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Abnormal developmental of hippocampal subfields and amygdalar subnuclei volumes in young adults with heavy cannabis use: A three-year longitudinal study
No full textBackground: Differences in the volumes of the hippocampus and amygdala have consistently been observed between young adults with heavy cannabis use relative to their non-using counterparts. However, it remains unclear whether the subfields of these functionally and structurally heterogenous regions exhibit similar patterns of change in young adults with long-term heavy cannabis use disorder (CUD). Objectives: This study aims to investigate the effects of long-term heavy cannabis use in young adults on the subregional structures of the hippocampus and amygdala, as well as their longitudinal alterations. Methods: The study sample comprised 20 young adults with heavy cannabis use and 22 matched non-cannabis using healthy volunteers. All participants completed the Cannabis Use Disorder Identification Test (CUDIT) and underwent two T1-structural magnetic resonance imaging (MRI) scans, one at baseline and another at follow-up 3 years later. The amygdala, hippocampus, and their subregions were segmented on T1-weighted anatomical MRI scans, using a previously validated procedure. Results: At baseline, young adults with heavy CUD exhibited significantly larger volumes in several hippocampal (bilateral presubiculum, subiculum, Cornu Ammonis (CA) regions CA1, CA2-CA3, and right CA4-Dentate Gyrus (DG)) and amygdala (bilateral paralaminar nuclei, right medial nucleus, and right lateral nucleus) subregions compared to healthy controls, but these differences were attenuated at follow-up. Longitudinal analysis revealed an accelerated volumetric decrease in these subregions in young adults with heavy CUD relative to controls. Particularly, compared to healthy controls, significant accelerated volume decreases were observed in the right hippocampal subfields of the parasubiculum, subiculum, and CA4-DG. In the amygdala, similar trends of accelerated volumetric decreases were observed in the left central nucleus, right paralaminar nucleus, right basal nucleus, and right accessory basal nucleus. Conclusions: The current findings suggest that long-term heavy cannabis use impacts maturational process of the amygdala and hippocampus, especially in subregions with high concentrations of cannabinoid type 1 receptors (CB1Rs) and involvement in adult neurogenesis.</p
Investor Preference-Aware Portfolio Optimization with Deep Reinforcement Learning
Get PDFRecently, deep reinforcement learning (RL) approaches have been adopted to optimize financial portfolios with the objective of maximizing total profits while reducing potential risks by spreading investment capital across a variety of assets. Despite achieving great advances in the trade-off between profits and risks, the existing deep RL-based frameworks rarely consider practical trading constraints when making decisions in real-world financial markets, which cannot fulfill the customized requirements of specific users and may violate market regulations. Accordingly, Multi-Agent and Self-Adaptive trading framework for Constrained portfolio optimization, namely the MASAC, is proposed in which the deep RL-based agent dynamically explores profit-maximization policies while the heuristic-based agent conducts min-conflict search to ensure the generated trading strategies satisfying all concerned constraints. Through sharing knowledge within the trading system, the agents of the proposed framework cooperatively produce new portfolios that can maximize overall profits while satisfying all investor requirements throughout the trading period. The experimental results reveal the advantages of the MASAC framework against many state-of-the-art approaches in investment performance and trading constraint satisfaction on the challenging data sets of real-world markets.published_or_final_versio
Microenvironment matters: In vitro 3D bone marrow niches differentially modulate survival, phenotype and drug responses of acute myeloid leukemia (AML) cells
No full textAcute myeloid leukemia (AML) is a deadly form of leukemia with ineffective traditional treatment and frequent chemoresistance-associated relapse. Personalized drug screening holds promise in identifying optimal regimen, nevertheless, primary AML cells undergo spontaneous apoptosis during cultures, invalidating the drug screening results. Here, we reconstitute a 3D osteogenic niche (3DON) mimicking that in bone marrow to support primary AML cell survival and phenotype maintenance in cultures. Specifically, 3DON derived from osteogenically differentiated mesenchymal stem cells (MSC) from healthy and AML donors are co-cultured with primary AML cells. The AML cells under the AML_3DON niche showed enhanced viability, reduced apoptosis and maintained CD33+ CD34−phenotype, associating with elevated secretion of anti-apoptotic cytokines in the AML_3DON niche. Moreover, AML cells under the AML_3DON niche exhibited low sensitivity to two FDA-approved chemotherapeutic drugs, further suggesting the physiological resemblance of the AML_3DON niche. Most interestingly, AML cells co-cultured with the healthy_3DON niche are highly sensitive to the same sample drugs. This study demonstrates the differential responses of AML cells towards leukemic and healthy bone marrow niches, suggesting the impact of native cancer cell niche in drug screening, and the potential of re-engineering healthy bone marrow niche in AML patients as chemotherapeutic adjuvants overcoming chemoresistance, respectively.</p
Strong, ductile, and hierarchical hetero-lamellar-structured alloys through microstructural inheritance and refinement
No full textThe strength−ductility trade-off exists ubiquitously, especially in brittle intermetalliccontaining multiple principal element alloys (MPEAs), where the intermetallic phases often induce premature failure leading to severe ductility reduction. Hierarchical heterogeneities represent a promising microstructural solution to achieve simultaneous strength−ductility enhancement. However, it remains fundamentally challenging to tailor hierarchical heterostructures using conventional methods, which often rely on costly and time-consuming processing. Here, we report a multiscale microstructural inheritance and refinement strategy to process “structural hierarchy precursors” in as-cast heterogeneous Al0.7CoCrFeNi MPEAs, which lead directly to a hierarchical hetero-lamellar structure (HLS) after simple rolling and annealing. Interestingly, it takes only 10 min of annealing time, two orders of magnitude less than that required to render the state-of-the-art properties during conventional processing of Al0.7CoCrFeNi, for us to achieve record-high strength−ductility combinations via the hierarchical HLS design that sequentially stimulates multiple unusual deformation and reinforcement mechanisms. In particular, the HLS-enabled high hetero-deformation-induced (HDI) internal stress triggers profuse -type dislocations on over five independent slip systems in the supposedly brittle intermetallic phase and activates extensive stacking faults (SFs) and nanotwinning in the adjoining soft phase with a rather high SF energy. These unexpected, dynamically reinforcing hetero-deformation mechanisms across multiple length scales facilitate high sustained HDI strain hardening, along with a salient microcrack-mediated extrinsic ductilization effect, suggesting that the proposed microstructural inheritance and refinement strategy provides an efficient, fast, and low-cost approach to overcome the strength−ductility trade-off in a broad range of structural materials
Semaphorin-4D signaling in recruiting dental stem cells for vascular stabilization
No full textBACKGROUND: Achieving a stable vasculature is crucial for tissue regeneration. Endothelial cells initiate vascular morphogenesis, followed by mural cells that stabilize new vessels. This study investigated the in vivo effects of Sema4D-Plexin-B1 signaling on stem cells from human exfoliated deciduous teeth (SHED)-supported angiogenesis, focusing on its mechanism in PDGF-BB secretion. We also explored macrophages as an endogenous source of Sema4D for vascular stabilization. METHODS: The in vivo Matrigel plug angiogenesis assay was conducted to examine the impact of Sema4D on vessel formation and stabilization supported by SHED. Knockdown of Plexin-B1 in human umbilical vein endothelial cells (HUVECs) and PDGFR-β inhibitors were utilized to explore the fundamental regulatory mechanisms. Furthermore, the m6A methylation levels of total RNA and the expression of Methyltransferase-like 3 (METTL3) were assessed under conditions of Sema4D treatment in vitro. An ELISA was employed to measure the levels of Sema4D in the supernatants derived from THP-1 cell-mediated macrophages. Additionally, a three-dimensional vasculature-on-a-chip microfluidic device was used to investigate the role of M2c macrophage-derived Sema4D in the stabilization of vascular structures. RESULTS: Sema4D induced the formation of a greater number of perfused vessels by HUVECs and enhanced the coverage of these vessels by SM22α-positive SHED (SM22α+SHED). Conversely, the knockdown of the Plexin-B1 receptor in HUVECs or inhibition of PDGFR-β reversed the Sema4D-induced vascular stabilization, thereby confirming the regulatory role of the Plexin-B1/PDGF-BB axis in the recruitment of mural cells mediated by Sema4D. Mechanistically, Sema4D was found to upregulate the expression of methyltransferases, specifically METTL3, and to elevate the level of m6A modification in HUVECs. This modification was determined to be critical for enhancing PDGF-BB secretion, suggesting that Sema4D activates an epigenetic regulatory mechanism. Additionally, we investigated the secretion of Sema4D by various macrophage phenotypes, identifying that M2c macrophages secrete significant levels of Sema4D. This secretion recruited SM22α+SHED as mural cells by inducing endothelial PDGF production on a vasculature-on-a-chip platform, indicating a potential role for macrophages in facilitating vascular stabilization. CONCLUSIONS: Sema4D acts on Plexin-B1, inducing METTL3-mediated PDGF-BB secretion to recruit SHED to stabilize vessels. Macrophages could be a key source of Sema4D for vascular stabilization
Study Protocol for the Hand OsteoArthritis Self-Management and Integrated Scheme (OASIS-H) to Improve Outcomes in Patients with Hand Osteoarthritis—an Open-Label Randomized Controlled Trial
No full textThe increasing prevalence of hand osteoarthritis (OA) in Hong Kong’s aging population and its economic burden necessitate more effective management strategies. This study examines the efficacy of the Hand OsteoArthritis Self-management and Integrated Scheme (OASIS-H) compared to routine clinical care for patients with symptomatic hand OA. In this open-label, randomized controlled trial, symptomatic OA hand patients are included and randomized into early intervention and routine clinical care groups. The early intervention group undergoes an 8-week integrated hand OA management program, consisting of modified self-management education sessions, exercise, education, and occupational therapy intervention. At 6 months, routine clinical care patients will cross over to receive the same program as the early intervention group. The primary endpoint is the change in finger pain on visual analogue scale (VAS) at 6 months from baseline. The study aims to determine if the integrated program is more efficacious than routine care in reducing pain and improving function in hand OA patients.</p
Using ChatGPT for medical education: the technical perspective
No full textBackground: The chatbot application Bennie and the Chats was introduced due to the outbreak of COVID-19, which is aimed to provide substitution for teaching conventional clinical history-taking skills. It was implemented with DialogFlow with preset responses, which consists of a large constraint on responding to different conversations. The rapid advancement of artificial intelligence, such as the recent introduction of ChatGPT, offers innovative conversational experiences with computer-generated responses. It provides an idea to develop the second generation of Bennie and the Chats. As the epidemic slows, it can become an assisting tool for students as additional exercise. In this work, we present the second generation of Bennie and the Chats with ChatGPT, which provides room for flexible and expandable improvement. Methods: The objective of this research is to examine the influence of the newly proposed chatbot on learning efficacy and experiences in bedside teaching, and its potential contributions to international teaching collaboration. This study employs a mixed-method design that incorporates both quantitative and qualitative approaches. From the quantitative approach, we launched the world’s first cross-territory virtual bedside teaching with our proposed application and conducted a survey between the University of Hong Kong (HKU) and the National University of Singapore (NUS). Descriptive statistics and Spearman’s Correlation were applied for data analysis. From the qualitative approach, a comparative analysis was conducted between the two versions of the chatbot. And, we discuss the interrelationship between the quantitative and qualitative results. Results: For the quantitative result, we collected a questionnaire from 45 students about the evaluation of virtual bedside teaching between territories. Over 75% of the students agreed that teaching can enhance learning effectiveness and experience. Moreover, by exchanging patients cases, 82.2% of students agreed that it helps to gain more experiences with diseases that may not be prevalent in their own locality. For the qualitative result, the new chatbot provides better usability and flexibility. Conclusion: Virtual bedside teaching with chatbots has revolutionized conventional bedside teaching by its advantages and allowing international collaborations. We believe that the training of history taking skills by chatbot will be a feasible supplementary teaching tool to conventional bedside teaching.</p
Dynamics of moral outrage : an analysis of the persistence and transformation of the Anti-Extradition Law Amendment Bill movement
No full textThe significance of networked social movements has been increasingly recognized in social movement studies. Prominent examples include the Arab Spring, France’s Yellow Vests Movement, Black Lives Matter, and Hong Kong’s Umbrella Movement. These movements were extensively organized using digital media and featured numerous incidents of violence and protester injuries, which evoked significant emotional responses among supporters. Previous research has predominantly examined how digital media are used for collaboration or explored the relationship between online activities and protest participation, while the role of violence in mobilization has been less frequently addressed. Similarly, emotional analyses in social movements have focused on the ways in which emotions facilitate or suppress participation and the development of movements, yet their interaction with digital media has remained underexplored.
To address this gap, emotional mobilization within networked social movements was investigated in this study, with the Anti-Extradition Law Amendment Bill (AntiELAB) Movement serving as a case study. Through process tracing, including interviews, observations, and post-event analysis, the role of emotions in shaping coordinated collective action was re-examined. The transition from emotional responses to event-driven mobilization and the emergence of coordinated actions were analyzed, and the internal mechanisms that shaped and sustained the movement were identified.
It was found that the Anti-ELAB Movement was primarily characterized as an eventdriven emotional mobilization process. Moral outrage over alleged police brutality served as a moral and emotional catalyst, driving supporters to engage in protest projects and form spontaneous organizations to initiate collective action. It was also observed that boycott actions were secondary phenomena, emerging as a result of several emotional mechanisms. Individual responses to perceived pro-government entities—whether businesses or public figures—were amplified on digital platforms such as the LIHKG forum, leading to targeted boycotts.
This thesis contributes to social movement studies by proposing a refined theory of emotional mobilization. It was demonstrated that emotional responses to recurring violent incidents, rather than strategic planning, were the primary drivers of the AntiELAB Movement. Mechanisms such as relational emotion elicitation, the formation of contentious projects, spontaneous organization, and online boycott mobilization were examined, enhancing understanding of the role of emotions in networked social movements. This research further complements existing perspectives by illustrating how emotions significantly influence the organizational forms and dynamics of such movements.published_or_final_versionSociologyDoctoralDoctor of Philosoph
Assessment of sperm DNA fragmentation and methylation for prediction of male fertility
No full textInfertility presents a significant global health challenge affecting around one-sixth of the population, with 30-50% of cases attributed to male infertility. Conventional semen analysis has been relied upon the World Health Organization (WHO) guidelines to assess male fertility based on parameters such as motility and morphology. However, its limited predictive power for sperm fertilising capacity and fertilisation outcome remains controversial. Sperm DNA fragmentation (sDF) has been shown to correlate with suboptimal artificial reproductive treatment (ART) outcomes such as lower blastulation rate or defective embryonic development. The incorporation of a standardised test for sperm DNA evaluation can improve the predictive power in assessing male infertility as it provides information from the genetic level.
Sperm DNA methylation is another proposed method in identifying infertile patients, and prior investigations have shown that DNA methylation is correlated to sperm function and quality. Methylation is the most prominent mechanism in sperm epigenetic regulation; chromatin modification and post-transcriptional regulation are very limited in spermatozoa due to the minimal amount of cytoplasm and RNA presented in the spermatozoa. Another factor is that the sperm genome is inherently transcriptional and translational silence. Our study aimed to identify biomarkers related to sperm DNA fragmentation and to understand the association between sperm DNA fragmentation and methylation.
In our retrospective study involving 135 infertile patients undergoing in-vitro fertilisation treatment, the TUNEL assay along with flow cytometry was employed as the standardised method for sDF assessment. Our findings revealed that elevated sDF rates were associated with advanced male age (p<0.001), with males over 38 years exhibiting significantly higher sDF levels compared to younger individuals (p<0.01). Moreover, sDF rates were negatively linked to normal fertilisation rates in male infertile couples (p<0.05) and embryo utilisation rates (p<0.01).
Regarding the association between sDF and methylation markers, samples were isolated from raw semen, swim-up samples, those with 0% normal WHO morphology, and normal morphology samples in our study. The global methylation levels across these samples remained consistent. Enzymatic methylation sequencing analysis comparing among sample groups highlighted gene ontology pathways related to cellular respiration and mitochondrial function. Notably, MT-ND2 emerged as a potential methylation biomarker linked to reactive oxygen species (ROS) production impacting sperm DNA integrity. MT-ND2 variants in males have been associated with reduced fertility, underscoring its significant role in male reproductive health in conjunction with our study's findings.published_or_final_versionObstetrics and GynaecologyMasterMaster of Philosoph