Automatic Detection of Distant Metastasis Mentions in Radiology Reports in Spanish.

PURPOSE: A critical task in oncology is extracting information related to cancer metastasis from electronic health records. Metastasis-related information is crucial for planning treatment, evaluating patient prognoses, and cancer research. However, the unstructured way in which findings of distant metastasis are often written in radiology reports makes it difficult to extract information automatically. The main aim of this study was to extract distant metastasis findings from free-text imaging and nuclear medicine reports to classify the patient status according to the presence or absence of distant metastasis. MATERIALS AND METHODS: We created a distant metastasis annotated corpus using positron emission tomography-computed tomography and computed tomography reports of patients with prostate, colorectal, and breast cancers. Entities were labeled M1 or M0 according to affirmative or negative metastasis descriptions. We used a named entity recognition model on the basis of a bidirectional long short-term memory model and conditional random fields to identify entities. Mentions were subsequently used to classify whole reports into M1 or M0. RESULTS: The model detected distant metastasis mentions with a weighted average F1 score performance of 0.84. Whole reports were classified with an F1 score of 0.92 for M0 documents and 0.90 for M1 documents. CONCLUSION: These results show the usefulness of the model in detecting distant metastasis findings in three different types of cancer and the consequent classification of reports. The relevance of this study is to generate structured distant metastasis information from free-text imaging reports in Spanish. In addition, the manually annotated corpus, annotation guidelines, and code are freely released to the research community.

Systematic analysis of different degrees of haemolysis on miRNA levels in serum and serum-derived extracellular vesicles from dogs.

BACKGROUND: Circulating microRNAs (miRNAs) are described as promising non-invasive biomarkers for diagnostics and therapeutics. Human studies have shown that haemolysis occurring during blood collection or due to improper sample processing/storage significantly alters the miRNA content in plasma and serum. Nevertheless, no similar research has been performed in dogs so far. We therefore investigated the effects of different degrees of haemolysis on the levels of selected miRNAs in serum and serum-derived extracellular vesicles (EVs) from dogs, by inducing a controlled in vitro haemolysis experiment. RESULTS: The abundance of miR-16, miR-92a, miR-191, miR-451 and miR-486 was significantly sensitive to haemolysis in serum and serum-derived EVs, while other selected miRNAs were not influenced by haemolysis. Furthermore, we found that the abundance of some canine miRNAs differs from data reported in the human system. CONCLUSIONS: Our results describe for the first time the impact of haemolysis on circulating miRNAs not only in whole serum, but also in serum-derived EVs from dogs. Hence, we provide novel data for further analyses in the discovery of canine circulating biomarkers. Our findings suggest that haemolysis should be carefully assessed to assure accuracy when investigating circulating miRNA in serum or plasma-based tests.

Deregulation of miR-27a may contribute to canine fibroblast activation after coculture with a mast cell tumour cell line.

The tumour microenvironment comprises a diverse range of cells, including fibroblasts, immune cells and endothelial cells, along with extracellular matrix. In particular, fibroblasts are of significant interest as these cells are reprogrammed during tumorigenesis to become cancer-associated fibroblasts (CAFs), which in turn support cancer cell growth. MicroRNAs (miRNAs) have been shown to be involved in this intercellular crosstalk in humans. To assess whether miRNAs are also involved in the activation of fibroblasts in dogs, we cocultured primary canine skin fibroblasts with the canine mast cell tumour cell line C2 directly or with C2-derived exosomes, and measured differential abundance of selected miRNAs. Expression of the CAF markers alpha-smooth muscle actin (ACTA2) and stanniocalcin 1 confirmed the activation of our fibroblasts after coculture. We show that fibroblasts displayed significant downregulation of miR-27a and let-7 family members. These changes correlated with significant upregulation of predicted target mRNAs. Furthermore, RNA interference knockdown of miR-27a revealed that cyclin G1 (CCNG1) exhibited negative correlation at the mRNA and protein level, suggesting that CCNG1 is a target of miR-27a in canine fibroblasts and involved in their activation. Importantly, miR-27a knockdown itself resulted in fibroblast activation, as demonstrated by the formation of ACTA2 filaments. In addition, interleukin-6 (IL-6) was strongly induced in our fibroblasts when cocultured, indicating potential reciprocal signalling. Taken together, our findings are consistent with canine fibroblasts being reprogrammed into CAFs to further support cancer development and that downregulation of miR-27a may play an important role in the tumour-microenvironment crosstalk.

Exploration of serum- and cell culture-derived exosomes from dogs.

BACKGROUND: Exosomes are defined as extracellular membrane vesicles, 30-150 nm in diameter, derived from all types of cells. They originate via endocytosis and then they are released through exocytosis to the extracellular space, being found in various biological fluids as well as in cell culture medium. In the last few years, exosomes have gained considerable scientific interest due to their potential use as biomarkers, especially in the field of cancer research. This report describes a method to isolate, quantify and identify serum- and cell culture-derived exosomes from dog samples, using small volumes (100 µL and 1 mL, respectively). RESULTS: Quantification and sizing of exosomes contained in serum and cell culture samples were assessed by utilizing nanoparticle tracking analysis, transmission electron microscopy and immunoelectron microscopy. Detected particles showed the normal size (30-150 nm) and morphology described for exosomes, as well as presence of the transmembrane protein CD63 known as exosomal marker. CONCLUSIONS: Based on a validated rapid isolation procedure of nanoparticles from small volumes of different types of dog samples, a characterization and exploration of intact exosomes, as well as facilitation for their analysis in downstream applications was introduced.

Synthesis of ß-alkoxy-N-protected phenethylamines via one-pot copper-catalyzed aziridination and ring opening.

A regioselective, copper-catalyzed, one-pot aminoalkoxylation of styrenes using primary and secondary alcohols and three different iminoiodanes as alkoxy and nitrogen sources respectively, is reported. The ß-alkoxy-N-protected phenethylamines obtained were used to synthesise ß-alkoxy-N-benzylphenethylamines which are interesting new compounds that could act as possible neuronal ligands.

Derivatives of alkyl gallate triphenylphosphonium exhibit antitumor activity in a syngeneic murine model of mammary adenocarcinoma.

We previously demonstrated that alkyl gallates coupled to triphenylphosphine have a selective and efficient antiproliferative effect by inducing mitochondrial uncoupling in vitro due to the increased mitochondrial transmembrane potential of tumor cells. Therefore, in this work, the in vivo antitumor activities of alkyl gallate triphenylphosphonium derivatives (TPP+C8, TPP+C10 and TPP+C12) were evaluated in a syngeneic murine model of breast cancer. We found that TPP+C10 increased the cytosolic ADP/ATP ratio and significantly increased the AMP levels in a concentration-dependent manner in TA3/Ha murine mammary adenocarcinoma cells. Interestingly, TPP+C10 induced a decrease in the levels of cellular proliferation markers and promoted caspase-3 activation in tumor-bearing mice. Additionally, TPP+C10 inhibited tumor growth in the syngeneic mouse model. Importantly, 30days of intraperitoneal (i.p.) administration of the combination of TPP+C10 (10mg/kg/48h) and the antibiotic doxycycline (10mg/kg/24h) completely eliminated the subcutaneous tumor burden in mice (n=6), without any relapses at 60days post-treatment. This enhancement of the individual activities of TPP+C10 and doxycycline is due to the uncoupling of oxidative phosphorylation by TPP+C10 and the inhibition of mitochondrial biogenesis by doxycycline, as demonstrated by loss of mitochondrial mass and overexpression of PGC1-α as an adaptive response. Moreover, i.p. administration of TPP+C10 (10mg/kg/24h) to healthy mice did not produce toxicity or damage in organs important for drug metabolism and excretion, as indicated by hematological, biochemical and histological assessments. These findings suggest that the combination of TPP+C10 with doxycycline is a valuable candidate therapy for breast cancer management.

Destabilization of mitochondrial functions as a target against breast cancer progression: Role of TPP(+)-linked-polyhydroxybenzoates.

Mitochondrion is an accepted molecular target in cancer treatment since it exhibits a higher transmembrane potential in cancer cells, making it susceptible to be targeted by lipophilic-delocalized cations of triphenylphosphonium (TPP(+)). Thus, we evaluated five TPP(+)-linked decyl polyhydroxybenzoates as potential cytotoxic agents in several human breast cancer cell lines that differ in estrogen receptor and HER2/neu expression, and in metabolic profile. Results showed that all cell lines tested were sensitive to the cytotoxic action of these compounds. The mechanism underlying the cytotoxicity would be triggered by their weak uncoupling effect on the oxidative phosphorylation system, while having a wider and safer therapeutic range than other uncouplers and a significant lowering in transmembrane potential. Noteworthy, while the TPP(+)-derivatives alone led to almost negligible losses of ATP, when these were added in the presence of an AMP-activated protein kinase inhibitor, the levels of ATP fell greatly. Overall, data presented suggest that decyl polyhydroxybenzoates-TPP(+) and its derivatives warrant future investigation as potential anti-tumor agents.

Philosophical and Psychopathological Perspective of Exile: On Time and Space Experiences.

This article addresses the experience of exile from an interdisciplinary perspective (philosophy and psychiatry). The main purpose is to try to understand the experience of exile by rehearsing a psychopathological perspective to address it, so it can help with the treatment of disorders that come with this experience. Furthermore, the article tries to explore the experience and reflection of philosophers and thinkers who, being exiled themselves, tried to understand and explain this radical human experience, focusing on the experience of time and space.

Utilización de factores de crecimiento plaquetarios autólogos en artrodesis lumbares posterolaterales / Utilização de fatores de crescimento plaquetários autólogos em artrodese lombar póstero-lateral / Use of autologous platelet growth factors in posterolateral lumbar spinal fusions

OBJETIVO: Evaluar calidad e índice de pseudoartrosis en la formación del callo óseo en artrodesis instrumentadas lumbares posteriores con injerto óseo autólogo enriquecido con factores de crecimiento plaquetarios (FCP). MÉTODOS: Estudio clínico analítico experimental simple ciego entre Junio de 2007 y Junio de 2009 comparando dos grupos, uno en el que se utilizó FCP en artrodesis lumbares posteriores y otro en el que no se aplicó el factor, evaluando las siguientes variables: índice de pseudoartrosis, formación del callo óseo y complicaciones postoperatorias. RESULTADOS: Se evaluaron 26 pacientes, edad promedio 61,23 años, divididos en dos grupos de 13 pacientes. El grupo en el que se utilizó FCP presentó fusiones radiográficamente sólidas en el 61,54 %, sin registro de pseudoartrosis pero con incidencia de infección y sangrado postoperatorios de 15.39%, mientras que en el grupo sin FCP el 69.23% alcanzó fusiones sólidas con 7.69% de pseudoartrosis sin otras complicaciones relacionadas con la intervención. CONCLUSIÓN: Si bien el grupo con FCP no presentó pseudoartrosis, registró mayor incidencia de complicaciones postoperatorias y menor número de fusiones radiográficamente sólidas. Aunque la cantidad de pacientes no permite obtener resultados estadísticamente significativos el presente puede ser el inicio de un estudio mayor.

OBJETIVO: Avaliar a qualidade e taxa de pseudoartrose em formação de calos em instrumentado fusão lombar com enxerto ósseo autólogo depois enriquecido com fatores de crescimento plaquetário (FCP). MÉTODOS: Analytical experimental tipo cego única clínica entre junho de 2007 e junho de 2009 comparando dois grupos, um que foi usado no FCP após artrodese lombar e outro que não se aplicam, avaliar as seguintes variáveis : taxa de pseudoartrose de formação de calos e as complicações pós-operatórias. RESULTADOS: Foram avaliados 26 pacientes, com idade média de 61,23 anos, divididos em dois grupos de 13 pacientes. O grupo que foi usado FCP apresentou fusões radiograficamente sólidos em 61,54%, sem registro, mas com incidência não-união de infecção e sangramento pós-operatório 15,39%, enquanto que no grupo sem o FCP% 69,23 alcançado fusões sólidas com 7,69% de pseudoartrose sem outras complicações relacionadas com a intervenção. CONCLUSÃO: Apesar de o grupo não se apresentar com FCP não sindicalizados, maior incidência de complicações pós-operatórias e menos fusões radiograficamente sólidos. Embora o número de pacientes que não é possível obter resultados estatisticamente significativos isso pode ser o início de um estudo maior.

OBJECTIVE: To evaluate quality and rate of pseudoarthrosis in callus formation in instrumented posterolateral lumbar fusion with the use of autologous bone graft enriched with platelet growth factors (PGFs). METHODS: A clinical analytical experimental single blind trial was carried out between June 2007 and June 2009 comparing two groups, one in which PGFs were used in lumbar spinal fusions while in the other the PGFs were not applied, to analyze the following variables: rate of pseudoarthrosis, callus formation and postoperative complications. RESULTS: We evaluated 26 patients, mean age 61.23 years, divided in two groups of 13 patients each. The group in which PGFs were used presented radiographically solid fusions at 61.54% with no record of pseudoarthrosis, although with incidence of infection and postoperative bleeding of 15.39%, while in the group without PGFs 69.23% achieved solid fusions presenting a rate of pseudoarthrosis of 7.69% with no other complications related to the intervention. CONCLUSION: Even though the group without PGFs did not present pseudoarthrosis, a higher incidence of postoperative complications and fewer radiographically solid fusions could be observed. Even though the number of patients is not sufficient to obtain statistically significant results, the present analysis may be the beginning of further study.

Hidrocefalia externa del adulto: manejo terapéutico y diagnóstico diferencial conhematoma subdural crónico e higroma subdural. Presentación de un caso y revisión de la literatura / Adult external hydrocephalus- therapeutical measures & differential diagnosis with chronic subdural hematoma & subdural higroma: case report & literature review

Objetivo: presentar un caso de hidrocefalia externa en un adulto. Presentación: paciente de 73 años con trastornos en la marcha y paresia braquial derecha de tres semanas de evolución secundarios a hematoma subdural (HSD) frontotemporoparietal izquierdo. Intervención: tras doble evacuación y craniectomía descompresiva por resangrado en postoperatorio inmediato, evolucionó con sensorio fluctuante y confuso, evidenciando en tomografías computadas (TAC) controles colecciones líquidas bilaterales extraaxialescon ventrículos, surcos y cisternas conservados, “signo de venas corticales” a través de cada colección con herniación de ésta a través de la craniectomía. Por punción transcutánea a través de ella se mide la presión del espacio subdural de 26 cm de H2O apoyando el diagnóstico de HEA. Se coloca drenaje subduroperitoneal bilateral logrando una evolución favorable. Conclusión: el manejo terapéutico óptimo de las colecciones subdurales aún no ha sido establecido. La conducta conservadora resulta adecuada en casos asintomáticos y sin efecto de masa mientras que en efusiones subdurales bastaría irrigar la cavidad o una derivación subduroperitoneal. Las derivaciones de LCR resultan de impredecible eficacia en HEA y las colecciones asociadas persisten o recidivan tras su evacuación, por lo que una correcta selección de pacientes es clave antes de cualquier decisión terapéutica.

Neurocitoma extraventricular atípico con siembra por trayecto de biopsia y diseminación leptomeníngea craneoespinal: reporte de primer caso y revisión de la literatura / Atipical extraventricular neurocytoma with needle tract seeding and craniospinal dissemination: case report and literature review

Objetivo: reportar el primer caso de EVN atípico con siembra neoplásica por trayecto de biopsia y diseminación craneoespinal. Descripción: paciente de 19 años con debilidad y parestesias en hemicuerpo derecho de dos meses de evolución evidenciando en resonancia magnética (IRM) tumor talámico izquierdo sin realce tras el contraste. Intervención: la biopsia esterotáctica revela un tumor redondo-celular compatible con oligodendroglioma. Se indica radioterapia y quimioterapia. Al tercer mes presenta hidrocefalia por progresión tumoral. Se coloca shunt de LCR. Al año se intensifica el síndrome talámico, presenta trastornos oculomotores y esfinterianos. IRM evidencia compromiso leptomeníngeo difuso con implantes nodulares espinales, en tronco encefálico y a nivel de abordaje estereotáctico frontal izquierdo compatible con siembra por trayecto de biopsia. Craneotomía centrada en trepanación previa permite resecar tejido neoplásico reinterpretado anatomopatológicamente como EVN atípico diseminado con Ki67>30%. Conclusión: los oligodendrogliomas representan el principal diagnóstico diferencial imagenológico y anatomopatológico de EVN. Se presume su origen en células precursoras biopotenciales de matriz germinal periventricular con capacidad de diferenciación glial y neuronal que explicaría su capacidad excepcional para la diseminación leptomeníngea. El Ki67 es el principal factor pronóstico evolutivo en neurocitomas. Aquellos con Ki67>2% (atípicos) requieren monitoreo estricto por mayor riesgo de recurrencia y diseminación.