A TEAD2-Driven Endothelial-Like Program Shapes Basal-Like Differentiation and Metastasis of Pancreatic Cancer.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA), with its highly metastatic propensity, is one of the most lethal subtypes of pancreatic cancer. Although recent large-scale transcriptomic studies have demonstrated that heterogeneous gene expressions play an essential role in determining molecular phenotypes of PDA, biological cues for and consequences of distinct transcriptional programs remain unclear. METHODS: We developed an experimental model that enforces the transition of PDA cells toward a basal-like subtype. We combined epigenome and transcriptome analyses with extensive in vitro and in vivo evaluations of tumorigenicity to demonstrate the validity of basal-like subtype differentiation in association with endothelial-like enhancer landscapes via TEA domain transcription factor 2 (TEAD2). Finally, we used loss-of-function experiments to investigate the importance of TEAD2 in regulating reprogrammed enhancer landscape and metastasis in basal-like PDA cells. RESULTS: Aggressive characteristics of the basal-like subtype are faithfully recapitulated in vitro and in vivo, demonstrating the physiological relevance of our model. Further, we showed that basal-like subtype PDA cells acquire a TEAD2-dependent proangiogenic enhancer landscape. Genetic and pharmacologic inhibitions of TEAD2 in basal-like subtype PDA cells impair their proangiogenic phenotypes in vitro and cancer progression in vivo. Last, we identify CD109 as a critical TEAD2 downstream mediator that maintains constitutively activated JAK-STAT signaling in basal-like PDA cells and tumors. CONCLUSIONS: Our findings implicate a TEAD2-CD109-JAK/STAT axis in the basal-like differentiated pancreatic cancer cells and as a potential therapeutic vulnerability.

Marked enhancement of the immunogenicity of plant-expressed IgG-Fc fusion proteins by inclusion of cholera toxin non-toxic B subunit within the single polypeptide.

Immunoglobulin G (IgG)-based fusion proteins have been widely exploited as a potential vaccine delivery platform but in the absence of exogenous adjuvants, the lack of robust immunity remains an obstacle. Here, we report on a key modification that overcomes that obstacle. Thus, we constructed an IgG-Fc vaccine platform for dengue, termed D-PCF, which in addition to a dengue antigen incorporates the cholera toxin non-toxic B subunit (CTB) as a molecular adjuvant, with all three proteins expressed as a single polypeptide. Following expression in Nicotiana benthamiana plants, the D-PCF assembled as polymeric structures of similar size to human IgM, a process driven by the pentamerization of CTB. A marked improvement of functional properties in vitro and immunogenicity in vivo over a previous iteration of the Fc-fusion protein without CTB [1] was demonstrated. These include enhanced antigen presenting cell binding, internalization and activation, complement activation, epithelial cell interactions and ganglioside binding, as well as more efficient polymerization within the expression host. Following immunization of mice with D-PCF by a combination of systemic and mucosal (intranasal) routes, we observed robust systemic and mucosal immune responses, as well as systemic T cell responses, significantly higher than those induced by a related Fc-fusion protein but without CTB. The induced antibodies could bind to the domain III of the dengue virus envelope protein from all four dengue serotypes. Finally, we also demonstrated feasibility of aerosolization of D-PCF as a prerequisite for vaccine delivery by the respiratory route.

Tumor self-seeding by circulating cancer cells.

Cancer cells that leave the primary tumor can seed metastases in distant organs, and it is thought that this is a unidirectional process. Here we show that circulating tumor cells (CTCs) can also colonize their tumors of origin, in a process that we call "tumor self-seeding." Self-seeding of breast cancer, colon cancer, and melanoma tumors in mice is preferentially mediated by aggressive CTCs, including those with bone, lung, or brain-metastatic tropism. We find that the tumor-derived cytokines IL-6 and IL-8 act as CTC attractants whereas MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 are mediators of CTC infiltration into mammary tumors. We show that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including the chemokine CXCL1. Tumor self-seeding could explain the relationships between anaplasia, tumor size, vascularity and prognosis, and local recurrence seeded by disseminated cells following ostensibly complete tumor excision.

Characterization of MET Alterations in 37 Gastroesophageal Cancer Cell Lines for MET-Targeted Therapy.

Capmatinib and savolitinib, selective MET inhibitors, are widely used to treat various MET-positive cancers. In this study, we aimed to determine the effects of these inhibitors on MET-amplified gastric cancer (GC) cells. Methods: After screening 37 GC cell lines, the following cell lines were found to be MET-positive with copy number variation >10: SNU-620, ESO51, MKN-45, SNU-5, and OE33 cell lines. Next, we assessed the cytotoxic response of these cell lines to capmatinib or savolitinib alone using cell counting kit-8 and clonogenic cell survival assays. Western blotting was performed to assess the effects of capmatinib and savolitinib on the MET signaling pathway. Xenograft studies were performed to evaluate the in vivo therapeutic efficacy of savolitinib in MKN-45 cells. Savolitinib and capmatinib exerted anti-proliferative effects on MET-amplified GC cell lines in a dose-dependent manner. Savolitinib inhibited the phosphorylation of MET and downstream signaling pathways, such as the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) pathways, in MET-amplified GC cells. Additionally, savolitinib significantly decreased the number of colonies formed on the soft agar and exerted dose-dependent anti-tumor effects in an MKN-45 GC cell xenograft model. Furthermore, a combination of trastuzumab and capmatinib exhibited enhanced inhibition of AKT and ERK activation in human epidermal growth factor receptor-2 (HER2)- and MET-positive OE33 cells. Targeting MET with savolitinib and capmatinib efficiently suppressed the growth of MET-amplified GC cells. Moreover, these MET inhibitors exerted synergistic effects with trastuzumab on HER2- and MET-amplified GC cells.

Effectiveness of simulation-based interventions on empathy enhancement among nursing students: a systematic literature review and meta-analysis.

BACKGROUND: This study aimed to secure and analyze evidence regarding the enhancement of nursing students' empathy through simulation-based interventions. It comprehensively analyzed self-reported emotions and reactions as primary outcomes, along with the results reported by nursing students who experienced simulation-based interventions, including empathy. METHODS: This systematic literature review and meta-analysis investigated the effects of simulation-based interventions on enhancing empathy among nursing students. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for the systematic review and meta-analysis. The following details were considered: population, nursing students; intervention, simulation-based interventions targeting empathy enhancement; comparators, control groups without intervention or those undergoing general non-simulation-based classes; and outcomes, self-reported empathy. RESULTS: In the systematic review of 28 studies, it was found that the use of simulation-based interventions among nursing students led to an increase in empathy, albeit with a small effect size. This was demonstrated through a pooled, random-effects meta-analysis, yielding an effect size (Hedge's g) of 0.35 (95% CI: 0.14, 0.57, p = 0.001). The results of meta-regression and subgroup analysis significantly increased in empathy for studies published after 2019 (Hedge's g = 0.52, 95% CI: 0.31 to 0.73, p < 0.001), quasi-experimental research design (Hedge's g = 0.51, 95% CI: 0.27 to 0.74, p < 0.001), more than 60 participants (Hedge's g = 0.31, 95% CI: 0.02 to 0.59, p = 0.034), and simulation-based interventions in nursing education (Hedge's g = 0.43, 95% CI: 0.22 to 0.65, p < 0.001). CONCLUSIONS: Considering factors such as variations in sample size, research approaches, and the effects of independent studies on empathy, this systematic literature review and meta-analysis suggests that simulation-based education can significantly improve nursing students' overall empathy skills.

Cancer epigenetics: Past, present and future.

Cancer was thought to be caused solely by genetic mutations in oncogenes and tumor suppressor genes. In the last 35 years, however, epigenetic changes have been increasingly recognized as another primary driver of carcinogenesis and cancer progression. Epigenetic deregulation in cancer often includes mutations and/or aberrant expression of chromatin-modifying enzymes, their associated proteins, and even non-coding RNAs, which can alter chromatin structure and dynamics. This leads to changes in gene expression that ultimately contribute to the emergence and evolution of cancer cells. Studies of the deregulation of chromatin modifiers in cancer cells have reshaped the way we approach cancer and guided the development of novel anticancer therapeutics that target epigenetic factors. There remain, however, a number of unanswered questions in this field that are the focus of present research. Areas of particular interest include the actions of emerging classes of epigenetic regulators of carcinogenesis and the tumor microenvironment, as well as epigenetic tumor heterogeneity. In this review, we discuss past findings on epigenetic mechanisms of cancer, current trends in the field of cancer epigenetics, and the directions of future research that may lead to the identification of new prognostic markers for cancer and the development of more effective anticancer therapeutics.

Epigenetic regulation of DHRS2 by SUV420H2 inhibits cell apoptosis in renal cell carcinoma.

Renal cell carcinoma (RCC), also known as kidney cancer, is a common malignant tumor of the urinary system. While surgical treatment is essential, novel therapeutic targets and corresponding drugs for RCC are still needed due to the high relapse rate and low five-year survival rate. In this study, we found that SUV420H2 is overexpressed in renal cancers and that high SUV420H2 expression is associated with a poor prognosis, as evidenced by RCC RNA-seq results derived from the TCGA. SUV420H2 knockdown using siRNA led to growth suppression and cell apoptosis in the A498 cell line. Furthermore, we identified DHRS2 as a direct target of SUV420H2 in the apoptosis process through a ChIP assay with a histone 4 lysine 20 (H4K20) trimethylation antibody. Rescue experiments showed that cotreatment with siSUV420H2 and siDHRS2 attenuated cell growth suppression induced by SUV420H2 knockdown only. Additionally, treatment with the SUV420H2 inhibitor A-196 induced cell apoptosis via upregulation of DHRS2. Taken together, our findings suggest that SUV420H2 may be a potential therapeutic target for the treatment of renal cancer.

NTRK Fusion in a Cohort of BRAF p. V600E Wild-Type Papillary Thyroid Carcinomas.

Owing to the availability of a potent tropomyosin receptor kinase (TRK) inhibitor, it is necessary to develop an effective strategy to identify an enriched population of NTRK fusions in papillary thyroid carcinoma (PTC) in routine diagnostic practice. The reported prevalence of NTRK fusion in a large cohort of PTC is ∼3%. We performed an analysis to refine the characteristic histologic features of PTCs harboring NTRK fusions and further validate the diagnostic utility of pan-TRK immunohistochemistry as a screening tool. In this study, 450 PTCs known to harbor no BRAF p. V600E mutations were screened by pan-TRK immunohistochemistry, and the cases with TRK expression were confirmed by RNA-based next-generation sequencing assay. Eleven NTRK fusion cases were detected (2.4%), and all PTCs were classical subtypes. NTRK1 and NTRK3 were involved in the fusion with 9 different partner genes. Most cases showed similar characteristic histologic findings. Nodular permeative border, multinodular growth with a predominantly follicular pattern, extensive lymphatic invasion, and prominent internodular and intratumoral fibrosis were the characteristic histologic features of NTRK-rearranged PTCs. The ill-defined margins in the ultrasonography findings, which could not be clearly distinguished from the adjacent nontumorous thyroid tissue, were nodular permeative margins in histologic findings. Therefore, preoperative ultrasonographic findings in nodule margins were consistent with the final histologic findings. NTRK1/3 fusion in PTCs showed an overall sensitivity of 100% (95% CI, 71.51%-100%) and specificity of 100% (95% CI, 71.51%-100%) in the 22 cases examined, as confirmed with next-generation sequencing. Our study provides an integrative report of the preoperative ultrasonographic, histologic, immunohistochemical, and molecular features of NTRK-rearranged PTCs. Based on these findings, we propose an algorithmic approach for the stepwise assessment of NTRK fusions in PTCs.

Associated factors with depression and sleep quality in T1DM patients: a cross-sectional descriptive study.

BACKGROUND: Individuals with type 1 diabetes (T1DM) may experience sleep problems, usually due to low blood sugar levels during sleep or performance of blood sugar management (e.g., blood sugar monitoring). This study aimed to identify the disease-related characteristics, psychosocial aspects, and related factors underlying sleep quality in patients with T1DM. METHODS: This study employed a descriptive research design. The participants were 159 individuals with T1DM who completed online questionnaires. The data were analyzed using descriptive statistics, correlations, and multiple regression analyses. RESULTS: The average score for depression in T1DM patients was 23.77 (SD 5.31), and sleep quality received a score of 4.58 (SD 3.22). Depression was positively correlated with sleep quality and negatively correlated with the total resilience score. The factors linked to depression in T1DM patients were duration of disease, sleep latency, sleep duration, sleep disturbance, and resilience-acceptance of self and life sub-factors, with an explanatory power of 44.4% for the depression variance. The associated factors with sleep quality in T1DM patients were complications, resilience-personal competence sub-factors, and depression, with an explanatory power of 37.4% for sleep quality variance. CONCLUSIONS: The results of this study suggest that to improve sleep quality in patients with T1DM, it is necessary to develop and support disease management to prevent complications and implement interventions for improving resilience and reducing negative emotions such as depression.

Effects of metaverse-based career mentoring for nursing students: a mixed methods study.

BACKGROUND: There is a lack of studies on metaverse-based career mentoring for college students in both quantitative and qualitative research. This study aimed to examine the effect of metaverse-based career mentoring among nursing students and explore the experiences of mentors and mentees. METHODS: This study used a mixed methods design using both a survey for collecting quantitative data and focus group interviews for a qualitative one. A total of 8 mentors and 43 mentees participated in the metaverse-based career mentoring program. The program covered eight career fields and was delivered across eight sessions of 60 min each, over six days. Career decision-making self-efficacy among mentees and platform and program satisfaction were measured before and after the program. Afterwards, 7 mentors and 12 mentees participated in the focus group interviews to investigate their experience of participating in the metaverse-based career mentoring program. Quantitative data were analyzed using descriptive statistics, paired t-test, Wilcoxon signed-rank test, and Mann-Whitney U test. The qualitative data underwent thematic analysis. RESULTS: After the metaverse-based career mentoring program, mentees' career decision-making self-efficacy increased significantly compared to the baseline level. From the mentor-mentee focus group interviews, three key themes were derived: (i) communicating frankly and openly, (ii) being satisfied with realistic communication and program functions, and (iii) expecting an even more optimized program. CONCLUSIONS: A metaverse-based career mentoring program for nursing students can have a positive effect on their career decision-making self-efficacy. In addition, in terms of education, it is helpful as a non-face-to-face medium and feeling a sense of reality, so it is expected that it will be beneficial in education by applying various contents in the future.

Time from Exposure to Diagnosis among Quarantined Close Contacts of SARS-CoV-2 Omicron Variant Index Case-Patients, South Korea.

To determine optimal quarantine duration, we evaluated time from exposure to diagnosis for 107 close contacts of severe acute respiratory syndrome coronavirus 2 Omicron variant case-patients. Average time from exposure to diagnosis was 3.7 days; 70% of diagnoses were made on day 5 and 99.1% by day 10, suggesting 10-day quarantine.

Comparison of factor structures of the Pittsburgh sleep quality index between mid- and late pregnancy among Korean women: a cross-sectional study.

BACKGROUND: Sleep disturbance in pregnant women needs to be accurately assessed in a timely manner during pregnancy, to receive assessment-driven accurate intervention. This study aims to compare the factor structure of the Pittsburgh Sleep Quality Index (PSQI) among women in mid- and late pregnancy and evaluate the psychometric features of the Korean version of the PSQI. METHODS: The survey questionnaire with the PSQI, Center for Epidemiological Studies Depression scale, and pregnancy stress, was completed by 281 women in mid- or late pregnancy. Exploratory factor analysis determined the best factor structure of the PSQI, and the Pearson correlation coefficient examined a convergent validity with depressive symptoms and pregnancy stress. Internal consistency was examined using Cronbach's alpha. RESULTS: In both mid- and late-pregnancy women, a two-factor structure model was identified. However, each factor's different components were named differently. For women in mid-pregnancy, it was named "quantitative sleep quality" and "subjective sleep quality," and for those in later stages of pregnancy, they were named "perceived sleep quality" and "daily disturbance." The PQSI score showed a significantly positive correlation between depressive symptoms and pregnancy stress in mid- (r = 0.57 and r = 0.39, respectively), and late pregnancy (r = 0.48 and 0.28, respectively). The overall Cronbach's alpha for the PSQI was 0.63. CONCLUSIONS: The Korean version of the PSQI demonstrated excellent construct and convergent validity, making it suitable to assess the sleep quality of women in middle to late stages of their pregnancy. The PSQI was found to have a two-factor structure in the mid-and late pregnancy, but the components were different. As sleep quality changes with each gestational stage, factors affecting it during mid- and late pregnancy need to be separately examined. It will make it easier for medical professionals to provide pregnant women sleeping irregularly, with the right kind of intervention.

Comparison of factors influencing fall recurrence in the young-old and old-old: a cross-sectional nationwide study in South Korea.

BACKGROUND: Recurrent falls are a concerning problem in the elderly. Elderly people aged > 65 years who are prone to fall often require medical treatment for severe fall-related injuries, which is associated with a substantial financial burden. Therefore, this study aimed to identify factors related to recurrent falls in the community-dwelling young-old (65-74 years old) and old-old (≥ 75 years) in South Korea. METHODS: This study used a cross-sectional, correlation design. Data from the 2017 National Survey of Older Koreans were used, and 5,838 young-old and 4,205 old-old elderly people were included in the analysis. The questionnaire included general characteristics, fall experience, physical status, mental status, and presence of chronic diseases. The data were analyzed using the chi-square test, one-way analysis of variance, and logistic regression analysis. RESULTS: In the young-old elderly people, limitations in activities of daily living (p < .001), use of visual aids (p = .002), cognitive function (p < .001), presence of suicidal ideations (p = .005), number of chronic diseases (p < .001), and number of prescribed medications used (p = .006) associated with fall recurrence. In the old-old elderly people, having a spouse (p = .034), being a beneficiary of the National Basic Livelihood Security System (p = .025), less exercise (p = .003), limitations in activities of daily living (p < .001), visual aid use (p = .002), presence of suicidal ideations (p = .015), number of chronic diseases (p < .001), and presence of Parkinson's disease (p < .001) associated with fall recurrence. CONCLUSIONS: This study identified differences in factors related to fall recurrence between the young-old and old-old elderly. The results of this study indicate that it is necessary to implement an intervention program to prevent fall recurrence by age group in consideration of the risk factors for fall recurrence in each elderly people group.

Particulate matter 2.5 promotes inflammation and cellular dysfunction via reactive oxygen species/p38 MAPK pathway in primary rat corneal epithelial cells.

PURPOSE: Numerous studies have linked particulate matter2.5 (PM2.5) to ocular surface diseases, but few studies have been conducted on the biological effect of PM2.5 on the cornea. The objective of this study was to evaluate the harmful effect of PM2.5 on primary rat corneal epithelial cells (RCECs) in vitro and identify the toxic mechanism involved. MATERIALS AND METHODS: Primary cultured RCECs were characterized by pan-cytokeratin (CK) staining. In PM2.5-exposed RCECs, cell viability, microarray gene expression, inflammatory cytokine levels, mitochondrial damage, DNA double-strand break, and signalling pathway were investigated. RESULTS: Exposure to PM2.5 induced cytotoxicity and morphological changes in RCECs. In addition, PM2.5 markedly up-regulated pro-inflammatory mediators but down-regulated the wound healing-related transforming growth factor-ß. Furthermore, PM2.5 promoted mitochondrial reactive oxygen species (ROS) production and mediated cellular damage to mitochondria and DNA, whereas these cellular alterations induced by PM2.5 were markedly suppressed by a potential ROS scavenger. Noteworthy, removal of ROS selectively down-regulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the activation of the nuclear factor-κB (NF-κB) p65 in PM2.5-stimulated cells. Additionally, SB203580, a p38 MAPK inhibitor, markedly suppressed these PM2.5-mediated cellular dysfunctions. CONCLUSIONS: Taken together, our findings show that PM2.5 can promote the ROS/p38 MAPK/NF-κB signalling pathway and lead to mitochondrial damage and DNA double-strand break, which is ultimately caused inflammation and cytotoxicity in RCECs. These findings indicate that the ROS/p38 MAPK/NF-κB signalling pathway is one mechanism involved in PM2.5-induced ocular surface disorders.

Sublobar Resection in Stage IA Non-Small Cell Lung Cancer: Role of Preoperative CT Features in Predicting Pathologic Lymphovascular Invasion and Postoperative Recurrence.

BACKGROUND. Prognostic factors on preoperative CT in stage IA non-small cell lung cancer (NSCLC) may help select patients for sublobar resection or lobectomy. OBJECTIVE. The purpose of this study was to identify CT features predictive of pathologic lymphovascular invasion (LVI) in stage IA NSCLC and to evaluate the features' prognostic value in patients who undergo sublobar resection. METHODS. This retrospective study included 904 patients (mean age, 62.0 years; 453 men, 451 women) who underwent lobectomy (n = 574) or sublobar resection (n = 330) for stage IA NSCLC. Two thoracic radiologists independently evaluated findings on pre-operative chest CT and then resolved discrepancies. Recurrences were identified from medical record review. Multivariable logistic regression was used to identify independent predictors of pathologic LVI. Multivariable Cox proportional hazards models were used to identify prognostic features. Interreader agreement was assessed. RESULTS. Pathologic LVI was present in 10.2% (92/904) of patients. It was present only in solid-dominant part-solid nodules (PSNs) and solid nodules and only in nodules with a solid portion diameter over 10 mm. Among solid-dominant PSNs and solid nodules with a solid portion diameter over 10 mm, independent (p < .05) predictors of pathologic LVI were peritumoral interstitial thickening (odds ratio [OR], 13.22) and pleural contact (defined as pleural contact measuring over one-quarter of the circumference of the nodule's solid portion) (OR, 2.45). Also among such nodules, peritumoral interstitial thickening achieved 80.4% sensitivity, 76.7% specificity, and 77.4% accuracy; pleural contact achieved 35.9% sensitivity, 82.5% specificity, and 74.3% accuracy; and presence of either feature achieved 90.2% sensitivity, 64.3% specificity, and 68.9% accuracy for predicting pathologic LVI. In patients undergoing sublobar resection, after adjusting for T category and operative type, recurrence-free survival (RFS) was independently (p < .05) predicted by solid-dominant PSN or solid nodule with a solid portion diameter over 10 mm also showing peritumoral interstitial thickening (hazard ratio [HR], 5.37) or also showing either peritumoral interstitial thickening or pleural contact (HR, 6.05). The interreader agreement kappa values were 0.67 for peritumoral interstitial thickening and 0.77 for pleural contact. CONCLUSION. Pathologic LVI occurred only in solid-dominant PSNs and solid nodules with solid portion over 10 mm. Among such nodules, peritumoral interstitial thickening and pleural contact independently predicted pathologic LVI and RFS. CLINICAL IMPACT. CT features may help select patients with stage IA NSCLC for sublobar resection rather than more extensive surgery.

Breast Cancer Metastasis.

Owing to increased awareness of the importance of mammogram and advances in surgical technology, survival rate of patients with primary breast cancer has dramatically increased. Despite all these advances in breast cancer treatment, there are no currently available treatments for this disease once it metastasizes to distant organs including bones, lungs, brain, and liver. This is mainly attributed to the complexity of metastatic process. Recent advances in technology enabled cancer biologists to dissect each step of the metastatic process, and this led to discovery of major players and molecules in this process. In this section, we will discuss recent discovery and advances in the field of breast cancer metastasis research.

Imaging surveillance for the detection of ipsilateral local tumor recurrence in patients who underwent oncoplastic breast-conserving surgery with acellular dermal matrix: abbreviated MRI versus conventional mammography and ultrasonography.

BACKGROUND: To evaluate the usefulness of surveillance-abbreviated magnetic resonance imaging (AB-MRI) for the detection of ipsilateral local tumor recurrence (LTR) in patients who underwent oncoplastic breast-conserving surgery (BCS) with acellular dermal matrix (ADM) by comparing its diagnostic performance with that of mammography (MG) and ultrasonography (US). METHODS: The postoperative MG, US, and AB-MRI findings of the ipsilateral breast and pathological results of 324 patients who underwent oncoplastic BCS using ADM were reviewed. The cancer detection rate (CDR), sensitivity, specificity, positive predictive value (PPV) for biopsy, accuracy, and area under the curve (AUC) for each imaging modality were calculated. RESULTS: A total of 8 ipsilateral LTRs were diagnosed, and most cancers (87.5%) were stage 0 or 1 (median size of invasive cancer, 1.44 cm; range, 0.7-2 cm). The CDRs of MG, US, MG + US, and AB-MRI were 0.009, 0.012, 0.015, and 0.025 per woman, respectively. Three cancers were detectable on only AB-MRI, and the additional CDR of AB-MRI was 0.010. The sensitivity and specificity of MG, US, MG + US, and AB-MRI were 37.5%, 50%, 62.5%, and 100% and 99.7%, 98.4%, 98.1%, and 97.8%, respectively. The PPVs for biopsy were 75%, 44.4%, 45.5%, and 53.3%, respectively. The AUC was significantly higher for AB-MRI (0.989) than for MG alone (0.686, P = 0.0009), US alone (0.742, P = 0.009), and MG + US (0.803, P = 0.04). A total of 66.7% of cancers visible on only AB-MRI were located at the deep posterior portion of the excision cavity, which might have been missed with MG or MG + US due to masking by the ADM filler. CONCLUSION: AB-MRI can improve the detection of ipsilateral LTR despite postoperative changes caused by ADM fillers compared to conventional MG and US. Patients who undergo BCS with ADM can be candidates for AB-MRI surveillance considering improved cancer detection and high sensitivity.

Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea, November 2021.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.

Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS.

Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H2O2)-induced oxidative stress model using human RPE cells. Our findings showed that 300 µM H2O2 increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 µM spermidine. Furthermore, spermidine significantly reduced H2O2-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H2O2 insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca2+ levels resulting from endoplasmic reticulum stress in H2O2-stimulated human RPE cells. Treatment with a cytosolic Ca2+ chelator markedly reversed H2O2-induced cellular dysfunction. Overall, spermidine protected against H2O2-induced cellular damage by blocking the increase of intracellular Ca2+ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases.

Invasive Pulmonary Aspergillosis in Patients With Severe Fever With Thrombocytopenia Syndrome.

Sixteen of 45 patients with severe fever with thrombocytopenia (36%) were admitted to an intensive care unit; 9 (56%) developed invasive pulmonary aspergillosis (IPA) within a median of 8 days (range, 2-11). Mortality was higher in the IPA vs non-IPA patients and in those without vs with antifungal therapy.