Impact of GAN-based Lesion-Focused Medical Image Super-Resolution on Radiomic Feature Robustness

Dissertation presented as the partial requirement for obtaining a Master's degree in Data Science and Advanced Analytics, specialization in Data ScienceRobust machine learning models based on radiomic features might allow for accurate diagnosis, prognosis, and medical decision-making. Unfortunately, the lack of standardized radiomic feature extraction has hampered their clinical use. Since the radiomic features tend to be affected by low voxel statistics in regions of interest, increasing the sample size would improve their robustness in clinical studies. Therefore, we propose a Generative Adversarial Network (GAN)-based lesion-focused framework for Computed Tomography (CT) image Super-Resolution (SR); for the lesion (i.e., cancer) patch-focused training, we incorporate Spatial Pyramid Pooling (SPP) into GANConstrained by the Identical, Residual, and Cycle Learning Ensemble (GAN-CIRCLE). At 2× SR, the proposed model achieved better perceptual quality with less blurring than the other considered state-of-the-art SR methods, while producing comparable results at 4× SR. We also evaluated the robustness of our model’s radiomic feature in terms of quantization on a different lung cancer CT dataset using Principal Component Analysis (PCA). Intriguingly, the most important radiomic features in our PCAbased analysis were the most robust features extracted on the GAN-super-resolved images. These achievements pave the way for the application of GAN-based image Super-Resolution techniques for studies of radiomics for robust biomarker discoveryModelos de machine learning robustos baseados em atributos radiômicos possibilitam diagnósticos e decisões médicas mais precisas. Infelizmente, por causa da falta de padronização na extração de atributos radiômicos, sua utilização em contextos clínicos tem sido restrita. Considerando que atributos radiômics tendem a ser afetados pelas estatítiscas de voxels de baixo volume nas regiões de interesse, o aumento to tamanho da amostra tem o potencial de melhorar a robustez desses atributos em estudos clínicos. Portanto, esse trabalho propões um framework baseado numa rede neural generativa (GAN) focada na região de interesse para a super-resolução de imagens de Tomografia Computadorizada (CT). Para treinar a rede de forma concentrada na lesão (i.e. cancer), incorporamos a tecnica de Spatial Pyramid Pooling no framework da GAN-CIRCLE. Nos experimentos de super-resolução 2×, o modelo proposto alcançou melhor qualidade perceptual com menos embaçamento do que outros métodos estado-da-arte considerados. A robustez dos atributos radiômics das imagens super-resolvidas geradas pelo modelo também foram analizadas em termos de quantização em um banco de imagens diferente, contendo imagens de tomografia computadorizada de câncer de pulmão, usando anaálise de componentes principaiss (PCA). Intrigantemente, os atributos radiômicos mais importantes nessa análise foram também os atributos mais robustos extraídos das imagens super-resolvidas pelo método proposto. Esses resultados abrem caminho para a aplicação de técnicas de super-resolução baseadas em redes neurais generativas aplicadas a estudos de radômica para a descoberta de biomarcadores robustos.This work was partially supported by The Mark Foundation for Cancer Research and Cancer Research UK Cambridge Centre [C9685/A25177], the Wellcome Trust Innovator Award, UK [215733/Z/19/Z] and the CRUK National Cancer Imaging Translational Accelerator (NCITA) [C42780/A27066]. Additional support was also provided by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014). This works was also finantially supported by national funds through the FCT (Fundação para a Ciência e a Tecnologia) by the projects GADgET (DSAIPA/DS/0022/2018) and the Slovenian Research Agency (research core funding no. P5-0410).This work was partially supported by The Mark Foundation for Cancer Research and Cancer Research UK Cambridge Centre [C9685/A25177], the Wellcome Trust Innovator Award, UK [215733/Z/19/Z] and the CRUK National Cancer Imaging Translational Accelerator (NCITA) [C42780/A27066]. Additional support was also provided by the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014). This works was also finantially supported by national funds through the FCT (Fundação para a Ciência e a Tecnologia) by the projects GADgET (DSAIPA/DS/0022/2018) and the Slovenian Research Agency (research core funding no. P5-0410)

Impact of GAN-based lesion-focused medical image super-resolution on the robustness of radiomic features

Abstract: Robust machine learning models based on radiomic features might allow for accurate diagnosis, prognosis, and medical decision-making. Unfortunately, the lack of standardized radiomic feature extraction has hampered their clinical use. Since the radiomic features tend to be affected by low voxel statistics in regions of interest, increasing the sample size would improve their robustness in clinical studies. Therefore, we propose a Generative Adversarial Network (GAN)-based lesion-focused framework for Computed Tomography (CT) image Super-Resolution (SR); for the lesion (i.e., cancer) patch-focused training, we incorporate Spatial Pyramid Pooling (SPP) into GAN-Constrained by the Identical, Residual, and Cycle Learning Ensemble (GAN-CIRCLE). At 2× SR, the proposed model achieved better perceptual quality with less blurring than the other considered state-of-the-art SR methods, while producing comparable results at 4× SR. We also evaluated the robustness of our model’s radiomic feature in terms of quantization on a different lung cancer CT dataset using Principal Component Analysis (PCA). Intriguingly, the most important radiomic features in our PCA-based analysis were the most robust features extracted on the GAN-super-resolved images. These achievements pave the way for the application of GAN-based image Super-Resolution techniques for studies of radiomics for robust biomarker discovery

Síntese, atividade antimicrobiana e estudo in silico de 1,2,4-oxadiazóis derivados do levulinato de etila

This study describes the synthesis, antimicrobial activity, and in silico assessment of 1,2,4-oxadiazoles from ethyl levulinate. For that, we prepared arylamidoximes and treated them with ethyl levulinate, obtaining the respective 1,2,4-oxadiazoles through a reaction sequence of O-acylation followed by cyclodehydration. Then, we assessed the antimicrobial activity of these compounds against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Candida utilis using the broth microdilution technique. We analyzed in silico studies using the online bioinformatics platforms SwissADME and PASS. We obtained arylamidoximes and 1,2,4-oxadiazoles in good yields. The 1,2,4-oxadiazoles showed moderate antimicrobial activity, inhibiting two microorganisms: the bacterium P. aeruginosa and the fungus C. utilis.  In silico studies of 1,2,4-oxadiazoles have shown promising properties, such as good oral absorption, low probability of toxicity, good body distribution, and potential to develop metabolic and enzymatic activities. The investigation of the antimicrobial activity together with the in silico studies showed that the synthesized 1,2,4-oxadiazoles are promising structures for the development of new therapeutic agents.Este trabajo describe la síntesis, la actividad antimicrobiana y el estudio in silico de 1,2,4-oxadiazoles derivados del levulinato de etilo. En este sentido, se llevó a cabo la síntesis de arilamidoxima, que reaccionó con levulinato de etilo mediante una reacción de O-acilación seguida de ciclohidratación que condujo a los compuestos de 1,2,4-oxadiazol. La evaluación de la acción antimicrobiana se realizó contra hongos y bacterias utilizando la técnica de microdilución en caldo. El estudio de sílice se realizó utilizando la plataforma de bioinformática digital SwissADME. Como resultado, se obtuvieron arilamidoxima y 1,2,4-oxadiazoles con buenos rendimientos. Los 1,2,4-oxadiazoles mostraron actividad antimicrobiana moderada, ya que mostraron inhibición contra dos microorganismos, la bacteria P. aeruginosa y el hongo C. utilis. Los estudios in silico de 1,2,4-oxadiazoles han mostrado propiedades prometedoras, como buena absorción oral, baja probabilidad de toxicidad, buena distribución corporal, así como el potencial para desarrollar actividades metabólicas y enzimáticas. En resumen, se sintetizaron tres compuestos de 1,2,4-oxadiazol con buenos rendimientos con acción antimicrobiana moderada y propiedades prometedoras de acuerdo con estudios in silico.Este estudo descreve a síntese, avaliação da atividade antimicrobiana e in silico de 1,2,4-oxadiazóis derivados do levulinato de etila. Nesse sentido, arilamidoximas foram preparadas e tratadas em seguida com o levulinato de etila, fornecendo os respectivos 1,2,4-oxadiazóis através de uma sequência reacional de O-acilação seguida de ciclodesidratação. A avaliação da ação antimicrobiana foi realizada contra Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa e Candida utilis através da técnica de microdiluição em caldo. Os estudos in sílico foram realizados através das plataformas digitais de bioinformática SwissADME e PASS online. As arilamidoximas e os 1,2,4-oxadiazóis foram obtidos em bons rendimentos. Os 1,2,4-oxadiazóis apresentaram atividade antimicrobiana moderada, uma vez que apresentaram inibição contra dois microrganismos, a bactéria P. aeruginosa e o fungo C. utilis. Os estudos in silico dos 1,2,4-oxadiazóis demonstraram propriedades promissoras, como boa absorção via oral, baixa probabilidade de apresentarem toxicidade, boa distribuição corpórea, bem como potencial de desenvolverem atividades metabólicas e enzimáticas. A investigação da ação antimicrobiana juntamente com os estudos in silico demostraram que os 1,2,4-oxadiazóis sintetizados são estruturas promissoras para o desenvolvimento de novos agentes terapêuticos

Um Avaliador Automático de Eficiência de Algoritmos para Ambientes Educacionais de Ensino de Programação

Existem características importantes que devem ser observadas no projeto de algoritmos que são fundamentais no seu uso, uma delas é a eficiência. Portanto, se torna necessário que esse aspecto seja enfatizado durante o processo de ensino e aprendizagem de algoritmos. Este trabalho propõe uma solução automática para a medição da eficiência dos algoritmos através da implementação de um componente que adota métodos matemáticos que combinam o uso de análise experimental e assintótica para avaliar a complexidade dos algoritmos. Este componente foi desenvolvido e testado para o IGED e MOCCA, ferramentas educacionais para ensino de algoritmos e estrutura de dados. Em nossos experimentos computacionais obtemos uma análise assintótica efetiva sobre sete algoritmos clássicos

ANALYSIS OF THE DAILY MOBILITY IN FLORIANÓPOLIS

O conceito de mobilidade é polissêmico e pode ser adjetivado para dar providência a diferentes explicações, dentre as quais destaca-se a mobilidade cotidiana, compreendida como aquela do trajeto de casa ao trabalho e vice-versa, cujas implicações forjam hábitos e práticas espaciais. Partindo desta acepção e com base na formação sócio-espacial, este artigo analisa como os Planos Diretores de Florianópolis constituíram a mobilidade cotidiana da cidade sob um paradigma desenvolvimentista e modernista que privilegia o automóvel individual. Por fim, verifica-se como a política de mobilidade atual de Florianópolis ainda obedece a esse paradigma, em que pese nacionalmente o estado da arte da literatura e das políticas públicas estar mais próximo dos conceitos de sustentabilidade e do direito à cidade

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The Management between Comorbidities and Pain Level with Physical Activity in Individuals with Hip Osteoarthritis with Surgical Indication: A Cross-Sectional Study

Background and Objectives: The degenerative pathology of the hip joint appears in young age groups, related to fem-oroacetabular impingement, and in advanced age, due to other inflammatory causes, with greater potential for severity in the presence of comorbidities. Objectives: To evaluate the participation of the main causes of osteoarthritis in relation to physical activities, s Body Mass Index (BMI) and television time (TV). Materials and Methods: 54 patients with surgical indication treated at an orthopedic referral university hospital were stratified into groups (Impact: I, Osteonecrosis/rheumatic: II, Infectious/traumatic: III), and the influence of comorbidities on physical activity performance, relative to BMI and TV time. Results: It was observed that the impact group was the most frequent (51.8%), with 79.6% under the age of 60 years. This group followed the general mean (p < 0.05), using the variables of comorbidity and the level of physical activity. Pain intensity, TV time, BMI showed no correlation with physical activity. Conclusion: Morphostructural changes (group I) represented the most frequent etiological group, and severe pain was common in almost the entire sample. Unlike BMI, comorbidity showed a significant relationship with the level of physical activity

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791