Identification of MicroRNA-like molecules derived from the antigenome RNA of hepatitis C virus: a bioinformatics approach

MicroRNAs (miRNAs) are small, noncoding RNA molecules that play important roles in the regula-tion of gene expression of the cell. Recent studies have described cytoplasmic RNA virus genome-derived miRNAs. Moreover, miRNAs have also been encountered in the reverse strand of the viral mRNA, revealing the presence of miRNAs in replication intermediaries. In order to get insight into the possible role of Hepatitis C Virus (HCV) antigenome in relation to miRNA coding, we computa-tionally identified potential miRNAs on the antigenome of HCV reference strain H77. By utilizing a series of bioinformatics tools, we identified a miRNA present in the antigenomeof HCV H77 strain. This miRNA maps in the 5’non-translated region (5’UTR) of the HCV genome and is found to be conserved among HCV genotypes and sub-types. In silico target prediction generated 17 cellular genes. These potential targets are involved in apoptosis as well as immune response pathways, suggesting that they could play a role in the pathogenesis caused by viral infection. The results of these studies revealed the presence of a viral miRNA in the negative-sense RNA strand used as a replication template for the HCV genome, as observed for other RNA viruses

Submandibular space infection: a potentially lethal infection.

Summary Objectives The aims of this study were to review the clinical characteristics and management of submandibular space infections and to identify the predisposing factors of life-threatening complications. Design and methods This was a retrospective study at a tertiary academic center. We retrieved and evaluated the records of all patients admitted to the University of Padua Otolaryngology Clinic at Treviso Regional Hospital with the diagnosis of submandibular space infection for the period 1998–2006. The following variables were reviewed: demographic data, pathogenesis, clinical presentation, associated systemic diseases, bacteriology, imaging studies, medical and surgical treatment, and complications. A multivariate logistic regression analysis was undertaken using a forward stepwise technique. Results Multivariate analysis identified four risk factors for complications. Anterior visceral space involvement (odds ratio (OR) 54.44; 95% confidence interval (CI) 5.80–511.22) and diabetes mellitus (OR 17.46; 95% CI 2.10–145.29) were the most important predictive factors in the model. Logistic regression analysis also confirmed other comorbidities (OR 11.66; 95% CI 1.35–100.10) and bilateral submandibular swelling (OR 10.67; 95% CI 2.73–41.75) as independent predictors for life-threatening complications. Conclusions Airway obstruction and spread of the infection to the mediastinum are the most troublesome complications of submandibular space infections. Therefore, the maintenance of a secure airway is paramount. Patients with cellulitis and small abscesses can respond to antibiotics alone. Surgical drainage should be performed in patients with larger abscesses, Ludwig's angina, anterior visceral space involvement, and in those who do not respond to antibiotic treatment. Moreover, the clinical assessment in patients with comorbidities, especially diabetes mellitus, requires a high level of suspicion for potential life-threatening complications. Early surgical drainage should always be considered in these patients, even in seemingly less critical cases

Comparative Phylogeography In The Atlantic Forest And Brazilian Savannas: Pleistocene Fluctuations And Dispersal Shape Spatial Patterns In Two Bumblebees

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Bombus morio and B. pauloensis are sympatric widespread bumblebee species that occupy two major Brazilian biomes, the Atlantic forest and the savannas of the Cerrado. Differences in dispersion capacity, which is greater in B. morio, likely influence their phylogeographic patterns. This study asks which processes best explain the patterns of genetic variation observed in B. morio and B. pauloensis, shedding light on the phenomena that shaped the range of local populations and the spatial distribution of intra-specific lineages. Results: Results suggest that Pleistocene climatic oscillations directly influenced the population structure of both species. Correlative species distribution models predict that the warmer conditions of the Last Interglacial contributed to population contraction, while demographic expansion happened during the Last Glacial Maximum. These results are consistent with physiological data suggesting that bumblebees are well adapted to colder conditions. Intra-specific mitochondrial genealogies are not congruent between the two species, which may be explained by their documented differences in dispersal ability. Conclusions: While populations of the high-dispersal B. morio are morphologically and genetically homogeneous across the species range, B. pauloensis encompasses multiple (three) mitochondrial lineages, and show clear genetic, geographic, and morphological differences. Because the lineages of B. pauloensis are currently exposed to distinct climatic conditions (and elevations), parapatric diversification may occur within this taxon. The eastern portion of the state of Sao Paulo, the most urbanized area in Brazil, represents the center of genetic diversity for B. pauloensis.16Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [10/50597-5, 13/12530-4, EF 2009/07124-1, 2010/20548-2, 2013/03961-1]Research Center on Biodiversity and Computing (BioComp)USP Provost's Office for ResearchFAPESP(BIOTA) [2013/50297-0]National Science Foundation [DOB 1343578, 1120487]NASAFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Cascading Convolutional Temporal Colour Constancy

Computational Colour Constancy (CCC) consists of estimating the colour of one or more illuminants in a scene and using them to remove unwanted chromatic distortions. Much research has focused on illuminant estimation for CCC on single images, with few attempts of leveraging the temporal information intrinsic in sequences of correlated images (e.g., the frames in a video), a task known as Temporal Colour Constancy (TCC). The state-of-the-art for TCC is TCCNet, a deep-learning architecture that uses a ConvLSTM for aggregating the encodings produced by CNN submodules for each image in a sequence. We extend this architecture with different models obtained by (i) substituting the TCCNet submodules with C4, the state-of-the-art method for CCC targeting images; (ii) adding a cascading strategy to perform an iterative improvement of the estimate of the illuminant. We tested our models on the recently released TCC benchmark and achieved results that surpass the state-of-the-art. Analyzing the impact of the number of frames involved in illuminant estimation on performance, we show that it is possible to reduce inference time by training the models on few selected frames from the sequences while retaining comparable accuracy

Differential identities of finite dimensional algebras and polynomial growth of the codimensions

Let $A$ be a finite dimensional algebra over a field $F$ of characteristic zero. If $L$ is a Lie algebra acting on $A$ by derivations, then such an action determines an action of its universal enveloping algebra $U(L)$. In this case we say that $A$ is an algebra with derivation or an $L$-algebra. Here we study the differential $L$-identities of $A$ and the corresponding differential codimensions, $c_n^L (A)$, when $L$ is a finite dimensional semisimple Lie algebra. We give a complete characterization of the corresponding ideal of differential identities in case the sequence $c_n^L (A)$, $n=1,2,\dots$, is polynomially bounded. Along the way we determine up to PI-equivalence the only finite dimensional $L$-algebra of almost polynomial growth

Correlação entre o diagnóstico clínico e análise do PCR de amostras do soro, aquoso e vítreo em pacientes com doença inflamatória ocular

PURPOSE: To study the applicability (sensitivity, specificity) of polymerase chain reaction (PCR) tests in the detection of cytomegalovirus (CMV), herpes virus (HSV) and varicella zoster (VZV), Epstein-Barr virus (EBV), Mycobacterium sp and Toxoplasma gondii in the diagnosis of patients with or without AIDS, with presumably infectious uveitis, using serum, aqueous humor and vitreous humor samples. METHODS: Twenty individuals with uveitis of presumed infectious origin were evaluated. Sixteen of them had AIDS, four were immunocompetent individuals. We also evaluated 4 normal controls who underwent vitrectomy surgery. Clinical evaluation of the patients was performed together by three clinicians. PCR evaluations of the serum, aqueous, and vitreous humor were performed in a masked fashion by the laboratory staff. RESULTS: Twelve patients had a clinical diagnosis of CMV retinitis. Of these 6 (50%) had a positive PCR for CMV in the vitreous, three (25%) had a positive PCR for CMV in the serum, and none were positive in the aqueous. Five patients had a clinical diagnosis of acute retinal necrosis (ARN). Three (60%) of these had positive PCR for HSV/VZV in the vitreous. One of these patients had a positive PCR reaction for both EBV and HSV/VZV in the vitreous samples. One patient with cutaneous herpes zoster had a positive PCR reaction for HSV/VZV in the serum. Four patients had a presumed diagnosis of ocular toxoplasmosis, one patient (25%) had a positive PCR for Toxoplasma gondii in the serum, 3 (75%) had positive results in the aqueous, and 2 (50%) had positive results in the vitreous. One patient with presumed ocular tuberculosis had a positive PCR reaction both in the serum and in the vitreous samples. Finally, none of the four control individuals revealed any positive PCR reaction. CONCLUSION: PCR is an auxiliary diagnostic procedure that should be evaluated together with ophthalmological aspects of the patient.OBJETIVOS: Avaliar a aplicabilidade (especificidade, sensibilidade) do teste da reação da cadeia de polimerase (PCR) na detecção de citomegalovírus (CMV), herpes vírus e varicela zoster (HSV, VZV), Epstein-Barr vírus (EBV), Mycobacterium sp e Toxoplasma gondii no diagnóstico de pacientes com ou sem AIDS, com uveíte infecciosa presumível, utilizando amostras de humor aquoso, humor vítreo e soro. MÉTODOS: Vinte pacientes com uveíte infecciosa presumível foram estudados. Dezesseis destes apresentavam AIDS e quatro eram imunocompetentes. Foram utilizados quatro pacientes como grupo controle que se submeteram a vitrectomia. A avaliação clínica foi feita conjuntamente com três oftalmologistas. O exame do PCR do soro, aquoso e vítreo foi feito sem o conhecimento da hipótese diagnóstica pela equipe do laboratório. RESULTADOS: Doze pacientes tinham o diagnóstico clínico de retinite por CMV. Deste subgrupo 6 (50%) eram PCR positivo para CMV no vítreo, 3 (25%) eram PCR positivos para CMV no soro e nenhum destes foi positivo no aquoso. Cinco pacientes tinham o diagnóstico clínico de necrose aguda de retina (ARN). Três (60%) destes eram PCR positivos para HSV/VZV no vítreo. Um destes pacientes era PCR positivo tanto para EBV e HSV/VZV na amostra do vítreo. Um destes pacientes com herpes zoster cutâneo era PCR positivo para HSV/VZV no soro. Quatro pacientes tinham o diagnóstico de toxoplasmose ocular presumida, um paciente (25%) era PCR positivo para Toxoplasma gondii no soro, 3 (75%) eram positivos no aquoso e 2 (50%) eram positivo no vítreo. Um paciente com tuberculose ocular presumível era PCR positivo tanto no soro quanto no vítreo. Nenhum dos pacientes do grupo controle era PCR positivo em qualquer amostra. CONCLUSÃO: O exame do PCR é procedimento diagnóstico auxiliar que deve ser utilizado conjuntamente com os aspectos clínicos.Universidade Federal de São Paulo (UNIFESP) Setor de Uveite e AIDSUNIFESP Departamento de OftalmologiaUniversidade de São Paulo Departamento de ImunologiaUNIFESP, Setor de Uveite e AIDSUNIFESP, Depto. de OftalmologiaSciEL

A Theoretical Framework for AI Models Explainability

EXplainable Artificial Intelligence (XAI) is a vibrant research topic in the artificial intelligence community, with growing interest across methods and domains. Much has been written about the subject, yet XAI still lacks shared terminology and a framework capable of providing structural soundness to explanations. In our work, we address these issues by proposing a novel definition of explanation that is a synthesis of what can be found in the literature. We recognize that explanations are not atomic but the combination of evidence stemming from the model and its input-output mapping, and the human interpretation of this evidence. Furthermore, we fit explanations into the properties of faithfulness (i.e., the explanation being a true description of the model's inner workings and decision-making process) and plausibility (i.e., how much the explanation looks convincing to the user). Using our proposed theoretical framework simplifies how these properties are operationalized and it provides new insight into common explanation methods that we analyze as case studies

Alternativa para reducir el subsidio al combustible en Ecuador a partir del 2017

TributaciónMediante el presente trabajo se ha revisado objetivamente las cifras de consumo de combustibles en el Ecuador, revisando los procesos de explotación, fabricación y refinación y determinando las instituciones que en la actualidad están jurídicamente facultadas para reportar cifras oficiales. Los organismos competentes para el caso nacional como Petroecuador E.P. son los facultados jurídicamente mediante Resolución Ejecutiva de octubre de 2015 para regular los precios de los combustibles, a pesar que dicha facultad está limitada a ciertos tipos de comercialización. Por lo que la subvención que el estado asume aún depende de los procesos productivos mediante los cuales se determina la cantidad de barriles de derivados que se necesitan importar para satisfacer la demanda nacional. Mediante la investigación se revisó los valores con respecto al precio de mercado de la gasolina y diesel comparándola con la de países como Colombia y Perú. De esta manera se estableció un punto de referencia para evaluar la eliminación del subsidio.Through this work it has objectively reviewed the fuel consumption figures in Ecuador, reviewing operating processes, production and refining and identifying the institutions that currently are legally entitled to official figures report. The competent bodies for the national case as Petroecuador E.P. They are empowered legally enforceable decision by October 2015 to regulate fuel prices, although this power is limited to certain types of marketing. So the subsidy that the state takes still depends on the productive processes by which the number of barrels of derivatives that need to import to meet domestic demand is determined. By investigating the values are reviewed with respect to the market price of super gasoline compared with that of countries like Colombia and Peru. Thus a benchmark was established to evaluate the elimination of the subsidy

Comparação da evolução clínica de pacientes com fibrose cística, antes e após a triagem neonatal no Estado do Rio Grande do Sul

OBJETIVO: O estudo traçou o perfil dos pacientes diagnosticados com Fibrose Cística (FC) após a implantação da triagem neonatal (TN) para a doença, no estado do Rio Grande do Sul (RS). Além disso, realizou a comparação de três anos de seguimento desses pacientes com os três anos após o diagnóstico dos pacientes anteriores à TN. MÉTODO: Experimento não randomizado observacional com controles históricos, realizado no período de junho de 2012 a junho de 2018, com 153 pacientes com diagnóstico de FC. As variáveis analisadas obtidas através da revisão dos prontuários foram: características demográficas, de diagnóstico e clínicas, identificação bacteriana em secreção respiratória, tratamento medicamentoso, internações e exacerbações. RESULTADOS: Os pacientes submetidos à TN tiveram menor idade ao diagnóstico e na primeira consulta em centro de referência, menor presença de sintomas digestivos e respiratórios antes do diagnóstico, maior percentual de pacientes com mutação F508del em ambos os alelos, cultura bacteriana de secreções respiratórias positiva identificada mais precocemente e menor número de internações no período de acompanhamento. Já os pacientes controles tiveram uma média de cloro no suor mais baixa ao diagnóstico, mais baixo peso no primeiro e segundo ano após o diagnóstico, maior déficit de estatura ao diagnóstico, maior frequência de colonização crônica por Pseudomonas aeruginosa (PSA), maior prescrição de antibiótico inalatório, broncodilatador e dornase-alfa no terceiro ano de seguimento. CONCLUSÃO: Esse trabalho permitiu caracterizar a população com diagnóstico de FC, após a TN, que estão em acompanhamento nos centros de referência 10 para a doença, no RS. Com o tempo de seguimento desse estudo, foi possível perceber importância da TN no adequado desenvolvimento pôndero-estatural desses pacientes, na diminuição do número de internações, na erradicação da PSA e na necessidade de menores quantidades de uso de medicação, nos 3 primeiros anos após o diagnóstico de FC.OBJECTIVE: The study outlined the profile of patients diagnosed with Cystic Fibrosis (CF) after the implementation of newborn screening (NS) for the disease in the state of Rio Grande do Sul (RS). In addition, we compared three years of follow-up of these patients with three years after the diagnosis of patients prior to NS. METHOD: Non-randomized observational experiment with historical controls, conducted from June 2012 to June 2018, with 153 patients diagnosed with CF. The variables analyzed obtained through the review of medical records were: demographic, diagnostic and clinical characteristics, bacterial identification in respiratory secretion, drug treatment, hospitalizations and exacerbations. RESULTS: Patients submitted to NS were older at diagnosis and at the first visit at a reference center, lower presence of digestive and respiratory symptoms before diagnosis, higher percentage of patients with F508del mutation in both allelos, lower age in the first bacterial culture of positive in respiratory secretions and lower number of hospitalizations in the follow-up period. On the other hand, the control patients had a lower mean chlorine in sweat at diagnosis, lower weight in the first and second year after diagnosis, greater height deficit at diagnosis, greater chronic colonization by Pseudomonas aeruginosa (PSA), higher prescription of inalatory antibiotic, bronchodilator and dornase-alpha in the third year of follow-up. CONCLUSION: This study allowed characterizing the population diagnosed with CF, after NS, who are under follow-up in referral centers for the disease, in RS. With the follow-up time of this study, it was possible to perceive the importance of NS in the adequate weight-height development of these patients, in the decrease in the number of hospitalizations, in the eradication of PSA and in the need for smaller amounts of medication use, in the first 3 years after the diagnosis of CF

MiR675-5p acts on HIF-1α to sustain hypoxic responses: A new therapeutic strategy for glioma

Hypoxia is a common feature in solid tumours. In glioma, it is considered the major driving force for tumour angiogenesis and correlates with enhanced resistance to conventional therapies, increased invasiveness and a poor prognosis for patients. Here we describe, for the first time, that miR675-5p, embedded in hypoxia-induced long non-coding RNA H19, plays a mandatory role in establishing a hypoxic response and in promoting hypoxia-mediated angiogenesis. We demonstrated, in vitro and in vivo, that miR675-5p over expression in normoxia is sufficient to induce a hypoxic moreover, miR675-5p depletion in low oxygen conditions, drastically abolishes hypoxic responses including angiogenesis. In addition, our data indicate an interaction of miR675-5p, HIF-1α mRNA and the RNA Binding Protein HuR in hypoxia-induced responses. We suggest the modulation of miR675-5p as a new therapeutic option to promote or abolish hypoxia induced angiogenesis