Exosomes in Action: Unraveling Their Role in Autoimmune Diseases and Exploring Potential Therapeutic Applications.

Exosomes are double phospholipid membrane vesicles that are synthesized and secreted by a variety of cells, including T cells, B cells, dendritic cells, immune cells, are extracellular vesicles. Recent studies have revealed that exosomes can play a significant role in under both physiological and pathological conditions. They have been implicated in regulation of inflammatory responses, immune response, angiogenesis, tissue repair, and antioxidant activities, particularly in modulating immunity in autoimmune diseases (AIDs). Moreover, variations in the expression of exosome-related substances, such as miRNA and proteins, may not only offer valuable perspectives for the early warning, and prognostic assessment of various AIDs, but may also serve as novel markers for disease diagnosis. This article examines the impact of exosomes on the development of AIDs and explores their potential for therapeutic application.

The Impact of Recent Life Events, Internalizing Symptoms, and Emotion Regulation on the Severity of Non-Suicidal Self-Injury in Adolescents: A Mediation Analysis.

Background: Previous studies have demonstrated a strong association between recent stressful life events and non-suicidal self-injury (NSSI) among adolescents. Internalizing symptoms and difficulty in emotion regulation (DER) may mediate this relationship. This study aimed to investigate the relationship between recent stressful life events and NSSI severity in adolescents and the potential moderating role of internalizing symptoms and DER. Methods: A total of 224 adolescent inpatients (78.6% female) participated in the study, with an age range of 12-18 years old. Data on recent stressful life events, internalizing symptoms, DER, and NSSI behaviors were collected using a clinician-rated questionnaire. A structural equation model was used to test the hypothesized model. Results: The rate of NSSI reporting among adolescents in the past 12 months was 65.18%. Recent stressful life events were found to be directly associated with NSSI severity (ß = 0.128, P = 0.023). A chain-mediating effect between recent stressful life events and NSSI was also confirmed (ß = 0.034, P = 0.023), with DER and internalizing symptoms playing a chain-mediating role and DER having a significantly indirect association with NSSI through internalizing symptoms. Conclusion: Recent stressful life events appear to play a role in the etiology of NSSI, particularly punishment and interpersonal relationship events that warrant special attention. DER and internalizing symptoms play a chain-mediating role in the relationship between life events and NSSI. Reducing recent stressful life events, screening for internalizing symptoms, and improving emotion regulation may decrease NSSI behavior among adolescents.

An exploration of the association between family functioning and nonsuicidal self-injury among Chinese adolescents with mood disorders

Background and objectives This study explored the correlation between nonsuicidal self-injury (NSSI) and family functioning among adolescents aged 12 to 17 years with mood disorders. Methods A total of 142 participants were clinically assessed for NSSI, with 85 in the NSSI group and 57 in the non-NSSI group. The correlation between NSSI and family functioning was compared and a regression prediction model was constructed to determine the risk probability of NSSI. Results A significant association was found between family functioning and NSSI (P = 0.017). The correlation between adolescents with NSSI and gender, communication, affective responsiveness, and behaviour control was statistically significant. A nomogram graph and ROC curve were constructed, with an AUC of 0.772. Conclusion The findings support the notion that family functioning is associated with a higher risk for NSSI among adolescents with mood disorders. Furthermore, gender, communication, affective responsiveness, and behaviour control may be contributing factors. (AU)

Camellia oil exhibits anti-fatigue property by modulating antioxidant capacity, muscle fiber, and gut microbial composition in mice.

Camellia seed oil (CO) has high nutritional value and multiple bioactivities. However, the specific anti-fatigue characteristics and the implied mechanism of CO have not yet been fully elucidated. Throughout this investigation, male C57BL/6J mice, aged 8 weeks, underwent exhaustive exercise with or without CO pretreatment (2, 4, and 6 mL/kg BW) for 28 days. CO could extend the rota-rod and running time, reduce blood urea nitrogen levels and serum lactic acid, and increase muscle and hepatic glycogen, adenosine triphosphate, and anti-oxidative indicators. Additionally, CO could upregulate the mRNA and Nrf2 protein expression levels, as well as enhance the levels of its downstream antioxidant enzymes and induce the myofiber-type transformation from fast to slow and attenuate the gut mechanical barrier. Moreover, CO could ameliorate gut dysbiosis by reducing Firmicutes to Bacteroidetes ratio at the phylum level, increasing the percentage of Alistipes, Alloprevotella, Lactobacillus, and Muribaculaceae, and decreasing the proportion of Dubosiella at the genus level. In addition, specific bacterial taxa, which were altered by CO, showed a significant correlation with partial fatigue-related parameters. These findings suggest that CO may alleviate fatigue by regulating antioxidant capacity, muscle fiber transformation, gut mechanical barrier, and gut microbial composition in mice. PRACTICAL APPLICATION: Our study revealed that camellia seed oil (CO) could ameliorate exercise-induced fatigue in mice by modulating antioxidant capacity, muscle fiber, and gut microbial composition in mice. Our results promote the application of CO as an anti-fatigue functional food that targets oxidative stress, myofiber-type transformation, and microbial community.

Striking Cholestatic Giant Cell Hepatitis Resulting in Fulminant Liver Failure After Garcinia Cambogia Use.

Garcinia cambogia, a weight control herbal, can cause mild liver toxicity with nonspecific histologic changes. Herein, we reported a case of herbal-induced fulminant cholestatic giant cell hepatitis due to garcinia cambogia use. A 65-year-old woman with breast cancer treated 18 years earlier was admitted for obstructive jaundice for 2 weeks. She started using garcinia cambogia 3 months ago for weight loss. Physical exam showed scleral icterus. Serum studies excluded Wilson's disease, systemic infection including COVID-19 (coronavirus disease 2019), autoimmune hepatitis, and metabolic or toxicologic causes. An urgent liver biopsy showed severe giant cell hepatitis in absence of HSV-1/2, cytomegalovirus, HBsAg and HBcAg (immunostain), and EBV (in situ hybridization). Despite supportive therapy, the patient developed grade 2-3 hepatic encephalopathy and necessitated liver transplant. The explanted liver was markedly atrophy, in which the most striking histologic finding was diffuse distribution of multinucleated giant hepatocytes with syncytial pattern in a background of extensive zone-1 accentuated, geographic, hemorrhagic, confluent hepatocytic necrosis, along with remarkable hepatocytic and canalicular cholestasis. Marked hepatocellular and sinusoidal iron orverload present. The patient recovered uneventfully.

Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15.

Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the colonic T cell homing receptor, GPR15, hence affecting the number of colonic FOXP3+ regulatory T (Treg) cells and local immune homeostasis. Ingested L-Trp is converted by host IDO1/2 enzymes, but not by gut microbiota, to compounds that induce GPR15 transcription preferentially in Treg cells via the aryl hydrocarbon receptor. Consequently, two weeks of dietary L-Trp supplementation nearly double the colonic GPR15+ Treg cells via GPR15-mediated homing and substantially reduce the future risk of colitis. In addition, humans consume 3-4 times less L-Trp per kilogram of body weight and have fewer colonic GPR15+ Treg cells than mice. Thus, we uncover a microbiota-independent mechanism linking dietary L-Trp and colonic Treg cells, that may have therapeutic potential.

The amplitude of low-frequency fluctuation characteristics in depressed adolescents with suicide attempts: a resting-state fMRI study.

Background: The amplitude of low-frequency fluctuation (ALFF) is a measure of spontaneous brain activity derived from resting-state functional magnetic resonance imaging (rs-fMRI). Previous research has suggested that abnormal ALFF values may be associated with major depressive disorder (MDD) and suicide attempts in adolescents. In this study, our aim was to investigate the differences in ALFF values between adolescent MDD patients with and without a history of suicide attempts, and to explore the potential utility of ALFF as a neuroimaging biomarker for aiding in the diagnosis and prediction of suicide attempts in this population. Methods: The study included 34 adolescent depression patients with suicide attempts (SU group), 43 depression patients without suicide attempts (NSU group), and 36 healthy controls (HC group). Depression was diagnosed using a threshold score greater than 17 on the Hamilton Depression Rating Scale (HDRS). The rs-fMRI was employed to calculate zALFF values and compare differences among the groups. Associations between zALFF values in specific brain regions and clinical variables such as emotion regulation difficulties were explored using Pearson partial correlation analysis. Receiver-Operating Characteristics (ROC) analysis assessed the ability of mean zALFF values to differentiate between SU and NSU groups. Results: Significant differences in zALFF values were observed in the left and right inferior temporal gyrus (l-ITG, r-ITG) and right fusiform gyrus (r-FG) among the three groups (GRF corrected). Both SU and NSU groups exhibited increased zALFF values in the inferior temporal gyrus compared to the HC group. Furthermore, the SU group showed significantly higher zALFF values in the l-ITG and r-FG compared to both the NSU group and the HC group. Partial correlation analysis revealed a negative correlation between zALFF values in the left superior and middle frontal gyrus (l-SFG, l-MFG) and the degree of emotional dysregulation in the SU group (R = -0.496, p = 0.003; R = -0.484, p = 0.005). Combining zALFF values from the l-ITG and r-FG achieved successful discrimination between depressed adolescents with and without suicide attempts (AUC = 0.855) with high sensitivity (86%) and specificity (71%). Conclusion: Depressed adolescents with suicidal behavior exhibit unique neural activity patterns in the inferior temporal gyrus and fusiform gyrus. These findings highlight the potential utility of these specific brain regions as biomarkers for identifying suicide risk in depressed adolescents. Furthermore, associations between emotion dysregulation and activity in their frontal gyrus regions were observed. These findings provide preliminary yet pertinent insights into the pathophysiology of suicide in depressed adolescents.

An Update on the Role of Immunohistochemistry in the Evaluation of Pancreatic/Liver/Gastrointestinal Luminal Tract Disorders.

CONTEXT.­: Immunohistochemistry serves as an ancillary diagnostic tool for a wide variety of neoplastic and nonneoplastic disorders, including infections, workup of inflammatory conditions, and subtyping neoplasms of the pancreas/liver/gastrointestinal luminal tract. In addition, immunohistochemistry is also used to detect a variety of prognostic and predictive molecular biomarkers for carcinomas of the pancreas, liver, and gastrointestinal luminal tract. OBJECTIVE.­: To highlight an update on the role of immunohistochemistry in the evaluation of pancreatic/liver/gastrointestinal luminal tract disorders. DATA SOURCES.­: Literature review and authors' research data and personal practice experience were used. CONCLUSIONS.­: Immunohistochemistry is a valuable tool, assisting in the diagnosis of problematic tumors and benign lesions of the pancreas, liver, and gastrointestinal luminal tract, and also in the prediction of prognosis and therapeutic response for carcinomas of the pancreas, liver, and gastrointestinal luminal tract.

Preparation and characterization of inclusion complex of Myristica fragrans Houtt. (nutmeg) essential oil with 2-hydroxypropyl-ß-cyclodextrin.

Nutmeg essential oil (NEO) is a natural condimentwith versatile biological activities. However, the application of NEO in food has several limitations due to its poor stability and low aqueous solubility. To overcome the shortcomings, this paper focused on the preparation of the inclusion complex (IC) of NEO with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by the coprecipitation method. The optimal condition was inclusion temperature 36 ℃, time 247 min, stirring speed 520 r/min, and wall-core ratio 12:1, resulting in a recovery of 80.63%. The formation of IC was verified by various methods such as scanning electron microscopy, Fourier transform infrared spectroscopy and nuclear magnetic resonance. The improvement of thermal stability, antioxidant, and nitrite scavenging activities of NEO after encapsulation was proven. Moreover, the controlled release of NEO from IC can be implemented by regulating the temperature and relative humidity. Overall, NEO/HP-ß-CD IC has great application potential in food industries.

Ubiquitous WiFi and Acoustic Sensing: Principles, Technologies, and Applications.

With the increasing pervasiveness of mobile devices such as smartphones, smart TVs, and wearables, smart sensing, transforming the physical world into digital information based on various sensing medias, has drawn researchers' great attention. Among different sensing medias, WiFi and acoustic signals stand out due to their ubiquity and zero hardware cost. Based on different basic principles, researchers have proposed different technologies for sensing applications with WiFi and acoustic signals covering human activity recognition, motion tracking, indoor localization, health monitoring, and the like. To enable readers to get a comprehensive understanding of ubiquitous wireless sensing, we conduct a survey of existing work to introduce their underlying principles, proposed technologies, and practical applications. Besides we also discuss some open issues of this research area. Our survey reals that as a promising research direction, WiFi and acoustic sensing technologies can bring about fancy applications, but still have limitations in hardware restriction, robustness, and applicability. Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-023-3073-5.

Aberrant p53 Expression in Gastric Biopsies and Resection Specimens Following Neoadjuvant Chemoradiation: A Diagnostic Pitfall.

Gastric mucosal biopsies and resections from patients treated with neoadjuvant radiation and/or chemotherapy are frequently encountered. These samples may show histologic features related to therapy including inflammation, ulceration, and epithelial atypia. In some cases, epithelial atypia may be marked, prompting the use of adjunct p53 immunohistochemistry. We examined p53 expression by immunohistochemistry in gastric mucosa following therapy.We evaluated the histology and p53 immunohistochemical expression in gastric mucosa from 57 resections and 3 mucosal biopsies, from 60 patients treated with radiation and/or chemotherapy for gastroesophageal carcinoma (n = 33) or pancreatic carcinoma (n = 27).We identified histomorphologic features of therapy-related epithelial changes in 50 of 60 cases (83%). Abnormal p53 expression was present at least focally in nearly half the cases (27 of 60 cases; 45%), all of which showed morphologic evidence of therapy-related epithelial changes. Neuroendocrine cell micronests were present in 37 of 60 cases (62%). Next-generation sequencing (NGS) of foci with therapy-related epithelial changes showing abnormal p53 expression and carcinoma from the same patient was attempted and yielded results in 1 patient. Interestingly, differing TP53 alterations in the patient's adenocarcinoma and in a histologically benign esophageal submucosal gland with therapy-related epithelial changes and abnormal p53 expression were identified.Our results demonstrate that abnormal p53 expression is relatively common in gastric mucosal samples following radiation and/or chemotherapy and suggest that p53 expression should be avoided when distinguishing therapy-related changes from dysplasia or carcinoma. Furthermore, our NGS results raise interesting biological questions, which may warrant further investigation.

BPA and its alternatives BPF and BPAF exaggerate hepatic lipid metabolism disorders in male mice fed a high fat diet.

Alternatives to Bisphenol A (BPA), such as BPF and BPAF, have found increasing industrial applications. However, toxicological research on these BPA analogues remains limited. This study aimed to investigate the effects of BPA, BPF, and BPAF exposure on hepatotoxicity in mice fed with high-fat diets (HFD). Male mice were exposed to the bisphenols at a dose of 0.05 mg per kg body weight per day (mg/kg bw/day) for eight consecutive weeks, or 5 mg/kg bw/day for the first week followed by 0.05 mg/kg bw/day for seven weeks under HFD. The low dose (0.05 mg/kg bw/day) was corresponding to the tolerable daily intake (TDI) of BPA and the high dose (5 mg/kg bw/day) was corresponding to its no observed adverse effect level (NOAEL). Biochemical analysis revealed that exposure to these bisphenols resulted in liver damage. Metabolomics analysis showed disturbances of fatty acid and lipid metabolism in bisphenol-exposed mouse livers. BPF and BPAF exposure reduced lipid accumulation in HFD mouse liver by lowering glyceride and cholesterol levels. Transcriptomics analysis demonstrated that expression levels of genes related to fatty acid synthesis and metabolism were changed, which might be related to the activation of the PPAR signaling pathway. Besides, a feedback regulation mechanism might exist to maintain hepatic metabolic homeostasis. For the first time, this study demonstrated the effects of BPF and BPAF exposure in HFD-mouse liver. Considering the reality of the high prevalence of obesity nowadays and the ubiquitous environmental distribution of bisphenols, this study provides insight and highlights the adverse effects of BPA alternatives, further contributing to the consideration of the safe use of such compounds.

Sarcomatoid renal cell tumor harboring a novel BYSL::TFEB fusion with concurrent TFEB amplification.

Transcription factor EB (TFEB)-rearranged renal cell carcinoma (RCC) exhibits diverse gene fusion patterns and heterogeneous clinicopathologic features. Rare TFEB-amplified RCCs have been described recently and are associated with a more aggressive clinical course. Herein, we report a case of an 86-year-old man with a solid 9.2-cm kidney tumor that showed a diffuse high-grade sarcomatoid morphology. The tumor demonstrated a novel BYSL::TFEB fusion containing exons 1-2 of the BYSL gene fused to exons 3-10 of TFEB via next-generation sequencing by using NextSeq sequencer. Fluorescence in situ hybridization (FISH) studies displayed concurrent high-copy number TFEB amplification in two distinct patterns, a balanced increase of 5' and 3' copies, and solely increased 5' copies, and mouse double minute 2 (MDM2) gene amplification by using TFEB (6p21.1) dual-color break-apart probe and MDM2 FISH probe. Notably, the tumor showed a distinctive immunoprofile with overexpressions of TFEB, epithelial membrane antigen, Cathepsin K, and PDL-1 (SP263). FISH test for transcription factor binding to IGHM enhancer 3 (TFE3) was negative for rearrangement and corresponding immunonegativity of TFE3. These findings not only expand the repertoire of known TFEB fusion partners implicated in tumorigenesis, but also may provide novel information for target therapy.

Child maltreatment exposure and adolescent nonsuicidal self-injury: the mediating roles of difficulty in emotion regulation and depressive symptoms.

BACKGROUND: Although child maltreatment (CM) experiences are recognized risk factors for nonsuicidal self-injury (NSSI), the mechanisms underlying this relationship remain unclear. The purpose of this study was to examine whether difficulty in emotion regulation (DER) and depressive symptoms mediate the relationship between child maltreatment experiences and NSSI severity, adjusting for demographic variables. METHODS: The participants were 224 adolescent inpatients recruited from a hospital in China (mean age 15.30 years, SD = 1.83; 78.6% females). Study measures included the Clinician-Rated Severity of Nonsuicidal Self-Injury (CRSNSSI), Childhood Trauma Questionnaire (CTQ-SF), Difficulties in Emotion Regulation Scale (DERS), and Patient Health Questionnaire-9 (PHQ-9). The hypothesized chain mediation model was tested using the structural equation model. RESULTS: A total of 146 (65.18%) adolescents reported engaging in NSSI during the past 12 months, and 103 (45.98%) participants met the DSM-5 diagnostic criteria for NSSI. Emotional neglect (48.1%) and emotional abuse (46.1%) had the highest prevalence, followed by physical neglect (43.1%) and physical abuse (24.1%), whereas sexual abuse (12.5%) was the least prevalent form of CM. Separately, both DER and depressive symptoms significantly mediated the association between CM and NSSI, with DER being the strongest mediator, with an indirect effect of 49.40% (p = 0.014). At the same time, we also proved a potential chain-mediated pathway of DER and depression in the relationship between CM and NSSI. CONCLUSION: Child maltreatment seems to play a role in the aetiology of NSSI. DER and depressive symptoms both have a mediating role in the relationship between CM and NSSI. Importantly, DER seems to be a mediator with a stronger indirect effect compared to depressive symptoms.

Circulating Toll-Like Receptor 4, Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3, and Cytokines in Patients with Bipolar Depression: A Case-Control Study.

Objective: The etiology of bipolar disorder (BD), a complex psychiatric condition, remains uncertain. Previous research has suggested a potential involvement of the host immune system in the development of BD. This study aims to investigate plasma levels of cytokines, circulating toll-like receptor 4 (TLR4), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in patients with bipolar depression. Methods: This study recruited patients with a depressive episode of BD and healthy controls (HCs). Inflammatory cytokines were quantified using enzyme linked immunosorbent assay (ELISA) analysis. Results: A total of 26 BD patients with a depressive episode and 14 HCs were enrolled in the study. The findings revealed that individuals with BD with a depressive episode exhibited elevated serum levels of NLRP3 and interleukin-18 compared to HCs. Correlation analyses indicated a favorable association between the frequency of episodes, duration of illness, and TLR4 levels. Conclusion: The results suggest a connection between cytokines associated with the activation of NLRP3 and their potential impact on the pathogenesis of BD.

Distribution patterns of rubber tire-related chemicals with particle size in road and indoor parking lot dust.

In recent years, concerns have arisen from the chemicals incorporated into tire material which are of potential to leach with the tire and road wear particles (TRWP) into the environment. In this study, the distributions of substituted benzothiazoles (BTHs) and p-phenylenediamines (PPDs), two groups of representative TRWP-related chemicals, were investigated in various size fractions (<20, 20-53, 53-125, 125-250, 250-500, 500-1000 µm) of dust samples from open roads and indoor parking lots in the urban region of Guangzhou (Guangdong, China). Mass weight distribution of the dust samples showed that fractions of <250 µm accounted for >72% of the total dust in both microenvironments. Widespread occurrence was observed with >80% detection frequency for almost all target compounds in all the particle fractions. Concentrations of BTHs and PPDs were similar between the two dust matrices. In addition, the newly defined transformation product of 6PPD, 6PPD-Q was at the median concentration of 122 ng/g in road dust and 154 ng/g in indoor parking lot dust. Overall, concentrations of the target BTHs and PPDs varied in different size fractions, which were mostly dominated in fine particle sizes (<53 µm). Specially, >70% of the target compounds were in the size fractions of <250 µm, suggesting the necessity of using <250 µm fractions of particles for monitoring and evaluating contamination levels and exposure risks of BTHs and PPDs from dust in future studies.

Research Into Mental Health Prediction of Community Workers Involved in the Prevention of COVID-19 Epidemic Based on Cloud Model.

To get to know the mental status of community workers involved in the prevention of COVID-19 epidemic, provide them with mental counseling and guidance, and predict their mental health status, a cloud model for the mental health prediction of community workers involved in the prevention of COVID-19 epidemic was constructed in this paper. First, the method to collect data about mental health was determined; second, the basic definition of cloud was discussed, the digital features of cloud were analyzed, and then, the cloud theory model was constructed; third, a model to predict the mental health of community workers involved in the prevention of COVID-19 epidemic was constructed based on the cloud theory, and corresponding algorithm was designed. Finally, a community was chosen as the research object to analyze and predict its mental health status. The research results suggest that the model can effectively predict the mental health status of community workers involved in the prevention of COVID-19 epidemic.

EEG Oscillatory Networks in Peri-Ictal Period of Absence Epilepsy.

Objective: To investigate the dynamical brain network changes before and after an absence seizure episode in absence epilepsy (AE). Methods: 21 AE patients with a current high frequency of seizures and 21 sex- and age-matched health control (HC) who reported no history of neurological or psychiatric disorders and visited the hospital for routine physical examinations were included. Each included subject underwent a 2-h and 19-channel video EEG examination. For AE patients, five epochs of 10-s EEG data in inter-ictal, pre-ictal, and post-ictal states were collected. For the HC group, five 10-s resting-state EEG epochs were extracted. Functional independent components analysis (ICA) was carried out using the LORETA KEY tool. Results: Compared with the resting-state EEG data of the HC group, the EEG data from AE patients during inter-ictal periods showed decreased alpha oscillations in regions involving the superior frontal gyrus (SFG) (BA11). From inter-ictal to pre-ictal, SFG (BA10) showed maximum decreased delta oscillations. Additionally, from pre-ictal to post-ictal, superior temporal gyrus (STG) (BA 22) presented maximum increased neural activity in the alpha band. Moreover, compared with inter-ictal EEG, post-ictal EEG showed significantly decreased theta activity in SFG (BA8). Conclusion: The changes in SFG alpha oscillations are the key brain network differences between inter-ictal EEG of AE patients and resting-state EEG of HCs. The brain networks of EEG oscillatory during peri-ictal episodes are mainly involving SFG and STG. Our study suggests that altered EEG brain networks dynamics exist between inter-ictal EEG of AE patients and resting-state EEG of HCs and between pre- and post-ictal EEG in AE patients.

Framing Climate Change Impacts as Moral Violations: The Pathway of Perceived Message Credibility.

Climate change has been increasingly discussed in moral terms in public discourse. Despite the growing body of research on the effectiveness of moral frames in bridging the ideological divide, few studies have examined the role that perceived credibility, an important element of any persuasive appeal, plays in facilitating the framing effect. With the objective of further understanding how moral frames may engage individuals with different ideologies in climate change and refining climate change messaging strategies, two experimental surveys were conducted to examine the effects of moral violation frames on climate engagement. Specifically, a moderated mediation model was tested. The model posits that message credibility mediates the relationship between moral frames and policy support, as well as the relationship between moral frames and behavior intention. Moreover, political ideology moderated the indirect effects of message credibility. Based on moral foundations theory, seven messages were designed to activate individualizing and binding moral foundations. The results indicated that credibility consistently mediated the effects of the moral violation frame on climate engagement and that liberal-leaning individuals were more likely to perceive an individualizing frame as more credible than a binding frame. However, this difference was smaller among conservative-leaning individuals, with evidence for this moderated mediation model found only for policy support among college students. This study suggests that credibility is key for effective moral violations arguments of climate change.

Utility of targeted next-generation sequencing assay to detect 1p/19q co-deletion in formalin-fixed paraffin-embedded glioma specimens.

Molecular classification of brain neoplasms is important for diagnosis, prognosis, and treatment outcome of histologically similar tumors. Oligodendroglioma is a glioma subtype characterized by 1p/19q co-deletion and IDH1/IDH2 mutations, which predict a good prognosis, responsiveness to therapy, and an improved overall survival compared to other adult gliomas. In a routine clinical setting, 1p/19q co-deletion is detected by interphase-FISH and SNP microarray, and somatic mutations are detected by targeted next-generation sequencing (NGS). The aim of this proof-of-principle study was to investigate the feasibility of using targeted NGS to simultaneously detect both 1p/19q co-deletion and somatic mutations. Among 247 consecutive patients with formalin-fixed paraffin-embedded brain tumors with various subtypes, NGS revealed 1p/19q co-deletion in 26 oligodendrogliomas and an IDH-wildtype astrocytoma, and partial loss across chromosomes 1p and 19q/whole-arm loss of 1p or 19q/copy neutral loss of heterozygosity in 11 nonoligodendrogliomas. For this 247 brain-tumor cohort, the overall sensitivity, specificity, and accuracy of detecting 1p/19q co-deletion by NGS in oligodendrogliomas were 96.2%, 99.6%, and 99.2%, respectively. The oligodendroglioma cohort had more mutations in IDH1/IDH2, CIC, FUBP1, and TERT, and fewer mutations in ATRX and TP53 than the nonoligodendroglioma cohort. This proof-of-concept study demonstrated that targeted NGS can simultaneously detect both 1p/19q co-deletion and somatic mutations, which can provide a more comprehensive genetic profiling for patients with gliomas using a single assay in a clinical setting.