Assessment of Narrow-Band Imaging Algorithm for Video Capsule Endoscopy Based on Decorrelated Color Space for Esophageal Cancer: Part II, Detection and Classification of Esophageal Cancer.

Esophageal carcinoma (EC) is a prominent contributor to cancer-related mortality since it lacks discernible features in its first phases. Multiple studies have shown that narrow-band imaging (NBI) has superior accuracy, sensitivity, and specificity in detecting EC compared to white light imaging (WLI). Thus, this study innovatively employs a color space linked to décor to transform WLIs into NBIs, offering a novel approach to enhance the detection capabilities of EC in its early stages. In this study a total of 3415 WLI along with the corresponding 3415 simulated NBI images were used for analysis combined with the YOLOv5 algorithm to train the WLI images and the NBI images individually showcasing the adaptability of advanced object detection techniques in the context of medical image analysis. The evaluation of the model's performance was based on the produced confusion matrix and five key metrics: precision, recall, specificity, accuracy, and F1-score of the trained model. The model underwent training to accurately identify three specific manifestations of EC, namely dysplasia, squamous cell carcinoma (SCC), and polyps demonstrates a nuanced and targeted analysis, addressing diverse aspects of EC pathology for a more comprehensive understanding. The NBI model effectively enhanced both its recall and accuracy rates in detecting dysplasia cancer, a pre-cancerous stage that might improve the overall five-year survival rate. Conversely, the SCC category decreased its accuracy and recall rate, although the NBI and WLI models performed similarly in recognizing the polyp. The NBI model demonstrated an accuracy of 0.60, 0.81, and 0.66 in the dysplasia, SCC, and polyp categories, respectively. Additionally, it attained a recall rate of 0.40, 0.73, and 0.76 in the same categories. The WLI model demonstrated an accuracy of 0.56, 0.99, and 0.65 in the dysplasia, SCC, and polyp categories, respectively. Additionally, it obtained a recall rate of 0.39, 0.86, and 0.78 in the same categories, respectively. The limited number of training photos is the reason for the suboptimal performance of the NBI model which can be improved by increasing the dataset.

Assessment of Narrow Band Imaging Algorithm for Video Capsule Endoscopy Based on Decorrelated Color Space for Esophageal Cancer.

Video capsule endoscopy (VCE) is increasingly used to decrease discomfort among patients owing to its small size. However, VCE has a major drawback of not having narrow band imaging (NBI) functionality. The current VCE has the traditional white light imaging (WLI) only, which has poor performance in the computer-aided detection (CAD) of different types of cancer compared to NBI. Specific cancers, such as esophageal cancer (EC), do not exhibit any early biomarkers, making their early detection difficult. In most cases, the symptoms are unnoticeable, and EC is diagnosed only in later stages, making its 5-year survival rate below 20% on average. NBI filters provide particular wavelengths that increase the contrast and enhance certain features of the mucosa, thereby enabling early identification of EC. However, VCE does not have a slot for NBI functionality because its size cannot be increased. Hence, NBI image conversion from WLI can presently only be achieved in post-processing. In this study, a complete arithmetic assessment of the decorrelated color space was conducted to generate NBI images from WLI images for VCE of the esophagus. Three parameters, structural similarity index metric (SSIM), entropy, and peak-signal-to-noise ratio (PSNR), were used to assess the simulated NBI images. Results show the good performance of the NBI image reproduction method with SSIM, entropy difference, and PSNR values of 93.215%, 4.360, and 28.064 dB, respectively.

Assessment of Brown and Beige Adipose Tissue Activation in Mice Using PET/CT Imaging.

In response to cold induction, brown adipose tissues (BAT) and emerged brown-like adipocytes (beige adipocytes) in subcutaneous white adipose tissues (WAT browning/beiging) are activated. Thermogenesis is increased during glucose and fatty acid uptake and metabolism in adult humans and mice. This activation of BAT or WAT beiging to generate heat helps to counteract diet-induced obesity. This protocol applies the glucose analog radiotracer 18F-fluorodeoxyglucose (FDG), coupled with positron emission tomography and computed tomography (PET/CT) scanning to evaluate cold-induced thermogenesis in the active BAT (interscapular region) and browned/beiged WAT (subcutaneous adipose region) in mice. The PET/CT scanning technique not only can quantify cold-induced glucose uptake in well-known BAT and beige-fat depots but also helps to visualize the anatomical location of novel uncharacterized mouse BAT and beige fat where cold-induced glucose uptake is high. Histological analysis is further employed to validate signals of delineated anatomical regions in PET/CT images as bona fide mouse BAT or beiged WAT fat depots.

Dosimetric delivery validation of dynamically collimated pencil beam scanning proton therapy.

Objective. Pencil beam scanning (PBS) proton therapy target dose conformity can be improved with energy layer-specific collimation. One such collimator is the dynamic collimation system (DCS), which consists of four nickel trimmer blades that intercept the scanning beam as it approaches the lateral extent of the target. While the dosimetric benefits of the DCS have been demonstrated through computational treatment planning studies, there has yet to be experimental verification of these benefits for composite multi-energy layer fields. The objective of this work is to dosimetrically characterize and experimentally validate the delivery of dynamically collimated proton therapy with the DCS equipped to a clinical PBS system.Approach. Optimized single field, uniform dose treatment plans for 3 × 3 × 3 cm3target volumes were generated using Monte Carlo dose calculations with depths ranging from 5 to 15 cm, trimmer-to-surface distances ranging from 5 to 18.15 cm, with and without a 4 cm thick polyethylene range shifter. Treatment plans were then delivered to a water phantom using a prototype DCS and an IBA dedicated nozzle system and measured with a Zebra multilayer ionization chamber, a MatriXX PT ionization chamber array, and Gafchromic™ EBT3 film.Main results. For measurements made within the SOBPs, average 2D gamma pass rates exceeded 98.5% for the MatriXX PT and 96.5% for film at the 2%/2 mm criterion across all measured uncollimated and collimated plans, respectively. For verification of the penumbra width reduction with collimation, film agreed with Monte Carlo with differences within 0.3 mm on average compared to 0.9 mm for the MatriXX PT.Significance. We have experimentally verified the delivery of DCS-collimated fields using a clinical PBS system and commonly available dosimeters and have also identified potential weaknesses for dosimeters subject to steep dose gradients.

One-Year Healthcare Utilization and Expenditures Among Patients with Clinically Significant Mitral Regurgitation in Taiwan.

INTRODUCTION: Mitral regurgitation (MR) is characterized by systolic blood flow reversal from the left ventricle to the left atrium. A 2019 study indicated that in the USA, clinically significant MR (sMR) is associated with a substantial healthcare cost burden. In Taiwan, few data are available to describe the clinical characteristics, treatment patterns, and economic burden of patients with sMR. METHODS: Using the National Health Insurance Research Database (NHIRD), a national, detailed claims database of all 23 million residents of Taiwan, we conducted a retrospective cohort study to identify patients with sMR and quantify the impact of the disease on Taiwan's healthcare system. We classified patients with sMR into three cohorts based on disease etiology: functional MR (sFMR), degenerative MR (sDMR), and uncharacterized MR (sUMR). RESULTS: We compared patient characteristics across cohorts and estimated attributable healthcare utilization and costs during the 12-month follow-up period. Our research shows that in Taiwan, patients with sFMR were older, sicker, and presented at casualty (emergency department) more frequently than those with sDMR and sUMR. Meanwhile, patients with sDMR had the highest 12-month healthcare expenditures across the cohorts. CONCLUSION: These findings are inconsistent with what has been shown in the USA, which warrants further investigation.

The Predictability of the Surgical Outcomes of Class III Patients in the Transverse Dimension-A Study of Three-Dimensional Assessment.

This study aimed to assess the outcomes of planned maxillary surgical movements in the transverse direction in patients possessing a Class III skeletal pattern. The available consecutive patients' records were retrospectively reviewed. Only those possessing a Class III skeletal pattern, and for whom the same virtual planning system was used, were enrolled. The waferless technique was used to guide the jawbone repositioning. A representative triangle in the virtual maxilla of each stage was used to validate the planned surgical movements (PSMs) and the outcome discrepancy (OD). The linear and angular measurements were retrieved for the assessments of the correlation between PSM and OD. In total, 44 adult patients who met the inclusion criteria were studied. The average linear OD of the A-point in the transverse direction was 0.66 ± 0.54 mm, and the yaw correction showed 1.02 ± 0.84 degrees in difference. There was no specific correlation between the linear PSMs and ODs; however, the angular ones were positively correlated. With the help of the waferless technique to transfer the virtual planning results, the practitioners could confidently predict the postsurgical maxillary position in the transverse direction in the orthognathic surgery of Class III patients. However, the yaw correction should be carefully planned to avoid postsurgical instabilities.

Low cost multifunctional 3D printed image quality and dose verification phantom for an image-guided radiotherapy system.

PURPOSE: Image-guided radiation therapy (IGRT) is used to precisely deliver radiation to a tumour to reduce the possible damage to the surrounding normal tissues. Clinics use various quality assurance (QA) equipment to ensure that the performance of the IGRT system meets the international standards set for the system. The objective of this study was to develop a low-cost and multipurpose module for evaluating image quality and dose. METHODS: A multipurpose phantom was designed to meet the clinical requirements of high accuracy, easy setup, and calibration. The outer shell of the phantom was fabricated using acrylic. Three dimensional (3D) printing technology was used to fabricate inner slabs with the characteristics of high spatial resolution, low-contrast detectability, a 3D grid, and liquid-filled uniformity. All materials were compatible with magnetic resonance (MR). Computed tomography (CT) simulator and linear accelerator (LINAC) modules were developed and validated. RESULTS: The uniformity slab filled with water is ideal for the assessment of Hounsfield units, whereas that filled with wax is suitable for consistency checks. The high-spatial-resolution slab enables measurements with a resolution up to 5 lp/cm. The low-contrast detectability slab contains rods of 5 different sizes that can be clearly visualised. These components meet the American College of Radiology (ACR) standards for QA of CT simulators and LINACs. CONCLUSIONS: The multifunctional phantom module meets the ACR recommended QA guidelines and is suitable for both LINACs and CT-sim. Further measurements in an MR simulator and an MR linear accelerator (MR-LINAC) will be arranged in the future.

The dosimetric enhancement of GRID profiles using an external collimator in pencil beam scanning proton therapy.

PURPOSE: The radiobiological benefits afforded by spatially fractionated (GRID) radiation therapy pairs well with the dosimetric advantages of proton therapy. Inspired by the emergence of energy-layer specific collimators in pencil beam scanning (PBS), this work investigates how the spot spacing and collimation can be optimized to maximize the therapeutic gains of a GRID treatment while demonstrating the integration of a dynamic collimation system (DCS) within a commercial beamline to deliver GRID treatments and experimentally benchmark Monte Carlo calculation methods. METHODS: GRID profiles were experimentally benchmarked using a clinical DCS prototype that was mounted to the nozzle of the IBA-dedicated nozzle system. Integral depth dose (IDD) curves and lateral profiles were measured for uncollimated and GRID-collimated beamlets. A library of collimated GRID dose distributions were simulated by placing beamlets within a specified uniform grid and weighting the beamlets to achieve a volume-averaged tumor cell survival equivalent to an open field delivery. The healthy tissue sparing afforded by the GRID distribution was then estimated across a range of spot spacings and collimation widths, which were later optimized based on the radiosensitivity of the tumor cell line and the nominal spot size of the PBS system. This was accomplished by using validated models of the IBA universal and dedicated nozzles. RESULTS: Excellent agreement was observed between the measured and simulated profiles. The IDDs matched above 98.7% when analyzed using a 1%/1-mm gamma criterion with some minor deviation observed near the Bragg peak for higher beamlet energies. Lateral profile distributions predicted using Monte Carlo methods agreed well with the measured profiles; a gamma passing rate of 95% or higher was observed for all in-depth profiles examined using a 3%/2-mm criteria. Additional collimation was shown to improve PBS GRID treatments by sharpening the lateral penumbra of the beamlets but creates a trade-off between enhancing the valley-to-peak ratio of the GRID delivery and the dose-volume effect. The optimal collimation width and spot spacing changed as a function of the tumor cell radiosensitivity, dose, and spot size. In general, a spot spacing below 2.0 cm with a collimation less than 1.0 cm provided a superior dose distribution among the specific cases studied. CONCLUSIONS: The ability to customize a GRID dose distribution using different collimation sizes and spot spacings is a useful advantage, especially to maximize the overall therapeutic benefit. In this regard, the capabilities of the DCS, and perhaps alternative dynamic collimators, can be used to enhance GRID treatments. Physical dose models calculated using Monte Carlo methods were experimentally benchmarked in water and were found to accurately predict the respective dose distributions of uncollimated and DCS-collimated GRID profiles.

Analysis of the Necrosis-Inducing Components of the Venom of Naja atra and Assessment of the Neutralization Ability of Freeze-Dried Antivenom.

Patients bitten by Naja atra who are treated with bivalent freeze-dried neurotoxic antivenom in Taiwan have an improved survival rate but develop necrotic wound changes. The World Health Organization (WHO) has suggested using the minimum necrotizing dose (MND) of venom as a method of evaluating the neutralization effect of antivenom. The aim of this study was to evaluate the effectiveness of antivenom for the prevention of necrosis based on the MND and clarify which component of the venom of N. atra induces necrosis. The neurotoxins (NTXs) were removed from the crude venom (deNTXs), and different concentrations of deNTXs were injected intradermally into the dorsal skin of mice. After three days, the necrotic lesion diameter was found to be approximately 5 mm, and the MND was calculated. A reduction in the necrotic diameter of 50% was used to identify the MND50. Furthermore, both phospholipase A2 (PLA2) and cytotoxins (CTXs) were separately removed from the deNTXs to identify the major necrosis-inducing factor, and the necrotic lesions were scored. All mice injected with deNTXs survived for three days and developed necrotic wounds. The MND of the deNTXs for mice was 0.494 ± 0.029 µg/g, that of the deNTXs-dePLA2 (major component retained: CTXs) was 0.294 ± 0.05 µg/g, and that of the deNTX-deCTX (major component retained: PLA2) venom was greater than 1.25 µg/g. These values show that CTX is the major factor inducing necrosis. These results suggest that the use of the deNTXs is necessary to enable the mice to survive long enough to develop venom-induced cytolytic effects. CTXs play a major role in N. atra-related necrosis. However, the MND50 could not be identified in this study, which meant that the antivenom did not neutralize venom-induced necrosis.

In Vitro Toxicological Assessment of Gadodiamide in Normal Brain SVG P12 Cells.

BACKGROUND/AIM: Magnetic resonance imaging (MRI) is a technique for evaluating patients with primary and metastatic tumors. The contrast agents improve the diagnostic accuracy of MRI. Large quantities of a contrast agent must be administrated into the patient to obtain useful images, which leads to cell injury. Gadolinium has been reported to cause central lobular necrosis of the liver and nephrogenic systemic fibrosis. However, the toxicity caused on brain tissue is uncertain. MATERIALS AND METHODS: This study mainly aimed on the in vitro study of high concentration (2 and 5-fold of normal concentration) gadolinium-based contrast agents (GBCAs), gadodiamide (Omniscan®), on normal brain glial SVG P12 cells. MTT assay, DAPI staining, immunofluorescent staining, LysoTracker Red staining, and western blotting analysis were applied on the cells. RESULTS: The viability of gadodiamide (1.3, 2.6, 5.2, 13 and 26 mM)-treated SVG P12 cells was significantly reduced after 24 h of incubation. Gadodiamide caused significant autophagic flux at 2.6, 5.2 and 13.0 mM as seen by acridine orange (AO) staining, LC-3-GFP and LysoTracker Red staining. The expression levels of autophagy-related proteins such as beclin-1, ATG-5, ATG-14 and LC-3 II were up-regulated after 24 h of gadodiamide incubation. Autophagy inhibitors including 3-methyladenine (3-MA), chloroquine (CQ) and bafilomycin A1 (Baf) significantly alleviated the autophagic cell death effect of gadodiamide on normal brain glial SVG P12 cells. Gadodiamide induced significant apoptotic effects at 5.2 mM and 13.0 mM as seen by DAPI staining and the pan-caspase inhibitor significantly alleviated the apoptotic effect. Gadodiamide at 5.2 mM and 13.0 mM inhibited antiapoptotic protein expression levels of Bcl-2 and Bcl-XL, while promoted pro-apoptotic protein expression levels of Bax, BAD, cytochrome c, Apaf-1, cleaved-caspase-9 and cleaved-caspase-3. CONCLUSION: Normal brain glial SVG P12 cells treated with high concentrations of gadodiamide can undergo autophagy and apoptosis.

Hospital Board of Directors' Composition and Financial Performance: Empirical Evidence from Taiwan.

The board of directors of a nonprofit proprietary hospital is responsible for supervising and managing major operational matters and reviewing operational results. This study investigates how hospital financial performance is influenced by director and supervisor characteristics among the board members of nonprofit proprietary hospitals in Taiwan. Data were obtained from the Division of Medical Services of the Ministry of Health and Welfare. A generalized linear model was used to evaluate 32 non-profit proprietary hospitals for the years 2006 to 2017, totaling 363 observations. The empirical results revealed a significant positive correlation between the proportion of directors with management qualifications and hospital financial performance. Moreover, the results represented that a higher proportion of board members with a medical background did not correspond to higher hospital financial performance. Although doctors accounted for the highest proportion of board members, indicating their key role in hospital management, the need for board members with management expertise cannot be ignored. Therefore, a balance between directors with management experience and medical knowledge on the board of directors is beneficial for hospital financial performance.

Development and validation of the Dynamic Collimation Monte Carlo simulation package for pencil beam scanning proton therapy.

PURPOSE: The aim of this work was to develop and experimentally validate a Dynamic Collimation Monte Carlo (DCMC) simulation package specifically designed for the simulation of collimators in pencil beam scanning proton therapy (PBS-PT). The DCMC package was developed using the TOPAS Monte Carlo platform and consists of a generalized PBS source model and collimator component extensions. METHODS: A divergent point-source model of the IBA dedicated nozzle (DN) at the Miami Cancer Institute (MCI) was created and validated against on-axis commissioning measurements taken at MCI. The beamline optics were mathematically incorporated into the source to model beamlet deflections in the X and Y directions at the respective magnet planes. Off-axis measurements taken at multiple planes in air were used to validate both the off-axis spot size and divergence of the source model. The DCS trimmers were modeled and incorporated as TOPAS geometry extensions that linearly translate and rotate about the bending magnets. To validate the collimator model, a series of integral depth dose (IDD) and lateral profile measurements were acquired at MCI and used to benchmark the DCMC performance for modeling both pristine and range shifted beamlets. The water equivalent thickness (WET) of the range shifter was determined by quantifying the shift in the depth of the 80% dose point distal to the Bragg peak between the range shifted and pristine uncollimated beams. RESULTS: A source model of the IBA DN system was successfully commissioned against on- and off-axis IDD and lateral profile measurements performed at MCI. The divergence of the source model was matched through an optimization of the source-to-axis distance and comparison against in-air spot profiles. The DCS model was then benchmarked against collimated IDD and in-air and in-phantom lateral profile measurements. Gamma analysis was used to evaluate the agreement between measured and simulated lateral profiles and IDDs with 1%/1 mm criteria and a 1% dose threshold. For the pristine collimated beams, the average 1%/1 mm gamma pass rates across all collimator configurations investigated were 99.8% for IDDs and 97.6% and 95.2% for in-air and in-phantom lateral profiles. All range shifted collimated IDDs passed at 100% while in-air and in-phantom lateral profiles had average pass rates of 99.1% and 99.8%, respectively. The measured and simulated WET of the polyethylene range shifter was determined to be 40.9 and 41.0 mm, respectively. CONCLUSIONS: We have developed a TOPAS-based Monte Carlo package for modeling collimators in PBS-PT. This package was then commissioned to model the IBA DN system and DCS located at MCI using both uncollimated and collimated measurements. Validation results demonstrate that the DCMC package can be used to accurately model other aspects of a DCS implementation via simulation.

A decentralized framework for cultivating research lifecycle transparency.

Research transparency has been advocated as a key means of addressing the current crisis of reproducibility. This article proposes an enhanced form of research transparency, termed lifecycle transparency. Over the entire lifecycle of a research effort, this approach captures the syntactical contexts of artifacts and stakeholders, such as timestamps, agreements, and/or dependency requirements for completing each research phase. For example, such contexts might include when, where, and from whom patients' consent and institutional review board approvals were received before a clinical trial was carried out. However, as existing open-science tools are often dedicated to certain research phases or disciplines, and thus insufficient to support lifecycle transparency, we propose a novel decentralized framework to serve as a common medium for interaction among open-science tools, and produces irrefutable and immutable proofs of progress that can be verified automatically.

Accuracy assessment of computer-aided three-dimensional simulation and navigation in orthognathic surgery (CASNOS).

PURPOSE: This study is aimed for measuring the accuracy of simulation and prediction of our CASNOS protocol in adult patients treated with 2-jaw orthognathic surgery. METHODS: Adult patients with skeletal Class III malocclusions requiring 2-jaw orthognathic surgery were enrolled in the study. Three-dimensional imaging data of 1-month pre-surgical (T1) and 6-month post-surgical (T2) CT were compared to assess accuracy of CASNOS planning. The accuracy of CASNOS protocol was evaluated by calculating the differences in the positions of selected landmarks between simulated surgical and post-surgical 3D images parameters, including ANB, A-Nv, Pog-Nv, and the positions of selected landmarks (ANS, Point A, Point B, Pog) changes in horizontal (x-axis) and vertical (y-axis) directions. Overall geographical discrepancy of planning was assessed by superimposing the color mapping of T1 and T2 imaging. RESULTS: Thirty adult patients with a mean age of 20.6 ± 1.5 years (female/male = 18/12) were enrolled. The geographical changes of overall superimposition between the planned and post-surgical imaging was 0.60 ± 0.19 mm (range: 0.42-1.08 mm). The discrepancies between simulated and post-surgical ANB, A-Nv, Pog-Nv were 1.16 ± 0.36°, 1.25 ± 0.33 mm, 1.19 ± 0.35 mm, respectively. The deviations between simulated and post-surgical Point A and Point B positions were within 1 mm in horizontal and vertical directions. CONCLUSION: The application of the pre-designed bony guiding splints of CASNOS protocol can allow surgeons to treat patients with craniofacial deformities precisely. CASNOS provides a novel approach for orthodontists and surgeons accurately remedying the patients with complex craniofacial discrepancies.

A Circulating Tumor Cell-RNA Assay for Assessment of Androgen Receptor Signaling Inhibitor Sensitivity in Metastatic Castration-Resistant Prostate Cancer.

Rationale: Our objective was to develop a circulating tumor cell (CTC)-RNA assay for characterizing clinically relevant RNA signatures for the assessment of androgen receptor signaling inhibitor (ARSI) sensitivity in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We developed the NanoVelcro CTC-RNA assay by combining the Thermoresponsive (TR)-NanoVelcro CTC purification system with the NanoString nCounter platform for cellular purification and RNA analysis. Based on the well-validated, tissue-based Prostate Cancer Classification System (PCS), we focus on the most aggressive and ARSI-resistant PCS subtype, i.e., PCS1, for CTC analysis. We applied a rigorous bioinformatic process to develop the CTC-PCS1 panel that consists of prostate cancer (PCa) CTC-specific RNA signature with minimal expression in background white blood cells (WBCs). We validated the NanoVelcro CTC-RNA assay and the CTC-PCS1 panel with well-characterized PCa cell lines to demonstrate the sensitivity and dynamic range of the assay, as well as the specificity of the PCS1 Z score (the likelihood estimate of the PCS1 subtype) for identifying PCS1 subtype and ARSI resistance. We then selected 31 blood samples from 23 PCa patients receiving ARSIs to test in our assay. The PCS1 Z scores of each sample were computed and compared with ARSI treatment sensitivity. Results: The validation studies using PCa cell line samples showed that the NanoVelcro CTC-RNA assay can detect the RNA transcripts in the CTC-PCS1 panel with high sensitivity and linearity in the dynamic range of 5-100 cells. We also showed that the genes in CTC-PCS1 panel are highly expressed in PCa cell lines and lowly expressed in background WBCs. Using the artificial CTC samples simulating the blood sample conditions, we further demonstrated that the CTC-PCS1 panel is highly specific in identifying PCS1-like samples, and the high PCS1 Z score is associated with ARSI resistance samples. In patient bloods, ARSI-resistant samples (ARSI-R, n=14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n=17) (Rank-sum test, P=0.003). In the analysis of 8 patients who were initially sensitive to ARSI (ARSI-S) and later developed resistance (ARSI-R), we found that the PCS1 Z score increased from the time of ARSI-S to the time of ARSI-R (Pairwise T-test, P=0.016). Conclusions: Using our new methodology, we developed a first-in-class CTC-RNA assay and demonstrated the feasibility of transforming clinically-relevant tissue-based RNA profiling such as PCS into CTC tests. This approach allows for detecting RNA expression relevant to clinical drug resistance in a non-invasive fashion, which can facilitate patient-specific treatment selection and early detection of drug resistance, a goal in precision oncology.

Decision tree-based classifier in providing telehealth service.

BACKGROUND: Although previous research showed that telehealth services can reduce the misuse of resources and urban-rural disparities, most healthcare insurers do not include telehealth services in their health insurance schemes. Therefore, no target variable exists for the classification approaches to learn from or train with. The problem of identifying the potential recipients of telehealth services when introducing telehealth services into health welfare or health insurance schemes becomes an unsupervised classification problem without a target variable. METHODS: We propose a HDTTCA approach, which is a systematic approach (the main process of HDTTCA involves (1) data set preprocessing, (2) decision tree model building, and (3) predicting and explaining of the most important attributes in the data set for patients who qualify for telehealth service) to identify those who are eligible for telehealth services. RESULTS: This work uses data from the NHIRD provided by the NHIA in Taiwan in 2012 as our research scope, which consist of 55,389 distinct hospitals and 653,209 distinct patients with 15,882,153 outpatient and 135,775 inpatient records. After HDTTCA produces the final version of the decision tree, the rules can be used to assign the values of the target variables in the entire NHIRD. Our data indicate that 3.56% (23,262 out of 653,209) of the patients are eligible for telehealth services in 2012. This study verifies the efficiency and validity of HDTTCA by using a large data set from the NHI of Taiwan. CONCLUSION: This study conducts a series of experiments 30 times to compare the HDTTCA results with the logistic regression findings by measuring their average performance and determining which model addresses the telehealth patient classification problem better. Four important metrics are used to compare the results. In terms of sensitivity, the decision trees generated by HDTTCA and the logistic regression model are on equal grounds. In terms of accuracy, specificity, and precision, the decision tree generated by HDTTCA provides a better performance than that of the logistic regression model. When HDTTCA is applied, the decision tree model generates a competitive performance and provides clear, easily understandable rules. Therefore, HDTTCA is a suitable choice in solving telehealth service classification problems.

Disease-free survival assessment by artificial neural networks for hepatocellular carcinoma patients after radiofrequency ablation.

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) provides an effective treatment for patients who exhibit early hepatocellular carcinoma (HCC) stages or are waiting for liver transplantation. It is important to assess patients after RFA. The goal of this study was to build artificial neural network models with HCC-related variables to predict the 1-year and 2-year disease-free survival (DFS) of HCC patients receiving RFA treatments. METHODS: This study was a retrospective study that tracked HCC patients who received computer tomography-guided percutaneous RFA between January 2009 and April 2012. The numbers of total patients with 1-year and 2-year DFS were 252 and 179, respectively. A total of 15 HCC clinical variables were collected for the construction of artificial neural network models for DFS prediction. Internal validation and validation conducted using simulated prospective data were performed. RESULTS: The results showed that the model with 15 inputs showed better performance compared with the models including only significant features. Parameters for performance assessment of 1-year DFS prediction were as follows: accuracy 85.0% (70.0%), sensitivity 75.0% (63.3%), specificity 87.5% (71.8%), and area under the curve 0.84 (0.77) for internal validation (simulated prospective validation). For 2-year DFS prediction, the values of accuracy, sensitivity, specificity, and area under the curve were 67.9% (63.9%), 50.0% (56.3%), 85.7% (70.0%), and 0.75 (0.72), respectively, for internal validation (simulated prospective validation). CONCLUSION: This study revealed that the proposed artificial neural network models constructed with 15 clinical HCC relevant features could achieve an acceptable prediction performance for DFS. Such models can support clinical physicians to deal with clinical decision-making processes on the prognosis of HCC patients receiving RFA treatments.

Usefulness of overnight pulse oximeter as the sleep assessment tool to assess the 6-year risk of road traffic collision: evidence from the Taiwan Bus Driver Cohort Study.

Background: In order to support health service organizations in arranging a system for prevention of road traffic collisions (RTC), it is important to study the usefulness of sleep assessment tools. A cohort study was used to evaluate the effectiveness of subjective and objective sleep assessment tools to assess for the 6-year risk of both first RTC event only and recurrent RTC events. Methods: The Taiwan Bus Driver Cohort Study (TBDCS) recruited 1650 professional drivers from a large bus company in Taiwan in 2005. The subjects were interviewed in person, completed the sleep assessment questionnaires and had an overnight pulse oximeter survey. Moreover, this cohort of drivers was linked to the National Traffic Accident Database (NTAD) and researchers found 139 new RTC events from 2005 to 2010. Primary outcomes were traffic collisions from NTAD, nocturnal oxygen desaturation index (ODI) from pulse oximeter, Pittsburg sleeping quality score, Epworth daytime sleepiness score, Snore Outcomes Survey score and working patterns from questionnaires. A Cox proportional hazards model and an extended Cox regression model for repeated events were performed to estimate the hazard ratio for RTC. Results: The RTC drivers had increased ODI4 levels (5.77 ± 4.72 vs 4.99 ± 6.68 events/h; P = 0.008) and ODI3 levels (8.68 ± 6.79 vs 7.42 ± 7.94 events/h; P = 0.007) in comparison with non-RTC drivers. These results were consistent regardless of whether ODI was evaluated as a continuous or a categorical variable. ODI4 and ODI3 levels increased the 6-year RTC risks among professional drivers even after adjusting for age, education, history of cardiovascular disease, caffeine intake, sleeping pills used, bus driving experience and shift modes. Moreover, there was an increased trend for ODI between the stratification of the number of RTCs in comparison with the non-RTC group. In the extended Cox regression models for repeated RTC events with the Anderson and Gill intensity model and Prentice-Williams-Petersen model, measurement of ODI increased hazards of the subsequent RTC events. Conclusion: This study showed that an increase in the 6-year risk of RTC was associated with objective measurement of ODI for a sign of sleep-disordered breathing (SDB), but was not associated with self-reported sleeping quality or daytime sleepiness. Therefore, the overnight pulse oximeter is an effective sleep assessment tool for assessing the risk of RTC. Further research should be conducted regarding measures to prevent against SDB among professional drivers.

Comparative assessment of therapeutic safety of norcantharidin, N-farnesyloxy-norcantharimide, and N-farnesyl-norcantharimide against Jurkat T cells relative to human normal lymphoblast: A quantitative pilot study.

The therapeutic safety of an anticancer drug is one of the most important concerns of the physician treating the cancer patient. Half maximal inhibitory concentration (IC50) and hillslope are usually used to represent the strength and sensitivity of an anticancer drug on cancer cells. The therapeutic safety of the anticancer drug can be assessed by comparing the IC50 and hillslope of anticancer drugs on cancer cells relative to normal cells. Since there are situations where "more anticancer activity" implies "more toxicity," the safety of an anticancer drug in these situations is hard to evaluate by using IC50 and hillslope alone. In a previous study, the "net effect" index was devised to represent the net therapeutic effects of one anticancer drug relative to the other. However, the therapeutic safety of one specific anticancer drug alone was not defined in the "net effect" index. This study introduced the "safety index (SI)" to quantify the degree of safety of an anticancer drug by using 4-parameter logistic model on cancer cells relative to normal cells. The therapeutic safety of norcantharidin (NCTD), N-farnesyloxy-norcantharimide (NOC15), and N-farnesyl-norcantharimide (NC15) in the treatment of Jurkat T cells relative to human normal lymphoblast was compared using the newly defined SI. We found that the SI of NOC15 and NC15 was significantly higher than that of NCTD, suggesting that both NOC15 and NC15 can damage more cancer cells and less normal cells than NCTD. We conclude that both NOC15 and NC15 are safer anticancer drugs than NCTD in the treatment of Jurkat T cells relative to human normal lymphoblast. The SI can be further applied to the screening, developments, and applications of anticancer drugs in the future.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.