Surface terminations control charge transfer from bulk to surface states in topological insulators.

Topological insulators (TI) hold significant potential for various electronic and optoelectronic devices that rely on the Dirac surface state (DSS), including spintronic and thermoelectric devices, as well as terahertz detectors. The behavior of electrons within the DSS plays a pivotal role in the performance of such devices. It is expected that DSS appear on a surface of three dimensional(3D) TI by mechanical exfoliation. However, it is not always the case that the surface terminating atomic configuration and corresponding band structures are homogeneous. In order to investigate the impact of surface terminating atomic configurations on electron dynamics, we meticulously examined the electron dynamics at the exfoliated surface of a crystalline 3D TI (Bi 2 Se 3 ) with time, space, and energy resolutions. Based on our comprehensive band structure calculations, we found that on one of the Se-terminated surfaces, DSS is located within the bulk band gap, with no other surface states manifesting within this region. On this particular surface, photoexcited electrons within the conduction band effectively relax towards DSS and tend to linger at the Dirac point for extended periods of time. It is worth emphasizing that these distinct characteristics of DSS are exclusively observed on this particular surface.

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids.

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

Ganoderma lucidum extract attenuates corticotropin-releasing hormone-induced cellular senescence in human hair follicle cells.

Corticotropin-releasing hormone (CRH) is a key mediator in stress-induced hair growth inhibition. Here, we investigated the impact of stress-induced senescence and evaluated the potential of Ganoderma lucidum (GL) extract in mitigating CRH-induced senescence in human hair follicle cells (hHFCs). We show that CRH treatment increased the senescence-associated beta-galactosidase (SA-ß-GAL) activity and reactive oxygen species (ROS) formation in hHFCs and suppressed alkaline phosphatase (ALP) activity and anagen-inducing genes. However, GL extract restored ALP activity and decreased the expression levels of anagen-related genes in CRH-treated hHFCs. It decreased SA-ß-GAL activity, reduced ROS production, and prevented the phosphorylation of MAPK signaling pathways in CRH-related stress response. Moreover, GL reversed the CRH-induced inhibition of two-cell assemblage (TCA) elongation and Ki67 expression. GL extract attenuates stress-induced hair follicular senescence by delaying catagen entry and scavenging ROS. Our findings suggest that GL extract could be used for treating stress-induced hair loss.

Guidelines for Manufacturing and Application of Organoids: Skin.

To address the limitations of animal testing, scientific research is increasingly focused on developing alternative testing methods. These alternative tests utilize cells or tissues derived from animals or humans for in vitro testing, as well as artificial tissues and organoids. In western countries, animal testing for cosmetics has been banned, leading to the adoption of artificial skin for toxicity evaluation, such as skin corrosion and irritation assessments. Standard guidelines for skin organoid technology becomes necessary to ensure consistent data and evaluation in replacing animal testing with in vitro methods. These guidelines encompass aspects such as cell sourcing, culture techniques, quality requirements and assessment, storage and preservation, and organoid-based assays.

Characterization of a new selective glucocorticoid receptor modulator with anorexigenic activity.

Obesity, a worldwide epidemic, leads to various metabolic disorders threatening human health. In response to stress or fasting, glucocorticoid (GC) levels are elevated to promote food intake. This involves GC-induced expression of the orexigenic neuropeptides in agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus (ARC) via the GC receptor (GR). Here, we report a selective GR modulator (SGRM) that suppresses GR-induced transcription of genes with non-classical glucocorticoid response elements (GREs) such as Agrp-GRE, but not with classical GREs, and via this way may serve as a novel anti-obesity agent. We have identified a novel SGRM, 2-O-trans-p-coumaroylalphitolic acid (Zj7), a triterpenoid extracted from the Ziziphus jujube plant, that selectively suppresses GR transcriptional activity in Agrp-GRE without affecting classical GREs. Zj7 reduces the expression of orexigenic genes in the ARC and exerts a significant anorexigenic effect with weight loss in both high fat diet-induced obese and genetically obese db/db mouse models. Transcriptome analysis showed that Zj7 represses the expression of a group of orexigenic genes including Agrp and Npy induced by the synthetic GR ligand dexamethasone (Dex) in the hypothalamus. Taken together, Zj7, as a selective GR modulator, showed beneficial metabolic activities, in part by suppressing GR activity in non-classical GREs in orexigenic genes. This study demonstrates that a potential anorexigenic molecule may allow GRE-specific inhibition of GR transcriptional activity, which is a promising approach for the treatment of metabolic disorders.

Precision off-the-shelf natural killer cell therapies for oncology with logic-gated gene circuits.

Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis (5-year survival rate of 30.5% in the United States). Designing cell therapies to target AML is challenging because no single tumor-associated antigen (TAA) is highly expressed on all cancer subpopulations. Furthermore, TAAs are also expressed on healthy cells, leading to toxicity risk. To address these targeting challenges, we engineer natural killer (NK) cells with a multi-input gene circuit consisting of chimeric antigen receptors (CARs) controlled by OR and NOT logic gates. The OR gate kills a range of AML cells from leukemic stem cells to blasts using a bivalent CAR targeting FLT3 and/or CD33. The NOT gate protects healthy hematopoietic stem cells (HSCs) using an inhibitory CAR targeting endomucin, a protective antigen unique to healthy HSCs. NK cells with the combined OR-NOT gene circuit kill multiple AML subtypes and protect primary HSCs, and the circuit also works in vivo.

Challenges and potential improvements in the Accreditation Standards of the Korean Institute of Medical Education and Evaluation 2019 (ASK2019) derived through meta-evaluation: a cross-sectional study

PURPOSE: This study aimed to identify challenges and potential improvements in Korea's medical education accreditation process according to the Accreditation Standards of the Korean Institute of Medical Education and Evaluation 2019 (ASK2019). Meta-evaluation was conducted to survey the experiences and perceptions of stakeholders, including self-assessment committee members, site visit committee members, administrative staff, and medical school professors. METHODS: A cross-sectional study was conducted using surveys sent to 40 medical schools. The 332 participants included self-assessment committee members, site visit team members, administrative staff, and medical school professors. The t-test, one-way analysis of variance and the chi-square test were used to analyze and compare opinions on medical education accreditation between the categories of participants. RESULTS: Site visit committee members placed greater importance on the necessity of accreditation than faculty members. A shared positive view on accreditation's role in improving educational quality was seen among self-evaluation committee members and professors. Administrative staff highly regarded the Korean Institute of Medical Education and Evaluation's reliability and objectivity, unlike the self-evaluation committee members. Site visit committee members positively perceived the clarity of accreditation standards, differing from self-assessment committee members. Administrative staff were most optimistic about implementing standards. However, the accreditation process encountered challenges, especially in duplicating content and preparing self-evaluation reports. Finally, perceptions regarding the accuracy of final site visit reports varied significantly between the self-evaluation committee members and the site visit committee members. CONCLUSION: This study revealed diverse views on medical education accreditation, highlighting the need for improved communication, expectation alignment, and stakeholder collaboration to refine the accreditation process and quality.

Stepwise development and expansion of an abdominal normothermic regional perfusion program for donation after circulatory determination of death organ procurement.

INTRODUCTION: Normothermic regional perfusion (NRP) represents an innovative technology that improves the outcomes for liver and kidney recipients of donation after circulatory determination of death (DCD) organs but protocols for abdominal-only NRP (A-NRP) DCD are lacking in the US. METHODS: We describe the implementation and expansion strategies of a transplant-center-based A-NRP DCD program that has grown in volume, geographical reach, and donor acceptance parameters, presented as four eras. RESULTS: In the implementation era, two donors were attempted, and one liver graft was transplanted. In the local expansion era, 33% of attempted donors resulted in transplantation and 42% of liver grafts from donors who died within the functional warm ischemic time (fWIT) limit were transplanted. In the Regional Expansion era, 25% of attempted donors resulted in transplantation and 50% of liver grafts from donors who died within the fWIT limit were transplanted. In the Donor Acceptance Expansion era, 46% of attempted donors resulted in transplantation and 72% of liver grafts from donors who died within the fWIT limit were transplanted. Eight discarded grafts demonstrated a potential opportunity for utilization. CONCLUSION: The stepwise approach to building an A-NRP program described here can serve as a model for other transplant centers.

Postschool Goal Expectations for Youth With Intellectual and Developmental Disabilities.

Using National Longitudinal Transition Study 2012 data, this study explored parent and youth expectations in the areas of postsecondary education, employment, independent living, and financial independence. Compared to youth with other disabilities, youth with intellectual and developmental disabilities and their parents had much lower expectations for the four postschool goals, and parent expectations were much lower than youth's own expectations. Also, youth's race, along with their daily living skills and functional abilities, were positively associated with parent and youth expectations in several future goal areas. Our discussion highlights implications for improving the transition experiences of youth with intellectual and developmental disabilities.

Measurements of Electrodermal Activity, Tissue Oxygen Saturation, and Visual Analog Scale for Different Cuff Pressures.

The quantification of comfort in binding parts, essential human-machine interfaces (HMI) for the functioning of rehabilitation robots, is necessary to reduce physical strain on the user despite great achievements in their structure and control. This study aims to investigate the physiological impacts of binding parts by measuring electrodermal activity (EDA) and tissue oxygen saturation (StO2). In Experiment 1, EDA was measured from 13 healthy subjects under three different pressure conditions (10, 20, and 30 kPa) for 1 min using a pneumatic cuff on the right thigh. In Experiment 2, EDA and StO2 were measured from 10 healthy subjects for 5 min. To analyze the correlation between EDA parameters and the decrease in StO2, a survey using the visual analog scale (VAS) was conducted to assess the level of discomfort at each pressure. The EDA signal was decomposed into phasic and tonic components, and the EDA parameters were extracted from these two components. RM ANOVA and a post hoc paired t-test were used to determine significant differences in parameters as the pressure increased. The results showed that EDA parameters and the decrease in StO2 significantly increased with the pressure increase. Among the extracted parameters, the decrease in StO2 and the mean SCL proved to be effective indicators. Such analysis outcomes would be highly beneficial for studies focusing on the comfort assessment of the binding parts of rehabilitation robots.

Determination of Gait Events and Temporal Gait Parameters for Persons with a Knee-Ankle-Foot Orthosis.

Gait event detection is essential for controlling an orthosis and assessing the patient's gait. In this study, patients wearing an electromechanical (EM) knee-ankle-foot orthosis (KAFO) with a single IMU embedded in the thigh were subjected to gait event detection. The algorithm detected four essential gait events (initial contact (IC), toe off (TO), opposite initial contact (OIC), and opposite toe off (OTO)) and determined important temporal gait parameters such as stance/swing time, symmetry, and single/double limb support. These gait events were evaluated through gait experiments using four force plates on healthy adults and a hemiplegic patient who wore a one-way clutch KAFO and a pneumatic cylinder KAFO. Results showed that the smallest error in gait event detection was found at IC, and the largest error rate was observed at opposite toe off (OTO) with an error rate of -2.8 ± 1.5% in the patient group. Errors in OTO detection resulted in the largest error in determining the single limb support of the patient with an error of 5.0 ± 1.5%. The present study would be beneficial for the real-time continuous monitoring of gait events and temporal gait parameters for persons with an EM KAFO.

A warm-up strategy with or without voluntary contraction on athletic performance, lower-leg temperature, and blood lactate concentration.

It is unclear whether temperature-related warm-up effects can be accomplished by passive warm-up (e.g., by external heat). Therefore, this study compared the effects of two different warm-up protocols with and without voluntary contraction on subsequent sprinting and jumping performance. Eighteen healthy male collegiate students (23.3 ± 2.4 years, 173.8 ± 7.2 cm, 70.5 ± 9.3 kg) randomly experienced 10 min of active (jogging on a treadmill; belt speed: 9.0 km/h at a 1% incline) and passive warm-up (lying down in the warm-up chamber; inner ambient temperature set at 35°C) protocols, followed by ten sets of intermittent exercises in two separate sessions. Athletic performance, lower-leg muscle temperature, and blood lactate concentration were statistically compared using analysis of variance with Tukey-Kramer post-hoc comparisons. Cohen's d effect sizes (ES) were also calculated. There was no warm-up protocol effect over time on 20 m sprint times (condition × time: F9,323 = 1.26, p = 0.25). Maximal vertical jump heights were different (condition × time: F9,323 = 2.0, p = 0.04) such that subjects who performed the active warm-up protocol jumped higher (51.4 cm) than those who did the passive warm-up (49.2 cm, p = 0.04). There was a warm-up protocol effect over time on lower-leg muscle temperature (condition × time: F12,425 = 13.99, p<0.0001) in that there was a 5.5% and 5.8% increase after active (32.8 to 34.6°C, ES = 2.91) and passive (32.9 to 34.9°C, ES = 3.28) warm-up protocols, respectively. Blood lactate concentration was different (condition × time: F2,85 = 3.61, p = 0.03) since the values at the post-warm-up measurements were different between warm-up conditions (active: 4.1 mmol/L; passive: 1.5 mmol/L, p = 0.004, ES = 1.69). Subsequent sprint and jump performance did not differ between the duration- and muscle temperature-matched active and passive warm-up protocols. Non-thermal effects from the warm-up activity may be minimal for sprinting and jumping performance in recreationally active males.

A Meta-Analysis of Treatment for Self-Injurious Behavior in Children and Adolescents With Intellectual and Developmental Disabilities.

Self-injurious behavior (SIB) among children and youth with developmental disabilities has not diminished in prevalence despite the availability of effective interventions, and the impact on quality of life for people and their families is devastating. The current meta-analysis reviews SIB intervention research between 2011 and 2021 using single-case experimental designs with children and youth up to 21 years old and provides a quantitative synthesis of data from high-quality studies including moderator analyses to determine effects of participant and study characteristics on intervention outcomes. Encouraging findings include a high level of effectiveness across studies in the decrease of SIB (Tau-U = -0.90) and increase of positive behavior (Tau-U = 0.73), as well as an increase in studies (relative to prior reviews) reporting intervention fidelity, generalization, maintenance, and social validity. However, our findings shed limited light on potential moderating variables in the development of interventions for children and youth who exhibit SIB. Of the potential moderators of intervention effects, only implementer (researcher/therapist vs. parent/caregiver) and setting (clinic vs. home) were significantly associated with improved outcomes. We discuss the need for more robust involvement of natural communities of implementers in SIB intervention research to better equip them to effectively and sustainably meet the needs of people they care for. We also discuss the importance of creating systems enabling broad access for children with SIB to effective interventions in service of reducing burden for people, families, and society over time.

Immersive virtual reality simulation training for cesarean section: a randomized controlled trial.

BACKGROUND: Caesarean section (CS) is a complex surgical procedure that involves many steps and requires careful precision. Virtual reality (VR) simulation has emerged as a promising tool for medical education and training, providing a realistic and immersive environment for learners to practice clinical skills and decision-making. This study aimed to evaluate the educational effectiveness of a VR simulation program in training the management of patients with premature rupture of membranes (PROM) and CS. MATERIALS AND METHODS: A two-arm parallel randomized controlled trial was conducted with 105 eligible participants randomly assigned to the VR group ( n =53) or the control group ( n =52) in a 1:1 ratio. The VR group received VR simulation training focused on PROM management and CS practice, while the control group watched a video presentation with narrative of clinical scenario and recording of CS. Both groups completed questionnaires assessing their prior experiences with VR, experience in managing patients with PROM and performing CS, as well as their confidence levels. These questionnaires were administered before and after the intervention, along with a mini-test quiz. RESULTS: Baseline characteristics and previous experiences were comparable between the two groups. After the intervention, the VR group had higher confidence scores in all four aspects, including managing patients with PROM, performing CS as an operator, and understanding the indications and complications of CS, compared to the control group. The VR group also achieved significantly higher scores on the mini-test quiz [median (interquartile range), 42 (37-48) in the VR group; 36 (32-40) in the control group, P <0.001]. CONCLUSION: VR simulation program can be an effective educational tool for improving participants' knowledge and confidence in managing patients with PROM and performing CS.

Activated somatostatin interneurons orchestrate memory microcircuits.

Despite recent advancements in identifying engram cells, our understanding of their regulatory and functional mechanisms remains in its infancy. To provide mechanistic insight into engram cell functioning, we introduced a novel local microcircuit labeling technique that enables the labeling of intraregional synaptic connections. Utilizing this approach, we discovered a unique population of somatostatin (SOM) interneurons in the mouse basolateral amygdala (BLA). These neurons are activated during fear memory formation and exhibit a preference for forming synapses with excitatory engram neurons. Post-activation, these SOM neurons displayed varying excitability based on fear memory retrieval. Furthermore, when we modulated these SOM neurons chemogenetically, we observed changes in the expression of fear-related behaviors, both in a fear-associated context and in a novel setting. Our findings suggest that these activated SOM interneurons play a pivotal role in modulating engram cell activity. They influence the expression of fear-related behaviors through a mechanism that is dependent on memory cues.

Effects of Post Traumatic Growth on Successful Aging in Breast Cancer Survivors in South Korea: The Mediating Effect of Resilience and Intolerance of Uncertainty.

This study aimed to identify post-traumatic growth and successful aging and the mediating effects of resilience and intolerance of uncertainty in breast cancer survivors. This study employed a descriptive survey approach. Data were collected from 143 breast cancer survivors between 27 January and 10 December 2021, at a cancer center in Gyeongsangnam-do, South Korea. SPSS/WIN 25.0 and PROCESS Macro version 3.5 were used for data analysis. Descriptive statistics were analyzed with SPSS. PROCESS was used to conduct a mediation analysis and the significance of the mediating effect was evaluated using 95% confidence intervals. Successful aging was significantly associated with post-traumatic growth, resilience, and the intolerance of uncertainty. The impact of post-traumatic growth on successful aging was mediated by resilience in breast cancer survivors. Resilience should be considered when developing nursing interventions to enhance post-traumatic growth and promote successful aging in breast cancer survivors.

Activation of mitochondrial aldehyde dehydrogenase 2 promotes hair growth in human hair follicles.

INTRODUCTION: Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion. OBJECTIVES: To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion. METHODS: The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2',7'- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen. RESULTS: During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3ß/ß-catenin signaling in HFs. CONCLUSIONS: Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction.

Effective data quality management for electronic medical record data using SMART DATA.

OBJECTIVES: In the medical field, we face many challenges, including the high cost of data collection and processing, difficult standards issues, and complex preprocessing techniques. It is necessary to establish an objective and systematic data quality management system that ensures data reliability, mitigates risks caused by incorrect data, reduces data management costs, and increases data utilization. We introduce the concept of SMART data in a data quality management system and conducted a case study using real-world data on colorectal cancer. METHODS: We defined the data quality management system from three aspects (Construction - Operation - Utilization) based on the life cycle of medical data. Based on this, we proposed the "SMART DATA" concept and tested it on colorectal cancer data, which is actual real-world data. RESULTS: We define "SMART DATA" as systematized, high-quality data collected based on the life cycle of data construction, operation, and utilization through quality control activities for medical data. In this study, we selected a scenario using data on colorectal cancer patients from a single medical institution provided by the Clinical Oncology Network (CONNECT). As SMART DATA, we curated 1,724 learning data and 27 Clinically Critical Set (CCS) data for colorectal cancer prediction. These datasets contributed to the development and fine-tuning of the colorectal cancer prediction model, and it was determined that CCS cases had unique characteristics and patterns that warranted additional clinical review and consideration in the context of colorectal cancer prediction. CONCLUSIONS: In this study, we conducted primary research to develop a medical data quality management system. This will standardize medical data extraction and quality control methods and increase the utilization of medical data. Ultimately, we aim to provide an opportunity to develop a medical data quality management methodology and contribute to the establishment of a medical data quality management system.

Effect of Household Type on the Prevalence of Climacteric Syndrome among Middle-Aged Men.

Research on climacteric syndrome among middle-aged men remains scant compared to the research among women. Research is also lacking on climacteric syndrome among older adults living alone, particularly men, who are more vulnerable than females living alone. This cross-sectional study investigated whether the prevalence of climacteric syndrome is associated with the type of household middle-aged men live in and identified the determinants of climacteric syndrome based on the household type. Six hundred middle-aged men living in multi-person households and six hundred living alone were surveyed about general characteristics, diet-related factors, and climacteric syndrome. Data were analyzed using Pearson's chi-squared test, Fisher's exact test, and logistic regression. The risk of climacteric syndrome in single-person households was found to be 1.6 times higher than that among multi-person households (p = 0.006). In multi-person households, income and breakfast frequency predicted climacteric syndrome (p < 0.05), while age, breakfast frequency, dinner frequency, and weekly eating out frequency predicted climacteric syndrome in single-person households (p < 0.05). Thus, dietary factors are more closely linked to the prevalence of climacteric syndrome in single-person households than in multi-person households. This highlights the need for climacteric syndrome interventions for middle-aged men, whose health concerns may persist into older adulthood.

TinyFallNet: A Lightweight Pre-Impact Fall Detection Model.

Falls represent a significant health concern for the elderly. While studies on deep learning-based preimpact fall detection have been conducted to mitigate fall-related injuries, additional efforts are needed for embedding in microcomputer units (MCUs). In this study, ConvLSTM, the state-of-the-art model, was benchmarked, and we attempted to lightweight it by leveraging features from image-classification models VGGNet and ResNet while maintaining performance for wearable airbags. The models were developed and evaluated using data from young subjects in the KFall public dataset based on an inertial measurement unit (IMU), leading to the proposal of TinyFallNet based on ResNet. Despite exhibiting higher accuracy (97.37% < 98.00%) than the benchmarked ConvLSTM, the proposed model requires lower memory (1.58 MB > 0.70 MB). Additionally, data on the elderly from the fall data of the FARSEEING dataset and activities of daily living (ADLs) data of the KFall dataset were analyzed for algorithm validation. This study demonstrated the applicability of image-classification models to preimpact fall detection using IMU and showed that additional tuning for lightweighting is possible due to the different data types. This research is expected to contribute to the lightweighting of deep learning models based on IMU and the development of applications based on IMU data.