PAK4 Is Involved in the Stabilization of PD-L1 and the Resistance to Doxorubicin in Osteosarcoma and Predicts the Survival of Diagnosed Patients.

PAK4 and PD-L1 have been suggested as novel therapeutic targets in human cancers. Moreover, PAK4 has been suggested to be a molecule closely related to the immune evasion of cancers. Therefore, this study evaluated the roles of PAK4 and PD-L1 in the progression of osteosarcomas in 32 osteosarcomas and osteosarcoma cells. In human osteosarcomas, immunohistochemical positivity for the expression of PAK4 (overall survival, p = 0.028) and PD-L1 (relapse-free survival, p = 0.002) were independent indicators for the survival of patients in a multivariate analysis. In osteosarcoma cells, the overexpression of PAK4 increased proliferation and invasiveness, while the knockdown of PAK4 suppressed proliferation and invasiveness. The expression of PAK4 was associated with the expression of the molecules related to cell cycle regulation, invasion, and apoptosis. PAK4 was involved in resistance to apoptosis under a treatment regime with doxorubicin for osteosarcoma. In U2OS cells, PAK4 was involved in the stabilization of PD-L1 from ubiquitin-mediated proteasomal degradation and the in vivo infiltration of immune cells such as regulatory T cells and PD1-, CD4-, and CD8-positive cells in mice tumors. In conclusion, this study suggests that PAK4 is involved in the progression of osteosarcoma by promoting proliferation, invasion, and resistance to doxorubicin and stabilized PD-L1 from proteasomal degradation.

Impact of antiresorptive agents on mortality risk in postmenopausal women with osteoporosis: insights from a nationwide cohort study.

IMPORTANCE: Osteoporosis-related fractures are associated with increased mortality risk among postmenopausal women, yet the impact of antiosteoporotic medications on mortality is not fully understood. OBJECTIVE: This study evaluates the effect of antiresorptive agents (ARs) on mortality risk in postmenopausal women with osteoporosis. DESIGN: This is a nationwide cohort study using data from the National Screening Program for Transitional Ages (2008-2017). SETTING: Data were derived from a national cohort of postmenopausal women in South Korea. PARTICIPANTS: This study included 117 871 postmenopausal women diagnosed with osteoporosis. Of them, 15 895 patients who used ARs, such as bisphosphonates or selective estrogen receptor modulators, for at least 1 year were matched 1:1 with nonusers using propensity scores. EXPOSURES: Exposure to ARs for at least 1 year was compared with no AR use. MAIN OUTCOMES AND MEASURE: Mortality outcomes were assessed using multivariable Cox proportional hazard regression models, focusing on all-cause mortality and cause-specific mortality, particularly cardiovascular disease (CVD) and injury-/fracture-related deaths. RESULTS: In AR users, there were 102 deaths (mortality rate 1.41 per 1000 person-years), compared with 221 deaths in non-users (mortality rate 3.14 per 1000 person-years), yielding a hazard ratio (HR) of 0.43 (95% CI, 0.34-0.54). Antiresorptive agent users showed a 52% reduction in CVD mortality risk (HR, 0.48; 95% CI, 0.34-0.69) and a 54% reduction in injury-/fracture-related mortality risk (HR, 0.46; 95% CI, 0.27-0.76). The analysis indicated a consistent decrease in all-cause and CVD mortality risks with longer durations of AR use. CONCLUSIONS AND RELEVANCE: The use of ARs in postmenopausal women with osteoporosis is associated with significantly lower risks of all-cause mortality, especially from cardiovascular events and fractures. The mortality reduction benefits appear to be enhanced with prolonged AR therapy, highlighting the potential importance of sustained treatment in this population.

Incidence and pattern of second primary cancer in patients diagnosed with primary cancer.

The long survival of patients with primary cancer increases the chance of such patients developing second primary cancer (SPC). The development of SPC in cancer survivors exerts a large psychological, social and economic burden on patients and their families. The aim of the present study was to assess the risk of cancer survivors developing SPC. The study included patients who had been diagnosed with a first primary cancer in five organs (stomach, colorectum, lung, breast and thyroid), which are the five most common sites of cancer in patients from Korea, at the regional cancer center in Jeonbuk National University Hospital between January 2007 and December 2009. The standardized incidence ratio (SIR) of SPC according to sex and site was calculated from 5,209 patients who were followed up to September 2017. General incidence was acquired from the National Cancer Registry of Republic of Korea. SPC occurred in 6.2% (323/5,209) of patients, and the incidence of SPC among the five major types of cancer was in the order of breast (8.8%, 46/524), colorectum (8.6%, 86/1,003), gastric (6.6%, 89/1,358), thyroid (4.7%, 67/1,437) and lung cancer (3.9%, 35/887). When all SPC sites were included, the SIRs of SPC in patients with colorectal cancer and breast cancer were >1.0 (1.21 and 1.66, respectively). Breast cancer and thyroid cancer exhibited a high site relationship (P<0.05), and colorectal cancer had a high site relationship with gastric cancer (P<0.05). The present study analyzed the incidence and pattern of SPC in patients with cancer who were diagnosed with primary carcinoma in five organs. The results of the study may be useful for effective follow-up and early detection of SPC in patients with cancer.

Colorectal cancer with a germline BRCA1 variant inherited paternally: a case report.

BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient's father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.

Attenuated adenomatous polyposis with MSH6 variation: Two case reports.

RATIONALE: Adenomatous polyposis (AP) is a genetic disorder characterized by the occurrence of numerous adenomatous polyps in the colon and rectum and can be classified into classical AP and attenuated AP (AAP). AAP is diagnosed when the number of observed adenomas is between 10 and 99. The detection of AAP is significantly increasing mainly due to the improvement of the imaging technique and application of the screening program for colorectal cancer detection. Currently, the germline variations of the APC and MUTYH genes are reported as the main cause of classical AP. However, the underlying genetic basis of AAP is not well understood. In this study, we report 2 cases of AAP with MSH6 variations. PATIENT CONCERNS: Both patients visited the hospital after multiple polyps were detected during colonoscopies conducted as part of their health checkups. DIAGNOSES: The 2 patients were diagnosed with AAP through colonoscopic examination at our hospital. INTERVENTIONS: The 2 received genetic consultation; and, for follow-up purposes, both patients agreed to be tested for an underlying genetic condition through next generation sequencing. And germline MSH6 variations were detected in both AAP patients. OUTCOMES: There was no recurrence for both patients for 3 years follow-up. LESSONS: Minor portion of AAP can cause by genetic mutation in MSH6, and further research is needed.

Association of sodium-glucose cotransporter 2 inhibitor use with risk of osteoporotic fracture among older women: A nationwide, population-based cohort study.

INTRODUCTION: We investigated the relationship between sodium-glucose cotransporter-2 inhibitor (SGLT2i) and fracture in elderly women diagnosed with type 2 diabetes mellitus (T2DM) and newly prescribed antidiabetic medications (ADMs). MATERIAL AND METHODS: We used the population-based cohort study data from the National Health Insurance Service of Korea (2013-2020). Women ≥65 years old with T2DM, who were newly prescribed ADMs other than glucagon-like peptide-1 receptor agonists and thiazolidinedione, and who had comprehensive health check-up data were included. RESULTS: A total of 1,333 SGLT2i users were matched in a 1:2 ratio with 2,626 non-SGLT2i users. After propensity score matching, mean age, body mass index, number of ADMs, and other covariates were well-balanced between SGLT2i users and non-SGLT2i users. During the follow-up period, a higher incidence of vertebral fractures in SGLT2i users than in non-SGLT2i users (incidence rate 19.2 vs. 13.8 per 1,000 person-years; hazard ratio 1.40, 95 % confidence interval 1.00-1.96, p = 0.049). No significant difference was noted in other types of fracture. CONCLUSION: SGLT2i use showed an increased risk of vertebral fracture than non-SGLT2i use in elderly women. Although further validation is required, SGLT2i should be cautiously prescribed in older women due to the potential association with fracture risk.

Network Structure and Clustering Analysis Relating to Individual Symptoms of Problematic Internet Use in a Community Adolescent Population.

INTRODUCTION: Problematic internet use (PIU) is a psychopathology that includes multiple symptoms and psychological constructs. Because no studies have considered both network structures and clusters among individual symptoms in the context of PIU in a Korean adolescent population, this study aimed to investigate network structures and clustering in relation to PIU symptoms in adolescents. METHODS: Overall, 73,238 adolescents were included. PIU severity was assessed using a self-rating scale comprising 20 items and 6 subscales, namely, the Internet Addiction Proneness Scale for Youth-Short Form; KS scale. Network structures and clusters among symptoms were analyzed using a Gaussian graphical model and exploratory graph analysis, respectively. Centrality of strength, closeness, and betweenness scores was also calculated. RESULTS: Our study identified four clusters: disturbance in adaptive functioning, virtual interpersonal relationships, withdrawal, and tolerance. The symptom of confidence served as a node bridging the cluster of virtual interpersonal relationships and other clusters of withdrawal and disturbances of adaptive function. The symptom of craving served as a bridge between the clusters of withdrawal and tolerance with high betweenness centrality. CONCLUSION: This study identified network structures and clustering among PIU symptoms in adolescents and revealed that positive experiences derived from online interpersonal relationships were an important mechanism underlying PIU. These are novel insights concerning the interconnection among multiple symptoms and related clustering for the mechanism of adolescent PIU in terms of KS-scale PIU assessment.

Deep-learning model for evaluating histopathology of acute renal tubular injury.

Tubular injury is the most common cause of acute kidney injury. Histopathological diagnosis may help distinguish between the different types of acute kidney injury and aid in treatment. To date, a limited number of study has used deep-learning models to assist in the histopathological diagnosis of acute kidney injury. This study aimed to perform histopathological segmentation to identify the four structures of acute renal tubular injury using deep-learning models. A segmentation model was used to classify tubule-specific injuries following cisplatin treatment. A total of 45 whole-slide images with 400 generated patches were used in the segmentation model, and 27,478 annotations were created for four classes: glomerulus, healthy tubules, necrotic tubules, and tubules with casts. A segmentation model was developed using the DeepLabV3 architecture with a MobileNetv3-Large backbone to accurately identify the four histopathological structures associated with acute renal tubular injury in PAS-stained mouse samples. In the segmentation model for four structures, the highest Intersection over Union and the Dice coefficient were obtained for the segmentation of the "glomerulus" class, followed by "necrotic tubules," "healthy tubules," and "tubules with cast" classes. The overall performance of the segmentation algorithm for all classes in the test set included an Intersection over Union of 0.7968 and a Dice coefficient of 0.8772. The Dice scores for the glomerulus, healthy tubules, necrotic tubules, and tubules with cast are 91.78 ± 11.09, 87.37 ± 4.02, 88.08 ± 6.83, and 83.64 ± 20.39%, respectively. The utilization of deep learning in a predictive model has demonstrated promising performance in accurately identifying the degree of injured renal tubules. These results may provide new opportunities for the application of the proposed methods to evaluate renal pathology more effectively.

Symptom clusters in adolescent depression and differential responses of clusters to pharmacologic treatment.

OBJECTIVE: Symptoms of depression in adolescents are widely variable, but they are often interactive and clustered. The analysis of interactions and clusters among individual symptoms may help predict treatment outcomes. We aimed to determine clusters of individual symptoms in adolescent depression and their changes in the response to pharmacological treatment. METHOD: A total of 95 adolescents, aged 12-17 years, with major depressive disorder were included. Participants were treated with escitalopram, and depressive symptoms were assessed at baseline (V1) and 1, 2, 4, 6, and 8 weeks (V6). The severity of depression was assessed using the Children's Depression Rating Scale-Revised. To construct network and clustering structures among symptoms, the Gaussian graphical model and Exploratory Graph Analysis with the tuning parameter to minimize the extended Bayesian information criterion were adopted. RESULTS: Exploratory Graph Analysis revealed that symptoms of depression comprised four clusters: impaired activity, somatic concerns, subjective mood, and observed affect. The main effect of visit with decreased symptom severity was significant in all four clusters; however, the degree of symptom improvement differed among the four clusters. The effect size of score differences from V1 to V6 was the highest in the subjective mood (Cohen's d = 1.075), and lowest in impaired activity (d = 0.501) clusters. CONCLUSION: The present study identified four symptom clusters associated with adolescent depression and their differential changes related to antidepressant treatment. This finding suggests that escitalopram was the most effective at improving subjective mood among different clusters. However, other therapeutic modalities may be needed to improve other clusters of symptoms, consequently leading to increased overall improvement of depression in adolescents.

Spontaneous splenic rupture associated with scrub typhus: a case report.

BACKGROUND: Scrub typhus, an acute febrile disease with mild to severe, life-threatening manifestations, potentially presents with a variety of complications, including pneumonia, acute respiratory distress syndrome, cardiac arrhythmias (such as atrial fibrillation), myocarditis, shock, peptic ulcer, gastrointestinal bleeding, meningitis, encephalitis, and renal failure. Of the various complications associated with scrub typhus, splenic rupture has rarely been reported, and its mechanisms are unknown. This study reports a case of scrub typhus-related spontaneous splenic rupture and identifies possible mechanisms through the gross and histopathologic findings. CASE PRESENTATION: A 78-year-old man presented to our emergency room with a 5-day history of fever and skin rash. On physical examination, eschar was observed on the left upper abdominal quadrant. The abdomen was not tender, and there was no history of trauma. The Orientia tsutsugamushi antibody titer using the indirect immunofluorescent antibody test was 1:640. On Day 6 of hospitalization, he complained of sudden-onset left upper abdominal quadrant pain and showed mental changes. His vital signs were a blood pressure of 70/40 mmHg, a heart rate pf 140 beats per min, and a respiratory rate of 20 breaths per min, with a temperature of 36.8 °C. There were no signs of gastrointestinal bleeding, such as hematemesis, melena, or hematochezia. Grey Turner's sign was suspected during an abdominal examination. Portable ultrasonography showed retroperitoneal bleeding, so an emergency exploratory laparotomy was performed, leading to a diagnosis of hemoperitoneum due to splenic rupture and a splenectomy. The patient had been taking oral doxycycline (100 mg twice daily) for 6 days; after surgery, this was discontinued, and intravenous azithromycin (500 mg daily) was administered. No arrhythmia associated with azithromycin was observed. However, renal failure with hemodialysis, persistent hyperbilirubinemia, and multiorgan failure occurred. The patient did not recover and died on the fifty-sixth day of hospitalization. CONCLUSIONS: Clinicians should consider the possibility of splenic rupture in patients with scrub typhus who display sudden-onset abdominal pain and unstable vital signs. In addition, splenic capsular rupture and extra-capsular hemorrhage are thought to be caused by splenomegaly and capsular distention resulting from red blood cell congestion in the red pulp destroying the splenic sinus.

Associations Between Physical Activity and the Risk of Hip Fracture Depending on Glycemic Status: A Nationwide Cohort Study.

CONTEXT: Although physical activity (PA) is recognized to reduce fracture risk, whether its benefits differ according to glycemic status remains unknown. OBJECTIVE: We investigated the effect of PA on incident hip fracture (HF) according to glycemic status. METHODS: We studied 3 723 097 patients older than 50 without type 1 diabetes mellitus (DM) or past fractures. HF risks were calculated using Cox proportional hazard regression. Participants were categorized by glycemic status into 5 groups: normal glucose tolerance, impaired fasting glucose, new-onset type 2 DM, type 2 DM less than 5 years, and type 2 DM of 5 years or greater. PA was evaluated using the Korean adaptation of the International Physical Activity Questionnaire Short Form. RESULTS: The highest HF risk were associated with the lowest PA level (<500 metabolic equivalent task [MET]-min/wk). While similar risks emerged across MET 500 to 1000, 1000 to 1500, and greater than 1500 categories, the relationship showed variations in different glycemic status groups. Exceptions were particularly noted in women with normoglycemia. However, a consistent inverse pattern, with few exceptions, was observed both in men and women with type 2 DM of 5 years or greater. Furthermore, the benefit of PA in the prevention of HFs was most evident in participants with type 2 DM of 5 years or greater. Compared to the reference group (lowest physical activity level <500 MET-min/wk within type 2 DM ≥5 years), the adjusted hazard ratios were 0.74 (0.62-0.88) in men and 0.74 (0.62-0.89) in women, suggesting a significant reduction in risk. CONCLUSION: Higher PA levels are associated with a lower risk of HF. This protective effect of PA on fracture risk is greatest in patients with DM, particularly in those with DM of 5 years or greater.

Combined Hepatocellular-Cholangiocarcinoma With Ductal Plate Malformation Pattern: A Case Report With Molecular Analysis.

Combined hepatocellular-cholangiocarcinoma with a ductal plate malformation pattern is an extremely rare entity with unelucidated pathogenesis. We present the case of a 60-year-old male patient who underwent a sectionectomy for pre-operative diagnosis of hepatocellular carcinoma based on clinical and image findings. Gross examination of the specimen revealed a well-defined tumor with cystic change measuring 6.7 × 6.2 cm. Microscopically, the lesion had classical features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma exhibited neoplastic glands with irregular-sized dilated lumens, resembling a ductal plate malformation. Postoperative diagnosis was combined hepatocellular-cholangiocarcinoma with ductal plate malformation pattern. Next-generation sequencing revealed genomic alteration in 15 genes: CDKN2A, CHD4, CYP2D6, ERBB3, KIR3DL1, KRAS, MDM2, PIM1, STAT6, TPMT amplification, FANCD2, FAT1, FLT4, RASA1, and TP53 point mutation. This is the first case report of molecular alteration in combined hepatocellular-cholangiocarcinoma with ductal plate malformation pattern.

Emergence of Stable Meron Quartets in Twisted Magnets.

The investigation of twist engineering in easy-axis magnetic systems has revealed remarkable potential for generating topological spin textures. Implementing twist engineering in easy-plane magnets, we introduce a novel approach to achieving fractional topological spin textures, such as merons. Through atomistic spin simulations on twisted bilayer magnets, we demonstrate the formation of a stable double Meron pair, which we refer to as the "Meron Quartet" (MQ). Unlike a single pair, the merons within the MQ exhibit exceptional stability against pair annihilation due to the protective localization mechanism induced by the twist that prevents collision of the Meron cores. Furthermore, we showcase that the stability of the MQ can be enhanced by adjusting the twist angle, resulting in an increased resistance to external perturbations such as external magnetic fields. Our findings highlight the twisted magnet as a promising platform for achieving merons as stable magnetic quasiparticles in van der Waals magnets.

Lymphangiogenesis after nonvascularized lymph node transplantation: Lymphangiographic findings in mice and minipigs.

The establishment of new connections after NVLNT (non-vascularized lymph node transplantation) is still poorly understood. The purpose of this study was to investigate lymphatic connections after NVLNT using lymphangiography. In a mice model, 40 mice were allocated to undergo NVLNT or sham surgery. On day 21 after NVLNT, the lymphatic vessels were observed on near-infrared fluorescence imaging with indocyanine green. In a minipig model, 12 minipigs underwent NVLNT. On day 14 after NVLNT, the transplanted lymph node and donor site were checked by ultrasound, and minipigs with viable transplanted LNs were allocated to lipiodol lymphangiography or MR lymphangiography groups. Transplanted LN engraftment was examined with immunohistochemical staining. After NVLNT in mice, the signal intensities in the popliteal region at 3 minutes and 5 minutes were higher in the transplanted side than the control side (21.3 ± 8.1 vs. 11.0 ± 4.6 at 3 minutes, 26.7 ± 6.8 vs. 19.7 ± 5.9 at 5 minutes), while in the sham group, there were no significant differences between sides. In minipigs, lipiodol lymphangiography (n = 5) showed Lipiodol accumulation in transplanted LNs with innumerable newly formed lymphatic vessels and lymphovenous shunts. MR lymphangiography (n = 5) showed higher enhancement on the transplanted side compared to the control side. Histology showed successful engraftment of transplanted LNs in 16 out of 20 (80%) mice and 9 out of 12 (75%) minipigs. Omnidirectional lymphangiogenesis forming a dense lymphatic network and spontaneous formation of lymphovenous shunts were shown after NVLNT.

The Factors Affecting Longitudinal Course of Posttraumatic Stress Disorder Symptoms in Sexual Assault Victims.

OBJECTIVE: This study aimed to identify the factors affecting posttraumatic stress disorder (PTSD) symptom remission prospectively through a 1-year follow-up of sexual assault (SA) victims. METHODS: A total 65 female SA victims who visited the crisis intervention center were included. Self-administered questionnaires regarding PTSD symptoms and PTSD related prognostic factors were conducted at both recruitment (T1) and 1 year after recruitment (T2). The multivariate analyses were used to determine the significant predictors of PTSD remission/non-remission state 1 year after SA. RESULTS: In logistic regression analysis, both anxiety and secondary victimization were identified as significant factors explaining the results on PTSD remission/non-remission state at T2 (Beck's Anxiety Inventory [BAI], p=0.003; Secondary Victimization Questionnaire, p=0.024). In a linear mixed analysis, both depression and anxiety were found to be significant variables leading to changes in Posttraumatic Diagnostic Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition from T1 to T2 (BAI, p<0.001; Center for Epidemiological Studies Depression Scale, p<0.001). CONCLUSION: Depression, anxiety symptoms, and secondary victimization after SA were associated with PTSD symptom non-remission 1 year after SA.

Theta and Gamma Activity Differences in Obsessive-Compulsive Disorder and Panic Disorder: Insights from Resting-State EEG with eLORETA.

Background: Obsessive-compulsive disorder (OCD) and panic disorder (PD) are debilitating psychiatric conditions, yet their underlying neurobiological differences remain underexplored. This study aimed to directly compare resting-state EEGs in patients with OCD and PD, without a healthy control group, using the eLORETA method. Methods: We collected retrospective EEG data from 24 OCD patients and 22 PD patients who were hospitalized due to significant impairment in daily life functions. eLORETA was used to analyze the EEG data. Results: Heightened theta activity was observed in the anterior cingulate cortex (ACC) of OCD patients compared to PD patients (PD vs. OCD, t = -2.168, p < 0.05). Conversely, higher gamma activity was found in the medial frontal gyrus (MFG) and paracentral lobule (PCL) in PD patients (PD vs. OCD, t = 2.173, p < 0.05). Conclusions: Our findings highlight neurobiological differences between OCD and PD patients. Specifically, the increased theta activity in the ACC for OCD patients and elevated gamma activity in the MFG and PCL for PD patients offer preliminary insights into the neural mechanisms of these disorders. Further studies are essential to validate these results and delve deeper into the neural underpinnings.

Effect of group sand play therapy on psychopathologies of adolescents with delinquent behaviors.

Prior research has established adolescent vulnerability to delinquent behavior. This single-arm, noninterventional, observational study investigated the effect of sand play therapy on the psychopathologies of adolescents with delinquent behavior. A total of 68 adolescents participated in the study. Participants were treated with 8 weekly sessions of sand play therapy, lasting 50 minutes each and conducted in groups of 3 to 4 members. The psychopathologies of depression, anxiety, self-esteem, impulsiveness, characteristics of attention-deficit hyperactivity disorder (ADHD), and impulsiveness were measured using self-reporting scales. Following therapy, depression (t = 3.28; P = .002; ES = 0.399) and anxiety (t = 4.00; P < .001; ES = 0.485) decreased significantly with moderate effect size. ADHD characteristics (t = 2.73; P = .008) and impulsiveness (t = 2.73; P = .009) also decreased significantly with effect size of 0.330 and 0.327, respectively. Self-esteem (t = -2.06, P = .043; ES = 0.251) was found to have significantly increased. The high-risk group within each psychopathology showed significantly higher improvement than the low-risk group. Results showed that group sand play therapy is effective in improving internalizing problems such as depression and anxiety, as well as externalizing problems of ADHD features and impulsiveness among adolescents with deviant behaviors.

Emotional and Behavioral Correlates of Exposure to Electronic Media in School-Aged Children: A Prospective Study.

BACKGROUND: Exposure to electronic media is increasing from early childhood. This study aimed to examine the association between screen time and behavioral outcomes in school-aged children with a prospective birth-cohort. METHODS: We examined the association between screen time and behavioral outcomes in school-aged children with a Korean birth-cohort study. Participants were 2,150 children, recruited during their fetal period, assessed annually for developmental outcomes. Media exposure was assessed at T4 (3.2 y/o), T8 (7.3 y/o), and T10 (9.4 y/o). After exclusions for missing data, 1,368 children were categorized into four groups (Low-Low, Low-High, High-Low, and High-High) based on average daily media time in early childhood and during schooldays, respectively. Children's temperament was assessed from T1 (0.5 y/o) to T4. Emotional and behavioral outcomes were assessed using the Child Behavior Checklist (DSM-oriented subscales) at T8 and T10. RESULTS: We found that early-years temperament was generally similar between the media-time groups: they only differed significantly on Activity at T1 and Emotionality at T2 (1.2 y/o). However, compared to the Low-Low group, the Low-High group had significantly higher odds of high-risk scores for Conduct Problems (increased odds ratios [ORs] of 1.82 at T8 and 1.83 at T10) and Anxiety Problems (increased ORs of 1.60 at T8 and 1.82 at T10). Self-rated self-esteem and overall happiness at T10 also significantly differed among the four groups. CONCLUSION: Our findings suggest the negative impacts of media exposure on the emotional and behavioral development of school-aged children, which substantiates the guidelines that restrict media exposure during childhood.

FAM83H Expression Is Associated with Tumor-Infiltrating PD1-Positive Lymphocytes and Predicts the Survival of Breast Carcinoma Patients.

BACKGROUND: FAM83H has been implicated in cancer progression, and PD1 is an important target for anti-cancer immune checkpoint therapy. Recent studies suggest an association between FAM83H expression and immune infiltration. However, studies on the roles of FAM83H and its relationship with PD1 in breast carcinomas have been limited. METHODS: Immunohistochemical expression of FAM83H and PD1 and their prognostic significance were evaluated in 198 breast carcinomas. RESULTS: The expression of FAM83H in cancer cells was significantly associated with the presence of PD1-positive lymphoid cells within breast carcinoma tissue. Individual and co-expression patterns of nuclear FAM83H and PD1 were significantly associated with shorter survival of breast carcinomas in univariate analysis. In multivariate analysis, the expression of nuclear FAM83H (overall survival, p < 0.001; relapse-free survival, p = 0.003), PD1 (overall survival, p < 0.001; relapse-free survival, p = 0.003), and co-expression patterns of nuclear FAM83H and PD1 (overall survival, p < 0.001; relapse-free survival, p < 0.001) were the independent indicators of overall survival and relapse-free survival of breast carcinoma patients. CONCLUSIONS: This study suggests a close association between FAM83H expression and the infiltration of PD1-positive lymphoid cells in breast carcinomas and their expression as the prognostic indicators for breast carcinoma patients, and further studies are needed to clarify this relationship.

Psychological aftereffects experienced by sexually abused children: Psychopathological characteristics revealed by the K-CBCL.

Children who have been sexually abused may experience various short- and long-term psychological sequelae and behavioral problems. This study assessed the mental health of sexually abused children using the Korean-Child Behavior Checklist (K-CBCL) and examined differences from a control group. The participants were 97 children who had been sexually abused and who visited a local Sunflower Center, and 178 control participants. Data were collected via the K-CBCL and analyzed using SPSS version 25.0. T-tests, cross-tabulation, and logistic regression analyses were performed. Scores from the K-CBCL Problem Behavior Syndrome scale were compared between sexually abused children and the control participants. Significant differences were observed between the 2 groups in all the subscales. Compared to the control group, children who were sexually abused showed statistically significant differences in the total problem behavior, internalization, anxiety/depression, withdrawal/depression (withdrawn), somatic symptoms, externalization, rule-breaking behavior (delinquency), aggressive behavior, social immaturity, thought problems, attention problems, and other subscale scores. Sexual violence hurts the overall mental health of children who are abused, including their emotional, behavioral, and social factors. Our findings suggest that multidisciplinary assessment and treatment are required for children who have experienced sexual abuse.