Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults, characterized by a highly aggressive, inflammatory and angiogenic phenotype. It is a remarkably heterogeneous tumor at ...several levels, including histopathologically, radiographically and genetically. The 2016 update of the WHO Classification of Tumours of the Central Nervous System highlighted molecular parameters as paramount features for the diagnosis, namely
mutations that distinguish primary and secondary GBM. An ideal biomarker is a molecule that can be detected/quantified through simple non- or minimally invasive methods with the potential to assess cancer risk; promote early diagnosis; increase grading accuracy; and monitor disease evolution and treatment response, as well as fundamentally being restricted to one aspect. Blood-based biomarkers are particularly attractive due to their easy access and have been widely used for various cancer types. A number of serum biomarkers with multiple utilities for glioma have been reported that could classify glioma grades more precisely and provide prognostic value among these patients. At present, screening for gliomas has no clinical relevance. This is because of the low incidence, the lack of sensitive biomarkers in plasma, and the observation that gliomas may develop apparently de novo within few weeks or months. To the best of our knowledge, there is no routine use of a serum biomarker for clinical follow-up. The purpose of this paper is to review the serum biomarkers described in the literature related to glioblastoma and their possible relationship with clinical features.
Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated ...inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L. acidophilus and Bifidobacterium bifidumi) on gut microbiota, changes in permeability, and insulin sensitivity and signaling in high-fat diet and control animals. More importantly, we investigated the effects of these gut modulations on hypothalamic control of food intake, and insulin and leptin signaling. Swiss mice were submitted to a high-fat diet (HFD) with probiotics or pair-feeding for 5 weeks. Metagenome analyses were performed on DNA samples from mouse feces. Blood was drawn to determine levels of glucose, insulin, LPS, cytokines and GLP-1. Liver, muscle, ileum and hypothalamus tissue proteins were analyzed by Western blotting and real-time polymerase chain reaction. In addition, liver and adipose tissues were analyzed using histology and immunohistochemistry. The HFD induced huge alterations in gut microbiota accompanied by increased intestinal permeability, LPS translocation and systemic low-grade inflammation, resulting in decreased glucose tolerance and hyperphagic behavior. All these obesity-related features were reversed by changes in the gut microbiota profile induced by probiotics. Probiotics also induced an improvement in hypothalamic insulin and leptin resistance. Our data demonstrate that the intestinal microbiome is a key modulator of inflammatory and metabolic pathways in both peripheral and central tissues. These findings shed light on probiotics as an important tool to prevent and treat patients with obesity and insulin resistance.
Vector borne diseases are susceptible to climate change because distributions and densities of many vectors are climate driven. The Amazon region is endemic for cutaneous leishmaniasis and is ...predicted to be severely impacted by climate change. Recent records suggest that the distributions of Lutzomyia (Nyssomyia) flaviscutellata and the parasite it transmits, Leishmania (Leishmania) amazonensis, are expanding southward, possibly due to climate change, and sometimes associated with new human infection cases. We define the vector's climatic niche and explore future projections under climate change scenarios. Vector occurrence records were compiled from the literature, museum collections and Brazilian Health Departments. Six bioclimatic variables were used as predictors in six ecological niche model algorithms (BIOCLIM, DOMAIN, MaxEnt, GARP, logistic regression and Random Forest). Projections for 2050 used 17 general circulation models in two greenhouse gas representative concentration pathways: "stabilization" and "high increase". Ensemble models and consensus maps were produced by overlapping binary predictions. Final model outputs showed good performance and significance. The use of species absence data substantially improved model performance. Currently, L. flaviscutellata is widely distributed in the Amazon region, with records in the Atlantic Forest and savannah regions of Central Brazil. Future projections indicate expansion of the climatically suitable area for the vector in both scenarios, towards higher latitudes and elevations. L. flaviscutellata is likely to find increasingly suitable conditions for its expansion into areas where human population size and density are much larger than they are in its current locations. If environmental conditions change as predicted, the range of the vector is likely to expand to southeastern and central-southern Brazil, eastern Paraguay and further into the Amazonian areas of Bolivia, Peru, Ecuador, Colombia and Venezuela. These areas will only become endemic for L. amazonensis, however, if they have competent reservoir hosts and transmission dynamics matching those in the Amazon region.
Over the last few decades, there has been significant interest in the automatic analysis of respiratory sounds. However, currently there are no publicly available large databases with which new ...algorithms can be evaluated and compared. Further developments in the field are dependent on the creation of such databases.
This paper describes a public respiratory sound database, which was compiled for an international competition, the first scientific challenge of the IFMBE's International Conference on Biomedical and Health Informatics. The database includes 920 recordings acquired from 126 participants and two sets of annotations. One set contains 6898 annotated respiratory cycles, some including crackles, wheezes, or a combination of both, and some with no adventitious respiratory sounds. In the other set, precise locations of 10 775 events of crackles and wheezes were annotated.
The best system that participated in the challenge achieved an average score of 52.5% with the respiratory cycle annotations and an average score of 91.2% with the event annotations.
The creation and public release of this database will be useful to the research community and could bring attention to the respiratory sound classification problem.
The incidence of vector-borne diseases is rising as deforestation, climate change, and globalization bring humans in contact with arthropods that can transmit pathogens. In particular, incidence of ...American Cutaneous Leishmaniasis (ACL), a disease caused by parasites transmitted by sandflies, is increasing as previously intact habitats are cleared for agriculture and urban areas, potentially bringing people into contact with vectors and reservoir hosts. Previous evidence has identified dozens of sandfly species that have been infected with and/or transmit Leishmania parasites. However, there is an incomplete understanding of which sandfly species transmit the parasite, complicating efforts to limit disease spread. Here, we apply machine learning models (boosted regression trees) to leverage biological and geographical traits of known sandfly vectors to predict potential vectors. Additionally, we generate trait profiles of confirmed vectors and identify important factors in transmission. Our model performed well with an average out of sample accuracy of 86%. The models predict that synanthropic sandflies living in areas with greater canopy height, less human modification, and within an optimal range of rainfall are more likely to be Leishmania vectors. We also observed that generalist sandflies that are able to inhabit many different ecoregions are more likely to transmit the parasites. Our results suggest that Psychodopygus amazonensis and Nyssomia antunesi are unidentified potential vectors, and should be the focus of sampling and research efforts. Overall, we found that our machine learning approach provides valuable information for Leishmania surveillance and management in an otherwise complex and data sparse system.
Objective: The double‐stranded RNA‐dependent protein kinase (PKR) was recently implicated in regulating molecular integration of nutrient‐ and pathogen‐sensing pathways in obese mice. However, its ...modulation in human tissues in situations of insulin resistance has not been investigated. The present study was performed to first determine the tissue expression and phosphorylation levels of PKR in the liver, muscle, and adipose tissue in obese humans, and also the modulation of this protein in the adipose tissue of obese patients after bariatric surgery.
Design and Methods: Eleven obese subjects who were scheduled to undergo Roux‐en‐Y Gastric Bypass Procedure participated in this study. Nine apparently healthy lean subjects as a control group were also included.
Results: Our data show that PKR is activated in liver, muscle, and adipose tissue of obese humans and, after bariatric surgery, there is a clear reduction in PKR activation accompanied by a decrease in protein kinase‐like endoplasmic reticulum kinase, c‐Jun N‐terminal kinase, inhibitor of kappa β kinase, and insulin receptor substrate‐1 serine 312 phosphorylation in subcutaneous adipose tissue from these patients.
Conclusion: Thus, it is proposed that PKR is an important mediator of obesity‐induced insulin resistance and a potential target for the therapy.
Lung sounds acquired by stethoscopes are extensively used in diagnosing and differentiating respiratory diseases. Although an extensive know-how has been built to interpret these sounds and identify ...diseases associated with certain patterns, its effective use is limited to individual experience of practitioners. This user-dependency manifests itself as a factor impeding the digital transformation of this valuable diagnostic tool, which can improve patient outcomes by continuous long-term respiratory monitoring under real-life conditions. Particularly patients suffering from respiratory diseases with progressive nature, such as chronic obstructive pulmonary diseases, are expected to benefit from long-term monitoring. Recently, the COVID-19 pandemic has also shown the lack of respiratory monitoring systems which are ready to deploy in operational conditions while requiring minimal patient education. To address particularly the latter subject, in this article, we present a sound acquisition module which can be integrated into a dedicated garment; thus, minimizing the role of the patient for positioning the stethoscope and applying the appropriate pressure. We have implemented a diaphragm-less acousto-electric transducer by stacking a silicone rubber and a piezoelectric film to capture thoracic sounds with minimum attenuation. Furthermore, we benchmarked our device with an electronic stethoscope widely used in clinical practice to quantify its performance.
•Demarcated Douro Region viticulture, ecosystem and environment.•Influence of Demarcated Douro Region terroir in Port wine quality.•Climate, soil, ampelography and human activity as the main pillars ...of terroir.•Color, aroma, and flavor of different styles of Port wines.
Port wine is an internationally acclaimed fortified wine produced in Douro Demarcated Region (DDR) in Portugal, and recognized with protected designation of origin. This review represents a compilation of the known chromatic and aromatic descriptors of Port wine. A comprehensive review of literature is performed regarding the influence of geography, climate, soil, grapevine cultivars, and vitivinicultural practices on the unique Port wine attributes. This manuscript provides an extensive insight regarding the different aspects that influence the quality and uniqueness of Port wine, especially its main sensory attributes: colour, aroma, and flavour. Its main goal is to assess the importance of the DDR as a unique and defined terroir that ensures quality and confers authenticity.
Purpose
To study whether ICU staffing features are associated with improved hospital mortality, ICU length of stay (LOS) and duration of mechanical ventilation (MV) using cluster analysis directed by ...machine learning.
Methods
The following variables were included in the analysis: average bed to nurse, physiotherapist and physician ratios, presence of 24/7 board-certified intensivists and dedicated pharmacists in the ICU, and nurse and physiotherapist autonomy scores. Clusters were defined using the partition around medoids method. We assessed the association between clusters and hospital mortality using logistic regression and with ICU LOS and MV duration using competing risk regression.
Results
Analysis included data from 129,680 patients admitted to 93 ICUs (2014–2015). Three clusters were identified. The features distinguishing between the clusters were: the presence of board-certified intensivists in the ICU 24/7 (present in Cluster 3), dedicated pharmacists (present in Clusters 2 and 3) and the extent of nurse autonomy (which increased from Clusters 1 to 3). The patients in Cluster 3 exhibited the best outcomes, with lower adjusted hospital mortality odds ratio 0.92 (95% confidence interval (CI), 0.87–0.98), shorter ICU LOS subhazard ratio (SHR) for patients surviving to ICU discharge 1.24 (95% CI 1.22–1.26) and shorter durations of MV SHR for undergoing extubation 1.61(95% CI 1.54–1.69). Cluster 1 had the worst outcomes.
Conclusion
Patients treated in ICUs combining 24/7 expert intensivist coverage, a dedicated pharmacist and nurses with greater autonomy had the best outcomes. All of these features represent achievable targets that should be considered by policy makers with an interest in promoting equal and optimal ICU care.
Plasmodium vivax remains a global health problem and its ability to cause relapses and subpatent infections challenge control and elimination strategies. Even in low malaria transmission settings, ...such as the Amazon basin, where progress in malaria control has caused a remarkable reduction in case incidence, a recent increase in P. vivax transmission demonstrates the continued vulnerability of P.vivax-exposed populations. As part of a search for complementary approaches to P.vivax surveillance in areas in which adults are the majority of the exposed-population, here we evaluated the potential of serological markers covering a wide range of immunogenicity to estimate malaria transmission trends. For this, antibodies against leading P. vivax blood-stage vaccine candidates were assessed during a 9 year follow-up study among adults exposed to unstable malaria transmission in the Amazon rainforest. Circulating antibody levels against immunogenic P. vivax proteins, such as the Apical Membrane Antigen-1, were a sensitive measure of recent P. vivax exposure, while antibodies against less immunogenic proteins were indicative of naturally-acquired immunity, including the novel engineered Duffy binding protein II immunogen (DEKnull-2). Our results suggest that the robustness of serology to estimate trends in P.vivax malaria transmission will depend on the immunological background of the study population, and that for adult populations exposed to unstable P.vivax malaria transmission, the local heterogeneity of antibody responses should be considered when considering use of serological surveillance.
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