Impact of automatic segmentation on the quality, productivity and self-reported post-editing effort of intralingual subtitles

This paper describes the evaluation methodology followed to measure the impact of using a machine learning algorithm to automatically segment intralingual subtitles. The segmentation quality, productivity and self-reported post-editing effort achieved with such approach are shown to improve those obtained by the technique based in counting characters, mainly employed for automatic subtitle segmentation currently. The corpus used to train and test the proposed automated segmentation method is also described and shared with the community, in order to foster further research in this are

Residuos de productos lácteos y de grasa de carne en dos recipientes cerámicos de la Edad del Bronce del Valle Medio del Duero

A través de análisis por cromatografía de gases-espectrometría de masas y del estudio de las reacciones inmunoquímicas de la caseína, se ha logrado identificar el residuo de sendos vasos cerámicos del horizonte inicial de Cogotas I de la provincia de Valladolid: un preparado de leche con cereales y grasa de carne. A partir de ahí, se insiste en la importancia de la actividad ganadera entre las comunidades del Bronce Medio de la Meseta y se considera, asimismo, la posibilidad de que el contenido de tales vasijas "completas" representara una ofrenda entre tantas otras atestiguadas en los "campos de hoyos" cogotianos.Through the application of Gas Chromatography-Mass Spectrometry and the determination of casein based on its immunochemical reactions, residues of animal fats and dairy products have been detected in two Bronze Age (Early Cogotas I culture) pottery vessels from Valladolid. The importance of cattle raising activities among the Middle Bronze Age societies of the Spanish Meseta is assessed here. It is argued that the original contents deposited in these vessels may have been offerings, as is the case with other materials that are found in the Cogotas I pit fields

Optimizing the procedure to manufacture clinical‐grade NK cells for adoptive immunotherapy

Natural killer (NK) cells represent promising tools for cancer immunotherapy. We report the optimization of an NK cell activation–expansion process and its validation on clinical‐scale. Methods: RPMI‐1640, stem cell growth medium (SCGM), NK MACS and TexMACS were used as culture mediums. Activated and expanded NK cells (NKAE) were obtained by coculturing total peripheral blood mononuclear cells (PBMC) or CD45RA+ cells with irradiated K562mbIL15‐41BBL or K562mbIL21‐41BBL. Fold increase, NK cell purity, activation status, cytotoxicity and transcriptome profile were analyzed. Clinical‐grade NKAE cells were manufactured in CliniMACS Prodigy. Results: NK MACS and TexMACs achieved the highest NK cell purity and lowest T cell contamination. Obtaining NKAE cells from CD45RA+ cells was feasible although PBMC yielded higher total cell numbers and NK cell purity than CD45RA+ cells. The highest fold expansion and NK purity were achieved by using PBMC and K562mbIL21‐41BBL cells. However, no differences in activation and cytotoxicity were found when using either NK cell source or activating cell line. Transcriptome profile showed to be different between basal NK cells and NKAE cells expanded with K562mbIL21‐41BBL or K562mbIL15‐41BBL. Clinical‐grade manufactured NKAE cells complied with the specifications from the Spanish Regulatory Agency. Conclusions: GMP‐grade NK cells for clinical use can be obtained by using different starting cells and aAPCThis work was supported by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI18/01301 to Pérez-Martínez A, CRIS Foundation to Beat Cancer to Escudero A, Fernández A; Navarro A, Mirones I, and Fundación Mari Paz Jiménez Casado and La Sonrisa de Álex to Vela

Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease.

BACKGROUND AND AIMS: Alpha-1 antitrypsin (AAT) is a product of SERPINA1 gene mainly expressed by hepatocytes. Clinically relevant mutations in the SERPINA1 gene, such as Z (Glu342Lys), results in an expression of misfolded AAT protein having high propensity to polymerize, accumulate in hepatocytes and thus to enhance a risk for hepatocyte damage and subsequent liver disease. So far, the relationship between the Z-AAT accumulation and liver cell damage remains not completely understood. We present three-dimensional organoid culture systems, as a novel tool for modeling Z-AAT-related liver diseases. METHODS: We have established liver organoids from liver biopsies of patients with homozygous (ZZ) and heterozygous (MZ) deficiency and normal (MM) genotypes of AAT. The features of these organoid models were characterized by analyzing AAT protein secretion and intracellular aggregation in MZ and ZZ genotypes as well as SERPINA1 expression in differentiated cultures. RESULTS: Transcriptional analysis of differentiated organoid cultures by RNA-Seq showed hepatocyte-specific gene expression profile. Genes, such as ALB, APOB, CYP3A4 and SERPINA1, were validated and confirmed through quantitative-PCR analysis. The organoids from MZ and ZZ cases showed intracellular aggregation and lower secretion of AAT protein, and lower expression of ALB and APOB, as typically seen in hepatocytes from Z-AAT deficiency patients. Furthermore, organoids responded to external stimulus. Treatment with oncostatin M, a well-known inducer of SERPINA1, increased expression of the full-length transcripts (AAT-1C) as well as the short transcript of AAT (AAT-ST1C4). CONCLUSIONS: Liver organoid model recapitulates the key features of Z-AAT deficiency and provides a useful tool for disease modeling

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Cursos vitales, envejecimiento y organización social de los cuidados

El presente trabajo propone compartir un andamiaje conceptual que viabilice la comprensión y análisis de los fenómenos sociales ligados al envejecimiento y la vejez. Reconociendo que en América Latina se produce el tránsito de una sociedad hacia la madurez demográfica como consecuencia de factores positivos (Huenchuan y Rodríguez-Piñero, 2010), y requiere del desarrollo de acciones político- institucionales que posibiliten atender la organización social y política de los cuidados. Se realizan aportes conceptuales desde el curso vital, reconociendo las nociones de trayectorias y expectativas sociales ligadas a la edad. La estructuración social de las edades opera en una tensión adultocéntrica que pone en jaque el deseo de envejecer. Y avanzamos en la identificación de la crisis de los cuidados como expresión de las contradicciones socio productiva del capitalismo financiero, y agregamos de la matriz cuatríada como modo de dominación.The present work proposes to share a conceptual scaffolding that enables the understanding and analysis of social phenomena linked to aging and old age. Recognizing that in Latin America the transition of a society towards demographic maturity occurs as a consequence of positive factors (Huenchuan and Rodríguez-Piñero, 2010), and requires the development of political-institutional actions that make it possible to address the social and political organization of care. Conceptual contributions are made from the life course, recognizing the notions of trajectories and social expectations linked to age. The social structuring of ages operates in an adult-centric tension that puts the desire to grow old in check. And we advance in the identification of the care crisis as an expression of the socio-productive contradictions of financial capitalism, and we add the fourfold matrix as a mode of domination.Facultad de Trabajo Socia

Analysis of Senior Citizens’ Participation in Social Organizations

The present study follows Chilean older persons’ social participation in organizations. The methodology used corresponds to the data delivery period from the National Socioeconomic Characterization Survey (CASEN), where the samples used are 2003 (n = 257,077), 2009 (n = 246,924), 2011 (n = 200,302), 2015 (n = 266,968), and 2017 (n = 216,439). The data were processed using SPSS statistical software (version 27.0) for a descriptive analysis of the data and variable crossing, along with a comparison based on presenting the data in maps via QGis geographical software (3.36.6 version). The main finding of the present study is that while social participation in organizations continues a cross-sectional downward trend across Chilean population age groups, there are still good indicators among elderly people, determining non-participation profiles for public policy implementation. Some determinants for participation in this age group above the rest of the population may be due to improved health conditions, more free time after retirement, and cultural determinants inciting active participation in society

The structure at 2 A resolution of Phycocyanin from Gracilaria chilensis and the energy transfer network in a PC-PC complex.

Phycocyanin is a phycobiliprotein involved in light harvesting and conduction of light to the reaction centers in cyanobacteria and red algae. The structure of C-phycocyanin from Gracilaria chilensis was solved by X-ray crystallography at 2.0 A resolution in space group P2(1). An interaction model between two PC heterohexamers was built, followed by molecular dynamic refinement. The best model showed an inter-hexamer rotation of 23 degrees . The coordinates of a PC heterohexamer (alphabeta)(6) and of the PC-PC complex were used to perform energy transfer calculations between chromophores pairs using the fluorescence resonance energy transfer approach (FRET). Two main intra PC ((I)beta(3)(82)-->(I)alpha(1)(84)-->(I)alpha(5)(84)-->(I)beta(6)(82) and (I)beta(3)(153)-->(I)beta(5)(153)) and two main inter PC ((I)beta(6)(82)-->(II)beta(3)(82) and (I)beta(5)(153)-->(II)beta(3)(153)) pathways were proposed based on the values of the energy transfer constants calculated for all the chromophore pairs in the hexamer and in the complex

Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease

Abstract: Background and aims: Alpha-1 antitrypsin (AAT) is a product of SERPINA1 gene mainly expressed by hepatocytes. Clinically relevant mutations in the SERPINA1 gene, such as Z (Glu342Lys), results in an expression of misfolded AAT protein having high propensity to polymerize, accumulate in hepatocytes and thus to enhance a risk for hepatocyte damage and subsequent liver disease. So far, the relationship between the Z-AAT accumulation and liver cell damage remains not completely understood. We present three-dimensional organoid culture systems, as a novel tool for modeling Z-AAT-related liver diseases. Methods: We have established liver organoids from liver biopsies of patients with homozygous (ZZ) and heterozygous (MZ) deficiency and normal (MM) genotypes of AAT. The features of these organoid models were characterized by analyzing AAT protein secretion and intracellular aggregation in MZ and ZZ genotypes as well as SERPINA1 expression in differentiated cultures. Results: Transcriptional analysis of differentiated organoid cultures by RNA-Seq showed hepatocyte-specific gene expression profile. Genes, such as ALB, APOB, CYP3A4 and SERPINA1, were validated and confirmed through quantitative-PCR analysis. The organoids from MZ and ZZ cases showed intracellular aggregation and lower secretion of AAT protein, and lower expression of ALB and APOB, as typically seen in hepatocytes from Z-AAT deficiency patients. Furthermore, organoids responded to external stimulus. Treatment with oncostatin M, a well-known inducer of SERPINA1, increased expression of the full-length transcripts (AAT-1C) as well as the short transcript of AAT (AAT-ST1C4). Conclusions: Liver organoid model recapitulates the key features of Z-AAT deficiency and provides a useful tool for disease modeling