Geographic Rotterdam Import Allocation Model to International Trade in Bananas

Agricultural Economic

Knowledge-driven Natural Language Understanding of English Text and its Applications

Understanding the meaning of a text is a fundamental challenge of natural language understanding (NLU) research. An ideal NLU system should process a language in a way that is not exclusive to a single task or a dataset. Keeping this in mind, we have introduced a novel knowledge driven semantic representation approach for English text. By leveraging the VerbNet lexicon, we are able to map syntax tree of the text to its commonsense meaning represented using basic knowledge primitives. The general purpose knowledge represented from our approach can be used to build any reasoning based NLU system that can also provide justification. We applied this approach to construct two NLU applications that we present here: SQuARE (Semantic-based Question Answering and Reasoning Engine) and StaCACK (Stateful Conversational Agent using Commonsense Knowledge). Both these systems work by "truly understanding" the natural language text they process and both provide natural language explanations for their responses while maintaining high accuracy.Comment: Preprint. Accepted by the 35th AAAI Conference (AAAI-21) Main Track

Glomerulonefritis proliferativa extracapilar pauciinmune, una manifestación paraneoplásica inusual asociada a linfoma B del manto

The relationship between neoplasia and secondary renal involvement is increasing. Membranous glomerulonephritis is the main cause of nephrotic syndrome, associated with solid tumors, and less frequently hematologic neoplasia. Hodgkin’s lymphoma is the hematologic neoplasia most closely associated with minimal change disease. However, there are case reports that describe a relationship with non-Hodgkin’s lymphomas and leukemias. The usual clinical manifestation is the nephrotic syndrome,which may precede for several months or coexist with the diagnosis of lymphoma. Its pathophysiology is not very clear. It is suggested that it is related to T lymphocyte dysfunction. In addition, there are reports of thrombotic microangiopathy, related to the use of biological therapy and antineoplastic agents.Rapidly progressive glomerulonephritis is a clinical syndrome associated with glomerular extracapillary proliferation, usually related to vasculitis associated with ANCA and vasculitis mediated by immunocomplexes. Neoplasias are also related to a large number of vasculopathies. Glomerulonephritis with extracapillary proliferation are much more common in malignant solid tumors. In addition, associations with myelodysplastic syndrome, chronic lymphocytic leukemia and Hodgking lymphoma have been reported. The association between Mantle Cell B lymphomas and glomerulonephritis with extracapillary proliferation is unusual. The following is a case of a patient diagnosed with Mantle Cell B lymphoma who has a rapidly progressive glomerulonephritis secondary to extracapillary, necrotizing and pauci-immune proliferative lesions.La relación entre neoplasia y compromiso renal secundario es creciente. La glomerulonefritis membranosa es la principal causa de síndrome nefrótico asociado a tumores sólidos y con menos frecuencia a neoplasia hematológica. El linfoma Hodgkin es la neoplasia hematológica que más se relaciona con enfermedad de cambios mínimos. Sin embargo, hay reportes de casos que describen una relación con linfomas no Hodgkin y leucemias. La manifestación clínica usual es el síndrome nefrótico; el cual puede preceder por varios meses o coexistir con el diagnóstico de linfoma. La fisiopatogénesis no está muy clara. Se sugiere que está relacionada con una disfunción del linfocito T. Adicionalmente, hay reportes de microangiopatía trombótica relacionada con el uso de terapia biológica y antineoplásicos.La glomerulonefritis rápidamente progresiva, es un síndrome clínico asociado a proliferación extracapilar glomerular; usualmente relacionado con vasculitis asociadas a ANCAS y vasculitis mediadas por inmunocomplejos. Las neoplasias también están relacionadas con un amplio número de vasculopatías. Las glomerulonefritis con proliferación extracapilar son mucho más frecuentes en tumores sólidos malignos.Además, se han descrito asociaciones con síndrome mielodisplásico, leucemia linfocítica crónica y linfoma Hodgkin. La asociación entre linfomas B del manto y glomerulonefritis con proliferación extracapilar, esinusual.A continuación, se describe un caso de un paciente con diagnóstico de linfoma B del manto que cursa con una glomerulonefritis rápidamente progresiva secundaria a lesiones proliferativas extracapilares, necrosantes y pauciinmunitaria

Glomerulonefritis membranoproliferativa secundaria a vasculitis crioglobulinémica mixta esencial

We present the case of a 48 years old man with no known comorbidities, who sought for medical atention at San Vicente Fundación Universitary Hospital, complaining of a two month history with progressive dyspnea, generalized edema and macroscopic urinary changes, in whom hypertension, progressive kidney function decline, azotemia, nephrotic syndrome (9 g/24 h proteinuria), active urinary sediment, hypocomplementemia (C3 and C4) and cryoglobulinemia were found on ancillary tests. The kidney ultrasonography did not reveal findings suggestive of chronicity and the electrophoresis/immunifixation tests showed a polyclonal hypergammaglobulinemic pattern (without light chains). On the kidney biopsy an immunocomplex mediated membranoproliferative glomerulonephritis pattern of lesion was found, with rheumatic and neoplastic etiologies being ruled out. The patient was diagnosed with idiopatic immunocomplex mediated membranoproliferative glomerulonephritis due to mixed essential cryoglobulinemic vasculitis and immunosuppressive therapy (for remission induction) was started, with resolution of edemas, recovery of kidney function and a progressive decline in proteinuria from 9gr/dl to less than 1.8gr/dl on follow up evaluation.Presentamos el caso de un paciente sin comorbilidad conocida quien consulta al HUSVF por cuadro clínico de 2 meses de evolución con deterioro progresivo de la clase funcional, edema generalizado asociado a cambios macroscópicos en la orina, documentándose hipertensión arterial, deterioro progresivo de la función renal, con hiperazoemia, sedimento urinario activo y proteinuria en 9 gramos con criterios de síndrome nefrótico, hipocomplementemia (C4 y C3), crioglobulinemia, electroforesis e inmunofijación sérica  y urinaria con patrón de hipergammaglobulinemia policlonal (sin cadenas livianas), ecografía renal sin hallazgos sugestivos de nefropatía crónica y hallazgos en biopsia renal compatibles con glomerulonefritis membranoproliferativa mediada por inmunocomplejos. Se descartaron las enfermedades reumatológicas, hematológicas e infecciosas implicadas en la etiología de esta entidad (HCV,HBV,HIV, entre otras causas) y bajo el diagnóstico de glomerulonefritis membranoproliferativa secundaria a vasculitis crioglobulinémica mixta esencial se administró terapia inmunosupresora para inducir remisión (en conjunto con manejo médico para sobrecarga hídrica), con resolución del cuadro de edemas, recuperación de la función renal y una reducción progresiva de la proteinuria.

LOXL2-A New Target in Antifibrogenic Therapy?

The concept of liver fibrosis and cirrhosis being static and therefore irreversible is outdated. Indeed, both human and animal studies have shown that fibrogenesis is a dynamic and potentially reversible process that can be modulated either by stopping its progression and/or by promoting its resolution. Therefore, the study of the molecular mechanisms involved in the pathogenesis of liver fibrosis is critical for the development of future antifibrotic therapies. The fibrogenesis process, common to all forms of liver injury, is characterized by the increased deposition of extracellular matrix components (EMCs), including collagen, proteoglycans, and glycoproteins (laminin and fibronectin 2). These changes in the composition of the extracellular matrix components alter their interaction with cell adhesion molecules, influencing the modulation of cell functions (growth, migration, and gene expression). Hepatic stellate cells and Kupffer cells (liver macrophages) are the key fibrogenic effectors. The antifibrogenic mechanism starts with the activation of Ly6Chigh macrophages, which can differentiate into macrophages with antifibrogenic action. The research of biochemical changes affecting fibrosis irreversibility has identified lysyl oxidase-like 2 (LOXL2), an enzyme that promotes the network of collagen fibers of the extracellular matrix. LOXL2 inhibition can decrease cell numbers, proliferation, colony formations, and cell growth, and it can induce cell cycle arrest and increase apoptosis. The development of a new humanized IgG4 monoclonal antibody against LOXL2 could open the window of a new antifibrogenic treatment. The current therapeutic target in patients with liver cirrhosis should focus (after the eradication of the causal agent) on the development of new antifibrogenic drugs. The development of these drugs must meet three premises: Patient safety, in non-cirrhotic phases, down-staging or at least stabilization and slowing the progression to cirrhosis must be achieved; whereas in the cirrhotic stage, the objective should be to reduce fibrosis and portal pressure.Funding: This research was funded by NEXT-VAL grant 15/12 from Health Research Institute Marques de Valdecilla (IDIVAL)

Multi-smart and scalable bioligands-free nanomedical platform for intratumorally targeted tambjamine delivery, a difficult to administrate highly cytotoxic drug

Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands