Ribosomal Protein L9 Maintains Stemness of Colorectal Cancer via an ID-1 Dependent Mechanism.

The identification of therapeutic target genes that are functionally involved in stemness is crucial to effectively cure patients with metastatic carcinoma. We have previously reported that inhibition of ribosomal protein L9 (RPL9) expression suppresses the growth of colorectal cancer (CRC) cells by inactivating the inhibitor of DNA-binding 1 (ID-1) signaling axis, which is functionally associated with cancer cell survival. In addition to cell proliferation, ID-1 is also involved in the maintenance of cancer stemness. Thus, we aimed in this study to investigate whether the function of RPL9 could correlate with CRC stem cell-like properties. Here, we demonstrated that siRNA silencing of RPL9 reduced the invasiveness and migrative capabilities of HT29 and HCT116 parental cell populations and the capacity for sphere formation in the HT29 parental cell population. CD133+ cancer stem cells (CSCs) were then separated from CD133- cancer cells of the HT29 parental cell culture and treated with RPL9-specific siRNAs to verify the effects of RPL9 targeting on stemness. As a result, knockdown of RPL9 significantly suppressed the proliferative potential of CD133+ colorectal CSCs, accompanied by a reduction in CD133, ID-1, and p-IκBα levels. In line with these molecular alterations, targeting RPL9 inhibited the invasion, migration, and sphere-forming capacity of CD133+ HT29 CSCs. Taken together, these findings suggest that RPL9 promotes CRC stemness via ID-1 and that RPL9 could be a potential therapeutic target for both primary CRC treatment and the prevention of metastasis and/or recurrence.

Lactate promotes fatty acid oxidation by the TCA cycle and mitochondrial respiration in muscles of obese mice.

Lower oxidative capacity in skeletal muscles (SKMs) is a prevailing cause of metabolic diseases. Exercise not only enhances the fatty acid oxidation (FAO) capacity of SKMs but also increases lactate levels. Given that lactate may contribute to tricarboxylic acid cycle (TCA) flux and impact monocarboxylate transporter 1 in the SKMs, we hypothesize that lactate can influence glucose and fatty acid (FA) metabolism. To test this hypothesis, we investigated the mechanism underlying lactate-driven FAO regulation in the SKM of mice with diet-induced obesity (DIO). Lactate was administered to DIO mice immediately after exercise over three weeks. We found that increased lactate levels enhanced energy expenditure mediated by fat metabolism during exercise recovery and decreased triglyceride levels in DIO mice SKMs. To determine the lactate-specific effects without exercise, we administered lactate to mice on a high-fat diet (HFD) for eight weeks. Similar to our exercise conditions, lactate increased FAO, TCA cycle activity, and mitochondrial respiration in the SKMs of HFD-fed mice. Additionally, under sufficient FA conditions, lactate increased uncoupling protein-3 abundance via the NADH/NAD+ shuttle. Conversely ATP synthase abundance decreased in the SKMs of HFD mice. Taken together, our results suggest that lactate amplifies the adaptive increase in FAO capacity mediated by the TCA cycle and mitochondrial respiration in SKMs under sufficient FA abundance.

Artificial intelligence-based evaluation of carotid artery compressibility via point-of-care ultrasound in determining the return of spontaneous circulation during cardiopulmonary resuscitation.

AIM: This study introduces RealCAC-Net, an artificial intelligence (AI) system, to quantify carotid artery compressibility (CAC) and determine the return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation. METHODS: A prospective study based on data from a South Korean emergency department from 2022 to 2023 investigated carotid artery compressibility in adult patients with cardiac arrest using a novel AI model, RealCAC-Net. The data comprised 11,958 training images from 161 cases and 15,080 test images from 134 cases. RealCAC-Net processes images in three steps: TransUNet-based segmentation, the carotid artery compressibility measurement algorithm for improved segmentation and CAC calculation, and CAC-based classification from 0 (indicating a circular shape) to 1 (indicating high compression). The accuracy of the ROSC classification model was tested using metrics such as the dice similarity coefficient, intersection-over-union, precision, recall, and F1 score. RESULTS: RealCAC-Net, which applied the carotid artery compressibility measurement algorithm, performed better than the baseline model in cross-validation, with an average dice similarity coefficient of 0.90, an intersection-over-union of 0.84, and a classification accuracy of 0.96. The test set achieved a classification accuracy of 0.96 and an F1 score of 0.97, demonstrating its efficacy in accurately identifying ROSC in cardiac arrest situations. CONCLUSIONS: RealCAC-Net enabled precise CAC quantification for ROSC determination during cardiopulmonary resuscitation. Future research should integrate this AI-enhanced ultrasound approach to revolutionize emergency care.

Establishing Three-Dimensional Explant Culture of Human Dental Pulp Tissue.

Mesenchymal stem cells in the dental tissue indicate a disposition for differentiation into diverse dental lineages and contain enormous potential as the important means for regenerative medicine in dentistry. Among various dental tissues, the dental pulp contains stem cells, progenitor cells and odontoblasts for maintaining dentin homeostasis. The conventional culture of stem cells holds a limit as the living tissue constitutes the three-dimensional (3D) structure. Recent development in the organoid cultures have successfully recapitulated 3D structure and advanced to the assembling of different types. In the current study, the protocol for 3D explant culture of the human dental pulp tissue has been established by adopting the organoid culture. After isolating dental pulp from human tooth, the intact tissue was placed between two layers for Matrigel with addition of the culture medium. The reticular outgrowth of pre-odontoblast layer continued for a month and the random accumulation of dentin was observed near the end. Electron microscopy showed the cellular organization and in situ development of dentin, and immunohistochemistry exhibited the expression of odontoblast and stem cell markers in the outgrowth area. Three-dimensional explant culture of human dental pulp will provide a novel platform for understanding stem cell biology inside the tooth and developing the regenerative medicine.

NF2-Related Schwannomatosis (NF2): Molecular Insights and Therapeutic Avenues.

NF2-related schwannomatosis (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2 deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2 deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

Characteristics of Severe Asthma in the Elderly: Observations From the Korean Severe Asthma Registry (KoSAR).

PURPOSE: Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients. METHODS: We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups. RESULTS: Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group (P < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group (P < 0.05 for all). CONCLUSIONS: SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.

Serum MRGPRX2 as a Long-term Biomarker for Iodinated Contrast Media-Induced Anaphylaxis.

The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, P = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 (P = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, P = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs.

Association of Cough Severity with Asthma Control and Quality of Life in Patients with Severe Asthma.

PURPOSE: Symptoms are important components in determining asthma control and in the adjustment of treatment levels. However, clinical relevance of cough in severe asthma is not well-understood. This study aimed to evaluate the severity and association of cough with patient-reported outcomes (PROs) in patients with severe asthma. METHODS: This study analyzed cross-sectional data from the Korean Severe Asthma Registry. The severity of coughing and wheezing symptoms was assessed using a Visual Analog Scale (VAS) ranging from 0 to 100 for each symptom. Additionally, PROs included the Asthma Control Test (ACT), the Severe Asthma Questionnaire (SAQ), and the EuroQoL 5-Dimension (EQ-5D) index. Multivariate linear regression analysis was employed to explore the relationship between cough severity and other PRO scores. RESULTS: A total of 498 patients with severe asthma (age: 57.9 ± 13.1 years, females: 60.2%) were analyzed. The cough VAS score was higher than the wheeze score (median 30, [interquartile range 10-50] vs. 20 [0-50]; P < 0.001). Additionally, 22.5% of patients ranked in a higher tertile for cough severity compared to wheezing, while 18.5% ranked higher for wheezing severity than cough. Significant correlations were observed between cough and wheeze VAS scores (r = 0.61, P < 0.05) and between each symptom's VAS score and the SAQ (cough: r = -0.41, P < 0.001; wheeze: r = -0.52, P < 0.001), ACT scores (cough: r = -0.50, P < 0.001; wheeze: r = -0.63, P < 0.001) and EQ-5D index (cough: r = -0.40, P < 0.001; wheeze: r = -0.45, P < 0.001). In univariate regression analysis, the cough VAS score had weaker descriptive power (R2) values than the wheeze VAS score in relation to the PRO measures. Nevertheless, cough severity remained significantly associated with ACT, SAQ scores and EQ-5D index in multivariate analyses adjusted for wheeze severity and other confounders. CONCLUSION: Cough frequently presents as a severe symptom in patients with severe asthma and could have distinct impact on asthma control and quality of life.

Subretinal fluid in macular edema secondary to branch retinal vein occlusion.

We identified characteristics of patients with subretinal fluid (SRF) in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and determined their clinical outcomes after anti-vascular endothelial growth factor (VEGF) treatment. Fifty-seven eyes of BRVO patients with ME were divided into two groups according to the presence or absence of SRF at diagnosis. We compared the aqueous profiles, ocular and systemic characteristics at baseline, and the clinical outcomes. The SRF group had significantly greater central subfield thickness (CST) values and poorer best-corrected visual acuity (BCVA) at baseline compared to the non-SRF group. The former group had significantly higher aqueous levels of interleukin-8, VEGF, and placental growth factor. CST reduction and BCVA improvement during treatment were significantly greater in the SRF group than in the non-SRF group. Consequently, CST values were significantly lower in the SRF group than in the non-SRF group at 12 months, when BCVA did not differ significantly between the two groups. The SRF group required more frequent anti-VEGF treatment over 12 months and exhibited a higher rate of macular atrophy. Based on the aqueous profiles and the number of treatments required, the presence of SRF in BRVO patients appears to be associated with higher disease activity.

Lessons From the Household Humidifier Disinfectant Tragedy (HHDT) With Focus on the Chemical Poisoning Surveillance System: Review and Recommendation.

BACKGROUND: Lessons learned from the Household Humidifier Disinfectant Tragedy (HHDT) in Korea, which poisoned thousands of citizens over a period of years, necessitated an examination of national poison prevention and surveillance systems. The objectives of this study are to identify essential changes needed in chemical poisoning prevention regulations and surveillance systems for effective poison control by comparing recent trends in international poison control center (PCC) operations, and to delineate the critical elements for establishing a state-of-the-art poison control surveillance system in Korea based on recent advances in PCCs with toxicovigilance. METHODS: A comprehensive review of Korea's regulatory and surveillance systems for chemical health hazards, with a focus on household products under the HHDT, was conducted. A review of toxicovigilance systems in major countries shows that creating an effective national PCC requires key elements: a centralized database of toxic substances and poisoning cases, mandatory or voluntary reporting of poisoning cases, real-time alerts, collaboration among health organizations, and targeted follow-up of poisoned individuals. RESULTS: Significant deficiencies in Korea's legislation, toxicological data management, and poisoning surveillance systems, explained the inadequate response of the Korean government to the HHDT for nearly 17 years until the end of 2011. Based on a review of PCC toxicovigilance systems in major countries, a national framework with five core components is recommended for establishing a modern comprehensive Korea PCC system with toxicovigilance capacity. The core components include establishment of a centralized database of toxic substances information and clinical poisoning cases, implementation of mandatory or permissive reporting of poisoning cases, real-time alert mechanisms, collaborative systems among health-related organizations, and clinical follow-up of poisoned sub-groups. CONCLUSION: A rationale and framework for a state-of-the-art national Korean PCC with toxicovigilance is justified and offered. This proposed system could assist neighboring countries in establishing their own sophisticated, globally integrated PCC networks.

Long-term effects of the school context on depressive symptoms among Asian Americans.

Despite the importance of the school environment for mental health outcomes, there is little research on how the school context during adolescence may impact depressive symptoms among Asian Americans (AAs) over time. The purpose of this study was to investigate (a) the long-term effects of perceived prejudice from peers and teachers on school belonging and depressive symptoms in adolescence, early young adulthood, and young adulthood among AAs and (b) the mediating effects of school belonging and two early depressive symptoms on the associations between perceived prejudice from peers and teachers and young adulthood depressive symptoms. The data came from the National Longitudinal Study on Adolescent Health. The present study used a subsample of 689 AAs who completed interviews during adolescence, young adulthood, and adulthood. The major data analysis strategy was structural equation modeling. The structural equation modeling results indicated that the major path coefficients from school context to depressive symptoms at the three time points for AAs were statistically significant, except for the path from adolescent depressive symptoms to young adulthood depressive symptoms. There were three significant mediating effects of school belonging and two early depressive symptoms on the association between perceived prejudice from teachers and young adulthood depressive symptoms in AAs. The results emphasize the importance of identifying school contextual risk factors leading to mental health disparities and developing culturally appropriate intervention strategies for AAs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Psychometric Characteristics of the Fear of Cancer Recurrence Inventory-Severity Subscale Among Korean Cancer Survivors.

Objectives: Despite the importance of choosing and using a valid assessment tool for fear of cancer recurrence (FCR) for early detection and interventions, the validity of the FCR inventory has yet to be thoroughly investigated in Korea. This study explored the psychometric properties of the Fear of Cancer Recurrence Inventory-Severity (FCRI-S) subscale and assessed its applicability to cancer survivors in Korea. Methods: The survey involved 93 Korean individuals who had survived cancer. The reliability of the FCRI-S subscale was assessed using Cronbach's α and composite reliability (CR). Confirmatory factor analysis (CFA), along with tests for discriminant and convergent validity, was conducted to evaluate the construct validity of the FCRI-S subscale. Results: The FCRI-S subscale showed excellent internal consistency (Cronbach's α = 0.88; CR = 0.89). CFA showed a good factor structure for the FCRI-S subscale, and the correlations of the FCRI-S subscale with FCR-related measures (r = 0.69 to 0.80) and other psychosocial measures (r = -0.23 to 0.37) confirmed both the convergent and discriminant validity of the FCRI-S subscale. Conclusions: This study confirmed the robust psychometric characteristics of the FCRI-S subscale among cancer survivors in Korea. The use of the FCRI-S subscale would be helpful for health professionals to rapidly screen FCR levels in clinical settings.

Response surface methodology mediated optimization of phytosulfokine and plant growth regulators for enhanced protoplast division, callus induction, and somatic embryogenesis in Angelica Gigas Nakai.

BACKGROUND: Angelica Gigas (Purple parsnip) is an important medicinal plant that is cultivated and utilized in Korea, Japan, and China. It contains bioactive substances especially coumarins with anti-inflammatory, anti-platelet aggregation, anti-cancer, anti-diabetic, antimicrobial, anti-obesity, anti-oxidant, immunomodulatory, and neuroprotective properties. This medicinal crop can be genetically improved, and the metabolites can be obtained by embryonic stem cells. In this context, we established the protoplast-to-plant regeneration methodology in Angelica gigas. RESULTS: In the present investigation, we isolated the protoplast from the embryogenic callus by applying methods that we have developed earlier and established protoplast cultures using Murashige and Skoog (MS) liquid medium and by embedding the protoplast in thin alginate layer (TAL) methods. We supplemented the culture medium with growth regulators namely 2,4-dichlorophenoxyaceticacid (2,4-D, 0, 0.75, 1.5 mg L- 1), kinetin (KN, 0, 0.5, and 1.0 mg L- 1) and phytosulfokine (PSK, 0, 50, 100 nM) to induce protoplast division, microcolony formation, and embryogenic callus regeneration. We applied central composite design (CCD) and response surface methodology (RSM) for the optimization of 2,4-D, KN, and PSK levels during protoplast division, micro-callus formation, and induction of embryogenic callus stages. The results revealed that 0.04 mg L- 1 2,4-D + 0.5 mg L- 1 KN + 2 nM PSK, 0.5 mg L- 1 2,4-D + 0.9 mg L- 1 KN and 90 nM PSK, and 1.5 mg L- 1 2,4-D and 1 mg L- 1 KN were optimum for protoplast division, micro-callus formation and induction embryogenic callus. MS basal semi-solid medium without growth regulators was good for the development of embryos and plant regeneration. CONCLUSIONS: This study demonstrated successful protoplast culture, protoplast division, micro-callus formation, induction embryogenic callus, somatic embryogenesis, and plant regeneration in A. gigas. The methodologies developed here are quite useful for the genetic improvement of this important medicinal plant.

Multivalent dendritic DNA aptamer molecules for the enhancement of therapeutic effects.

Dendritic DNA molecules, referred to as DNA dendrons, consist of multiple covalently linked strands and are expected to improve the cellular uptake and potency of therapeutic oligonucleotides because of their multivalency. In this study, we developed an efficient synthetic method for producing DNA dendrons using strain-promoted azide-alkyne cycloaddition. Integration of the antitumor aptamer AS1411 into DNA dendrons enhanced cellular uptake and antiproliferative activity in cancer cells. These findings demonstrate that the incorporation of multivalent aptamers into DNA dendrons can effectively boost their therapeutic effects.

Functional brain network analysis using electroencephalography in late-onset Lennox-Gastaut syndrome.

OBJECTIVE: We aimed to explore the clinical characteristics and functional network properties of patients with late-onset Lennox-Gastaut syndrome (LGS). METHODS: Late-onset LGS was defined by the appearance of LGS features after 8 years of age. We reviewed the medical charts of 9 patients with late-onset LGS, and performed electroencephalography connectivity analysis using graph theory. We assessed the clustering coefficient (CC) and characteristic path length (CPL), which are common basic measures of functional networks that represent local segregation and global integration. The characteristics and brain parameters of late-onset LGS were compared with a typical age-onset LGS group. RESULTS: Late onset LGS subjects were older than typical age onset LGS at the time of testing, but otherwise there were no significant differences in clinical characteristics. The late-onset group showed higher median CC values in the alpha (p = 0.045) and beta (p < 0.001) bands over brain regions implicated in cognitive processing. There were no significant differences in CPL between the LGS groups. CONCLUSIONS: Higher clustering coefficient values, in alpha/beta bands over brain regions implicated in cognitive processing, are consistent with increased cognitive network segregation in late onset LGS compared to typical age-onset LGS. Given network segregation is a normal aspect of brain maturation, these results imply that this process is less disturbed when the LGS process begins later in childhood.

Bioconjugated Antibody-Trojan Immune Converter Enhance Cancer Immunotherapy with Minimized Toxicity by Programmed Two-Step Immunomodulation of Myeloid Cells.

Current immune checkpoint blockade therapy (ICBT) predominantly targets T cells to harness the antitumor effects of adaptive immune system. However, the effectiveness of ICBT is reduced by immunosuppressive innate myeloid cells in tumor microenvironments (TMEs). Toll-like receptor 7/8 agonists (TLR7/8a) are often used to address this problem because they can reprogram myeloid-derived suppressor cells (MDSCs) and tumor-associated M2 macrophages, and boost dendritic cell (DC)-based T-cell generation; however, the systemic toxicity of TLR7/8a limits its clinical translation. Here, to address this limitation and utilize the effectiveness of TLR7/8a, this work suggests a programmed two-step activation strategy via Antibody-Trojan Immune Converter Conjugates (ATICC) that specifically targets myeloid cells by anti-SIRPα followed by reactivation of transiently inactivated Trojan TLR7/8a after antibody-mediated endocytosis. ATICC blocks the CD47-SIRPα ("don't eat me" signal), enhances phagocytosis, reprograms M2 macrophages and MDSCs, and increases cross-presentation by DCs, resulting in antigen-specific CD8+ T-cell generation in tumor-draining lymph nodes and TME while minimizing systemic toxicity. The local or systemic administration of ATICC improves ICBT responsiveness through reprogramming of the immunosuppressive TME, increased infiltration of antigen-specific CD8+ T cells, and antibody-dependent cellular phagocytosis. These results highlight the programmed and target immunomodulation via ATICC could enhance cancer immunotherapy with minimized systemic toxicities.

Loneliness is associated with more trust but worse trustworthiness expectations.

Subjective feelings of loneliness emerge due to unsatisfactory social relationships, representing a major risk for mental and physical well-being. Despite its social nature, evidence on how loneliness affects social behaviours and expectations is lacking. Using Bayesian analyses and economic games, we show in three different studies that lonelier individuals trusted their partners to a greater extent despite less favourable trustworthiness expectations, showing a greater discrepancy between their trusting behaviours and their expectations of others' trustworthiness. Such discrepancy was reversed in extravert individuals who also reported to be less lonely. These results provide evidence on two opposing effects of loneliness as a motivator for social connections and promoter of social withdrawal, and demonstrate the moderating role of personality traits. This work contributes to a better understanding of how loneliness impacts social behaviour and social expectations, with important downstream clinical implications for varying health conditions associated with heightened feelings of loneliness.

Work-related asthma in adults with severe asthma from the Korean Severe Asthma Registry (KoSAR).

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P < 0.001). Conclusion: Patients with severe asthma and WRA are more likely to experience anxiety and depression and have lower QoL than those without WRA.