Mediamusic (E-Journal)
Not a member yet
40683 research outputs found
Sort by
An Ethnography of Child Growth:socio-cultural context and meanings attached to child growth in southeastern Tanzania
No full textCaregivers of under-fives have local knowledge about what child growth entails, yet their perspectives are not currently reflected in growth monitoring practices. Similarly, while children live in different socio-economic and cultural contexts, only information about children’s physical growth – i.e., their weight and height – is collected in assessing child growth. This also has consequences for how interventions are developed and evaluated. We conducted research in Tanzania to understand how caregivers conceptualize child growth, and to examine the familial/societal conditions that affect mothers’ abilities to ensure healthy growth. The caregivers’ definitions of child growth within their socio-cultural context are broader than just weight and height, as they use multiple cultural markers in ascertaining healthy growth. They perceive height as unrelated to nutrition, health, or overall growth; and shortness as a normal condition caused by God and/or heredity. The cultural signs that a child is short for his/her age include a mature face; poor weight; unhealthy skin/hair; abnormal thinness; inability to crawl, stand, or walk on schedule; not being cheerful or playful; and frequent illness. The parents’ failure to adhere to postpartum sexual abstinence norms was considered a cause of poor growth and development among children. The mothers’ abilities to ensure healthy growth in their children were limited by unequal gendered norms and structures. These findings point to the importance of giving caregivers a voice in their localities, taking into account the meanings they give to aspects of child growth, and updating the available framework to be more respectful of these local concepts
Chemogenetic Tags with Probe Exchange for Live-Cell Fluorescence Microscopy
No full textFluorogenic protein tagging systems have been less developed for prokaryotes than for eukaryotic cell systems. Here, we extend the concept of noncovalent fluorogenic protein tags in bacteria by introducing transcription factor-based tags, namely, LmrR and RamR, for probe binding and fluorescence readout under aerobic and anaerobic conditions. We developed two chemogenetic protein tags that impart fluorogenicity and a longer fluorescence lifetime to reversibly bound organic fluorophores, hence the name Chemogenetic Tags with Probe Exchange (CTPEs). We present an extensive characterization of 30 fluorophores reversibly interacting with the two different CTPEs and conclude that aromatic planar structures bind with high specificity to the hydrophobic pockets of these tags. The reversible binding of organic fluorophores to the CTPEs and the superior photophysical properties of organic fluorophores enable long-term fluorescence microscopy of living bacterial cells. Our protein tags provide a general tool for investigating (sub)cellular protein localization and dynamics, protein-protein interactions, and prolonged live-cell microscopy, even under oxygen-free conditions.</p
Vasculitis therapy refines vasculitis mechanistic classification
No full textThe primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood vessels affected (Chapel Hill classification). In recent years, several drugs with well-characterized immunological targets have been tested in clinical trials in large vessel vasculitis and small vessel vasculitis. Such trials provide "reverse translational" or bedside to bench information about underlying pathogenic mechanisms. Therefore, the aim of this systematic literature review was to examine the evidence base for a more refined mechanistic immunological classification of vasculitis. A total of 40 studies (20 randomized controlled trials (RCTs), 16 prospective studies, 1 retrospective cohort study and 3 case series) were included for full qualitative assessment. RCTs concerning biologic therapy for large vessel vasculitis mainly supports interleukin 6 receptor inhibition (tocilizumab). RCTs concerning biologic therapy for granulomatosis with polyangiitis and microscopic polyangiitis mainly support anti-CD20 treatment (rituximab) and complement inhibition with a small molecule C5a receptor antagonist (avacopan) is an emerging treatment option. The biologic treatment of eosinophilic granulomatosis with polyangiitis is centered around interleukin 5 inhibition (mepolizumab). Studies on tumor necrosis factor alpha inhibition (adalimumab, infliximab, and etanercept) showed negative results in giant cell arteritis but some effect in Takayasu arteritis. Taken together, clinical studies with cytokine and cell specific drugs are dissecting the heterogeneous immunopathogenic mechanisms of vasculitis and support a mechanistic immunological classification. Especially, cytokine antagonism is pointing towards immunological distinctions between eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis/microscopic polyangiitis and differences between giant cell arteritis and Takayasu arteritis.</p
Nanogels:A novel approach in antimicrobial delivery systems and antimicrobial coatings
No full textThe implementation of nanotechnology to develop efficient antimicrobial systems has a significant impact on the prospects of the biomedical field. Nanogels are soft polymeric particles with an internally cross-linked structure, which behave as hydrogels and can be reversibly hydrated/dehydrated (swollen/shrunken) by the dispersing solvent and external stimuli. Their excellent properties, such as biocompatibility, colloidal stability, high water content, desirable mechanical properties, tunable chemical functionalities, and interior gel-like network for the incorporation of biomolecules, make them fascinating in the field of biological/biomedical applications. In this review, various approaches will be discussed and compared to the newly developed nanogel technology in terms of efficiency and applicability for determining their potential role in combating infections in the biomedical area including implant-associated infections.</p
The BRAF P.V600E Mutation Status of Melanoma Lung Metastases Cannot Be Discriminated on Computed Tomography by LIDC Criteria nor Radiomics Using Machine Learning
No full textPatients with BRAF mutated (BRAF-mt) metastatic melanoma benefit significantly from treatment with BRAF inhibitors. Currently, the BRAF status is determined on archival tumor tissue or on fresh tumor tissue from an invasive biopsy. The aim of this study was to evaluate whether radiomics can predict the BRAF status in a non-invasive manner. Patients with melanoma lung metastases, known BRAF status, and a pretreatment computed tomography scan were included. After semi-automatic annotation of the lung lesions (maximum two per patient), 540 radiomics features were extracted. A chest radiologist scored all segmented lung lesions according to the Lung Image Database Consortium (LIDC) criteria. Univariate analysis was performed to assess the predictive value of each feature for BRAF mutation status. A combination of various machine learning methods was used to develop BRAF decision models based on the radiomics features and LIDC criteria. A total of 169 lung lesions from 103 patients (51 BRAF-mt; 52 BRAF wild type) were included. There were no features with a significant discriminative value in the univariate analysis. Models based on radiomics features and LIDC criteria both performed as poorly as guessing. Hence, the BRAF mutation status in melanoma lung metastases cannot be predicted using radiomics features or visually scored LIDC criteria.</p
Simultaneous Identification of EGFR, KRAS, ERBB2, and TP53 Mutations in Patients with Non-Small Cell Lung Cancer by Machine Learning-Derived Three-Dimensional Radiomics
No full textSimple SummaryMultiple genetic mutations are associated with the outcomes of patients with non-small cell lung cancer (NSCLC) after using tyrosine kinase inhibitor, but the cost for detecting multiple genetic mutations is high. Few studies have investigated whether multiple genetic mutations can be simultaneously detected based on image features in patients with NSCLC. We developed a machine learning-derived radiomics approach that can simultaneously discriminate the presence of EGFR, KRAS, ERBB2, and TP53 mutations on CT images in patients with NSCLC. These findings suggest that machine learning-derived radiomics may become a noninvasive and low-cost method to screen for multiple genetic mutations in patients with NSCLC before using next-generation sequencing tests, which can help to improve individualized targeted therapies.Purpose: To develop a machine learning-derived radiomics approach to simultaneously discriminate epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene (KRAS), Erb-B2 receptor tyrosine kinase 2 (ERBB2), and tumor protein 53 (TP53) genetic mutations in patients with non-small cell lung cancer (NSCLC). Methods: This study included consecutive patients from April 2018 to June 2020 who had histologically confirmed NSCLC, and underwent pre-surgical contrast-enhanced CT and post-surgical next-generation sequencing (NGS) tests to determine the presence of EGFR, KRAS, ERBB2, and TP53 mutations. A dedicated radiomics analysis package extracted 1672 radiomic features in three dimensions. Discriminative models were established using the least absolute shrinkage and selection operator to determine the presence of EGFR, KRAS, ERBB2, and TP53 mutations, based on radiomic features and relevant clinical factors. Results: In 134 patients (63.6 +/- 8.9 years), the 20 most relevant radiomic features (13 for KRAS) to mutations were selected to construct models. The areas under the curve (AUCs) of the combined model (radiomic features and relevant clinical factors) for discriminating EGFR, KRAS, ERBB2, and TP53 mutations were 0.78 (95% CI: 0.70-0.86), 0.81 (0.69-0.93), 0.87 (0.78-0.95), and 0.84 (0.78-0.91), respectively. In particular, the specificity to exclude EGFR mutations was 0.96 (0.87-0.99). The sensitivity to determine KRAS, ERBB2, and TP53 mutations ranged from 0.82 (0.69-90) to 0.92 (0.62-0.99). Conclusions: Machine learning-derived 3D radiomics can simultaneously discriminate the presence of EGFR, KRAS, ERBB2, and TP53 mutations in patients with NSCLC. This noninvasive and low-cost approach may be helpful in screening patients before invasive sampling and NGS testing.</p
Seasonal prevalence and characteristics of low-dose CT detected lung nodules in a general Dutch population
No full textWe investigated whether presence and characteristics of lung nodules in the general population using low-dose computed tomography (LDCT) varied by season. Imaging in Lifelines (ImaLife) study participants who underwent chest LDCT-scanning between October 2018 and October 2019 were included in this sub-study. Hay fever season (summer) was defined as 1st April to 30th September and Influenza season (winter) as 1st October to 31st March. All lung nodules with volume of ≥ 30 mm3 (approximately 3 mm in diameter) were registered. In total, 2496 lung nodules were found in 1312 (38%) of the 3456 included participants (nodules per participant ranging from 1 to 21, median 1). In summer, 711 (54%) participants had 1 or more lung nodule(s) compared to 601 (46%) participants in winter (p = 0.002). Of the spherical, perifissural and left-upper-lobe nodules, relatively more were detected in winter, whereas of the polygonal-, irregular-shaped and centrally-calcified nodules, relatively more were detected in summer. Various seasonal diseases with inflammation as underlying pathophysiology may influence presence and characteristics of lung nodules. Further investigation into underlying pathophysiology using short-term LDCT follow-up could help optimize the management strategy for CT-detected lung nodules in clinical practice.</p
On how thrombosis drives progression of liver and lung disease
No full textLiver disease can be acute or chronic and can be accompanied by a severe loss of liver function. Ultimately, liver function can deteriorate to such an extent that a liver transplant will be required. The course of serious liver diseases is different for each individual because there are several factors that influence the speed of the disease process. This thesis focuses on the development of thrombosis, or a dangerous blood clot, as a complication of liver disease, but also as a factor that can contribute to the worsening of the disease. Thrombosis can develop anywhere in the body, but we now know that this can also happen in the liver itself. This can then lead to an accelerated disease process because the supply of oxygen and nutrients is cut off in the smaller liver blood vessels. Thrombosis within the liver is likely caused by damage to the liver and the inflammatory response resulting from this damage. The liver also produces many of the proteins involved in the development of thrombosis. The coagulation balance is disturbed in patients with liver disease and these changes in the blood coagulation system are likely to contribute to thrombosis in the liver. Liver failure thus appears to be able to accelerate itself through a tendency to develop thrombosis in the liver. However, we do not know exactly what changes in the coagulation system are behind this, in whom they will occur and, above all, what we can do about it. This thesis has helped unravel some of these mechanisms. We also describe how similar changes in the blood coagulation system can increase the risk of thrombosis in a number of other diseases and procedures, such as lung transplantation. We provide advice from which others can develop therapies. This could be, for example, a new anticoagulant therapy that can slow down the disease process by preventing thrombosis
