An AIE-based fluorescent probe to detect peroxynitrite levels in human serum and its cellular imaging.

An AIE-based fluorescent probe was designed to evaluate peroxynitrite levels in complex biological samples. The newly synthesized hydrazone-conjugated probe fluoresces strongly in the presence of peroxynitrite. Clinically, the peroxynitrite levels can be measured in human serum and cellular mitochondria with an LOD of 6.5 nM by fluorescence imaging in vitro.

Ultrasound-Guided Modified Thread Carpal Tunnel Release for Carpal Tunnel Syndrome: A Pilot Study.

PURPOSE: This study aimed to investigate the effectiveness and safety of modified thread carpal tunnel release (mTCTR) using Smartwire-01 in patients with carpal tunnel syndrome (CTS). MATERIALS AND METHODS: Patients with CTS who required CTR were enrolled. Symptom severity and functional status were assessed using the Boston Carpal Tunnel Syndrome Questionnaire-Symptom Severity Scale (BCTQ-SSS) and Functional Status Scale (BCTQ-FSS), and pain was assessed using a numerical rating scale (NRS) at 4, 8, and 12 weeks after mTCTR. The scores were compared with the pre-procedural scores. The electrophysiologic study and median nerve cross-sectional area (CSA) measurements at the wrist before and 12 weeks after mTCTR were compared. RESULTS: A total of 11 patients were included. No adverse effects were reported throughout the study period. The NRS, BCTQ-SSS, and BCTQ-FSS scores significantly improved at 4 weeks after mTCTR, and this improvement persisted throughout the follow-up period (NRS and BCTQ-SSS, P < 0.001; BCTQ-FSS, P = 0.012). After 12 weeks, the latency and velocity of the median sensory nerve action potential significantly improved, compared with those before mTCTR (latency, 5.4 ± 1.3 to 4.7 ± 1.1 ms, P = 0.01; velocity 27.8 ± 6.8 to 31.8 ± 7.4 m/s, P = 0.019). No significant change was observed in the median nerve CSA before and after mTCTR. CONCLUSION: mTCTR using Smartwire-01 is a safe and effective procedure and a possible alternative to surgery.

Characterisation of runs of homozygosity and inbreeding coefficients in the red-brown Korean native chickens.

Objective: The analysis of runs of homozygosity (ROH) has been applied to assess the level of inbreeding and identify selection signatures in various livestock species. The objectives of this study were to characterize the ROH pattern, estimate the rate of inbreeding, and identify signatures of selection in the red-brown Korean native chickens. Methods: The Illumina 60K SNP chip data of 651 chickens was used in the analysis. Runs of homozygosity were analysed using the PLINK v1.9 software. Inbreeding coefficients were estimated using the GCTA software and their correlations were examined. Genomic regions with high levels of ROH were explored to identify selection signatures. Results: A total of 32,176 ROH segments were detected in this study. The majority of the ROH segments were shorter than 4 Mb. The average ROH inbreeding coefficients (FROH) varied with the length of ROH segments. The means of inbreeding coefficients calculated from different methods were also variable. The correlations between different inbreeding coefficients were positive and highly variable (r = 0.18 -1). Five ROH islands harbouring important Quantitative trait loci were identified. Conclusion: This study assessed the level of inbreeding and patterns of homozygosity in Red-brown native Korean chickens. The results of this study suggest that the level of recent inbreeding is low which indicates substantial progress in the conservation of red-brown Korean native chickens. Additionally, Candidate genomic regions associated with important production traits were detected in homozygous regions.

Change in femoral cartilage cross-sectional area after aerobic and resistance exercise.

We compared the immediate response and recovery of femoral cartilage morphology following aerobic or resistance exercise to a control condition. Fifteen healthy young males (23.9 years; 170.1 cm; 69.7 kg) visited the laboratory three separate days and randomly performed one of the 30 min exercise aerobic exercise (treadmill running); resistance exercises (leg presses, back squats, and knee extensions); or seated rest as the control, each followed by the 50 min recovery. Ultrasonographic images of the femoral cartilage cross-sectional area (CSA) were obtained before and after exercise and every 5 min thereafter. To test exercise effects over time, a mixed model analysis of variance and Tukey-Kramer post-hoc tests were performed (p<0.05). The femoral cartilage CSA was different (condition × time: F34,742=4.30, p<0.0001) that the femoral cartilage CSA was decreased after the aerobic (-5.8%, p<0.0001) and the resistance (-3.4%, p=0.04) exercises, compared to the pre-exercise levels. Deformed femoral cartilage CSA took 35- and 10 min to return to the pre-exercise levels after aerobic and resistance exercises (p>0.09), respectively. Thirty minutes of moderate exertion performing aerobic or resistance exercises immediately reduced the femoral cartilage CSA. A rest period ranging from 10 to 35 min was required for cartilage recovery after weight-bearing exercises.

Design of DNA Storage Coding Scheme with LDPC Codes and Interleaving.

In this paper, we propose a new coding scheme for DNA storage using low-density parity-check (LDPC) codes and interleaving techniques. While conventional coding schemes generally employ error correcting codes in both inter and intra-oligo directions, we show that inter-oligo LDPC codes, optimized by differential evolution, are sufficient in ensuring the reliability of DNA storage due to the powerful soft decoding of LDPC codes. In addition, we apply interleaving techniques for handling non-uniform error characteristics of DNA storage to enhance the decoding performance. Consequently, the proposed coding scheme reduces the required number of oligo reads for perfect recovery by 26.25% ~ 38.5% compared to existing state-of-the-art coding schemes. Moreover, we develop an analytical DNA channel model in terms of non-uniform binary symmetric channels. This mathematical model allows us to demonstrate the superiority of the proposed coding scheme while isolating the experimental variation, as well as confirm the independent effects of LDPC codes and interleaving techniques.

Increased Upper Extremity Muscle Mass in Ambulatory Children with Cerebral Palsy.

AIM: To compare muscle mass in the upper and lower extremities between ambulatory children with cerebral palsy (CP) and typically developing (TD) children. MATERIALS AND METHODS: A total of 21 children aged 2 to 12 years with CP and a Gross Motor Function Classification System (GMFCS) level of I, II, or III were matched with 21 TD children for age, sex, and body mass index. The lean body mass (LBM) of each extremity was calculated from whole-body dual-energy X-ray absorptiometry. RESULTS: The LBM of the upper extremities was greater in children with CP compared to TD children, and the difference was significant in the GMFCS level II group (1340.6 g vs. 1004.2 g, p = 0.027). There was no significant difference in the LBM of the lower extremities between the CP and TD groups (p = 0.190). The ratio of lower extremity LBM to total extremity LBM was lower in children with CP, while the ratio of upper extremity LBM to total extremity LBM was higher in children with CP (73.2% vs. 78.5% [p < 0.001] and 26.7% vs. 21.5% [p < 0.001], respectively). CONCLUSIONS: Ambulatory children with CP, especially in the GMFCS level II group, exhibit greater muscle mass in the upper extremities compared to TD children.

Development of an innovative approach using portable eye tracking to assist ADHD screening: a machine learning study.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) affects a significant proportion of the pediatric population, making early detection crucial for effective intervention. Eye movements are controlled by brain regions associated with neuropsychological functions, such as selective attention, response inhibition, and working memory, and their deficits are related to the core characteristics of ADHD. Herein, we aimed to develop a screening model for ADHD using machine learning (ML) and eye-tracking features from tasks that reflect neuropsychological deficits in ADHD. Methods: Fifty-six children (mean age 8.38 ± 1.58, 45 males) diagnosed with ADHD based on the Diagnostic and Statistical Manual of Mental Disorders, fifth edition were recruited along with seventy-nine typically developing children (TDC) (mean age 8.80 ± 1.82, 33 males). Eye-tracking data were collected using a digital device during the performance of five behavioral tasks measuring selective attention, working memory, and response inhibition (pro-saccade task, anti-saccade task, memory-guided saccade task, change detection task, and Stroop task). ML was employed to select relevant eye-tracking features for ADHD, and to subsequently construct an optimal model classifying ADHD from TDC. Results: We identified 33 eye-tracking features in the five tasks with the potential to distinguish children with ADHD from TDC. Participants with ADHD showed increased saccade latency and degree, and shorter fixation time in eye-tracking tasks. A soft voting model integrating extra tree and random forest classifiers demonstrated high accuracy (76.3%) at identifying ADHD using eye-tracking features alone. A comparison of the model using only eye-tracking features with models using the Advanced Test of Attention or Stroop test showed no significant difference in the area under the curve (AUC) (p = 0.419 and p=0.235, respectively). Combining demographic, behavioral, and clinical data with eye-tracking features improved accuracy, but did not significantly alter the AUC (p=0.208). Discussion: Our study suggests that eye-tracking features hold promise as ADHD screening tools, even when obtained using a simple digital device. The current findings emphasize that eye-tracking features could be reliable indicators of impaired neurobiological functioning in individuals with ADHD. To enhance utility as a screening tool, future research should be conducted with a larger sample of participants with a more balanced gender ratio.

Symptom clusters in adolescent depression and differential responses of clusters to pharmacologic treatment.

OBJECTIVE: Symptoms of depression in adolescents are widely variable, but they are often interactive and clustered. The analysis of interactions and clusters among individual symptoms may help predict treatment outcomes. We aimed to determine clusters of individual symptoms in adolescent depression and their changes in the response to pharmacological treatment. METHOD: A total of 95 adolescents, aged 12-17 years, with major depressive disorder were included. Participants were treated with escitalopram, and depressive symptoms were assessed at baseline (V1) and 1, 2, 4, 6, and 8 weeks (V6). The severity of depression was assessed using the Children's Depression Rating Scale-Revised. To construct network and clustering structures among symptoms, the Gaussian graphical model and Exploratory Graph Analysis with the tuning parameter to minimize the extended Bayesian information criterion were adopted. RESULTS: Exploratory Graph Analysis revealed that symptoms of depression comprised four clusters: impaired activity, somatic concerns, subjective mood, and observed affect. The main effect of visit with decreased symptom severity was significant in all four clusters; however, the degree of symptom improvement differed among the four clusters. The effect size of score differences from V1 to V6 was the highest in the subjective mood (Cohen's d = 1.075), and lowest in impaired activity (d = 0.501) clusters. CONCLUSION: The present study identified four symptom clusters associated with adolescent depression and their differential changes related to antidepressant treatment. This finding suggests that escitalopram was the most effective at improving subjective mood among different clusters. However, other therapeutic modalities may be needed to improve other clusters of symptoms, consequently leading to increased overall improvement of depression in adolescents.

Differentiation of Human-induced Pluripotent Stem Cell-derived Dental Stem Cells through Epithelial-Mesenchymal Interaction.

Research on tooth regeneration using human-induced pluripotent stem cells (hiPSCs) is valuable for autologous dental regeneration. Acquiring mesenchymal and epithelial cells as a resource for dental regeneration is necessary because mesenchymal-epithelial interactions play an essential role in dental development. We reported the establishment of hiPSCs-derived dental epithelial-like cell (EPI-iPSCs), but hiPSCs-derived dental mesenchymal stem cells (MSCs) have not yet been reported. This study was conducted to establish hiPSCs-derived MSCs and to differentiate them into dental cells with EPI-iPSCs. Considering that dental MSCs are derived from the neural crest, hiPSCs were induced to differentiate into MSCs through neural crest formation to acquire the properties of dental MSCs. To differentiate hiPSCs into MSCs through neural crest formation, established hiPSCs were cultured and differentiated with PA6 stromal cells and differentiated hiPSCs formed neurospheres on ultralow-attachment plates. Neurospheres were differentiated into MSCs in serum-supplemented medium. Neural crest-mediated MSCs (NC-MSCs) continuously showed typical MSC morphology and expressed MSC markers. After 8 days of odontogenic induction, the expression levels of odontogenic/mineralization-related genes and dentin sialophosphoprotein (DSPP) proteins were increased in the NC-MSCs alone group in the absence of coculturing with dental epithelial cells. The NC-MSCs and EPI-iPSCs coculture groups showed high expression levels of amelogenesis/odontogenic/mineralization-related genes and DSPP proteins. Furthermore, the NC-MSCs and EPI-iPSCs coculture group yielded calcium deposits earlier than the NC-MSCs alone group. These results indicated that established NC-MSCs from hiPSCs have dental differentiation capacity with dental epithelial cells. In addition, it was confirmed that hiPSCs-derived dental stem cells could be a novel cell source for autologous dental regeneration.

Identification of new major histocompatibility complex-B Haplotypes in Bangladesh native chickens.

OBJECTIVE: The major histocompatibility complex in chicken demonstrates a great range of variations within varities, breeds, populations and that can eventually influence their immuneresponses. The preset study was conducted to understand the major histocompatibility complex-B (MHC-B) variability in five major populations of Bangladesh native chicken: Aseel, Hilly, Junglefowl, Non-descript Deshi, and Naked Neck. METHODS: These five major populations of Bangladesh native chicken were analyzed with a subset of 89 single nucleotide polymorphisms (SNPs) in the high-density MHC-B SNP panel and Kompetitive Allele-Specific polymerase chain reaction genotyping was applied. To explore haplotype diversity within these populations, the results were analyzed both manually and computationally using PHASE 2.1 program. The phylogenetic investigations were also performed using MrBayes program. RESULTS: A total of 136 unique haplotypes were identified within these five Bangladesh chicken populations, and only one was shared (between Hilly and Naked Neck). Phylogenetic analysis showed no distinct haplotype clustering among the five populations, although they were shared in distinct clades; notably, the first clade lacked Naked Neck haplotypes. CONCLUSION: The present study discovered a set of unique MHC-B haplotypes in Bangladesh chickens that could possibly cause varied immune reponses. However, further investigations are required to evaluate their relationships with global chicken populations.

Depression and posttraumatic stress disorder in adolescents with nonsuicidal self-injury: comparisons of the psychological correlates and suicidal presentations across diagnostic subgroups.

BACKGROUND: Nonsuicidal self-injury (NSSI) combined with suicide ideation increases the risk of suicidal behaviors. Depression and posttraumatic stress disorder (PTSD) are comorbidities of NSSI compounding this relationship. The present study compared diagnostic subgroups of NSSI based on current depression and PTSD on psychological correlates (i.e., vulnerabilities and impairment) and suicidal presentations (i.e., suicidal cognitions and behaviors) in a psychiatric sample of adolescents. METHODS: Eighty-seven adolescents meeting DSM-5 criteria for NSSI and 104 age-range-matched nonclinical controls (NC) participated. Participants completed self-report measures on psychological vulnerabilities and impairment (e.g., emotion regulation difficulties, negative cognitions). Adolescents with NSSI also completed clinical interviews on psychiatric diagnoses and a recent self-injurious behavior (SIB). Scores on the psychological correlates of NSSI were compared between adolescents with NSSI and NC, and across three diagnostic subgroups of NSSI (A: NSSI+/depression-/PTSD-, n = 14; B: NSSI+/depression+/PTSD-, n = 57; C: NSSI+/depression+/PTSD+, n = 14). Differences between NSSI diagnostic subgroups were tested on the motives for SIB and accompanying suicidal presentations (e.g., desire, intent, motive, lethality). RESULTS: Common comorbidities of NSSI included depression, panic disorder, generalized anxiety disorder, and PTSD. The NSSI subgroup classification was significantly associated with panic disorder, which was controlled for in the subsequent group comparisons. Overall, adolescents who engage in NSSI with vs. without depression reported more psychological vulnerabilities and impairment and a greater degree of suicidal thoughts/desire in SIB (i.e., groups B, C >A), which remained significant after controlling for panic disorder. An increased odds of the suicidal motive for SIB was found in adolescents with all three conditions (i.e., group C: NSSI+/depression+/PTSD+) compared to those with NSSI but neither depression nor PTSD (i.e., group A: NSSI+/depression-/PTSD-); however, this was not significant after controlling for panic disorder. CONCLUSIONS: Psychological underpinnings of adolescent NSSI in clinical contexts may be largely associated with concurrent depression. Suicidal motives in adolescents who engage in NSSI in the presence of depression and PTSD may be confounded by the co-occurrence of panic disorder. This study warrants the importance of attending to the comorbid depression with NSSI in adolescents as it is related to an increase in suicidal desire accompanying SIB.

Evaluation of Vertical Level Differences Between Left and Right Vocal Folds Using Artificial Intelligence System in Excised Canine Larynx.

OBJECTIVES: This study aimed to establish an artificial intelligence (AI) system to classify vertical level differences between vocal folds during vocalization and to evaluate the accuracy of the classification. METHODS: We designed models with different depths between the right and left vocal folds using an excised canine larynx. Video files for the data set were obtained using a high-speed camera system and a color complementary metal oxide semiconductor camera with global shutter. The data sets were divided into training, validation, and testing. We used 20,000 images for building the model and 8000 images for testing. To perform deep learning multiclass classification and to estimate the vertical level difference, we introduced DenseNet121-ConvLSTM. RESULTS: The model was trained several times using different numbers of epochs. We achieved the most optimal results at 100 epochs, and the batch size used during training was 16. The proposed DenseNet121-ConvLSTM model achieved classification accuracies of 99.5% and 88.0% for training and testing, respectively. After verification using an external data set, the overall accuracy, precision, recall, and f1-score were 90.8%, 91.6%, 90.9%, and 91.2%, respectively. CONCLUSIONS: The newly developed AI system may be an easy and accurate method for classifying superior and inferior vertical level differences between vocal folds. Thus, this AI system can be applied and may help in the assessment of vertical level differences in patients with unilateral vocal fold paralysis.

Varus-valgus Alignment of Humeral Short Stem in Reverse Total Shoulder Arthroplasty: Does It Really Matter?

BACKGROUND: The utilization of short humeral stems in reverse total shoulder arthroplasty (RTSA) has gained attention in recent times. However, concerns regarding the risk of misalignment during implant insertion are associated with their use. METHODS: Eight fresh-frozen cadaveric shoulders were prepared for dissection and biomechanical testing. A bespoke humeral implant was fabricated to facilitate assessment of neutral, varus, and valgus alignments using a single stem, and 10° was established as the maximum permissible angle for misalignments. Shift in humerus position and changes in deltoid length attributable to misalignments relative to the neutral position were evaluated using a Microscribe 3DLx system. The impingement-free range of motion (IFROM), encompassing abduction, adduction, internal rotation (IR), and external rotation (ER), was gauged using a digital goniometer. The capacity for abduction was evaluated at maximal abduction angles under successive loading on the middle deltoid. A specialized traction system coupled with a force transducer was employed to measure anterior dislocation forces. RESULTS: Relative to the neutral alignment, valgus alignment resulted in a more distal (10.5 ± 2.4 mm) and medial (8.3 ± 2.2 mm) translation of the humeral component, whereas the varus alignment resulted in the humerus shifting more superiorly (11.2 ± 1.3 mm) and laterally (9.9 ± 0.9 mm) at 0° abduction. The valgus alignment exhibited the highest abduction angle than neutral alignment (86.2°, P<0.001). Conversely, the varus alignment demonstrated significantly higher adduction (18.4±7.4°, P<0.001), IR (68.9±15.0°, P=0.014), and ER (45.2±10.5°, P=0.002) at 0° abduction compared to the neutral alignments. Anterior dislocation forces were considerably lower (23.8N) in the varus group compared to the neutral group at 0°ER (P=0.047). Additionally, abduction capability was markedly higher in varus alignment at low deltoid loads than the neutral alignment (5N, P=0.009; 7.5N, P=0.007). CONCLUSIONS: The varus position enhances rotational ROM but increases instability, while the valgus position does not significantly impact ROM or instability compared to the neutral position.

Iterative Soft Decoding Algorithm for DNA Storage Using Quality Score and Redecoding.

Ever since deoxyribonucleic acid (DNA) was considered as a next-generation data-storage medium, lots of research efforts have been made to correct errors occurred during the synthesis, storage, and sequencing processes using error correcting codes (ECCs). Previous works on recovering the data from the sequenced DNA pool with errors have utilized hard decoding algorithms based on a majority decision rule. To improve the correction capability of ECCs and robustness of the DNA storage system, we propose a new iterative soft decoding algorithm, where soft information is obtained from FASTQ files and channel statistics. In particular, we propose a new formula for log-likelihood ratio (LLR) calculation using quality scores (Q-scores) and a redecoding method which may be suitable for the error correction and detection in the DNA sequencing area. Based on the widely adopted encoding scheme of the fountain code structure proposed by Erlich et al., we use three different sets of sequenced data to show consistency for the performance evaluation. The proposed soft decoding algorithm gives 2.3%  âˆ¼  7.0% improvement of the reading number reduction compared to the state-of-the-art decoding method and it is shown that it can deal with erroneous sequenced oligo reads with insertion and deletion errors.

Combining chromosomal microarray and clinical exome sequencing for genetic diagnosis of intellectual disability.

Despite the current widespread use of chromosomal microarray analysis (CMA) and exome/genome sequencing for the genetic diagnosis of unexplained intellectual disability (ID) in children, gaining improved diagnostic yields and defined guidelines remains a significant challenge. This is a cohort study of children with unexplained ID. We analyzed the diagnostic yield and its correlation to clinical phenotypes in children with ID who underwent concurrent CMA and clinical exome sequencing (CES). A total of 154 children were included (110 [71.4%] male; mean [SD] age, 51.9 [23.1] months). The overall diagnosis yield was 26.0-33.8%, with CMA contributing 12.3-14.3% and CES contributing 13.6-19.4%, showing no significant difference. The diagnostic rate was significantly higher when gross motor delay (odds ratio, 6.69; 95% CI, 3.20-14.00; P < 0.001), facial dysmorphism (odds ratio, 9.34; 95% CI 4.29-20.30; P < 0.001), congenital structural anomaly (odds ratio 3.62; 95% CI 1.63-8.04; P = 0.001), and microcephaly or macrocephaly (odds ratio 4.87; 95% CI 2.05-11.60; P < 0.001) were presented. Patients with only ID without any other concomitant phenotype (63/154, 40.9%) exhibited a 6.3-11.1% diagnostic rate.

Validation and development of Voice Handicap Index-Throat (VHI-T) for Koreans.

INTRODUCTION: This study aimed to develop, validate, and analyze the reliability of the Korean version of the Voice Handicap Index-Throat (VHI-Tk). METHODS: This prospective study included 103 patients in the case group with voice problems (18 with functional dysphonia, 44 with mass in the larynx, 18 with neurological voice disorder, 23 with throat problems) and 27 in the control group without voice problems. All participants completed these questionnaires at their initial visit: the Korean version of the Voice Handicap Index (K-VHI), VHI-Tk, and the Korean version of the Voice Symptom Scale (K-VoiSS). Case group patients in the case group re-completed the VHI-Tk questionnaire to assess test-retest reliability. Finally, a one-way analysis of variance was implemented to assess differences in VHI-Tk scores among the four diagnosis types in the case group. RESULTS: The VHI-Tk scores in the case group were significantly higher than in the control group. The VHI-Tk was significantly correlated with the subscales of K-VHI and K-VoiSS. The VHI-Tk has significant test-retest reliability, and its internal consistency is good to excellent (Cronbach's alpha correlation coefficient range: 0.895-0.901). There was significant difference in the mean VHI-Tk scores according to the four diagnosis types (throat problems group > neurological voice disorder group). CONCLUSION: We validated the VHI-T questionnaire to measure self-perceived voice and throat problems among Koreans. A large sample size and various diagnosis types are required in future studies to fully validate the VHI-T for use in multiple cultures.

The Factors Affecting Longitudinal Course of Posttraumatic Stress Disorder Symptoms in Sexual Assault Victims.

OBJECTIVE: This study aimed to identify the factors affecting posttraumatic stress disorder (PTSD) symptom remission prospectively through a 1-year follow-up of sexual assault (SA) victims. METHODS: A total 65 female SA victims who visited the crisis intervention center were included. Self-administered questionnaires regarding PTSD symptoms and PTSD related prognostic factors were conducted at both recruitment (T1) and 1 year after recruitment (T2). The multivariate analyses were used to determine the significant predictors of PTSD remission/non-remission state 1 year after SA. RESULTS: In logistic regression analysis, both anxiety and secondary victimization were identified as significant factors explaining the results on PTSD remission/non-remission state at T2 (Beck's Anxiety Inventory [BAI], p=0.003; Secondary Victimization Questionnaire, p=0.024). In a linear mixed analysis, both depression and anxiety were found to be significant variables leading to changes in Posttraumatic Diagnostic Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition from T1 to T2 (BAI, p<0.001; Center for Epidemiological Studies Depression Scale, p<0.001). CONCLUSION: Depression, anxiety symptoms, and secondary victimization after SA were associated with PTSD symptom non-remission 1 year after SA.

Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer.

Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.

Sublimation-based wafer-scale monolayer WS2 formation via self-limited thinning of few-layer WS2.

Atomically-thin monolayer WS2 is a promising channel material for next-generation Moore's nanoelectronics owing to its high theoretical room temperature electron mobility and immunity to short channel effect. The high photoluminescence (PL) quantum yield of the monolayer WS2 also makes it highly promising for future high-performance optoelectronics. However, the difficulty in strictly growing monolayer WS2, due to its non-self-limiting growth mechanism, may hinder its industrial development because of the uncontrollable growth kinetics in attaining the high uniformity in thickness and property on the wafer-scale. In this study, we report a scalable process to achieve a 4 inch wafer-scale fully-covered strictly monolayer WS2 by applying the in situ self-limited thinning of multilayer WS2 formed by sulfurization of WOx films. Through a pulsed supply of sulfur precursor vapor under a continuous H2 flow, the self-limited thinning process can effectively trim down the overgrown multilayer WS2 to the monolayer limit without damaging the remaining bottom WS2 monolayer. Density functional theory (DFT) calculations reveal that the self-limited thinning arises from the thermodynamic instability of the WS2 top layers as opposed to a stable bottom monolayer WS2 on sapphire above a vacuum sublimation temperature of WS2. The self-limited thinning approach overcomes the intrinsic limitation of conventional vapor-based growth methods in preventing the 2nd layer WS2 domain nucleation/growth. It also offers additional advantages, such as scalability, simplicity, and possibility for batch processing, thus opening up a new avenue to develop a manufacturing-viable growth technology for the preparation of a strictly-monolayer WS2 on the wafer-scale.

Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents.

Importance: Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression. Objective: To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control. Design, Setting, and Participants: This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022. Main Outcomes and Measures: Depressive symptoms were assessed using the Children's Depression Rating Scale-Revised. The outcome measure was defined as the change in Children's Depression Rating Scale-Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not. Results: Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment. Conclusions and Relevance: The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.