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Maintaining an effective testing program is critical to the success and credibility of the anti-doping movement. However, a low detection ratio compared to the assumed real prevalence of sport doping has led some to question and criticize the effectiveness of the current testing system. In this perspective article, we review the results of the global testing program, discuss the purpose of testing, and compare benefits and limitations of performance indicators commonly used to evaluate testing efforts. We suggest that an effective testing program should distinguish between preventive testing and testing aimed at detecting the use of prohibited substances and prohibited methods. In case of preventive testing, the volume of the test program in terms of number of samples, tests and analyses is likely to be positively related to the extent of the deterrent effect achieved. However, there is a lack of literature on how the deterrent effect works in the practical context of doping testing. If the primary goal is to detect doping, the testing must be risk- and intelligence-based, and quality in test planning is more important than quantity in sample collection. The detection ratio can be a useful tool for evaluating the effectiveness of doping testing, but for the calculation one should take into account the number of athletes tested and not just the number of collected samples, as the former would provide a more precise measure of the tests' ability to detect doping among athletes.
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[This corrects the article DOI: 10.3389/falgy.2023.1333570.].
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The implementation of neural networks (NNs) on edge devices enables local processing of wireless data, but faces challenges such as high computational complexity and memory requirements when deep neural networks (DNNs) are used. Shallow neural networks customized for specific problems are more efficient, requiring fewer resources and resulting in a lower latency solution. An additional benefit of the smaller network size is that it is suitable for real-time processing on edge devices. The main concern with shallow neural networks is their accuracy performance compared to DNNs. In this paper, we demonstrate that a customized adaptive activation function (AAF) can meet the accuracy of a DNN. We designed an efficient FPGA implementation for a customized segmented spline curve neural network (SSCNN) structure to replace the traditional fixed activation function with an AAF. We compared our SSCNN with different neural network structures such as a real-valued time-delay neural network (RVTDNN), an augmented real-valued time-delay neural network (ARVTDNN), and deep neural networks with different parameters. Our proposed SSCNN implementation uses 40% fewer hardware resources and no block RAMs compared to the DNN with similar accuracy. We experimentally validated this computationally efficient and memory-saving FPGA implementation of the SSCNN for digital predistortion of radio-frequency (RF) power amplifiers using the AMD/Xilinx RFSoC ZCU111. The implemented solution uses less than 3% of the available resources. The solution also enables an increase of the clock frequency to 221.12 MHz, allowing the transmission of wide bandwidth signals.
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BACKGROUND: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown. METHODS: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within the past 12 months, body mass index, physiologic frailty (VACS Index 2.0), illicit substance and alcohol use disorders, and measures of multimorbidity and polypharmacy. We separately fit multivariable logistic models to each outcome using generalized estimating equations. From these models, the longitudinal extensions of average attributable fraction (LE-AAF) for modifiable risk factors were estimated. RESULTS: Key risk factors for both outcomes included physiologic frailty (VACS Index 2.0) (serious falls [15%; 95% CI 14%-15%]; fractures [13%; 95% CI 12%-14%]), a serious fall in the past year (serious falls [7%; 95% CI 7%-7%]; fractures [5%; 95% CI 4%-5%]), polypharmacy (serious falls [5%; 95% CI 4%-5%]; fractures [5%; 95% CI 4%-5%]), an opioid prescription in the past month (serious falls [7%; 95% CI 6%-7%]; fractures [9%; 95% CI 8%-9%]), and diagnosis of alcohol use disorder (serious falls [4%; 95% CI 4%-5%]; fractures [8%; 95% CI 7%-8%]). CONCLUSIONS: This study confirms the contributions of risk factors important in the general population to both serious falls and fragility fractures among older PWH. Successful prevention programs for these outcomes should build on existing prevention efforts while including risk factors specific to PWH.
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Alcoolismo , Fraturas Ósseas , Fragilidade , Infecções por HIV , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Fragilidade/epidemiologia , Fragilidade/complicações , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Fatores de Risco , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologiaRESUMO
INTRODUCTION AND OBJECTIVES: Thyroid nodules frequently require ultrasound and Fine Needle Aspiration Cytology (FNAC) evaluation. However, FNA cytology does not allow differentiation between follicular adenoma and carcinoma on Bethesda type IV lesions. This situation leads to many unnecessary surgical procedures because it is not possible to assure the benignity of the lesions, even when most of the specimens correspond to adenomas or even other benign lesions. The objective is this study is to establish if there are any US characteristics that would help us to predict the risk of malignancy of nodules with a pathological diagnosis of follicular neoplasm in order to achieve a more conservative management for non-suspicious nodules. MATERIAL AND METHODS: We studied 61 nodules in 61 patients (51 women and 10 men) that underwent thyroid surgery and had histopathological results of either follicular adenoma or carcinoma. Different US characteristics of the nodules were analysed (composition, echogenicity, margin, calcification status, the presence of halo and overall observer suspicion of malignancy) and were correlated with the histopathological analysis. RESULTS: We have found a statistically significant association between the presence of calcifications, ill-defined borders and overall observer suspicion or impression (defined by well-known suspicious for malignancy ultrasonographic features, such as calcification, poorly defined margin, and a markedly hypoechoic solid nodule; and benign ultrasonographic features, such as predominantly cystic echogenic composition and the presence of a perinodular hypoechogenic halo) with follicular carcinoma. However all those features have shown low sensitivities in the present study (30%, 30% and 50%, respectively). On the other hand, the absence of halo sign has shown a sensitivity of 100% and a negative predictive value (NPV) of 100% in our study. CONCLUSIONS: The presence of calcifications, ill-defined borders and the overall impression or suspicion of malignancy associate with a higher risk for follicular carcinoma in Bethesda type IV thyroid nodules but their absence do not allow to predict benignity in these nodules. Inversely, when a halo sign lesion is observed, benign follicular neoplasm should be considered.
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Adenocarcinoma Folicular , Adenoma , Calcinose , Carcinoma , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Masculino , Humanos , Feminino , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adenoma/patologia , Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/cirurgia , Adenocarcinoma Folicular/patologia , Ultrassonografia , Carcinoma/patologiaRESUMO
Introducción y objetivosLos nódulos tiroideos requieren con frecuencia evaluación mediante ecografía y biopsia por aspiración con aguja fina (BAAF). No obstante, la BAAF no permite la diferenciación entre adenoma y carcinoma folicular en lesiones de tipo IV según la clasificación de Bethesda. Esto provoca numerosas intervenciones quirúrgicas innecesarias porque no es posible garantizar el carácter benigno de las lesiones, ni siquiera cuando la mayoría de las muestras corresponden a adenomas o incluso a otras lesiones benignas. El objetivo de este estudio es establecer si hay características ecográficas que nos ayudarían a pronosticar el riesgo de malignidad de los nódulos con un diagnóstico anatomopatológico de neoplasia folicular para conseguir un abordaje más conservador de los nódulos sin sospecha de malignidad.Material y métodosEstudiamos 61 nódulos en 61 pacientes (51 mujeres y 10 varones) que se habían sometido a intervención quirúrgica de la glándula tiroides y tenían resultados histopatológicos de adenoma o carcinoma folicular. Se analizaron diversas características ecográficas de los nódulos (composición, ecogenicidad, borde, estado de calcificación, presencia de halo y sospecha general de malignidad según el observador) y se estableció su correlación con el análisis histopatológico.ResultadosObservamos una relación estadísticamente significativa entre el carcinoma folicular y la presencia de calcificaciones, bordes mal definidos y la sospecha o impresión general del observador (definida por sospecha clara de signos ecográficos de malignidad, como calcificación, borde mal definido y un nódulo sólido marcadamente hipoecoico; y signos ecográficos de benignidad, como composición ecogénica predominantemente quística y presencia de halo hipoecogénico perinodular). Sin embargo, todas estas características han mostrado una sensibilidad baja en el estudio que nos ocupa (30%, 30% y 50%, respectivamente)...(AU)
Introduction and objectivesThyroid nodules frequently require ultrasound and Fine Needle Aspiration Cytology (FNAC) evaluation. However, FNA cytology does not allow differentiation between follicular adenoma and carcinoma on Bethesda type IV lesions. This situation leads to many unnecessary surgical procedures because it is not possible to assure the benignity of the lesions, even when most of the specimens correspond to adenomas or even other benign lesions.The objective is this study is to establish if there are any US characteristics that would help us to predict the risk of malignancy of nodules with a pathological diagnosis of follicular neoplasm in order to achieve a more conservative management for non-suspicious nodules.Material and methodsWe studied 61 nodules in 61 patients (51 women and 10 men) that underwent thyroid surgery and had histopathological results of either follicular adenoma or carcinoma.Different US characteristics of the nodules were analysed (composition, echogenicity, margin, calcification status, the presence of halo and overall observer suspicion of malignancy) and were correlated with the histopathological analysis.ResultsWe have found a statistically significant association between the presence of calcifications, ill-defined borders and overall observer suspicion or impression (defined by well-known suspicious for malignancy ultrasonographic features, such as calcification, poorly defined margin, and a markedly hypoechoic solid nodule; and benign ultrasonographic features, such as predominantly cystic echogenic composition and the presence of a perinodular hypoechogenic halo) with follicular carcinoma. However all those features have shown low sensitivities in the present study (30%, 30% and 50%, respectively). On the other hand, the absence of halo sign has shown a sensitivity of 100% and a negative predictive value (NPV) of 100% in our study... (AU)
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Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adenoma/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Estudos Retrospectivos , Diagnóstico Diferencial , Ultrassonografia/métodosRESUMO
The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.
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Córtex Auditivo , Neurônios , Estimulação Acústica/métodos , Neurônios/fisiologia , Córtex Auditivo/fisiologia , Percepção Auditiva , Células PiramidaisRESUMO
The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.
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Estimulação Acústica/métodos , Neurônios/fisiologia , Córtex Auditivo/fisiologia , Percepção Auditiva , Células PiramidaisRESUMO
The COVID-19 pandemic led to supply chain disruptions causing a severe shortage of infant formula. The shortage impacted parents of infants with cow's milk protein allergy (CMPA) who rely on specialized formulas. However, research on parent perspectives during formula shortages is limited. We aimed to understand the factors guiding parents' decisions when transitioning to alternative amino acid formula (AAF) or extensively hydrolyzed formula (eHF) during the national formula shortage. We conducted a survey using the ZSMoments platform and found that before the shortage, parents valued safety (83%), tolerability (78%), and reputability (78%) as primary factors in selecting eHFs and AAFs. Post-shortage, formula tolerability (86%), assurance (84%), and safety (80%) gained more importance. Among those switching eHF (n = 54), health care provider recommendations (81%), reputability (78%), taste (78%), and tolerability (78%) were rated as "extremely important." Among those switching AAF (n = 26), top factors included tolerability (77%), assurance (73%), safety (73%), cost-effectiveness (73%), and formula trustworthiness (73%). These data suggest that parents carefully weigh various factors when managing their child's CMPA and transitioning to different AAF or eHF options.
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Enteroaggregative Escherichia coli (EAEC) is an important cause of diarrhea in children and adults worldwide. This pathotype is phenotypically characterized by the aggregative-adherence (AA) pattern in HEp-2 cells and genetically associated to the presence of the aatA gene. EAEC pathogenesis relies in different virulence factors. At least, three types of adhesins have been specifically associated with EAEC strains: the five variants of the aggregative adherence fimbriae (AAF), the aggregative forming pilus (AFP) and more recently, a fibrilar adhesin named CS22. Our study aimed to evaluate the presence of AAF, AFP and CS22-related genes among 110 EAEC strains collected from feces of children with diarrhea. The presence of aggR (EAEC virulence regulator) and genes related to AAFs (aggA, aafA, agg3A, agg4A, agg5A and agg3/4C), AFP (afpA1 and afpR) and CS22 (cseA) was detected by PCR, and the adherence patterns were evaluated on HeLa cells. aggR-positive strains comprised 83.6% of the collection; among them, 80.4% carried at least one AAF-related gene and presented the AA pattern. aggA was the most frequent AAF-related gene (28.4% of aggR+ strains). cseA was detected among aggR+ (16.3%) and aggR- strains (22.2%); non-adherent strains or strains presenting AA pattern were observed in both groups. afpR and afpA1 were exclusively detected among aggR- strains (77.8%), most of which (71.4%) also presented AA pattern. Our results indicate that AAF- and AFP-related genes may contribute to identify EAEC strains, while the presence of cseA and its importance as an EAEC virulence factor and genotypic marker needs to be further evaluated.
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Adesinas Bacterianas , Escherichia coli , alfa-Fetoproteínas , Criança , Humanos , Adesinas Bacterianas/genética , Aderência Bacteriana/genética , Biomarcadores , Diarreia/microbiologia , Escherichia coli/genética , Células HeLa , Fatores de Virulência/genéticaRESUMO
Secondary aorto-atrial fistula is a rare but potentially life-threatening complication of ascending aortic dissection surgical repair. Secondary aorto-atrial fistulas commonly lead to symptomatic heart failure requiring emergent repair. We present a rare case of secondary aorto-atrial fistula after surgical repair of aortic dissection that remained asymptomatic for a decade. (Level of Difficulty: Intermediate.).
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Alkali-activated composites of lightweight aggregates (LWAs, with beneficial insulating properties) and alkali-activated foams (AAFs, higher added value products due to their production from waste materials at well below 100 °C) allow for the expectation of superior properties if a chemical bonding reaction or mechanical interlocking occurs during production. However, the interfaces between LWAs and an AAF have not been studied in detail so far. Chemical reactions are possible if the LWA contains an amorphous phase which can react with the alkaline activators of the AAF, increase the bonding, and thus, also their mechanical strengths. These, in turn, allow for an improvement of the thermal insulation properties as they enable a further density reduction by incorporating low density aggregates. This work features a first-detailed analyses of the interfaces between the LWAs' expanded polystyrene, perlite, expanded clay and expanded glass, and the alkali-activated foam matrices produced using industrial slags and fly ash. Some are additionally reinforced by fibers. The goal of these materials is to replace cement by alkali-activated waste as it significantly lowers the environmental impact of the produced building components.
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Enteroaggregative Escherichia coli (EAEC) is an important cause of diarrhea in children and adults worldwide. This pathotype is phenotypically characterized by the aggregative-adherence (AA) pattern in HEp-2 cells and genetically associated to the presence of the aatA gene. EAEC pathogenesis relies in different virulence factors. At least, three types of adhesins have been specifically associated with EAEC strains: the five variants of the aggregative adherence fimbriae (AAF), the aggregative forming pilus (AFP) and more recently, a fibrilar adhesin named CS22. Our study aimed to evaluate the presence of AAF, AFP and CS22-related genes among 110 EAEC strains collected from feces of children with diarrhea. The presence of aggR (EAEC virulence regulator) and genes related to AAFs (aggA, aafA, agg3A, agg4A, agg5A and agg3/4C), AFP (afpA1 and afpR) and CS22 (cseA) was detected by PCR, and the adherence patterns were evaluated on HeLa cells. aggR-positive strains comprised 83.6% of the collection; among them, 80.4% carried at least one AAF-related gene and presented the AA pattern. aggA was the most frequent AAF-related gene (28.4% of aggR+ strains). cseA was detected among aggR+ (16.3%) and aggR- strains (22.2%); non-adherent strains or strains presenting AA pattern were observed in both groups. afpR and afpA1 were exclusively detected among aggR- strains (77.8%), most of which (71.4%) also presented AA pattern. Our results indicate that AAF- and AFP-related genes may contribute to identify EAEC strains, while the presence of cseA and its importance as an EAEC virulence factor and genotypic marker needs to be further evaluated.
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Obesity is a modifiable risk factor in breast cancer patients and is predictive of disease outcomes in early-onset breast cancer survivors. The purpose of this review is to summarize the current evidence in the association between early-onset breast cancer and obesity, specifically in African-American women. Reviewing the molecular mechanisms and social determinants of disease in this population can provide a foundation for future interventions in prevention, detection, and treatment aiming at improving outcomes for young breast cancer patients.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Negro ou Afro-Americano , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , SobreviventesRESUMO
The applications of terahertz (THz) technology can be greatly extended using non-diffractive beams with unique field distributions and non-diffractive transmission characteristics. Here, we design and experimentally demonstrate a set of dual non-diffractive THz beam generators based on an all-dielectric metasurface. Two kinds of non-diffractive beams with dramatically opposite focusing properties, Bessel beam and abruptly autofocusing (AAF) beam, are considered. A Bessel beam with long-distance non-diffractive characteristics and an AAF beam with low energy during transmission and abruptly increased energy near the focus are generated for x- and y-polarized incident waves, respectively. These two kinds of beams are characterized and the results agree well with simulations. In addition, we show numerically that these two kinds of beams can also carry orbital angular momentum by further imposing proper angular phases in the design. We believe that these metasurface-based beam generators have great potential use in THz imaging, communications, non-destructive evaluation, and many other fields.
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Whereas the O104:H4 enterohemorrhagic Escherichia coli (EHEC) outbreak strain from 2011 expresses aggregative adherence fimbriae of subtype I (AAF/I), its close relative, the O104:H4 enteroaggregative Escherichia coli (EAEC) strain 55989, encodes AAF of subtype III. Tight adherence mediated by AAF/I in combination with Shiga toxin 2 production has been suggested to result in the outbreak strain's exceptional pathogenicity. Furthermore, the O104:H4 outbreak strain adheres significantly better to cultured epithelial cells than archetypal EAEC strains expressing different AAF subtypes. To test whether AAF/I expression is associated with the different virulence phenotypes of the outbreak strain, we heterologously expressed AAF subtypes I, III, IV, and V in an AAF-negative EAEC 55989 mutant and compared AAF-mediated phenotypes, incl. autoaggregation, biofilm formation, as well as bacterial adherence to HEp-2 cells. We observed that the expression of all four AAF subtypes promoted bacterial autoaggregation, though with different kinetics. Disturbance of AAF interaction on the bacterial surface via addition of α-AAF antibodies impeded autoaggregation. Biofilm formation was enhanced upon heterologous expression of AAF variants and inversely correlated with the autoaggregation phenotype. Co-cultivation of bacteria expressing different AAF subtypes resulted in mixed bacterial aggregates. Interestingly, bacteria expressing AAF/I formed the largest bacterial clusters on HEp-2 cells, indicating a stronger host cell adherence similar to the EHEC O104:H4 outbreak strain. Our findings show that, compared to the closely related O104:H4 EAEC strain 55989, not only the acquisition of the Shiga toxin phage, but also the acquisition of the AAF/I subtype might have contributed to the increased EHEC O104:H4 pathogenicity.
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Aderência Bacteriana/genética , Escherichia coli O104/genética , Escherichia coli O104/patogenicidade , Fímbrias Bacterianas/genética , Fímbrias Bacterianas/fisiologia , Fenótipo , Biofilmes/crescimento & desenvolvimento , Infecções por Escherichia coli , Escherichia coli O104/classificação , Fímbrias Bacterianas/classificação , Humanos , Família Multigênica , Sorogrupo , Virulência/genéticaRESUMO
INTRODUCTION AND OBJECTIVES: Thyroid nodules frequently require ultrasound and Fine Needle Aspiration Cytology (FNAC) evaluation. However, FNA cytology does not allow differentiation between follicular adenoma and carcinoma on Bethesda type IV lesions. This situation leads to many unnecessary surgical procedures because it is not possible to assure the benignity of the lesions, even when most of the specimens correspond to adenomas or even other benign lesions. The objective in this study is to establish if there are any US characteristics that would help us to predict the risk of malignancy of nodules with a pathological diagnosis of follicular neoplasm in order to achieve a more conservative management for non-suspicious nodules. MATERIAL AND METHODS: We studied 61 nodules in 61 patients (51 women and 10 men) that underwent thyroid surgery and had histopathological results of either follicular adenoma or carcinoma. Different US characteristics of the nodules were analysed (composition, echogenicity, margin, calcification status, the presence of halo and overall observer suspicion of malignancy) and were correlated with the histopathological analysis. RESULTS: We have found a statistically significant association between the presence of calcifications, ill-defined borders and overall observer suspicion or impression (defined by well-known suspicious for malignancy ultrasonographic features, such as calcification, poorly defined margin, and a markedly hypoechoic solid nodule; and benign ultrasonographic features, such as predominantly cystic echogenic composition and the presence of a perinodular hypoechogenic halo) with follicular carcinoma. However all those features have shown low sensitivities in the present study (30%, 30% and 50%, respectively). On the other hand, the absence of halo sign has shown a sensitivity of 100% and a negative predictive value (NPV) of 100% in our study. CONCLUSIONS: The presence of calcifications, ill-defined borders and the overall impression or suspicion of malignancy are associated with a higher risk for follicular carcinoma in Bethesda type IV thyroid nodules but their absence does not allow to predict benignity in these nodules. Inversely, when a halo sign lesion is observed, benign follicular neoplasm should be considered.
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A novel approach is developed to address the challenge of annotating with phenotypic effects those exome variants for which relevant empirical data are lacking or minimal. The predictive annotation method is implemented as a stacked ensemble of supervised base-learners, including distributed random forest and gradient boosting machines. Ensemble models were trained and cross-validated on evidence-based categorical variant effect annotations from the ClinVar database, and were applied to 84 million non-synonymous single nucleotide variants (SNVs). The consensus model combined 39 functional mutation impacts, cross-species conservation score, and gene indispensability score. The indispensability score, accounting for differences in variant pathogenicities including in essential and mutation-tolerant genes, considerably improved the predictions. The consensus combination is consistent with as many input scores as possible while minimizing false predictions. The input scores are ranked based on their ability to predict effects. The score rankings and categorical phenotypic variant effect predictions are aimed for direct use in clinical and biological applications to prioritize human exome variants and mutations.
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Biologia Computacional/métodos , Doença/genética , Exoma , Anotação de Sequência Molecular , Mutação , Polimorfismo de Nucleotídeo Único , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Software , Sequenciamento do ExomaRESUMO
INTRODUCTION: 2-AAF and DEN are well-known liver toxicants commonly used to stimulate tumors in laboratory animals. AIM: The aim of this study was to investigate the effect of octreotide on DEN-induced and 2-AAF-supplemented hepatocarcinogenesis in Wistar albino rats. MATERIALS AND METHODS: In this study, 64 Wistar albino rats were divided into 8 groups. DEN (175 mg/kg) initiated and 2-AAF (20 mg/kg) promoted liver carcinogenesis in rats. The tumor growth inhibitor octreotide (300 µg/kg) was used. Rats were sacrificed at the end of experiment and their liver tissues were taken for the study. SOD, GSH-Px, CAT activities, NO and MDA levels were measured spectrophotometrically. Also, Hsp70 and 8-OHdG was measured by the ELISA method. RESULTS: In group 7, MDA, 8-OHdG, and Hsp70 levels were significantly increased. In addition, SOD, GSH-Px activity was significantly reduced in this group. MDA, 8-OHdG and Hsp70 levels were significantly reduced in Group 8, which received octreotide for treatment. CONCLUSION: DEN and 2-AAF cause very serious liver damage. Octreotide protects the liver from carcinogenesis, increases the activity of cellular antioxidant enzymes and helps reduce DNA damage. Therefore, octreotide may be an inhibitor in tumor cells and may reduce oxidative stress.