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33 result(s) for "Wai, Heung On"
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CD44+ Cancer Stem-Like Cells in EBV-Associated Nasopharyngeal Carcinoma
Nasopharyngeal carcinoma (NPC) is a unique EBV-associated epithelial malignancy, showing highly invasive and metastatic phenotype. Despite increasing evidence demonstrating the critical role of cancer stem-like cells (CSCs) in the maintenance and progression of tumors in a variety of malignancies, the existence and properties of CSC in EBV-associated NPC are largely unknown. Our study aims to elucidate the presence and role of CSCs in the pathogenesis of this malignant disease. Sphere-forming cells were isolated from an EBV-positive NPC cell line C666-1 and its tumor-initiating properties were confirmed by in vitro and in vivo assays. In these spheroids, up-regulation of multiple stem cell markers were found. By flow cytometry, we demonstrated that both CD44 and SOX2 were overexpressed in a majority of sphere-forming C666-1 cells. The CD44+SOX2+ cells was detected in a minor population in EBV-positive xenografts and primary tumors and considered as potential CSC in NPC. Notably, the isolated CD44+ NPC cells were resistant to chemotherapeutic agents and with higher spheroid formation efficiency, showing CSC properties. On the other hand, microarray analysis has revealed a number of differentially expressed genes involved in transcription regulation (e.g. FOXN4, GLI1), immune response (CCR7, IL8) and transmembrane transport (e.g. ABCC3, ABCC11) in the spheroids. Among these genes, increased expression of CCR7 in CD44+ CSCs was confirmed in NPC xenografts and primary tumors. Importantly, blocking of CCR7 abolished the sphere-forming ability of C666-1 in vitro. Expression of CCR7 was associated with recurrent disease and distant metastasis. The current study defined the specific properties of a CSC subpopulation in EBV-associated NPC. Our findings provided new insights into developing effective therapies targeting on CSCs, thereby potentiating treatment efficacy for NPC patients.
CD9 blockade suppresses disease progression of high-risk pediatric B-cell precursor acute lymphoblastic leukemia and enhances chemosensitivity
CD9 has been implicated in cancer progression but its prognostic relevance and therapeutic potential in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are largely unknown. In a cohort of pediatric BCP-ALL patients, we found that CD9+ cases had a significantly lower 5-year relapse-free survival rate than CD9− cases. Multivariate analysis demonstrated that CD9 positivity independently predicted inferior survival outcomes, and could be applied with established prognostic features, including prednisone response and cytogenetic status, to refine patient stratification. Administration of CD9 antibody substantially suppressed disease progression in NOD/SCID mice xenografted with CD9+ cell lines and primary leukemic blasts from patients with high-risk and refractory BCP-ALL, without compromising hematopoietic stem cell engraftment. Combination of anti-CD9 with conventional chemotherapy further reduced leukemic burden and prolonged animal survival. Mechanistically, CD9 blockade inhibited leukemic cell proliferation, induced G0/G1 cell cycle arrest, activated p38, and enhanced chemotherapeutic agent-induced apoptosis. Further, CD9 physically interacted with integrin very late antigen-4, regulated affinity to vascular cell adhesion molecule-1, and was involved in leukemia–stroma interaction. Collectively, our study established CD9 as a new prognostic marker, validated the preclinical efficacy of CD9 antibody, and laid the foundation for clinical development of CD9-targeted therapy for high-risk and refractory pediatric BCP-ALL.
Momentary dynamics of inner speech varieties, auditory verbal hallucinations, and affect in schizophrenia spectrum disorders: an experience sampling study
Auditory verbal hallucinations (AVH) in schizophrenia spectrum disorders (SSDs) may arise from misattributed inner speech. However, it is unclear if inner speech frequency and phenomenology differ in schizophrenia-spectrum voice-hearers compared with healthy individuals, and how different inner speech varieties relate to AVH and affect. Using experience sampling methodology (ESM), this study examined the moment-to-moment dynamics between inner speech varieties, AVH, and affect. Participants completed 6 days of ESM on an electronic device, responding to 10 daily prompts on inner speech varieties (i.e. dialogic, evaluative, other people, condensed, and positive), AVH, and affect. Responses from 32 individuals with SSDs with current AVH ('SSD') and 34 healthy controls ('HC') were analyzed using linear mixed modeling. SSD reported significantly more inner speech moments and higher momentary intensity of evaluative, other people, condensed, and positive inner speech compared with HC, but not for dialogic inner speech. Within SSD, higher momentary intensities of dialogic, evaluative, other people, and condensed inner speech were associated with higher AVH levels. Momentary negative affect (NA) moderated the association between evaluative inner speech and AVH, with a stronger association at higher NA levels. SSDs with current AVH experience more frequent inner speech and exhibit a distinct phenomenological profile compared with healthy individuals. Several inner speech varieties are associated with AVH severity momentarily, supporting the hypothesis that inner speech contributes to AVH at the phenomenological level. This study highlights the emotional state as an important moderator of the inner speech-AVH relationship and as a potential therapeutic target.
MERP: A Music Dataset with Emotion Ratings and Raters’ Profile Information
Music is capable of conveying many emotions. The level and type of emotion of the music perceived by a listener, however, is highly subjective. In this study, we present the Music Emotion Recognition with Profile information dataset (MERP). This database was collected through Amazon Mechanical Turk (MTurk) and features dynamical valence and arousal ratings of 54 selected full-length songs. The dataset contains music features, as well as user profile information of the annotators. The songs were selected from the Free Music Archive using an innovative method (a Triple Neural Network with the OpenSmile toolkit) to identify 50 songs with the most distinctive emotions. Specifically, the songs were chosen to fully cover the four quadrants of the valence-arousal space. Four additional songs were selected from the DEAM dataset to act as a benchmark in this study and filter out low quality ratings. A total of 452 participants participated in annotating the dataset, with 277 participants remaining after thoroughly cleaning the dataset. Their demographic information, listening preferences, and musical background were recorded. We offer an extensive analysis of the resulting dataset, together with a baseline emotion prediction model based on a fully connected model and an LSTM model, for our newly proposed MERP dataset.
Chromosome-Level Genome Assembly of Eden's Whale Clarifies the Taxonomy and Speciation of Bryde's Whale Complex
Abstract Eden's whale (Balaenoptera edeni), a poorly understood baleen cetacean, has long been shrouded in taxonomic ambiguity due to limited genomic resources, obscuring its distinction from closely related species and its position within the cetacean Tree of Life. In this paper, we present a high-quality chromosomal-level genome of B. edeni and conduct comparative genomic analyses to address long-standing taxonomic confusion and elucidate speciation of balaenopterids. Our phylogenomic analysis and demographic reconstruction reveal that B. edeni is a distinct sister to Bryde's whale (Balaenoptera brydei), sharing a common ancestor that diverged approximately 7.84 million years ago during the late Miocene. Their genetic divergence exceeds typical intraspecific variation in whales, supporting the reinstatement of B. brydei as a valid species. Chromosomal syntenic analyses suggest that macro-fragment inversions contributed to speciation in balaenopterid whales and uncover unexpected large-scale complex genome rearrangements in Bryde's whale, offering novel insights into cetacean genome evolution. Functional enrichment analysis of inverted regions between B. edeni and Balaenoptera musculus indicates their predominant association with metabolism and biosynthesis, as well as responses to various substances, stress, and stimuli. These genomic resources for B. edeni not only lay a critical foundation for comparative genetic and evolutionary research of cetaceans but also advance our understanding of the taxonomy and evolutionary dynamics of the Bryde's whale complex, with broader implications for baleen whale conservation and biodiversity.
Moment-to-moment dynamics between auditory verbal hallucinations and negative affect and the role of beliefs about voices
Negative affect (NA) has been suggested to be both an antecedent and a consequence of auditory verbal hallucinations (AVH). Furthermore, negative appraisals of voices have been theorized to contribute to the maintenance of AVH. Using the experience sampling method (ESM), this study examined the bi-directional relationship between NA and AVH, and the moderating effect of negative beliefs about voices. Forty-seven patients diagnosed with schizophrenia spectrum disorders with frequent AVH completed a clinical interview, followed by ESM for 10 times a day over 6 days on an electronic device. Time-lagged analyses were conducted using multilevel regression modeling. Beliefs about voices were assessed at baseline. A total of 1654 data points were obtained. NA predicted an increase in AVH in the subsequent moment, and AVH predicted an increase in NA in the subsequent moment. Baseline beliefs about voices as malevolent and omnipotent significantly strengthened the association between NA and AVH within the same moment. In addition, the belief of omnipotence was associated with more hallucinatory experiences in the moment following NA. However, beliefs about voices were not associated directly with momentary levels of NA or AVH. Experiences of NA and AVH drove each other, forming a feedback loop that maintained the voices. The associations between NA and AVH, either within the same moment or across moments, were exacerbated by negative beliefs about voices. Our results suggest that affect-improving interventions may stop the feedback loop and reduce AVH frequency.
The Associations Between Accelerometer-Measured Physical Activity Levels and Mental Health in Children and Adolescents with Intellectual Disabilities During the COVID-19 Pandemic
To examine the associations between physical activity (PA) levels and mental health in children and adolescents with intellectual disabilities (IDs) during the COVID-19 pandemic, 117 participants aged between 6 and 17 years with IDs from 10 Hong Kong special schools were included. There were positive dose–response associations between PA (i.e., light PA, moderate PA, and vigorous PA) and mental health, and participants with higher levels of moderate-to-vigorous PA (MVPA) and self-concept (SC) had better social quality of life (QoL) than those with lower levels of MVPA and SC. Moreover, personal and environmental factors such as age, body mass index, school, sex, ID level, and parental education level influenced the PA levels and QoL in children and adolescents with IDs.
Associations between perceived and actual physical literacy level in Chinese primary school children
Background The concept of physical literacy (PL) is gaining popularity within public health and physical education circles. However, little is known about the relationship between perceived and actual PL levels among school-aged children. The aim of this study is to explore the associations between perceived and actual levels of PL of primary school students in China. Methods A total of 327 children (153 boys and 174 girls) with a mean (SD) age of 10.0 (±1.0) years were included for analysis. PL perceptions were measured using the Perceived Physical Literacy Instrument. Children’s actual level of PL was objectively assessed by the Chinese version of the Canadian Assessment of Physical Literacy, 2nd edition, which consists of four domains: Daily Behavior, Physical Competence, Motivation and Confidence, and Knowledge and Understanding. Pearson’s correlation coefficients were calculated to examine the relationship between students’ perceived and actual PL levels, whereas Multivariate Analysis of Variance (MANOVA) was calculated to investigate the gender, relative age differences, and interaction effect (2 × 4) on perceived and actual PL levels respectively. Results Significant correlations were observed between the perceptions and actual PL scores in both boys ( r  = .46, p  < .01) and girls ( r  = .41, p  < .01). Low to moderate significances were shown between each domain of perceived PL and actual PL (from .16 to .49). Further MANOVA results revealed that there were significant gender differences in the Daily Behavior domain of actual PL ( F (1, 319) = 30.15, p  < .001, Wilks’ Λ = 540.88, η 2 partial  = .09). Overall, boys had both higher actual PL scores (58.9) and PL perceptions (37.3) than girls. Neither relative age effect nor interaction effect (2 × 4) was observed for the current participants in all the variables. Conclusions This study is the first to examine the associations between the perceived and actual levels of PL in Chinese children. Additional studies should explore the importance of children’s perceptions of PL when assessing the actual level of PL in physical education and health settings. Girls should be more encouraged by PE teachers to participate actively in physical activities in the school environment.
Exploratory use of ultrasound to determine whether demyelination following carpal tunnel syndrome co-exists with axonal degeneration
Carpal tunnel syndrome (CTS) accompanied by secondary axonal degeneration cannot be clearly dis- criminated using the current cross-validated ultrasound severity classification system. This study aimed at exploring cut-off values of ultrasound parameters, including wrist cross-sectional area (W-CSA), wrist perimeter (W-P), ratio of cross-sectional area (R-CSA) and perimeter (R-P), changes of CSA and P from wrist to one third distal forearm (△CSA&AP) for differentiation. Seventy-three patients (13 male and 60 female) were assigned into group A (demyelination only, n = 40) and group B (demyelination with secondary axonal degeneration, n = 33) based on the outcomes of nerve conduction studies (NCS). Receiver Operative Characteristics (ROC) curves were plotted to obtain sensitivity, specificity, and accuracy of cut- off values for all the ultrasound parameters. The overall identified cut-off values (W-CSA 12.0 mm2, W-P 16.27 mm, R-CSA 1.85, R-P 1.48, △CSA 6.98 mm2, △P 5.77 mm) had good sensitivity (77.1-88.6%), fair specificity (40-62.2%) and fair-to-good accuracy (0.676-0.758). There were also significant differences in demographics (age and severity gradation, P 〈 0.001), NCS findings (wrist motor latency and conduction velocity, P 〈 0.0001; wrist motor amplitude, P 〈 0.05; distal sensory latency, P 〈 0.05; sensory amplitude, P 〈 0.001) and ultrasound measurements (W-CSA, W-P, R-CSA, R-P, △CSA&△P, P 〈 0.05) between groups. These findings suggest that ultrasound can be potentially used to differentiate demyelinating CTS with sec- ondary axonal degeneration and provide better treatment guidance.