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OBJECTIVE: With the onset of the Coronavirus Disease 2019 (COVID-19) pandemic, there has been a surge in the number of publicly available biomedical information sources, which makes it an increasingly challenging research goal to retrieve a relevant text to a topic of interest. In this paper, we propose a Contextual Query Expansion framework based on the clinical Domain knowledge (CQED) for formalizing an effective search over PubMed to retrieve relevant COVID-19 scholarly articles to a given information need. MATERIALS AND METHODS: For the sake of training and evaluation, we use the widely adopted TREC-COVID benchmark. Given a query, the proposed framework utilizes a contextual and a domain-specific neural language model to generate a set of candidate query expansion terms that enrich the original query. Moreover, the framework includes a multi-head attention mechanism that is trained alongside a learning-to-rank model for re-ranking the list of generated expansion candidate terms. The original query and the top-ranked expansion terms are posed to the PubMed search engine for retrieving relevant scholarly articles to an information need. The framework, CQED, can have four different variations, depending upon the learning path adopted for training and re-ranking the candidate expansion terms. RESULTS: The model drastically improves the search performance, when compared to the original query. The performance improvement in comparison to the original query, in terms of RECALL@1000 is 190.85% and in terms of NDCG@1000 is 343.55%. Additionally, the model outperforms all existing state-of-the-art baselines. In terms of P@10, the model that has been optimized based on Precision outperforms all baselines (0.7987). On the other hand, in terms of NDCG@10 (0.7986), MAP (0.3450) and bpref (0.4900), the CQED model that has been optimized based on an average of all retrieval measures outperforms all the baselines. CONCLUSION: The proposed model successfully expands queries posed to PubMed, and improves search performance, as compared to all existing baselines. A success/failure analysis shows that the model improved the search performance of each of the evaluated queries. Moreover, an ablation study depicted that if ranking of generated candidate terms is not conducted, the overall performance decreases. For future work, we would like to explore the application of the presented query expansion framework in conducting technology-assisted Systematic Literature Reviews (SLR).
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COVID-19 , Almacenamiento y Recuperación de la Información , Humanos , PubMed , Motor de Búsqueda , SemánticaRESUMEN
Individuals with bicuspid aortic valve (BAV) have historically been advised to avoid contact sports and isometric exercise for risk of increasing aortic dilation and valve disease. There is mounting evidence that current sports participation guidelines qualify children for a high rate of sports exclusion, and that this population is at increased risk of obesity. The primary aim of this study was to evaluate relationship between sports participation and aortic dilation in children with bicuspid aortic valve and secondarily the relationship between competitive sports participation and obesity. We performed a review of children between the ages of 8 and 17 years with isolated BAV followed at Oregon Health & Science University. We excluded those with other congenital heart diseases, genetic conditions, prior cardiac intervention, and inability to ambulate independently. Parents completed a phone survey detailing their child's level of daily activity and participation in competitive sports. Demographic information and most recent echo findings were collected from the electronic medical record. We found no difference between the aortic diameters of athletes vs non-athletes. We also found that sports participation and daily activity were both associated with a decreased likelihood of obesity (OR 0.24, 95% CI 0.078-0.73 and OR 0.24, 95% CI 0.081-0.71 respectively). In summary, in our sample population, competitive sports participation was associated with a decreased risk of obesity. Competitive sports participation does not appear to be associated with an increased risk of aortic dilation in our population.
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BACKGROUND: Children with CHD are at risk for obesity and low levels of activity. These factors are associated with an increased risk of poor outcome. Participation in organised sports is an important avenue for children to maintain physical activity, though the relationship between sports participation and obesity has not been examined in the Fontan population. METHODS: We performed a cross-sectional study of children aged 8-18 who had been evaluated between January 1, 2015 and October 1, 2019 at the Doernbecher Children's Hospital outpatient paediatric cardiology clinic and had previously undergone a Fontan. Patients were excluded if they were unable to ambulate independently or if they had undergone a heart transplant. Patient characteristics were recorded from the electronic medical record. Parents were interviewed via a telephone survey and asked to describe their child's activity levels and sports participation. RESULTS: Our final cohort included 40 individuals, 74% were male. The overall prevalence of obesity (CDC BMI >95% for sex/age) in the cohort (23%) was significantly higher in non-athletes (33%) than athletes (0) (p = 0.02). There was no difference in cardiac complications or comorbidities between athletes and non-athletes. Athletes were more likely to meet daily activity recommendations (p = 0.05). CONCLUSION: Fontan patients who do not participate in sports are significantly more likely to be obese and less likely to be active than those who do. This is the first study to demonstrate the association between competitive sports participation and decreased likelihood of obesity in the Fontan population.
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Procedimiento de Fontan , Cardiopatías , Obesidad Infantil , Deportes , Niño , Estudios Transversales , Femenino , Procedimiento de Fontan/efectos adversos , Cardiopatías/etiología , Humanos , MasculinoRESUMEN
The core structure of the extracellular basement membrane is made up of self-assembling networks of collagen and laminin which associate with each other through the bridging adapter proteins including the sulfated monomeric glycoprotein nidogen. While collagen and laminin are known to support platelet adhesion and activation via ß1 integrins and glycoprotein (GP) VI, respectively, whether nidogen contributes to platelet activation and hemostasis is unknown. In this study, we demonstrate that recombinant human nidogen-1 supports platelet adhesion and stimulates platelet activation in a phospholipase-C γ-2 (PLCγ2), Src and Syk kinase-dependent manner downstream. Platetet adhesion to nidogen-1 was inhibited by blocking the platelet receptors GPVI and ß1 integrins. Platelet adhesion to nidogen-1 activated the IκB kinase (IKK) complex, while pharmacological inhibition of IKK blocked platelet spreading on nidogen. Taken together our results suggest that nidogen may play a redundant role in hemostasis by activating platelets downstream of GPVI.
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Glicoproteínas de Membrana/metabolismo , Activación Plaquetaria/fisiología , Adhesividad Plaquetaria/fisiología , HumanosAsunto(s)
Lesión Renal Aguda , Sepsis , Humanos , Lesión Renal Aguda/terapia , Lesión Renal Aguda/complicaciones , Fluidoterapia , Medicago , Resucitación , Sepsis/complicaciones , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BackgroundApproximately 40% of adolescent women experience heavy menstrual bleeding (HMB), and 10-62% of them have an underlying bleeding disorder (BD). Diagnosing a BD remains challenging because of limitations of available clinical platelet function assays. The aim of this study was to characterize platelet function in a population of adolescent women with HMB using small-volume whole-blood assays.MethodsAnticoagulated whole blood was used to assess platelet GPIIbIIIa activation, α-granule secretion, and aggregation in response to multiple agonists. Platelet adhesion on collagen or von Willebrand Factor (VWF) under static and shear flow was also assessed.ResultsFifteen participants with HMB were included in the study, of which eight were diagnosed with a clinically identifiable BD. Platelet activation was blunted in response to calcium ionophore in participants without a BD diagnosis compared with that in all other participants. Impaired GPIIbIIIa activation was observed in response to all GPCR agonists, except adenosine diphosphate (ADP), in participants with qualitative platelet disorders. Our assays detected platelet aggregation in the majority of participants with a BD in response to ADP, collagen-related peptide (CRP), thrombin receptor activator 6 (TRAP-6), or U46619. Platelet adhesion and aggregation on collagen and VWF was decreased for participants with VWD.ConclusionParticipants with and without BD exhibited aberrant platelet function in several assays in response to select agonists.
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Menorragia/sangre , Menorragia/fisiopatología , Agregación Plaquetaria , Pruebas de Función Plaquetaria/instrumentación , Pruebas de Función Plaquetaria/métodos , Adenosina Difosfato/química , Adolescente , Plaquetas , Niño , Colágeno/química , Femenino , Hemodinámica , Hemostasis , Humanos , Fragmentos de Péptidos/metabolismo , Proyectos Piloto , Activación Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/química , Resistencia al Corte , Adulto Joven , Factor de von Willebrand/metabolismoRESUMEN
Purpose: Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial. Methods: We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction. Results: Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen's Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) (p-value-for-interaction = 0.03). Conclusion: Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.
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Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.