Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For ...localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.
A correct differentiation between hepatocellular carcinoma (HCC) and intracellular cholangiocarcinoma (ICC) is essential for clinical management and prognostic prediction. However, non-invasive ...differential diagnosis between HCC and ICC remains highly challenging. Dynamic contrast-enhanced ultrasound (D-CEUS) with standardized software is a valuable tool in the diagnostic approach to focal liver lesions and could improve accuracy in the evaluation of tumor perfusion. Moreover, the measurement of tissue stiffness could add more information concerning tumoral environment. To explore the diagnostic performance of multiparametric ultrasound (MP-US) in differentiating ICC from HCC. Our secondary aim was to develop an US score for distinguishing ICC and HCC. Between January 2021 and September 2022 consecutive patients with histologically confirmed HCC and ICC were enrolled in this prospective monocentric study. A complete US evaluation including B mode, D-CEUS and shear wave elastography (SWE) was performed in all patients and the corresponding features were compared between the tumor entities. For better inter-individual comparability, the blood volume-related D-CEUS parameters were analyzed as a ratio between lesions and surrounding liver parenchyma. Univariate and multivariate regression analysis was performed to select the most useful independent variables for the differential diagnosis between HCC and ICC and to establish an US score for non-invasive diagnosis. Finally, the diagnostic performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis. A total of 82 patients (mean age ± SD, 68 ± 11 years, 55 men) were enrolled, including 44 ICC and 38 HCC. No statistically significant differences in basal US features were found between HCC and ICC. Concerning D-CEUS, blood volume parameters (peak intensity, PE; area under the curve, AUC; and wash-in rate, WiR) showed significantly higher values in the HCC group, but PE was the only independent feature associated with HCC diagnosis at multivariate analysis (
= 0.02). The other two independent predictors of histological diagnosis were liver cirrhosis (
< 0.01) and SWE (
= 0.01). A score based on those variables was highly accurate for the differential diagnosis of primary liver tumors, with an area under the ROC curve of 0.836 and the optimal cut-off values of 0.81 and 0.20 to rule in or rule out ICC respectively. MP-US seems to be a useful tool for non-invasive discrimination between ICC and HCC and could prevent the need for liver biopsy at least in a subgroup of patients.
Repeatable tumor measurements are key to accurately assessing tumor growth and treatment efficacy. A preliminary study that we conducted showed that a novel 3D and thermal imaging system (3D-TI) for ...measuring subcutaneous tumors in rodents significantly reduced interoperator variability across 3 in vivo efficacy studies. Here we further studied this reduction in interoperator variability across a much larger dataset. A dataset consisting of 6,532 paired 3D-TI and caliper interoperator measurements was obtained from tumor scans and measurements in 27 laboratories across 289 studies, 153 operators, over 20 mouse strains, and 100 cell lines. Interoperator variability in both measurement methods was analyzed using coefficient of variation (CV), intraclass correlation (ICC) analysis, and significance testing. The median 3D-TI CV was significantly lower than the median caliper CV. The effects of large interoperator variability at critical points in the study were also investigated. At stratified randomization, changing the operator performing caliper measurements resulted in a 59% probability that a mouse would be reassigned to a different group. The probability that this would occur when using 3D-TI was significantly lower at 29%. In studies in which a tumor was expected to regress, changing the operator during the study was associated with a tumor volume increase of approximately 500mm3 when using calipers. This change did not occur when using 3D-TI. We conclude that 3D-TI significantly reduces interoperator variability as compared with calipers and can improve reproducibility of in vivo studies across a wide range of mouse strains and cell lines.
To investigate the size and morphology of the temporomandibular joint (TMJ) articular disc and condyle in young asymptomatic adults by using magnetic resonance imaging (MRI) and to provide a ...reference for clinical diagnosis and scientific study of temporomandibular disorders (TMD).
Overall, 93 undergraduate volunteers without TMD were enrolled from the freshmen pool at the Qingdao University. All participants underwent MRI of the oblique sagittal and oblique coronal TMJ planes. The articular disc and condyle were subsequently measured, and their morphology was evaluated. The obtained data were then grouped and analyzed statistically. Finally, intragroup correlation coefficient (ICC) was used to evaluate the interobserver measurement reliability.
We totally received 186 TMJ imaging samples. Based on our analysis, disc's anterior band in young asymptomatic adult females were thicker than males of the same age (
= 0.024). Moreover, the media-lateral dimensions of the condylar head of adult females were shorter than males of equal age (
＜0.001). The bilateral articular disc morphology was the same in 72.4% of subjects while the condylar morphology was the same in 63.4% of participants. Finally, using measurement reliability assessment, we demonstrated that our conclusions are reliable (ICC ≥0.7).
The thickness of the anterior band of the disc and the media-lateral dimensions of the condylar head were gender-related. Additionally, the morphology of the bilateral articular disc and condyle was different among the subset of young asymptomatic adults.
•Mutations in the ROC, COR and Kinase domain of LRRK2 alter the autophagic response to starvation.•LC3-I/II ratio following starvation is altered by mutations, as well as p62 and WIPI2 positive ...puncta.•This occurs independently of any alteration in downstream targets of mTORC1.
LRRK2 is one of the most important genetic contributors to Parkinson’s disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consistently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using a combination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal function compared to wild type cells. These data highlight the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations.
The Davos Assessment of Cognitive Biases Scale (DACOBS) is widely used to assess cognitive biases in patients who have schizophrenia. However, the lack of a modified Chinese-language version of the ...DACOBS (MCL-DACOBS) precludes Chinese schizophrenic patients from treatment aimed at normalizing cognitive biases, impacting their prognosis. Here, we aimed to produce a DACOBS for China and test the validity and reliability of the resultant MCL-DACOBS.
Eighteen researchers collaborated to develop the MCL-DACOBS: A total of 15 researchers modified and translated the English version of the DACOBS, 1 native-English-speaking researcher back-translated the scale, and 2 Chinese sinologists localized and optimized the language of the MCL-DACOBS. Forty-two volunteers checked the scale items' comprehensibility, and the two sinologists performed further localization and optimization based on their feedback. The final version of the MCL-DACOBS used in this study was thus derived from the harmonized English-language version of the scale. Confirmatory factor analyses (CFAs) were used to examine the best latent structure of the MCL-DACOBS. Cronbach's α and intraclass correlation coefficients (ICCs) were used to check the reliability. The discriminative ability of the MCL-DACOBS was assessed according to the area under the receiver operating characteristic curve.
The CFA showed that all items loaded onto factors with loadings >0.400. A two-factor structure showed a good model fit (root mean square error of approximation = .018, Tucker-Lewis index = .978, comparative fit index = .984). Promax rotation demonstrated that each item had a high factor load (0.432-0.774). Cronbach's α coefficient and ICC for the MCL-DOCABS were .965 and .957, respectively, indicating that the scale has ideal reliability.
The MCL-DACOBS has good validity and good reliability, and its psychometric properties indicate that it is a valid tool for measuring cognitive biases in Chinese patients with schizophrenia.
Besides their application in point and shoot cameras, webcams, and cell phones, it has been shown that CMOS image sensors (CIS) can be used for dosimetry, X-ray and neutron imaging applications. In ...this work we will discuss the application of an ON Semiconductor MT9M001 CIS, in low energy X-ray spectroscopy. The device is a monochromatic front-side illuminated sensor, very popular in consumer electronics. In this work we introduce the configuration selected for the mentioned sensor, the image processing techniques and event selection criteria, implemented in order to measure the X-ray energy in the range from 1 to 10 keV. Several fluorescence lines of different samples have been resolved, and for first time the line resolution have been measured and analyzed. We achieved a FWHM of 232 eV at 6.4 keV, and we concluded that incomplete charge collection (ICC) of the charge produced by the X-ray contributes to the resolution, being this effect more important at higher X-ray energies. The results analyzed in this work indicate that the mentioned CIS are specially suitable for X-ray applications in which energy and spatial resolutions are simultaneously required.
To evaluate the results of 18F-FDG PET/MRI in relation to the histopathologic subtypes and histologic grades of mass-forming primary intrahepatic neoplasms.
We retrospectively evaluated 18F-FDG ...positron emission tomography/magnetic resonance imaging (PET/MRI) results for 39 patients with histopathologically confirmed primary hepatic neoplasms, 15 with mass-forming intrahepatic cholangiocarcinoma (ICC) and 24 with hepatocellular carcinoma (HCC). The apparent diffusion coefficient (ADC) and standardized uptake value (SUV) were analyzed in relation to the histopathologic diagnosis and histologic grade, including calculating the sensitivity and specificity of the imaging findings.
The median SUV of ICC (6.0 interquartile range, 5-10) was significantly higher than that of HCC (4.0 2.62-6.50) (p = 0.002). An area under the curve (AUC) of 0.79 (95% confidence interval 0.649-0.932) had a sensitivity of 86.7% and a specificity of 67% at the best cut-off SUV of 4.41 to differentiate between ICC and HCC. ADC values did not differ significantly between HCCs and ICCs (p = 0.283). Both SUV and ADC values differed significantly between low-grade (well- and moderately differentiated) and high-grade (poorly differentiated) HCCs. Combining ADC and SUV further improved differentiation of low- from high-grade HCCs to a significant level (0.929). The SUV did not differ significantly between ICC histologic grades (p = 0.280), while the ADC differed significantly only between well and poorly differentiated ICCs (p = 0.004).
Assessing primary hepatic neoplasms with 18F-Fluorodeoxyglucose PET/MRI may help to predict tumor grade and differentiate between types of intrahepatic neoplasms.
Heat shock protein B8 (HSPB8) has been recently discovered to be participated in the regulation of tumor progression. However, the function of HSPB8 in intrahepatic cholangiocarcinoma (ICC) has not ...yet been elucidated. This study studied the function of HSPB8 in ICC progression.
ICC patients (n = 150) were enrolled. The relationship between clinicopathological characteristics and HSPB8 expression was analyzed. RBE cells were transfected and treated by 3-MA. The RBE cells morphology was observed under a transmission electron microscope. Cell counting kit-8 assay, wound healing assay and Transwell experiment was conducted to detect RBE cells proliferation, migration and invasion. Quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, Western blot and immunofluorescence were used for genes detection in clinical tissues and RBE cells.
HSPB8 was up-regulated in ICC tissues than that in adjacent normal tissues. High HSPB8 expression in ICC indicated poor prognosis of patients. HSPB8 expression was mainly expressed in cell cytoplasm and aberrantly increased in RBE cells (P < 0.01). HSPB8 up-regulation promoted RBE cells proliferation, migration and invasion (P < 0.05). HSPB8 down-regulation reduced RBE cells proliferation, migration and invasion (P < 0.01). HSPB8 overexpression facilitated Vimentin expression, LC3-II/LC3-I ratio and inhibited E-cadherin, p62 expression in RBE cells (P < 0.05). Treatment of 3-MA partially reversed HSPB8 promotion on RBE cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) (P < 0.05 or P < 0.01).
HSPB8 promoted ICC progression by enhancing EMT and autophagy. HSPB8 might be an effective target for ICC treatment.
•High HSPB8 expression in ICC patients was associated with poor prognosis.•HSPB8 promoted ICC cells migration and invasion abilities.•HSPB8 facilitated epithelial-mesenchymal transition in ICC cells.•HSPB8 induced autophagy in ICC cells.•Autophagy inhibition partially reversed HSPB8 promotion on ICC progression.
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