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Abstract Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, accentuated by its heterogeneity and complex tumour microenvironment (TME). The role of TME on tumour pathophysiology is pivotal, especially the influence of components of the extracellular matrix (ECM), such as collagen. We introduce a novel multimodal imaging strategy to unravel the complex spatial heterogeneity of CRC by integrating the imaging features from two-photon laser scanning microscopy (2PLSM) and histology with proteomics signatures from matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI MSI). Our study is the first to correlate the structural coherence of collagen fibres and the nuclei distribution profile of tumour tissue with the peptide signatures, offering insights into the proteomic landscape of CRC within regions of high nuclei distribution (HND), as well as chaotic and organised regions of collagen. We use this approach to distinguish the patient tissues originating from left-sided colorectal cancer (LSCC) and from right-sided colorectal cancer (RSCC). This discriminative signature highlights the role of high nuclei distribution and collagen architecture in tumour progression. Complementary m/z values of several proteins associated to components of ECM, such as plectin, vinculin, vimentin, and myosin, have shown differentially intensity distributions between LSCC and RSCC. Our findings demonstrate the potential of combining structural information with peptide features to identify molecular signatures in different tumour regions and retrieve new insights into CRC pathophysiology.

Colorectal cancer (CRC) is the third most common cancer type and second leading cause of cancer‐related deaths worldwide, requiring novel drug‐delivery concepts. ITC@ZrO(TocP)/ZrO(FdUMP) core@shell nanocarriers (designated ITC‐FdUMP‐NC) with the clinically relevant chemotherapeutics irinotecan (ITC) and fluoro‐2′‐deoxyuridine‐5′‐phosphate (FdUMP) (active derivative of 5′‐fluorouracil/5‐FU) are a new type of nanocarrier with high drug payload (22 wt% of lipophilic ITC: particle core; 10 wt% of hydrophilic FdUMP: particle shell). The nanocarriers are tested in different CRC cell lines, a normal cell line, and rectal cancer patient‐derived organoids (PDOs). Fluorescence‐labeled nanocarriers show efficient uptake by all CRC cells and allow to distinctly track the intracellular trafficking toward endolysosomal compartments. Although free chemotherapeutic drugs exhibit a greater potency in 2D cell cultures, ITC‐FdUMP‐NC demonstrate equivalent cytotoxic efficacies as the freely dissolved drugs in the more complex 3D rectal cancer PDOs. The sustained drug‐release profile of the nanocarriers contrasts favorably with conventional free drugs, potentially enhancing the therapeutic outcome in vivo. With a chemotherapeutic cocktail comparable to the clinically applied FOLFIRI (ITC + 5‐FU), the ITC‐FdUMP‐NC represent a novel type of nanocarrier with high anti‐tumor effect and high drug payload, offering a promising strategy to circumvent chemoresistance and to improve therapy efficacy in vivo with less side effects.

Abstract Mouse models for the study of pancreatic ductal adenocarcinoma (PDAC) are well-established and representative of many key features observed in human PDAC. To monitor tumor growth, cancer cells that are implanted in mice are often transfected with reporter genes, such as firefly luciferase (Luc), enabling in vivo optical imaging over time. Since Luc can induce an immune response, we aimed to evaluate whether the expression of Luc could affect the growth of KPC tumors in mice by inducing immunogenicity. Although both cell lines, KPC and Luc transduced KPC (KPC-Luc), had the same proliferation rate, KPC-Luc tumors had significantly smaller sizes or were absent 13 days after orthotopic cell implantation, compared to KPC tumors. This coincided with the loss of bioluminescence signal over the tumor region. Immunophenotyping of blood and spleen from KPC-Luc tumor-bearing mice showed a decreased number of macrophages and CD4+ T cells, and an increased accumulation of natural killer (NK) cells in comparison to KPC tumor mice. Higher infiltration of CD8+ T cells was found in KPC-Luc tumors than in their controls. Moreover, the immune response against Luc peptide was stronger in splenocytes from mice implanted with KPC-Luc cells compared to those isolated from KPC wild-type mice, indicating increased immunogenicity elicited by the presence of Luc in the PDAC tumor cells. These results must be considered when evaluating the efficacy of anti-cancer therapies including immunotherapies in immunocompetent PDAC or other cancer mouse models that use Luc as a reporter for bioluminescence imaging.

Abstract The molecular pathogenesis of colorectal cancer is known to differ between the right and left side of the colon. Several previous studies have focussed on the differences in clinicopathological features, proteomic and genetic biomarkers, the composition of gut microbiota, response to therapy, and the characteristics of the tumour microenvironment. However, the morphology and density of collagen in the extracellular matrix (ECM) have not been studied intensively. In this study, we employed 2-photon laser scanning microscopy (2PLSM) to visualise the intrinsic second-harmonic generation (SHG) signal emitted by collagen fibres in the heterogeneous ECM of human colon tumour tissues. Through texture analysis of the SHG signal, we quantitatively distinguished the imaging features generated by structural differences of collagen fibres in healthy colon and cancers and found marked differences. The fibres inside of tumours exhibited a loss of organisation, particularly pronounced in right-sided colon cancer (RSCC), where the chaotic regions were significantly increased. In addition, a higher collagen content was found in left-sided colon cancer (LSCC). In future, this might aid in subclassification and therapeutic decisions or even in designing new therapy regimens by taking into account the differences between collagen fibres features between colon tumours located at different sides.

Resumo: Durante a pandemia da COVID-19, o negacionismo científico teve uma imensa repercussão midiática e a palavra negacionista se tornou um dos termos depreciativos mais utilizados no Brasil. Porém, nem sempre ele é definido com precisão, em toda a sua complexidade e nuances. A utilização errônea de conceitos pode criar confusões epistêmicas com noções adjacentes, que não equivalem ao negacionismo, como ceticismo, ignorância, pseudociência ou agnotologia. O objetivo do presente artigo é definir negacionismo, com base em revisão teórica, e diferenciá-lo destes termos. Como conclusão, propõe-se uma reflexão sobre as implicações éticas do negacionismo, que pode levar à perda de vidas em casos extremos, e da importância do letramento científico na tomada de decisões.

Background: Aging is characterized by a decline in the cardiovascular hemodynamic response, which may be aggravated by undernutrition. However, no study has evaluated whether low caloric intake may affect cardiovascular hemodynamics and its possible relation with functional capacity and immune response in older adults. Methods: Sixty-one older adults of both genders were enrolled in this study and were classified as normocaloric (n = 18) and hypocaloric (n = 43). All volunteers were evaluated for cardiovascular hemodynamics using impedance cardiography (PhysioFlow®); functional capacity by the 1′ sit-to-stand test with SpO2 monitoring; whole-blood analysis using an automated hematocytometer (Sysmex®); and levels of IL-6, TNF-alpha, IL-10, and Klotho by ELISA. Results: The hypocaloric group presented impaired functional capacity, measured by a reduced number of sit-to-stand repetitions (p < 0.0251) and impaired delta of SpO2 (p < 0.0307). In contrast, the hypocaloric group presented an improved stroke volume (p < 0.0352), systemic vascular resistance (p < 0.0075), and systemic vascular resistance index (p < 0.0184). In addition, no changes were observed in the whole-blood analysis (p > 0.05) or for IL-6 (p > 0.05), TNF-alpha (p < 0.05), IL-10 (p < 0.05), and Klotho (p > 0.05). Conclusions: A long-term hypocaloric diet in eutrophic older adults' resulted in an enhanced cardiovascular hemodynamic response but was associated with reduced functional capacity without changes in the immune response. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer type and second leading cause of cancer‐related deaths worldwide, requiring novel drug‐delivery concepts. ITC@ZrO(TocP)/ZrO(FdUMP) core@shell nanocarriers (designated ITC‐FdUMP‐NC) with the clinically relevant chemotherapeutics irinotecan (ITC) and fluoro‐2′‐deoxyuridine‐5′‐phosphate (FdUMP) (active derivative of 5′‐fluorouracil/5‐FU) are a new type of nanocarrier with high drug payload (22 wt% of lipophilic ITC: particle core; 10 wt% of hydrophilic FdUMP: particle shell). The nanocarriers are tested in different CRC cell lines, a normal cell line, and rectal cancer patient‐derived organoids (PDOs). Fluorescence‐labeled nanocarriers show efficient uptake by all CRC cells and allow to distinctly track the intracellular trafficking toward endolysosomal compartments. Although free chemotherapeutic drugs exhibit a greater potency in 2D cell cultures, ITC‐FdUMP‐NC demonstrate equivalent cytotoxic efficacies as the freely dissolved drugs in the more complex 3D rectal cancer PDOs. The sustained drug‐release profile of the nanocarriers contrasts favorably with conventional free drugs, potentially enhancing the therapeutic outcome in vivo. With a chemotherapeutic cocktail comparable to the clinically applied FOLFIRI (ITC + 5‐FU), the ITC‐FdUMP‐NC represent a novel type of nanocarrier with high anti‐tumor effect and high drug payload, offering a promising strategy to circumvent chemoresistance and to improve therapy efficacy in vivo with less side effects. [ABSTRACT FROM AUTHOR]

The [1,2,3]-triazolo [1,5-a] quinoxalin-4(5H)-one scaffold and its analogues triazole-fused heterocyclic compounds are relevant structural templates in both natural and synthetic biologically active compounds. However, their medicinal chemistry applications are often limited due to the lack of synthetic protocols combining straightforward generation of the central core while also allowing extensive decoration activity for drug discovery purposes. Herein, we report a “refreshed” synthesis of the [1,2,3]-triazolo [1,5-a]quinoxalin-4(5H)-one core, encompassing the use of eco-compatible catalysts and reaction conditions. We have also performed a sustainable and extensive derivatization campaign at both the endocyclic amide nitrogen and the ester functionality, comprehensively exploring the reaction scope and overcoming some of the previously reported difficulties in introducing functional groups on this structural template. Finally, we unveiled a preliminary biological investigation for the newly generated chemical entities. Our assessment of the compounds on different bacterial species (two S. aureus strains, three P. aeruginosa strains, K. pneumonia), and two fungal C. albicans strains, as well as the evaluation of their activity on S. epidermidis biofilm formation, foster further optimization for the retrieved hit compounds 9, 14, and 20.

O futebol a nível competitivo tem sido alvo de bastante interesse entre os jovens logo, avaliação nutricional é fundamental ao garantir monitoramento e ajustes dietéticos adequados que focam essencialmente na saúde do atleta e no seu êxito em campo. O presente estudo tem como objetivo avaliar o estado nutricional e o consumo alimentar em atletas adolescentes de futebol de campo de um clube esportivo da Cidade de Recife-PE. Foi realizado um estudo com 18 atletas do sexo masculino da categoria Sub-13 no Ambulatório de Nutrição no Sport Clube do Recife-PE. Foram coletadas as medidas antropométricas para estimar a necessidade calórica e avaliação do estado nutricional, %GC e MMkg, e foram aplicados também dois R24h para análise da ingestão de macronutrientes, fibras alimentares e micronutrientes (ferro e cálcio). Verificou-se que 27,78% dos atletas estão com sobrepeso através do parâmetro IMC/I, e o %GC de 20,19±3,34%, sendo 9 atletas classificados em moderadamente alto, e apresentaram a massa magra de 41,99±5,19kg. Os atletas mostraram também déficit energético entre a ingestão de 1.901,6±419,28kcal e as necessidades calóricas, 2.767,5±278,94kcal, o consumo insuficiente de carboidratos (54,55±3,89%) e de lipídios (23,45±4,14%) e excesso no consumo de proteínas que foi de 1,97±0,56g/kg/dia, por fim, houve uma baixa ingestão de fibras alimentares (18,77±5,77g) e de cálcio (670,56±316,56mg) e excesso de ferro (16,75±4,23mg). Nesse contexto, ressalta-se a importância da intervenção nutricional com foco na saúde e desempenho dos atletas em campo tampouco, a necessária educação alimentar voltada a práticas alimentares saudáveis que perpetuem por toda a vida.

Introduction: Spinal anesthesia combined with sedation and general anesthesia combined with epidural are two techniques often used for patients undergoing abdominal hysterectomy. There is no consensus that one of these techniques is superior regarding the perception of patients towards the quality of postoperative recovery. This observational cross-sectional study aimed to assess the quality of postoperative recovery in women undergoing open abdominal hysterectomy by comparing both anesthetic techniques. Method: We recruited 162 women aged between 30 and 74 years to be submitted to abdominal hysterectomy. The anesthetic technique used followed the preference of the attending anesthesiologist without interference of the investigators. After applying the exclusion criteria, 80 patients underwent spinal anesthesia combined with sedation (Group 1) and 62 women underwent epidural anesthesia combined with general anesthesia (Group 2). The quality of postoperative recovery was evaluated using the questionnaire Quality of Recovery-40 (QoR-40) completed 24 hours after the end of the surgery. Results: Eighty patients in Group 1 answered the QoR-40 questionnaire with an average rating of 179.4 points, median of 186.5, standard deviation of 17.4 and a confidence interval of 3.8. The 60 patients in Group 2 answered the QoR-40 with an average of 174.9 points, median of 178 points, standard deviation of 16 points and a confidence interval of 4.0 (p = 0.024). Conclusion: Women who received spinal anesthesia combined with sedation considered quality of postoperative recovery better.

Abstract With the spread of SARS-CoV-2, contingency measures and plans to facilitate the screening of infected patients are needed. Changes in olfaction have been cited as symptoms of the disease, and it is important to prove or exclude its association with this condition to refine the symptomatic criteria for early isolation. This article aims to analyze the association between olfactory disorders and SARS-CoV-2 infection as well as investigate the possible underlying pathophysiological mechanisms. The research was carried out using the PubMed, Science Direct, and LILACS databases on May 9, 2020, and updated on May 21. Combinations of MeSH descriptors and the Boolean operator, “AND,” were used: coronavirus infections AND olfactory disorders, coronavirus infections, and neurological manifestations. A total of 1187 articles were found in the databases, of which 17 were included in the study. The data suggest that changes in smell are strongly associated with Covid-19, especially in women and patients with fever; these changes increase the degree of suspicion of Covid-19, and they warrant early implementation of isolation and surveillance measures. There are still gaps in the elucidation of the pathways involved in the loss of smell caused by SARS-CoV-2; however, the great affinity of the virus for ACE-2 receptors, which are present in large quantities in the nasal cavity and olfactory bulb, has been considered.

O presente trabalho busca analisar a forma de apropriação feita pelo jogo Child of Light das narrativas tradicionais de passagem para vida adulta em seu caráter metafórico e transmidiático. A narrativa do jogo, apresentada em versos, dialoga com alguns contos de fadas, principalmente com A Bela Adormecida. Tanto o nome da protagonista, Aurora, quanto sua condição inicial no jogo, a de estar em um sono profundo, remete-nos ao clássico infantil. Sendo assim, para a investigação proposta, pretende-se identificar e analisar as características específicas dos gêneros contos de fadas e videogame, assim como analisar sua estrutura narrativa, temática e elementos que contribuem para a interação leitor-obra nos dois gêneros em questão, a saber: os elementos textuais e paratextuais nos contos de fadas e os relacionados à jogabilidade no videogame. Pretende-se ainda comparar as narrativas, analisando a presença da intertextualidade. Como principal fundamentação teórica desta pesquisa destacamos: os estudos sobre literatura infantil de Peter Hunt; os estudos sobre a estrutura dos contos de fadas de Vladimir Propp; os estudos sobre jogos digitais de Juul, de Murray e de Ryan.

Abstract Osteoid osteoma is a benign neoplasm commonly found in young men, but that can be found in every age, which affects mainly long bones, clinically characterized by continuous and limiting pain that is relieved by salicylates. It is a small lesion composed of immature osteoid tissue, central hypervascularization and surrounding sclerotic area. Its diagnosis is performed by the clinic and aided by imaging tests, such as common radiography and computed tomography. Radiography shows a central radiolucent lesion and peripheral sclerosis. The biopsy takes place only in cases of diagnostic doubt. Surgical treatment involves resection of the niche, providing greater symptomatic relief, as well as percutaneous techniques. The technique of radioisotope-guided resection has good acceptance in the scientific community for its fast surgical procedure directed to the lesion; however, the percutaneous technique that stands out is radiofrequency ablation. In the present study, all of the patients submitted to the technique presented total improvement of the pain.

Nanomaterials are increasingly used for the diagnosis and treatment of cancer, including lung cancer. For the clinical translation of nano-based theranostics, it is vital to detect and monitor their accumulation in the tumor, as well as their interaction with tumor, immune cells, and the tumor microenvironment (TME). While high resolution microscopy of fixed tumor specimens can provide some of this information from individual thin slices, it cannot capture cellular events over time and lacks 3D information of the tumor tissue. On the other hand, in vivo optical procedures either fall short of providing the necessary cellular resolution, as in the case of epifluorescence optical imaging, or are very demanding, as for instance intravital lung microscopy. We describe an alternative approach to investigate nanoparticle-cell interactions in entire mouse lung lobes, by longitudinal live cell confocal microscopy at nanometer resolution. By filling the lung ex vivo with 1% agarose, we were able to stabilize the lung lobes and visualize the interaction of fluorescent cells and nanoparticles for at least 4 hours post mortem. This high resolution ex vivo live cell imaging approach is an easy 4D tool for assessing several dynamic processes in tumor tissue, such as the traffic of cells, shedding of extracellular vesicles (EVs), and the accumulation of nanoparticles in tumor tissue.Graphic abstract: Schematic of the workflow for live cell imaging in the mouse lung.

Abstract Patellar tumors are rare. Commonly benign, giant-cell tumors and chondroblastomas are the most frequent types of this tumor. Aneurysmal bone cysts are a less common type, corresponding to less than 1% of the cases. The authors present a case of a 23-year-old male patient who presented left patellar pain and swelling for two years. The radiographic images suggested tumoral causes, and the biopsy was negative for neoplasm. The treatment approach was a complete patellectomy, without complications. The imaging follow-up showed no recurrence.

O primeiro objetivo deste estudo piloto é descrever a influência dos repertórios linguísticos dos reality show estadunidense RuPaul Drag Race, e da websérie brasileira do youtube Girls In The House, no repertório linguístico dos adolescentes, jovens e adultos na comunidade LGBTTI. Para o desenvolvimento deste estudo, foram considerados os aspectos ideológicos e identitários (BAUMAN, 2005; MOITA LOPES, 2002) que permeiam as expressões linguísticas desses grupos. Além disso, ao refletir sobre o atual contexto de superdiversidade (VERTOVEC, 2007), de globalização (KUMARAVADIVELU, 2006) e de contatos linguísticos-culturais muito mais intensos (RYMES, 2010), notamos que o repertório linguístico que nasce dentro de grupos LGBTTIs (e que é disseminado pelos programas) também reconfigura-se em grupos de adolescentes e jovens adultos que se identificam com os aspectos culturais e ideológicos de grupos LGBTTI, sem necessariamente fazerem parte dessa comunidade. Um segundo objetivo deste estudo piloto é descrever e analisar o repertório de adolescentes e jovens adultos, por meio de dados retirados do Facebook, especificamente de postagens do grupo secreto LDRV: Melodrama Era que, atualmente, possui mais de um milhão de membros. Posteriormente, foi realizado um estudo de caso a partir de entrevistas com membros do grupo a fim de descrever e analisar os usos linguísticos adotados pelos indivíduos e relacioná-los ao repertório dos programas de televisão e da comunidade LGBTTIs. Os resultados apontam que as séries funcionam como modelo de uso linguístico para os falantes que, assim, expressam suas ideologias e questões identitárias.

The present paper refers to the work carried out by the educational team during the exhibition of "Folhetos de Cordel Portugueses - Arnaldo Saraiva Collection", held at Academia Mineira de Letras between November 7 and November 26, 2017. During the exhibition guided visits and workshops were conducted by the team for students of Belo Horizonte public and private schools, as well as visits from the general public and accessibility, however, in this paper we will focus on the visits related to accessibility. We will reflect on how these workshops promote literary literacy and the empowerment of visitors through the appreciation of the popular culture present in the cordeis. It will also raise the question of the performance of professionals from various areas as mediators of art and promoters of accessibility promoters, as well as educational wage initiatives beyond schoolar discourse, also the role played by the cultural mediators in this paper. To do so, we will use Michelle Pettit's concepts regarding reading mediation, Rezende and Mayer in the scope of the audio description and accessibility, regarding the theme of the exhibition itself, the cordeis, we will use the texts of Arnaldo Saraiva himself, who besides being a collector is a relevant scholar of the subject and, carried out part of the training of the team.

ABSTRACT The gold standard for the laboratory diagnosis of COVID-19 is the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) assay, which searches for SARS-CoV-2 target genes in nasopharyngeal/oropharyngeal (NP/OP) samples, and its performance depends on the quantity and quality of the RNA input. This study compared the performance and cost-effectiveness of three different kits/reagents for RNA extraction used in COVID-19 diagnosis in Sao Paulo, Brazil. A total of 300 NP/OP samples belonging to suspected cases of COVID-19 stored in a biorepository were randomly selected, and RNA was extracted using (i) automated extraction (Loccus, Extracta Kit FAST), (ii) manual extraction (BioGene Kit, Bioclin, Quibasa), and (iii) quick extraction methods (Lucigen, Quick DNA Extract Kit). Next, the samples were tested using RT-qPCR for SARS-CoV-2 with the Allplex 2019-nCoV modified assay and the Charité-Berlin protocol. All assays/kits were used according to the manufacturer’s instructions. For the Allplex kit, the sensitivity in detecting SARS-CoV-2 with previously extracted RNA by different procedures was 100.0% for Loccus, 100.0% for BioGene and 91.9% for Quick. Using the Charité-Berlin protocol, the sensitivities were 81.4% for Loccus, 81.2% for BioGene and 60.7% for Quick. The least sensitive target gene and the gene most affected by RNA extraction procedures was the RNA-dependent RNA polymerase gene (Charité-Berlin protocol). No false-positive SARS-CoV-2 results were detected using RNA obtained from any of the different protocols. In conclusion, Loccus and BioGene RNA extractions were efficient for RT-qPCR assays, and although the BioGene procedure is less expensive, Loccus is the best choice because it allows the rapid handling of hundreds or thousands of samples, a desirable feature during pandemics. Although less sensitive, the Quick extraction is useful during outbreaks coupled with the Allplex amplification kit for SARS-CoV-2 diagnosis (κ = 0.925).

Resumo: Este artigo apresenta o relato de experiência do projeto de extensão Inclusão Digital para Adultos. O projeto teve como objetivo principal desenvolver a inclusão digital do educando, fazendo com que após sua inserção no mundo digital ele possa interagir com esse novo paradigma social, sentindo-se valorizado como indivíduo, realizando-se como profissional, contribuindo assim para a melhoria de seu contexto social, de acordo com a formação obtida por meio das oficinas práticas. O projeto desenvolveu, por meio de oficinas educativas e práticas, a inclusão do público específico a ser atendido, contribuindo assim para a aproximação da comunidade externa com o Instituto Federal de Santa Catarina - campus Tubarão. Ao final do projeto conclui-se que os objetivos foram alcançados. No total, foram atendidos 30 alunos.

A successful clinical translation of novel nanoparticle-based cancer therapeutics requires a thorough preclinical investigation of their interaction with immune, tumor and endothelial cells as well as components of the tumor-microenvironment. Although high-resolution microscopy images of fixed tumor tissue specimens can provide valuable information in this regard, they are only static snapshots of a momentary event. Here we describe a superior alternative fluorescence microscopy approach to assess the feasibility of investigating nanoparticle-cell interactions in the mouse lung live and over time at nanometer resolution. We applied fluorescent lung tumor cells and Barium-based fluorescently labeled nanoparticles to nude mice or to CD68-EGFP transgenic mice for visualization of the monocyte-macrophage lineage. Shortly before imaging, fluorescently labeled lectin was intravenously injected for staining of the blood vessels. The lung was filled ex vivo with 1% agarose and individual lung lobes were imaged over time using a confocal microscope with Airyscan technology. Time series demonstrate that live cell imaging of lung lobes can be performed for at least 4 h post mortem. Time-lapse movies illustrate the dynamics of the nanoparticles within the pulmonary circulation and their uptake by immune cells. Moreover, the exchange of nanoparticle material between cancer cells was observed over time. Fluorescent monocytes in lungs of CD68-EGFP transgenic mice could be visualized within blood vessels in the process of interaction with tumor cells and nanoparticles. This high resolution ex vivo live cell imaging approach provides an excellent 4D tool to obtain valuable information on the behavior of tumor and immune cells at first encounter with nanoparticles and may contribute to the understanding of how nanoparticles interact with cells supporting the development of therapeutic strategies based on nanoparticulate drug delivery systems.

Energy consumption is crucial in high-performance computing (HPC), especially to enable the next exascale generation. Hence, modern systems implement various hardware and software features for power management. Nonetheless, due to numerous different implementations, we can always push the limits of software to achieve the most efficient use of our hardware. To be energy efficient, the software relies on dynamic voltage and frequency scaling (DVFS), as well as dynamic power management (DPM). Yet, none have privileged information on the hardware architecture and application behavior, which may lead to energy-inefficient software operation. This study proposes analytical modeling for architecture and application behavior that can be used to estimate energy-optimal software configurations and provide knowledgeable hints to improve DVFS and DPM techniques for single-node HPC applications. Additionally, model parameters, such as the level of parallelism and dynamic power, provide insights into how the modeled application consumes energy, which can be helpful for energy-efficient software development and operation. This novel analytical model takes the number of active cores, the operating frequencies, and the input size as inputs to provide energy consumption estimation. We present the modeling of 13 parallel applications employed to determine energy-optimal configurations for several different input sizes. The results show that up to 70% of energy could be saved in the best scenario compared to the default Linux choice and 14% on average. We also compare the proposed model with standard machine-learning modeling concerning training overhead and accuracy. The results show that our approach generates about 10 times less energy overhead for the same level of accuracy.

In this article, we investigate tradition and innovation in the work Beauty and the Sleeping by analyzing the construction of the narrative, considering the important role of graphic design and illustrations. In this way, we approach the collaborations between two important British authors: the writer Neil Gaiman and the illustrator ChrisRiddell. As a theoretical reference we give priority to studies on illustration and graphic design of children's books - Nikolajeva and Scott. Moraes, Linden and Ramos -, dialoguing with studies on fairy tales - Betelheim, Corso and Corso, Coelho and Propp. We could observe that even if it is not an illustrated book, according to the English conception of picturebook, the narrative is told not only by the written text, but also by illustrations and graphic design. The dialogue between writer and illustrator and the freedom he had to present his point of view were fundamental for the success of the work.

Abstract Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use of nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) and fluorescent quantum dots (QDs) for single- and two-photon detection and imaging of human micrometastases and disseminated tumour cells in ex vivo biological samples of breast and pancreatic metastatic tumour mouse models expressing human epidermal growth factor receptor 2 (HER2) or carcinoembryonic antigen (CEA). By staining thin (5–10 µm) paraffin and thick (50 µm) agarose tissue sections, we detected HER2- and CEA-positive human tumour cells infiltrating the surrounding tissues or metastasizing to different organs, including the brain, testis, lung, liver, and lymph nodes. Compared to conventional fluorescently labelled antibodies the sdAb-HER2-QD and sdAb-CEA-QD nanoprobes are superior in detecting micrometastases in tissue sections by lower photobleaching and higher brightness of fluorescence signals ensuring much better discrimination of positive signals versus background. Very high two-photon absorption cross-sections of QDs and small size of the nanoprobes ensure efficient imaging of thick tissue sections unattainable with conventional fluorescent probes. The nanobody–QD probes will help to improve early cancer diagnosis and prognosis of progression by assessing metastasis.

Abstract Fabrication of polyelectrolyte microcapsules and their use as carriers of drugs, fluorescent labels, and metal nanoparticles is a promising approach to designing theranostic agents. Semiconductor quantum dots (QDs) are characterized by extremely high brightness and photostability that make them attractive fluorescent labels for visualization of intracellular penetration and delivery of such microcapsules. Here, we describe an approach to design, fabricate, and characterize physico-chemical and functional properties of polyelectrolyte microcapsules encoded with water-solubilized and stabilized with three-functional polyethylene glycol derivatives core/shell QDs. Developed microcapsules were characterized by dynamic light scattering, electrophoretic mobility, scanning electronic microscopy, and fluorescence and confocal microscopy approaches, providing exact data on their size distribution, surface charge, morphological, and optical characteristics. The fluorescence lifetimes of the QD-encoded microcapsules were also measured, and their dependence on time after preparation of the microcapsules was evaluated. The optimal content of QDs used for encoding procedure providing the optimal fluorescence properties of the encoded microcapsules was determined. Finally, the intracellular microcapsule uptake by murine macrophages was demonstrated, thus confirming the possibility of efficient use of developed system for live cell imaging and visualization of microcapsule transportation and delivery within the living cells.

Deep Neural Networks (DNNs) deployment for IoT Edge applications requires strong skills in hardware and software. In this paper, a novel design framework fully automated for Edge applications is proposed to perform such a deployment on System-on-Chips. Based on a high-level Python interface that mimics the leading Deep Learning software frameworks, it offers an easy way to implement a hardware-accelerated DNN on an FPGA. To do this, our design methodology covers the three main phases: (a) customization: where the user specifies the optimizations needed on each DNN layer, (b) generation: the framework generates on the Cloud the necessary binaries for both FPGA and software parts, and (c) deployment: the SoC on the Edge receives the resulting files serving to program the FPGA and related Python libraries for user applications. Among the study cases, an optimized DNN for the MNIST database can speed up more than 60× a software version on the ZYNQ 7020 SoC and still consume less than 0.43W. A comparison with the state-of-the-art frameworks demonstrates that our methodology offers the best trade-off between throughput, power consumption, and system cost.

Purpose: To report the case of a patient with persistent right eye (RE) hemovitreous secondary to occlusive retinal vasculitis secondary to tuberculosis. Methods: Male patient, 35 years old, Indian descent, with no history of previous systemic illness. First presented to our outpatient clinic with decreased visual acuity RE with 8 months duration. On exam, BCVA RE: