Safety outcomes of selective serotonin reuptake inhibitors in adolescent attention-deficit/hyperactivity disorder with comorbid depression: the ASSURE study.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is related to depressive disorder, and adolescents with both present poor outcomes. However, evidence for the safety of concomitantly using a methylphenidate (MPH) and a selective serotonin reuptake inhibitor (SSRI) among adolescent ADHD patients is limited, a literature gap aimed to address through this investigation. METHODS: We conducted a new-user cohort study using a nationwide claims database in South Korea. We identified a study population as adolescents who were diagnosed both ADHD and depressive disorder. MPH-only users were compared with patients who prescribed both a SSRI and a MPH. Fluoxetine and escitalopram users were also compared to find a preferable treatment option. Thirteen outcomes including neuropsychiatric, gastrointestinal, and other events were assessed, taking respiratory tract infection as a negative control outcome. We matched the study groups using a propensity score and used the Cox proportional hazard model to calculate the hazard ratio. Subgroup and sensitivity analyses were conducted in various epidemiologic settings. RESULTS: The risks of all the outcomes between the MPH-only and SSRI groups were not significantly different. Regarding SSRI ingredients, the risk of tic disorder was significantly lower in the fluoxetine group than the escitalopram group [HR 0.43 (0.25-0.71)]. However, there was no significant difference in other outcomes between the fluoxetine and escitalopram groups. CONCLUSION: The concomitant use of MPHs and SSRIs showed generally safe profiles in adolescent ADHD patients with depression. Most of the differences between fluoxetine and escitalopram, except those concerning tic disorder, were not significant.

Exosomal microRNAs shuttling between tumor cells and macrophages: cellular interactions and novel therapeutic strategies.

Extracellular vesicles secreted by tumor microenvironment (TME) cells are vital players in tumor progression through transferring nucleic acids and proteins. Macrophages are the main immune cells in TME and tumor associated macrophages (TAM) express M2 phenotype, which induce tumor proliferation, angiogenesis, invasion, metastasis and immune elimination, resulting in the subsequent evolution of malignancies. There are a high number of studies confirmed that tumor cells and TAM interact with each other through extracellular vesicles in various cancers, like pancreatic ductal adenocarcinoma, gastric cancer, breast cancer, ovarian cancer, colon cancer, glioblastoma, hepatocellular cancer, and lung cancer. Herein, this review summarizes the current knowledge on mechanisms of communications between tumor cells and TAM via extracellular vesicles, mainly about microRNAs, and targeting these events might represent a novel approach in the clinical implications of this knowledge into successful anti-cancer strategies.

Lower-Income Predicts Increased Smartphone Use and Problematic Behaviors Among Schoolchildren During COVID-19 Related School Modification: A Longitudinal Study.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) has continued for a couple of years, the long-term effects of the pandemic and the subsequent school curriculum modification on the mental health of children and parents need to be investigated. To clarify the changes that can occur during one school year and to predict the risk factors for vulnerable groups, this study identified parameters relative to children's screen time, their problematic behavior, and parental depression. METHODS: A total of 186 participants were analyzed who were parents of elementary schoolchildren in South Korea. These parents were required to complete a web-based questionnaire twice. The questionnaires were conducted in June 2020 and September 2021. Participants' general demographics including family income, children's screen time, sleep patterns, problematic behavior, and parental depression were assessed via the parental questionnaire that included various measurement tools. RESULTS: Children's body mass index (BMI) increased significantly in 2021 (18.94 ± 3.75 vs. 18.14 ± 3.30, P < 0.001). Smartphone frequency of use per week (5.35 vs. 4.54, P < 0.001) and screen time per day (3.52 vs. 3.16, P < 0.001) significantly increased during the period of the COVID-19 pandemic. The television screen time (2.88 vs. 3.26, P < 0.001), frequency of viewing (3.77 vs. 4.77, P < 0.001), and children's problematic behaviors significantly decreased (9.15 vs. 11.85, P < 0.001). A lower income household was a key predictor of increased smartphone frequency (B = 1.840, 95% confidence interval [CI], 0.923-2.757, P < 0.001) and smartphone screen time (B = 1.992, 95% CI, 1.458-2.525, P < 0.001). The results showed that the lower income household (B = 5.624, 95% CI, 2.927-8.320, P < 0.001) and a child's psychiatric treatment history (B = 7.579, 95% CI, 5.666-9.492, P < 0.001) was the most significant predictor of problematic behaviors of children and parental depression (B = 3.476, 95% CI, 1.628-5.325, P < 0.001; B = 3.138, 95% CI, 1.827-4.450, P < 0.001). CONCLUSION: This study suggested that children's smartphone screen time and BMI increased during COVID-19 because of the school curriculum modification following school closures in South Korea. The increased children's problematic behaviors and parental depression were predicted by lower-income households and the previous psychiatric history of children. These results indicate that multiple social support systems to the vulnerable group are needed during the ongoing pandemic and that a modified school setting is required.

Anti-Inflammatory, Antioxidative, and Nitric Oxide-Scavenging Activities of a Quercetin Nanosuspension with Polyethylene Glycol in LPS-Induced RAW 264.7 Macrophages.

Quercetin (Qu) is a dietary antioxidant and a member of flavonoids in the plant polyphenol family. Qu has a high ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) molecules; hence, exhibiting beneficial effects in preventing obesity, diabetes, cancer, cardiovascular diseases, and inflammation. However, quercetin has low bioavailability due to poor water solubility, low absorption, and rapid excretion from the body. To address these issues, the usage of Qu nanosuspensions can improve physical stability, solubility, and pharmacokinetics. Therefore, we developed a Qu and polyethylene glycol nanosuspension (Qu-PEG NS) and confirmed its interaction by Fourier transform infrared analysis. Qu-PEG NS did not show cytotoxicity to HaCaT and RAW 264.7 cells. Furthermore, Qu-PEG NS effectively reduced the nitrogen oxide (NO) production in lipopolysaccharide (LPS)-induced inflammatory RAW 264.7 cells. Additionally, Qu-PEG NS effectively lowered the levels of COX-2, NF-κB p65, and IL-1ß in the LPS-induced inflammatory RAW 264.7 cells. Specifically, Qu-PEG NS exhibited anti-inflammatory properties by scavenging the ROS and RNS and mediated the inhibition of NF-κB signaling pathways. In addition, Qu-PEG NS had a high antioxidant effect and antibacterial activity against Escherichia coli and Bacillus cereus. Therefore, the developed novel nanosuspension showed comparable antioxidant, anti-inflammatory, and antibacterial functions and may also improve solubility and physical stability compared to raw quercetin.

Association of decreased grip strength with lower urinary tract symptoms in women: a cross-sectional study from Korea.

BACKGROUND: Lower urinary tract symptoms (LUTS) including frequency, nocturia, urgency, and incontinence, are common in women and cause significant discomfort in daily life. However, diagnosis and treatment of LUTS are often delayed because many patients with such symptoms do not complain to the physician of discomfort and do not seek medical attention. LUTS are known to be associated with muscle weakness. We investigated the association between grip strength and LUTS in women of different ages. METHODS: This study included 4225 women (mean age 48.6 years) who underwent self-referred health screening between April 2015 and December 2019. LUTS were evaluated using a self-reported questionnaire, and the overactive bladder symptom score was used to screen for an overactive bladder. Low muscle strength was defined as a hand grip strength of < 18 kg (decreased grip strength). RESULTS: We observed decreased grip strength in 13.7% (n = 580) of the participants. Nocturia, urgency, incontinence, and overactive bladder were more common in women with decreased grip strength than in women with normal grip strength. After adjusting for age, comorbidities (hypertension, diabetes, hyperlipidemia), smoking status, alcohol consumption, regular exercise, and stress, nocturia (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01-1.52), urinary incontinence (OR 1.32, 95% CI 1.01-1.72), and an overactive bladder (OR 1.75, 95% CI 1.35-2.27) were significantly associated with decreased grip strength. CONCLUSIONS: The findings suggest that LUTS, especially nocturia, incontinence, and an overactive bladder are associated with decreased grip strength in women. Therefore, physicians should be aware that patients may not seek help, even if they are uncomfortable, and it is important to obtain a detailed medical history and perform additional tests, even in the absence of complaints, in patients with low grip strength, who are at high risk of LUTS.

Parental Mental Health and Children's Behaviors and Media Usage during COVID-19-Related School Closures.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is different from previous disasters in that it continues to the present and has affected all aspects of family life. During epidemics, psychosocial support is not less important than infection control. During COVID-19-related school closures, prolonged partial closures of schools could have detrimental social and health consequences for children and may increase the burden on the family. Based on a community sample in Korea, this study identified parental concerns, children's media usage, other various factors and examined whether parental stress level or depression were positively associated with problem behaviors, media exposure, and sleep problems of the primary school children during school closure under COVID-19. METHODS: Participants were 217 parents residing in Suwon, South Korea, who had primary school children and responded to a web-based questionnaire on parental concerns from school closure under COVID-19, subjective stress, depression, whether having received mental health services, and family characteristics; children's sleep patterns, problem behaviors, media usage during the online-only class period, and changes in activity level following the pandemic. RESULTS: During school closure, children gained body weight, spent less time in physical activities and more in media usage. Besides online learning content (97.2%), YouTube was highly used content (87.6%), and games followed (78.3%). Parental subjective stress index was highly associated with parental depression (Pearson correlation 0.439, P < 0.001), children's sleep problems (0.283, P < 0.001), tablet time (0.171, P = 0.012) and behavior problems (0.413, P < 0.001). Parental depression was associated with children's sleep problems (0.355, P < 0.001), TV time (0.153, P = 0.024), tablet time (0.159, P = 0.019), and behavior problems (0.524, P < 0.001). Parents who previously received mental services seemed to be more concerned about the problems their children already have getting worse because of COVID-19 than the disease itself. Children's sleep problem was associated with tablet (0.172, P = 0.011) and smartphone time (0.298, P < 0.001), but not its frequency. CONCLUSION: During COVID-19-related school closures, many parents and children had various difficulties relating to mental health. Ongoing monitoring of mental health of high-risk groups and multiple support systems may need to be expanded to cover those parents having difficulty in caring for their children.

Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes.

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

The miR-30 family: Versatile players in breast cancer.

The microRNA family, miR-30, plays diverse roles in regulating key aspects of neoplastic transformation, metastasis, and clinical outcomes in different types of tumors. Accumulating evidence proves that miR-30 family is pivotal in the breast cancer development by controlling critical signaling pathways and relevant oncogenes. Here, we review the roles of miR-30 family members in the tumorigenesis, metastasis, and drug resistance of breast cancer, and their application to predict the prognosis of breast cancer patients. We think miR-30 family members would be promising biomarkers for breast cancer and may bring a novel insight in molecular targeted therapy of breast cancer.

MiRNAs-mediated cisplatin resistance in breast cancer.

Cisplatin is a widely used chemotherapeutic agent in breast cancer treatments with inevitable rapidly acquired resistance or intrinsically resistance. Enormous evidence points to the bioprocesses of resistant formation consisting of diverse miRNAs direct and indirect actions on relevant encoding genes. In this report, we overview detailed information on the miRNAs effect on cisplatin-induced resistance, including alterations in cell survival, modification of DNA damage response, changes in cellular uptake or efflux of the drug, altered DNA methylation, and perturbations in the miRNA biogenesis pathway. This will provide potential miRNA-targeted strategies for the treatment of breast cancer therapy and requires further clinical application.

miR-222 induces Adriamycin resistance in breast cancer through PTEN/Akt/p27kip1 pathway.

The high resistant rate of Adriamycin (Adr) is associated with a poor prognosis of breast cancer in women worldwide. Since miR-222 might contribute to chemoresistance in many cancer types, in this study, we aimed to investigate its efficacy in breast cancer through PTEN/Akt/p27 kip1 pathway. Firstly, in vivo, we verified that miR-222 was upregulated in chemoresistant tissues after surgery compared with the paired preneoadjuvant samples of 21 breast cancer patients. Then, human breast cancer Adr-resistant cell line (MCF-7/Adr) was constructed to validate the pathway from the parental sensitive cell line (MCF-7/S). MCF-7/Adr and MCF-7/S were transfected with miR-222 mimics, miR-222 inhibitors, or their negative controls, respectively. The results showed that inhibition of miR-222 in MCF-7/Adr significantly increased the expressions of PTEN and p27 kip1 and decreased phospho-Akt (p-Akt) both in mRNA and protein levels (p < 0.05) by using quantitative real-time PCR (qRT-PCR) and western blot. MTT and flow cytometry suggested that lower expressed miR-222 enhanced apoptosis and decreased the IC50 of MCF-7/Adr cells. Additionally, immunofluorescence demonstrated that the subcellular location of p27 kip1 was dislocated resulting from the alteration of miR-222. Conversely, in MCF-7/S transfected with miR-222 mimics, upregulation of miR-222 is associated with decreasing PTEN and p27 kip1 and increasing Akt accompanied by less apoptosis and higher IC50. Importantly, Adr resistance induced by miR-222 overexpression through PTEN/Akt/p27 was completely blocked by LY294002, an Akt inhibitor. Taken together, these data firstly elucidated that miR-222 could reduce the sensitivity of breast cancer cells to Adr through PTEN/Akt/p27 kip1 signaling pathway, which provided a potential target to increase the sensitivity to Adr in breast cancer treatment and further improved the prognosis of breast cancer patients.

Exosomes from adriamycin-resistant breast cancer cells transmit drug resistance partly by delivering miR-222.

Breast cancer (BCa) is one of the major deadly cancers in women. However, treatment of BCa is still hindered by the acquired-drug resistance. It is increasingly reported that exosomes take part in the development, metastasis, and drug resistance of BCa. However, the specific role of exosomes in drug resistance of BCa is poorly understood. In this study, we investigate whether exosomes transmit drug resistance through delivering miR-222. We established an adriamycin-resistant variant of Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line (MCF-7/Adr) from a drug-sensitive variant (MCF-7/S). Exosomes were isolated from cell supernatant by ultracentrifugation. Cell viability was assessed by MTT assay and apoptosis assay. Individual miR-222 molecules in BCa cells were detected by fluorescence in situ hybridization (FISH). Then, FISH was combined with locked nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH). Individual miR-222 could be detected as bright photostable fluorescent spots and then the quantity of miR-222 per cell could be counted. Stained exosomes were taken in by the receipt cells. MCF-7/S acquired drug resistance after co-culture with exosomes from MCF-7/Adr (A/exo) but did not after co-culture with exosomes from MCF-7/S (S/exo). The quantity of miR-222 in A/exo-treated MCF-7/S was significantly greater than in S/exo-treated MCF-7/S. MCF-7/S transfected with miR-222 mimics acquired adriamycin resistance while MCF-7/S transfected with miR-222 inhibitors lost resistance. In conclusion, exosomes are effective in transmitting drug resistance and the delivery of miR-222 via exosomes may be a mechanism.

Perioperative propofol-paravertebral anesthesia decreases the metastasis and progression of breast cancer.

Propofol-paravertebral anesthesia (PPA) is a unique combination of paravertebral nerve blocks (PVBs) and propofol that regulates the cellular microenvironment during surgical period. Growing evidence points to its ability to attenuate perioperative immunosuppression of cancers. Abundant studies show that cancer patients who undergo perioperative PPA exhibit less recurrence as well as metastasis. Breast cancer remains a leading cause of cancer-induced death in women. Over the last decades, increasing concerns have been put on the promotional role of PPA in the prognosis of breast cancer patients. Among them, PPA participates in several bioprocesses in the development of breast cancer, including inhibiting hypoxia-inducible factor (HIF) activity, elevating serum concentration of nitric oxide index (NOx), depression of the neuroepithelial cell transforming gene 1 (NET1) signal pathway, blocking the nuclear factor kappa B (NF-κB) pathway following an decreased expression of matrix metalloproteinase (MMP), increasing NK cytotoxicity, and affecting transforming growth factor (TGF)-ß-targeted ras and HER2/neu gene pathways. In this review, we discuss the effect of PPA on breast cancer metastasis and progression. This will provide an alteration pattern of surgical anesthesia technique in breast cancer patients with poor prognosis.

Size-inclusive advertising in the Asian fashion market: Female consumers' responses to a plus-size vs. Thin-size model in South Korea.

Global fashion brands have embraced size-inclusive advertising featuring plus-size models, yet the responses of Asian consumers to such advertising-where the average body size of women is smaller than in Western markets-have garnered little attention. This study, utilizing the S-O-R model, aimed to investigate whether the relationships among perceived actual and ideal self-congruence, perceived attractiveness and familiarity of a fashion model, and purchase intention vary based on the body size of the fashion model. We tested the hypothesized relationships using ANCOVA, confirmatory factor analysis, and multi-group structural equation modeling, analyzing 623 online survey responses from South Korean female consumers. Actual self-congruence had a greater influence on perceived familiarity in consumers exposed to a thin-sized model compared to those exposed to a plus-sized model. In contrast, ideal self-congruence had a more significant positive impact on the perceived physical attractiveness of the plus-size model than the thin-size model. Furthermore, the plus-size model's perceived physical attractiveness had a more significant positive effect on purchase intention than that of the thin-size model. This study highlights the importance of crafting advertising images that portray plus-size models as physically attractive to elicit favorable responses from Asian consumers.

Lymphocyte-mediated macrophage apoptosis during IL-12 stimulation.

In contrast to the well known immunostimulatory roles of IL-12, little has been known about its immunosuppressive roles. In the present study, IL-12-activated lymphocyte-mediated macrophage apoptosis was investigated by employing murine lymphocyte/macrophage cocultures. IL-12-activated lymphocytes and their culture supernatants induced an inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) synthesis in macrophages. The NO synthesis was markedly inhibited by blocking antibodies to IFN-γ and TNF-α, suggesting the key role of these lymphocyte cytokines in mediating the NO synthesis. The endogenously produced NO inhibited macrophage proliferation, and induced apoptosis in concordance with the accumulation of p53, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and DR5, and the activation of caspase-3, processes that were inhibited by N(G)-monomethyl-l-arginine, aminoguanidine (NO synthase inhibitors) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (an NO scavenger). These results were further supported by the findings obtained from the experiments employing IFN-γ-knockout and iNOS-knockout mice. Our study demonstrated a novel, non-contact-dependent mechanism of macrophage suppression by IL-12-activated lymphocytes: induction of growth inhibition and apoptosis of macrophages due to endogenous NO synthesis induced by cytokines secreted from IL-12-activated lymphocytes.

Differences in predictors of traditional and cyber-bullying: a 2-year longitudinal study in Korean school children.

Traditional bullying has received considerable research but the emerging phenomenon of cyber-bullying much less so. Our study aims to investigate environmental and psychological factors associated with traditional and cyber-bullying. In a school-based 2-year prospective survey, information was collected on 1,344 children aged 10 including bullying behavior/experience, depression, anxiety, coping strategies, self-esteem, and psychopathology. Parents reported demographic data, general health, and attention-deficit hyperactivity disorder (ADHD) symptoms. These were investigated in relation to traditional and cyber-bullying perpetration and victimization at age 12. Male gender and depressive symptoms were associated with all types of bullying behavior and experience. Living with a single parent was associated with perpetration of traditional bullying while higher ADHD symptoms were associated with victimization from this. Lower academic achievement and lower self esteem were associated with cyber-bullying perpetration and victimization, and anxiety symptoms with cyber-bullying perpetration. After adjustment, previous bullying perpetration was associated with victimization from cyber-bullying but not other outcomes. Cyber-bullying has differences in predictors from traditional bullying and intervention programmes need to take these into consideration.

Effects of Screen Time on Problematic Behavior in Children During the COVID-19 Pandemic in South Korea.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has led to a decrease in face-to-face classes worldwide, affecting the mental health of children and their parents. The global pandemic has increased children's overall use of electronic media. This study analyzed the effect of children's screen time on problematic behaviors during the COVID-19 pandemic. Methods: A total of 186 parents from Suwon, South Korea, were recruited to participate in an online survey. The mean age of the children was 10.14 years old, and 44.1% were females. The questionnaire included questions on children's screen time, problematic behaviors, and parental stress. Children's behavioral problems were evaluated using the Behavior Problem Index, whereas the Parental Stress Scale was used to estimate parental stress. Results: The mean smartphone usage frequency of the children was 5.35 days per week, and the mean smartphone screen time was 3.52 hours per day. Smartphone screen time (Z=4.49, p <0.001) and usage frequency (Z=2.75, p=0.006) were significantly correlated with children's behavioral problem scores. The indirect effect of parental stress on this relationship was also statistically significant (p=0.049, p=0.045, respectively). Conclusion: This study suggests that children's smartphone screen time has affected problematic behaviors during the COVID-19 pandemic. Furthermore, parental stress is related to the relationship between children's screen time and problematic behaviors.

Validation of the Korean self-administered computerized versions of the kiddie schedule for affective disorders and schizophrenia for school-age children (KSADS-COMP).

The purpose of the present study was to examine the validity of the Korean version of the parent and youth self-administered versions of the KSADS-COMP (The Kiddie Schedule for Affective Disorders and Schizophrenia for school-age children). To assess the criterion validity of the KSADS-COMP, diagnoses made by the selfadministered KSADS-COMP were compared to the gold-standard diagnoses made by the child-adolescent psychiatrists in 41 participants (mean age=14.93 ± 2.16 years, female=41.46 %). Gwet's first order agreement coefficient (AC1) concordance ratings showed moderate to good range. The present study shows promising validity of the Korean self-administered versions of the KSADS-COMP in Korean youths.

Computerized Version of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS-COMP): Development and Validation of the Korean Clinician-Administered Version.

OBJECTIVE: The purpose of the present study was to develop and validate the Korean version of the clinician-administered KSADSCOMP, which is the recently updated, web-based computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia for school-age children (KSADS). METHODS: A total of 71 participants (mean age=12.04±3.86 years, female=29.57%) participated in the study. A child-adolescent psychiatrist established a diagnosis for the participant after a thorough psychiatric interview with the participant and the parent. Researchers who were blind to the diagnoses administered the clinician-administered KSADS-COMP to the parents and participants. The gold-standard diagnoses made by child-adolescent psychiatrists were compared to the current diagnoses generated by the clinician-administered KSADS-COMP. Percent agreement, Cohen's Kappa, Gwet's first-order agreement coefficient (AC1), sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Gwet's AC1, our preferred measure of agreement, showed excellent range between 0.78 and 1. Sensitivity, specificity, positive predicted value and negative predictive value also showed high scores. CONCLUSION: The current study demonstrated excellent criterion validity of the Korean version of the clinician-administered KSADSCOMP, though the small sample size could be a limitation. The current study was the first study to examine the criterion validity of the KSADS-COMP. Due to its readily usable format and efficient and accurate diagnostic process, widely-use of KSADS-COMP is expected.

Hyperthermia promotes M1 polarization of macrophages via exosome-mediated HSPB8 transfer in triple negative breast cancer.

PURPOSE: To investigate the mechanism underlying the modulation of M1 macrophage polarization by exosomes released from hyperthermia-treated triple-negative breast cancer (TNBC) cells. MATERIALS AND METHODS: In this study, the effects of hyperthermia on TNBC cells were examined using cell counting kit-8, apoptosis, and cell cycle assays. Transmission electron microscopy was used to identify the structure of exosomes, while bicinchoninic acid and nanoparticle tracking analysis were used to detect particle size and amounts of exosomes released after hyperthermia. The polarization of macrophages incubated with exosomes derived by hyperthermia-pretreated TNBC cells were assessed by RT-qPCR and flow cytometry analysis. Next, RNA sequencing was performed to determine the targeting molecules changed in hyperthermia-treated TNBC cells in vitro. Finally, the mechanism underlying the modulation of macrophage polarization by exosomes derived from hyperthermia-treated TNBC cells was examined by using RT-qPCR, immunofluorescence and flow cytometry analysis. RESULTS: Hyperthermia markedly reduced cell viability in TNBC cells and promoted the secretion of TNBC cell-derived exosomes. The hub genes of hyperthermia-treated TNBC cells were significantly correlated with macrophage infiltration. Additionally, hyperthermia-treated TNBC cell-derived exosomes promoted M1 macrophage polarization. Furthermore, the expression levels of heat shock proteins, including HSPA1A, HSPA1B, HSPA6, and HSPB8, were significantly upregulated upon hyperthermia treatment, with HSPB8 exhibiting the highest upregulation. Moreover, hyperthermia can induce M1 macrophage polarization by promoting exosome-mediated HSPB8 transfer. CONCLUSION: This study demonstrated a novel mechanism that hyperthermia can induce M1 polarization of macrophages via exosome-mediated HSPB8 transfer. These results will help with future development of an optimized hyperthermia treatment regime for clinical application, especially for combination treatment with immunotherapy.