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Obesity is associated with an increased risk of cardiovascular disease. Gambi-jung (GBJ), a modified herbal formula of Taeumjowi-tang, induces weight loss in high-fat diet (HFD)-fed obese mice. Meanwhile, concerns have been raised regarding Ephedra sinica Stapf (ES), the primary herb of GBJ, having potential adverse cardiovascular effects. However, there have been no reports on the effects of ES and ephedrine-containing products on obesity-induced cardiac apoptosis. Therefore, to investigated the effect of GBJ and ES on HFD-induced cardiac apoptosis, we utilized Western blot analysis, TUNEL-staining, and histological staining of heart tissues from HFD-fed obese mice. Western blot analysis showed that there were significant changes in the protein levels of anti-apoptotic markers (B-cell lymphoma (BCL) protein 2 (BCL-2), BCL-XL, and X-linked inhibitor of apoptosis protein) and pro-apoptotic markers (Fas, Fas-associated protein with death domain, BCL-2 agonist of cell death, BCL-2 associated X, cytochrome C, and cleaved caspase-9) in the heart of HFD-fed mice. In contrast administration of 250 mg/kg GBJ for 12 weeks significantly reversed the protein levels related to the apoptosis signaling pathway, which was greater than that of ES administration. Furthermore, GBJ-treated mice had markedly decreased number of TUNEL-stained apoptotic cells compared to the HFD group. Moreover, GBJ improved the mitochondrial function by regulating the genes expression of uncoupling protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, optic atrophy protein 1, and fission protein 1. Notably, hematoxylin and eosin histological staining showed no changes in the heart tissues of GBJ- and ES-treated mice, indicating that long-term administration of GBJ and ES did not exert any adverse effects on the cardiac tissue. The present study lays the foundation to support the efficacy of GBJ in protecting cardiac cell apoptosis induced by HFD feeding, as well as to verify the cardiac safety of GBJ administration.

Abstract Background This systematic literature review explored the general characteristics, validation, and reliability of pediatric simulation-based education (P-SBE). Methods A literature search was conducted between May 23 and 28 using the PRISMA guidelines, which covered databases such as MEDLINE, EMBASE, CINAHL, and Cochrane Library. In the third selection process, the original texts of 142 studies were selected, and 98 documents were included in the final content analysis. Results A total of 109 papers have been published in the ten years since 2011. Most of the study designs were experimental studies, including RCT with 76 articles. Among the typologies of simulation, advanced patient simulation was the most common (92), and high-fidelity simulation was the second most common (75). There were 29 compatibility levels and professional levels, with 59 scenarios related to emergency interventions and 19 scenarios related to communication feasibility and decision making. Regarding the effect variable, 65 studies confirmed that skills were the most common. However, validity of the scenarios and effect variables was not verified in 56.1% and 67.3% of studies, respectively. Conclusion Based on these findings, simulation based-education (SBE) is an effective educational method that can improve the proficiency and competence of medical professionals dealing with child. Learning through simulation provides an immersive environment in which learners interact with the presented patient scenario and make decisions, actively learning the attitudes, knowledge, and skills necessary for medical providers. In the future, it is expected that such research on SBE will be actively followed up and verified for its validity and reliability.

Abstract Although the role of the Wnt pathway in colon carcinogenesis has been described previously, it has been recently demonstrated that Wnt signaling originates from highly dynamic nano-assemblies at the plasma membrane. However, little is known regarding the role of oncogenic APC in reshaping Wnt nanodomains. This is noteworthy, because oncogenic APC does not act autonomously and requires activation of Wnt effectors upstream of APC to drive aberrant Wnt signaling. Here, we demonstrate the role of oncogenic APC in increasing plasma membrane free cholesterol and rigidity, thereby modulating Wnt signaling hubs. This results in an overactivation of Wnt signaling in the colon. Finally, using the Drosophila sterol auxotroph model, we demonstrate the unique ability of exogenous free cholesterol to disrupt plasma membrane homeostasis and drive Wnt signaling in a wildtype APC background. Collectively, these findings provide a link between oncogenic APC, loss of plasma membrane homeostasis and CRC development.

IntroductionResearchers have highlighted concerns regarding the limited diagnostic utility and ecological validity of the Continuous Performance Test (CPT). Recent advancements in VR-based CPTs have attempted to address these concerns by simulating real-life scenarios and enhancing attention deficit hyperactivity disorder (ADHD) diagnosis; however, certain areas require improvement for obtaining reliable data from both healthy individuals and those with ADHD. To tackle these issues, we developed an enhanced VR-based CPT program featuring four distinct difficulty levels, advancing toward home-based assessment.MethodOur feasibility study involved subjects without ADHD to establish a normative profile for VR-based CPT before extending it to ADHD assessment. Our sample included 20 Korean adults. They received a VR device with the VR-based CPT program installed and were asked to perform 1-2 blocks per day at home. Participants were instructed to complete 12 blocks over the subsequent 2 weeks. Psychological assessments and electroencephalograms (EEGs) were administered before and after the program. Post-study usability measures were also collected.ResultHigher commission errors were notably evident in the “very high” difficulty level which featured complex stimuli and increased distraction. A notable correlation emerged between the overall distraction level and CPT accuracy, along with a significant link between intensity scores and commission errors. No significant differences were found in psychological assessment and there were no significant changes in the Theta-Beta Ratio (TBR) index before and after the program. The usability of our program was fair.DiscussionThe study reveals that the newly designed VR-CPT program, simulating diverse real-life environments and offering varying task difficulty levels, proved acceptable and feasible. The key point of our study was that the adjustment and segmentation of difficulty levels in the VR-based CPT were achieved, and that this effort was validated by examining the impact of different levels of difficulty on CPT measures. Implementing this experimental setup in a home-based environment increased ecological validity, as well as clinical utility. Limitations and suggested directions for further investigation are described in detail.

In a double homozygous mouse model of myotonic dystrophy type 1, Hu et al. use antisense oligonucleotide correction of myotonia to induce a therapeutic shift from an overabundance of oxidative muscle fibers to mechanically stronger glycolytic fibers.

This study explored feeding recycled food waste-based diets for gut health, nutrient digestibility, bone morphology, and bone mineral level in laying hens. Hy-Line Brown laying hens (n = 150) were randomly allocated to three experimental treatments consisting of a commercial control diet, a recycled food waste-based diet, and a 50:50 blend of the control and food waste-based diets, with 50 replicates of a single bird per cage per treatment from 24 to 63 weeks of age. Egg production was recorded daily and feed intake was measured weekly. The gut pH, jejunal and ileal morphology, nutrient digestibility, bone morphology, and mineral composition were measured at 63 weeks of age. Hens on the food waste-based treatment had similar egg production but lower feed conversion ratio (FCR, 1.948 vs. 2.172 kg feed/kg egg, p < 0.001) and higher ileal pH (p < 0.001) and bone ash content (p < 0.001) compared to birds on the control treatment. Moreover, hens fed the food waste-based diets had higher ileal digestible energy (p < 0.001); ileal energy digestibility (p < 0.01); tibia S, Fe, Mn, and Zn levels (p < 0.05); and Mg, K, S, Mn, and Mo digestibility (p < 0.05) compared to hens fed the control diets. Hens offered the 50:50 blend diets had higher tibia P, Mg, and Mo levels (p < 0.05) and higher Ca digestibility (p < 0.05) compared to those fed the control diets. Thus, feeding recycled food waste-based diets is effective to improve laying performance, nutrient digestibility, and bone mineralization in laying hens.

Background: Older adults are vulnerable to comorbid depression and anxiety symptoms; however, these conditions are widely underrecognized and often untreated. Understanding their combined manifestation using objective measurements, such as clinician-rated scales and heart rate variability (HRV), can help refine the diagnosis and select a treatment strategy for geriatric patients. Methods: This study included patients over 65 years who were mainly diagnosed with either category of depressive or anxiety disorders from the psychiatric outpatient clinic in a university hospital. A total of 114 patients met eligibility with a completed collection of electrocardiograms, the Hamilton Depression Rating Scale (HDRS; clinician-rated depression), and the Hamilton Anxiety Scale (HAS; clinician-rated anxiety) to assess the severity of symptoms. Both main and interaction effects between HDRS and HAS on HRV parameters were examined. Results: Significant interaction effects between clinician-rated depression and anxiety (HDRS × HAS) on HRV reduction in frequency parameters (i.e., nuLF, nuHF, LF/HF ratio) were found, which consistently indicated autonomic nervous system dysregulation. Findings imply that HRV could reflect synergistic effects of comorbid depressive and anxiety symptoms, perhaps due to the amplification of individual symptoms in geriatric patients. Conclusions: The results imply that using objective measurements can improve diagnostic accuracy, particularly in geriatric patients with comorbid status, and the normalization of the autonomic nervous system might be a candidate target for prevention and treatment.

Objective The present study examined the effects of exogenous emulsifiers and multi-enzyme supplementation into a low energy density diet on growth performance, visceral organ parameters, blood metabolites, ileal morphology, and nutrient digestibility in broiler chickens from hatch to 21 days. Methods One hundred and sixty-eight one-day-old Ross 308 broiler chickens were allocated in a completely randomized design to 24 pens and each pen was assigned to one of four dietary treatments to give six replications with seven chickens in a cage. Dietary treatments were: i) positive control with standard energy level (PC); ii) negative control with 100 kcal/kg lower energy of the standard level (NC); iii) NC diet supplemented 0.05% calcium stearoyl-2 lactylate as an emulsifier (NC+E); and iv) NC diet supplemented with both 0.05% calcium stearoyl-2 lactylate and 0.05% multi-enzyme (NC+E+M). Corn and soybean meal-based control diets containing vegetable oil were formulated to meet the Ross 308 nutrition specification. Chickens were fed ad-libitum with the treatment diets and sampling was conducted on day 21. Results Our results revealed that emulsifier and multi-enzyme supplementation into NC diets improved (p0.05) visceral organ weight, blood metabolites, and intestinal morphology in broiler chickens fed NC diets. Conclusion Supplementation of emulsifier and multi-enzyme in the NC diet would support improving growth performance in young broiler chickens with improved feed efficiency and increased nutrient digestibility thereby curtailing the negative impact of energy reduction in the diets.

The present study evaluated the impacts of fibre-degrading enzymes on the profiles of non-starch polysaccharides (NSP) and oligosaccharides (OS) in the ileum of broiler chickens offered wheat- or maize-based diets under subclinical necrotic enteritis (NE) challenge. A 2 × 2 × 4 factorial arrangement of treatments was used. Factors were the following: NE challenge, no or yes; diet type, wheat- or maize-based; and supplemental enzymes, control (no enzyme), family 10 xylanase (XYN10), family 11 xylanase (XYN11) or β-mannanase (MAN). Birds in the challenged group were inoculated with Eimeria on d 9 and Clostridium perfringens on d 14 and 15. A 3-way interaction (P = 0.047) occurred on overall (d 0 to 16) weight gain. When NE was present, all the supplemental enzymes increased weight gain in birds fed the wheat-based diet; whereas in those fed the maize-based diet supplemental XYN10 and XYN11 decreased weight gain. When NE was absent, birds fed the wheat-based diet supplemented with XYN10 or MAN presented increased weight gain compared to non-supplemented birds, but no improvements with enzyme addition were observed in birds fed the maize-based diet. A 3-way interaction (P = 0.002) was observed on insoluble NSP level in the ileum. When NE was absent, all the supplemental enzymes reduced the ileal level of insoluble NSP, regardless of diet type. In the challenged birds, supplementing XYN10 and MAN reduced insoluble NSP level in the ileum, but only in birds fed the wheat-based diet. Ileal soluble NSP level was reduced by supplemental XYN11 and MAN, but only in birds fed the wheat-based diet, resulting in a 2-way diet type × enzyme interaction (P

The present study investigated whether supplementing fibre-degrading enzymes can ameliorate the severity of subclinical necrotic enteritis (NE) in broiler chickens offered wheat- or maize-based diets. A total of 1,544 mixed-sex broiler chickens were assigned to 16 experimental treatments as a 2 × 2 × 4 factorial arrangement of treatments. The factors were the following: NE challenge, yes or no; diet type, wheat- or maize-based; and enzyme supplementation, control (no enzyme), family 10 xylanase (XYN10), family 11 xylanase (XYN11) or β-mannanase (MAN). Each treatment was replicated 6 times, with 16 birds per replicate pen. A three-way challenge × diet type × enzyme interaction occurred for body weight at 21 d of age (P = 0.025) and overall feed conversion ratio (P = 0.001). In the non-challenged birds fed the wheat-based diet, supplementing MAN increased d 21 body weight compared to the control. In challenged birds fed the maize-based diet, supplemental XYN11 impeded body weight and overall FCR compared to the control. Birds offered the maize-based diet presented heavier relative gizzard weights at both 16 and 21 d of age (P

ABSTRACT: This study was conducted to determine the effects of dietary yeast cell wall (YCW) on growth performance, intestinal health, and immune responses of broiler chickens. In a randomized completely block design (block: initial body weight), a total of 800 broilers (Ross 308; 45.18 ± 3.13 g of initial body weight) were assigned to 2 dietary treatments (40 birds/pen; 10 replicates/treatment) and fed for 5 wk: 1) a basal broiler diet based on corn-soybean meal (CON) and 2) CON + 0.05% dietary YCW. Growth performance was measured at intervals in 3 phase feed program. On the final day of the study, one bird per pen was randomly selected and euthanized for sample collection. Broilers fed YCW had decreased (P < 0.05) feed conversion ratio during the grower phase compared with those fed CON. The YCW increased (P < 0.05) villus height to crypt depth ratio in the duodenum, jejunum, and ileum compared with the CON. In addition, the YCW tended to higher (P < 0.10) number of goblet cells in the duodenum than in the CON. Broilers fed YCW had increased (P < 0.05) serum TGF- β1, ileal gene expression of the claudin family, and relative abundance of Lactobacillus, Prevotella, and Enterococcus compared with the CON, but decreased serum TNF-α (P < 0.05), IL-1β (P < 0.05), and IL-6 (P < 0.10), ileal gene expression of IL-6 (P < 0.05), and relative abundance of Clostridium (P < 0.05). The present study demonstrated that the addition of dietary YCW in broiler diets enhanced the intestinal health of broiler chickens and may be associated with modulated intestinal morphology and integrity by upregulating tight junction-related protein gene expression and modifying the ileal microbiota. In addition, dietary YCW modulated immune responses and inflammatory cytokine gene expression in the ileum.

The present study characterised the types and amounts of non-starch polysaccharides (NSP) remaining undigested along the gastrointestinal tract (GIT) of broiler chickens offered a typical wheat- or maize-based diet. One-day old Cobb 500 mixed-sex chicks were assigned to 24 pens, with 10 birds/pen and 12 pens/treatment. Birds were offered the experimental diets in 3 phases (starter, day 0 to 10; grower, day 11 to 24 and finisher, day 25 to 35). Excreta and digesta samples from the crop, gizzard, duodenum, jejunum, ileum and caeca were collected at 12 and 35 days of age, and analysed for the NSP flow. The wheat-based diet contained higher levels of soluble NSP than the maize-based diet, whereas insoluble NSP levels were similar between the 2 diets. Detailed analysis of NSP constituents revealed that arabinoxylans were the primary NSP in the wheat-based diet, mostly in insoluble form. Pectins were the predominant NSP in the maize-based diet, followed by arabinoxylans. Overall, birds offered the wheat-based diet presented higher levels of soluble NSP remaining in all gut sections compared to birds offered the maize-based diet, at both 12 and 35 days of age (P

Heart rate variability (HRV) is a known psychophysiological marker for diverse psychiatric symptoms. In this study, we aimed to explore the potential for clinical use of HRV by investigating the interrelationship between HRV indices and clinical measures mainly used to assess depressive and anxious symptoms. Participants who reported depressive and anxious symptoms were designated into the following groups: group 1, clinician-rated and self-rated depression; group 2, only self-rated depression; group 3, clinician-rated and self-rated anxiety; group 4, only self-rated anxiety. Statistical comparisons were performed between these groups to investigate the association between HRV and clinical measures. As a result, HRV variables showed significant correlations only with the clinician-rated assessments. Moreover, both time and frequency domain HRV indices were significantly different between groups 1 and 2, but groups 3 and 4 showed significant differences only in frequency domain HRV indices. Our study showed that HRV is an objective indicator for depressive or anxious symptoms. Additionally, it is considered a potential indicator for predicting the severity or state of depressive symptoms rather than of anxious symptoms. This study will contribute to increasing the diagnostic utility of discriminating those symptoms based on HRV in the future.

Abstract To facilitate rapid determination of cellular viability caused by the inhibitory effect of drugs, numerical deep learning algorithms was used for unlabeled cell culture images captured by a light microscope as input. In this study, A549, HEK293, and NCI-H1975 cells were cultured, each of which have different molecular shapes and levels of drug responsiveness to doxorubicin (DOX). The microscopic images of these cells following exposure to various concentrations of DOX were trained with the measured value of cell viability using a colorimetric cell proliferation assay. Convolutional neural network (CNN) models for the study cells were constructed using augmented image data; the predicted cell viability using CNN models was compared to the cell viability measured by colorimetric assay. The linear relationship coefficient (r2) between measured and predicted cell viability was determined as 0.94–0.95 for the three cell types. In addition, the measured and predicted IC50 values were not statistically different. When drug responsiveness was estimated using allogenic models that were trained with a different cell type, the correlation coefficient decreased to 0.004085–0.8643. Our models could be applied to label-free cells to conduct rapid and large-scale tests while minimizing cost and labor, such as high-throughput screening for drug responsiveness.

Objective The study was conducted to investigate the impact of boron supplementation on nutrient digestibility, inflammatory responses, blood metabolites and diarrhea index, and their relevance to growth performance in weaned pigs housed in good and poor sanitary environments for 14 days after weaning. Methods A total of 108 male pigs (Duroc×[Yorkshire×Landrace]) weaned at 21 days of age were used in a randomized complete block design with 2×3 factorial arrangement. Pigs were assigned to three boron treatments (0, 5, and 10 mg/kg) under two environments (good and poor sanitary) to give six replicates per treatment (3 pigs per replicate). On 0, 7, and 14 days, one pig per replicate was euthanized to collect, ileum tissue samples, and rectal fecal samples. Results Boron supplementation quadratically influenced (p

This study was to characterise the undigested nutrients present along the gastrointestinal tract of birds offered common wheat- or maize-based diets, with the goal of optimising utilisation of enzymes to enhance digestive efficiency. Wheat- and maize-based diets were offered to 240 mixed-sex broilers (10 birds/pen; n = 12) from 1 to 35 d post–hatch. Digestibility of dry matter, starch, crude protein and non-starch polysaccharides (NSP) were measured in the crop, gizzard, duodenum, jejunum, ileum, caeca and excreta at d 12 and 35 post–hatch. Analysis of nutrient levels in the excreta presented that more than 30% of nutrients provided in the feed was wasted, irrespective of wheat or maize diet type. On average, 92 g/kg crude protein, 92 g/kg insoluble NSP and 14 g/kg oligosaccharides were not utilised by birds at d 12 post–hatch. The quantity of water-insoluble NSP in the small intestine at d 12 was lower in birds offered the wheat-based diet compared to those fed the maize-based diet (P

Abstract Background In 2019, the South Korean government started designating rehabilitation medical institutions to facilitate the early return of patients with stroke (PWS) to their communities after discharge. However, a detailed operating model has not yet been suggested. We aimed to develop a hospital-based early supported community reintegration model for PWS that is suitable for South Korea based on knowledge translation in cooperation with clinical experts and PWS. Methods Clinical experts (n = 13) and PWS (n = 20) collaboratively participated in the process of developing the early supported community reintegration model at a national hospital in South Korea, using the following phases of the knowledge-to-action cycle: (1) identifying knowledge, (2) adapting the knowledge to the local situation, (3) assessing barriers and facilitators to local use of knowledge, and (4) tailoring and developing the program. Barriers and facilitators to local use of knowledge were assessed multidimensionally at the individual, interpersonal, organizational, and community level based on the social-ecological model. Literature reviews, workshops, individual and group interviews, and group meetings using nominal group technique were conducted in each phase of the knowledge-to-action cycle. Results Each phase of the knowledge-to-action cycle for developing the early supported community reintegration model and a newly developed model including the following components were reported: (1) revision of strategies of organizations related to community reintegration support, (2) establishment of a multidepartmental and multidisciplinary community reintegration support system, (3) standardization of patient-centered multidisciplinary goal setting, (4) multidimensional classification of community reintegration support areas, and (5) development of guidelines for a tailored community reintegration support program. Conclusions We designed a hospital-based multidimensional and multidisciplinary early supported community reintegration model that comprehensively included several elements of community rehabilitation in connection with hospitals and communities, taking into account the South Korean situation of lacking community rehabilitation infrastructure. In developing a guideline for a tailored community reintegration support program, we attempted to take into consideration various situations faced by PWS in South Korea, which is in a transitional stage for community rehabilitation. It is expected that this early supported community reintegration model can be referenced in other countries that are in a transitional stage of community rehabilitation.

Objective This experiment was conducted to investigate the effect of insoluble cellulose supplementation to diets on the growth performance, intestinal morphology, the incidence of diarrhea, nutrients digestibility, and inflammatory responses in altering environmental conditions of animals housing. Methods A total of 108 male pigs (Duroc×[Yorkshire×Landrace]) were randomly allocated to one of three dietary treatments (cellulose 0%, 1%, 2%) and two environmental conditions (good sanitary condition vs. poor sanitary condition) to give 6 replicate pens per treatment with three pigs per each pen at 14 days post-weaning. Results Pigs were in good sanitary condition had higher average daily gain (p

While interest in developing the human microbiome as a biomarker for attention-deficit hyperactivity disorder (ADHD) is increasing, there has been limited exploration in utilizing urine samples. In this study, we analysed urine microbiome profiles by extracting 16S ribosomal DNA from purified bacteria-derived extracellular membrane vesicles obtained from urine samples. Sequencing libraries were constructed by amplifying V3–V4 hypervariable regions sequenced using Illumina MiSeq. Profiles of male Korean children and adolescents with ADHD (n = 33) were compared with healthy sex-matched controls (n = 39). Statistically controlling for age, we found decreased alpha diversity in the urine bacteria of the ADHD group, as evidenced by reduced Shannon and Simpson indices (p < 0.05), and significant differences in beta diversity between the two groups (p < 0.001). The phyla Firmicutes and Actinobacteriota, as well as the genera Ralstonia and Afipia, were relatively more abundant in the ADHD group. The phylum Proteobacteria and the genera Corynebacterium and Peptoniphilus were more abundant in the control group. Notably, the genus Afipia exhibited significant correlations with the Child Behavior Checklist Attention Problems score and DSM-oriented ADHD subscale. This study is the first to propose the urine microbiome as a potential biomarker for pediatric ADHD.

BackgroundAttention deficit hyperactivity disorder (ADHD) is clinically diagnosed; however, quantitative analysis to statistically analyze the symptom severity of children with ADHD via the measurement of head movement is still in progress. Studies focusing on the cues that may influence the attention of children with ADHD in classroom settings, where children spend a considerable amount of time, are relatively scarce. Virtual reality allows real-life simulation of classroom environments and thus provides an opportunity to test a range of theories in a naturalistic and controlled manner. The objective of this study was to investigate the correlation between participants’ head movements and their reports of inattention and hyperactivity, and to investigate how their head movements are affected by different social cues of different sensory modalities.MethodsThirty-seven children and adolescents with (n = 20) and without (n = 17) ADHD were recruited for this study. All participants were assessed for diagnoses, clinical symptoms, and self-reported symptoms. A virtual reality-continuous performance test (VR-CPT) was conducted under four conditions: (1) control, (2) no-cue, (3) visual cue, and (4) visual/audio cue. A quantitativecomparison of the participants’ head movements was conducted in three dimensions (pitch [head nods], yaw [head turns], and roll [lateral head inclinations]) using a head-mounted display (HMD) in a VR classroom environment. Task-irrelevant head movements were analyzed separately, considering the dimension of movement needed to perform the VR-CPT.ResultsThe magnitude of head movement, especially task-irrelevant head movement, significantly correlated with the current standard of clinical assessment in the ADHD group. Regarding the four conditions, head movement showed changes according to the complexity of social cues in both the ADHD and healthy control (HC) groups.ConclusionChildren and adolescents with ADHD showed decreasing task-irrelevant movements in the presence of social stimuli toward the intended orientation. As a proof-of-concept study, this study preliminarily identifies the potential of VR as a tool to understand and investigate the classroom behavior of children with ADHD in a controlled, systematic manner.

After a nuclear accident, population monitoring is necessary to determine the radiation exposure levels of the affected population. One of the monitoring components is direct thyroid measurements to assess the internal thyroid dose (mainly from 131I with a relatively short physical half-life: 8.02 days). These measurements are particularly important for young children but were not adequately performed after the 2011 Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. Herein we propose a feasible and robust method to obtain as much reliable human data as possible for the dose reconstructions following a nuclear accident. The method employs three types of measurements: simplified, additional, and detailed measurements. The simplified measurements are performed using conventional NaI(Tl) survey meters to quickly triage heavily exposed individuals. The additional measurements are conducted using mobile whole-body counters to detect cesium (Cs; with longer retention in the body) as a tracer of 131I. And the detailed measurements are taken using spectrometric devices; they provide the most reliable data and are used to confirm the other measurements. We also discussed the target subjects and the monitoring period based on the experiences gained following the FDNPP accident. The early post-nuclear-accident phase is the most important period for the dose reconstruction for the affected populations; however, it is also the most challenging period in terms of allocating the necessary monitoring resources. It is thus vital that all countries that operate nuclear power plants establish and maintain a system for nuclear emergency preparedness and response.

Patients with myotonic dystrophy type 1 (DM1) identify chronic fatigue as the most debilitating symptom, which manifests in part as prolonged recovery after exercise. Clinical features of DM1 result from pathogenic gain-of-function activity of transcripts containing an expanded microsatellite CUG repeat (CUGexp). In DM1 mice, therapies targeting the CUGexp transcripts correct the molecular phenotype, reverse myotonia, and improve muscle pathology. However, the effect of targeted molecular therapies on fatigue in DM1 is unknown. Here, we use two mouse models of DM1, age-matched wild-type controls, an exercise-activity assay, electrical impedance myography, and therapeutic antisense oligonucleotides (ASOs) to show that exaggerated exercise-induced fatigue progresses with age, is unrelated to muscle fiber size, and persists despite correction of the molecular phenotype for 3 months. In old DM1 mice, ASO treatment combined with an exercise training regimen consisting of treadmill walking 30 min per day 6 days per week for 3 months reverse all measures of fatigue. Exercise training without ASO therapy improves some measures of fatigue without correction of the molecular pathology. Our results highlight a key limitation of ASO monotherapy for this clinically important feature and support the development of moderate-intensity exercise as an adjuvant for targeted molecular therapies of DM1.

Low social capital has been reported to be associated with depression in adolescents. In general, adolescents with immigrant backgrounds lack social capital. By employing a latent profile analysis (LPA) for the specification of social capital among multicultural adolescents, depression interventions can be explored through the framework of social capital. The purpose of this study was to identify distinct latent profiles of social capital and explore the depressive symptoms of multicultural adolescents in those profiles. Data of 1,244 adolescents from the Multicultural Adolescents Panel Survey (MAPS) were used, which was conducted for 3rd-year middle school students in 2016. An LPA was used to identify profiles by different social capital classes and Quade's non-parametric ANCOVA was used to confirm the differences in depressive symptoms between profiles. Latent profile analysis indicated four classes. Analysis revealed that there were differences in the level of depressive symptoms according to the social capital sub-profiles (F = 44.42, p < 0.001). Class 1 had the lowest level of depressive symptoms (13.91 ± 4.43) and Class 4 had the highest level (18.07 ± 5.25). The depressive symptoms scores of Classes 2 and 3 were 16.49 ± 5.27 and 16.74 ± 4.95, respectively. These findings provide insight into the interplay between social capital and depressive symptoms among multicultural adolescents. Support in consideration of differences in social capital is needed to reduce depression among multicultural adolescents.

Abstract Guanine-rich quadruplex (G-QD) are formed by conversion of nucleotides with specific sequences by stabilization of positively charged K+ or Na+. These G-QD structures differentially absorb two-directional (right- and left-handed) circularly polarized light, which can discriminate the parallel or anti-parallel structures of G-QDs. In this study, G-QDs stabilized by Pb2+ were analyzed by a circular dichroism (CD) spectroscopy to determine Pb2+ concentration in water samples. Thrombin aptamer (TBA), PS2.M, human telomeric DNA (HTG), AGRO 100, and telomeric related sequence (T2) were studied to verify their applicability as probes for platform- and label-free detection of Pb2+ in environmental as well as laboratory samples. Among these nucleotides, TBA and PS2.M exhibited higher binding constants for Pb2+, 1.20–2.04 × 106/M at and 4.58 × 104–1.09 × 105/M at 100 micromolar and 100 mM K+ concentration, respectively. They also exhibited excellent selectivity for Pb2+ than for Al3+, Cu2+, Ni2+, Fe3+, Co2+, and Cr2+. When Pb2+ was spiked into an effluent sample from a wastewater treatment plant (WWTP), its existence was detected by CD spectroscopy following a simple addition of TBA or PS2.M. By the addition of TBA and PS2.M, the Pb2+ signals were observed in effluent samples over 0.5 micromolar (100 ppb) concentration. Furthermore, PS2.M caused a Pb2+-specific absorption band in the effluent sample without spiking of Pb2+, and could be induced to G-QD structure by the background Pb2+ concentration in the effluent, 0.159 micromolar concentration (3.30 ppb). Taken together, we propose that TBA and PS2.M are applicable as platform- and label-free detection probes for monitoring Pb2+ in environmental samples such as discharged effluent from local WWTPs, using CD spectroscopy.

The production performance of broiler breeder hens in response to different levels of total lysine during the early laying period was investigated. A total of 126 Ross 308 parent stock hens were offered one of seven dietary treatments formulating elevated contents of total lysine ranging from 0.55% to 0.79% (0.04 scale; 133 g of feed) from 23 to 29 weeks of age. Each treatment had six replicates with three birds per pen. Body weight was recorded triweekly and eggs were collected and weighted at 9:00 am daily. One hen from each pen was euthanized to collect blood samples and visceral organs were harvested and weighed. Egg production, egg weight and egg mass were lower (p < 0.05) in hens offered a diet containing 0.55% total lysine compared to those fed the diet containing higher total lysine. Hens offered a diet containing 0.71%, 0.75%, and 0.79% total lysine had greater (p = 0.008) egg production rate compared to those offered a diet containing lysine less than 0.71%. The number of total eggs produced tended to be greater (p = 0.083) in hens offered a diet containing 0.71 and 0.75% total lysine compared to the other treatments. The number of settable egg production was higher (p < 0.001) in hens offered a diet contacting 0.79% total lysine compared to those fed the diet containing lower levels of total lysine. The relative weights of oviduct and ovary were lower (p < 0.05) in hens offered a diet containing 0.59% total lysine compared to the other treatments. No difference found in body weight, the number of total eggs, double-yolk eggs and abnormal shell eggs among the treatments. The urea nitrogen, estradiol-17 beta and progesterone in plasma were not affected by treatments. Based on linear- and quadratic-plateau models, total lysine requirements for egg production, settable egg production and egg mass at the early laying period were to be 0.73%, 0.77%, and 0.71%, respectively. Modern broiler breeder hens likely require higher total lysine than NRC recommendation in a diet for enhancing productivity during the early-laying period.

Objective To evaluate calcium stearoyl-2 lactylate (CSL) performance as an exogenous emulsifier together with lipase for broiler diets. Methods In total, 252 one-day-old Ross 308 broiler chickens were allocated in a completely randomized design to give 6 replications per treatment with 7 birds in each cage. There were six dietary treatments representing a 2×3 factorial arrangement consisted of two energy levels (standard energy [positive control, PC] and −100 kcal/kg of the requirement level [negative control, NC]) and three dietary treatments (without additives [CON], CON+CSL [CSL], and CON+CSL+lipase [CSL-Lipase]). Corn and soybean meal-based experimental diets containing vegetable oil were formulated. Growth performance, blood parameters, visceral organ weights, ileal morphology, nutrient digestibility, and cytokine gene expression were measured. Results Birds fed a diet including CSL increased (p0.05) the weight gain, feed efficiency, ileal morphology, and cytokine concentrations during the experiment period, regardless of dietary energy levels. Conclusion Our results indicated that CSL has a role in improving nutrient digestibility in young birds when supplemented to a corn-soybean meal based broiler diet.

Abstract Background Functional communication is vital in many areas of daily life, and modifying dysfunctional communication has been emphasized in various social areas, including family and school. The present preliminary study addressed the feasibility of a virtual reality (VR)-based interactive feedback program for the modification of dysfunctional communication. Methods Thirty-seven healthy young males completed psychological assessments associated with functional communication and participated in the VR-based program, consisting of the three tasks of ‘exploring the communication style,’ ‘practicing functional communication,’ and ‘expressing empathy.’ Behavioral parameters were recorded based on the participants’ choices among available options and the visual analog scale scores that resulted in responses to questions in the tasks. Results Participants completed the program without dropping-out and reported 10.76 (SD, 9.66) in the Simulator Sickness Questionnaire and 106.97 (SD, 16.66) in the Presence Questionnaire. In exploring the communication style, there was no difference between the dysfunction level-with family and dysfunction level-with a friend, but only the dysfunction level-with family showed significant correlations with the level of communication with parents. In practicing functional communication, the communication scores with the placating, blaming, and computing styles significantly increased according to the repetition of trials. In expressing empathy, the empathetic feeling score was negatively correlated with the perspective-taking score, whereas the emotional intensity score was positively correlated with the level of differentiation of the self. Conclusion These results suggest that the program may have a tolerable level of cybersickness, an adequate level of presence, an improvement in the behavioral parameters that may reflect the important aspects of communication, and a proper reflection of psychological states or interpersonal characteristics. The use of this program can be an important starting point for the development of a more convenient method for delivering VR programs designed to modify dysfunctional communication, which can further increase computerized dissemination.

Objective An experiment was conducted to investigate the response of laying hens fed corn distiller’s dried grains with solubles (DDGS) that are naturally contaminated with deoxynivalenol (DON). Methods One hundred and sixty 52-week-old Lohmann Brown Lite hens were randomly allotted to five dietary treatments with 8 replicates per treatment. The dietary treatments were formulated to provide a range of corn DDGS contaminated with DON from 0% to 20% (i.e., 5% scale of increment). All laying hens were subjected to the same management practices in a controlled environment. Body weight, feed intake and egg production were measured biweekly for the entire 8-week experiment. The egg quality was measured biweekly for 8 weeks. On weeks 4 and 8, visceral organ weights, blood metabolites, intestinal morphology, and blood cytokine concentrations were measured. Results The inclusion of corn DDGS contaminated with DON in the diet did not alter (p> 0.05) the body weight, feed intake, hen-day egg production, egg mass and feed efficiency of the laying hens. No difference was found (p>0.05) in the egg quality of hens that were fed the dietary treatments. Furthermore, hens that were fed a diet containing corn DDGS contaminated with DON showed no change (p>0.05) in the visceral organ weights, the blood metabolites, and the cytokine concentrations. The crypt depth increased (p

The present study investigated the effects of supplementing a low protein (LP) diet supplemented with key essential amino acids (AA) to broilers on growth performance, intestinal tract function, blood metabolites, and nitrogen excretion when the animals were maintained under various sanitary conditions for 35 D after hatching. Three hundred eighty-four one-day-old male broilers (Ross 308) were randomly allotted to groups that received one of 6 dietary treatments in a 2 × 3 factorial arrangement (i.e., 2 environmental conditions and 3 dietary treatments) to give 8 replicates per treatment. Broilers were challenged with 2 environmental conditions (sanitary vs. poor sanitary). The dietary treatments were (1) high protein (HP) diet, (2) LP diet, and (3) LP diet with synthetic key essential AA (LPA): the LP diet was supplemented with synthetic AA up to the required levels for broilers. On day 14, birds consumed the LP diet impaired growth performance compared with those fed the HP diet, while the average daily weight gain-to-feed conversion ratio of birds fed the LPA diet improved to the level of birds fed the HP diet under poor sanitary conditions (P < 0.05). Broilers raised under poor sanitary conditions and fed the LP diet displayed higher (P < 0.05) zonula occludens (ZO-1) expression on day 14 than broilers fed either the HP or LPA diet. Under sanitary conditions, birds fed HP and LPA diets showed higher villus height and crypt depth compared with those of broilers fed the LP diet on day 35. Moreover, broilers raised in the poor sanitary environment had higher (P < 0.05) serum endotoxins than those raised in the sanitary environment. Broilers fed the LPA diet showed reduced (P < 0.05) nitrogen excretion on days 14 and 35 compared with those fed the LP and HP diets independent of the environment. In conclusion, the LPA diet did not impair growth performance under poor sanitary conditions for 14 D after hatch while resulting in lower nitrogen excretion in any environment conditions throughout the experiment.

This study investigated bioaccumulation and toxicity derived from heavy metals in laying hens. The 160 52-week old laying hens were divided into 5 treatments with 8 replicates of 4 birds per pen. The treatments consisted of the control diet (without heavy metals), control diet with half the available dosage (AD, 5 ppm lead and 0.2 ppm mercury), AD (10 ppm lead and 0.4 ppm mercury), 2-fold AD (20 ppm lead and 0.8 ppm mercury), and 3-fold AD (30 ppm lead and 1.2 ppm mercury), and were provided to the laying hens for 8 weeks. Food and water were provided on an ad libitum basis at all times. Body weight and food intake were recorded once every two weeks, and eggs were collected and recorded daily. Two birds from each pen were euthanized to collect blood and organ samples on week 4 and 8. The 3-fold AD diet reduced food intake compared to that of the control and AD diets (P0.05). Heavy metal concentrations in the liver, eggs, and feathers were not detected at both week 4 and 8. Our results indicate that in-feed heavy metals for layer diets up to 30 ppm of lead and 1.2 ppm of mercury brought on hepatic dysfunction increasing blood metabolites that are associated with liver inflammation.

In this study, we investigated the effect of methionine isomers (D- and L-methionine) on growth performance, blood metabolite levels, nutrient digestibility, intestinal morphology, and foot pad dermatitis in broilers challenged with acute heat stress. In total, 240 broilers were randomly allocated in a 2×2 factorial arrangement consisting of two dietary treatments (D- vs. L-methionine) and two thermal environmental conditions (thermo-neutral vs. acute heat stress). Methionine isomers were added to the diet as an ingredient according to the diet formulation. The broilers were exposed to acute heat stress at 33°C for 5 h on day 14. The average daily gain and feed conversion ratio of birds fed L-methionine were higher than those fed D-methionine (P

Abstract Time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) is an imaging‐based analytical technique that can characterize the surfaces of biomaterials. We used TOF‐SIMS to identify important metabolites and oncogenic KRAS mutation expressed in human colorectal cancer (CRC). We obtained 540 TOF‐SIMS spectra from 180 tissue samples by scanning cryo‐sections and selected discriminatory molecules using the support vector machine (SVM) algorithm. Each TOF‐SIMS spectrum contained nearly 860,000 ion profiles and hundreds of spectra were analyzed; therefore, reducing the dimensionality of the original data was necessary. We performed principal component analysis after preprocessing the spectral data, and the principal components (20) of each spectrum were used as the inputs of the SVM algorithm using the R package. The performance of the algorithm was evaluated using the receiver operating characteristic (ROC) area under the curve (AUC) (0.9297). Spectral peaks (m/z) corresponding to discriminatory molecules used to classify normal and tumor samples were selected according to p‐value and were assigned to arginine, α‐tocopherol, and fragments of glycerophosphocholine. Pathway analysis using these discriminatory molecules showed that they were involved in gastrointestinal disease and organismal abnormalities. In addition, spectra were classified according to the expression of KRAS somatic mutation, with 0.9921 AUC. Taken together, TOF‐SIMS efficiently and simultaneously screened metabolite biomarkers and performed KRAS genotyping. In addition, a machine learning algorithm was provided as a diagnostic tool applied to spectral data acquired from clinical samples prepared as frozen tissue slides, which are commonly used in a variety of biomedical tests.

Virtual reality (VR) neuropsychological tests have emerged as a method to explore drug effects in real-life contexts in attention deficit hyperactivity disorder (ADHD) children. Functional near-infrared spectroscopy (fNIRS) is a useful tool to measure brain activity during VR tasks in ADHD children with motor restlessness. The present study aimed to explore the acute effects of methylphenidate (MPH) on behavioral performance and brain activity during a VR-based working memory task simulating real-life classroom settings in ADHD children. In total, 23 children with ADHD performed a VR n-back task before and 2 h after MPH administration concurrent with measurements of oxygenated hemoglobin signal changes with fNIRS. Altogether, 12 healthy control (HC) subjects participated in the same task but did not receive MPH treatment. Reaction time (RT) was shortened after MPH treatment in the 1-back condition, but changes in brain activation were not observed. In the 2-back condition, activation of the left dorsolateral prefrontal cortex (DLPFC) and bilateral medial prefrontal cortex (mPFC) was decreased alongside behavioral changes such as shorter RT, lower RT variability, and higher accuracy after MPH administration. Bilateral mPFC activation in the 2-back condition inversely correlated with task accuracy in the pre-MPH condition; this inverse correlation was not observed after MPH administration. In ADHD children, deactivation of the default mode network mediated by mPFC reduced during high working memory load, which was restored through MPH treatment. Our results suggest that the combination of VR classroom tasks and fNIRS examination makes it easy to assess drug effects on brain activity in ADHD children in settings simulating real-life.

Molecular changes during aging have been studied to understand the mechanism of aging progress. Herein, changes in microRNA (miRNA) expression in the whole blood of mice were studied to systemically reverse aging and propose them as non-invasive biomarkers. Through next-generation sequencing analysis, we selected 27 differentially expressed miRNAs during aging. The most recognized function involved was liver steatosis, a type of non-alcoholic fatty liver disease (NAFLD). Among 27 miRNAs, six were predicted to be involved in NAFLD, miR-16-5p, miR-17-5p, miR-21a-5p, miR-30c-5p, miR-103-3p, and miR-130a-3p; alterations in their blood and liver levels were confirmed by real-time qPCR. The expression of the genes associated in the network of these miRNAs, Bcl2, Ppara, E2f1, E2f2, Akt, Ccnd1, and Smad2/3, also was altered in the liver of aged mice. Following transfection of these miRNAs into 18-month-old mice, levels of miR-21a-5p, miR-103-3p, and miR-30c-5p increased, and their related genes exhibited a reversed expression in the liver. Expression of Mre11a, p16INK4a, and Mtor, reported to be aging-associated molecules, also was reversed in the livers of miRNA-transfected mice. These miRNAs could be non-invasive biomarkers for aging, and they might induce a reverse regulation of aging-associated pathways. This study provides preliminary data on reverse aging, which could be applied further for treatments of adult diseases. Keywords: reverse aging, circulating miRNA, aging biomarker, non-alcoholic fatty liver disease, telomerase

In this paper, an analysis for consumer perception of the level of electricity price, the amount of household electricity consumption and consumer perception on dynamic electricity pricing system in South Korea are investigated. A survey was conducted between July 24 and August 17, 2015 and then for the preference analysis, Binary Logistic Model is applied for the acceptance, Ordered Probit Model is applied. The major findings say that the less they have monthly income, the more satisfied dynamic pricing. In dynamic electricity tariff, real time pricing is most preferred dynamic pricing system and it reaches about 40% of respondents.

Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI–TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker—detected via a liquid biopsy—for the noninvasive diagnosis of lung cancer.

With the identification of Lgr5 as a definitive marker for intestinal stem cells, we used the highly novel, recently described, Lgr5-EGFP-IRES-cre ERT2 knock in mouse model. Mice were injected with azoxymethane (AOM, a colon carcinogen) or saline (control) and fed a chemo-protective diet containing n-3 fatty acids and fermentable fiber (n-3 PUFA+pectin) or a control diet (n-6 PUFA + cellulose). Single cells were isolated from colonic mucosa crypts and three discrete populations of cells were collected via fluorescence activated cell sorting (FACS): Lgr5high (stem cells), Lgr5low (daughter cells) and Lgr5negative (differentiated cells). microRNA profiling and RNA sequencing were performed from the same sample and analyzed. These data refer to ‘Comparative effects of diet and carcinogen on microRNA expression in the stem cell niche of the mouse colonic crypt’ (Shah et al., 2016) [5].

This study implemented a self-study design to examine the researchers' own experiences of transferring in-person co-teaching in teacher education courses into a virtual setting during COVID-19. Multiple qualitative data including planning and reflection discussions for each co-teaching session, students' exit notes, and focus group interviews were collected and analyzed to identify the themes of the experience. Five themes emerged from the data including preparation, technology, instructional management, student engagement, and co-teaching strategies. These themes are described in ways that address how we navigated the transition of co-teaching from in-person to a synchronous virtual setting, steps we took to improve the learning experience of PSTs, and adjustments we carried forward to improve teaching and learning in an in-person co-teaching setting. Related to these themes, we share five lessons we learned about virtual co-teaching and how this experience has also impacted our co-teaching that has returned to in-person. The lessons include depth vs. breath, explicitly detailed planning, maximizing interactions with digital Active Student Response strategies, flexibility, and affordances and constraints of virtual settings for co-teaching strategies.

Background and aims: Discrepancy between ideal self-guide and actual self-concept evoke dejection-related feeling, and often individuals with internet gaming disorder (IGD) use games as the tool to escape those negative emotions. The aim of this study was to evaluate the pattern of self-discrepancy based on actual and ideal self-images and elucidate the neural correlates underlying the distorted self in individuals with IGD.Methods: Nineteen male individuals with IGD and 20 healthy controls (HCs) underwent functional magnetic resonance imaging where they decided on whether they agreed with the adjectives describing their actual or ideal self on a four-point Likert Scale. Two-sample t-test on the self-discrepancy contrast was conducted for neuroimaging analysis and correlation analysis was performed between the behavioral data and regional activities.Results: The IGD group evaluated both their ideal self and actual self more negatively than the HC group. Actual self-concept was associated with satisfaction with psychological needs as opposed to ideal self-guide. Brain activity in the inferior parietal lobule was significantly decreased in individuals with IGD relative to HCs in the self-discrepancy contrast. In addition, neural activity during evaluating actual self-concept showed a significant group difference.Conclusion: These results provide novel evidence for distorted self-concept of people with IGD. Individuals with IGD had a negative ideal and actual self-image. Neurobiologically, dysfunction in the inferior parietal lobule associated with emotional regulation and negative self-evaluation was found in IGD. Considering the characteristics of IGD that often develop in adolescence, this self-concept problem should be noted and applied with appropriate therapy.

Internet gaming disorder (IGD) is a new disorder that warrants further investigation, as recently noted in the research criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Offering controlled environments that increase cue-induced craving, virtual reality cue-exposure therapy has been shown to be effective for some addiction disorders. To assess the feasibility of virtual reality for patients with IGD, this study aimed to develop virtual environments that represent risk situations for inducing craving, and assess the effect of virtual reality in cue reactivity. A total of 64 male adolescents and young adults (34 with IGD and 30 without) were recruited for participation. We developed a virtual internet café environment and the participants were exposed to four different tasks. As the primary feasibility outcome, cravings were measured with a visual analogue scale measuring current urge to play a game after exposure to each task. The virtual internet café induced significantly greater cravings in patients with IGD compared to controls. Additionally, patients exhibited a significantly higher acceptance rate of an avatar's invitation to play a game together than that of controls. In IGD, craving response to the tasks was positively associated with the symptom severity score as measured by Young's Internet Addiction Test. These findings reveal that virtual reality laden with complex game-related cues could evoke game craving in patients with IGD and could be used in the treatment of IGD as a cue-exposure therapy tool for eliciting craving.

Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous condition and identification of clinically meaningful subgroups would open up a new window for personalized medicine. Thus, we aimed to identify new clinical phenotypes in children and adolescents with ADHD and to investigate whether neuroimaging findings validate the identified phenotypes. Neuroimaging and clinical data from 67 children with ADHD and 62 typically developing controls (TDCs) from the ADHD-200 database were selected. Clinical measures of ADHD symptoms and intelligence quotient (IQ) were used as input features into a topological data analysis (TDA) to identify ADHD subgroups within our sample. As external validators, graph theoretical measures obtained from the functional connectome were compared to address the biological meaningfulness of the identified subtypes. The TDA identified two unique subgroups of ADHD, labelled as mild symptom ADHD (mADHD) and severe symptom ADHD (sADHD). The output topology shape was repeatedly observed in the independent validation dataset. The graph theoretical analysis showed a decrease in the degree centrality and PageRank in the bilateral posterior cingulate cortex in the sADHD group compared with the TDC group. The mADHD group showed similar patterns of intra- and inter-module connectivity to the sADHD group. Relative to the TDC group, the inter-module connectivity between the default mode network and executive control network were significantly increased in the sADHD group but not in the mADHD group. Taken together, our results show that the data-driven TDA is potentially useful in identifying objective and biologically relevant disease phenotypes in children and adolescents with ADHD.

We performed dye-enhanced imaging of mouse brain microvessels using spectral focusing coherent anti-Stokes Raman scattering (SF-CARS) microscopy. The resonant signals from C-H stretching in forward CARS usually show high background intensity in tissues, which makes CARS imaging of microvessels difficult. In this study, epi-detection of back-scattered SF-CARS signals showed a negligible background, but the overall intensity of resonant CARS signals was too low to observe the network of brain microvessels. Therefore, Evans blue (EB) dye was used as contrasting agent to enhance the back-scattered SF-CARS signals. Breakdown of brain microvessels by inducing hemorrhage in a mouse was clearly visualized using backward SF-CARS signals, following intravenous injection of EB. The improved visualization of brain microvessels with EB enhanced the sensitivity of SF-CARS, detecting not only the blood vessels themselves but their integrity as well in the brain vasculature.

This study aims to develop a Modular Object-Oriented Dynamic Learning Environment (Moodle)-based online learning system and derive a class model to enhance learners’ creative collaboration capabilities. The research method for this is first to analyze the functional elements of the online learning system to enhance creative collaboration among the functions of the Moodle online learning system. Second, a class model is derived to enhance creative collaboration by applying the constructivist teaching−learning principle. Third, we conduct a verification of the effectiveness of the Moodle-based class model that was developed to enhance creative collaboration. The results of the study show that, among the functions of the Moodle online learning system, forms, real-time conferencing, reciprocal evaluation, Wiki, and blogs have the ability to enhance creative collaboration. Second, the class model for promoting creative collaboration based on a mood-based online learning system consists of self-reflections, learner-driven learning, professional learning, practical task, and the role of the processor. Third, after verifying the application effect of the Moodle-based class model for university students, a significant effect is found in the creative collaboration of university students. The results of this study suggest that: First, the Moodle online learning system should be utilized to provide learners with a variety of online learning opportunities to promote creative collaboration. Second, the teaching−learning operation manual needs to be developed later in order for the class model to be effectively implemented at the classroom site to promote creative collaboration based on the Moodle online learning system.

Attention-deficit/hyperactivity disorder (ADHD) is currently diagnosed by a diagnostic interview, mainly based on subjective reports from parents or teachers. It is necessary to develop methods that rely on objectively measureable neurobiological data to assess brain-behavior relationship in patients with ADHD. We investigated the application of a topological data analysis tool, Mapper, to analyze the brain functional connectivity data from ADHD patients.To quantify the disease severity using the neuroimaging data, the decomposition of individual functional networks into normal and disease components by the healthy state model (HSM) was performed, and the magnitude of the disease component (MDC) was computed. Topological data analysis using Mapper was performed to distinguish children with ADHD (n = 196) from typically developing controls (TDC) (n = 214).In the topological data analysis, the partial clustering results of patients with ADHD and normal subjects were shown in a chain-like graph. In the correlation analysis, the MDC showed a significant increase with lower intelligence scores in TDC. We also found that the rates of comorbidity in ADHD significantly increased when the deviation of the functional connectivity from HSM was large. In addition, a significant correlation between ADHD symptom severity and MDC was found in part of the dataset.The application of HSM and topological data analysis methods in assessing the brain functional connectivity seem to be promising tools to quantify ADHD symptom severity and to reveal the hidden relationship between clinical phenotypic variables and brain connectivity.