Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms and Clinical Trials of Hepatocellular Carcinoma Immunotherapy

Hepatocellular carcinoma (HCC), one of the most common and lethal tumors worldwide, is usually not diagnosed until the disease is advanced, which results in ineffective intervention and unfavorable prognosis. Small molecule targeted drugs of HCC, such as sorafenib, provided only about 2.8 months of survival benefit, partially due to cancer stem cell resistance. There is an urgent need for the development of new treatment strategies for HCC. Tumor immunotherapies, including immune check point inhibitors, chimeric antigen receptor T cells (CAR-T) and bispecific antibodies (BsAb), have shown significant potential. It is known that the expression level of glypican-3 (GPC3) was significantly increased in HCC compared with normal liver tissues. A bispecific antibody (GPC3-S-Fabs) was reported to recruit NK cells to target GPC3 positive cancer cells. Besides, bispecific T-cell Engagers (BiTE), including GPC3/CD3, an aptamer TLS11a/CD3 and EpCAM/CD3, were recently reported to efficiently eliminate HCC cells. It is known that immune checkpoint proteins programmed death-1 (PD-1) binding by programmed cell death-ligand 1 (PD-L1) activates immune checkpoints of T cells. Anti-PD-1 antibody was reported to suppress HCC progression. Furthermore, GPC3-based HCC immunotherapy has been shown to be a curative approach to prolong the survival time of patients with HCC in clinically trials. Besides, the vascular endothelial growth factor (VEGF) inhibitor may inhibit the migration, invasion and angiogenesis of HCC. Here we review the cutting-edge progresses on mechanisms and clinical trials of HCC immunotherapy, which may have significant implication in our understanding of HCC and its immunotherapy.
Resilience as a Buffering Variable Between the Big Five Components and Factors and Symptoms of Academic Stress at University

The aim of this cross-sectional study was to establish predictive relationships of the Big Five personality factors (according to their self-regulatory level), together with resilience (proactive and reactive factors), for factors and symptoms of academic stress related to teaching and learning in the University context. A total of 405 female undergraduate students were selected, and completed questionnaires that had been previously validated in Spanish University students (Big Five personality factors, resilience, and academic stress symptoms and factors). A linear, ex-post facto design was used, including linear regression, Structural Equation Modeling (SEM), and mediational analyses. Specific linear regression showed the expected gradation: that self-regulatory personality factors (conscientiousness, extraversion) were positive linear predictors of proactive resilience, as well as significant negative predictors of stress factors and symptoms of academic stress; while the non-regulatory personality factors (openness to experience, agreeableness) showed little relationship. By contrast, the dysregulatory personality factor (neuroticism) was a negative predictor of proactive resilience, a positive predictor of reactive resilience, and positively predicted academic stress factors in the teaching and learning process, as well as stress symptoms. SEM general analysis showed that personality factors positively predicted resilience, and resilience negatively predicted factors and symptoms of academic stress. Specific mediational model analysis, with each personality factor, confirmed the different mediating relationships that appeared in the linear regression analyses. These results are discussed from the perspective of promoting resilience and healthy personalities in the University context. Implications for addressing academic stress at University are discussed.
Dual-Organ Transcriptomic Analysis of Rainbow Trout Infected With Ichthyophthirius multifiliis Through Co-Expression and Machine Learning

Ichthyophthirius multifiliis is a major pathogen that causes a high mortality rate in trout farms. However, systemic responses to the pathogen and its interactions with multiple organs during the course of infection have not been well described. In this study, dual-organ transcriptomic responses in the liver and head kidney and hemato-serological indexes were profiled under I. multifiliis infection and recovery to investigate systemic immuno-physiological characteristics. Several strategies for massive transcriptomic interpretation, such as differentially expressed genes (DEGs), Poisson linear discriminant (PLDA), and weighted gene co-expression network analysis (WGCNA) models were used to investigate the featured genes/pathways while minimizing the disadvantages of individual methods. During the course of infection, 6,097 and 2,931 DEGs were identified in the head kidney and liver, respectively. Markers of protein processing in the endoplasmic reticulum, oxidative phosphorylation, and the proteasome were highly expressed. Likewise, simultaneous ferroptosis and cellular reconstruction was observed, which is strongly linked to multiple organ dysfunction. In contrast, pathways relevant to cellular replication were up-regulated in only the head kidney, while endocytosis- and phagosome-related pathways were notably expressed in the liver. Moreover, interestingly, most immune-relevant pathways (e.g., leukocyte trans-endothelial migration, Fc gamma R-mediated phagocytosis) were highly activated in the liver, but the same pathways in the head kidney were down-regulated. These conflicting results from different organs suggest that interpretation of co-expression among organs is crucial for profiling of systemic responses during infection. The dual-organ transcriptomics approaches presented in this study will greatly contribute to our understanding of multi-organ interactions under I. multifiliis infection from a broader perspective.
Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR)-T cells. In this review, we will highlight the mechanism of action of immuno-therapy currently available in clinical practice to target CD38, SLAMF7, and BCMA, focusing on the biological role of the targets and on mechanisms of actions of the different immunotherapeutic approaches underlying their advantages and disadvantages with critical review of the literature data.
The Impact of Emotional Labor on User Stickiness in the Context of Livestreaming Service—Evidence From China

Improving the user stickiness becomes increasingly valued, due to the severe user churn of livestreaming services. Previous studies pay much attention to the influencing factors of technology on user stickiness, ignoring the emotional factors. This study examined the impact of the emotional labor of network anchors (deep acting vs. surface acting) on user stickiness in the context of livestreaming service. We extended prior findings in three ways. The results of Study 1 (i.e., questionnaire method, 305 livestreaming users, and 56.4% females) demonstrated that the emotional labor of network anchor positively influenced user stickiness, and immersion experience plays a mediating role. The results of Study 2 (i.e., situational simulation method, 203 volunteers, and 54.09% females) demonstrated that the deep acting strategies of emotional labor had a stronger effect when compared with surface acting strategies. The results of Study 3 (i.e., situational simulation method, 235 volunteers, and 51.9% females) demonstrated that the effect of emotional labor on user stickiness was stronger for the users with prevention focus compared with promotion focus. Based on the perspective of emotional labor, this study extends the previous research on user stickiness and is valuable for guiding the practice of livestreaming services.
Influence of Life Meaning on Subjective Well-Being of Older People: Serial Multiple Mediation of Exercise Identification and Amount of Exercise

Objective: This study aimed to explore the relationship between life meaning and subjective well-being among older people and the mediating role of subjective exercise identification and objective amount of exercise. Methods: A total of 352 older respondents completed four questionnaires: the Chinese life meaning scale, the University of Newfoundland Happiness Scale, the physical activity habits questionnaire, and the exercise identification questionnaire designed for this study. Results: Gender differences existed in the respondents' perception of life meaning, and men had a better perception of life meaning (t = 2.28, SE = 0.63, p < 0.05). There were age differences in the subjective well-being of older people (F = 5.69, partial η2 = 0.03, p < 0.01); the subjective well-being of older individuals steadily declines with rising age. Life meaning not only directly affected the subjective well-being of the respondents but also indirectly influenced their subjective well-being through the following three pathways: life meaning → exercise identification → subjective well-being (mediating effect of 22%); life meaning → amount of exercise → subjective well-being (mediating effect of 22%); and life meaning → exercise identification → amount of exercise → subjective well-being (serial multiple mediation effect of 27%). Conclusion: The more positive the life meaning perception of older people is, the higher their experience of subjective well-being. For older people to sense the meaning of life, we recommend that they realize the importance of physical activities and take the initiative to engage in physical activities to obtain higher subjective well-being.
Characterization and Stage-Dependent Lineage Analysis of Intermediate Progenitors of Cortical GABAergic Interneurons

Intermediate progenitors of both excitatory and inhibitory neurons, which can replenish neurons in the adult brain, were recently identified. However, the generation of intermediate progenitors of GABAergic inhibitory neurons (IPGNs) has not been studied in detail. Here, we characterized the spatiotemporal distribution of IPGNs in mouse cerebral cortex. IPGNs generated neurons during both embryonic and postnatal stages, but the embryonic IPGNs were more proliferative. Our lineage tracing analyses showed that the embryonically proliferating IPGNs tended to localize to the superficial layers rather than the deep cortical layers at 3 weeks after birth. We also found that embryonic IPGNs derived from the medial and caudal ganglionic eminence (CGE) but more than half of the embryonic IPGNs were derived from the CGE and broadly distributed in the cerebral cortex. Taken together, our data indicate that the broadly located IPGNs during embryonic and postnatal stages exhibit a different proliferative property and layer distribution.
Childhood Maltreatment Was Correlated With the Decreased Cortical Function in Depressed Patients Under Social Stress in a Working Memory Task: A Pilot Study

Background: Major depressive disorder (MDD) is a common psychiatric disorder associated with working memory (WM) impairment. Neuroimaging studies showed divergent results of the WM process in MDD patients. Stress could affect the occurrence and development of depression, in which childhood maltreatment played an important role. Methods: Thirty-seven MDD patients and 54 healthy control subjects were enrolled and completed a WM functional magnetic resonance imaging task with maintenance and manipulation conditions under stress and non-stress settings. We collected demographical and clinical data, using 17-item Hamilton Depression Scale (HAMD-17) and Childhood Trauma Questionnaire (CTQ) in MDD patients. In the WM task, we analyzed the main diagnosis effect and explored the correlation of impaired brain regions in MDD patients with CTQ and HAMD-17. Results: No group differences were found in the accuracy rate and reaction time between the two groups. MDD patients had lower brain activation in following regions (PFWE < 0.05). The left fusiform gyrus showed less activation in all conditions. The right supplementary motor area (SMA) exhibited decreased activation under non-stress. The anterior prefrontal cortex showed reduced activation during manipulation under stress, with the β estimations of the peak voxel showing significant group difference negatively correlated with childhood sex abuse (PBonferroni < 0.05). Conclusions: In our pilot study, MDD patients had reduced brain activation, affecting emotional stimuli processing function, executive function, and cognitive control function. Childhood maltreatment might affect brain function in MDD. This work might provide some information for future studies on MDD.
Cyber-Personality and Liking Expression: A Study From WeChat Users in China

Clicking the like button following a post on social media has become a common means of expressing and gathering social support online. Little is known about how liking expression is linked and regulated by personality traits and communication motives. Following a preliminary survey (n = 168) about the usage of the like function on WeChat, a Chinese social media platform, we conducted an online study (n = 183) to map the Big-Five personality traits and five communication motives to the frequency (likelihood) of liking expression. The results showed that each user had, on average, 385 WeChat friends and spent 2.2 hours and used the liking function 1.1 times each day on WeChat. The personality trait conscientiousness was negatively related to the liking expression (β = −0.505, p < 0.05). In contrast, agreeableness promoted the expression of liking directly (β = 0.153, p < 0.05) and indirectly via two communication motives, enjoyment (a: β = 0.377, p < 0.01; b: β = 0.433, p < 0.001) and passing time (c: β = 0.578, p < 0.05; d: β = 0.523, p < 0.001). The liking expression may serve as a simple index for understanding dispositional underpinnings of social media networking.
The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

The glymphatic system (GS) is a novel defined brain-wide perivascular transit network between cerebrospinal fluid (CSF) and interstitial solutes that facilitates the clearance of brain metabolic wastes. The complicated network of the GS consists of the periarterial CSF influx pathway, astrocytes-mediated convective transport of fluid and solutes supported by AQP4 water channels, and perivenous efflux pathway. Recent researches indicate that the GS dysfunction is associated with various neurological disorders, including traumatic brain injury, hydrocephalus, epilepsy, migraine, and Alzheimer’s disease (AD). Meanwhile, the GS also plays a pivotal role in the pathophysiological process of stroke, including brain edema, blood–brain barrier (BBB) disruption, immune cell infiltration, neuroinflammation, and neuronal apoptosis. In this review, we illustrated the key anatomical structures of the GS, the relationship between the GS and the meningeal lymphatic system, the interaction between the GS and the BBB, and the crosstalk between astrocytes and other GS cellular components. In addition, we contributed to the current knowledge about the role of the GS in the pathology of stroke and the role of AQP4 in stroke. We further discussed the potential use of the GS in early risk assessment, diagnostics, prognostics, and therapeutics of stroke.
Case Report: The First Report of NUP214-ABL1 Fusion Gene in Acute Myeloid Leukemia Patient Detected by Next-Generation Sequencing

The NUP214-ABL1 fusion gene is a constitutively active tyrosine kinase that can be detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL) patients, and it can also be found in B-cell acute lymphoblastic leukaemia (B-ALL). However the NUP214-ABL1 fusion in acute myeloid leukemia (AML) has not yet been reported. Up to now, the sensitivity of NUP214-ABL1-positive patients to tyrosine kinase inhibitor (TKI) is still controversial. Here we report the first case of an AML patient carrying NUP214-ABL1 fusion gene. The conventional AML chemotherapy regimen for the patient was successful. Identification of additional AML patients with NUP214-ABL1 fusion gene will provide treatment experience and prognostic evaluation.
The Relationship Between Perceived Corporate Social Responsibility and Employee-Related Outcomes: A Meta-Analysis

Although there is much research on the relationships of corporate social responsibility and employee-related outcomes, a systematic and quantitative integration of research findings is needed to substantiate and broaden our knowledge. A meta-analysis allows the comparison of the relations of different types of CSR on several different outcomes, for example to learn what type of CSR is most important to employees. From a theoretical perspective, social identity theory is the most prominent theoretical approach in CSR research, so we aim to investigate identification as a mediator of the relationship between CSR and employee-related outcomes in a meta-analytical mediation model. This meta-analysis synthesizes research findings on the relationship between employees' perception of CSR (people, planet, and profit) and employee-related outcomes (identification, engagement, organizational attractiveness, turnover (intentions), OCB, commitment, and job satisfaction), thereby distinguishing attitudes and behavior. A total of 143 studies (N = 89,396) were included in the meta-analysis which was conducted according to the methods by Schmidt and Hunter (except of the meta-analytical structural equation model). Mean effect sizes for the relationship between CSR and employee-related attitudes and behaviors were medium-sized to large. For attitudes, the relationships were stronger than for behavior. For specific types of CSR, average effect sizes were large. Identification mediated the relation between CSR and commitment, job satisfaction, and OCB, respectively. Based on our results, we give recommendations concerning the design of CSR initiatives in a way that benefits employees.
Local Destruction of Tumors and Systemic Immune Effects

Current immune-based therapies signify a major advancement in cancer therapy; yet, they are not effective in the majority of patients. Physically based local destruction techniques have been shown to induce immunologic effects and are increasingly used in order to improve the outcome of immunotherapies. The various local destruction methods have different modes of action and there is considerable variation between the different techniques with respect to the ability and frequency to create a systemic anti-tumor immunologic effect. Since the abscopal effect is considered to be the best indicator of a relevant immunologic effect, the present review focused on the tissue changes associated with this effect in order to find determinants for a strong immunologic response, both when local destruction is used alone and combined with immunotherapy. In addition to the T cell-inflammation that was induced by all methods, the analysis indicated that it was important for an optimal outcome that the released antigens were not destroyed, tumor cell death was necrotic and tumor tissue perfusion was at least partially preserved allowing for antigen presentation, immune cell trafficking and reduction of hypoxia. Local treatment with controlled low level hyperthermia met these requisites and was especially prone to result in abscopal immune activity on its own.
MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy

Inhibition of the MDM2/X-p53 interaction is recognized as a potential anti-cancer strategy, including the treatment of glioblastoma (GB). In response to cellular stressors, such as DNA damage, the tumor suppression protein p53 is activated and responds by mediating cellular damage through DNA repair, cell cycle arrest and apoptosis. Hence, p53 activation plays a central role in cell survival and the effectiveness of cancer therapies. Alterations and reduced activity of p53 occur in 25-30% of primary GB tumors, but this number increases drastically to 60-70% in secondary GB. As a result, reactivating p53 is suggested as a treatment strategy, either by using targeted molecules to convert the mutant p53 back to its wild type form or by using MDM2 and MDMX (also known as MDM4) inhibitors. MDM2 down regulates p53 activity via ubiquitin-dependent degradation and is amplified or overexpressed in 14% of GB cases. Thus, suppression of MDM2 offers an opportunity for urgently needed new therapeutic interventions for GB. Numerous small molecule MDM2 inhibitors are currently undergoing clinical evaluation, either as monotherapy or in combination with chemotherapy and/or other targeted agents. In addition, considering the major role of both p53 and MDM2 in the downstream signaling response to radiation-induced DNA damage, the combination of MDM2 inhibitors with radiation may offer a valuable therapeutic radiosensitizing approach for GB therapy. This review covers the role of MDM2/X in cancer and more specifically in GB, followed by the rationale for the potential radiosensitizing effect of MDM2 inhibition. Finally, the current status of MDM2/X inhibition and p53 activation for the treatment of GB is given.
Users’ Responsiveness to Persuasive Techniques in Recommender Systems

Understanding user’s behavior and their interactions with artificial-intelligent-based systems is as important as analyzing the performance of the algorithms used in these systems. For instance, in the Recommender Systems domain, the accuracy of the recommendation algorithm was the ultimate goal for most systems designers. However, researchers and practitioners have realized that providing accurate recommendations is insufficient to enhance users’ acceptance. A recommender system needs to focus on other factors that enhance its interactions with the users. Recent researches suggest augmenting these systems with persuasive capabilities. Persuasive features lead to increasing users’ acceptance of the recommendations, which, in turn, enhances users’ experience with these systems. Nonetheless, the literature still lacks a comprehensive view of the actual effect of persuasive principles on recommender users. To fill this gap, this study diagnoses how users of different characteristics get influenced by various persuasive principles that a recommender system uses. The study considers four users’ aspects: age, gender, culture (continent), and personality traits. The paper also investigates the impact of the context (or application domain) on the influence of the persuasive principles. Two application domains (namely eCommerce and Movie recommendations) are considered. A within-subject user study was conducted. The analysis of (279) responses revealed that persuasive principles have the potential to enhance users’ experience with recommender systems. The study also shows that, among the considered factors, culture, personality traits, and the domain of recommendations have a higher impact on the influence of persuasive principles than other factors. Based on the analysis of the results, the study provides insights and guidelines for recommender systems designers. These guidelines can be used as a reference for designing recommender systems with users’ experience in mind. We suggest that considering the results presented in this paper could help to improve recommender-users interaction.