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Biological weapons, primarily dispersed as aerosols, can spread not only to the targeted area but also to adjacent regions following the movement of air driven by wind. Thus, there is a growing demand for toxin analysis because biological weapons are among the most influential and destructive. Specifically, such a technique should be hand-held, rapid, and easy to use because current methods require more time and well-trained personnel. Our study demonstrates the use of a novel lateral flow immunoassay, which has a confined structure like a double barbell in the detection area (so called c-LFA) for toxin detection such as staphylococcal enterotoxin B (SEB), ricinus communis (Ricin), and botulinum neurotoxin type A (BoNT-A). Additionally, we have explored the integration of machine learning (ML), specifically, a toxin chip boosting (TOCBoost) hybrid algorithm for improved sensitivity and specificity. Consequently, the ML powered c-LFA concurrently categorized three biological toxin types with an average accuracy as high as 95.5%. To our knowledge, the sensor proposed in this study is the first attempt to utilize ML for the assessment of toxins. The advent of the c-LFA orchestrated a paradigm shift by furnishing a versatile and robust platform for the rapid, on-site detection of various toxins, including SEB, Ricin, and BoNT-A. Our platform enables accessible and on-site toxin monitoring for non-experts and can potentially be applied to biosecurity.
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BACKGROUND: The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance. METHODS: Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors. RESULTS: Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI. CONCLUSIONS: Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.
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Adenocarcinoma , Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Humanos , Biomarcadores Tumorais/metabolismo , Adenocarcinoma/patologia , Fator de Transcrição CDX2/metabolismo , Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/patologia , Imuno-Histoquímica , Prognóstico , Queratina-20/metabolismo , Queratina-7/metabolismoRESUMO
OBJECTIVE: To evaluate whether the computer-aided diagnosis (CAD)-extracted kinetic heterogeneity of breast cancer on MRI and changes therein during treatment were associated with the pathological response to neoadjuvant systemic therapy (NST). MATERIALS AND METHODS: Consecutive patients with invasive breast cancer, who underwent NST followed by surgery between 2014 and 2020, were retrospectively evaluated. Using a commercial CAD system, kinetic features (angiovolume, peak enhancement, delayed enhancement profiles, and kinetic heterogeneity) of breast cancer were assessed with pre- and mid-treatment MRI. Multivariate logistic regression was used to identify the associations between CAD-extracted kinetic features and pathological complete response (pCR). RESULTS: A total of 130 patients (mean age, 55 years) were included, 37 (28.5%) of whom achieved a pCR. When the pre- and mid-treatment MRI data were compared, the pCR group exhibited greater changes in kinetic heterogeneity (86.14 ± 32.05% vs. 8.50 ± 141.01%, p < 0.001) and angiovolume (95.20 ± 14.29% vs. 19.89 ± 320.16%; p < 0.001) than the non-pCR group. Multivariate regression analysis showed that a large change in kinetic heterogeneity (odds ratio (OR) = 1.030, p < 0.001), age (OR = 0.931, p = 0.005), progesterone receptor negativity (OR = 7.831, p = 0.001), and HER2 positivity (OR = 3.455, p = 0.017) were associated with pCR. CONCLUSIONS: A greater change in the CAD-extracted kinetic heterogeneity of breast cancer between pre- and mid-treatment MRI was associated with a pCR in patients on NST. KEY POINTS: A greater change in kinetic heterogeneity was associated with a pathological complete response. Computer-aided diagnosis-extracted kinetic heterogeneity might serve as a quantitative biomarker of therapeutic efficacy.
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Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética , ComputadoresRESUMO
Despite recent genome-wide investigations of functional DNA elements, the mechanistic details about their actions remain elusive. One intriguing possibility is that DNA sequences with special patterns play biological roles, adopting non-B-DNA conformations. Here we investigated dynamics of thymine-guanine (TG) repeats, microsatellite sequences and recurrently found in promoters, as well as cytosine-guanine (CG) repeats, best-known Z-DNA forming sequence, in the aspect of Z-DNA formation. We measured the energy barriers of the B-Z transition with those repeats and discovered the sequence-dependent penalty for Z-DNA generates distinctive thermodynamic and kinetic features in the torque-induced transition. Due to the higher torsional stress required for Z-form in TG repeats, a bubble could be induced more easily, suppressing Z-DNA induction, but facilitate the B-Z interconversion kinetically at the transition midpoint. Thus, the Z-form by TG repeats has advantages as a torsion buffer and bubble selector while the Z-form by CG repeats likely behaves as torsion absorber. Our statistical physics model supports quantitatively the populations of Z-DNA and reveals the pivotal roles of bubbles in state dynamics. All taken together, a quantitative picture for the transition was deduced within the close interplay among bubbles, plectonemes and Z-DNA.
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DNA de Forma B/química , DNA Forma Z/química , Modelos Químicos , Modelos Moleculares , Cinética , Repetições de Microssatélites , Modelos Estatísticos , Sequências Repetitivas de Ácido Nucleico , TermodinâmicaRESUMO
Cisplatin is one of the most potent anti-cancer drugs developed so far. Recent studies highlighted several intriguing roles of histones in cisplatin's anti-cancer effect. Thus, the effect of nucleosome formation should be considered to give a better account of the anti-cancer effect of cisplatin. Here we investigated this important issue via single-molecule measurements. Surprisingly, the reduced activity of cisplatin under [NaCl] = 180 mM, corresponding to the total concentration of cellular ionic species, is still sufficient to impair the integrity of a nucleosome by retaining its condensed structure firmly, even against severe mechanical and chemical disturbances. Our finding suggests that such cisplatin-induced fastening of chromatin can inhibit nucleosome remodelling required for normal biological functions. The in vitro chromatin transcription assay indeed revealed that the transcription activity was effectively suppressed in the presence of cisplatin. Our direct physical measurements on cisplatin-nucleosome adducts suggest that the formation of such adducts be the key to the anti-cancer effect by cisplatin.
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Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias/tratamento farmacológico , Histonas/metabolismo , Proteínas de Membrana/metabolismo , Nucleossomos/metabolismoRESUMO
BACKGROUND: There have been few reports comparing image quality and radiation dose of aorta computed tomography angiography (CTA) between the high-pitch and the hybrid technique. PURPOSE: To compare the image quality and radiation dose among non-electrocardiogram (ECG)-gated high-pitch CTA and hybrid ECG-gated CTA of the aorta using 512-slice CT. MATERIAL AND METHODS: This retrospective study included 110 patients who underwent non-ECG-gated high-pitch CTA (group 1) or hybrid ECG-gated CTA (group 2) of the entire aorta. Interpretability, image noise, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and the mean effective radiation dose were compared. RESULTS: The mean image noise of the whole aorta was significantly lower (15.7 ± 1.8 HU vs. 16.5 ± 1.2 HU, P = 0.008) in group 1 than in group 2. The CNR (22.3 ± 4.7 vs. 20.0 ± 3.9, Pâ <â 0.001) and SNR (26.5 ± 4.9 vs. 23.2 ± 4.0, Pâ <â 0.001) were higher in group 2 compared with group 1. Neither group showed a significant difference in interpretability of the ascending aorta, cardiac chamber, aortic valve, right ostium, and left ostium (all P = 1). The mean effective radiation dose was significantly lower in group 1 than in group 2 (3.5 ± 0.9 mSv vs. 4.3 ± 0.8 mSv, Pâ <â 0.001). CONCLUSION: The non-ECG-gated high-pitch technique shows significantly improved CNR and SNR due to reduced noise with lower radiation exposure. The interpretability of the cardiac structure, ascending aorta, aortic valve, and both ostia did not differ significantly between the two groups.
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Aorta , Angiografia por Tomografia Computadorizada , Humanos , Angiografia por Tomografia Computadorizada/métodos , Aortografia/métodos , Estudos Retrospectivos , Doses de Radiação , Aorta/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Eletrocardiografia/métodos , Valva Aórtica , Angiografia Coronária/métodosRESUMO
BACKGROUND: The associations between diffusion kurtosis imaging (DKI)-derived parameters and clinical prognostic factors of breast cancer have not been fully evaluated; this knowledge may have implications for outcome prediction and treatment strategies. PURPOSE: To determine associations between quantitative diffusion parameters derived from DKI and diffusion-weighted imaging (DWI) and the prognostic factors and molecular subtypes of breast cancer. STUDY TYPE: Retrospective. POPULATION: A total of 383 women (mean age, 53.8 years; range, 31-82 years) with breast cancer who underwent preoperative breast MRI including DKI and DWI. FIELD STRENGTH/SEQUENCE: A 3.0 T; DKI using a spin-echo echo-planar imaging (EPI) sequence (b values: 200, 500, 1000, 1500, and 2000 sec/mm2 ), DWI using a readout-segmented EPI sequence (b values: 0 and 1000 sec/mm2 ) and dynamic contrast-enhanced breast MRI. ASSESSMENT: Two radiologists (J.Y.K. and H.S.K. with 9 years and 1 year of experience in MRI, respectively) independently measured kurtosis, diffusivity, and apparent diffusion coefficient (ADC) values of breast cancer by manually placing a regions of interest within the lesion. Diffusion measures were compared according to nodal status, grade, and molecular subtypes. STATISTICAL TESTS: Kruskal-Wallis test, Mann-Whitney U test with Bonferroni correction, receiver operating characteristic (ROC) analysis, and multivariate logistic regression analysis. (Statistical significance level of P < 0.05). RESULTS: All diffusion measures showed significant differences according to axillary nodal status and histological grade. Kurtosis showed significant differences among molecular subtypes. The luminal subtype (median 1.163) showed a higher kurtosis value compared to the HER2-positive (median 0.962) or triple-negative subtypes (median 1.072). ROC analysis for differentiating HER2-positive from luminal subtypes revealed that kurtosis yielded the highest area under the curve of 0.781. In multivariate analyses, kurtosis remained a significant factor associated with differentiation between HER2-positive and luminal (odds ratio [OR] = 0.993), triple-negative and luminal (OR = 0.995), and HER2-positive and triple-negative subtypes (OR = 0.994). DATA CONCLUSION: Quantitative diffusion parameters derived from DKI and DWI are associated with prognostic factors for breast cancer. Moreover, DKI-derived kurtosis can help distinguish between the molecular subtypes of breast cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 3.
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Neoplasias da Mama , Neoplasias da Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To investigate whether intratumoral heterogeneity, assessed via dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI), reflects the molecular subtypes of invasive breast cancers. MATERIAL AND METHODS: We retrospectively evaluated data from 248 consecutive women (mean age ± standard deviation, 54.6 ± 12.2 years) with invasive breast cancer who underwent preoperative DCE-MRI and DWI between 2019 and 2020. To evaluate intratumoral heterogeneity, kinetic heterogeneity (a measure of heterogeneity in the proportions of tumor pixels with delayed washout, plateau, and persistent components within a tumor) was assessed with DCE-MRI using a commercially available computer-aided diagnosis system. Apparent diffusion coefficients (ADCs) were obtained using a region-of-interest technique, and ADC heterogeneity was calculated using the following formula: (ADCmax-ADCmin)/ADCmean. Possible associations between imaging-based heterogeneity values and breast cancer subtypes were analyzed. RESULTS: Of the 248 invasive breast cancers, 61 (24.6%) were classified as luminal A, 130 (52.4%) as luminal B, 25 (10.1%) as HER2-enriched, and 32 (12.9%) as triple-negative breast cancer (TNBC). There were significant differences in the kinetic and ADC heterogeneity values among tumor subtypes (p < 0.001 and p = 0.023, respectively). The TNBC showed higher kinetic and ADC heterogeneity values, whereas the HER2-enriched subtype showed higher kinetic heterogeneity values compared to the luminal subtypes. Multivariate linear analysis showed that the HER2-enriched (p < 0.001) and TNBC subtypes (p < 0.001) were significantly associated with higher kinetic heterogeneity values. The TNBC subtype (p = 0.042) was also significantly associated with higher ADC heterogeneity values. CONCLUSIONS: Quantitative assessments of heterogeneity in enhancement kinetics and ADC values may provide biological clues regarding the molecular subtypes of breast cancer. KEY POINTS: ⢠Higher kinetic heterogeneity was associated with HER2-enriched and triple-negative breast cancer. ⢠Higher ADC heterogeneity was associated with triple-negative breast cancer. ⢠Aggressive breast cancer subtypes exhibited higher intratumoral heterogeneity based on MRI.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Adulto , Idoso , Mama , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagemRESUMO
The early diagnosis of hepatic steatosis is important. No study has assessed hepatic fat quantification by using low-dose dual-energy computed tomography (CT). We assessed the accuracy of hepatic fat quantification using the multi-material decomposition (MMD) algorithm with low-dose non-contrast material-enhanced dual-energy CT. We retrospectively reviewed 33 prospectively enrolled patients who had undergone low-dose non-contrast material-enhanced dual-energy CT and magnetic resonance image (MRI) proton density fat fraction (PDFF) on the same day. Percentage fat volume fraction (FVF) images were generated using the MMD algorithm on the low-dose dual-energy CT data. We assessed the correlation between FVFs and MRI-PDFFs by using Spearman's rank correlation. With a 5% cutoff value of MRI-PDFF for fatty liver, a receiver operating characteristic (ROC) curve analysis was performed to identify the optimal criteria of FVF for diagnosing fatty liver. CTDIvol of CT was 2.94 mGy. FVF showed a strong correlation with MRI-PDFF (r = 0.756). The ROC curve analysis demonstrated that FVF ≥ 4.61% was the optimal cutoff for fatty liver. With this cutoff value for diagnosing the fatty liver on low-dose dual-energy CT, the sensitivity, specificity, and area under the curve were 90%, 100%, and 0.987, respectively. The MMD algorithm using low-dose non-contrast material-enhanced dual-energy CT is feasible for quantifying hepatic fat.
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Fígado Gorduroso , Prótons , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado Gorduroso/diagnóstico por imagem , Algoritmos , Imageamento por Ressonância Magnética/métodosRESUMO
OBJECTIVES: To validate the functional liver imaging score (FLIS) for prediction of hepatic function in gadoxetic acid-enhanced MRI. METHODS: We retrospectively identified 134 patients (88 men, 46 women; mean age, 58.8 years) between January 2015 and December 2018 with the following inclusion criteria: patients diagnosed with liver cirrhosis or chronic liver disease (CLD) who underwent gadoxetic acid-enhanced MRI. Three parameters on hepatobiliary phase images were evaluated for FLIS: liver parenchymal enhancement, biliary excretion, and signal intensity of the portal vein. Patients were classified as CLD (n = 11), Child-Pugh (CP) class A (n = 87), CP B (n = 22), or CP C (n = 14). We assessed the correlation between CP score and both FLIS and its components using Spearman rank correlation. Receiver operating characteristic (ROC) curve analysis was performed to demonstrate the cutoff value of FLIS for differentiating between CP classes. The associations between patient characteristics, serum markers, FLIS, and hepatic decompensation were evaluated with Cox proportional hazard models. RESULTS: FLIS and three FLIS parameters showed strong to very strong correlation with CP score (r = -0.60 to 0.82). ROC curve analysis showed that FLIS ≥ 5 was the optimal cutoff for prediction of CP class A or CLD (sensitivity, 83.7%; specificity, 94.4%; area under the curve [AUC], 0.93). FLIS < 5 was independently associated with the development of first hepatic decompensation in patients with CP A (HR, 50.0; 95% confidence interval, 6.2, 400.4). CONCLUSION: FLIS showed a strong correlation with hepatic function and can stratify the CP class. In addition, FLIS can help prediction for the development of first decompensation. KEY POINTS: ⢠Functional liver imaging scores (FLIS) and its three parameters, derived from hepatobiliary phase image, have strong to very strong correlations with Child-Pugh (CP) scores. ⢠FLIS can stratify patients with chronic liver disease or liver cirrhosis according to CP classification. ⢠Low FLIS is an independent predictor for first hepatic decompensation in patients with CP class A.
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Meios de Contraste , Hepatopatias , Feminino , Gadolínio DTPA , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Hepatopatias/complicações , Hepatopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Determining if a given patient with primary pancreatic adenocarcinoma (PDA) has hepatic metastasis is important for treatment planning. Several previous studies reported on the diagnostic performance of MRI for liver metastasis in patients with PDA. But the reported data are quite variable. PURPOSE: To systematically determine the diagnostic performance of MRI for liver metastasis in patients with PDA, including comparing it with computed tomography (CT). STUDY TYPE: Systemic review and meta-analysis. SUBJECTS: In all, 457 patients from five eligible articles. FIELD STRENGTH/SEQUENCE: Conventional MR sequences with or without contrast enhancement at 1.5T and 3T. ASSESSMENT: Two reviewers independently performed the data extraction. The reviewers identified and reviewed the original articles reporting the diagnostic performance of MRI for liver metastases in patients with PDA, including those articles making comparisons with CT. STATISTICAL TESTS: Meta-analytic summary sensitivity and specificity were calculated on a per-patient basis using a bivariate random effects model. We compared the meta-analytic summary sensitivity and specificity between MRI and CT. RESULTS: The meta-analytic summary sensitivity and specificity were 85% (95% confidence interval [CI], 74-92%; I2 = 0%) and 98% (95% CI, 78-100%; I2 = 85%), respectively. In comparison with CT, MRI showed a higher sensitivity (85% vs. 75%) but similar specificity (98% vs. 94%). DATA CONCLUSION: MRI had good overall diagnostic performance for liver metastasis in patients with PDA, with a higher sensitivity than CT. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1737-1744.
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Adenocarcinoma , Neoplasias Hepáticas , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico por imagem , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) is a newly developed system of bladder cancer staging with multiparametric MRI (mpMRI), which can be used to predict the presence of muscle invasion for bladder cancer. PURPOSE: To evaluate the accuracy of three mpMRI series (T2 WI, diffusion-weighted imaging [DWI], and dynamic contrast-enhanced image [DCEI]) and VI-RADS for diagnosing the muscle invasive bladder cancer (MIBC). STUDY TYPE: Retrospective. POPULATION: In all, 66 pathologically proven bladder cancers in 32 patients. FIELD STRENGTH/SEQUENCE: Before the diagnostic MRI with an intramuscular antispasmodic agent, optimal bladder distension was confirmed. 3.0T MRI with T2 WI, DWI, and DCEI. ASSESSMENT: Three reviewers independently assessed and scored the bladder cancers in T2 WI, DWI, and DCEI using a five-point score system. Based on the scores in the three sequences, reviewers scored each bladder cancer with reference to VI-RADS categories. We evaluated the diagnostic performance of each of three mpMRI sequences and the final VI-RADS categorization for diagnosing MIBC. STATISTICAL TESTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of each of three sequences separately and VI-RADS categorization for diagnosing the MIBC. RESULTS: The diagnostic performances of each of the three mpMRI series and VI-RADS for diagnosing MIBC were excellent. Especially using the optimal cutoff score >3 for predicting MIBC on DWI, DCEI, and VI-RADS, the sensitivity, specificity, PPV, NPV, and AUC values were 90% (95% confidence interval [CI]: 0.56, 1.00), 100% (95% CI: 0.94, 1.00), 100% (95% CI: 0.66. 1.00), 98.3% (95% CI: 0.91, 1.00), and 0.95, respectively. DATA CONCLUSION: mpMRI based on VI-RADS can stratify patients with bladder cancer according to the presence of muscle invasion. LEVEL OF EVIDENCE: 3. TECHNICAL EFFICACY STAGE: 2. J. Magn. Reson. Imaging 2020;52:1249-1256.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Humanos , Masculino , Músculos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/diagnóstico por imagemRESUMO
OBJECTIVES: To investigate possible associations between quantitative apparent diffusion coefficient (ADC) metrics derived from whole-lesion histogram analysis and breast cancer recurrence risk in women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer who underwent the Oncotype DX assay. METHODS: This retrospective study was conducted on 105 women (median age, 48 years) with ER-positive, HER2-negative, node-negative breast cancer who underwent the Oncotype DX test and preoperative diffusion-weighted imaging (DWI). Histogram analysis of pixel-based ADC data of whole tumors was performed, and various ADC histogram parameters (mean, 5th, 25th, 50th, 75th, and 95th percentiles of ADCs) were extracted. The ADC difference value (defined as the difference between the 5th and 95th percentiles of ADCs) was calculated to assess intratumoral heterogeneity. Associations between quantitative ADC metrics and the recurrence risk, stratified using the Oncotype DX recurrence score (RS), were evaluated. RESULTS: Whole-lesion histogram analysis showed that the ADC difference value was different between the low-risk recurrence (RS < 18) and the non-low-risk recurrence (RS ≥ 18; intermediate to high risk of recurrence) groups (0.600 × 10-3 mm2/s vs. 0.746 × 10-3 mm2/s, p < 0.001). Multivariate regression analysis demonstrated that a lower ADC difference value (< 0.559 × 10-3 mm2/s; odds ratio [OR] = 5.998; p = 0.007) and a small tumor size (≤ 2 cm; OR = 3.866; p = 0.012) were associated with a low risk of recurrence after adjusting for clinicopathological factors. CONCLUSIONS: The ADC difference value derived from whole-lesion histogram analysis might serve as a quantitative DWI biomarker of the recurrence risk in women with ER-positive, HER2-negative, node-negative invasive breast cancer. KEY POINTS: ⢠A lower ADC difference value and a small tumor size were associated with a low risk of recurrence of breast cancer. ⢠The ADC difference value could be a quantitative marker for intratumoral heterogeneity. ⢠Whole-lesion histogram analysis of the ADC could be helpful for discriminating the low-risk from non-low-risk recurrence groups.
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Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Algoritmos , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Genes erbB-2 , Humanos , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Estudos Retrospectivos , Fatores de RiscoRESUMO
We measure the free energy of a model filament, which undergoes deformations and structural transitions, as a function of its extension, in silico. We perform Brownian Dynamics (BD) simulations of pulling experiments at various speeds, following a protocol close to experimental ones. The results from the fluctuation theorems are compared with the estimates from Monte Carlo (MC) simulation, where the rugged free energy landscape is produced by the density of states method. The fluctuation theorems (FT) give accurate estimates of the free energy up to moderate pulling speeds. At higher pulling speeds, the work distributions do not efficiently sample the domain of small work and FT slightly overestimates free energy. In order to comprehend the differences, we analyze the work distributions from the BD simulations in the framework of trajectory thermodynamics and propose the generalized fluctuation theorems that take into account the information (relative entropy) evaluated in the expanded phase space. The measured work - free energy relation is consistent with the results obtained from the generalized fluctuation theorems. We discuss operational methods to improve the estimates at high pulling speed.
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Left-handed Z-DNA is an extraordinary conformation of DNA, which can form by special sequences under specific biological, chemical or physical conditions. Human ADAR1, prototypic Z-DNA binding protein (ZBP), binds to Z-DNA with high affinity. Utilizing single-molecule FRET assays for Z-DNA forming sequences embedded in a long inactive DNA, we measure thermodynamic populations of ADAR1-bound DNA conformations in both GC and TG repeat sequences. Based on a statistical physics model, we determined quantitatively the affinities of ADAR1 to both Z-form and B-form of these sequences. We also reported what pathways it takes to induce the B-Z transition in those sequences. Due to the high junction energy, an intermediate B* state has to accumulate prior to the B-Z transition. Our study showing the stable B* state supports the active picture for the protein-induced B-Z transition that occurs under a physiological setting.
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Adenosina Desaminase/metabolismo , DNA de Forma B/química , DNA Forma Z/química , Proteínas de Ligação a RNA/metabolismo , DNA de Forma B/metabolismo , DNA Forma Z/metabolismo , Transferência Ressonante de Energia de Fluorescência , Modelos EstatísticosRESUMO
PURPOSE: We evaluated the detection rate and degree of motion artifact of the modified CAIPIRINHA-VIBE (mC-VIBE) without view-sharing and compare them with the CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE) with view-sharing on multi-arterial gadoxetic acid-enhanced liver MRI in the assessment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: We retrospectively identified 114 pathological-proven hepatic tumors in 114 patients with risk of HCC who underwent multi-arterial gadoxetic acid-enhanced MRI between June 2016 and June 2018. All patients underwent triple arterial phase imaging using the mC-VIBE without view-sharing (54 patients; 49 HCCs and 5 non-HCCs) or the CDT-VIBE with view-sharing (60 patients; 55 HCCs and 5 non-HCCs). We compared the detection rate of two sequences for HCC, with reference to LI-RADS.V.2017. We also compared the mean motion scores and proportions of transient severe motion (TSM) in two sequences. RESULT: For the examination using the mC-VIBE, the HCC-detection rate was significantly higher, compared with that using CDT-VIBE (93.9% [46/49] vs 80.0% [44/55], respectively; p = 0.047). For the examination with the mC-VIBE, mean motion scores were significantly lower compared with those of CDT-VIBE for all multi-arterial phases (1.21, 1.19, and 1.15 vs. 1.82, 1.85, and 1.84, respectively; p < 0.001 for all three comparisons). The proportion of TSM in the CDT-VIBE was significantly higher than that in the mC-VIBE (15.0% [9/60] vs 0.0% [0/54], respectively; p = 0.003). CONCLUSION: In multi-arterial phase gadoxetic acid-enhanced MRI, the mC-VIBE sequence without view-sharing has slightly higher HCC-detection rate and fewer motion artifacts compared with CDT-VIBE with view-sharing. KEY POINTS: ⢠Multi-arterial phase using the mC-VIBE without view-sharing can overcome motion artifacts, resulting in providing optimal arterial phase imaging. ⢠The HCC-detection rate is slightly higher with the mC-VIBE vs. CAIPIRINHA-Dixon-TWIST-VIBE with view-sharing (CDT-VIBE). ⢠View-sharing of CDT-VIBE in the multi-arterial phase is associated with increased frequency of TSM.
Assuntos
Artefatos , Carcinoma Hepatocelular/diagnóstico , Gadolínio DTPA/farmacologia , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Meios de Contraste/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate the value of the whole-lesion histogram apparent diffusion coefficient (ADC) metrics for differentiating low-risk from non-low-risk ductal carcinoma in situ (DCIS). METHODS: The authors identified 93 women with pure DCIS who had undergone preoperative MR imaging and diffusion-weighted imaging from 2013 to 2016. Histogram analysis of pixel-based ADC data of the whole tumour volume was performed by two radiologists using a software tool. The results were compared between low-risk and non-low-risk DCIS. Associations between quantitative ADC metrics and low-risk DCIS were evaluated by receiver operating characteristics (ROC) curve and logistic regression analyses. RESULTS: In whole-lesion histogram analysis, mean ADC and 5th, 50th and 95th percentiles of ADC were significantly different between low-risk and non-low-risk DCIS (1.522, 1.207, 1.536 and 1.854 × 10-3 mm2/s versus 1.270, 0.917, 1.261 and 1.657 × 10-3 mm2/s, respectively; p = .004, p = .003, p = .004 and p = .024, respectively). ROC curve analysis for differentiating low-risk DCIS revealed that 5th percentile ADC yielded the largest area under the curve (0.786) among the metrics of whole-lesion histogram, and the optimal cut-off point was 1.078 × 10-3 mm2/s (sensitivity 80%, specificity 75.9%, p = .001). Multivariate regression analysis revealed that a high 5th percentile of ADC (> 1.078× 10-3 mm2/s; odds ratio [OR] = 10.494, p = .016), small tumour size (≤ 2 cm; OR = 12.692, p = .008) and low Ki-67 status (< 14%; OR = 10.879, p = .046) were significantly associated with low-risk DCIS. CONCLUSIONS: Assessment with whole-lesion histogram analysis of the ADC could be helpful for identifying patients with low-risk DCIS. KEY POINTS: ⢠Whole-lesion histogram ADC metrics could be helpful for differentiating low-risk from non-low-risk DCIS. ⢠A high 5th percentile ADC was a significant factor associated with low-risk DCIS. ⢠Risk stratification of DCIS is important for their management.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Progressão da Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Sensibilidade e Especificidade , Carga Tumoral , Adulto JovemRESUMO
OBJECTIVE. The purpose of this study was to evaluate and compare the diagnostic performance and image quality of low-dose CT performed with adaptive statistical iterative reconstruction (ASIR)-V with those of routine-dose CT with filtered back projection (FBP) in the evaluation of abdominal organ injury. MATERIALS AND METHODS. The study enrolled 197 patients with trauma who underwent multiphase abdominal CT, including routine-dose portal venous phase imaging with FBP and low-dose delayed phase imaging with 50% ASIR-V. The presence of abdominal organ injuries (liver, spleen, pancreas, kidney) was reviewed, and injuries were graded according to American Association for the Surgery of Trauma (AAST) scales. CT detection rates of organ injury and AAST grading with the two protocols were compared by McNemar test. Subjective analysis of image noise and artifacts and objective analysis of CT noise were performed by unpaired t test. RESULTS. Compared with the routine-dose protocol, the low-dose protocol enabled an mean dose reduction of 59.8%. The detection rates and diagnostic performance of AAST grading did not differ significantly between the two protocols (detection rate, p = 0.289; diagnostic performance, p > 0.999). Objective image noise was significantly less with the low-dose protocol than with the routine-dose protocol (p < 0.001). Subjective imaging artifacts were similar between the low-dose and routine-dose protocols (p = 0.539). CONCLUSION. Compared with routine-dose protocol with FBP, low-dose CT with ASIR-V was useful for assessing multiorgan abdominal injury without impairing image quality.
Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Abdominal/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Estudos RetrospectivosRESUMO
We theoretically study dense polymer solutions under open (capillary and slit) and closed (box) confinement. The theory is formulated for grand-canonical polymers and corrections to the self-consistent mean-field results are discussed. In contrast to the mean-field prediction, we found that the partition function of a labeled chain is affected by confinement even under neutral von Neumann boundary conditions and the chain length distribution is biased to short chains. As the container size increases, the contribution of the transverse excited states to the free energy of a labeled chain is found to approach its bulk value nonmonotonically (through an extremum) for the box and the capillary confinement but not for the slit. So does the confinement free energy of a labeled chain. The confinement energy of the solution is well behaved for open confinement but formally diverges for a closed box in the limit that the average chain length goes to infinity. Counted per chain, the confinement energy of the dense solution is qualitatively weaker than for a single ideal chain under similarly strong confinement (by one power in transverse container size). The container boundary contributes a surface tension to the free energy, which makes the effective monomer-wall affinity more repulsive. This correction increases with the average chain length. If present, edge or vertex singularities also contribute to the grand potential of the solution.
RESUMO
In synthetic chemistry and biological or biomimetic systems, polymers are often grown in cavities. Polymerizations in microemulsions, biopolymers grown in cells, or in vesicles containing artificial organelles have an influence on the shape of liquid boundaries. We consider confined grand-canonical polymers to address equilibrium properties of annealed polymers. We calculate the concentration profiles established by annealed (star-) polymers inside a confining cavity. Our emphasis is on the description of pressure fields derived from the contact theorem. We further show how the pressure field exerted by a localized annealed polymer (or pair of polymers) deforms the confining vesicle/ microemulsions droplet.