Phenotypic characterization of liver tissue heterogeneity through a next-generation 3D single-cell atlas.

Three-dimensional (3D) geometrical models are potent tools for quantifying complex tissue features and exploring structure-function relationships. However, these models are generally incomplete due to experimental limitations in acquiring multiple (> 4) fluorescent channels in thick tissue sections simultaneously. Indeed, predictive geometrical and functional models of the liver have been restricted to few tissue and cellular components, excluding important cellular populations such as hepatic stellate cells (HSCs) and Kupffer cells (KCs). Here, we combined deep-tissue immunostaining, multiphoton microscopy, deep-learning techniques, and 3D image processing to computationally expand the number of simultaneously reconstructed tissue structures. We then generated a spatial single-cell atlas of hepatic architecture (Hep3D), including all main tissue and cellular components at different stages of post-natal development in mice. We used Hep3D to quantitatively study 1) hepatic morphodynamics from early post-natal development to adulthood, and 2) the effect on the liver's overall structure when changing the hepatic environment after removing KCs. In addition to a complete description of bile canaliculi and sinusoidal network remodeling, our analysis uncovered unexpected spatiotemporal patterns of non-parenchymal cells and hepatocytes differing in size, number of nuclei, and DNA content. Surprisingly, we found that the specific depletion of KCs results in morphological changes in hepatocytes and HSCs. These findings reveal novel characteristics of liver heterogeneity and have important implications for both the structural organization of liver tissue and its function. Our next-gen 3D single-cell atlas is a powerful tool to understand liver tissue architecture, opening up avenues for in-depth investigations into tissue structure across both normal and pathological conditions.

A comprehensive database of active and potentially-active continental faults in Chile at 1:25,000 scale.

In seismically-active regions, mapping active and potentially-active faults is the first step to assess seismic hazards and site selection for paleoseismic studies that will estimate recurrence rates. Here, we present a comprehensive database of active and potentially-active continental faults in Chile based on existing studies and new mapping at 1:25,000 scale using geologic and geomorphic criteria and digital elevation models derived from TanDEM-X and LiDAR data. The database includes 958 fault strands grouped into 17 fault systems and classified based on activity (81 proved, 589 probable, 288 possible). The database is a contribution to the world compilation of active faults with applications among others in seismic hazard assessments, territorial planning, paleoseismology, geodynamics, landscape evolution processes, geothermal exploration, and in the study of feedbacks between continental deformation and the plate-boundary seismic cycle along subduction zones.

Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients.

BACKGROUND: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. METHODS: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. RESULTS: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. CONCLUSIONS: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management.

Detección de un mosaico de trisomía 21 en líquido amniótico / Detection of a mosaicism of trisomy 21 in amniotic liquid

Resumen Se analizó un resultado con alteración cromosómica tomado de una base de datos conformada por un total de 4755 muestras de líquido amniótico extraídos mediante amniocentesis con indicación de su médico tratante, riesgo sérico y edad materna avanzada. En este reporte se presenta la detección de un mosaico de trisomía 21 en líquido amniótico, mediante la técnica de Banda G donde se analizaron 20 metafases. Los resultados obtenidos documentan una composición cromosómica 47, XY+21 y 46, XY con una relación 9:11 respecto a las metafases analizadas, confirmándose así el diagnóstico del Síndrome de Down secundario a mosaico.

Abstract A result with chromosomal alteration was analyzed from a database consisting of a total of 4755 samples of amniotic fluid extracted by amniocentesis with indication of the attending physician, serum risk and advanced maternal age. This report presents the detection of a mosaicism of trisomy 21 in amniotic fluid, using G- Banding where 20 metaphases were analyzed. The results obtained document a chromosomal composition 47, XY + 21 and 46, XY with a 9:11 ratio with respect to the metaphases analyzed, confirming the diagnosis of Down syndrome secondary to mosaicism.

Registro de pacientes con miopatía inflamatoria de la Sociedad Madrileña de Reumatología: análisis descriptivo / Multicenter registry on inflammatory myositis from the Rheumatology Society in Madrid, Spain: descriptive analysis

Objetivos. Describir las características clínicas, mortalidad y causas de muerte de una serie de pacientes diagnosticados de miositis inflamatoria idiopática del registro REMICAM de la Sociedad de Reumatología de la Comunidad de Madrid (SORCOM). Métodos. Estudio descriptivo retrospectivo multicéntrico de una cohorte de pacientes con diagnóstico de miositis inflamatoria idiopática en seguimiento en servicios de reumatología de hospitales de la Comunidad de Madrid entre enero de 1980 y diciembre de 2014. Se han recogido hasta un total de 313 variables acerca de aspectos demográficos, clínicos y de morbimortalidad, y se ha realizado una comparación entre subgrupos clínicos. Resultados. Se han reclutado 479 pacientes procedentes de 12 centros, con un 14% de pérdidas durante el periodo de seguimiento. El 74% de los casos eran mujeres, una edad al diagnóstico de 44±23 años, y una media de seguimiento de 10±8 años. Los subgrupos clínicos más frecuentes fueron las formas primarias (PM 29%, DM 22%), seguidas de síndrome de solapamiento (20,5%), miopatías juveniles (18%), miopatías asociadas a cáncer (8%), miopatías necrosantes inmunomediadas (1%) y miositis por cuerpos de inclusión (1%). Durante el periodo de seguimiento se produjeron un total de 114 fallecimientos (28%), siendo las principales causas el cáncer (24%), las infecciones (23%) y los eventos cardiovasculares (21%). Conclusiones. En el registro REMICAM de miopatías inflamatorias de la Comunidad de Madrid se han reclutado 479 casos de miositis inflamatoria idiopática con datos sociodemográficos, clínicos y pronósticos, suponiendo el mayor registro multicéntrico español en el ámbito de la Reumatología hasta la fecha, y constituyendo una fuente importante para la realización de posteriores subestudios (AU)

Objective. To analyze clinical characteristics, survival and causes of death of patients diagnosed with autoimmune inflammatory myositis in the REMICAM registry from the Society of Rheumatology in the Community of Madrid (SORCOM). Methods. Multicenter cohort of patients diagnosed with autoimmune inflammatory myopathy with follow-up between January 1980 and December 2014. A total of 313 variables concerning demographic, clinical and morbidity data were collected, and a comparison was performed between clinical subgroups. Results. A total of 479 patients were recruited from 12 centers, with 14% of patients lost to follow-up. Seventy-four percent of cases were women, age at diagnosis of 44±23 years and a mean follow-up period of 10±8 years. The most frequent clinical subgroups were primary myositis (PM 29%, DM 22%), followed by overlap myositis (20.5%), juvenile myositis (18%), myositis associated with cancer (8%), immune-mediated necrotizing myositis (1%) and inclusion body myositis (1%). During the follow-up period, a total of 114 deaths (28%) were registered, the main causes being cancer (24%), infections (23%) and cardiovascular events (21%). Conclusions. A total of 479 patients were recruited in the REMICAM registry of inflammatory myopathies. Including sociodemographic, clinical and prognostic information, it represents the largest Spanish multicenter registry to date in rheumatology, and constitutes an important source for conducting further substudies (AU)

Multicenter registry on inflammatory myositis from the Rheumatology Society in Madrid, Spain: Descriptive Analysis. / Registro de pacientes con miopatía inflamatoria de la Sociedad Madrileña de Reumatología: análisis descriptivo.

OBJECTIVE: To analyze clinical characteristics, survival and causes of death of patients diagnosed with autoimmune inflammatory myositis in the REMICAM registry from the Society of Rheumatology in the Community of Madrid (SORCOM). METHODS: Multicenter cohort of patients diagnosed with autoimmune inflammatory myopathy with follow-up between January 1980 and December 2014. A total of 313 variables concerning demographic, clinical and morbidity data were collected, and a comparison was performed between clinical subgroups. RESULTS: A total of 479 patients were recruited from 12 centers, with 14% of patients lost to follow-up. Seventy-four percent of cases were women, age at diagnosis of 44±23 years and a mean follow-up period of 10±8 years. The most frequent clinical subgroups were primary myositis (PM 29%, DM 22%), followed by overlap myositis (20.5%), juvenile myositis (18%), myositis associated with cancer (8%), immune-mediated necrotizing myositis (1%) and inclusion body myositis (1%). During the follow-up period, a total of 114 deaths (28%) were registered, the main causes being cancer (24%), infections (23%) and cardiovascular events (21%). CONCLUSIONS: A total of 479 patients were recruited in the REMICAM registry of inflammatory myopathies. Including sociodemographic, clinical and prognostic information, it represents the largest Spanish multicenter registry to date in rheumatology, and constitutes an important source for conducting further substudies.

Cirrosis biliar primaria: presentación de un caso clínico y revisión bibliográfica / Primary biliary cirrhosis: presentation of a case report and literature review

La Cirrosis Biliar Primaria (CBP) es una enfermedad hepática colestásica-crónica y progresiva de patogenia autoinmune, que ha aumentado su prevalencia en los últimos años. En el presente trabajo exponemos un caso clínico sobre una paciente femenina con síndrome colestásico, anticuerpos anti-mitocondriales (AMA) positivo y el informe anatomopatológico compatible con CBP cirrosis biliar primaria en tercer estadío. Su tratamiento principal fue farmacológico con ácido ursodeoxicólico (AUDC).

Primary biliary cirrhosis (PBC) is a chronic-cholestatic and progressive liver disease with autoimmune pathogenesis, which has increased in prevalence in recent years. In this paper we present a case of a female patient with cholestatic syndrome, anti-mitochondrial antibody (AMA) positive and the pathology report compatible with PBC primary biliary cirrhosis in the third stage. Her main treatment was with the drug called ursodeoxycholic acid (UDCA).