[Effect of CD8+ CD28- T Cells on Acute Graft-Versus-Host Disease after Haploidentical Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the effect of CD8+ CD28- T cells on acute graft-versus-host disease(aGVHD) after haploidentical hematopoietic stem cell transplantation(haplo-HSCT). METHODS: The relationship between absolute count of CD8+ CD28- T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT, and the differences in the incidence rate of chronic graft-versus host disease(cGVHD), infection and prognosis between different CD8+ CD28- T absolute cells count groups were compared. RESULTS: aGVHD occurred in 40 of 60 patients after haplo-HSCT, with an incidence rate of 66.67%. The median occurrence time of aGVHD was 32.5(20-100) days. At 30 days after the transplantation, the absolute count of CD8+ CD28- T cells of aGVHD group was significantly lower than that of non-aGVHD group (P =0.03). Thus the absolute count of CD8+ CD28- T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent. At 30 days after transplantation, the incidence rate of aGVHD in the low cell count group (CD8+ CD28- T cells absolute count < 0.06/µl) was significantly higher than that in the high cell count group (CD8+ CD28- T cells absolute count ≥0.06/µl,P =0.011). Multivariate Cox regression analysis further confirmed that the absolute count of CD8+ CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD, and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group (P =0.015). The incidence of cGVHD, fungal infection, EBV infection and CMV infection were not significantly different between the two groups with different CD8+ CD28- T cells absolute count. The overall survival, non-recurrent mortality and relapse rates were not significantly different between different CD8+ CD28- T cells absolute count groups. CONCLUSION: Patients with delayed CD8+ CD28- T cells reconstitution after haplo-HSCT are more likely to develop aGVHD, and the absolute count of CD8+ CD28- T cells can be used to predict the incidence of aGVHD to some extent. The absolute count of CD8+ CD28- T cells after haplo-HSCT was not associated with cGVHD, fungal infection, EBV infection, and CMV infection, and was also not significantly associated with the prognosis after transplantation.

Perivascular adipose tissue remodeling impairs vasoreactivity in thermoneutral-housed rats.

Objective: Vascular pathology, characterized by impaired vasoreactivity and mitochondrial respiration, differs between the sexes. Housing rats under thermoneutral (TN) conditions causes vascular dysfunction and perturbed metabolism. We hypothesized that perivascular adipose tissue (PVAT), a vasoregulatory adipose depot with brown adipose tissue (BAT) phenotype, remodels to a white adipose (WAT) phenotype in rats housed at TN, driving diminished vasoreactivity in a sex-dependent manner. Methods: Male and female Wistar rats were housed at either room temperature (RT) or TN. Endpoints included changes in PVAT morphology, vasoreactivity in vessels with intact PVAT or transferred to PVAT of the oppositely-housed animal, vessel stiffness, vessel mitochondrial respiration and cellular signaling. Results: Remodeling of PVAT was observed in rats housed at TN; animals in this environment showed PVAT whitening and displayed diminished aortae vasodilation (p<0.05), different between the sexes. Juxtaposing PVAT from RT rats onto aortae from TN rats in females corrected vasodilation (p<0.05); this did not occur in males. In aortae of all animals housed at TN, mitochondrial respiration was significantly diminished in lipid substrate experiments (p<0.05), and there was significantly less expression of peNOS (p<0.001). Conclusions: These data are consistent with TN-induced remodeling of PVAT, notably associated with sex-specific blunting of vasoreactivity, diminished mitochondrial respiration, and altered cellular signaling.

Association of Childhood Attention Deficit/Hyperactivity Disorder With Adolescent Traditional and Cyberbullying Victimization in the Digital Generation: A Population-Based Cohort Study.

PURPOSE: This population-based cohort study aimed to examine the association with childhood attention deficit/hyperactivity disorder (ADHD) and bullying experiences during adolescence among Digital Generation individuals, exploring both traditional and cyberbullying. METHODS: This study included data from 15,240 participants, collected from the Taiwan Adolescent to Adult Longitudinal Study project. Participants, initially in seventh and 10th grade in 2015, were selected through a multistage stratified sampling approach. Self-report questionnaires assessed traditional and cyberbullying victimization experiences during adolescence, with 5-year longitudinal follow-up. Childhood ADHD diagnoses were identified by linking data to Taiwan's National Health Insurance Research Database from 2000 to 2015. Logistic regression models were employed to examine the relationship between childhood ADHD and bullying victimization while controlling for relevant covariates. RESULTS: Individuals diagnosed with childhood ADHD exhibited a significantly higher likelihood of experiencing bullying during adolescence (adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.28-1.80). This association extended to various forms of bullying, including physical (aOR = 1.42, 95% CI: 1.20-1.68), verbal (aOR = 1.42, 95% CI: 1.20-1.67), relational (aOR = 1.45, 95% CI: 1.22-1.71), and cyber (aOR = 1.35, 95% CI: 1.14-1.61). Additional factors positively associated with bullying victimization included male, binge drinking, and depression, while a positive campus atmosphere was protective against bullying. However, there is no evidence for interactions between these factors and ADHD in their associations with bullying. DISCUSSION: Childhood ADHD increases the risk of both traditional and cyberbullying during adolescence. Recognizing this risk is essential for targeted interventions and further research on underlying mechanisms.

Effects of bilateral tDCS over DLPFC on response inhibition, craving, and brain functional connectivity in Internet gaming disorder: A randomized, double-blind, sham-controlled trial with fMRI.

Background and aims: Impaired inhibitory control accompanied by enhanced craving is hallmark of addiction. This study investigated the effects of transcranial direct current stimulation (tDCS) on response inhibition and craving in Internet gaming disorder (IGD). We examined the brain changes after tDCS and their correlation with clinical variables. Methods: Twenty-four males with IGD were allocated randomly to an active or sham tDCS group, and data from 22 participants were included for analysis. Participants self-administered bilateral tDCS over the dorsolateral prefrontal cortex (DLPFC) for 10 sessions. Stop-signal tasks were conducted to measure response inhibition and participants were asked about their cravings for Internet gaming at baseline and post-tDCS. Functional magnetic resonance imaging data were collected at pre- and post-tDCS, and group differences in resting-state functional connectivity (rsFC) changes from the bilateral DLPFC and nucleus accumbens were examined. We explored the relationship between changes in the rsFC and behavioral variables in the active tDCS group. Results: A significant group-by-time interaction was observed in response inhibition. After tDCS, only the active group showed a decrease in the stop-signal reaction time (SSRT). Although craving decreased, there were no significant group-by-time interactions or group main effects. The anterior cingulate cortex (ACC) showed group differences in post- versus pre-tDCS rsFC from the right DLPFC. The rsFC between the ACC and left middle frontal gyrus was negatively correlated with the SSRT. Discussion and conclusion: Our study provides preliminary evidence that bilateral tDCS over the DLPFC improves inhibitory control and could serve as a therapeutic approach for IGD.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

[Characteristics and Prognosis in Adult Patients with Early T-Cell Precursor Acute Lymphoblastic Leukemia/Lymphoma from Multicenter].

OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of adult patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL). METHODS: Clinical data of 113 T lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients from January 2006 to January 2019 were collected from three hematology research centers, including Peking University Third Hospital, the First Medical Center of Chinese PLA General Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Medical University. The clinical characteristics and prognosis of ETP-ALL/LBL patients were analyzed compared with non-ETP-ALL/LBL patients. RESULTS: In 113 T-ALL/LBL patients, 13 cases (11.5%) were diagnosed as ETP-ALL/LBL, including 11 males, with a median age of 28(18-53) years. Compared with non-ETP-ALL/LBL patients, there were no significant differences in age, sex, incidence of large mediastinal mass, clinical stage, international prognostic index (IPI) score, white blood cell (WBC) count and lactate dehydrogenase (LDH) level among ETP-ALL/LBL patients. Among 13 ETP-ALL/LBL patients, 9 cases (69.2%) achieved complete remission (CR), and there was no statistically significant difference in response rate induced by chemotherapy between ETP-ALL/LBL patients and non-ETP-ALL/LBL patients. Among patients who received chemotherapy without allogeneic hematopoietic stem cell transplantation (allo-HSCT), ETP-ALL/LBL group had a worse 5-year overall survival (OS) rate compared with non-ETP-ALL/LBL group (0 vs 7.1%, P =0.008), while in patients with allo-HSCT, there was no significant difference for 5-year OS rate between the two group (37.5% vs 40.2%, P >0.05). Multivariate Cox regression analysis showed that CR after induction therapy, allo-HSCT, and LDH level were independent prognostic factors affecting T-ALL/LBL patients. CONCLUSION: No significant difference in response rate induced by chemotherapy is observed between ETP-ALL/LBL and non-ETP-ALL/LBL patients. Allo-HSCT consolidation after induction of remission therapy may have significant favorable influence on OS for patients with ETP-ALL/LBL.

Developing a Cost-Effectiveness Model of Digital Therapeutics for Smoking Cessation.

The purpose of this research was to construct a Markov model of digital therapeutics to predict the lifetime costs and consequences that would be incurred by a hypothetical group of adult smokers in Korea who only made a single attempt to stop smoking. To determine the efficacy of DTx, we created an annual cycle Markov model. The result shows that the NRT strategy is determined as the dominant strategy. Digital therapeutics acts as a complement to pharmacotherapy and is a low-cost option.

The effect of childhood depression trajectories on sugar-sweetened beverage habit trajectories in adolescence: Exploring sleep problems as a mediator.

Although depression has been linked to the habit of consuming sugar-sweetened beverages (SSBs), little is known about their long-term relationships and the mediating role of sleep problems. This study examines the associations between childhood depressive symptoms trajectories and adolescent SSB-habit trajectories and whether these associations were mediated by sleep problems. Data came from 1560 adolescents participating in a longitudinal study across grades 1 through 12 in northern Taiwan. Group-based trajectory modeling was used to identify development of childhood depressive symptoms and an SSB habit in adolescence. Multinomial logistic regression was conducted to examine the influence of childhood depressive symptoms and adolescent SSB habit. Mediation analysis was conducted to test whether sleep problems mediated the associations examined. Four distinct trajectories of childhood depressive symptoms were identified: low-stable (30.79%), moderate-stable (42.32%), increasing (12.29%), and high-stable (11.60%). Three distinct trajectories of SSB habit in adolescence were identified: low-stable (44.32%), increasing (15.02%), and high-stable (40.65%). Children who had moderate-stable (aOR = 1.35; CI: 1.04-1.77), high-stable (aOR = 2.01; CI: 1.28-3.15), or increasing (aOR = 1.97; CI: 1.26-3.06) trajectories of depressive symptoms relative to those in the low-stable group were significantly more likely to belong to the high-stable trajectory of SSBs than to the low-stable SSBs group. The Z-mediation test showed that sleep problems significantly mediated the associations between trajectories of childhood depressive symptoms and trajectories of SSBs during adolescence (all p < 0.05). Childhood depressive symptoms conferred risks for adolescent SSB habits; and the effects were seen, in part, through increasing sleep problems.

23-valent pneumococcal polysaccharide vaccine and the risk of renal progression in older patients with chronic kidney disease.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) ensures favorable outcomes and reduces the risk of cardiac events in patients on dialysis. However, the effect of PPSV23 vaccination on renal function remains unknown, particularly in patients with chronic kidney disease (CKD). Therefore, we investigated the association between PPSV23 efficacy and renal progression in older patients (age ≥ 75 years) with CKD. METHODS: This multicenter, longitudinal cohort study was conducted using data (2008-2016) from the Epidemiology and Risk Factors Surveillance of CKD database. This database was associated with Taiwan's National Health Insurance Research Database (for period: 2008-2019). A total of 1195 older patients with CKD were recruited from 14 hospitals and communities across Taiwan. Renal progression was defined as a > 25% reduction in estimated glomerular filtration rate from the baseline value. RESULTS: A significant reduction in the risk of renal progression was observed in patients who had received PPSV23 (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.35-0.91). However, when stratified by CKD stage, this significant reduction was observed in patients with early-stage CKD but not in those with late-stage CKD. Furthermore, a significant reduction in the risk of renal progression was noted in male patients and those with hypertension. CONCLUSION: Our findings support the protective effect of PPSV23 against renal deterioration in older patients with CKD.

[Efficacy and Prognosis of Transplant-Associated Thrombotic Microangiopathy Based on Different Prognostic Risk Models].

OBJECTIVE: To investigate the clinical features of transplant-associated thrombotic microangiopathy (TA-TMA) and the prognostic value of different prognostic risk models for TA-TMA. METHODS: The clinical characteristics of 32 TA-TMA patients diagnosed at the First Medical Center of the PLA General Hospital from January 2018 to February 2022 in terms of short-term prognosis and influencing factors were retrospectively analyzed. In addition, the risk population composition ratio, treatment response, and overall survival between the BATAP risk model and the TMA index model were compared, as well as the efficacy of two prognostic risk models for predicting death in patients with TA-TMA. RESULTS: Independent risk factors affecting the short-term prognosis of TA-TMA include III-IV aGVHD prior to TA-TMA diagnosis (P=0.001), renal or neurological dysfunction (P=0.006), and Hb<70 g/L (P=0.043). In the TMA index model, treatment response was worst in the high-risk group (P=0.008), while there was no significant difference in treatment response between different risk groups in the BATAP model (P=0.105). In the BATAP model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (87.5% vs 61.1% vs 16.7%, χ2＝6.7, P=0.014). In the TMA index model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (77.8% vs 45.5% vs 0.0%, χ2＝7.3, P=0.017). The area under the ROC curve (AUC) of the TMA index model was 0.745 (95%CI: 0.56-0.88, P<0.05), and the AUC of the BATAP model was 0.743 (95%CI: 0.56-0.88, P<0.05), indicating that both prognostic risk models have good predictive value. CONCLUSION: The short-term prognosis of TA-TMA patients might be accurately determined using both the BATAP model and the TMA index model. When predicting the efficacy of TA-TMA in different risk groups, the TMA index model may perform better than the BATAP model.

Cellular toxicity profile of a new ophthalmic sponge.

Introduction: Ophthalmic sponges are used for cleaning the eye surface and absorbing fluids during ophthalmic procedures. This study compared the biological safety and stability of a new ophthalmic sponge, Occucell® (OccuTech Inc, Seongnam, Korea), on the human conjunctival epithelial cells with those of preexisting products to evaluate its clinical application.Materials and Methods: The cytotoxicity of four products, Occucell, a new product, Ultracell®, Eyetec-1, and Eyetec-2, on conjunctival epithelial cells, was evaluated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) analysis. Additionally, human conjunctival epithelial cells were stained with a Live & Dead marker and observed using a fluorescence microscope. To evaluate the effect of the ophthalmic sponges on the secretion of IL-1ß and TNF-α, cultured conjunctival epithelial cells were treated with 0.5% DMSO eluates of the ophthalmic sponges, and IL-1ß and TNF-α mRNA levels were estimated using real-time polymerase chain reaction assays.Results: Cells treated with Occucell showed comparable viability to those treated with other preexisting products. Conjunctival epithelial cells showed more than 90% viability when treated with the ophthalmic sponge extracts, as determined by the MTT assay. No significant differences in the number of live & dead cells were observed between the control and treatment groups. Cells treated with all four ophthalmic sponge eluates showed similar IL-1ß and TNF-α mRNA levels.Discussion: Occucell, an eye sponge used during ophthalmic surgery in clinical practice, did not affect the viability of conjunctival epithelial cells, and more than 90% of the cells were viable after the treatment. Further, Occucell showed similar effects on IL-1ß and TNF-α secretion as that of other ophthalmic sponges used in the clinic. This suggested that Occucell is a safe product comparable to the preexisting products.

Potential Determinants Contributing to COVID-19 Vaccine Acceptance and Hesitancy in Taiwan: Rapid Qualitative Mixed Methods Study.

BACKGROUND: Although vaccination has been shown to be one of the most important interventions, COVID-19 vaccine hesitancy remains one of the top 10 global public health challenges worldwide. OBJECTIVE: The objective of this study is to investigate (1) major determinants of vaccine hesitancy, (2) changes in the determinants of vaccine hesitancy at different time periods, and (3) the potential factors affecting vaccine acceptance. METHODS: This study applied a mixed methods approach to explore the potential determinants contributing to vaccine hesitancy among the Taiwanese population. The quantitative design of this study involved using Google Trends search query data. We chose the search term "" (vaccine), selected "" (Taiwan) as the location, and selected the period between December 18, 2020, and July 31, 2021. The rising keywords related to vaccine acceptance and hesitancy were collected. Based on the responses obtained from the qualitative study and the rising keywords obtained in Google Trends, the 3 most popular keywords related to vaccine hesitancy were identified and used as search queries in Google Trends between December 18, 2020, and July 31, 2021, to generate relative search volumes (RSVs). Lastly, autoregressive integrated moving average modeling was used to forecast the RSVs for the 3 keywords between May 29 and July 31, 2021. The estimated RSVs were compared to the observed RSVs in Google Trends within the same time frame. RESULTS: The 4 prevailing factors responsible for COVID-19 vaccine acceptance and hesitancy were doubts about the government and manufacturers, side effects, deaths associated with vaccination, and efficacy of vaccination. During the vaccine observation period, "political role" was the overarching consideration leading to vaccine hesitancy. During the peak of the pandemic, side effects, death, and vaccine protection were the main factors contributing to vaccine hesitancy. The popularity of the 3 frequently searched keywords "side effects," "vaccine associated deaths," and "vaccine protection" continued to rise throughout the pandemic outbreak. Lastly, the highest Google search queries related to COVID-19 vaccines emerged as "side effects" prior to vaccination, deaths associated with vaccines during the period when single vaccines were available, and "side effects" and "vaccine protection" during the period when multiple vaccines were available. CONCLUSIONS: Investigating the key factors influencing COVID-19 vaccine hesitancy appears to be a fundamental task that needs to be undertaken to ensure effective implementation of COVID-19 vaccination. Google Trends may be used as a complementary infoveillance tool by government agencies for future vaccine policy implementation and communication.

The Present and Future of Artificial Intelligence-Based Medical Image in Diabetes Mellitus: Focus on Analytical Methods and Limitations of Clinical Use.

Artificial intelligence (AI)-based diagnostic technology using medical images can be used to increase examination accessibility and support clinical decision-making for screening and diagnosis. To determine a machine learning algorithm for diabetes complications, a literature review of studies using medical image-based AI technology was conducted using the National Library of Medicine PubMed, and the Excerpta Medica databases. Lists of studies using diabetes diagnostic images and AI as keywords were combined. In total, 227 appropriate studies were selected. Diabetic retinopathy studies using the AI model were the most frequent (85.0%, 193/227 cases), followed by diabetic foot (7.9%, 18/227 cases) and diabetic neuropathy (2.7%, 6/227 cases). The studies used open datasets (42.3%, 96/227 cases) or directly constructed data from fundoscopy or optical coherence tomography (57.7%, 131/227 cases). Major limitations in AI-based detection of diabetes complications using medical images were the lack of datasets (36.1%, 82/227 cases) and severity misclassification (26.4%, 60/227 cases). Although it remains difficult to use and fully trust AI-based imaging analysis technology clinically, it reduces clinicians' time and labor, and the expectations from its decision-support roles are high. Various data collection and synthesis data technology developments according to the disease severity are required to solve data imbalance.

The HDAC2-MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c-Myc and cyclin D1.

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation sequencing followed by motif analysis showed that HDAC2 can bind to c-Myc in rs13213007 A/A 293T cells. Cell Counting Kit-8, colony formation, wound-healing, and Transwell assays revealed that HDAC2 upregulates c-Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co-immunoprecipitation, quantitative reverse transcription-polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC.

Association between clustering of unhealthy behaviors and depressive symptom among adolescents in Taiwan: A nationwide cross-sectional survey.

Background: Among Taiwanese adolescents, how the clustering of unhealthy behaviors, including insufficient physical activity, screen-based sedentary behavior and frequent sugar-sweetened beverage consumption affecting depressive symptom remains unclear. This study aims to examine the cross-sectional association between clustering of unhealthy behaviors and depressive symptom. Methods: We analyzed 18,509 participants from the baseline survey of the Taiwan Adolescent to Adult Longitudinal Survey in 2015. The outcome was depressive symptoms, and the main exposures were insufficient physical activity, screen-based sedentary behaviors and frequent sugar-sweetened beverage consumption. Generalized linear mixed models were performed to find key factor associated with depressive symptom. Results: Depressive symptoms were common among participants (31.4%), particularly in female and older adolescents. After adjustments for covariates including sex, school type, other lifestyle factors and social determinants, individuals exhibiting clustering of unhealthy behaviors were more likely (aOR = 1.53, 95% CI: 1.48-1.58) to exhibit depressive symptoms than those who have no or only one unhealthy behavior. Conclusions: Clustering of unhealthy behaviors is positively associated with depressive symptom among Taiwanese adolescents. The findings highlight the importance of strengthening public health interventions to improve physical activity and decrease sedentary behaviors.

High-contrast visualization of human skin cancers with combined reflectance confocal and moxifloxacin-based two-photon microscopy: An ex vivo study.

BACKGROUND AND OBJECTIVES: Precise determination of cancer margin during skin cancer surgery is crucial for complete resection and further clinical prognosis. Although reflection confocal microscopy (RCM) has been used for perioperative guiding, its reflection contrast has limitations in detecting cancer cells in the dermis. We previously developed combined reflection confocal (RC) and moxifloxacin-based two-photon (MB-TP) microscopy for sensitive cancer detection by using multiple contrast mechanisms. In this study, the performance of combined microscopy was characterized in various skin cancer specimens and compared with standard methods. MATERIALS AND METHODS: Seven human skin specimens in total including two normal ones, three basal cell carcinomas (BCCs), and two squamous cell carcinomas (SCCs) were collected and imaged in fresh condition. Moxifloxacin ophthalmic solution was topically instilled for cell labeling for 3-5 minutes, then mosaic imaging with the combined microscopy was conducted. The imaged specimens were imaged again after exogenous nuclear labeling for comparison and then processed for standard hematoxylin and eosin histology. RESULTS: Combined RC and MB-TP microscopy visualized both cell and extracellular matrix structures of the skin specimens with multiple contrasts of reflection, moxifloxacin fluorescence, autofluorescence, and second harmonic generation. It distinguished normal cell structures in the skin dermis such as hair follicles, sebaceous and eccrine glands from BCC nests, and SCCs based on cell organization. Normal cell structures had organized cell arrangements for their functions, while cancer cell structures had dense and disorganized cell arrangements. Cellular features found by combined microscopy images were confirmed by both TP microscopy with nuclear labeling and histological examination. CONCLUSIONS: The imaging results showed the potential of combined microscopy for sensitive cancer detection and in vivo guiding of skin cancer surgery.

(-)-Epicatechin Reverses Glucose Intolerance in Rats Housed at Thermoneutrality.

Diabetes is a life-threatening and debilitating disease with pathological hallmarks, including glucose intolerance and insulin resistance. Plant compounds are a source of novel and effective therapeutics, and the flavonoid (-)-epicatechin, common to popular foods worldwide, has been shown to improve carbohydrate metabolism in both clinical studies and preclinical models. We hypothesized that (-)-epicatechin would alleviate thermoneutral housing-induced glucose intolerance. Male rats were housed at either thermoneutral (30 °C) or room temperature (24 °C) for 16 weeks and gavaged with either 1 mg/kg body weight or vehicle for the last 15 days before sacrifice. Rats housed at thermoneutrality had a significantly elevated serum glucose area under the curve (p < 0.05) and reduced glucose-mediated insulin secretion. In contrast, rats at thermoneutrality treated with (-)-epicatechin had improved glucose tolerance and increased insulin secretion (p < 0.05). Insulin tolerance tests revealed no differences in insulin sensitivity in any of the four groups. Pancreatic immunohistochemistry staining showed significantly greater islet insulin positive cells in animals housed at thermoneutrality. In conclusion, (-)-epicatechin improved carbohydrate tolerance via increased insulin secretion in response to glucose challenge without a change in insulin sensitivity.

Study of the factors influencing the use of MyData platform based on personal health record data sharing system.

BACKGROUND: The application of telemedicine and electronic health (eHealth) technology has grown in importance during the COVID-19 pandemic, and a new approach in personal data management and processing MyData, has emerged. Data portability and informational self-determination are fundamental concepts of MyData. This study analysed the factors that influence acceptance of the MyData platform, which, reflects the right to self-determine personal data. METHODS: The study involved participants having experience using the MyData platform, and the key factors of the unified theory of acceptance and use of technology were used in the research model (performance expectancy, effort expectancy, social influence, facilitation condition and behavioural intention to use). The questionnaire comprided 27 items, and system usage log data were used to confirm that behavioural intention to use affected actual use behaviour through structural equation modeling. RESULTS: In total, 1153 participants completed the survey. The goodness of fit in the structural equation model indices indicates that the data fit the research model well. Performance expectancy, social influence, and facilitating conditions had direct effects on behavioural intention to use. We used system usage log data to confirm that behavioural intention to use positively affected actual use behaviour. The impact of the main factors in the unified theory of acceptance and use of technology was not moderated by age or gender, except for performance expectancy. CONCLUSIONS: This study is the first to examine the factors influencing the use of the MyData platform based on the personal health record data sharing system in Korea. In addition, the study confirmed the use behaviour of the MyData platform utilising the system's actual usage log for each function and analysing the effect of the intention of use on actual use. Our study serves as a significant foundation for the acceptance of data portability and sharing concepts. It also lays the foundation for expanding the data economy and ecosystem in the pandemic era.

Thermoneutrality induces vascular dysfunction and impaired metabolic function in male Wistar rats: a new model of vascular disease.

OBJECTIVE: Cardiovascular disease is of paramount importance, yet there are few relevant rat models to investigate its pathology and explore potential therapeutics. Housing at thermoneutral temperature (30 °C) is being employed to humanize metabolic derangements in rodents. We hypothesized that housing rats in thermoneutral conditions would potentiate a high-fat diet, resulting in diabetes and dysmetabolism, and deleteriously impact vascular function, in comparison to traditional room temperature housing (22 °C). METHODS: Male Wistar rats were housed at either room temperature or thermoneutral temperatures for 16 weeks on either a low or high-fat diet. Glucose and insulin tolerance tests were conducted at the beginning and end of the study. At the study's conclusion, vasoreactivity and mitochondrial respiration of aorta and carotid were conducted. RESULTS: We observed diminished vasodilation in vessels from thermoneutral rats ( P  < 0.05), whereas high-fat diet had no effect. This effect was also observed in endothelium-denuded aorta in thermoneutral rats ( P  < 0.05). Vasoconstriction was significantly elevated in aorta of thermoneutral rats ( P  < 0.05). Diminished nitric oxide synthase activity and nitrotyrosine, and elevated glutathione activity were observed in aorta from rats housed under thermoneutral conditions, indicating a climate of lower nitric oxide and excess reactive oxygen species in aorta. Thermoneutral rat aorta also demonstrated less mitochondrial respiration with lipid substrates compared with the controls ( P  < 0.05). CONCLUSION: Our data support that thermoneutrality causes dysfunctional vasoreactivity, decreased lipid mitochondrial metabolism, and modified cellular signaling. These are critical observations as thermoneutrality is becoming prevalent for translational research models. This new model of vascular dysfunction may be useful for dissection of targetable aspects of cardiovascular disease and is a novel and necessary model of disease.