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Objective@#It is difficult to predict the treatment response of tissue after stereotactic radiosurgery (SRS) because radiation necrosis (RN) and tumor recurrence can coexist. Our study aimed to predict tumor recurrence, including the recurrence site, after SRS of brain metastasis by performing a longitudinal tumor habitat analysis. @*Materials and Methods@#Two consecutive multiparametric MRI examinations were performed for 83 adults (mean age, 59.0 years; range, 27–82 years; 44 male and 39 female) with 103 SRS-treated brain metastases. Tumor habitats based on contrastenhanced T1- and T2-weighted images (structural habitats) and those based on the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) images (physiological habitats) were defined using k-means voxel-wise clustering. The reference standard was based on the pathology or Response Assessment in Neuro-Oncologycriteria for brain metastases (RANO-BM). The association between parameters of single-time or longitudinal tumor habitat and the time to recurrence and the site of recurrence were evaluated using the Cox proportional hazards regression analysis and Dice similarity coefficient, respectively. @*Results@#The mean interval between the two MRI examinations was 99 days. The longitudinal analysis showed that an increase in the hypovascular cellular habitat (low ADC and low CBV) was associated with the risk of recurrence (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.46–4.91; P = 0.001). During the single-time analysis, a solid low-enhancing habitat (low T2 and low contrast-enhanced T1 signal) was associated with the risk of recurrence (HR, 1.54; 95% CI, 1.01–2.35; P= 0.045). A hypovascular cellular habitat was indicative of the future recurrence site (Dice similarity coefficient = 0.423). @*Conclusion@#After SRS of brain metastases, an increased hypovascular cellular habitat observed using a longitudinal MRI analysis was associated with the risk of recurrence (i.e., treatment resistance) and was indicative of recurrence site. A tumor habitat analysis may help guide future treatments for patients with brain metastases.
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Objective@#Preoperative differential diagnosis of follicular-patterned lesions is challenging. This multicenter cohort study investigated the clinicoradiological characteristics relevant to the differential diagnosis of such lesions. @*Materials and Methods@#From June to September 2015, 4787 thyroid nodules (≥ 1.0 cm) with a final diagnosis of benign follicular nodule (BN, n = 4461), follicular adenoma (FA, n = 136), follicular carcinoma (FC, n = 62), or follicular variant of papillary thyroid carcinoma (FVPTC, n = 128) collected from 26 institutions were analyzed. The clinicoradiological characteristics of the lesions were compared among the different histological types using multivariable logistic regression analyses. The relative importance of the characteristics that distinguished histological types was determined using a random forest algorithm. @*Results@#Compared to BN (as the control group), the distinguishing features of follicular-patterned neoplasms (FA, FC, and FVPTC) were patient’s age (odds ratio [OR], 0.969 per 1-year increase), lesion diameter (OR, 1.054 per 1-mm increase), presence of solid composition (OR, 2.255), presence of hypoechogenicity (OR, 2.181), and presence of halo (OR, 1.761) (all p < 0.05). Compared to FA (as the control), FC differed with respect to lesion diameter (OR, 1.040 per 1-mm increase) and rim calcifications (OR, 17.054), while FVPTC differed with respect to patient age (OR, 0.966 per 1-year increase), lesion diameter (OR, 0.975 per 1-mm increase), macrocalcifications (OR, 3.647), and non-smooth margins (OR, 2.538) (all p < 0.05). The five important features for the differential diagnosis of follicular-patterned neoplasms (FA, FC, and FVPTC) from BN are maximal lesion diameter, composition, echogenicity, orientation, and patient’s age. The most important features distinguishing FC and FVPTC from FA are rim calcifications and macrocalcifications, respectively. @*Conclusion@#Although follicular-patterned lesions have overlapping clinical and radiological features, the distinguishing features identified in our large clinical cohort may provide valuable information for preoperative distinction between them and decision-making regarding their management.
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Purpose@#This study aimed to investigate the optimal threshold value in Hounsfield units (HU) on CT to detect the solid components of pulmonary subsolid nodules using pathologic invasive foci as reference. @*Materials and Methods@#Thin-section non-enhanced chest CT scans of 25 patients with pathologically confirmed minimally invasive adenocarcinoma were retrospectively reviewed. On CT images, the solid portion was defined as the area with higher attenuation than various HU thresholds ranging from -600 to -100 HU in 50-HU intervals. The solid portion was measured as the largest diameter on axial images and as the maximum diameter on multiplanar reconstruction images. A linear mixed model was used to evaluate bias in each threshold by using the pathological size of invasive foci as reference. @*Results@#At a threshold of -400 HU, the biases were lowest between the largest/maximum diameter of the solid portion of subsolid nodule and the size of invasive foci of the pathological specimen, with 0.388 and -0.0176, respectively. They showed insignificant difference (p = 0.2682, p = 0.963, respectively) at a threshold of -400 HU. @*Conclusion@#For quantitative analysis, -400 HU may be the optimal threshold to define the solid portion of subsolid nodules as a surrogate marker of invasive foci.
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Purpose@#Adenosine monophosphate-activated protein kinase (AMPK) is thought to inhibit cell proliferation or promote cell death, but the details remain unclear. In this study, we propose that AMPK inhibits the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) by relying on the hypoxia-inducible factor 1 alpha (HIF-1α)-induced caveolin-1 (Cav-1) expression pathway in noninvasive human bladder tumor (RT4) cells. @*Methods@#In cells exposed to a hypoxic environment (0.5% oxygen), the levels of expression and phospho-activity of the relevant signaling enzymes were examined via Western blots and reverse transcription-polymerase chain reaction. Cell proliferation was assessed using a Cell Counting Kit-8 assay. @*Results@#The level of expression of Cav-1 was very low or undetectable in RT4 cells. Hypoxia was associated with significantly decreased cell growth, along with marked induction of HIF-1α and Cav-1 expression; additionally, it suppressed the expression of the antiapoptotic marker Bcl-2 while leaving AMPK activity unchanged. Under hypoxic conditions, HIF-1α acts as a transcription factor for Cav-1 mRNA gene expression. The cell growth and Bcl-2 expression suppressed under hypoxia were reversed along with decreases in the induced HIF-1α and Cav-1 levels by AMPK activation with metformin (1mM) or phenformin (0.1mM). In addition, pretreatment with AMPK small interfering RNA not only increased the hypoxia-induced expression of HIF-1α and Cav-1, but also reversed the suppression of Bcl-2 expression. These results suggest that HIF-1α and Cav-1 expression in hypoxic environments is regulated by basal AMPK activity; therefore, the inhibition of Bcl-2 expression cannot be expected when AMPK activity is suppressed, even if Cav-1 expression is elevated. @*Conclusions@#For the first time, we find that AMPK activation can regulate HIF-1α induction as well as HIF-1α-induced Cav1 expression, and the hypoxia-induced inhibitory effect on the antiapoptotic pathway in RT4 cells is due to Cav-1-dependent AMPK activity.
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Purpose@#This study aimed to investigate the optimal threshold value in Hounsfield units (HU) on CT to detect the solid components of pulmonary subsolid nodules using pathologic invasive foci as reference. @*Materials and Methods@#Thin-section non-enhanced chest CT scans of 25 patients with pathologically confirmed minimally invasive adenocarcinoma were retrospectively reviewed. On CT images, the solid portion was defined as the area with higher attenuation than various HU thresholds ranging from -600 to -100 HU in 50-HU intervals. The solid portion was measured as the largest diameter on axial images and as the maximum diameter on multiplanar reconstruction images. A linear mixed model was used to evaluate bias in each threshold by using the pathological size of invasive foci as reference. @*Results@#At a threshold of -400 HU, the biases were lowest between the largest/maximum diameter of the solid portion of subsolid nodule and the size of invasive foci of the pathological specimen, with 0.388 and -0.0176, respectively. They showed insignificant difference (p = 0.2682, p = 0.963, respectively) at a threshold of -400 HU. @*Conclusion@#For quantitative analysis, -400 HU may be the optimal threshold to define the solid portion of subsolid nodules as a surrogate marker of invasive foci.
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Purpose@#Adenosine monophosphate-activated protein kinase (AMPK) is thought to inhibit cell proliferation or promote cell death, but the details remain unclear. In this study, we propose that AMPK inhibits the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) by relying on the hypoxia-inducible factor 1 alpha (HIF-1α)-induced caveolin-1 (Cav-1) expression pathway in noninvasive human bladder tumor (RT4) cells. @*Methods@#In cells exposed to a hypoxic environment (0.5% oxygen), the levels of expression and phospho-activity of the relevant signaling enzymes were examined via Western blots and reverse transcription-polymerase chain reaction. Cell proliferation was assessed using a Cell Counting Kit-8 assay. @*Results@#The level of expression of Cav-1 was very low or undetectable in RT4 cells. Hypoxia was associated with significantly decreased cell growth, along with marked induction of HIF-1α and Cav-1 expression; additionally, it suppressed the expression of the antiapoptotic marker Bcl-2 while leaving AMPK activity unchanged. Under hypoxic conditions, HIF-1α acts as a transcription factor for Cav-1 mRNA gene expression. The cell growth and Bcl-2 expression suppressed under hypoxia were reversed along with decreases in the induced HIF-1α and Cav-1 levels by AMPK activation with metformin (1mM) or phenformin (0.1mM). In addition, pretreatment with AMPK small interfering RNA not only increased the hypoxia-induced expression of HIF-1α and Cav-1, but also reversed the suppression of Bcl-2 expression. These results suggest that HIF-1α and Cav-1 expression in hypoxic environments is regulated by basal AMPK activity; therefore, the inhibition of Bcl-2 expression cannot be expected when AMPK activity is suppressed, even if Cav-1 expression is elevated. @*Conclusions@#For the first time, we find that AMPK activation can regulate HIF-1α induction as well as HIF-1α-induced Cav1 expression, and the hypoxia-induced inhibitory effect on the antiapoptotic pathway in RT4 cells is due to Cav-1-dependent AMPK activity.
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OBJECTIVE: To develop a diagnostic model for superficial soft tissue lesions to differentiate epidermal cyst (EC) from other lesions based on ultrasound (US) features. MATERIALS AND METHODS: This retrospective study included 205 patients who had undergone US examinations for superficial soft tissue lesions and subsequent surgical excision. The study population was divided into the derivation set (n = 112) and validation set (n = 93) according to the imaging date. The following US features were analyzed to determine those that could discriminate EC from other lesions: more-than-half-depth involvement of the dermal layer, “submarine sign” (focal projection of the hypoechoic portion to the epidermis), posterior acoustic enhancement, posterior wall enhancement, morphology, shape, echogenicity, vascularity, and perilesional fat change. Using multivariable logistic regression, a diagnostic model was constructed and visualized as a nomogram. The performance of the diagnostic model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curve and calibration plot in both the derivation and validation sets. RESULTS: More-than-half-depth involvement of the dermal layer (odds ratio [OR] = 3.35; p = 0.051), “submarine sign” (OR = 12.2; p < 0.001), and morphology (OR = 5.44; p = 0.002) were features that outweighed the others when diagnosing EC. The diagnostic model based on these features showed good discrimination ability in both the derivation set (AUC = 0.888, 95% confidence interval [95% CI] = 0.825–0.950) and validation set (AUC = 0.902, 95% CI = 0.832–0.972). CONCLUSION: More-than-half-depth of involvement of the dermal layer, “submarine sign,” and morphology are relatively better US features than the others for diagnosing EC.
Subject(s)
Humans , Acoustics , Calibration , Discrimination, Psychological , Epidermal Cyst , Logistic Models , Nomograms , Retrospective Studies , ROC Curve , UltrasonographyABSTRACT
We evaluated the association between sleep duration, dental caries, and periodontitis by using representative nationwide data. We examined 8,356 subjects aged ≥19 years who participated in the sixth Korea National Health and Nutrition Examination Survey (2013~2014). Sleep duration were grouped into ≤5, 6, 7, 8, and ≥9 hours. Presence of dental caries was defined as caries in ≥1 permanent tooth on dental examination. Periodontal status was assessed by using the community periodontal index (CPI), and a CPI code of ≥3 was defined as periodontitis. A chi-square test and multiple logistic regression analysis were used to determine statistical significance. Model 1 was adjusted for age and sex, model 2 for household income, educational level, and marital status plus model 1, and model 3 for smoking status, alcohol consumption, blood pressure level, fasting blood glucose level, total cholesterol level, and body mass index plus model 2. The prevalence of dental caries according to sleep duration showed a U-shaped curve of 33.4%, 29.4%, 28.4%, 29.4%, and 31.8% with ≤5, 6, 7, 8, and ≥9 hours of sleep, respectively. In the fully adjusted model 3, the risk of developing dental caries was significantly higher with ≤5 than with 7 hours of sleep (odds ratio, 1.23; 95% confidence interval, 1.06~1.43). The prevalence of periodontitis according to sleep duration showed a U-shaped curve of 34.4%, 28.6%, 28.1%, 31.3%, and 32.5%, respectively. The risk of periodontitis was significantly higher with ≥9 than with 7 hours of sleep in models 1 and 2, whereas the significant association disappeared in model 3. In a nationally representative sample, sleep duration was significantly associated with dental caries formation and weakly associated with periodontitis. Adequate sleep is required to prevent oral diseases such as dental caries and periodontitis.
Subject(s)
Adult , Humans , Alcohol Drinking , Blood Glucose , Blood Pressure , Body Mass Index , Cholesterol , Dental Caries , Family Characteristics , Fasting , Health Surveys , Korea , Logistic Models , Marital Status , Nutrition Surveys , Periodontal Index , Periodontitis , Prevalence , Smoke , Smoking , ToothABSTRACT
Generally, both lipopolysaccharide (LPS)- and hypoxia-induced nuclear factor kappa B (NF-κB) effects are alleviated through differential posttranslational modification of NF-κB phosphorylation after pretreatment with 5'-AMP-activated protein kinase (AMPK) activators such as 5'-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or the hypoglycemic agent metformin. We found that AICAR or metformin acts as a regulator of LPS/NF-κB-or hypoxia/NF-κB-mediated cyclooxygenase induction by an AMPK-dependent mechanism with interactions between p65-NF-κB phosphorylation and acetylation, including in a human bladder cancer cell line (T24). In summary, we highlighted the regulatory interactions of AMPK activity on NF-κB induction, particularly in posttranslational phosphorylation and acetylation of NF-κB under inflammatory conditions or hypoxia environment.