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•Mechanistic model characterizing acute immune response and HBV system interactions.•Key role of the cellular and regulatory response triggering hepatitis B chronicity.•Modelling ...framework to easily incorporate and explore additional biological mechanisms.
Hepatitis B liver infection is caused by hepatitis B virus (HBV) and represents a major global disease problem when it becomes chronic, as is the case for 80–90% of vertical or early life infections. However, in the vast majority (>95%) of adult exposures, the infected individuals are capable of mounting an effective immune response leading to infection resolution. A good understanding of HBV dynamics and the interaction between the virus and immune system during acute infection represents an essential step to characterize and understand the key biological processes involved in disease resolution, which may help to identify potential interventions to prevent chronic hepatitis B.
In this work, a quantitative systems pharmacology model for acute hepatitis B characterizing viral dynamics and the main components of the innate, adaptive, and tolerant immune response has been successfully developed. To do so, information from multiple sources and across different organization levels has been integrated in a common mechanistic framework. The final model adequately describes the chronology and plausibility of an HBV-triggered immune response, as well as clinical data from acute patients reported in the literature. Given the holistic nature of the framework, the model can be used to illustrate the relevance of the different immune pathways and biological processes to ultimate response, observing the negligible contribution of the innate response and the key contribution of the cellular response on viral clearance. More specifically, moderate reductions of the proliferation of activated cytotoxic CD8+ lymphocytes or increased immunoregulatory effects can drive the system towards chronicity.
Abstract
Many different studies have shown that a wealth of cosmological information resides on small, nonlinear scales. Unfortunately, there are two challenges to overcome to utilize that ...information. First, we do not know the optimal estimator that will allow us to retrieve the maximum information. Second, baryonic effects impact that regime significantly and in a poorly understood manner. Ideally, we would like to use an estimator that extracts the maximum cosmological information while marginalizing over baryonic effects. In this work we show that neural networks can achieve that when considering some simple scenarios. We made use of data where the maximum amount of cosmological information is known: power spectra and 2D Gaussian density fields. We also contaminate the data with simplified baryonic effects and train neural networks to predict the value of the cosmological parameters. For this data, we show that neural networks can (1) extract the maximum available cosmological information, (2) marginalize over baryonic effects, and (3) extract cosmological information that is buried in the regime dominated by baryonic physics. We also show that neural networks learn the priors of the data they are trained on, affecting their extrapolation properties. We conclude that a promising strategy to maximize the scientific return of cosmological experiments is to train neural networks on state-of-the-art numerical simulations with different strengths and implementations of baryonic effects.
•Increased generalised theta with posterior pre-alpha relative power are reproducible findings in Parkinson’s Disease.•Functional Data Analysis is a potential tool to overcome potential limitations ...of epochs averaging in rs-EEG spectral analysis.•Functional Data Analysis constitutes a reliable method to analyse epoch-to-epoch variability of the rs-EEG.
This study aims 1) To analyse differences in resting-state electroencephalogram (rs-EEG) spectral features of Parkinson's Disease (PD) and healthy subjects (non-PD) using Functional Data Analysis (FDA) and 2) To explore, in four independent cohorts, the external validity and reproducibility of the findings using both epoch-to-epoch FDA and averaged-epochs approach.
We included 169 subjects (85 non-PD; 84 PD) from four centres. Rs-EEG signals were preprocessed with a combination of automated pipelines. Sensor-level relative power spectral density (PSD), dominant frequency (DF), and DF variability (DFV) features were extracted. Differences in each feature were compared between PD and non-PD on averaged epochs and using FDA to model the epoch-to-epoch change of each feature.
For averaged epochs, significantly higher theta relative PSD in PD was found across all datasets. Also, higher pre-alpha relative PSD was observed in three of four datasets in PD patients. For FDA, similar findings were achieved in theta, but all datasets showed consistently significant posterior pre-alpha differences across multiple epochs.
Increased generalised theta, with posterior pre-alpha relative PSD, was the most reproducible finding in PD.
Rs-EEG theta and pre-alpha findings are generalisable in PD.
FDA constitutes a reliable and powerful tool to analyse epoch-to-epoch the rs-EEG.
Objective This study aims to describe demographic and clinical characteristics and the factors associated with the risk of COVID-19 general hospitalization and intensive care unit (ICU) care of ...patients who consulted in a third-level hospital in Santander, Colombia. Methods We used baseline data from an ambidirectional cohort study. We included all patients with positive real-time polymerase chain reaction (PCR) tests for COVID-19 who came to the emergency room (ER) for respiratory symptoms related to COVID-19. Information regarding patients' baseline characteristics and symptoms was collected through telephone interviews and review of medical records. Vital signs were extracted from medical records as well. Results We enrolled 3,030 patients, predominantly men, with a median age of 60 (interquartile range (IQR): 44-73). Symptoms of the acute phase varied between men and women. Men presented with more respiratory symptoms, and women had general symptoms. Hypertension, obesity, and diabetes were common risk factors for hospital admission. Antibiotic consumption may also play a role in hospital admission. Conclusions Male sex, older age, hypertension, obesity, prior thrombotic events, and self-medicated antibiotics were associated with general hospitalization. Hypertension, obesity, diabetes, and cancer were associated with ICU admission. The Charlson comorbidity index (CCI) is a powerful tool for evaluate the impact of pre-existing health conditions on COVID-19 hospital admission. We highlight the importance of these findings as possible predictors in our region.
Monoclonal antibodies (mAbs) represent a therapeutic strategy that has been increasingly used in different diseases. mAbs are highly specific for their targets leading to induce specific effector ...functions. Despite their therapeutic benefits, the presence of immunogenic reactions is of growing concern. The immunogenicity identified as anti-drug antibodies (ADA) production due to the continuous administration of mAbs may affect the pharmacokinetics (PK) and/or the pharmacodynamics (PD) of mAbs administered to patients. Therefore, the immunogenicity and its clinical impact have been studied by several authors using PK modeling approaches. In this review, the authors try to present all those models under a unique theoretical mechanism-based framework incorporating the main considerations related to ADA formation, and how ADA may affect the efficacy or toxicity profile of some therapeutic biomolecules.
After acute phase of SARS-CoV-2 infection, some patients persist with clinical symptoms, a phenomenon known as Long COVID syndrome. It is necessary to understand the factors associated with the ...persistence of these symptoms to develop individualized preventive approaches and effectively address this challenge.
To determine the factors associated with the persistence of symptoms six months after COVID-19 infection.
A ambidirectional cohort, single-center study, that included individuals previously diagnosed with COVID-19 by real-time polymerase chain reaction (PCR) positive test, who were followed for a period of six months. Univariate, bivariate and a multivariate binomial regression model were performed to determine risk factors associated with the persistence of COVID-19 symptoms at the six months of follow-up.
The prevalence of long COVID syndrome was 47%. Age demonstrated no significant association with Long COVID (RR 0.999 95% CI 0.996-1.002); however, female sex (RR 1.148 95% CI 1.038-1.268), requirement of mechanical ventilation (RR 1.278 95% CI 1.050-1.555), presence of Chronic Obstructive Pulmonary Disease (COPD) (RR 1.340 95% CI 1.104-1.626), Rheumatic Disease (RR 1.259 95% CI 1.055-1.504) and the Hospitalization Type: General Hospitalization (RR 1.247 95% CI 1.090-1.427) and ICU Hospitalization (RR 1.490 95% CI 1.221-1.818) were significantly associated with the persistence of symptoms at the six month of follow-up.
Female sex, presence of COPD, rheumatic disease, hospitalization type and requirement of mechanical ventilation during index infection were identified as significant risk factors for the diagnosis of Long COVID. These findings emphasize the importance of addressing Long COVID syndrome in terms of prevention and management, taking these risk factors into consideration.
El experimento se llevó a cabo en la granja avícola de la Universidad Nacional de Cajamarca, durante veinticuatro semanas para determinar efectos de los niveles dietarios de metionina y ácido ...linoleico sobre la producción y la calidad del huevo de codorniz (Coturnix coturnix var. japónica). Se inició la evaluación con 576 aves de 42 días de edad, alojadas en jaulas distribuidas según nueve combinaciones de tratamientos, con cuatro repeticiones de 16 aves por cada tratamiento, considerando tres niveles de metionina (0,40, 0,50 y 0,60% MET) y tres niveles de ácido linoleico (1,63, 2,05 y 2,47% LIN). El rendimiento productivo y la calidad del huevo se analizaron según diseño completamente randomizado en arreglo factorial de 3 x 3. Las medias se compararon mediante prueba de Tukey. Las aves alimentadas con dietas con 0,50 y 0,60% de MET tuvieron mayor ingesta de alimento y producción de huevos (p <0,05) que aquellas alimentadas con dietas con 0,40% de MET. Hubo interacción significativa (p <0,05) entre la MET y los niveles de Lin en el peso del huevo. Se observó una mejor conversión alimenticia y masa de huevo para las aves alimentadas con dietas con 0,60% de MET en comparación con aquellas alimentadas con dietas con 0,40% y 0,50% de MET. La producción y la calidad del huevo no mejoraron (p> 0,05) con los niveles altos de LIN.
Extranodal Rosai-Dorfman Disease Mantilla, Jose G; Goldberg-Stein, Shlomit; Wang, Yanhua
American journal of clinical pathology,
02/2016, Letnik:
145, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Objectives: To describe the radiologic and clinicopathologic features of extranodal Rosai-Dorfman disease (RDD) in our patient population.
Methods: Via a data mining engine, we evaluated 13 cases of ...extranodal RDD in 10 patients treated at our institution from 2000 to 2014.
Results: There was a marked female predominance (90%) in our series. The most common clinical presentation was a palpable, painless mass, which often simulated a neoplasm. Only two cases occurred in children. Multicentric and recurrent disease were uncommon. Histologically, all cases showed large histiocytes with emperipolesis in a mixed inflammatory background, with areas of dense, storiform collagen fibrosis. Positive S-100 and CD68 with negative CD1a in histiocytes are characteristic.
Conclusions: Extranodal RDD is rare and its manifestations varied. It may constitute a clinical and pathologic diagnostic challenge. Clinical suspicion and recognition of its histologic features are necessary for correct diagnosis and avoiding unnecessary treatment. Resection is curative in most cases.
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