficacy and availability of vaccine development with different formulations, especially liposome plus mRNA vaccines, has been observed. We believe that the application of new strategies used with mRNA vaccines in combination with personalized medicine (guided by different omic's strategies) could give good results in glioma therapy. In addition, a large part of the possible advances in new immunotherapy strategies focused on GBM may be key improving current therapies of immune checkpoint inhibitors (ICI), given the fact that this type of tumor has been highly refractory to ICI.

Multi-Annual Evaluation of Time Series of Sentinel-1 Interferometric Coherence as a Tool for Crop Monitoring.

Interferometric coherence from SAR data is a tool used in a variety of Earth observation applications. In the context of crop monitoring, vegetation indices are commonly used to describe crop dynamics. The most frequently used vegetation indices based on radar data are constructed using the backscattered intensity at different polarimetric channels. As coherence is sensitive to the changes in the scene caused by vegetation and its evolution, it may potentially be used as an alternative tool in this context. The objective of this work is to evaluate the potential of using Sentinel-1 interferometric coherence for this purpose. The study area is an agricultural region in Sevilla, Spain, mainly covered by 18 different crops. Time series of different backscatter-based radar vegetation indices and the coherence amplitude for both VV and VH channels from Sentinel-1 were compared to the NDVI derived from Sentinel-2 imagery for a 5-year period, from 2017 to 2021. The correlations between the series were studied both during and outside the growing season of the crops. Additionally, the use of the ratio of the two coherences measured at both polarimetric channels was explored. The results show that the coherence is generally well correlated with the NDVI across all seasons. The ratio between coherences at each channel is a potential alternative to the separate channels when the analysis is not restricted to the growing season of the crop, as its year-long temporal evolution more closely resembles that of the NDVI. Coherence and backscatter can be used as complementary sources of information, as backscatter-based indices describe the evolution of certain crops better than coherence.

Retroviral Infection and Commensal Bacteria Dependently Alter the Metabolomic Profile in a Sterile Organ.

Both viruses and bacteria produce "pathogen associated molecular patterns" that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites, while viruses could change the metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of murine leukemia virus-infected mice monocolonized with Lactobacillus murinus to show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus open a new avenue for future investigations.

Retroviral infection and commensal bacteria dependently alter the metabolomic profile in a sterile organ.

Both viruses and bacteria produce 'pathogen associated molecular patterns' that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites while viruses could change metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of Murine Leukemia Virus-infected mice monocolonized with Lactobacillus murinus to show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus, open a new avenue for future investigations.

Efficiency of reactive nitrogen removal in a model Mediterranean high-mountain lake and its downwater river ecosystem: Biotic and abiotic controls.

High-mountain lakes and rivers are usually oligotrophic and strongly influenced by atmospheric transport processes. Thus, wet deposition of reactive N species (Nr), mainly in the form of nitrate (NO3-), is a major source of N input in these high-mountain ecosystems. Bacterial denitrifiers are thought to be largely responsible for reduction of NO3- to nitrous oxide (N2O) and molecular dinitrogen (N2) as main biological pathway of N removal in these ecosystems. Nitrifiers, through the oxidation of ammonium to NO3-, can also be a source of NO3- and N2O. However, there is uncertainty regarding the abiotic and biotic factors controlling Nr elimination from aquatic ecosystems at different altitudes and seasons. We examined the efficiency of Nr removal as N2O and N2 (total removal) or N2 only (clean removal) in a model lake and its downwater river ecosystem (Sierra Nevada, Spain) representative of Mediterranean high-mountain freshwater ecosystems along an altitudinal gradient during the warm period of the year. Denitrification activity and the abundance of nitrifiers and denitrifiers in sediments were measured at thaw, mid ice-free and late ice-free periods. We found the efficiency of total and clean removal of Nr increased from the downwater river to the high-mountain lake. Regardless of the location, the efficiency of total removal of Nr decreased over the ice-free period whereas that of clean removal of Nr peaked at mid ice-free period. The efficiency of total removal of Nr was mainly controlled by the abundance of archaeal nitrifiers and bacterial denitrifiers. Abiotic (ammonium and NO3- concentration) and biotic (mainly nosZI-type denitrifiers) factors drove changes in the efficiency of clean removal of Nr. Our results suggest that abiotic and biotic factors can control the efficiencies of Nr removal in Mediterranean high-mountain lakes and their downwater rivers, and that these efficiencies increase with altitude and vary over the ice-free period.

The effect of pregnancy on the course of uveitis in single and multiple pregnancies.

PURPOSE: To explore the effect of pregnancy on the clinical course, outcome, and treatment in multiparous women with non-infectious uveitis. METHODS: Retrospective study of women with a history of non-infectious uveitis and pregnancies prior to and during disease course. Disease activity and severity 1-year prior pregnancy, during pregnancy, and 1-year postpartum were recorded as well as patients' and diseases' characteristics. The main outcome measures included the rate and severity of uveitis attacks and the effect on ocular complications and therapies. RESULTS: Included were 32 women (70 pregnancies, mean of 2.6 pregnancies/patient), with a mean follow-up time of 6.5 years. The most common uveitis types were anterior (31%) and pan-uveitis (31%). Flare-ups were more frequent in the year prior to pregnancy, in the first trimester, and in the postpartum period and decreased markedly during pregnancy. Women who experienced a flare-up during pregnancy had a higher rate of flare-ups in the year prior pregnancy than those who did not experience a flare-up during pregnancy (p-0.047). The rate of flare-ups 12 months' postpartum was also higher compared to women without any flare-up during pregnancy (p = 0.01). Severity of flare-ups in the postpartum period was worse in women who experienced a flare-up during pregnancy compared to women without flare-ups (p = 0.001). The severity of flare-ups was higher in the first pregnancy compared to subsequent pregnancies. CONCLUSIONS: Women who had active or non-controlled uveitis prior to pregnancy have higher disease activity and severity during pregnancy as well. The first pregnancy seems to behave differently from subsequent pregnancies, in terms of disease severity.

Bibliometric analysis of publications discussing the use of the artificial intelligence technique agent-based models in sustainable agriculture.

The purpose of this article consists of analyzing publications discussing the use of agent-based artificial intelligence models in sustainable agriculture research. The analysis involved bibliometric indicators and the Rstudio software with Bibliometrix library. The methodology is descriptive with a quantitative approach. Scientific databases SCOPUS and Web of Science were consulted and the PRISMA methodology was used during the selection process. This led to finding 86 publications that met the inclusion criteria. Amongst the results, United States was listed as the country with the highest production of scientific material, although France had a higher impact. Additionally, the bibliographical resources that help promote scientific development are open source. It was concluded that the agent-based model has been adopted to simulate different scenarios, which help decision-makers to formulate public policies in favor of sustainable agriculture. This optimizes the use of natural resources and reduces negative consequences for the environment, while also delivering value for the stakeholders of the agricultural system.

Mentoring: what to expect from our surgical mentors in Colombia? A Latin American example.

OBJECTIVE: Identifying the scope of surgical mentoring at Pontificia Universidad Javeriana and compare the perceptions of teachers and students to recognize characteristics and competences of such practice and future needs. METHOD: Two surveys were designed to evaluate the existence and importance of mentoring and inquire about the characteristics, qualities and skills expected on mentors. RESULTS: Both groups agree on the importance of having a mentor. 84.2% of teachers consider themselves mentors, however, only 38.6% of students considered them as such. The most relevant quality of the mentor recognized by students was the willingness and ability to teach, while for teachers it was respect. For the students, the most important competence was the ability to explain and teach about the procedures to be performed, while for teachers it was the ability to provide confidence and security. CONCLUSIONS: There is a paradoxical behavior, most students consider they do not have a mentor while most teachers consider to be such. The need to expand the literature regarding mentoring in Colombia specifically in the surgical field was identified.

OBJETIVO: Identificar el alcance del mentoring quirúrgico en la Facultad de Medicina de la Pontificia Universidad Javeriana y comparar las percepciones de docentes y estudiantes, con el fin de reconocer características y competencias de dicha práctica y necesidades a futuro. MÉTODO: Se diseñaron dos encuestas para evaluar la existencia y la importancia del proceso de mentoring e indagar acerca de las características, las cualidades y las competencias esperadas de los mentores. RESULTADOS: Ambos grupos coinciden en la importancia de contar con un mentor. El 84.2% de los docentes consideran ser mentores, pero solo el 38.6% de los estudiantes los consideraron a ellos como tales. Las cualidad más relevantes del mentor reconocidas por los estudiantes fueron la disposición y la habilidad para enseñar, mientras que para los docentes fue el respeto. Para los estudiantes, la competencia más importante fue la capacidad de explicar y enseñar sobre los procedimientos a realizar, mientras que para los docentes fue la capacidad de brindar confianza y seguridad. CONCLUSIONES: Existe un comportamiento paradójico, pues los estudiantes no consideraron contar con un mentor mientras que los docentes sí estimaron serlo. Se identificó la necesidad de ampliar la literatura respecto al mentoring en Colombia, específicamente en el ámbito quirúrgico.

On optimal temozolomide scheduling for slowly growing glioblastomas.

Background: Temozolomide (TMZ) is an oral alkylating agent active against gliomas with a favorable toxicity profile. It is part of the standard of care in the management of glioblastoma (GBM), and is commonly used in low-grade gliomas (LGG). In-silico mathematical models can potentially be used to personalize treatments and to accelerate the discovery of optimal drug delivery schemes. Methods: Agent-based mathematical models fed with either mouse or patient data were developed for the in-silico studies. The experimental test beds used to confirm the results were: mouse glioma models obtained by retroviral expression of EGFR-wt/EGFR-vIII in primary progenitors from p16/p19 ko mice and grown in-vitro and in-vivo in orthotopic allografts, and human GBM U251 cells immobilized in alginate microfibers. The patient data used to parametrize the model were obtained from the TCGA/TCIA databases and the TOG clinical study. Results: Slow-growth "virtual" murine GBMs benefited from increasing TMZ dose separation in-silico. In line with the simulation results, improved survival, reduced toxicity, lower expression of resistance factors, and reduction of the tumor mesenchymal component were observed in experimental models subject to long-cycle treatment, particularly in slowly growing tumors. Tissue analysis after long-cycle TMZ treatments revealed epigenetically driven changes in tumor phenotype, which could explain the reduction in GBM growth speed. In-silico trials provided support for implementation methods in human patients. Conclusions: In-silico simulations, in-vitro and in-vivo studies show that TMZ administration schedules with increased time between doses may reduce toxicity, delay the appearance of resistances and lead to survival benefits mediated by changes in the tumor phenotype in slowly-growing GBMs.

Range Spectral Filtering in SAR Interferometry: Methods and Limitations.

A geometrical decorrelation constitutes one of the sources of noise present in Synthetic Aperture Radar (SAR) interferograms. It comes from the different incidence angles of the two images used to form the interferograms, which cause a spectral (frequency) shift between them. A geometrical decorrelation must be compensated by a specific filtering technique known as range filtering, the goal of which is to estimate this spectral displacement and retain only the common parts of the images' spectra, reducing the noise and improving the quality of the interferograms. Multiple range filters have been proposed in the literature. The most widely used methods are an adaptive filter approach, which estimates the spectral shift directly from the data; a method based on orbital information, which assumes a constant-slope (or flat) terrain; and slope-adaptive algorithms, which consider both orbital information and auxiliary topographic data. Their advantages and limitations are analyzed in this manuscript and, additionally, a new, more refined approach is proposed. Its goal is to enhance the filtering process by automatically adapting the filter to all types of surface variations using a multi-scale strategy. A pair of RADARSAT-2 images that mapped the mountainous area around the Etna volcano (Italy) are used for the study. The results show that filtering accuracy is improved with the new method including the steepest areas and vegetation-covered regions in which the performance of the original methods is limited.

Validación de los modelos de predicción de desenlaces cardiacos adversos CARPREG II (Cardiac Disease in Pregnancy) y clasificación modificada de la Organización Mundial de la Salud (OMS) en gestantes con cardiopatía / Validation of the CARPREG II risk stratification model and the WHO scale in pregnant women with heart disease

Resumen Introducción: En gestantes con cardiopatía, los modelos de estratificación del riesgo de desenlaces adversos permiten guiar las decisiones clínicas y establecer estrategias de seguimiento y manejo de acuerdo con cada categoría. Objetivo: Validar los modelos de predicción de riesgo de desenlaces cardiacos adversos CARPREG II y OMSm en gestantes con cardiopatía. Materiales y método: Estudio de validación y comparación de dos modelos de predicción de riesgo en una cohorte prospectiva de gestantes con cardiopatía, valoradas por un equipo cardioobstétrico en un país de ingresos medios. Se evaluaron los desenlaces cardiovasculares y perinatales y se determinó la calibración y el nivel de discriminación de estas herramientas. Resultados: Entre 328 gestantes (27 años DE = 7), el 33% (n = 110) tenían cardiopatía congénita, el 30% (n = 98) arritmias, el 14% (n = 46) valvulopatías y el 9% (n = 29) miocardiopatía. Un evento cardiaco ocurrió en el 15% (10% primario y 5% secundario). La discriminación de ambos modelos fue adecuada (AUC-ROC: 0.74; IC 95%: 0.64-0.84 para CARPREG II y 0.77 para OMSm; IC 95%: 0.69-0.86). La calibración también es buena (Hosmer-Lemeshow > 0.05). Las variables numéricas fracción de eyección y presión sistólica de la arteria pulmonar, pueden mejorar la capacidad de predicción del CARPREG II. Conclusiones: Los modelos CARPREG II y OMSm tienen buena capacidad de predicción del riesgo de desenlaces cardiacos adversos y se ajustan a nuestras gestantes con cardiopatía.

Abstract Introduction: In pregnant women with heart disease, risk stratification models for adverse outcomes allow guiding clinical decisions and establish monitoring and management strategies according to each category. Objective: To validate CARPREG II and WHOm adverse cardiac outcome risk prediction models in this population. Materials and methods: Validation and comparison study of two risk prediction models in a prospective cohort of pregnant women with heart disease, assessed by a team cardio-obstetrician in a middle-income country. We assessed cardiovascular and perinatal outcomes and determined the calibration and level of discrimination of these tools. Results: Among 328 pregnant women (27 years SD = 7), 33% (n = 110) had congenital heart disease, 30% (n = 98) arrhythmias, 14% (n = 46) valvular pathologies and 9% (n = 29) cardiomyopathies. A cardiac event occurred in 15% (10% primary and 5% secondary). Discrimination of both models was adequate (AUC-ROC 0.74 CI 95% 0.64-0.84 for CARPREG II and 0.77 for WHOm 95% CI 0.69-0.86). The calibration is also good (Hosmer-Lemeshow >0.05). The Numerical variables of fraction of ejection and systolic pressure of the pulmonary artery can improve the predictive ability of CARPREG II. Conclusions: The CARPREG II and WHOm risk stratification models have good ability to predict the risk of adverse cardiac outcomes and are adjusted to our pregnant women with heart disease.