Adjuvant Chemotherapy in Patients with Locally Advanced Upper Tract Urothelial Carcinoma with or without Kidney Transplantation.

Background: The incidence of upper tract urothelial carcinoma (UTUC) is uniquely high in kidney transplant (KT) recipients in Taiwan. The evidence of adjuvant chemotherapy (AC) in UTUC is contradictory. We have sought to determine whether AC is associated with potential benefits related to locally advanced UTUC after KT. Methods: We retrospectively analyzed 134 patients with locally advanced UTUC (at least stage T2) and patients who were administrated AC after unilateral or bilateral nephroureterectomy with bladder cuff excision. Of these 134 patients, 57 patients fulfilled our inclusion criteria. We used 23 KT and 34 non-KT locally advanced UTUC patients for comparison. Results: The mean follow-up time was 52.35 ± 34.56 and 64.71 ± 42.29 months for the KT and non-KT groups, respectively. The five-year disease-free survival (DFS) and overall survival (OS) rates were 45.7% vs. 70.2% and 62.8% vs. 77.6%, for the KT and non-KT groups. The Kaplan-Meier curve and the log rank test revealed significant differences in the DFS and OS rates between the two groups, p = 0.015 and 0.036. The influence of chemotherapy on graft kidney function was mild. Only three in the KT group and two in the non-KT group developed > grade 2 nephrotoxicity. Conclusions: Our study suggested that KT patients with locally advanced UTUC who had been administered AC after surgery presented worse OS and DFS than non-KT patients. KT patients tolerated the AC course well, and their nephrotoxicity levels were mild and acceptable.

Effect of iodized oil embolization on temperature change during cryoablation for renal cell carcinoma.

INTRODUCTION: We aimed to evaluate the effect of transcatheter arterial embolization (TAE) with iodized oil (Lipiodol) on temperature change during cryoablation (CA) for renal cell carcinoma (RCC). MATERIAL AND METHODS: We retrospectively reviewed patients receiving CA for RCC from February 2020 to July 2021, including those who received Lipiodol TAE prior to CA (TAE group) and those who underwent only CA with comparable clinical and tumor characteristics (non-TAE group). Clinical data and tumor characteristics of both groups were recorded. The temperature readings of each cryoprobe at every 15 s and 'time to -100 °C' were compared between the groups. RESULTS: A total of 17 patients with 18 RCCs were recruited (seven in the TAE group and 11 in the non-TAE group). The 'time to -100 °C' was significantly longer in the TAE group than in the non-TAE group (64.5 ± 24.3 s vs. 48.8 ± 9.7 s, p = 0.018). Positive correlation between 'time to -100 °C' and tumor maximal diameter, RENAL nephrometry and PADUA score were observed in the non-TAE group, while no corresponding correlation was found in the TAE group. CONCLUSIONS: Pre-embolization with iodized oil influences the temporal temperature changes during cryoablation by disrupting the positive correlation between the time to reach the target temperature and tumor characteristics.

Feasibility estimation of injected hydrodissection before definitive radiotherapy of pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however, no study has discussed which patients are suitable for the procedure. METHODS: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk. RESULTS: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for 1 patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images. CONCLUSION: Our results suggested that about half of the patients could have benefited from hydrodissection before radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control.

Single-Cell Transcriptomics Reveals Cellular Heterogeneity and Complex Cell-Cell Communication Networks in the Mouse Cornea.

Purpose: To generate a single-cell RNA-sequencing (scRNA-seq) map and construct cell-cell communication networks of mouse corneas. Methods: C57BL/6 mouse corneas were dissociated to single cells and subjected to scRNA-seq. Cell populations were clustered and annotated for bioinformatic analysis using the R package "Seurat." Differential expression patterns were validated and spatially mapped with whole-mount immunofluorescence staining. Global intercellular signaling networks were constructed using CellChat. Results: Unbiased clustering of scRNA-seq transcriptomes of 14,732 cells from 40 corneas revealed 17 cell clusters of six major cell types: nine epithelial cell, three keratocyte, two corneal endothelial cell, and one each of immune cell, vascular endothelial cell, and fibroblast clusters. The nine epithelial cell subtypes included quiescent limbal stem cells, transit-amplifying cells, and differentiated cells from corneas and two minor conjunctival epithelial clusters. CellChat analysis provided an atlas of the complex intercellular signaling communications among all cell types. Conclusions: We constructed a complete single-cell transcriptomic map and the complex signaling cross-talk among all cell types of the cornea, which can be used as a foundation atlas for further research on the cornea. This study also deepens the understanding of the cellular heterogeneity and heterotypic cell-cell interaction within corneas.

Ectopic ATP synthase stimulates the secretion of extracellular vesicles in cancer cells.

ABSTARCT: Ectopic ATP synthase on the plasma membrane (eATP synthase) has been found in various cancer types and is a potential target for cancer therapy. However, whether it provides a functional role in tumor progression remains unclear. Here, quantitative proteomics reveals that cancer cells under starvation stress express higher eATP synthase and enhance the production of extracellular vesicles (EVs), which are vital regulators within the tumor microenvironment. Further results show that eATP synthase generates extracellular ATP to stimulate EV secretion by enhancing P2X7 receptor-triggered Ca2+ influx. Surprisingly, eATP synthase is also located on the surface of tumor-secreted EVs. The EVs-surface eATP synthase increases the uptake of tumor-secreted EVs in Jurkat T-cells via association with Fyn, a plasma membrane protein found in immune cells. The eATP synthase-coated EVs uptake subsequently represses the proliferation and cytokine secretion of Jurkat T-cells. This study clarifies the role of eATP synthase on EV secretion and its influence on immune cells.

Lockdown period during SARS COVID-19 endemic outbreak in Taiwan did not cause an increase of the complications nor mortality of patients received endoscopic retrograde cholangiopancreatography: A single-center retrospective study.

BACKGROUND: Coronavirus disease 2019, known as a widespread, aerosol spreading disease, has affected >549 000 000 people since 2019. During the lockdown period, dramatic reduction of elective endoscopic procedures, including endoscopic retrograde cholangiopancreatography, had been reported worldwide, leading to delayed diagnosis and treatment. Nevertheless, whether patients' hospital stays and complication rate of endoscopic retrograde cholangiopancreatography (ERCP) during the lockdown period were influenced by the pandemic still remains controversial. METHODS: Patients who diagnosed with obstructive jaundice and acute cholangitis in the lockdown period, May 16 to July 26, 2021, were compared to the same prepandemic period in 2019. RESULTS: A total of 204 patients in 2019 and 168 patients in 2021 were diagnosed with acute biliary cholangitis or obstructive jaundice, and 82 of the patients in 2019 and 77 patients in 2021 underwent ERCP ( p = 0.274). Patients whose quick Sequential Organ Failure Assessment (qSOFA) score was ≥ 2 occurred more during the lockdown period than during the normal period (24/77, 31.1% vs 12/82, 14.6%; p = 0.013). The initial laboratory data, including, total bilirubin (4.12 in 2021 vs 3.08 mg/dL in 2019; p = 0.014), gamma-glutamyl transferase (378 in 2021 vs 261 U/L in 2019; p = 0.009), and alkaline phosphatase (254 in 2021 vs 174 U/L in 2019; p = 0.002) were higher during the lockdown period compared to 2019. Hospital stay was statistically significant longer in the lockdown period (11 days [7.00-22.00] in 2021 vs 8 days in 2019 [6.00-12.00]; p value = 0.02). Multivariate analysis showed that qSOFA ≥ 2 (hazard ratio [HR] = 3.837, 95% confidence interval [CI] = 1.471-10.003; p = 0.006), and malignant etiology (HR = 2.932, 95% CI = 1.271-6.765; p = 0.012) were the statistically significant factors for a prolonged hospital stay, which was defined as hospital stay >21 days. ERCP-related complications and mortality rate were not statistically different between the two periods. CONCLUSION: Patients from May 16 to July 26, 2021, the lockdown period, had longer hospital stays and higher biliary tract enzyme levels, which indicated more severe disease. Nevertheless, ERCP could be safely and successfully performed even during the medical level 3 alert lockdown period without causing an increase in procedure-related complications and mortality.

First-Pass Arrival Interval of Ultrasound Contrast Medium in the Hepatic Artery and Portal Vein as a Marker for Assessment of Liver Transplant Recipients.

BACKGROUND: This study measures the first-pass arrival times in the hepatic artery and portal vein of the transplanted liver using contrast-enhanced ultrasound (CEUS) and assess its correlation with graft performance in the early posttransplant period. METHODS: This study evaluated 35 liver transplant recipients who underwent CEUS examination within 1 month of transplant surgery. CEUS under contrast-specific harmonic imaging mode were recorded for 60 seconds immediately after intravenous administration of microbubble ultrasound contrast medium (Sonazoid, GE Healthcare, Oslo, Norway). The recorded video clips were reviewed by 2 readers to determine the first-pass arrival times in the hepatic artery and portal vein, and the difference between the 2 was defined as the arterial-portal arrival interval (APAI). Laboratory data on the same date of CEUS examination were collected as indicators to correlate with APAI. RESULTS: The intra- and inter-rater reliability for APAI measurement were excellent, with intraclass correlation coefficients > .95. The mean APAI was 4.5 ± 1.8 seconds (range, 2.0-10.5 seconds). The APAI was positively correlated with the serum total bilirubin level (r = 0.357, P = .035) and negatively correlated with the platelet count (r = -0.354, P = .037). At the 5 second cutoff point, a total serum bilirubin of >8 mg/dL was reported in 5 of 11 patients (45.4%) with APAI of >5 seconds and in only 3 of 24 patients (12.5%) with APAI of <5 seconds (P < .05). CONCLUSIONS: The APAI is a quantitative marker that links the hemodynamics and the clinical status of the liver graft.

Trends of Testicular Cancer Mortality-to-Incidence Ratios in Relation to Health Expenditure: An Ecological Study of 54 Countries.

Favorable testicular cancer mortality-to-incidence ratios (MIRs) are associated with health care disparities, including health care expenditures, but the trends of testicular MIR and health care disparity remain unclear. We evaluated changes in MIR as the difference between 2012 and 2018, termed delta MIR (δMIR). Health care expenditures and the human development index (HDI) were obtained from the World Health Organization and the Human Development Report Office of the United Nations Development Programme. The association between the variables was analyzed by Spearman's rank correlation coefficient. A total of 54 countries were included in the criteria of data quality reports and missing data. By continent, the most favorable MIR was in Oceania (0.03) while it was 0.36 in Africa. In these areas, the incidence rates were positively correlated to health care expenditure, but the mortality rates showed a reversed correlation. The MIR ranged from 0.01 to 0.34 and the δMIR ranged from -0.05 to 0.34. The favorable MIRs are correlated to high health care expenditure and HDI (all p < 0.001). Interestingly, favorable δMIRs tend to be seen in countries with relatively low health care expenditure and HDI (all p < 0.001). In conclusion, favorable testicular cancer MIRs are associated with high HDI and health care expenditure, but the improvement in MIR between 2012 and 2018 (δMIR) is negatively correlated with HDI and health care expenditure.

The RNA degradation pathway is involved in PPARα-modulated anti-oral tumorigenesis.

BACKGROUND: The activation of peroxisome proliferator-activated receptor alpha (PPARα) has been shown to reprogram tumor metabolism and exhibits great potential for treating anti-oral tumorigenesis. METHODS: In this study, we used a pathway-based strategy to explore possible functional pathways involved in the anticancer activity of PPARα in oral cancer cells through next-generation sequencing (NGS) and bioinformatic approaches. RESULTS: We found that 3919 genes were upregulated and 1060 genes were downregulated through PPARα activation. These genes were mainly involved in the proteasomal, mRNA surveillance, spliceosomal, RNA transport, and RNA degradation pathways, as indicated by GO and KEGG enrichment analysis. Importantly, a total of 13 upregulated genes in the RNA degradation pathway were identified including 3 core exosome factor genes (RRP43, RRP42, and CSL4), 2 TRAMP complex genes (TRF4 and Mtr4), 2 exosome cofactor genes (RRP6 and MPP6), 2 CCR4-NOT complex genes (CNOT2 and CNOT3), 2 Ski complex genes (SKI2 and Ski3), 1 decapping complex gene (EDC4), and 1 gene involved in 5' exoribonuclease activity (XRN1). CONCLUSION: Our findings suggest that the activation of PPARα to upregulate the RNA degradation pathway might provide a new strategy for oral cancer treatment.

Peroxisome proliferator-activated receptor alpha accelerates neuronal differentiation and this might involve the mitogen-activated protein kinase pathway.

Activation of peroxisome proliferator-activated receptor alpha (PPARα) has been reported to modulate cell proliferation, migration, and differentiation in astrocytes. In this study, we used a retinoic acid (RA)-induced differentiation model of NTERA-2/clone D1 (NT2) cells to explore the functional significance of PPARα in neuronal differentiation. We found that activating PPARα by Wy14643 accelerated neuronal differentiation via regulating the expression of neuronal markers. RT-PCR assays showed a significant increase in NeuroD expression and a decrease in nestin expression in cells treated concomitantly with RA and Wy14643 for 2 days compared to the levels in cells treated with RA alone. Expression of MAP2 protein, a mature neuronal marker, was markedly upregulated at day 10 of Wy14643 treatment, which was maintained after 21 days of neuronal formation. Corresponding to the changes in MAP2 expression, the expression of Cdk5 was upregulated with Wy14643 exposure from day 10 to day 21. Moreover, cells treated with Wy14643 displayed higher expression levels of phospho-ERK and phospho-p38 in the differentiation process than cell treated with RA alone. These results indicated that activation of PPARα accelerated neuronal differentiation through upregulating the expression of NeuroD, MAP2, and Cdk5 and downregulating the expression of nestin. MAPK signals, ERK and p38, might contribute to the accelerated differentiation process. These findings suggest that PPARα plays a role in regulating neuronal differentiation and may be beneficial for functional recovery from neurological disorders.

Proteomic analysis of oral cancer reveals new potential therapeutic targets involved in the Warburg effect.

Activation of peroxisome proliferator-activated receptor alpha (PPARα) has been reported to disrupt tumour metabolism and to promote anticancer activity through interfering with the Warburg effect. This study is to investigate whether Warburg effect-related proteins also could be identified in oral tumour lesions and to explore the functional significance of PPARα in metabolic shift. Five pairs of tongue tumour tissues and adjacent reference tissues obtained from 4-NQO/arecoline induced mouse model were analyzed by 2-d-gel-electrophoresis and LC-MS. Further, the hexokinase II level, pyruvate dehydrogenase (PDH) activity, and metabolites of glycolysis and TCA cycle were all examined in order to validate the effect of PPARα on metabolic shift. Changes in protein expression levels revealed that seven proteins, which were involved in glycolysis, the tricarboxylic acid cycle, and the respiratory chain, were down-regulated in tumour tissues. We found that activation of PPARα through fenofibrate could inhibit oral cancer cell growth and switch the way of energy production from the Warburg effect to oxidative phosphorylation. Fenofibrate induced a reduction of hexokinase II protein levels, increases in PDH activity and metabolites of the TCA cycle, and an impairment of ATP production. These findings suggested that activation of the PPARα to reprogram the metabolic pathway might impair the Warburg effect and trigger cancer cell death. The study provides a novel view of changes in protein expression profiles involved in the Warburg effect during oral tumourigenesis. Activation of the PPARα to impair the Warburg effect might offer a new strategy for oral cancer treatment.

Biomarker identification of hepatocellular carcinoma using a methodical literature mining strategy.

Hepatocellular carcinoma (HCC), one of the most common causes of cancer-related deaths, carries a 5-year survival rate of 18%, underscoring the need for robust biomarkers. In spite of the increased availability of HCC related literatures, many of the promising biomarkers reported have not been validated for clinical use. To narrow down the wide range of possible biomarkers for further clinical validation, bioinformaticians need to sort them out using information provided in published works. Biomedical text mining is an automated way to obtain information of interest within the massive collection of biomedical knowledge, thus enabling extraction of data for biomarkers associated with certain diseases. This method can significantly reduce both the time and effort spent on studying important maladies such as liver diseases. Herein, we report a text mining-aided curation pipeline to identify potential biomarkers for liver cancer. The curation pipeline integrates PubMed E-Utilities to collect abstracts from PubMed and recognize several types of named entities by machine learning-based and pattern-based methods. Genes/proteins from evidential sentences were classified as candidate biomarkers using a convolutional neural network. Lastly, extracted biomarkers were ranked depending on several criteria, such as the frequency of keywords and articles and the journal impact factor, and then integrated into a meaningful list for bioinformaticians. Based on the developed pipeline, we constructed MarkerHub, which contains 2128 candidate biomarkers extracted from PubMed publications from 2008 to 2017. Database URL: http://markerhub.iis.sinica.edu.tw.

Fenofibrate Suppresses Oral Tumorigenesis via Reprogramming Metabolic Processes: Potential Drug Repurposing for Oral Cancer.

One anticancer strategy suggests targeting mitochondrial metabolism to trigger cell death through slowing down energy production from the Warburg effect. Fenofibrate is a clinical lipid-lowering agent and an effective anticancer drug. In the present study, we demonstrate that fenofibrate provided novel mechanisms for delaying oral tumor development via the reprogramming of metabolic processes. Fenofibrate induced cytotoxicity by decreasing oxygen consumption rate (OCR) that was accompanied with increasing extracellular acidification rate (ECAR) and reducing ATP content. Moreover, fenofibrate caused changes in the protein expressions of hexokinase II (HK II), pyruvate kinase, pyruvate dehydrogenase, and voltage-dependent anion channel (VDAC), which are associated with the Warburg effect. In addition, fenofibrate reprogrammed the metabolic pathway by interrupting the binding of HK II to VDAC. In an oral cancer mouse model, fenofibrate exhibited both preventive and therapeutic efficacy on oral tumorigenesis. Fenofibrate administration suppressed the incidence rate of tongue lesions, reduced the tumor sizes, decreased the tumor multiplicity, and decreased the immunoreactivities of VDAC and mTOR. The molecular mechanisms involved in fenofibrate's ability to delay tumor development included the down-regulation of mTOR activity via TSC1/2-dependent signaling through activation of AMPK and inactivation of Akt, or via a TSC1/2-independent pathway through direct suppression of raptor. Our findings provide a molecular rationale whereby fenofibrate exerts anticancer and additional beneficial effects for the treatment of oral cancer patients.

PPARα modulates gene expression profiles of mitochondrial energy metabolism in oral tumorigenesis.

Metabolic reprogramming plays a crucial role in the development of cancer. The aim of this study was to explore the effect of fenofibrate, an agonist of peroxisome proliferator-activated receptor alpha (PPARα), on gene expression profiles of mitochondrial energy metabolism. Our results showed that PPARα expression was negatively correlated with tumor progression in an oral cancer mouse model. Activation of PPARα through fenofibrate suppressed migration of oral cancer cells. Differential protein profiling demonstrated that expressions of genes related to mitochondrial energy metabolism were either up-regulated (Atp5g3, Cyc1, Ndufa5, Ndufa10, and Sdhd) or down-regulated (Cox5b, Ndufa1, Ndufb7, and Uqcrh) through PPARα activation and response. Our results indicate that PPARα exhibits a great potential for anti-oral cancer therapies by modulating cancer cell mitochondrial energy metabolism.

AMPK-dependent signaling modulates the suppression of invasion and migration by fenofibrate in CAL 27 oral cancer cells through NF-κB pathway.

Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist and lipid-lowering agent, has been used worldwide for treatment of hyperlipidemia. The clinical trials demonstrate that fenofibrate possesses multiple pharmacological activities, including antitumor effects. However, the precise mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we investigated the anticancer effects of fenofibrate on the migration and invasion of human oral cancer CAL 27 cells. Fenofibrate inhibited the cell migration and invasion of CAL 27 cells by the wound healing and Boyden chamber transwell assays, respectively. In addition, fenofibrate reduced the protein expressions of MMP-1, MMP-2, MMP-7, and MMP-9 by Western blotting and inhibited enzyme activities of MMP-2/-9 using gelatin zymography assay. Results from immunoblotting analysis showed that the proteins of p-LKB1 (Ser428), LKB1, p-AMPKα (Thr172), p-AMPKα1/α2 (Ser425/Ser491), p-AMPKß1 (Ser108), and AMPKγ1 were upregulated by fenofibrate; the levels of p-IKKα/ß (Ser176) and p-IκBα were reduced in fenofibrate-treated cells. Also, fenofibrate suppressed the expressions of nuclear NF-κB p65 and p50 by immunoblotting and NF-κB DNA binding activity by EMSA assay. The anti-invasive effect of fenofibrate was attenuated by compound C [an adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor] or dominant negative form of AMPK (DN-AMPKα1). Thus, fenofibrate considerably inhibited metastatic behaviors of CAL 27 cells might be mediated through blocking NF-κB signaling, resulting in the inhibition of MMPs; these effects were AMPK-dependent rather than PPARα signaling. Our findings provide a molecular rationale, whereby fenofibrate exerts anticancer effects and additional beneficial effects for the treatment of cancer patients. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 866-876, 2016.

miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database.

MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.

A context-aware approach for progression tracking of medical concepts in electronic medical records.

Electronic medical records (EMRs) for diabetic patients contain information about heart disease risk factors such as high blood pressure, cholesterol levels, and smoking status. Discovering the described risk factors and tracking their progression over time may support medical personnel in making clinical decisions, as well as facilitate data modeling and biomedical research. Such highly patient-specific knowledge is essential to driving the advancement of evidence-based practice, and can also help improve personalized medicine and care. One general approach for tracking the progression of diseases and their risk factors described in EMRs is to first recognize all temporal expressions, and then assign each of them to the nearest target medical concept. However, this method may not always provide the correct associations. In light of this, this work introduces a context-aware approach to assign the time attributes of the recognized risk factors by reconstructing contexts that contain more reliable temporal expressions. The evaluation results on the i2b2 test set demonstrate the efficacy of the proposed approach, which achieved an F-score of 0.897. To boost the approach's ability to process unstructured clinical text and to allow for the reproduction of the demonstrated results, a set of developed .NET libraries used to develop the system is available at https://sites.google.com/site/hongjiedai/projects/nttmuclinicalnet.

Coronary artery disease risk assessment from unstructured electronic health records using text mining.

Coronary artery disease (CAD) often leads to myocardial infarction, which may be fatal. Risk factors can be used to predict CAD, which may subsequently lead to prevention or early intervention. Patient data such as co-morbidities, medication history, social history and family history are required to determine the risk factors for a disease. However, risk factor data are usually embedded in unstructured clinical narratives if the data is not collected specifically for risk assessment purposes. Clinical text mining can be used to extract data related to risk factors from unstructured clinical notes. This study presents methods to extract Framingham risk factors from unstructured electronic health records using clinical text mining and to calculate 10-year coronary artery disease risk scores in a cohort of diabetic patients. We developed a rule-based system to extract risk factors: age, gender, total cholesterol, HDL-C, blood pressure, diabetes history and smoking history. The results showed that the output from the text mining system was reliable, but there was a significant amount of missing data to calculate the Framingham risk score. A systematic approach for understanding missing data was followed by implementation of imputation strategies. An analysis of the 10-year Framingham risk scores for coronary artery disease in this cohort has shown that the majority of the diabetic patients are at moderate risk of CAD.

The effect of gender on health-related quality of life and related factors in post-lobectomy lung-cancer patients.

PURPOSE: While studies have documented gender differences by histologic type among lung cancer patients, the effect of these differences on the health-related quality of life (HRQoL) of post-lobectomy lungcancer patients and related factors remain uncertain. This study examines gender-specific HRQoL and related factors in post-lobectomy lung-cancer patients. METHODS: A cross-sectional study design was applied. A convenience sample of 231 post-lobectomy lungcancer patients was recruited from the thoracic surgery outpatient departments of two teaching hospitals in Taipei, Taiwan from March to December 2012. Patients performed a spirometry test and completed instruments that included a Beck Depression Inventory-II, an Interpersonal Support Evaluation List, and the symptom and function scales of the Quality of Life Questionnaire. Data analysis used descriptive statistics, including mean and standard deviations, frequency, and percentage values. Independent-sample Student's t-tests and multivariate analyses were used for comparative purposes. RESULTS: This study confirmed a significant gender effect on HRQoL and HRQoL-related factors such as marital status, religious affiliation, smoking status, histologic type, symptoms, pulmonary function, depression, and family support. Moreover, multivariate analysis found gender to be a significant determinant of the HRQoL aspects of physical functioning, emotional functioning, and cognitive functioning. Finally, results indicated that factors other than gender were also significant determinants of HRQoL. CONCLUSION: Gender impacts the HRQoL and related factors of postoperative lung-cancer patients. Therefore, gender should be considered in assessing and addressing the individual care needs of these patients in order to attain optimal treatment outcomes.

PPARα activation attenuates amyloid-ß-dependent neurodegeneration by modulating Endo G and AIF translocation.

The accumulation of a large amount of amyloid-ß (Aß42) in brain neurons is one of the debilitating characteristics of Alzheimer's disease. In this study, we determined the effects of peroxisome proliferator-activated receptor alpha (PPARα) activation on neuronal degeneration using a model of Aß42-induced cytotoxicity. We found that 0.5 µM Aß42 induced DNA damage and apoptosis in NT2N cells after 6 h of treatment. Co-treatment of Aß42-treated cells with Wy14643, a PPARα ligand, significantly increased cell viability after 24 h compared with cells treated with Aß42 alone. There were no differences in the protein levels of caspase-3, Bcl-2/Bax or p53 between cells treated with Aß42 alone and those treated with both Aß42 and Wy14643. However, the addition of Wy14643 significantly suppressed the Aß42-induced upregulation of Endo G and AIF protein levels. Immunohistochemical analyses further demonstrated that Wy14643 reduced the expression of Endo G and AIF translocated from the cytoplasm into the nucleus, which occurred concomitantly with the decrease in DNA damage in Aß42-treated cells. Our data clearly show that PPARα activation prevents DNA damage and neuronal cell apoptosis by decreasing the expression and translocation of AIF/Endo G to the nucleus in a caspase-3- and p53-independent pathway in the NT2N cell model. This role of PPARα in promoting neuron survival suggests a possible clinical application in treating Aß42-associated neurotoxicity in Alzheimer's disease.