Material decomposition using dual-energy CT with unsupervised learning.

Material decomposition (MD) is an application of dual-energy computed tomography (DECT) that decomposes DECT images into specific material images. However, the direct inversion method used in MD often amplifies noise in the decomposed material images, resulting in lower image quality. To address this issue, we propose an image-domain MD method based on the concept of deep image prior (DIP). DIP is an unsupervised learning method that can perform different tasks without using a large training dataset with known targets (i.e., basis material images). We retrospectively recruited patients who underwent non-contrast brain DECT scans and investigated the feasibility of using the proposed DIP-based method to decompose DECT images into two (i.e., bone and soft tissue) and three (i.e., bone, soft tissue, and fat) basis materials. We evaluated the decomposed material images in terms of signal-to-noise ratio (SNR) and modulation transfer function (MTF). The proposed DIP-based method showed greater improvement in SNR in the decomposed soft-tissue images compared to the direct inversion method and the iterative method. Moreover, the proposed method produced similar MTF curves in both two- and three-material decompositions. Additionally, the proposed DIP-based method demonstrated better separation ability than the other two studied methods in the case of three-material decomposition. Our results suggest that the proposed DIP-based method is capable of unsupervisedly generating high-quality basis material images from DECT images.

Prevalence and predictors of advance directive among terminally ill patients in Taiwan before enactment of Patient Right to Autonomy Act: a nationwide population-based study.

BACKGROUND: Signing advance directives (ADs) ensures that terminally ill patients receive end-of-life care, according to their wishes, thereby promoting human dignity and sparing them from unnecessary suffering. Despite the enactment of the Hospice Palliative Care Act in Taiwan in 2000, the completion rates of ADs have been found to be low among patients with chronic illness conditions. To date, limited existing research is available regarding the factors associated with AD completion in terminally ill patients in Taiwan. To explore signed AD characteristics, compare differences in signing ADs between patients with and without cancer, and examine the factors associated with signing ADs in terminally ill patients. METHODS: A nationwide study was conducted using data collected via a retrospective review of medical death records from 18 randomly selected hospitals in the northern, central, and southern parts of Taiwan. We collected 200 records, including both cancer and non-cancer-related deaths, from each hospital. Univariate and multivariate logistics regressions were conducted to examine factors associated with signing advance directives among all patients- with and without cancer. RESULTS: Among the 3004 reviewed medical records, 79% had signed ADs, with most (95%) being signed by patients' caregivers. A higher education level (OR = 1.52, 95% CI = 1.10, 2.08, p = 0.010); cancer diagnosis (OR = 2.37, 95% CI = 1.79, 3.16, p < 0.001); having family members (OR = 5.62, 95% CI = 2.95, 10.69, p < 0.001), care homes (OR = 4.52, 95% CI = 1.97, 10.38, p < 0.001), friends, or maids (OR = 3.82, 95% CI = 1.76, 8.29, p = 0.001) as primary caregivers; and patients knowing about their poor prognosis (OR = 15.39, 95% CI = 5.66, 41.83, p < 0.001) were associated with a higher likelihood of signing ADs. CONCLUSIONS: Patients with non-malignant chronic illnesses were less likely to have ADs signed by either patients or family caregivers than those with cancer, with the lowest likelihood observed in patients with cardiovascular diseases. Whenever possible, primary caregivers should be involved in discussing ADs with patients, and the importance of truth telling should be reinforced. Following these principles, each patient's end-of-life care preferences can be respected, thereby promoting quality of care before the patient's death.

AKR1B1-Induced Epithelial-Mesenchymal Transition Mediated by RAGE-Oxidative Stress in Diabetic Cataract Lens.

PURPOSE: Cataracts are a major cause of visual acuity deterioration in diabetes mellitus (DM) in developed and developing countries. Studies have demonstrated that overproduction of AKR1B1 and receptor for advanced glycation end products (RAGE) plays a major role in the pathogenesis of diabetic cataracts, but it is unclear whether the prevalence of diabetic cataracts is related to epithelial-mesenchymal transition (EMT) in lens epithelial cells. This study aimed to analyze the role of EMT in cataract formation of DM patients. METHODS: Immunofluorescence and immunohistochemistry assays were used to estimate AKR1B1, RAGE, AMPK, and EMT levels in epithelial human lens of DM or non-DM cataracts. RESULTS: Immunohistochemical staining demonstrated that pathologic phases and N-cadherin expression levels were significantly higher in epithelial human lens of DM (+) compared to DM (-) cataracts. Immunofluorescent staining showed that AKR1B1 and RAGE were significantly higher in epithelial human lens of DM (+) compared to DM (-) cataracts. Interestingly, acetyl superoxide dismutase 2 (AcSOD2) levels were significantly higher in DM patients' lens epithelial cells (LECs), whereas AMPKT172 phosphorylation was significantly increased in non-DM patients. This indicates that AMPKT172 might be related to superoxide reduction and diabetic cataract formation. CONCLUSIONS: Our results suggest that AKR1B1 overexpression can decrease AMPK activation, thereby increasing AcSOD2 and RAGE-induced EMT in epithelial human lens of DM cataracts. These novel findings suggest that AKR inhibitors may be candidates for the pharmacological prevention of cataracts in patients with DM.

High snail expression predicts a poor prognosis in breast invasive ductal carcinoma patients with HER2/EGFR-positive subtypes.

BACKGROUND: High Snail expression is known as a poor prognostic factor in breast cancer. However, its prognostic impact for breast cancer with different molecular subtypes is still controversial. METHODS: Snail expression was examined by immunohistochemistry in tissue microarray slides of 85 corresponding tumor-adjacent normal (CTAN) and 247 breast invasive ductal carcinoma (IDC) tissues. Multivariable Cox regression analysis was used to assess the impact of Snail expression on survival rate by different molecular subtypes of breast IDC patients. RESULTS: The level of Snail expression in IDC tumor tissues was significantly higher than that in CTAN tissues. Moreover, high Snail expression had direct impacts on poor disease specific survival (DSS) and disease-free survival (DFS) in breast IDC patients with human epidermal growth factor receptor 2 (HER2)-positive and human epidermal growth factor receptor (EGFR)-positive statuses as well as the HER2 intrinsic subtype. Additionally, breast IDC patients with a combination of three prognostic factors, including high Snail expression and HER2-positive and EGFR-positive statuses, had much poor DSS and DFS with a statistically significant linear trend. CONCLUSION: High Snail expression could predict a poor prognosis for breast IDC patients with HER2/EGFR-positive subtypes.

Isocitrate dehydrogenase 1-snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability.

BACKGROUND: The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. METHODS: In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion. RESULTS: The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast cancer. CONCLUSION: Our findings revealed that a IDH1low/Snailhigh molecular signature could serve as an independent biomarker for poor prognosis in breast cancer.

Reduction of global 5-hydroxymethylcytosine is a poor prognostic factor in breast cancer patients, especially for an ER/PR-negative subtype.

DNA methylation at the 5 position of cytosine (5 mC) is an epigenetic hallmark in cancer. The 5 mC can be converted to 5-hydroxymethylcytosine (5 hmC) through a ten-eleven-translocation (TET). We investigated the impact of 5 mC, 5 hmC, TET1, and TET2 on tumorigenesis and prognosis of breast cancer. Immunohistochemistry was used to assess the levels of 5 mC, 5 hmC, TET1, and TET2 in the corresponding tumor adjacent normal (n = 309), ductal carcinoma in situ (DCIS, n = 120), and invasive ductal carcinoma (IDC, n = 309) tissues for 309 breast ductal carcinoma patients. 5 mC, 5 hmC, TET1-n, and TET2-n were significantly decreased during DCIS and IDC progression. In IDC, the decrease of 5 hmC was correlated with the cytoplasmic mislocalization of TET1 (p < 0.001) as well as poor disease-specific survival (DSS) (adjusted hazard ratio [AHR] 1.95, p = 0.003) and disease-free survival (DFS) (AHR 1.91, p = 0.006). The combined decrease of 5 mC and 5 hmC was correlated with worse DSS (AHR 2.19, p = 0.008) and DFS (AHR 1.99, p = 0.036). Stratification analysis revealed that the low level of 5 mC was associated with poor DSS (AHR 1.89, p = 0.044) and DFS (AHR 2.02, p = 0.035) for the ER/PR-positive subtype. Conversely, the low level of 5 hmC was associated with worse DSS (AHR 2.77, p = 0.002) and DFS (AHR 2.69, p = 0.006) for the ER/PR-negative subtype. The decreases of 5 mC, 5 hmC, TET1-n, and TET2-n were biomarkers of tumor development. The global reduction of 5 hmC was a poor prognostic factor for IDC, especially for ER/PR-negative subtype.

A rare case of metachronous triple cancers involving the tympanic membrane.

Multiple primary malignancies are not rare. While metachronous triple cancers are rare and a triple tumor case involving maxillary sinus and tympanic membrane is exceptionally rare. We present such an extremely rare case with the index tumor of adenoid cystic carcinoma of the maxillary sinus and 14 years later esophageal cancer was observed as a metachronous tumor. One year after esophageal cancer, squamous cell carcinoma arising from tympanic membrane was detected. Before the tumor of tympanic membrane was observed, the patient had received total three radiation courses. Prior radiation therapy is suspected to be playing a role in inducing the squamous cell carcinoma of the tympanic membrane.

Developing a web 2.0 diabetes care support system with evaluation from care provider perspectives.

Diabetes is a life-long illness condition that many diabetic patients end up with related complications resulted largely from lacking of proper supports. The success of diabetes care relies mainly on patient's daily self-care activities and care providers' continuous support. However, the self-care activities are socially bounded with patient's everyday schedules that can easily be forgotten or neglected and the care support from providers has yet been fully implemented. This study develops a Web 2.0 diabetes care support system for patients to integrate required self-care activities with different context in order to enhance patient's care knowledge and behavior adherence. The system also supports care managers in a health service center to conduct patient management through collecting patient's daily physiological information, sharing care information, and maintaining patient-provider relationships. After the development, we evaluate the acceptance of the system through a group of nursing staffs.

[Construction of the method for quantitative detection of epidermal growth factor receptor variant III by real-time polymerase chain reaction with TaqMan probe and its application].

OBJECTIVE: To construct the recombinant plasmid and standard curve for detection of epidermal growth factor receptor variant III (EGFRv III) by real-time quantitive polymerase chain reaction (PCR) and establish the RT-PCR assay for accurate detection of EGFRv III. METHODS: To amplify the DNA sequences of exon 1 and exon 8 to exon 9 of EGFR separately and fuse the above sequences by overhang extension PCR. Then constructing the recombinant plasmid of EGFRv III by highly specific primers with the fused sequence as its template. The recombinant plasmid of EGFRv III was then sent for sequence analysis. The gradient diluted recombinant plasmid were used as the template to amplify the EGFRv III by RT-PCR with TaqMan probe and then applied it in 32 laryngeal carcinoma tissues. RESULTS: The recombinant plasmid of EGFRv III was successfully constructed. The gradient diluted recombinant plasmid could be used in RT-PCR for quantitative analysis of EGFRv III. In all, 5 tumor samples expressing EGFRv III were detected, with its positive rate of about 15.6%. The expression of EGFRv III was tumor specific with only one exception for extraordinarily low expression of EGFRv III in macroscopically normal laryngeal mucosas adjacent to the tumor. CONCLUSIONS: RT-PCR with TaqMan probe was good at sensitivity, specificity, quantification and linear function. It can be a standard method for quantitative detection for EGFRv III. Expression of EGFRv III was detected in laryngeal carcinoma tissues with relatively low level. Whether EGFRv III was a suitable target for biological therapy in laryngeal carcinomas remained to be discussed.