From an exclusive national sample of Brazilian university laboratories, this study examines the relationship between the intensity of university-industry collaboration (UIC) and the scale of research ...resources and the scope of activities at the laboratory level. We defined the scale of the laboratories' research resources in terms of staff and capital stock. The staff of laboratories was proxied by the number of permanent researchers, non-permanent researchers, and non-researchers who made up their personnel structure. The capital stock was proxied by the value of the laboratories’ equipment infrastructure. The scope of activities conducted in the laboratories covered teaching, research, technological development, the provision of technological services, and technological extension. Results of the ordered logit model indicated that the number of non-researchers in the laboratory staff is positively associated with the intensity of the UIC, emphasizing the relevance of the non-academic experience for the establishment of links between laboratories and industry. A new type of evidence showed that the latent variable for the UIC intensity increased with the scale of the equipment infrastructure. We also found a positive relationship between UIC and technological activities at the laboratory level. Idiosyncrasies concerning the knowledge fields of the laboratories are discussed.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
We previously showed that supernatants of
Lactobacillus
biofilms induced an anti-inflammatory response by affecting the secretion of macrophage-derived cytokines, which was abrogated upon ...immunodepletion of the stress protein GroEL.
Methods
We purified GroEL from
L. reuteri
and analysed its anti-inflammatory properties in vitro in human macrophages isolated from buffy coats, ex vivo in explants from human biopsies and in vivo in a mouse model of DSS induced intestinal inflammation. As a control, we used GroEL purified (LPS-free) from
E. coli
.
Results
We found that
L. reuteri
GroEL (but not
E. coli
GroEL) inhibited pro-inflammatory M1-like macrophages markers, and favored M2-like markers. Consequently,
L. reuteri
GroEL inhibited pro-inflammatory cytokines (TNFα, IL-1β, IFNγ) while favouring an anti-inflammatory secretome. In colon tissues from human biopsies,
L. reuteri
GroEL was also able to decrease markers of inflammation and apoptosis (caspase 3) induced by LPS. In mice, we found that rectal administration of
L. reuteri
GroEL (but not
E. coli
GroEL) inhibited all signs of haemorrhagic colitis induced by DSS including intestinal mucosa degradation, rectal bleeding and weight loss. It also decreased intestinal production of inflammatory cytokines (such as IFNγ) while increasing anti-inflammatory IL-10 and IL-13. These effects were suppressed when animals were immunodepleted in macrophages. From a mechanistic point of view, the effect of
L. reuteri
GroEL seemed to involve TLR4, since it was lost in TRL4
−/−
mice, and the activation of a non-canonical TLR4 pathway.
Conclusions
L. reuteri
GroEL, by affecting macrophage inflammatory features, deserves to be explored as an alternative to probiotics.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Nucleic acid extraction (NAE) plays a vital role in molecular biology as the primary step for many downstream applications. Many modifications have been introduced to the original 1869 method. Modern ...processes are categorized into chemical or mechanical, each with peculiarities that influence their use, especially in point-of-care diagnostics (POC-Dx). POC-Dx is a new approach aiming to replace sophisticated analytical machinery with microanalytical systems, able to be used near the patient, at the point of care or point of need. Although notable efforts have been made, a simple and effective extraction method is still a major challenge for widespread use of POC-Dx. In this review, we dissected the working principle of each of the most common NAE methods, overviewing their advantages and disadvantages, as well their potential for integration in POC-Dx systems. At present, it seems difficult, if not impossible, to establish a procedure which can be universally applied to POC-Dx. We also discuss the effects of the NAE chemicals upon the main plastic polymers used to mass produce POC-Dx systems. We end our review discussing the limitations and challenges that should guide the quest for an efficient extraction method that can be integrated in a POC-Dx system.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The new coronavirus disease (COVID-19) is a challenge for clinical decision-making and the effective allocation of healthcare resources. An accurate prognostic assessment is necessary to improve ...survival of patients, especially in developing countries. This study proposes to predict the risk of developing critical conditions in COVID-19 patients by training multipurpose algorithms. We followed a total of 1040 patients with a positive RT-PCR diagnosis for COVID-19 from a large hospital from São Paulo, Brazil, from March to June 2020, of which 288 (28%) presented a severe prognosis, i.e. Intensive Care Unit (ICU) admission, use of mechanical ventilation or death. We used routinely-collected laboratory, clinical and demographic data to train five machine learning algorithms (artificial neural networks, extra trees, random forests, catboost, and extreme gradient boosting). We used a random sample of 70% of patients to train the algorithms and 30% were left for performance assessment, simulating new unseen data. In order to assess if the algorithms could capture general severe prognostic patterns, each model was trained by combining two out of three outcomes to predict the other. All algorithms presented very high predictive performance (average AUROC of 0.92, sensitivity of 0.92, and specificity of 0.82). The three most important variables for the multipurpose algorithms were ratio of lymphocyte per C-reactive protein, C-reactive protein and Braden Scale. The results highlight the possibility that machine learning algorithms are able to predict unspecific negative COVID-19 outcomes from routinely-collected data.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Exosomes, via heat shock protein 70 (HSP70) expressed in their membrane, are able to interact with the toll-like receptor 2 (TLR2) on myeloid-derived suppressive cells (MDSCs), thereby activating ...them.
We analyzed exosomes from mouse (C57Bl/6) and breast, lung, and ovarian cancer patient samples and cultured cancer cells with different approaches, including nanoparticle tracking analysis, biolayer interferometry, FACS, and electron microscopy. Data were analyzed with the Student's t and Mann-Whitney tests. All statistical tests were two-sided.
We showed that the A8 peptide aptamer binds to the extracellular domain of membrane HSP70 and used the aptamer to capture HSP70 exosomes from cancer patient samples. The number of HSP70 exosomes was higher in cancer patients than in healthy donors (mean, ng/mL ± SD = 3.5 ± 1.7 vs 0.17 ± 0.11, respectively, P = .004). Accordingly, all cancer cell lines examined abundantly released HSP70 exosomes, whereas "normal" cells did not. HSP70 had higher affinity for A8 than for TLR2; thus, A8 blocked HSP70/TLR2 association and the ability of tumor-derived exosomes to activate MDSCs. Treatment of tumor-bearing C57Bl/6 mice with A8 induced a decrease in the number of MDSCs in the spleen and inhibited tumor progression (n = 6 mice per group). Chemotherapeutic agents such as cisplatin or 5FU increase the amount of HSP70 exosomes, favoring the activation of MDSCs and hampering the development of an antitumor immune response. In contrast, this MDSC activation was not observed if cisplatin or 5FU was combined with A8. As a result, the antitumor effect of the drugs was strongly potentiated.
A8 might be useful for quantifying tumor-derived exosomes and for cancer therapy through MDSC inhibition.
Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance ...of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients. We evaluated 76 individuals, with tuberculosis active, treated and subjects with positive PPD. Granuloma formation was induced in the presence or absence of Infliximab for up to 10 days. The use of Infliximab in cultures significantly blocked TNF-α production (p <0.05), and led to significant changes in granuloma structure, in vitro, only in the treated TB group. On the other hand, there was a significant reduction in the levels of IFN-γ, IL-12p40, IL-10 and IL-17 after TNF-α blockade in the three experimental groups (p <0.05). Taken together, our results demonstrate that TNF-α blockade by Infliximab directly influenced the structure of granuloma only in the treated TB group, but negatively modulated the production of Th1, Th17 and regulatory T cytokines in the three groups analyzed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Virtual machine consolidation has been a widely explored topic in recent years due to Cloud Data Centers’ effect on global energy consumption. Thus, academia and companies made efforts to achieve ...green computing, reducing energy consumption to minimize environmental impact. By consolidating Virtual Machines into a fewer number of Physical Machines, resource provisioning mechanisms can shutdown idle Physical Machines to reduce energy consumption and improve resource utilization. However, there is a tradeoff between reducing energy consumption while assuring the Quality of Service established on the Service Level Agreement. This work introduces a Systematic Literature Review of one year of advances in virtual machine consolidation. It provides a discussion on methods used in each step of the virtual machine consolidation, a classification of papers according to their contribution, and a quantitative and qualitative analysis of datasets, scenarios, and metrics.
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IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
To predict the risk of absence from work due to morbidities of teachers working in early childhood education in the municipal public schools, using machine learning algorithms.OBJECTIVETo predict the ...risk of absence from work due to morbidities of teachers working in early childhood education in the municipal public schools, using machine learning algorithms.This is a cross-sectional study using secondary, public and anonymous data from the Relação Anual de Informações Sociais, selecting early childhood education teachers who worked in the municipal public schools of the state of São Paulo between 2014 and 2018 (n = 174,294). Data on the average number of students per class and number of inhabitants in the municipality were also linked. The data were separated into training and testing, using records from 2014 to 2016 (n = 103,357) to train five predictive models, and data from 2017 to 2018 (n = 70,937) to test their performance in new data. The predictive performance of the algorithms was evaluated using the value of the area under the ROC curve (AUROC).METHODSThis is a cross-sectional study using secondary, public and anonymous data from the Relação Anual de Informações Sociais, selecting early childhood education teachers who worked in the municipal public schools of the state of São Paulo between 2014 and 2018 (n = 174,294). Data on the average number of students per class and number of inhabitants in the municipality were also linked. The data were separated into training and testing, using records from 2014 to 2016 (n = 103,357) to train five predictive models, and data from 2017 to 2018 (n = 70,937) to test their performance in new data. The predictive performance of the algorithms was evaluated using the value of the area under the ROC curve (AUROC).All five algorithms tested showed an area under the curve above 0.76. The algorithm with the best predictive performance (artificial neural networks) achieved 0.79 of area under the curve, with accuracy of 71.52%, sensitivity of 72.86%, specificity of 70.52%, and kappa of 0.427 in the test data.RESULTSAll five algorithms tested showed an area under the curve above 0.76. The algorithm with the best predictive performance (artificial neural networks) achieved 0.79 of area under the curve, with accuracy of 71.52%, sensitivity of 72.86%, specificity of 70.52%, and kappa of 0.427 in the test data.It is possible to predict cases of sickness absence in teachers of public schools with machine learning using public data. The best algorithm showed a better result of the area under the curve when compared with the reference model (logistic regression). The algorithms can contribute to more assertive predictions in the public health and worker health areas, allowing to monitor and help prevent the absence of these workers due to morbidity.CONCLUSIONIt is possible to predict cases of sickness absence in teachers of public schools with machine learning using public data. The best algorithm showed a better result of the area under the curve when compared with the reference model (logistic regression). The algorithms can contribute to more assertive predictions in the public health and worker health areas, allowing to monitor and help prevent the absence of these workers due to morbidity.
Cancer immunotherapy has tremendous promise, but it has yet to be clinically applied in a wider variety of tumor situations. Many therapeutic combinations are envisaged to improve their ...effectiveness. In this way, strategies capable of inducing immunogenic cell death (e.g., doxorubicin, radiotherapy, hyperthermia) and the reprogramming of the immunosuppressive tumor microenvironment (TME) (e.g., M2-to-M1-like macrophages repolarization of tumor-associated macrophages (TAMs)) are particularly appealing to enhance the efficacy of approved immunotherapies (e.g., immune checkpoint inhibitors, ICIs). Due to their modular construction and versatility, iron oxide-based nanomedicines such as superparamagnetic iron oxide nanoparticles (SPIONs) can combine these different approaches in a single agent. SPIONs have already shown their safety and biocompatibility and possess both drug-delivery (e.g., chemotherapy, ICIs) and magnetic capabilities (e.g., magnetic hyperthermia (MHT), magnetic resonance imaging). In this review, we will discuss the multiple applications of SPIONs in cancer immunotherapy, focusing on their theranostic properties to target TAMs and to generate MHT. The first section of this review will briefly describe immune targets for NPs. The following sections will deal with the overall properties of SPIONs (including MHT). The last section is dedicated to the SPION-induced immune response through its effects on TAMs and MHT.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The beta3 adrenergic receptor (β3-AR) stimulation plays a protective role against preterm labor by blocking myometrial contraction, cytokine production, remodeling and apoptosis. We previously ...demonstrated that macrophage-induced ROS production in the myometrium was a key element leading to the induction of all these labor-associated features. We thus aimed to investigate if the β3-AR could be expressed in human macrophages and could trigger its protective role in the myometrium by directly inhibiting ROS production. Using lipopolysaccharide (LPS)-stimulated myometrial samples and cell co-culture experiments, we demonstrated that β3-AR stimulation inhibits the activation of the NADPH oxidase, leading to the subsequent inhibition of ROS production by macrophages. This antioxidant effect was associated with a potent anti-inflammatory response in macrophages. Furthermore, we observed that β3-AR leads to the expression of catalase not only in macrophages but also in myometrial cells, thereby preventing the transactivation of myometrial cells by hydrogen peroxide. Pharmacological experiments allowed us to demonstrate that these effects were driven by an Erk1/2-mediated activation of the antioxidant transcription factor PPARγ. These results suggest that β3-AR protective effects in the myometrium could be due to its dual antioxidant properties. Further, the effects observed in a macrophage could highlight new applications in chronic inflammatory diseases.
•β3-AR stimulation in the myometrium prevents labor onset via antioxidant effects.•The β3-AR is expressed in macrophages where its stimulation prevents inflammation.•β3-AR antioxidant effects depends upon the activation of PPARγ.•PPARγ has antioxidant effects by inhibiting Nox2 and promoting catalase expression.•β3-AR/PPARγ induction could be an interesting target on inflammatory diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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