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Human herpesvirus 8 (HHV-8) is causally related to human malignancies. HHV-8 latent viral FLICE-inhibitory protein (vFLIP) is a viral oncoprotein that is linked to pathogenesis, but how its expression is regulated is largely unknown. In an attempt to understand the role of the mitochondrial antiviral signaling (MAVS) adaptor in HHV-8 infection, we discovered that vFLIP expression was post-translationally up-regulated by the MAVS signaling complex on peroxisomes. Furthermore, we demonstrated that vFLIP could be targeted to the peroxisomes, where it was oncogenically active, in a PEX19-dependent manner. Targeted disruption of vFLIP and MAVS interaction resulted in a decrease in vFLIP expression and selectively promoted death of latently HHV-8-infected cells, providing therapeutic potential for treating HHV-8 diseases. Collectively, our experimental results suggest novel involvement of peroxisomes and MAVS in the stabilization of vFLIP and thereby in the establishment or maintenance of HHV-8 latency and associated pathogenesis.

Even though research on perceiving a calling has been growing, our understanding of its double-edged sword effects and psychological mechanisms remain unclear, especially in terms of work engagement and workaholism. Based on the heavy working investment (HWI) and dualistic model of passion (DMP) theories, we established a dual-path structural model to examine the effects of callings on work engagement and workaholism through two types of passion: harmonious (HP) and obsessive (OP) passions. Our results showed that the association between perceiving a calling and work engagement was partially mediated by HP, while the association between perceiving a calling and workaholism was fully mediated by OP. This study contributes to the literature in that it reveals how perceiving a calling has different effects on work engagement and workaholism through the HWI theoretical lens, as well as the mediating roles of HP and OP, based on the DMP theory. Our findings can be practically applied in organizations and counseling.

Background Efficacy of Axicabtagene ciloleucel (Axi-cel) as a frontline regimen for high-risk large B-cell lymphoma (LBCL) has been described in ZUMA-12 single-arm trial, yet there is a paucity of data on head-to-head effectiveness comparison between axi-cel vs. conventional therapy. Methods We conducted an external comparator arm study to compare overall survival (OS) and progression-free survival (PFS) in patients treated with axi-cel from ZUMA-12 with external comparator arm treated with conventional therapies from SMC-LCS (Samsung Medical Center-Lymphoma Cohort Study 2017–2023); published summary data from ZUMA-12 and individual patient data from SMC-LCS were used. Patients from SMC-LCS fulfilling the key eligibility criteria of ZUMA-12 were included: double- or triple-hit lymphoma (MYC, BCL2, or BCL6 translocations) or LBCL and an International Prognostic Index score of ≥ 3. OS was defined as a time interval between initiation of the index treatment and date of all-cause death or last follow-up visit. PFS was defined as a time interval between initiation of the index treatment and occurrence of the events related to disease progression or all-cause death. Kaplan-Meier curves for OS and PFS in the ZUMA-12 were extracted using Engauge Digitizer software (Version 12.1). Propensity score weighting using matching-adjusted indirect comparison (MAIC) approach was used to compare OS and PFS, adjusting for the baseline characteristics. The adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards model. Results Of 279 patients with high-risk LBCL in SMC-LCS, 45 fulfilled ZUMA-12 eligibility criteria. By the end of study, all-cause mortality rates were 13.5% for axi-cel and 49.5% for weighted external comparator arm, corresponding to a lower hazard of death for axi-cel with aHR of 0.30 (95% CI 0.13–0.73). Median PFS of axi-cel arm was not reached vs. 2.7 months in the weighted external comparator arm, corresponding to improved PFS for axi-cel with aHR of 0.23 (95% CI 0.11–0.46). Conclusions In the present study, we leveraged real-world data as a source for external comparator to present clinically meaningful evidence on the comparative effectiveness of axi-cel for treatment of high-risk LBCL.

We aimed to determine the effect of optic disc tilt on deep learning-based optic disc classification. A total of 2507 fundus photographs were acquired from 2236 eyes of 1809 subjects (mean age of 46 years; 53% men). Among all photographs, 1010 (40.3%) had tilted optic discs. Image annotation was performed to label pathologic changes of the optic disc (normal, glaucomatous optic disc changes, disc swelling, and disc pallor). Deep learning-based classification modeling was implemented to develop optic-disc appearance classification models with the photographs of all subjects and those with and without tilted optic discs. Regardless of deep learning algorithms, the classification models showed better overall performance when developed based on data from subjects with non-tilted discs (AUC, 0.988 ± 0.002, 0.991 ± 0.003, and 0.986 ± 0.003 for VGG16, VGG19, and DenseNet121, respectively) than when developed based on data with tilted discs (AUC, 0.924 ± 0.046, 0.928 ± 0.017, and 0.935 ± 0.008). In classification of each pathologic change, non-tilted disc models had better sensitivity and specificity than the tilted disc models. The optic disc appearance classification models developed based all-subject data demonstrated lower accuracy in patients with the appearance of tilted discs than in those with non-tilted discs. Our findings suggested the need to identify and adjust for the effect of optic disc tilt on the optic disc classification algorithm in future development.

Biophysical cues can improve the direct reprogramming of fibroblasts into neurons that can be used for therapeutic purposes. However, the effects of a three-dimensional (3D) environment on direct neuronal reprogramming remain unexplored. Here, we show that brain extracellular matrix (BEM) decellularized from human brain tissue facilitates the plasmid-transfection-based direct conversion of primary mouse embryonic fibroblasts into induced neuronal (iN) cells. We first show that two-dimensional (2D) surfaces modified with BEM significantly increase the generation efficiency of iN cells and enhance neuronal transdifferentiation and maturation. Moreover, in an animal model of ischaemic stroke, iN cells generated on the BEM substrates and transplanted into the brain led to significant improvements in locomotive behaviours. We also show that compared with the 2D BEM substrates, 3D BEM hydrogels recapitulating brain-like microenvironments further promote neuronal conversion and potentiate the functional recovery of the animals. Our findings suggest that 3D microenvironments can boost nonviral direct reprogramming for the generation of therapeutic neuronal cells. Hydrogels made from decellularized human brain tissue facilitate the direct conversion of primary mouse embryonic fibroblasts into induced neuronal cells that lead to therapeutic outcomes after transplantation in an animal model of ischaemic stroke.

Synaptic adhesion molecules regulate diverse aspects of neuronal synapse development, including synapse specificity, formation, and maturation. Neph2, also known as Kirrel3, is an immunoglobulin superfamily adhesion molecule implicated in intellectual disability, neurocognitive delay associated with Jacobsen syndrome, and autism spectrum disorders. We here report mice lacking Neph2 (Neph2(-/-) mice) display moderate hyperactivity in a familiar, but not novel, environment and defective novel object recognition with normal performances in Morris water maze spatial learning and memory, contextual fear conditioning and extinction, and pattern separation tests. These mice also show normal levels of anxiety-like behaviors, social interaction, and repetitive behaviors. At the synapse level, Neph2(-/-) dentate gyrus granule cells exhibit unaltered dendritic spine density and spontaneous excitatory synaptic transmission. These results suggest that Neph2 is important for normal locomotor activity and object recognition memory.

Background: Moral Growth Mindset (MGM) is a belief about whether one can become a morally better person through efforts. Prior research showed that MGM is positively associated with promotion of moral motivation among adolescents and young adults. We developed and tested the English version of the MGM measure in this study with data collected from college student participants. Methods: In Study 1, we tested the reliability and validity of the MGM measure with two-wave data ( N = 212, Age mean = 24.18 years, SD = 7.82 years). In Study 2, we retested the construct validity of the MGM measure once again and its association with other moral and positive psychological indicators to test its convergent and discriminant validity ( N = 275, Age mean = 22.02 years, SD = 6.34 years). Results: We found that the MGM measure was reliable and valid from Study 1. In Study 2, the results indicated that the MGM was well correlated with other moral and positive psychological indicators as expected. Conclusions: We developed and validated the English version of the MGM measure in the present study. The results from studies 1 and 2 supported the reliability and validity of the MGM measure. Given this, we found that the English version of the MGM measure can measure one's MGM as we intended.

In semiconductor fabrication (FAB), wafers are placed into carriers known as Front Opening Unified Pods (FOUPs), transported by the Overhead Hoist Transport (OHT). The OHT, a type of Automated Guided Vehicle (AGV), moves along a fixed railway network in the FAB. The routes of OHTs on the railway network are typically determined by a Single Source Shortest Path (SSSP) algorithm such as Dijkstra’s. However, the presence of hundreds of operating OHTs often leads to path interruptions, causing congestion or deadlocks that ultimately diminish the overall productivity of the FAB. This research focused on identifying structurally vulnerable links within the OHT railway network in semiconductor FAB and developing a visualization system for enhanced on-site decision-making. We employed betweenness centrality as a quantitative index to evaluate the structural vulnerability of the OHT railway network. Also, to accommodate the unique hierarchical node-port structure of this network, we modified the traditional Brandes algorithm, a widely-used method for calculating betweenness centrality. Our modification of the Brandes algorithm integrated node-port characteristics without increasing computation time while incorporating parallelization to reduce computation time further and improve usability. Ultimately, we developed an end-to-end web-based visualization system that enables users to perform betweenness centrality calculations on specific OHT railway layouts using our algorithm and view the results through a web interface. We validated our approach by comparing our results with historically vulnerable links provided by Samsung Electronics. The study had two main outcomes: the development of a new betweenness centrality calculation algorithm considering the node-port structure and the creation of a visualization system. The study demonstrated that the node-port structure betweenness centrality effectively identified vulnerable links in the OHT railway network. Presenting these findings through a visualization system greatly enhanced their practical applicability and relevance.

We examined the relationship between moral foundations, empathic traits, and moral identity using an online survey via Mechanical Turk. In order to determine how moral foundations contribute to empathic traits and moral identity, we performed classical correlation analysis as well as Bayesian correlation analysis, Bayesian ANCOVA, and Bayesian regression analysis. Results showed that individualizing foundations (harm/care, fairness/reciprocity) and binding foundations (ingroup/loyalty, authority/respect, purity/sanctity) had various different relationships with empathic traits. In addition, the individualizing versus binding foundations showed somewhat reverse relationships with internalization and symbolization of moral identity. This suggests that moral foundations can contribute to further understanding of empathic traits and moral identity and how they relate to moral behavior in reality. We discuss the implications of these results for moral educators when starting to teach students about moral issues.

Background: Moral Growth Mindset (MGM) is a belief about whether one can become a morally better person through efforts. Prior research showed that MGM is positively associated with promotion of moral motivation among adolescents and young adults. We developed and tested the English version of the MGM measure in this study with data collected from college student participants. Methods: In Study 1, we tested the reliability and validity of the MGM measure with two-wave data ( N = 212, Age mean = 24.18 years, SD = 7.82 years). In Study 2, we retested the construct validity of the MGM measure once again and its association with other moral and positive psychological indicators to test its convergent and discriminant validity ( N = 275, Age mean = 22.02 years, SD = 6.34 years). Results: We found that the MGM measure was reliable and valid from Study 1. In Study 2, the results indicated that the MGM was well correlated with other moral and positive psychological indicators as expected. Conclusions: We developed and validated the English version of the MGM measure in the present study. The results from studies 1 and 2 supported the reliability and validity of the MGM measure. Given this, we found that the English version of the MGM measure can measure one's MGM as we intended.