Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells.

CD8 T cells play essential roles in anti-tumor immune responses. Here, we performed genome-scale CRISPR screens in CD8 T cells directly under cancer immunotherapy settings and identified regulators of tumor infiltration and degranulation. The in vivo screen robustly re-identified canonical immunotherapy targets such as PD-1 and Tim-3, along with genes that have not been characterized in T cells. The infiltration and degranulation screens converged on an RNA helicase Dhx37. Dhx37 knockout enhanced the efficacy of antigen-specific CD8 T cells against triple-negative breast cancer in vivo. Immunological characterization in mouse and human CD8 T cells revealed that DHX37 suppresses effector functions, cytokine production, and T cell activation. Transcriptomic profiling and biochemical interrogation revealed a role for DHX37 in modulating NF-κB. These data demonstrate high-throughput in vivo genetic screens for immunotherapy target discovery and establishes DHX37 as a functional regulator of CD8 T cells.

A prospective study of nightmare disorder among Chinese adults in Hong Kong: Persistence and mental health outcomes.

OBJECTIVES: Previous studies showed that nightmares are prevalent and are associated with negative health outcomes. However, no empirical data is available demonstrating the extent to which nightmare disorder persists over time. Current literature provides a limited understanding of the trajectory and wider mental health outcomes of nightmare disorder. This longitudinal study examined the persistence and mental health outcomes of nightmare disorder. METHODS: A total of 230 Hong Kong Chinese adults completed standardized assessments twice with an interval of about 6 months. RESULTS: Over half (66.7%) of the participants with probable nightmare disorder at baseline remained to meet the DSM-5 criteria for the disorder at follow-up. Participants with probable nightmare disorder at baseline were significantly more likely to screen positive for PTSD (82.1% vs 18.3%) (p < .001) (p < .001), and they reported higher rates of mental health service usage at both timepoints (p = .001 to .003). Baseline nightmare disorder severity was negatively associated with subsequent self-rated mental health (ß = -.151, p = .010) and self-esteem (ß = -.141, p = .009) and it also predicted subsequent PTSD symptoms (ß = .122, p = .012). CONCLUSIONS: This study provides first empirical data showing that nightmare disorder could be persistent over time. Nightmare disorder symptoms are associated not only with PTSD symptoms but also with a broader range of mental health issues. This study points to the public health importance of identifying and managing nightmare disorder symptoms in the community. Additionally, the presence of nightmare disorder symptoms may be a helpful indicator for identifying post-traumatic stress.

A Culturally Specific Community Supported Agriculture (CSA) Program to Improve Diet in Immigrant Communities in Brooklyn, New York.

Anti-Asian and anti-immigrant sentiment has surged in the country in the last 3 years. Food insecurity is also on the rise; in our local needs assessment of n = 1,270 Asian American adults in New York City, accessing food was cited as the number 1 priority among those who needed help. Finally, racial discrimination and food access are related to fear of being attacked-driving feelings of safety and therefore willingness to travel for food. To combat these narratives and leveraging pivots by our community partners, we implemented a community-supported agriculture pilot program (n = 38) to assess whether culturally appropriate food access can improve diet and foster cross-cultural learning among immigrant families in Brooklyn, NY. Over a 20-week period from June to October 2022, participants received Chinese-specific produce and nutrition education. Participants reported eating more and a greater variety of vegetables and had higher vegetable intake measured via skin carotenoid scores. This pilot may inform the adaptation of nutrition interventions to reduce inequities in chronic diseases in immigrant communities.

Hurting myself to cope: Using network analysis to understand the association between perceived stigma and non-suicidal self-injury functions among men who have sex with men in China.

Prior studies have demonstrated that perceived stigma is robustly associated with risky and life-threatening behaviors, including non-suicidal self-injury (NSSI), among men who have sex with men (MSM). However, studies regarding the relationship between perceived stigma and NSSI are limited. The present study aimed to investigate the network structure of perceived stigma and NSSI functions, along with bridge nodes, to elucidate how they co-exist. A sample of 2610 Chinese MSM (mean age = 23.99, age range: 18-68 years) was recruited from an online survey platform. All participants completed a web-based survey with measures of perceived stigma and NSSI functions. Results indicated that 'negative attitudes towards homosexuality' and 'disappointment in gay son' were identified as the most central nodes in the perceived stigma network, whereas 'seeking attention' and 'influencing others to change' ranked highest on centrality in the NSSI network. Two bridge connections were exhibited within the combined perceived stigma and NSSI network model: 'unwelcoming in public' and 'avoiding unpleasant tasks' from perceived stigma and NSSI communities, respectively. This is among the first studies investigating the co-occurrence between perceived stigma and NSSI from the network approach. Our findings provide an empirically-based perspective on the importance of family- and community-based interventions, with potential clinical implications for reducing NSSI among sexual and gender minority groups.

A Preliminary Longitudinal Analysis of Symptom Management, Post-traumatic Stress, and Depressive Symptoms in Chinese Adults with Dissociative Symptoms.

People with dissociative symptoms are generally poly-symptomatic and require high levels of healthcare resources. Post-traumatic stress disorder (PTSD) and depressive symptoms are two major disabling comorbid symptoms in people with dissociative symptoms. While the sense of control over symptoms may be associated with PTSD and dissociative symptoms, the interplay among these factors over time remains unexplored. This study examined the predictors of PTSD and depressive symptoms in people with dissociative symptoms. Longitudinal data from 61 participants with dissociative symptoms were analyzed. Participants completed self-report measures of dissociative, depressive, and PTSD symptoms and the sense of control over symptoms two times (T1 & T2) with an interval of over one month. PTSD and depressive symptoms were not transient or time-specific, but they persisted over time in our sample. Hierarchical multiple regression analyses revealed that, after controlling for age, treatment usage and baseline symptom severity, T1 symptom management scores (ß = -.264, p = .006) negatively predicted T2 PTSD symptoms, while T1 PTSD symptoms (ß = .268, p = .017) positively predicted T2 depressive symptoms. T1 depressive symptoms (ß = -.087, p = .339) did not predict T2 PTSD symptoms. The findings highlight the importance of improving symptom management skills and treating comorbid PTSD symptoms when working with people with dissociative symptoms.

Association Between Psychotic and Dissociative Symptoms: Further Investigation Using Network Analysis.

The association and overlap between psychotic and dissociative phenomena have been increasingly recognized. Previous studies found that psychotic symptoms are closely associated with post-traumatic and dissociative symptoms and that these trauma-related phenomena may mediate the relationship between trauma and psychotic symptoms. It remained less explored which specific post-traumatic and dissociative symptom clusters are particularly associated with psychotic symptoms. This cross-sectional study used a data-driven approach (network analysis) to explore the associations among different psychotic and post-traumatic/dissociative symptom clusters in an online convenience predominantly female sample (N = 468)(59.2% had ever seen a psychiatrist). Participants completed well-established multidimensional measures that assessed different symptom clusters of psychosis, dissociation, and PTSD. In addition, multiple mediation analysis was conducted to examine which post-traumatic/dissociative symptoms could mediate the relationship between childhood and adulthood trauma and different psychotic symptoms. Our results confirmed previous findings that PTSD and dissociative symptoms are closely associated with psychotic symptoms. More importantly, both data-driven and multiple mediation analysis results indicated that identity dissociation was particularly associated with perceptual anomalies and bizarre experiences, while emotional constriction was particularly associated with negative symptoms. It is important to screen for trauma and dissociation and provide trauma-and dissociation-informed care when working with people at risk of or experiencing psychosis. Further longitudinal studies using more representative samples are needed.

Trauma, Emotional Regulation, and Coping Styles in Individuals with and without Probable Dissociative Disorders in Hong Kong.

Previous studies showed that dissociation and dissociative disorders (DDs) are prevalent and are associated with considerable individual and social consequences. There are ongoing debates regarding whether dissociation is a response to betrayal trauma across cultures and whether dissociation can be explained by maladaptive coping. Additionally, little is known about the clinical features of individuals with DDs in the Chinese context. This study aimed to investigate the relationship between trauma, emotional regulation, coping, and dissociation. We analyzed baseline data from a randomized controlled trial (N = 101). Participants with dissociative symptoms in Hong Kong completed self-report assessments. Structured interviews were also conducted subsequently. Participants with probable DDs reported more traumatic events (p = .009 to .017) and exhibited significantly higher levels of dysfunctional coping (p < .001) compared to those who reported dissociative symptoms but did not have a DD. Dissociative symptoms were more strongly associated with betrayal trauma than with non-betrayal trauma. Among different emotion regulation and coping strategies, dysfunctional coping was the only significant factor associated with dissociative symptoms (ß = .309, p = .003). Dysfunctional coping was a statistically significant mediator that may explain the relationship between betrayal trauma and dissociative symptoms. Although other mediation paths are also possible and further longitudinal studies are required, our findings highlight the strong link between dysfunctional coping and dissociative symptoms and suggest that coping skills training should be incorporated into interventions for betrayal trauma survivors with dissociative symptoms. Additionally, this study provides evidence for the cross-cultural validity of the betrayal trauma theory. Further studies, however, are required.

COULD FAMILY WELL-BEING MODERATE THE RELATIONSHIP BETWEEN ADVERSE CHILDHOOD EXPERIENCES AND SOMATOFORM DISSOCIATION? A PRELIMINARY INVESTIGATION.

The impacts of adverse childhood experiences (ACEs) have been well documented. One possible consequence of ACEs is dissociation, which is a major feature of post-traumatic psychopathology and is also associated with considerable impairment and health care costs. Although ACEs are known to be associated with both psychoform and somatoform dissociation, much less is known about the mechanisms behind this relationship. Little is known about whether social and interpersonal factors such as family environments would moderate the relationship between ACEs and somatoform dissociation. This paper discusses the importance of having a positive and healthy family environment in trauma recovery. We then report the findings of a preliminary study in which we examined whether the association between ACEs and somatoform dissociation would be moderated by family well-being in a convenience sample of Hong Kong adults (N = 359). The number of ACEs was positively associated with somatoform dissociative symptoms, but this association was moderated by the level of family well-being. The number of ACEs was associated with somatoform dissociation only when the family well-being scores were low. These moderating effects were medium. The findings point to the potential importance of using family education and intervention programs to prevent and treat trauma-related dissociative symptoms, but further investigation is needed.

Interpersonal stress mediates the relationship between childhood trauma and depressive symptoms: Findings from two culturally different samples.

OBJECTIVE: Childhood trauma is associated with adulthood depressive symptoms, but very few studies explored potential social and interpersonal mediators behind this association. This study made the first attempt to test the potential mediating effects of interpersonal stress in the associations between childhood betrayal and non-betrayal trauma and depressive symptoms. METHOD: We analyzed data in a sample of English-speaking adults from diverse backgrounds (from 19 different countries, mainly from Western countries) (N = 468). We then replicated and compared the results with those in another convenience sample of Chinese-speaking younger adults with different cultural backgrounds and mental health status (N = 205). RESULTS: The results in both samples indicated that (1) childhood betrayal trauma had a stronger relationship with depressive symptoms than childhood non-betrayal trauma and that (2) interpersonal stress was a significant mediator in the relationship between childhood betrayal trauma and depressive symptoms, even when childhood non-betrayal trauma was included as a covariate. The indirect effect of childhood non-betrayal trauma on depressive symptoms through interpersonal stress was not consistent in two samples. CONCLUSIONS: Our findings point to the importance of taking social and interpersonal contexts into account when investigating, preventing and managing depression in trauma-exposed populations. Early social interventions such as family interventions, interpersonal skills training and building social resources may have the potential to change the trajectory of the development of mental health problems in trauma survivors.

Genome Engineering for Next-Generation Cellular Immunotherapies.

Over the past decade, cellular immunotherapies such as CAR-T, TCR-T, and NK cell therapies have achieved tremendous success in cancer treatment. However, various challenges and obstacles remain, including antigen escape, immunosuppression in the tumor microenvironment, toxicities, and on-target off-tumor effects. Recent strategies for overcoming these roadblocks have included the use of genome engineering. Multiplexed CRISPR-Cas and synthetic biology approaches facilitate the development of cell therapies with higher potency and sophisticated modular control; they also offer a toolkit for allogeneic therapy development. Engineering approaches have targeted genetic modifications to enhance long-term persistence through cytokine modulation, knockout of genes mediating immunosuppressive signals, and genes such as the endogenous TCR and MHC-I that elicit adverse host-graft interactions in an allogeneic context. Genome engineering approaches for other immune cell types are also being explored, such as CAR macrophages and CAR-NK cells. Future therapeutic development of cellular immunotherapies may also be guided by novel target discovery through unbiased CRISPR genetic screening approaches.

Effects of a family-focused dyadic psychoeducational intervention for stroke survivors and their family caregivers: a pilot study.

BACKGROUND: Stroke is one of the leading causes of disability in China and worldwide, affecting the health and well-being of both stroke survivors and their family caregivers (i.e. stroke dyads). Dyadic interventions targeting both as active participants can be beneficial for the dyads' health and well-being. Psychoeducation is a potentially acceptable approach to developing participants' knowledge about their disease management to promote their recovery. This study aims to explore the feasibility, acceptability, and preliminary effects of a family-focused dyadic psychoeducational intervention for stroke dyads. METHODS: This study was a single-blinded, parallel-group randomised controlled trial. Totally, a convenience sample of 40 stroke dyads was recruited. The intervention included three in-hospital face-to-face education sessions and four weekly post-discharge follow-up telephone counselling sessions. Feasibility was assessed by the rates of recruitment, attritions, and adherence to the intervention. Acceptability was evaluated via semi-structured qualitative interviews. Preliminary intervention effects were evaluated on primary (survivors' functioning and caregivers' burden) and secondary (caregivers' competence and dyads' coping, depressive and anxiety symptoms, family functioning, and dyadic relationship) outcomes. RESULTS: Intervention feasibility was established with satisfactory recruitment (76.9%), attrition (10%), and intervention completion (75%) rates. Qualitative interviews suggested that the intervention was acceptable and useful to stroke dyads. The intervention effects on survivors' functioning were significant in the memory and thinking (F = 8.39, p = 0.022, η = 0.18) and mobility (F = 5.37, p = 0.026, η = 0.12) domains, but not significant on their overall functioning (F = 2.39, p = 0.131). Caregiver burden in the intervention group was significantly greater reduced at post-test than the control group, with a large effect size (F = 7.55, p = 0.013, η = 0.28). For secondary outcomes, this intervention suggested a significant effect on caregivers' competence (F = 5.20, p = 0.034, η = 0.22), but non-significant effects on other outcomes. CONCLUSIONS: The family-focused dyadic psychoeducation programme was feasible and acceptable for stroke dyads and showed preliminary effects for stroke dyads. These findings support a larger-scale controlled trial to further examine its intervention effects over a longer-term follow-up. TRIAL REGISTRATION: This study was retrospectively registered as a randomised controlled trial in the ISRCTN Registry. Registration Date: October 10, 2022. REGISTRATION NUMBER: ISRCTN18158500.

Factors affecting nursing students' intention to use a 3D game to learn field triage skills: a structural equation modelling analysis.

BACKGROUND: As mass casualty incidents are low-probability events, students often do not have the chance to practise field triage skills during their clinical placement. This study used a 3D game to engage participants in experiential learning in a realistic virtual environment. The purpose of the study was to explore factors affecting nursing students' intention to use a 3D game to learn field triage skills. METHODS: This was a cross-sectional survey study. The technology acceptance model augmented by computer self-efficacy was used as a research model and a questionnaire was used to evaluate students' intention to use the 3D game to learn field triage. Data was collected from nursing students of a degree-awarding higher education institution in Hong Kong. RESULTS: A total of 177 valid questionnaires were returned, and structural equation modeling was used to test the research model and hypotheses. Consistent with the technology acceptance model, perceived usefulness (0.21, p < 0.05) and perceived ease of use (0.91, p < 0.001) had a positive effect on the behavioral intention to use the 3D game. Computer self-efficacy positively influenced both perceived usefulness (0.66, p < 0.001) and perceived ease of use (0.73, p < 0.001). The research model explained 42 percent of the variance in the behavioral intention to use the 3D game. CONCLUSION: Students believed that using the 3D game would enhance their field triage skills and found the game easy to use. Using 3D games to facilitate learning is a worthwhile educational approach for preparing healthcare professionals to handle low-probability clinical tasks, such as field triage in mass casualty incidents. Insights provided by findings of this study included the best way to design and promote interactive education programmes in a virtual environment.

Efficacy of 5% Dextrose Water Injection for Peripheral Entrapment Neuropathy: A Narrative Review.

Current non-surgical treatment for peripheral entrapment neuropathy is considered insignificant and unsustainable; thus, it is essential to find an alternative novel treatment. The technique of perineural injection therapy using 5% dextrose water has been progressively used to treat many peripheral entrapment neuropathies and has been proven to have outstanding effects in a few high-quality studies. Currently, the twentieth edition of Harrison's Principles of Internal Medicine textbook recommends this novel injection therapy as an alternative local treatment for carpal tunnel syndrome (CTS). Hence, this novel approach has become the mainstream method for treating CTS, and other studies have revealed its clinical benefit for other peripheral entrapment neuropathies. In this narrative review, we aimed to provide an insight into this treatment method and summarize the current studies on cases of peripheral entrapment neuropathy treated by this method.

Emergency nurses' perceptions of their roles and practices during epidemics: a qualitative study.

BACKGROUND: although emergency nurses have a pivotal role in the public health response to epidemics, little is known about their responsibilities and practice in terms of epidemic management. AIMS: this study aimed to explore how emergency nurses understand and perform their professional roles and practice during epidemics. METHODS: a qualitative descriptive study design was used. Data were collected from 24 participants through semistructured interviews and subjected to thematic analysis. FINDINGS: the analysis yielded two overarching themes: expansion in the practice of emergency care; and the altered role of emergency nurses. CONCLUSION: emergency nurses perceive their practice during the management of an epidemic expanded in that they shouldered a greater responsibility in the control of infectious diseases. This expansion led to role ambiguity among them.

Nurses' preparedness for infectious disease outbreaks: A literature review and narrative synthesis of qualitative evidence.

AIMS AND OBJECTIVES: To explore the core components that constitute nurses' preparedness in an epidemic event. BACKGROUND: Healthcare service providers have worked to augment efforts to protect the public from the impact of epidemic events. While constituting the major healthcare taskforce, nurses are frequently tasked with fronting the response to an infectious disease outbreak. Given the crucial role of nurses in the management of prevailing epidemics, the constituents of their preparedness in epidemic events should be identified. DESIGN: A systematic search was undertaken to identify eligible studies from the literature. A narrative synthesis approach was employed to extract and synthesise findings of the reviewed qualitative studies. METHODS: Seven qualitative studies on nurses' experience and perceptions of epidemic events were examined for scientific quality using the Critical Appraisal Skills Programme Qualitative Checklist. Findings of these studies were synthesised adopting a narrative synthesis approach. RESULTS: Three interplaying themes were identified as follows: (i) personal resources, (ii) workplace resources and (iii) situational influences. The findings suggest that an effective epidemic outbreak response would require further effort to reinforce the interplay between individual nurses, healthcare institutions and the governments. CONCLUSIONS: The practical interplay among individual nurses, healthcare institutions and the governments is crucial in establishing an effective epidemic response. Further research on the understanding of the dynamic process of preparedness development is recommended to set future directions in research. RELEVANCE TO CLINICAL PRACTICE: This study offers important insights for devising future strategies in enhancing nurses' preparedness and response to an epidemic event. These include recommendations on providing education and training to nurses regarding infectious diseases, fostering institutional assistance and support in an outbreak and revising government policies and planning.

Bridging the gap between guidelines and practice in the management of emerging infectious diseases: a qualitative study of emergency nurses.

AIMS AND OBJECTIVES: To explore the difficulties and strategies regarding guideline implementation among emergency nurses. BACKGROUND: Emerging infectious diseases remain an underlying source of global health concern. Guidelines for accident and emergency departments would require adjustments for infectious disease management. However, disparities between guidelines and nurses' practice are frequently reported, which undermines the implementation of these guidelines into practice. This article explores the experience of frontline emergency nurses regarding guideline implementation and provides an in-depth account of their strategies in bridging guideline-practice gaps. DESIGN: A qualitative descriptive design was used. METHODS: Semi-structured, face-to-face, individual interviews were conducted between November 2013-May 2014. A purposive sample of 12 frontline emergency nurses from five accident and emergency departments in Hong Kong were recruited. The audio-recorded interviews were transcribed verbatim and analysed with a qualitative content analysis approach. RESULTS: Four key categories associated with guideline-practice gaps emerged, including getting work done, adapting to accelerated infection control measures, compromising care standards and resolving competing clinical judgments across collaborating departments. The results illustrate that the guideline-practice gaps could be associated with inadequate provision of corresponding organisational supports after guidelines are established. CONCLUSIONS: The nurses' experiences have uncovered the difficulties in the implementation of guidelines in emergency care settings and the corresponding strategies used to address these problems. The nurses' experiences reflect their endeavour in adjusting accordingly and adapting themselves to their circumstances in the face of unfeasible guidelines. RELEVANCE TO CLINICAL PRACTICE: It is important to customise guidelines to the needs of frontline nurses. Maintaining cross-departmental consensus on guideline interpretation and operation is also indicated as an important component for effective guideline implementation.

Can dissociative symptoms be explained by coping and emotion regulation? A longitudinal investigation.

OBJECTIVE: Dissociative symptoms are prevalent and are associated with considerable impairments. There are ongoing debates regarding how to conceptualize these phenomena. This study examined whether dissociative symptoms could be explained by coping and emotion regulation strategies. METHOD: We conducted a secondary analysis of data from a randomized controlled trial. A total of 115 Hong Kong Chinese adults completed standardized self-report assessments of trauma exposure, dissociative symptoms, coping, and emotion regulation at baseline. They provided data regarding dissociative symptoms again after 2 months. RESULTS: After controlling for baseline dissociative symptoms and trauma exposure, baseline active coping (ß = -.157, p = .035) and dysfunctional coping (ß = .227, p = .005) predicted more subsequent dissociative symptoms at follow-up. Furthermore, baseline dysfunctional coping mediated the relationship between trauma exposure and subsequent dissociative symptoms. CONCLUSIONS: This study provides insights into the ongoing debate concerning factors that could contribute to dissociation. As dysfunctional coping could particularly predict dissociative symptoms, we call for future studies to evaluate whether coping skills training could effectively prevent and treat dissociative symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

AAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells.

Engineering cells for adoptive therapy requires overcoming limitations in cell viability and, in the efficiency of transgene delivery, the duration of transgene expression and the stability of genomic integration. Here we report a gene-delivery system consisting of a Sleeping Beauty (SB) transposase encoded into a messenger RNA delivered by an adeno-associated virus (AAV) encoding an SB transposon that includes the desired transgene, for mediating the permanent integration of the transgene. Compared with lentiviral vectors and with the electroporation of plasmids of transposon DNA or minicircle DNA, the gene-delivery system, which we named MAJESTIC (for 'mRNA AAV-SB joint engineering of stable therapeutic immune cells'), offers prolonged transgene expression, as well as higher transgene expression, therapeutic-cell yield and cell viability. MAJESTIC can deliver chimeric antigen receptors (CARs) into T cells (which we show lead to strong anti-tumour activity in vivo) and also transduce natural killer cells, myeloid cells and induced pluripotent stem cells with bi-specific CARs, kill-switch CARs and synthetic T-cell receptors.

Prevalence and clinical correlates of dissociative symptoms in people with complex PTSD: Is complex PTSD a dissociative disorder?

The extent to which complex post-traumatic stress disorder (C-PTSD) can be conceptualized as a dissociative disorder remains an ongoing debate. This study investigated the prevalence and correlates of dissociative symptoms in people with C-PTSD. We analyzed baseline data from an international randomized controlled trial. A total of 165 intervention seekers who met the ICD-11 criteria for C-PTSD completed standardized self-report measures of trauma, C-PTSD symptoms, dissociative symptoms, depressive symptoms, and work and social impairments. In this sample, only 42.3 % of participants exhibited clinically significant dissociative symptoms. Dissociative symptoms had a unique association with depressive symptoms and work and social impairments in our participants with C-PTSD, even after controlling for trauma exposure and C-PTSD symptoms. The data does not support the theory that C-PTSD is a dissociative disorder. However, the findings highlight the importance of recognizing dissociation in people with C-PTSD.