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IntroductionCardiovascular disease is the major cause of premature death in chronic kidney disease (CKD) and vascular damage is often detected belatedly, usually evaluated by expensive and invasive techniques. CKD involves specific risk factors that lead to vascular calcification and atherosclerosis, where inflammation plays a critical role. However, there are few inflammation-related markers to predict vascular damage in CKD. This study aimed to investigate immune populations in pre-dialysis patients to (i) identify subset alterations, (ii) assess longitudinal changes, and (iii) evaluate their applicability as biomarkers of subclinical vascular indices.Methods43 pre-dialysis CKD patients in stages CKD-2 to CKD-5 and 38 controls were recruited at baseline and after 18-month follow-up. Aortic stiffness was determined by carotid-femoral pulse wave velocity (PWV) and abdominal aortic calcification was quantified by the Kauppila index on X-rays. Carotid intima-media thickness, the number of carotid plaques and adventitial neovascularization were evaluated by Superb Microvascular Imaging. Peripheral blood mononuclear cells were isolated and immune cell populations were assessed by flow cytometry: senescent T cells (CD4+CD28null), Tang (CD3+CD31+CD184+) and derived subsets, and monocyte subsets (classical, intermediate and non-classical; and ACE expression).ResultsSenescent T cells were increased in CKD. Despite Tang levels were unchanged compared to controls, this subset exhibited enhanced immunosenescence traits (CD28null and inverted CD4+CD8+ ratio) in CKD. Furthermore, Tang were negatively correlated with CKD progression. Slight alterations within monocyte subsets were observed. These findings were validated at the 18-month follow-up. Tang were correlated with several subclinical indices, and further analyses revealed an independent effect on PWV and their potential value as biomarkers. Intermediate monocytes were positively correlated with PWV.ConclusionPre-dialysis CKD stages are hallmarked by alterations in immune cell populations related to vascular homeostasis, including early T-cell immunosenescence traits and a stage-dependent Tang depletion, which was independently related to vascular stiffness. All these features were replicated upon follow-up, thus providing validation toward our results. Our findings pave the ground for future studies addressing the functional contribution of these cellular mediators at the local level, assessing their potential predictive value in the long-term and implementing preventive strategies in the clinical setting.

Introduction: Diffuse intrinsic pontine glioma (DIPG) is the most common malignant brainstem tumour in children. Despite advances in understanding its biology, current treatments have shown minimal impact on overall survival in this fatal disease. Focal radiotherapy (RT) is the only treatment proven to improve symptoms and extend progression-free survival. Albeit palliative, re-irradiation (rRT) has emerged as the best alternative for progressive disease. This study presents the Spanish experience with re-irradiation in DIPG. Results: Between April 2015 and December 2023, 44 paediatric patients with progressive DIPG underwent rRT in 16 Spanish institutions. Median time from diagnosis to progression was 9.9 months (range, 4.2–24.3 months). Median dose of rRT was 20 Gy (range, 18–40 Gy) in 2 Gy fractions (range, 1.3–4 Gy). Twenty-two patients (50 %) received other treatments besides RT. Clinical improvement was seen in 77.3 %, and radiological improvement in 60 %. Treatment was well tolerated (1 case toxicity >grade 2 related to rRT). Median overall survival was 15.5 months (range, 8.2–63.2 months), with a median time from rRT to death of 4.2 months (range, 0.6–10.3 months). Longer time between diagnosis and rRT (>10 months) and dose of rRT >20 Gy were statistically significantly correlated with better overall survival. There was no survival benefit in patients receiving additional treatments. Conclusions: Re-irradiation is safe and effective in progressive DIPG patients, not only improving symptoms but also prolonging survival. However, the ideal candidates for rRT remain undefined, as well as the best irradiation scheme. Prospective studies are needed.

En este trabajo reflexionaré sobre una presencia permanente en la vida cotidiana de familiares de detenidos-desaparecidos de la dictadura de Pinochet, que como categoría nativa es denominada «pena» y hace referencia a un estado de tristeza que puede provocar enfermedades, pero también lleva a la acción. Lo que veremos es que, si bien la recuperación de los cuerpos y los funerales asociados permiten el enfrentamiento a la muerte, el cierre de ciertos ciclos, y la elaboración de los procesos de duelo, no siempre éstos son atravesados superando la pena, ya que ésta deriva de la experiencia de «crueldad», «deshumanización» tortura, y tipo de muerte que sufrieron sus familiares. Propondré el concepto analítico de Pena Raíz ya que, como entidad en la que se ancla una combinación de agencias, genera atenciones recíprocas por estar asociada directamente con la experiencia del duelo del familiar y la esencia del sujeto fallecido al que se quiere y necesita seguir cuidando a pesar de los años transcurridos. Para ello trabajaré con experiencias de familiares de detenidos desaparecidos en el marco de un trabajo de campo prolongado y focalizaré en algunos casos del Norte de Chile en los que los familiares recuperaron los cuerpos.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD (''Chronic Kidney Disease-Mineral and Bone Disorders'') complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism. Resumen: La valoración del riesgo de fractura del paciente con enfermedad renal crónica (ERC) ha sido incluida en el complejo CKD-MBD («Chronic Kidney Disease-Mineral and Bone Disorders») en guías nefrológicas internacionales y nacionales, sugiriéndose por primera vez la evaluación de la densidad mineral ósea (DMO) si los resultados pueden condicionar la toma de decisiones terapéuticas. Sin embargo, existe muy poca información en práctica clínica real en esta población. El objetivo principal del estudio ERCOS (ERC-Osteoporosis) es describir el perfil de los pacientes con ERC G 3-5 D con osteoporosis (OP) y/o fracturas por fragilidad atendidos en consultas especializadas de nefrología, reumatología y medicina interna en España. Participaron 15 centros y se incluyeron 162 pacientes (siendo en su mayoría mujeres [71,2%] postmenopáusicas [98,3%]) con una mediana de edad de 77 años. La mediana del filtrado glomerular estimado (FGe) fue de 36 mL/min/1,73m2 y 38% de pacientes incluidos estaban en diálisis. Destacamos la elevada frecuencia de fracturas por fragilidad prevalentes [37,7%), principalmente vertebrales (52,5%) y de cadera (24,6%)], el antecedente desproporcionado de pacientes con patología glomerular en comparación a series puramente nefrológicas (corticoides) y el infratratamiento para la prevención de fracturas, fundamentalmente en consultas nefrológicas. Este estudio supone una inmediata llamada a la acción con la difusión de las nuevas guías clínicas, más proactivas, y subraya la necesidad de homogeneizar el enfoque asistencial/terapéutico multidisciplinar coordinado de estos pacientes de un modo eficiente para evitar las actuales discrepancias y el nihilismo terapéutico.

Abstract Dark bubble cosmology is an alternative paradigm to compactification, which can circumvent issues of moduli stabilization and scale separation. In this paper we investigate how electromagnetic fields can be incorporated in this framework. Worldvolume fields backreact on the ambient universe in which the bubble expands, which in turn affects the energy-momentum distribution and the effective gravity induced on the brane. We compute these effects, showing that the resulting four-dimensional cosmology consistently includes electromagnetic waves.

Context.--In 2019, papillary renal neoplasm with reverse polarity (PRNRP) was defined as a new neoplasm because it has a predominately tubulopapillary pattern lined by a single layer of cuboidal and eosinophilic cells with apically located round nuclei. Immunohistochemically, this neoplasm showed expression of GATA-3 and L1CAM and had recurrent KRAS mutations. Objective.--To estimate the incidence of PRNRP and provide 8 additional cases with some variations in the morphology. Design.--We reviewed 1627 renal tumors from our hospital during a 21-year period (2000-2020). We reexamined 196 papillary renal cell carcinomas and selected those that met the diagnostic criteria for PRNRP. Results.--We found 8 cases consistent with PRNRP. The median age of the patients was 64.75 years; 7 patients were male, and 1 was female. Two patients had end-stage renal disease. No recurrence, metastasis, or tumor-related death occurred in a mean follow-up period of 67.62 months. Tumor size ranged from 1.6 to 3.7 cm. All cases were (7 of 8; 87.5%) had predominantly cystic changes, and 1 had solid architecture. No foamy cells, clear cell change, or psammoma bodies were seen in any cases. All cases were positive for CK7, EMA, GATA3, and L1CAM. KRAS gene mutation was detected in 5 cases (5 of 8; 62.5%). Conclusions.--PRNRP represents 4.08% (8 of 196 cases) of papillary renal cell carcinomas and 0.49% (8 of 1627 cases) of all renal tumors in the 21-year period in our series. In our study, all cases exhibited an indolent clinical course. This supports that PRNRP has characteristic morphologic and molecular features. (Arch Pathol Lab Med. 2023;147:692-700; doi: 10.5858/arpa.2022-0156-OA), Papillary renal cell carcinoma (PRCC) is the second most frequent histologic type of renal cell carcinoma. Since 1997, it has been classified into type 1 and type 2 according to [...]

Sawfish conservation is a critical concern, yet insufficient baseline data on their presence and status has hindered conservation efforts at national and regional levels. Between 2015 and 2017, interviews were conducted in fishing communities in Ecuador and Peru to assess the historical and current status of largetooth sawfish Pristis pristis. Interviews with cockfighting practitioners in Peru aimed to gauge the use and demand for cockfighting spurs made from sawfish rostral teeth. Our study confirmed the presence of largetooth sawfish in the waters of both countries. Importantly, some fishermen are aware of the value of rostral teeth, which may influence their decisions not to release sawfish alive. Of the interviewees (n = 188), a majority (88%) reported a perceived decline in sawfish abundance during their lifetimes. In this region, as in other sawfish habitats, bycatch and habitat loss pose significant threats. To address these challenges, potential actions include strategic conservation planning, reinforced national and international trade regulations, education campaigns targeting the cockfighting community, public outreach initiatives, and the live release of sawfish specimens. These efforts can enhance the conservation status of largetooth sawfish, particularly in a region isolated from other persisting populations that potentially harbours vital genetic diversity. Furthermore, safeguarding sawfish contributes to the implementation of national instruments like the National Action Plans for Sharks in both countries. Neglecting these threats could perpetuate sawfish capture and mortality in a region where local populations are already severely depleted, elevating the risk of regional extinction. Prioritizing sawfish conservation is imperative to prevent further decline and preserve their ecological importance.

Low latency and high bandwidth heralded with 5G networks will allow transmission of large amounts of Mission-Critical data over a short time period. 5G hence unlocks several capabilities for novel Public Protection and Disaster Relief (PPDR) applications, developed to support first responders in making faster and more accurate decisions during times of crisis. As various research initiatives are giving shape to the Network Application ecosystem as an interaction layer between vertical applications and the network control plane, in this article we explore how this concept can unlock finer network service management capabilities that can be leveraged by PPDR solution developers. In particular, we elaborate on the role of Network Applications as means for developers to assure prioritization of specific emergency flows of data, such as high-definition video transmission from PPDR field users to remote operators. To demonstrate this potential in future PPDR-over-5G services, we delve into the transfer of network-intensive PPDR solutions to the Network Application model. We then explore novelties in Network Application experimentation platforms, aiming to streamline development and deployment of such integrated systems across existing 5G infrastructures, by providing the reliability and multi-cluster environments they require.

La lectura y la escritura son actividades irremplazables para la formación del ciudadano en una sociedad moderna y democrática, de individuos libres que poseen un elevado autoconocimiento. Se comprende que la reducción de la formación lingüística y literaria de la población ha sido uno de los rasgos más regresivos (por deshumanizadores) de los últimos tiempos. Y a la inversa, su incipiente rehabilitación actual abre perspectivas de trabajo positivo a quienes detectamos el poder humanizador del lenguaje. En este artículo se sostiene la idea de que no hay mejor manera de enseñar a escribir que enseñando a leer, porque escribir y leer son actividades recíprocas (Roca, 2021). Partiendo de esa premisa, se va a proponer una pedagogía del texto literario basada en las tres fases de la hermenéutica de Ricoeur (1980): comprender, explicar y aplicar. La comprensión de la estructura (morfo)-lógica, la explicación de la validez de la interpretación -y su discusión-, y la aplicación, que se refiere a la capacidad de unir horizontes y de ampliarlos a través del diálogo, de una actitud que deja manifestarse a la obra y que invita, al lector, la escritura creativa (Galvan, 2004, Montilla-Narváez, 2021). Esta manera de estudiar la obra literaria centrada en el concepto de aplicación proporciona orientaciones para un pluralismo abierto a la esencia de las obras, incentiva el pensamiento crítico y permite la emergencia de procesos de mejora y transformación (Bain, 2006; Aguirre-Romero, 2019; Roca, 2021). En el capítulo se detallarán los vértices sobre los que se sustenta la aplicación didáctica de esta teoría (la teoría de la complejidad de la competencia comunicativa, el aprendizaje basado en problemas y la hermenéutica literaria).

* Context.--Cardiac metastases are more prevalent than primary cardiac tumors, and although rare, the incidence is anticipated to increase with the extended survival of oncology patients. Objective.--To estimate the current incidence of cardiac metastasis from solid tumors in adult autopsies. Design.--Adult autopsy cases from 1984 through 2019 from patients diagnosed with any type of solid cancer were retrieved. The medical charts and pathologic autopsy data were reviewed in detail. Results.--A total of 1294 adult autopsies performed on patients diagnosed with any type of cancer within the past 35 years were reviewed. We found 124 secondary cardiac tumors. Eighty-five were due to cardiac involvement by solid tumors. Of these, 61 were true cardiac metastases of solid cancers. We focused on these 61 cases. The age range was 32 to 85 years. Forty-four patients were men and 17 were women. The lung was the most common primary site, with 21 cases (34.43%). The most frequent histologic type was carcinoma, with 54 cases (88.52%). The predominant layer of the heart involved was the pericardium, with 35 cases (57.38%). Twenty-one cases (34.43%) had pericardial effusion, with 4 being hemorrhagic. All cases had multiple extracardiac metastases, with 56 cases (91.8%) having distant metastases in 4 or more different organs. Conclusions.--Cardiac metastasis is a rare occurrence, with an incidence of 4.71% (61 of 1294 cases) in our series. Lung cancer accounted for most of the cardiac metastases seen, and carcinomas were the most frequent histologic type. The pericardium was the most frequent location. Cardiac metastases occurred most frequently in cases of massive metastatic dissemination. doi: 10.5858/arpa.2021-0418-OA, According to earlier autopsy studies, the frequency of primary cardiac tumors ranges from 0.001% to 0.3%. (1,2) Most primary cardiac tumors (~75%) are benign, with atrial myxoma being the most [...]

The aim of IEEE Time-Sensitive Networking (TSN) standards is to grant deterministic communication in traditional Ethernet networks for Industry 4.0. Insofar as the use cases in the Factory need some mobility, the extension of the TSN capabilities over the fifth-generation (5G) cellular network is the next step. Some challenges in TSN over 5G, such as TSN translators time synchronization functionality, are well defined in the standards, even if they have not yet been addressed in the market. However other challenges, such as the dynamic configuration of the entire network (or part of the it) based on quality requirements of the current TSN traffic pattern, are defined at a very high level and delegated to vendors for implementation. This paper addresses this challenge, using an Automata Learning approach to monitor and reconfigure the end-to-end 5G QoS flow to keep the quality of a TSN session within the required values. Additionally, algorithms are provided to build the automata from network data and predict potential deviations of the requirements to meet the expected quality. Moreover, this work presents a functional TSN over a 5G testbed where the algorithms have been tested, demonstrating that the proposed solution achieves an improvement of around 40% compared to the usual operation of the network.

Cell therapy utilizing chimeric antigen receptors (CARs) in conjunction with immune cells, primarily T lymphocytes, is known as CAR-T cell therapy. This innovative approach is revolutionizing the landscape of oncohaematology by precisely targeting specific antigens for elimination. However, despite its promising prospects, CAR-T therapy presents several challenges, including a notable rate of disease relapse, intricate pathologies impeding widespread adoption, prolonged manufacturing timelines, and substantial costs. Looking forward, ongoing research and progress aim to address these challenges to mitigate these constraints, underlining the continuous efforts to enhance the efficacy and accessibility of this transformative therapy

The success of the Internet of Things (IoT) has driven the development, among others, of many different software architectures for producing, processing, and analyzing heterogeneous data. In many cases, IoT applications share common features, such as the use of a platform or middleware, also known as message broker, that collects and manages data traffic between endpoints. However, in general, data processing is very dependent on the case study (sensors that send temperature data, drones that send images, etc.). Thus, the applications responsible for receiving and processing data, which we call consumers, have to be built ad hoc, since some of their elements have to be specially configured to solve specific needs of the case study. This paper presents Flextory, a software factory tool to make it easier for IoT developers to automatically construct configurable consumer applications, which we call FLEX-consumers. Flextory guides developers through the process of generating Java consumers by selecting some desired features such as, for instance, the particular communication protocol to be used. This way, the developer only has to concentrate on designing the algorithm to process the data. In short, the use of Flextory will result in consumer applications with configurable behavior, namely FLEX-consumers, that can connect to a messaging server (for example RabbitMQ) and process the received messages.

En la Fundación A LA PAR llevamos más de 70 años trabajando con las personas con discapacidad intelectual por sus derechos y su participación en nuestra sociedad, diseñando apoyos y tendiendo puentes donde ellos encuentran barreras. Una de las principales herramientas que utilizamos para alcanzar el objetivo anteriormente descrito, es la práctica de actividad física adaptada (AFA), entendida como un cuerpo de conocimientos interdisciplinares dedicados a la identificación, aceptación y solución de las diferencias individuales en actividad física, adecuándolas al contexto en el que se desarrollan, en nuestro caso dirigido a personas con discapacidad intelectual. Además, también consideramos relevante la práctica de deporte inclusivo, entendida como aquella actividad física y deportiva que permite la participación conjunta de personas con y sin discapacidad, ajustándose a las posibilidades de los practicantes y manteniendo el objetivo y las características de la especialidad deportiva que se trate. El objetivo de este análisis, es reflexionar y aportar nuestra experiencia y visión como Club Deportivo acerca de si los modelos de práctica de actividad física adaptada e inclusiva, pueden desarrollarse de forma paralela dentro de los programas deportivos o si, por el contrario, una opción tendría que prevalecer y adquirir cierta relevancia sobre la otra.

Introducción. El 65 % de las infecciones humanas son producidas por bacterias o levaduras, cuya capacidad de formar biopelículas las hace más resistentes a los antimicrobianos y antifúngicos. Objetivo. Determinar la capacidad de formación de biopelículas en aislamientos bacterianos y fúngicos por medio de los métodos cuantitativo de microtitulación con cristal violeta y cualitativo de cultivo en agar con rojo Congo. Materiales y métodos. Con el método cuantitativo, se utilizaron los medios de cultivo infusión cerebro-corazón, tripticasa de soya y Müeller-Hinton para aislamientos bacterianos; para levaduras, se usaron caldo infusión cerebro-corazón y Sabouraud dextrosa. Para el método cualitativo de cultivo en agar, se utilizaron los mismos medios de cultivo más una solución con 3 % de rojo Congo y 10 % de dextrosa. Cómo método de referencia, se utilizó la propuesta de Stepanovic et al. Resultados. Se evaluaron 103 aislamientos bacterianos y 108 de levaduras. No es recomendable sustituir el caldo infusión cerebro-corazón por los caldos tripticasa de soya y Müeller-Hinton en el método cuantitativo, para evaluar la formación de biopelículas en los aislamientos bacterianos. El medio Sabouraud dextrosa, en caldo y agar, puede sustituir al de infusión de cerebro-corazón para evaluar la formación de biopelículas en levaduras, tanto por el método cuantitativo como por el cualitativo. Conclusión. El estudio de las biopelículas en el laboratorio de microbiología, a partir del método cualitativo de cultivo en agar con rojo Congo, es un procedimiento sencillo, rápido y de bajo costo, que proporciona información útil para el diagnóstico y la terapéutica de infecciones persistentes causadas por bacterias y levaduras.

In this study, we describe a patient of primary cutaneous acral CD8-positive lymphoproliferative disorder located in a nonacral region. A 65-year-old male presented with an ill-defined lesion of rubbery consistency and a maximum diameter of 2.5 cm localized in the right thigh. Histologically, it was composed of a diffuse dermal infiltration of medium-sized atypical lymphocytes that expressed CD3, CD8, and TIA-1. In addition, a characteristic paranuclear positivity with CD68 was observed. During the follow-up, the patient had a recurrence of the disease in the abdomen with a lesion showing similar morphology and phenotype. To our knowledge, < 20 patients of primary cutaneous acral CD8-positive lymphoproliferative disorder with a nonacral presentation have been described in English literature. Although rare, its identification is essential to differentiate it from other T-cell lymphoma that express CD8 and cytotoxic markers, and whose clinical courses are very aggressive. [ABSTRACT FROM AUTHOR]

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management. [ABSTRACT FROM AUTHOR]