Lactate concentration gradient from right atrium to pulmonary artery

INTRODUCTION: We compared simultaneous measurements of blood lactate concentration ([Lac]) in the right atrium (RA) and in the pulmonary artery (PA). Our aim was to determine if the mixing of right atrial with coronary venous blood, having substantially lower [Lac], results in detectable decreases in [Lac] from the RA to the PA. METHODS: A prospective, sequential, observational study was conducted in a medical-surgical intensive care unit. We enrolled 45 critically ill adult individuals of either sex requiring pulmonary artery catheters (PACs) to guide fluid therapy. Immediately following the insertion of the PAC, one paired set of blood samples per patient was drawn in random order from the PAC's proximal and distal ports for measurement of hemoglobin concentration, O(2 )saturation (SO(2)) and [Lac]. We defined Δ[Lac] as ([Lac](ra )- [Lac](pa)), ΔSO(2 )as (S(ra)O(2 )- S(pa)O(2)) and the change in O(2 )consumption (ΔVO(2)) as the difference in systemic VO(2 )calculated using Fick's equation with either S(ra)O(2 )or S(pa)O(2 )in place of mixed venous SO(2). Data were compared by paired Student's t-test, Spearman's correlation analysis and by the method of Bland and Altman. RESULTS: We found S(ra)O(2 )> S(pa)O(2 )(74.2 ± 9.1 versus 69.0 ± 10.4%; p < 0.001) and [Lac](ra )> [Lac](pa )(3.9 ± 3.0 versus 3.7 ± 3.0 mmol.l(-1); p < 0.001). Δ[Lac] correlated with ΔVO(2 )(r(2 )= 0.34; p < 0.001). CONCLUSION: We found decreases in [Lac] from the RA to PA in this sample of critically ill individuals. We conclude that parallel decreases in SO(2 )and [Lac] from the RA to PA support the hypothesis that these gradients are produced by mixing RA with coronary venous blood of lower SO(2 )and [Lac]. The present study is a preliminary observation of this phenomenon and further work is needed to define the physiological and clinical significance of Δ[Lac]

Hematopoiesis under telomere attrition at the single-cell resolution

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells’ self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA, overcomes interferon signaling activation in telomere-dysfunctional hematopoietic stem cells and these cells’ skewed differentiation towards the megakaryocytic lineage. This study challenges the historical hypothesis that telomere attrition limits the proliferative potential of hematopoietic stem cells by inducing apoptosis, autophagy, or senescence, and suggests that targeting IFI16 signaling axis might prevent hematopoietic stem cell functional decline in conditions affecting telomere maintenance

Improving Latin American soil information database for digital soil mapping enhances its usability and scalability

Spatial soil databases can help model complex phenomena in which soils are decisive, for example, evaluating agricultural potential or estimating carbon storage capacity. The Soil Information System for Latin America and the Caribbean, SISLAC, is a regional initiative promoted by the FAO's South American Soil Partnership to contribute to the sustainable management of soil. SISLAC includes data coming from 49,084 soil profiles distributed unevenly across the continent, making it the region's largest soil database. However, some problems hinder its usages, such as the quality of the data and its high dimensionality. The objective of this research is twofold. First, to evaluate the quality of SISLAC and its data values and generate a new, improved version that meets the minimum quality requirements to be used by different interests or practical applications. Second, to demonstrate the potential of improved soil profile databases to generate more accurate information on soil properties, by conducting a case study to estimate the spatial variability of the percentage of soil organic carbon using 192 profiles in a 1473 km2 region located in the department of Valle del Cauca, Colombia. The findings show that 15 percent of the existing soil profiles had an inaccurate description of the diagnostic horizons. Further correction of an 4.5 additional percent of existing inconsistencies improved overall data quality. The improved database consists of 41,691 profiles and is available for public use at ttps://doi.org/10.5281/zenodo.6540710 (Díaz-Guadarrama, S. & Guevara, M., 2022). The updated profiles were segmented using algorithms for quantitative pedology to estimate the spatial variability. We generated segments one centimeter thick along with each soil profile data, then the values of these segments were adjusted using a spline-type function to enhance vertical continuity and reliability. Vertical variability was estimated up to 150 cm in-depth, while ordinary kriging predicts horizontal variability at three depth intervals, 0 to 5, 5 to 15, and 15 to 30 cm, at 250 m-spatial resolution, following the standards of the GlobalSoilMap project. Finally, the leave-one-out cross validation provides information for evaluating the kriging model performance, obtaining values for the RMSE index between 1.77% and 1.79% and the R2 index greater than 0.5. The results show the usability of SISLAC database to generate spatial information on soil properties and suggest further efforts to collect a more significant amount of data to guide sustainable soil management.Fil: Diaz Guadamarra, Sergio. Universidad Nacional de Colombia. Facultad de Ciencias Agrarias. Departamento de Agronomía; ColombiaFil: Lizarazo, Iván. Universidad Nacional de Colombia. Facultad de Ciencias Agrarias. Departamento de Agronomía; ColombiaFil: Guevara, Mario. Universidad Nacional Autónoma de México. Campus Juriquilla. Centro de Geociencias; MéxicoFil: Guevara, Mario. Universidad Nacional Autónoma de México.Campus Juriquilla. Centro de Geociencias; México. United States Department of Agriculture. Soil Salinity National Laboratory, Estados UnidosFil: Angelini, Marcos Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Wageningen University. Soil Geography and Landscape Group; Países Bajos. International Soil Reference and Information Centre. World Soil Information; Países BajosFil: Araujo Carrillo, Gustavo A. Corporación Colombiana de Investigación Agropecuaria AGROSAVIA; ColombiaFil: Argeñal, Jainer. Universidad Nacional Autónoma de Honduras. Facultad de Ciencias; Honduras.Fil: Armas, Daphne. Universidad de Almería. Departamento de Agronomía, Edif. CITEIIB, España.Fil: Balsa, Rafael A. Ministerio de Desarrollo Agrario y Riego. Dirección General de Asuntos Ambientales Agrarios, Perú.Fil: Bolivar, Adriana. Instituto Geográfico Agustín Codazzi. Subdirección Agrología; ColombiaFil: Bustamante, Nelson. Servicio Agrícola y Ganadero; Chile.Fil: Dart, Ricardo O. Embrapa Solos; BrasilFil: Dell Acqua, Martín. Ministerio de Ganadería, Agricultura y Pesca. Dirección General de Recursos Naturales; UruguayFil: Lencina, Arnulfo. Universidad Nacional de Asunción. Facultad de Ciencias Agrarias; ParaguayFil: Figueredo, Hernán. Sociedad Boliviana de la Ciencia del Suelo; Bolivia.Fil: Fontes, Fernando. Ministerio de Ganadería, Agricultura y Pesca. Dirección General de Recursos Naturales; UruguayFil: Gutierrez Diaz, Joan S. Aarhus University. Faculty of Science and Technology,.Department of Agroecology; DinamarcaFil: Jiménez, Wilmer. Ministerio de Agricultura y Ganadería; Ecuador.Fil: Rodriguez, Dario Martin. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Schulz, Guillermo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Tenti Vuegen, Leonardo Mauricio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentin

Classification methods to identify lesions in skin starting from spectra of diffuse reflectance

Con el objetivo de discriminar lesiones benignas y malignas en la piel humana a partir de espectros de reflexión difusa, se han analizado diferentes algoritmos de clasificación usando el software de aprendizaje automático y reconocimiento de patrones WEKA. Además, dada la alta dimensionalidad de la señal espectral, fue empleada una técnica selección de atributos para determinar las variables que aporten la mayor cantidad de información. Se probó la clasificación de la señal usando los algoritmos de máquinas de vectores de soporte, redes neuronales y bosques aleatorios, el desempeño fue evaluado usando el promedio de la k-fold cross-validation tomando en cuenta los porcentajes de instancias clasificadas correctamente, el índice kappa, el área bajo la curva ROC, la sensibilidad, y la especifidad. Finalmente se demuestra que el algoritmo de redes neuronales con los parámetros momentum y learning rate en 0,6 y 0,3 respectivamente, es el que mejor se adapta al problema de reconocimiento de patrones ya que clasifica correctamente al 89,89% de los casos.In order to differentiate between benign and malignant lesions in the human skin using diffuse reflection spectra, different classification algorithms were tested using the WEKA data mining software. In addition, due to the high dimensionality of the spectral signal, an attribute selection technique was applied to determine the variables that contribute with more information. The spectral signal classification was tested using support vector machines, neural networks and random forests, their performance was measured using the k-fold cross-validation percentages of the Kappa statistic, area under the ROC curve, specificity and sensitivity. Finally it is shown that the one layer neural network with 6 neurons and the parameters momentum and learning rate in 0.6 and 0.3 respectively, is best suited to the problem of pattern recognition, achieving correctly classify 89.89% of the cases

Response-adapted treatment with rituximab, bendamustine, mitoxantrone, and dexamethasone followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma after first-line immunochemotherapy: Results of the RBMDGELTAMO08 phase II trial

Background Consensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy. Methods This phase II trial evaluated the efficacy and safety of response-adapted therapy with rituximab, bendamustine, mitoxantrone, and dexamethasone (RBMD) in follicular lymphoma patients who relapsed after or were refractory to first-line immunochemotherapy. Sixty patients received three treatment cycles, and depending on their response received an additional one (complete/unconfirmed complete response) or three (partial response) cycles. Patients who responded to induction received rituximab maintenance therapy for 2 years. Results Thirty-three (55%) and 42 (70%) patients achieved complete/unconfirmed complete response after three cycles and on completing induction therapy (4-6 cycles), respectively (final overall response rate, 88.3%). Median progression-free survival was 56.4 months (median follow-up, 28.3 months; 95% CI, 15.6-51.2). Overall survival was not reached. Progression-free survival did not differ between patients who received four vs six cycles (P = .6665), nor between patients who did/did not receive rituximab maintenance after first-line therapy (P = .5790). Median progression-free survival in the 10 refractory patients was 25.5 months (95% CI, 0.6-N/A) and was longer in patients who had shown progression of disease after 24 months of first-line therapy (median, 56.4 months; 95% CI, 19.8-56.4) than in those who showed early progression (median, 42.31 months; 95% CI, 24.41-NA) (P = .4258). Thirty-six (60%) patients had grade 3/4 neutropenia. Grade 3/4 febrile neutropenia and infection were recorded during induction (4/60 [6.7%] and 5/60 [8.3%] patients, respectively) and maintenance (2/43 [4.5%] and 4/43 [9.1%] patients, respectively). Conclusions This response-adapted treatment with RBMD followed by rituximab maintenance is an effective and well-tolerated salvage treatment for relapsed/refractory follicular lymphoma following first-line immunochemotherapy

Deepint.net: A rapid deployment platform for smart territories

This paper presents an efficient cyberphysical platform for the smart management of smart territories. It is efficient because it facilitates the implementation of data acquisition and data management methods, as well as data representation and dashboard configuration. The platform allows for the use of any type of data source, ranging from the measurements of a multi-functional IoT sensing devices to relational and non-relational databases. It is also smart because it incorporates a complete artificial intelligence suit for data analysis; it includes techniques for data classification, clustering, forecasting, optimization, visualization, etc. It is also compatible with the edge computing concept, allowing for the distribution of intelligence and the use of intelligent sensors. The concept of smart cities is evolving and adapting to new applications; the trend to create intelligent neighbourhoods, districts or territories is becoming increasingly popular, as opposed to the previous approach of managing an entire megacity. In this paper, the platform is presented, and its architecture and functionalities are described. Moreover, its operation has been validated in a case study where the bike renting service of Paris—Vélib’ Métropole has been managed. This platform could enable smart territories to develop adapted knowledge management systems, adapt them to new requirements and to use multiple types of data, and execute efficient computational and artificial intelligence algorithms. The platform optimizes the decisions taken by human experts through explainable artificial intelligence models that obtain data from IoT sensors, databases, the Internet, etc. The global intelligence of the platform could potentially coordinate its decision-making processes with intelligent nodes installed in the edge, which would use the most advanced data processing techniques.This work has been partially supported by the European Regional Development Fund (ERDF) through the Interreg Spain-Portugal V-A Program (POCTEP) under grant 0677_DISRUPTIVE_2_E, the project My-TRAC: My TRAvel Companion (H2020-S2RJU-2017), the project LAPASSION, CITIES (CYTED 518RT0558) and the company DCSC. Pablo Chamoso’s research work has been funded through the Santander Iberoamerican Research Grants, call 2020/2021, under the direction of Paulo Novais

Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8+ T-Cell Response: Reversal by Adenoviral Vaccine

MHC class Ia-restricted CD8+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination

Astro2020 APC White Paper: The MegaMapper: a z &gt; 2 spectroscopic instrument for the study of Inflation and Dark Energy

MegaMapper is a proposed ground-based experiment to measure Inflation parameters and Dark Energy from galaxy redshifts at