RESUMO
AIMS: The aim of this study was to investigate the association between VKORC1 and CYP2C9 genes polymorphisms and the maintenance dose of warfarin in Peruvian patients. METHODS: An observational study was conducted on outpatients from the Hospital Grau ESSALUD in Lima, Peru. The participants were selected using nonprobabilistic convenience sampling. Inclusion criteria required patients to have been on anticoagulation therapy for >3 months, maintain stable doses of warfarin (consistent dose for at least 3 outpatient visits), and maintain an international normalized ratio within the therapeutic range of 2.5-3.5. DNA samples were obtained from peripheral blood for gene analysis. RESULTS: Seventy patients (mean age of 69.6 ± 13.4 years, 45.7% female) were included in the study. The average weekly warfarin dose was 31.6 ± 15.2 mg. The genotypic frequencies of VKORC1 were as follows: 7.1% (95% confidence interval, 2.4-15.9) for AA; 44.3% (32.4-56.7) for GA; and 48.6% (36.4-60.8) for GG. No deviation from the Hardy-Weinberg equilibrium was observed in the variants studied (P = .56). The mean weekly warfarin doses for AA, GA and GG genotypes were 16.5 ± 2.9, 26.5 ± 9.5 and 37.9 ± 17.1 mg, respectively (P < .001). The genotypic frequencies of CYP2C9 were as follows: 82.8% (72.0-90.8) for CC (*1/*1); 4.3% (1.0-12.0) for CT (*1/*2); and 12.9% (6.1-23.0) for TT (*2/*2). We did not find a significant association between the CYP2C9 gene polymorphism and the dose of warfarin. CONCLUSIONS: The AA genotype of the VKORC1 gene was associated with a lower maintenance dose of warfarin in Peruvian patients.
Assuntos
Anticoagulantes , Varfarina , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Citocromo P-450 CYP2C9/genética , Peru , Anticoagulantes/efeitos adversos , Vitamina K Epóxido Redutases/genética , Polimorfismo Genético , Genótipo , Coeficiente Internacional NormatizadoRESUMO
OBJECTIVE: The Fluid And White matter Suppression (FLAWS) MRI sequence provides multiple T1-weighted contrasts of the brain in a single acquisition. However, the FLAWS acquisition time is approximately 8 min with a standard GRAPPA 3 acceleration factor at 3 T. This study aims at reducing the FLAWS acquisition time by providing a new sequence optimization based on a Cartesian phyllotaxis k-space undersampling and a compressed sensing (CS) reconstruction. This study also aims at showing that T1 mapping can be performed with FLAWS at 3 T. MATERIALS AND METHODS: The CS FLAWS parameters were determined using a method based on a profit function maximization under constraints. The FLAWS optimization and T1 mapping were assessed with in-silico, in-vitro and in-vivo (10 healthy volunteers) experiments conducted at 3 T. RESULTS: In-silico, in-vitro and in-vivo experiments showed that the proposed CS FLAWS optimization allows the acquisition time of a 1 mm-isotropic full-brain scan to be reduced from [Formula: see text] to [Formula: see text] without decreasing image quality. In addition, these experiments demonstrate that T1 mapping can be performed with FLAWS at 3 T. DISCUSSION: The results obtained in this study suggest that the recent advances in FLAWS imaging allow to perform multiple T1-weighted contrast imaging and T1 mapping in a single [Formula: see text] sequence acquisition.
Assuntos
Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Neuroimagem , Cabeça , Processamento de Imagem Assistida por ComputadorRESUMO
Radiotherapy is one of the main treatments for localized head and neck (HN) cancer. To design a personalized treatment with reduced radio-induced toxicity, accurate delineation of organs at risk (OAR) is a crucial step. Manual delineation is time- and labor-consuming, as well as observer-dependent. Deep learning (DL) based segmentation has proven to overcome some of these limitations, but requires large databases of homogeneously contoured image sets for robust training. However, these are not easily obtained from the standard clinical protocols as the OARs delineated may vary depending on the patient's tumor site and specific treatment plan. This results in incomplete or partially labeled data. This paper presents a solution to train a robust DL-based automated segmentation tool exploiting a clinical partially labeled dataset. We propose a two-step workflow for OAR segmentation: first, we developed longitudinal OAR-specific 3D segmentation models for pseudo-contour generation, completing the missing contours for some patients; with all OAR available, we trained a multi-class 3D convolutional neural network (nnU-Net) for final OAR segmentation. Results obtained in 44 independent datasets showed superior performance of the proposed methodology for the segmentation of fifteen OARs, with an average Dice score coefficient and surface Dice similarity coefficient of 80.59% and 88.74%. We demonstrated that the model can be straightforwardly integrated into the clinical workflow for standard and adaptive radiotherapy.
RESUMO
PURPOSE: To demonstrate that fluid and white matter suppression (FLAWS) imaging can be used for high-resolution T1 mapping with low transmitted bias field ( B1+ ) sensitivity at 7T. METHODS: The FLAWS sequence was optimized for 0.8-mm isotropic resolution imaging. The theoretical accuracy and precision of the FLAWS T1 mapping was compared with the one of the magnetization-prepared two rapid gradient echoes (MP2RAGE) sequence optimized for low B1+ sensitivity. FLAWS images were acquired at 7T on six healthy volunteers (21 to 48 years old; two women). MP2RAGE and saturation-prepared with two rapid gradient echoes (SA2RAGE) datasets were also acquired to obtain T1 mapping references and B1+ maps. The contrast-to-noise ratio (CNR) between brain tissues was measured in the FLAWS-hco and MP2RAGE-uni images. The Pearson correlation was measured between the MP2RAGE and FLAWS T1 maps. The effect of B1+ on FLAWS T1 mapping was assessed using the Pearson correlation. RESULTS: The FLAWS-hco images were characterized by a higher brain tissue CNR ( CNRWM/GM=5.5 , CNRWM/CSF=14.7 , CNRGM/CSF=10.3 ) than the MP2RAGE-uni images ( CNRWM/GM=4.9 , CNRWM/CSF=6.6 , CNRGM/CSF=3.7 ). The theoretical accuracy and precision of the FLAWS T1 mapping ( acc=91.9%;prec=90.2% ) were in agreement with those provided by the MP2RAGE T1 mapping ( acc=90.0%;prec=86.8% ). A good agreement was found between in vivo T1 values measured with the MP2RAGE and FLAWS sequences (r = 0.91). A weak correlation was found between the FLAWS T1 map and the B1+ map within cortical gray matter and white matter segmentations ( rWM=-0.026 ; rGM=0.081 ). CONCLUSION: The results from this study suggest that FLAWS is a good candidate for high-resolution T1 -weighted imaging and T1 mapping at the field strength of 7T.
Assuntos
Substância Branca , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Cell-free DNA (cfDNA) is used in clinical research to identify biomarkers for diagnosis of and follow-up on cancer. Here, we propose a fast and innovative approach using traditional housekeeping genes as cfDNA targets in a copy number analysis. We focus on the application of highly sensitive technology such as digital PCR (dPCR) to differentiate breast cancer (BC) patients and controls by quantifying regions of PUM1 and RPPH1 (RNase P) in plasma samples. METHODS: We conducted a case-control study with 82 BC patients and 82 healthy women. cfDNA was isolated from plasma using magnetic beads and quantified by spectrophotometry to estimate total cfDNA. Then, both PUM1 and RPPH1 genes were specifically quantified by dPCR. Data analysis was calibrated using a reference genomic DNA in different concentrations. RESULTS: We found RNase P and PUM1 values were correlated in the patient group (intraclass correlation coefficient [ICC] = 0.842), but they did not have any correlation in healthy women (ICC = 0.519). In dPCR quantification, PUM1 showed the capacity to distinguish early-stage patients and controls with good specificity (98.67%) and sensitivity (100%). Conversely, RNase P had lower cfDNA levels in triple-negative BC patients than luminal subtypes (p < 0.025 for both), confirming their utility for patient classification. CONCLUSION: We propose the PUM1 gene as a cfDNA marker for early diagnosis of BC and RNase P as a cfDNA marker related to hormonal status and subtype classification in BC. Further studies with larger sample sizes are warranted.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Proteínas de Ligação a RNA/genética , Ribonuclease P/genética , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Estrogênios/metabolismo , Feminino , Fluorescência , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas de Ligação a RNA/metabolismo , Curva ROC , Ribonuclease P/metabolismo , Sensibilidade e Especificidade , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
Studies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most widely spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here, we explore the genetic structure of 176 individuals from these three domains, genotyped with the Affymetrix Human Origins array. We infer multiple sources of ancestry within the Native American ancestry component; one with clear predominance on the Coast and in the Andes, and at least two distinct substrates in neighboring Amazonia, including a previously undetected ancestry characteristic of northern Ecuador and Colombia. Amazonian populations are also involved in recent gene-flow with each other and across ecogeographic domains, which does not accord with the traditional view of small, isolated groups. Long-distance genetic connections between speakers of the same language family suggest that indigenous languages here were spread not by cultural contact alone. Finally, Native American populations admixed with post-Columbian European and African sources at different times, with few cases of prolonged isolation. With our results we emphasize the importance of including understudied regions of the continent in high-resolution genetic studies, and we illustrate the potential of SNP chip arrays for informative regional-scale analysis.
Assuntos
Genoma Humano , Migração Humana/história , História Antiga , Humanos , Idioma , Peru , FilogeografiaRESUMO
Background: Deformable image registration (DIR) is increasingly used in the field of radiation therapy (RT) to account for anatomical deformations. The aims of this paper are to describe the main applications of DIR in RT and discuss current DIR evaluation methods. Methods: Articles on DIR published from January 2000 to October 2018 were extracted from PubMed and Science Direct. Our search was restricted to articles that report data obtained from humans, were written in English, and address DIR methods for RT. A total of 207 articles were selected from among 2506 identified in the search process. Results: At planning, DIR is used for organ delineation using atlas-based segmentation, deformation-based planning target volume definition, functional planning and magnetic resonance imaging-based dose calculation. In image-guided RT, DIR is used for contour propagation and dose calculation on per-treatment imaging. DIR is also used to determine the accumulated dose from fraction to fraction in external beam RT and brachytherapy, both for dose reporting and adaptive RT. In the case of re-irradiation, DIR can be used to estimate the cumulated dose of the two irradiations. Finally, DIR can be used to predict toxicity in voxel-wise population analysis. However, the evaluation of DIR remains an open issue, especially when dealing with complex cases such as the disappearance of matter. To quantify DIR uncertainties, most evaluation methods are limited to geometry-based metrics. Software companies have now integrated DIR tools into treatment planning systems for clinical use, such as contour propagation and fraction dose accumulation. Conclusions: DIR is increasingly important in RT applications, from planning to toxicity prediction. DIR is routinely used to reduce the workload of contour propagation. However, its use for complex dosimetric applications must be carefully evaluated by combining quantitative and qualitative analyses.
Assuntos
Neoplasias/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Braquiterapia , Humanos , Imageamento por Ressonância Magnética , Ilustração Médica , Imagem Multimodal/métodos , Neoplasias/radioterapia , Dosagem Radioterapêutica , Reirradiação , IncertezaRESUMO
This study focuses on the descendants of the royal Inka family. The Inkas ruled Tawantinsuyu, the largest pre-Columbian empire in South America, which extended from southern Colombia to central Chile. The origin of the royal Inkas is currently unknown. While the mummies of the Inka rulers could have been informative, most were destroyed by Spaniards and the few remaining disappeared without a trace. Moreover, no genetic studies have been conducted on present-day descendants of the Inka rulers. In the present study, we analysed uniparental DNA markers in 18 individuals predominantly from the districts of San Sebastian and San Jerónimo in Cusco (Peru), who belong to 12 families of putative patrilineal descent of Inka rulers, according to documented registries. We used single-nucleotide polymorphisms and short tandem repeat (STR) markers of the Y chromosome (Y-STRs), as well as mitochondrial DNA D-loop sequences, to investigate the paternal and maternal descent of the 18 alleged Inka descendants. Two Q-M3* Y-STR clusters descending from different male founders were identified. The first cluster, named AWKI-1, was associated with five families (eight individuals). By contrast, the second cluster, named AWKI-2, was represented by a single individual; AWKI-2 was part of the Q-Z19483 sub-lineage that was likely associated with a recent male expansion in the Andes, which probably occurred during the Late Intermediate Period (1000-1450 AD), overlapping the Inka period. Concerning the maternal descent, different mtDNA lineages associated with each family were identified, suggesting a high maternal gene flow among Andean populations, probably due to changes in the last 1000 years.
Assuntos
Cromossomos Humanos Y/genética , Indígenas Sul-Americanos/genética , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Feminino , Humanos , Masculino , PeruRESUMO
OBJECTIVE: To assess the performance of computed tomography (CT) texture analysis to predict the presence of adherent perinephric fat (APF). MATERIALS AND METHODS: Seventy patients with small renal tumors treated with robot-assisted partial nephrectomy were included. Patients were divided into two groups according to the presence of APF. We extracted 15 image features from unenhanced CT and contrast-enhanced CT corresponding to first-order and second-order Haralick textural features. Predictors of APF were evaluated by univariable and multivariable analysis. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) to predict APF was calculated for the independent predictors. RESULTS: APF was observed in 26 patients (37%). We identified entropy (p = 0.01), sum entropy (p = 0.02) and difference entropy (p = 0.05) as significant independent predictors of APF. In the portal phase, we identified correlation (p = 0.03), inverse difference moment (p = 0.01), sum entropy (p = 0.02), entropy (p = 0.01), difference variance (p = 0.04) and difference entropy (p = 0.02) as significant independent predictors of APF. Combining these parameters yielded to an ROC-AUC of 0.82 (95% CI 0.65-0.86). CONCLUSION: Results from this preliminary study suggest that CT texture analysis might be a promising quantitative imaging tool that helps urologist to identify APF.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Rim/diagnóstico por imagem , Nefrectomia/métodos , Tomografia Computadorizada por Raios X , Idoso , Análise de Variância , Índice de Massa Corporal , Feminino , Humanos , Rim/patologia , Rim/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos , Carga TumoralRESUMO
MP2RAGE is a T1 weighted MRI sequence that estimates a composite image providing much reduction of the receiver bias, has a high intensity dynamic range, and provides an estimate of T1 mapping. It is, therefore, an appealing option for brain morphometry studies. However, previous studies have reported a difference in cortical thickness computed from MP2RAGE compared with widely used Multi-Echo MPRAGE. In this article, we demonstrated that using standard segmentation and partial volume estimation techniques on MP2RAGE introduces systematic errors, and we proposed a new model to estimate partial volume of the cortical gray matter. We also included in their model a local estimate of tissue intensity to take into account the natural variation of tissue intensity across the brain. A theoretical framework is provided and validated using synthetic and physical phantoms. A repeatability experiment comparing MPRAGE and MP2RAGE confirmed that MP2RAGE using our model could be considered for structural imaging in brain morphology study, with similar cortical thickness estimate than that computed with MPRAGE. Hum Brain Mapp 38:5115-5127, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Simulação por Computador , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/diagnóstico por imagem , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética/instrumentação , Modelos Neurológicos , Método de Monte Carlo , Tamanho do Órgão , Imagens de Fantasmas , Reprodutibilidade dos Testes , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagemRESUMO
PURPOSE: To explore the association between magnetic resonance imaging (MRI), including Haralick textural features, and biochemical recurrence following prostate cancer radiotherapy. MATERIALS AND METHODS: In all, 74 patients with peripheral zone localized prostate adenocarcinoma underwent pretreatment 3.0T MRI before external beam radiotherapy. Median follow-up of 47 months revealed 11 patients with biochemical recurrence. Prostate tumors were segmented on T2 -weighted sequences (T2 -w) and contours were propagated onto the coregistered apparent diffusion coefficient (ADC) images. We extracted 140 image features from normalized T2 -w and ADC images corresponding to first-order (n = 6), gradient-based (n = 4), and second-order Haralick textural features (n = 130). Four geometrical features (tumor diameter, perimeter, area, and volume) were also computed. Correlations between Gleason score and MRI features were assessed. Cox regression analysis and random survival forests (RSF) were performed to assess the association between MRI features and biochemical recurrence. RESULTS: Three T2 -w and one ADC Haralick textural features were significantly correlated with Gleason score (P < 0.05). Twenty-eight T2 -w Haralick features and all four geometrical features were significantly associated with biochemical recurrence (P < 0.05). The most relevant features were Haralick features T2 -w contrast, T2 -w difference variance, ADC median, along with tumor volume and tumor area (C-index from 0.76 to 0.82; P < 0.05). By combining these most powerful features in an RSF model, the obtained C-index was 0.90. CONCLUSION: T2 -w Haralick features appear to be strongly associated with biochemical recurrence following prostate cancer radiotherapy. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:103-117.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Seguimentos , Humanos , Aumento da Imagem/métodos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/prevenção & controle , Variações Dependentes do Observador , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
This study focuses on the genetic history of the Quechua-Lamistas, inhabitants of the Lamas Province in the San Martin Department, Peru, who speak their own distinct variety of the Quechua family of languages. It has been suggested that different pre-Columbian ethnic groups from the Peruvian Amazonia, like the Motilones or "shaven heads", assimilated the Quechua language and then formed the current native population of Lamas. However, many Quechua-Lamistas claim to be direct descendants of the Chankas, a famous pre-Columbian indigenous group that escaped from Inca rule in the Andes. To investigate the Quechua-Lamistas and Chankas' ancestries, we compared uniparental genetic profiles (17 STRs of Q-M3 Y-chromosome and mtDNA complete control region haplotypes) among autochthonous Amazonian and Andean populations from Peru, Bolivia and Ecuador. The phylogeographic and population genetic analyses indicate a fairly heterogeneous ancestry for the Quechua-Lamistas, while they are closely related to their neighbours who speak Amazonian languages, presenting no direct relationships with populations from the region where the ancient Chankas lived. On the other hand, the genetic profiles of self-identified Chanka descendants living in Andahuaylas (located in the Apurimac Department, Peru, in the Central Andes) were closely related to those living in Huancavelica and the assumed Chanka Confederation area before the Inca expansion.
Assuntos
Cromossomos Humanos Y/genética , DNA Mitocondrial/genética , Genética Populacional , Indígenas Sul-Americanos/genética , Bolívia , Equador , Haplótipos , Humanos , Masculino , Peru , Análise EspacialRESUMO
Many single-nucleotide polymorphisms (SNPs) in the non-recombining region of the human Y chromosome have been described in the last decade. High-coverage sequencing has helped to characterize new SNPs, which has in turn increased the level of detail in paternal phylogenies. However, these paternal lineages still provide insufficient information on population history and demography, especially for Native Americans. The present study aimed to identify informative paternal sublineages derived from the main founder lineage of the Americas-haplogroup Q-L54-in a sample of 1841 native South Americans. For this purpose, we used a Y-chromosomal genotyping multiplex platform and conventional genotyping methods to validate 34 new SNPs that were identified in the present study by sequencing, together with many Y-SNPs previously described in the literature. We updated the haplogroup Q phylogeny and identified two new Q-M3 and three new Q-L54*(xM3) sublineages defined by five informative SNPs, designated SA04, SA05, SA02, SA03 and SA29. Within the Q-M3, sublineage Q-SA04 was mostly found in individuals from ethnic groups belonging to the Tukanoan linguistic family in the northwest Amazon, whereas sublineage Q-SA05 was found in Peruvian and Bolivian Amazon ethnic groups. Within Q-L54*, the derived sublineages Q-SA03 and Q-SA02 were exclusively found among Coyaima individuals (Cariban linguistic family) from Colombia, while Q-SA29 was found only in Maxacali individuals (Jean linguistic family) from southeast Brazil. Furthermore, we validated the usefulness of several published SNPs among indigenous South Americans. This new Y chromosome haplogroup Q phylogeny offers an informative paternal genealogy to investigate the pre-Columbian history of South America.Journal of Human Genetics advance online publication, 31 March 2016; doi:10.1038/jhg.2016.26.
Assuntos
Cromossomos Humanos Y , Genética Populacional , Indígenas Sul-Americanos/genética , Alelos , Evolução Molecular , Genótipo , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Repetições de Microssatélites , Mutação , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms usually caused by somatic mutations in the genes KIT (c-kit) or PDGFRA. Mutation characterization has become an important exam for GIST patients because it is useful in predicting the response to the inhibitors of receptor tyrosine kinase (RTK). OBJECTIVES: The aim of this study was to determine the frequency of KIT and PDGFRA mutations in 25 GIST samples collected over two years at two national reference hospitals in Peru. There were 21 samples collected from the Instituto Nacional de Enfermedades Neoplásicas (INEN, national cancer center) and 4 samples collected from Hospital A. Loayza. METHODS AND MATERIALS: In this retrospective study, we performed polymerase chain reaction (PCR) amplification and deoxyribonucleic acid (DNA) sequencing of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes in 20 FFPE (formalin-fixed, paraffin-embedded) and 5 frozen GIST samples. RESULTS: We report 21 mutations, including deletions, duplications, and missense, no mutations in 2 samples, and 2 samples with no useful DNA for further analysis. Eighty-six percent of these mutations were located in exon 11 of KIT, and 14 % were located in exon 18 of PDGFRA. CONCLUSIONS: Our study identified mutations in 21 out of 25 GIST samples from 2 referential national hospitals in Peru, and the mutation proportion follows a global tendency observed from previous studies (i.e., the majority of samples presented KIT mutations followed by a minor percentage of PDGFRA mutations). This study presents the first mutation data of the KIT and PDGFRA genes from Peruvian individuals with GIST.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peru , Estudos RetrospectivosRESUMO
The photocalytic degradation of dicloxacillin (DXC) using TiO2 was studied in synthetic and natural waters. The degradation route and the effect of different experimental variables such as pH, applied power, and the initial concentrations of DXC and the catalyst were investigated. The best performances were achieved at a natural pH 5.8 and using 2.0 g L(-1) of TiO2 with 150 W of applied power. The photodegradation process followed Langmuir-Hinshelwood kinetics. The water matrix effect was evaluated in terms of degradation efficiency in the presence of organic compounds (oxalic acid, glucose), Fe(2+) ion and natural water. An increase in degradation was observed when ferrous ion was part of the solution, but the process was inhibited with all evaluated organic compounds. Similarly, inhibition was observed when natural water was used instead of distilled water. The extent of degradation of the process was evaluated following the evolution of chemical oxygen demand (COD), antimicrobial activity (AA), total organic carbon (TOC) and biochemical oxygen demand (BOD5). Total removal of DXC was achieved after 120 min of treatment and 95% mineralization was observed after 480 min of treatment. Additionally, the total removal of antimicrobial activity and a high level of biodegradability were observed after the photocalytical system had been operating for 240 min.
Assuntos
Antibacterianos/análise , Dicloxacilina/análise , Fotólise , Titânio/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Antibacterianos/química , Antibacterianos/efeitos da radiação , Análise da Demanda Biológica de Oxigênio , Catálise , Dicloxacilina/química , Dicloxacilina/efeitos da radiação , Água Doce/química , Concentração de Íons de Hidrogênio , Cinética , Águas Residuárias/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/efeitos da radiação , Purificação da Água/instrumentaçãoRESUMO
OBJECTIVE: To analyze late urinary toxicity after prostate cancer radiotherapy (RT): symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms. METHODS: Nine hundred and sixty-five patients underwent RT in seventeen French centers for localized prostate cancer. Median total dose was 70 Gy (range, 65-80 Gy), using different fractionations (2 or 2.5 Gy/day) and techniques. Late urinary toxicity and the corresponding symptoms (urinary frequency, incontinence, dysuria/decreased stream, and hematuria) were prospectively assessed in half of the patients using the LENT-SOMA classification. Univariate and multivariate Cox regression models addressed patient or treatment-related predictors of late urinary toxicity (≥grade 2). Nomograms were built up, and their performance was assessed. RESULTS: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, dysuria, and urinary incontinence rates were 15, 10, 5, 3 and 1 %, respectively. The 5-year (≥grade 3) urinary toxicity rate was 3 %. The following parameters significantly increased the 5-year risk of global urinary toxicity (≥grade 2): anticoagulant treatment (RR = 2.35), total dose (RR = 1.09), and age (RR = 1.06). Urinary frequency was increased by the total dose (RR = 1.07) and diabetes (RR = 4). Hematuria was increased by anticoagulant treatment (RR = 2.9). Dysuria was increased by the total dose (RR = 1.1). Corresponding nomograms and their calibration plots were generated. Nomogram performance should be validated with external data. CONCLUSIONS: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.
Assuntos
Nomogramas , Neoplasias da Próstata/radioterapia , Lesões por Radiação/diagnóstico , Sistema Urinário/efeitos da radiação , Micção , Doenças Urológicas/etiologia , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta à Radiação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias da Próstata/urina , Lesões por Radiação/fisiopatologia , Urinálise , Doenças Urológicas/fisiopatologiaRESUMO
Purpose of this study is to explore the extraction of potentially valuable cosmetic ingredients from rice crop residues, aiming to mitigate their environmental impact. Methods: We employed AOAC methods to analyze the fat, protein, ash, fiber, soluble, and insoluble carbohydrate content in these residues. To identify sugars rich in galactose and acidic sugars, a total soluble carbohydrate extraction was performed. Cellulose, as part of the insoluble carbohydrates, was isolated through alkaline and acid hydrolysis, while sodium silicate was derived from the ash. Characterization of insoluble cellulose and silicate involved techniques like FTIR, DSC, PXRD, microphotography, porosity assessments, and water absorption studies. For proteins, alkaline solubilization and precipitation at the isoelectric point were utilized, with quantification via BCA and amino acid profiling through gas chromatography. Evaluation of radical scavenging capacity using DPPH led to the calculation of apparent molecular weight via SDS-PAGE. Results: The results revealed low levels of gum, mucilage, and pectin in both residues, contrasting with a high concentration of insoluble polysaccharides. Among these, Iß cellulose displayed potential attributes for cosmetic applications due to its oil and water adsorption characteristics. However, silicates obtained from the ashes did not exhibit direct use potential. In terms of protein extraction, we observed antioxidant properties, with enhanced performance through enzymatic hydrolysis, achieving a hydrolysis degree of 30.41% and a DPPH radical absorption rate exceeding 70%. Conclusion: Rice residues, particularly husk and straw, shown valuable substances suitable for potential cosmetic applications, encompassing cellulose, hydrolyzed proteins, and ash as a silicate precursor.
RESUMO
Background and purpose: Magnetic resonance imaging (MRI)-to-computed tomography (CT) synthesis is essential in MRI-only radiotherapy workflows, particularly through deep learning techniques known for their accuracy. However, current supervised methods are limited to specific center's learnings and depend on registration precision. The aim of this study was to evaluate the accuracy of unsupervised and supervised approaches in the context of prostate MRI-to-CT generation for radiotherapy dose calculation. Methods: CT/MRI image pairs from 99 prostate cancer patients across three different centers were used. A comparison between supervised and unsupervised conditional Generative Adversarial Networks (cGAN) was conducted. Unsupervised training incorporates a style transfer method with. Content and Style Representation for Enhanced Perceptual synthesis (CREPs) loss. For dose evaluation, the photon prescription dose was 60 Gy delivered in volumetric modulated arc therapy (VMAT). Imaging endpoint for sCT evaluation was Mean Absolute Error (MAE). Dosimetric endpoints included absolute dose differences and gamma analysis between CT and sCT dose calculations. Results: The unsupervised paired network exhibited the highest accuracy for the body with a MAE at 33.6 HU, the highest MAE was 45.5 HU obtained with unsupervised unpaired learning. All architectures provided clinically acceptable results for dose calculation with gamma pass rates above 94 % (1 % 1 mm 10 %). Conclusions: This study shows that multicenter data can produce accurate sCTs via unsupervised learning, eliminating CT-MRI registration. The sCTs not only matched HU values but also enabled precise dose calculations, suggesting their potential for wider use in MRI-only radiotherapy workflows.
RESUMO
In order to investigate the underlying genetic structure and genomic ancestry proportions of Peruvian subpopulations, we analyzed 551 human samples of 25 localities from the Andean, Amazonian, and Coastal regions of Peru with a set of 40 ancestry informative insertion-deletion polymorphisms. Using genotypes of reference populations from different continents for comparison, our analysis indicated that populations from all 25 Peruvian locations had predominantly Amerindian genetic ancestry. Among populations from the Titicaca Lake islands of Taquile, Amantani, Anapia, and Uros, and the Yanque locality from the southern Peruvian Andes, there was no significant proportion of non-autochthonous genomes, indicating that their genetic background is effectively derived from the first settlers of South America. However, the Andean populations from San Marcos, Cajamarca, Characato and Chogo, and coastal populations from Lambayeque and Lima displayed a low but significant European ancestry proportion. Furthermore, Amazonian localities of Pucallpa, Lamas, Chachapoyas, and Andean localities of Ayacucho and Huancayo displayed intermediate levels of non-autochthonous ancestry, mostly from Europe. These results are in close agreement with the documented history of post-Columbian immigrations in Peru and with several reports suggesting a larger effective size of indigenous inhabitants during the formation of the current country's population.
Assuntos
Indígena Americano ou Nativo do Alasca/genética , Mutação INDEL , População Branca/genética , Análise por Conglomerados , Genótipo , Humanos , Metagenômica , Peru , Análise de Componente PrincipalRESUMO
Radiation therapy is moving from CT based to MRI guided planning, particularly for soft tissue anatomy. An important requirement of this new workflow is the generation of synthetic-CT (sCT) from MRI to enable treatment dose calculations. Automatic methods to determine the acceptable range of CT Hounsfield Unit (HU) uncertainties to avoid dose distribution errors is thus a key step toward safe MRI-only radiotherapy. This work has analysed the effects of controlled errors introduced in CT scans on the delivered radiation dose for prostate cancer patients. Spearman correlation coefficient has been computed, and a global sensitivity analysis performed following the Morris screening method. This allows the classification of different error factors according to their impact on the dose at the isocentre. sCT HU estimation errors in the bladder appeared to be the least influential factor, and sCT quality assessment should not only focus on organs surrounding the radiation target, as errors in other soft tissue may significantly impact the dose in the target volume. This methodology links dose and intensity-based metrics, and is the first step to define a threshold of acceptability of HU uncertainties for accurate dose planning.