Correction: A Novel mHealth Approach for a Patient-Centered Medication and Health Management System in Taiwan: Pilot Study.

[This corrects the article DOI: 10.2196/mhealth.9987.].

Healthcare utilization and costs of atopic dermatitis in Taiwan.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disease. Only relatively scant studies from Asian countries have attempted to quantify AD-associated healthcare utilization and costs by using population-based databases. This study aims to evaluate the AD-associated annual healthcare utilization and costs in Taiwan. METHODS: A retrospective matched-cohort study was conducted by matching the AD cases with controls at a 1:4 (cases:controls) ratio, with the data for both the cases and controls being sourced from the 2017 National Health Insurance Research Database (NHIRD). The AD patients were stratified by disease severity based on their treatments. Differences in the regression-adjusted frequency of care and costs between the cases and controls were compared using t-tests by the severity level of AD. RESULTS: The incremental frequency of outpatient visits per year increased with AD severity (9.60, 11.28, and 16.23 for mild, moderate, and severe cases, respectively). However, the frequency of inpatient care and emergency room visits per year showed no consistent pattern associated with disease severity. The incremental total costs per year were NT$9,511.64, NT$9,705.20, and NT$15,762.09 for mild, moderate, and severe cases, respectively, and the outpatient and drug costs accounted for 46.65%-54.82% and 17.01%-31.20% of the total costs, respectively. CONCLUSION: AD was found to impose significant healthcare costs, with estimated total cost burdens of NT$3.61 billion in 2017, which is 0.314% of Taiwan's national health expenditure and 0.020% of Taiwan's gross domestic product.

Gender and Age Differences of Genitourinary Cancers Among Chronic Dialysis Patients in Taiwan.

BACKGROUND: To investigate the age and gender differences among chronic dialysis patients who developed genitourinary cancers in Taiwan. PATIENTS AND METHODS: Incident hemodialysis patients aged 20 years or older were selected for retrospective cohort study from the National Health Insurance Research Database between 2002 and 2015, and the Taiwan Cancer Registry Database between 2007 and 2015. A two-step approach was employed to find the respective matched controls of non-dialysis patients. Finally, 65,450 dialysis patients and 261,800 non-dialysis patients were matched for further analysis. New diagnosis of genitourinary cancers during follow-up was the primary outcome of interest. RESULTS: Dialysis was significantly associated with increased risk of all types of genitourinary cancers (P < .001), substantially within the first two years after dialysis initiation. Cox proportional hazard analysis showed a significantly increased hazard ratio (HR 6.58, 95% CI 6.05-7.16) among dialysis patients after multivariate adjustment, and the highest risk was bladder cancer (HR 7.85, 95% CI 6.97-8.84). Subgroup analysis showed younger dialysis patients (20-49 years old) had the highest risk of genitourinary cancer, especially females, in this subgroup with the highest risk of bladder cancer (HR 58.08, 95% CI 13.88-243.06). CONCLUSION: The risks of all site-specific genitourinary cancers were increased in chronic dialysis patients, especially in younger females. Developing different screening strategies for these high-risk patients is necessary. MICRO ABSTRACT: This study compared the effect of sex, age and dialysis duration on the susceptibility to develop genitourinary cancers in dialysis patients through the national health database linkage in Taiwan. We matched 65,450 dialysis patients and 261,800 non-dialysis patients for further analysis. Younger and female dialysis patients were at higher risk of kidney and bladder cancers.

Treatment patterns and survival in patients with small cell lung cancer in Taiwan.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. The chemotherapy regimens and their efficacy in practice are seldom reported. We aimed to investigate treatment patterns and survival outcomes of patients with SCLC in Taiwan. METHODS: Patients newly diagnosed with SCLC from 2011 to 2015 were identified from the Cancer Registry database. Their clinical characteristics, treatment regimens, and survival status were obtained from National Health Insurance Research database. The Kaplan-Meier method and Cox-proportional hazard model were used to analyze the survival outcomes. RESULTS: Among a total of 2707 patients enrolled, 439 were in the limited stage (LS, 16.22%) and 2268 were in the extensive stage of the disease (ES, 83.78%). The median age was 66 and the majority were male (90.36%). The first-line regimen used for the patients was etoposide/cisplatin-based treatment, followed by etoposide/carboplatin-based regimen, and etoposide only. The median overall survival (OS) was 16.92 months (95% confidence interval [CI] 15.31-18.92) and 8.71 months (95% CI 8.38-9.07) in LS and ES patients, respectively. Chemotherapy regimen, Eastern Cooperative Oncology Group performance status, and history of radiotherapy were significant factors associated with OS. On the other hand, the major second-line treatment was a topotecan-based regimen (68.3%). However, this showed inferior survival outcome compared to etoposide-based regimen (5.09 months [95% CI 4.76-5.62] versus 8.77 months [95% CI 6.31-11.89], p < 0.001). CONCLUSION: Etoposide is the preferred and superior first-line chemotherapy regimen in combination with platinum, and an alternative choice of second-line regimen for Taiwanese patients with SCLC.

End-to-end deep learning for recognition of ploidy status using time-lapse videos.

PURPOSE: Our retrospective study is to investigate an end-to-end deep learning model in identifying ploidy status through raw time-lapse video. METHODS: By randomly dividing the dataset of time-lapse videos with known outcome of preimplantation genetic testing for aneuploidy (PGT-A), a deep learning model on raw videos was trained by the 80% dataset, and used to test the remaining 20%, by feeding time-lapse videos as input and the PGT-A prediction as output. The performance was measured by an average area under the curve (AUC) of the receiver operating characteristic curve. RESULT(S): With 690 sets of time-lapse video image, combined with PGT-A results, our deep learning model has achieved an AUC of 0.74 from the test dataset (138 videos), in discriminating between aneuploid embryos (group 1) and others (group 2, including euploid and mosaic embryos). CONCLUSION: Our model demonstrated a proof of concept and potential in recognizing the ploidy status of tested embryos. A larger scale and further optimization on the exclusion criteria would be included in our future investigation, as well as prospective approach.

Prevalence of baseline comorbidities in patients with atopic dermatitis: A population-based cohort study in Taiwan.

BACKGROUND: Atopic dermatitis has been linked to increased risk of many comorbidities. However, the risks of certain comorbidities are still debated. OBJECTIVE: To better characterize the basic demographics, treatment patterns, and associations between atopic dermatitis and comorbidities and to further investigate the influence of severity on comorbidities. METHODS: We used a sample cohort of 999,992 people from the National Health Insurance Research Database of Taiwan to evaluate atopic dermatitis in the general population. RESULTS: A total of 12,780 patients with atopic dermatitis in 2010 were identified. The prevalence was 1.28%. The proportions of severe and moderate cases were 7.43% and 19.26%, respectively. The most commonly used systemic treatment was corticosteroids. Compared with the general population, atopic dermatitis patients showed increased risks of all 9 groups of comorbidities, including autoimmune disorders, atopic disorders, chronic urticaria, ocular disorders, metabolic disorders, hypertensive disorders, ischemic heart disorders, cerebrovascular disorders, and psychiatric disorders. The severity and persistence of atopic dermatitis were correlated with the development of certain comorbidities. LIMITATIONS: Miscoding and misclassification might have occurred, and only patients with active disease were enrolled. CONCLUSION: Patients with atopic dermatitis have higher risks of various comorbidities. Comprehensive monitoring and treatment plans are needed to better manage these patients.

Increased Risk of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients and Patients on Chronic Dialysis: A Cancer Registry-based Study in Taiwan.

This study investigated the predominant skin cancer subtype among organ transplant recipients, patients on chronic dialysis, and patients with chronic kidney disease in Asian subjects. Among 23,644 patients with skin cancer, identified from Taiwan Cancer Registry Database, 53 were organ transplant recipients, 255 were on chronic dialysis, 1,792 had chronic kidney disease, and 21,544 were in the control group. The proportions of squamous cell carcinoma were 52.8%, 47.8%, 40.1%, and 33.5%, respectively. Compared with the control group, organ transplant recipients (1.99-fold) and patients on chronic dialysis (1.25-fold) were at higher risk of developing squamous cell carcinoma than other skin cancers after adjustment for potential confounders. Subgroups or covariates associated with increased squamous cell carcinoma compared with other skin cancer risk included patients with chronic kidney disease aged < 70 years (vs. control group; 1.3-fold), old age (vs. young age; 2.8-fold), male sex (vs. female sex; 1.1-fold), and south Taiwan residency (vs. north Taiwan residency; 1.1-fold). Organ transplant recipients and patients on chronic dialysis had immune dysregulation, resulting in a higher risk of squamous cell carcinomas.

A Novel mHealth Approach for a Patient-Centered Medication and Health Management System in Taiwan: Pilot Study.

BACKGROUND: Mobile health (mHealth) apps have recently demonstrated the potential to engage and empower people to improve their own health. Although the availability of health-related apps is increasing, their adoption rate in Taiwan is exceptionally low mainly due to the preponderance of Western culture-based app designs that are challenging for non-English-speaking individuals. To our knowledge, no mHealth app is available in Taiwan that is culturally tailored for Chinese-speaking users and that applies a patient-centered approach to self-manage medication and health. OBJECTIVE: The purpose of this study was to design and deploy a culturally tailored mHealth system that could be easily integrated into current clinical practice and to evaluate how this mHealth system could support the continuity of patient care in Taiwan. METHODS: An mHealth information system and a mobile app were designed. To promote the best patient experience, a Quick Response (QR) code system was developed to enable efficient registration of personal medication information through the mobile app. The app also supported notifications for drug utilization, refills, and symptom checks. Patients were encouraged to record medication use, symptoms, and self-assessments in the app during their treatment period. Evaluation of the novel mHealth system was conducted from August 1, 2016 to December 31, 2016 at MacKay Memorial Hospital, Taipei, Taiwan. Population data and app usage statistics were analyzed. RESULTS: During the 5-month implementation period, a total of 25,909 users downloaded the app with an overall 7-day retention rate of 15.4% (SD 3.9). Young male adults (range 25-44 years) were the predominant user population. Patients' feedback on app usability and design, QR code system as drug input method, medication reminders, and linking family or friends into care networks was generally positive. Physicians showed great interest in utilizing patient-generated data in their care process, and the positive medication adherence rate was the most highly valued component of this system. CONCLUSIONS: This pilot study demonstrated the value of a novel mHealth approach for individualized medication and health management in Taiwan. The mHealth system shows the potential to optimize personalized care into existing clinical services and may help hospitals and health authorities perform continuous quality improvement and policy development.

Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification.

Cytokines are low molecular weight regulatory proteins, or glycoproteins, with both tumor-promoting and inhibitory effects on breast cancer growth. Different cytokines play important roles in breast cancer initiation and progression. Here, we show that of the 39 interleukin (IL) genes, IL-20 is the only gene over-expressed in MCF-7 cells treated with estradiol (E2) and that induction of IL-20 expression by estrogen was epigenetically regulated. Methylation of histone H3K4 in the IL-20 promoter was shown to occur via the specific recruitment of KMT2B by estrogen receptor alpha (ERα), but not by other members of the mixed-lineage leukemia (MLL) family of histone methyltransferases. Depletion of KMT2B, or IL-20, disrupts estrogen signaling, attenuates cell proliferation, reduces colony formation, and results in cell cycle arrest. Furthermore, we demonstrated that KMT2B-mediated epigenetic modification also affected the expression of several ERα target genes. IL-20 and KMT2B expression were also associated with ERα-positive breast cancer tissues. We have revealed an important role for KMT2B in the epigenetic transcriptional regulation of cytokine IL-20, and other ERα-responsive genes, in breast cancer cells. Inhibition of IL-20 and KMT2B may have therapeutic benefits in ERα-positive breast cancer.

Matrix dimensionality and stiffness cooperatively regulate osteogenesis of mesenchymal stromal cells.

Osteogenic potential of mesenchymal stromal cells (MSCs) is mechanosensitive. It's affected by the mechanical properties of the cellular microenvironment, particularly its mechanical modulus. To explore the effect of mechanical modulus on osteogenesis in the third dimension (3D), this study used a novel polyacrylamide (PA) scaffold whose pores are monodisperse and spherical, the mechanical moduli of which can be tuned across a wide range. It was found that MSCs have similar proliferation rates in PA scaffolds independent of the matrix stiffness. The contractile force exerted by MSCs inside PA scaffolds was strong enough to deform the pores of scaffolds made of more compliant PAs (whose shear modulus, G'scaffold<4 kPa). Only scaffolds of the highest stiffness (G'scaffold=12 kPa) can withhold the contraction from MSCs. After osteogenic induction for 21 days, the expression profiles of marker genes showed that PA scaffolds of G'scaffold=12 kPa promoted osteogenesis of MSCs. Confocal image analysis demonstrated that there are more F-actin cytoskeletons and bundled stress fibers at higher matrix moduli in 2D and 3D. Moreover, the 3D porous structure promotes osteogenesis of MSCs more than 2D flat substrates. Together, the differences of cellular behaviors when cultured in 2D and 3D systems are evident. The PA scaffolds developed in the present study can be used for further investigation into the mechanism of MSC mechanosensing in the 3D context. STATEMENT OF SIGNIFICANCE: Mechanical properties of the microenvironment affect cellular behaviors, such as matrix stiffness. Traditionally, cell biological investigations have mostly employed cells growing on 2D substrates. The 3D porous PA scaffolds with the same topological conformation and pore sizes but different stiffness generated in this study showed that the differences of cellular behaviors in 2D and 3D systems are evident. Our 3D scaffolds provide insights into tissue engineering when stem cells incorporated with 3D scaffolds and support the future studies of cellular mechanobiology as well as the elucidation the role mechanical factor plays on the physiology and fate determination of MSCs in the 3D context.

A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease.

Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), ß-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation.

Micro-Spec: an ultracompact, high-sensitivity spectrometer for far-infrared and submillimeter astronomy.

High-performance, integrated spectrometers operating in the far-infrared and submillimeter ranges promise to be powerful tools for the exploration of the epochs of reionization and initial galaxy formation. These devices, using high-efficiency superconducting transmission lines, can achieve the performance of a meter-scale grating spectrometer in an instrument implemented on a 4 inch silicon wafer. Such a device, when combined with a cryogenic telescope in space, provides an enabling capability for studies of the early universe. Here, the optical design process for Micro-Spec (µ-Spec) is presented, with particular attention given to its two-dimensional diffractive region, where the light of different wavelengths is focused on the different detectors. The method is based on the stigmatization and minimization of the light path function in this bounded region, which results in an optimized geometrical configuration. A point design with an efficiency of ~90% has been developed for initial demonstration and can serve as the basis for future instruments. Design variations on this implementation are also discussed, which can lead to lower efficiencies due to diffractive losses in the multimode region.

Chitosan-guar gum-silver nanoparticles hybrid matrix with immobilized enzymes for fabrication of beta-glucan and glucose sensing photometric flow injection system.

Simple and fast photometric flow injection analysis system was developed for sensing of ß-1,3-glucan from medicinal mushroom Ganoderma lucidum during fermentation. For this purpose, the chitosan-guar gum-silver nanoparticle-beta glucanase (Ch-GG-AgNPs-ßG) beads and Ch-GG-AgNPs-GOD (glucose oxidase) beads were prepared. The bead packed mini-columns were then used to assemble a flow injection analysis (FIA) system for the detection of ß-(1→3)-d-glucan biomarker or glucose. This colorimetric flow system can detect glucose and glucan with detection limits as low as 50ngmL(-1) and 100ngmL(-1) (S/N=3), respectively. The analysis time of this FIA was approximately 40s, which is faster than the previously reported glucan sensors. The glucose and glucan calibration curves were obtained in the range of 0.25-1.25µgmL(-1) (R(2)=0.988) and 0.2-1.0µgmL(-1)(R(2)=0.979), respectively. The applicability of the nano-bio-composite FIA sensor system for spiked and real ß-(1→3)-d-glucan samples were tested, and the accuracy of the results were greater than 95%. Thus, the designed FIA provides a simple, interference free and rapid tool for monitoring glucose and ß-glucan content, which can be used for various food samples with a little modification.

Hematopoietic and myeloprotective activities of an acidic Angelica sinensis polysaccharide on human CD34+ stem cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (AS) is a Chinese herbal medicine traditionally used in prescriptions for replenishing blood and treating abnormal menstruation and other women's diseases. AIM OF THE STUDY: This study aimed to separate and identify the major hematopoietic fraction from Angelica sinensis polysaccharides (ASPS), and to investigate the myeloprotective activity of the major bioactive fraction of ASPS as a possible supporting agent for cancer treatments. MATERIALS AND METHODS: The ASPS was fractionated with DEAE-Sepharose CL-6B column to obtain four fractions (F1, F2, F3 and F4). Each fraction was cultured with human peripheral blood mononuclear cells (MNCs) to collect conditioned medium (CM). The hematopoietic ability of various MNC-CM was then evaluated by the colony-forming assay on CD34(+) cells collected by the MACS method from human umbilical cord blood (UCB). In myeloprotective experiment, Adriblastina was used to act as the myelosuppressive agent. The monosaccharide composition of ASPS was analyzed by high-performance anion-exchange chromatography-pulse amperometric detector. RESULTS: The F2 fraction, which was found to have the highest hematopoietic activity, stimulated the human peripheral blood MNCs to secret GM-CSF and IL-3. F2 could also protect the hematopoietic function of CD34(+) cells from Adriblastina. F2 occupies 19% of ASPS and contains 0.53% protein. The monosaccharide composition of F2 was arabinose (51.82%), fructose (1.65%), galactose (29.96%), glucose (4.78%) and galacturonic acid (14.80%), with molecular weight 2.5-295 kDa. CONCLUSIONS: The bioactive fraction identified and fractionated from ASPS may be used as a health-promoting agent for anemia patients and cancer patients under chemoradiation treatment.

Hematopoietic effect of water-soluble polysaccharides from Angelica sinensis on mice with acute blood loss.

OBJECTIVE: To assess the hematopoietic effects of Angelica sinensis and to investigate the possible mechanism related to its hematopoietic activity. MATERIALS AND METHODS: The crude extract of Angelica sinensis (AS) was separated into two fractions, polysaccharides (ASPS) and small molecular weight compounds. The AS, ASPS, and small molecular weight compounds were incubated with mice spleen cells to obtain conditioned mediums, and then their hematopoietic activities were evaluated by granulocyte macrophage (GM) colony-forming assay in vitro. During in vivo test, we used mice that were bled approximately 0.5 mL by retro-orbital bleeding at day 0 as our anemia model. RESULTS: We found that polysaccharide (ASPS) was the major component responsible for the hematopoietic effect of Angelica sinensis. The hematopoietic activity was through the stimulation of secretion of interleukin-6 and GM colony-stimulating factor, and the amounts of these hematopoietic growth factors secreted, in general, agreed with the number of GM colony formations. Administration of low-dose ASPS (2.3 mg ASPS/kg body weight per day) could significantly accelerate the recovery of hemoglobin level of the blood-loss mice to its original value, as compared to the control (p < 0.05). Moreover, the colony-forming ability of bone marrow cells that were removed from mice that received ASPS was also markedly increased (p < 0.05) during ex vivo test. CONCLUSIONS: Results of this study demonstrated the potential of ASPS for treatment of anemia.