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Purpose@#This study aimed to identify the impact of nursing organizational culture and nursing practice environment on generational conflict in organization among hospital nurses. @*Methods@#This study utilized a cross-sectional design.The participants consisted of 214 nurses working at two tertiary general hospitals, which were located in B city. Data were collected from January 15 to January 31, 2022, using self-report questionnaires. Data were analyzed by descriptive statistics, one-way ANOVA, independent t-test, Pearson's correlation coefficient and multiple regression analysis using IBM/SPSS 28.0 for Windows. @*Results@#The mean generational conflict in organization was 2.60±0.74 points on a 5-point scale. Multiple regression indicated that the factors influencing generational conflict in organization included relation-oriented nursing organizational culture (β=-.29, p<.001), hierarch-oriented nursing organizational culture (β=-.29, p<.001), hierarch-oriented nursing organizational culture (β=.17, p=.006) and clinical career, and these variables explained 23.0% of generational conflict in organization. @*Conclusion@#The findings of this study suggest that it is necessary to improve relation-oriented nursing organizational culture and avoid hierarch-oriented nursing organizational culture to decrease generational conflict in organization.
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Background/Aims@#Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone. @*Methods@#This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either EsoduoⓇ/sup> (esomeprazole 20 mg with sodium bicarbonate 800 mg) or NexiumⓇ/sup> (esomeprazole 20 mg) once daily for 4 weeks from January 2019 to December 2019. The patients had a history of heartburn for at least 2 days in the week before randomization as well as in the last 3 months and no esophageal mucosal breaks on endoscopy. The primary endpoint was a complete cure of heartburn at week 4. The secondary and exploratory endpoints as well as the safety profiles were compared in the groups at weeks 2 and 4. @*Results@#A total of 355 patients completed the study (180 in the EsoduoⓇ/sup> group and 175 in the NexiumⓇ/sup> group). The proportions of patients without heartburn in the entire 4th week of treatment were not different between the two groups (33.33% in the EsoduoⓇ/sup> group and 35% in the NexiumⓇ/sup> group, p=0.737). There were no significant differences in most of the secondary and exploratory endpoints as well as the safety profiles. @*Conclusions@#EsoduoⓇ/sup> is as effective and safe as NexiumⓇ/sup> for managing typical symptoms in patients with NERD (ClinicalTrial.gov identifier: NCT03928470).
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Purpose@#Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. @*Materials and Methods@#Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. @*Results@#A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. @*Conclusion@#Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.
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Background/Aims@#Recently, 1 L of polyethylene glycol (PEG) plus ascorbic acid (Asc) has been introduced in Korea as a colonoscopy preparation agent. Data on its efficacy and safety in older adults have been limited. We aimed to evaluate the safety and efficacy of 1 L PEG/Asc in older adults by comparing it with oral sulfate solution (OSS). @*Methods@#A prospective multicenter randomized study was conducted with subjects aged ≥ 65 years who underwent colonoscopy. The participants were randomized to receive 1 L PEG/Asc or OSS. The primary endpoint was successful bowel preparation, defined as total Boston Bowel Preparation Scale ≥ 6, and ≥ 2 at each segment. Patient satisfaction, adverse events, and renal function changes were compared between the groups. @*Results@#Among the 106 patients, 104 were finally included in the analysis. Overall, successful bowel preparation was achieved in 96.2% of both 1 L PEG/Asc and OSS groups. The satisfaction scores for taste, total amount ingested, overall feeling, and willingness to repeat the same regimen were not significantly different between the groups. Adverse events of moderate or higher severity occurred in 16 and 10 cases in the 1 L PEG/Asc and OSS group, respectively. There were no significant changes in electrolyte levels or renal function from baseline. @*Conclusions@#The successful bowel preparation rate was > 90% in both groups without severe adverse effects and significant changes in renal function. As a new low-dose preparation regimen for colonoscopy in older adults, 1 L PEG/Asc, is as effective and safe as OSS.
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Background/Aims@#Increasing resistance to clarithromycin (CAM) of Helicobacter pylori (H. pylori) is one of the main causes of recent decrease in eradication rate of standard triple therapy. The aim of this study was to evaluate the usefulness of 7-day tailored therapy based on the existence of CAM resistance. @*Methods@#From January 2017 to May 2022, a total of 481 consecutive patients with H. pylori infection were recruited in Daegu Catholic University Medical Center. Treatment regimen was selected based on the result of CAM resistance test. Patients with CAM resistance (R group) were treated with bismuth-based quadruple therapy for 7 days. Patients without CAM resistance (S group) were treated with standard triple therapy for 7 days. @*Results@#The overall H. pylori eradication rate was 89.4% (379 of 424) by per-protocol (PP) analysis. Patients with CAM resistance mutation included 166 patients (34.5%). The eradication rates of each group were 88.8% (135 of 152) and 89.7% (244 of 272) by PP analysis, for R and S group respectively. By intention-to-treat (ITT) analysis, the eradication rates were 81.3% (135 of 166) and 77.5% (244 of 315) for R and S group. CAM resistance was identified with a dual-priming oligonucleotide-based multiplex PCR. @*Conclusions@#In spite of this high CAM resistance (34.5%), the eradication rate of 7-day tailored therapy based on the existence of CAM resistance was 89.4%. The 7-day tailored therapy based on CAM resistance could be an acceptable treatment selection strategy for H. pylori eradication.
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Purpose@#Laparoscopic surgery is a choice in several emergency settings. However, there has been no nationwide study or survey that has compared the clinical use of laparoscopic emergency surgery (LES) versus open abdominal emergency surgery (OES) in Korea.Therefore, we examined the state of LES across multiple centers in Korea and further compared this data with the global state based on published reports. @*Methods@#Data of 2,122 patients who received abdominal emergency surgery between 2014 and 2019 in three hospitals in Korea were collected and retrospectively analyzed. Several clinical factors were investigated and analyzed. @*Results@#Of the patients, 1,280 (60.3%) were in the OES group and 842 (39.7%) were in the LES group. The most commonly operated organ in OES was the small bowel (25.8%), whereas that for LES was the appendix. In appendectomy and cholecystectomy, 93.7% and 88.0% were in the LES group. In small bowel surgery, gastric surgery, and large bowel surgery, 89.4%, 92.0%, and 79.1% were in the OES group. The severity-related factors of patient status demonstrated statistically significant limiting factors of selection between LES and OES. @*Conclusion@#Although our study has several limitations, compared to the LES data from other countries, the general LES state was similar in appendectomies, cholecystectomies, and small bowel surgeries. However, in gastric and colorectal surgeries, the LES state was different from those of other countries. This study demonstrated the LES state and limiting factors of selection between LES and OES in various operated organs. Further studies are required to analyze these differences and the various limiting factors.
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Purpose@#This study aimed to develop and test a reward scale for hospital nurses. @*Methods@#The initial items were identified through a literature review and focus group interviews with ten hospital nurses. The content validity of the items was evaluated by ten experts. Fifty-one items were derived from the pilot survey. Four hundred eighty-eight nurses participated in the study: 248 for exploratory factor analysis (EFA) and 240 confirmatory factor analysis (CFA). Data were analyzed using item analysis, EFA, CFA, convergent validity, known-group validity, and internal consistency using IBM SPSS Statistics 29.0 and IBM SPSS AMOS 29.0. @*Results@#The final scale consisted of 31 items and eight factors (decent wage, opportunity to grow and develop, support for special situations, various benefits, flexibility of work, job-related achievement, reflecting career and performance, and recognition), which explained 67.3% of the total variance. The eight-subscale model was validated by CFA. Convergent validity was evaluated by analyzing correlation with intention to leave (r = - .63, p < .001) and job satisfaction (r = .54, p < .001). The known-group validity was evaluated by comparing the reward scales according to age, clinical career, income level and hospital type. The scale was found to be reliable with a Cronbach’s α of .89. @*Conclusion@#Both the validity and reliability of the reward scale for hospital nurses are verified, which can enhance the understanding of the range of rewards and may assist nurse managers in establishing an effective reward system.
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Background and Objectives@#Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed. @*Methods@#and Results: In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3’ untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation in vitro. In vivo results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease. @*Conclusions@#Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regu-late muscle and vascular differentiation during embryonic development.
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Purpose@#The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and proliferation by growth factor coordination and amino acid availability. Leucyl-tRNA synthetase 1 (LARS1) senses the intracellular leucine concentration and mediates amino acid-induced activation of mTORC1. Thus, LARS1 inhibition could be useful in cancer treatment. However, the fact that mTORC1 can be stimulated by various growth factors and amino acids suggests that LARS1 inhibition alone has limitations in inhibiting cell growth and proliferation. We investigated the combined effects of BC-LI-0186, a LARS1 inhibitor, and trametinib, an MEK inhibitor, on non–small cell lung cancer (NSCLC). @*Materials and Methods@#Protein expression and phosphorylation were observed by immunoblotting, and genes differentially expressed between BC-LI-0186–sensitive and –resistant cells were identified by RNA sequencing. The combined effect of the two drugs was inferred from the combination index values and a xenograft model. @*Results@#LARS1 expression was positively correlated with mTORC1 in NSCLC cell lines. BC-LI-0186 treatment of A549 and H460 cells maintained in media supplemented with fetal bovine serum revealed paradoxical phosphorylation of S6 and activation of mitogen- activated protein kinase (MAPK) signaling. Compared with BC-LI-0186–sensitive cells, –resistant cells showed enrichment of the MAPK gene set. The combination of trametinib and BC-LI-0186 inhibited the phosphorylation of S6, MEK, and extracellular signal-regulated kinase and their synergistic effects were confirmed in a mouse xenograft model. @*Conclusion@#The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.
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Background@#Brain metastases of peri-Rolandic area is crucial as it directly impacts the quality of life for cancer patients. Surgery or stereotactic radiosurgery (SRS) is considered for peri-Rolandic brain metastases as for other brain metastases. However, the benefit of each treatment modality on functional outcome has not been clearly defined for this tumor. The purpose of this study is to compare the functional course of each treatment and to suggest an effective treatment for patients’ quality of life. @*Methods@#Fifty-two patients who had undergone SRS or surgery for brain metastasis confirmedby enhanced MRI were enrolled retrospectively. Overall survival (OS), progression free survival (PFS), and functional outcomes were estimated using the Kaplan-Meier method, univariate, multivariate analysis, and Cox proportional hazards regression. @*Results@#Median OS and PFS were 13.3 months and 8.9 months in our study population.Treatment modalities were not significant factors for OS and PFS. Extracranial systemic cancer progression was significant factor for both parameters (p=0.030 for OS and p=0.040 for PFS). Median symptom improvement (improvement of at least 1 grade after surgery compared to preoperative state) time was significantly shorter in surgery group than in the SRS group (10.5 days vs. 37.5 days, p=0.034). @*Conclusion@#Surgery for brain metastases can contribute to a positive quality of life for the remain-ing duration of the patient’s life.
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Lung cancer is representative of a high frequency and high mortality disease and ranks at the top in incidence and mortality in Korea, when excluding thyroid cancer. In this manuscript, we focused on current targeted therapies for lung cancer used widely in the medical field.Current Concepts: The majority of patients with lung cancer cannot be treated with surgery only and require chemotherapeutics or radiation therapy. Currently, classical chemotherapeutic agents, targeted agents, and immune checkpoint inhibitors are the most widely used. Recently, the Research and Development of antibody-drug conjugates is gaining attention, and this may become a more widely prescribed treatment in the future. Among the available treatment options, targeted therapy is becoming increasingly feasible and widespread for treating inoperable lung cancers, where driver mutations have been identified, and for adjuvant or neoadjuvant therapies. Next-generation sequencing (NGS) improves the ability to identify driver mutations that were previously difficult to detect and can also be performed on blood samples where no cancer tissue is available for testing. This makes it possible to identify therapeutic targets for targeted therapy more rapidly.Discussion and Conclusion: The most common type of lung cancer in Korea is adenocarcinoma, for which a driver mutation has been identified. Newly developed drugs target previously problematic mutations or cancer cell lines that have acquired resistance induced during the treatment process. The survival rate of patients with lung cancer is expected to improve with the development of tailored treatments for targets identified from the NGS data of the patient. This paper will help clinicians understand the current state of targeted therapies for lung cancer treatment.
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Background@#Low-density lipoprotein cholesterol is an important marker highly associated with cardiovascular disease. Since the direct measurement of it is inefficient in terms of cost and time, it is common to estimate through the Friedewald equation developed about 50 years ago. However, various limitations exist since the Friedewald equation was not designed for Koreans. This study proposes a new low-density lipoprotein cholesterol estimation equation for South Koreans using nationally approved statistical data. @*Methods@#This study used data from the Korean National Health and Nutrition Examination Survey from 2009 to 2019. The 18,837 subjects were used to develop the equation for estimating low-density lipoprotein cholesterol. The subjects included individuals with low-density lipoprotein cholesterol levels directly measured among those with high-density lipoprotein cholesterol, triglycerides, and total cholesterol measured. We compared twelve equations developed in the previous studies and the newly proposed equation (model 1) developed in this study with the actual low-density lipoprotein cholesterol value in various ways. @*Results@#The low-density lipoprotein cholesterol value estimated using the estimation formula and the actual low-density lipoprotein cholesterol value were compared using the root mean squared error. When the triglyceride level was less than 400 mg/dL, the root mean squared of the model 1 was 7.96, the lowest compared to other equations, and the model 2 was 7.82. The degree of misclassification was checked according to the NECP ATP III 6 categories. As a result, the misclassification rate of the model 1 was the lowest at 18.9%, and Weighted Kappa was the highest at 0.919 (0.003), which means it significantly reduced the underestimation rate shown in other existing estimation equations. Root mean square error was also compared according to the change in triglycerides level. As the triglycerides level increased, the root mean square error showed an increasing trend in all equations, but it was confirmed that the model 1 was the lowest compared to other equations. @*Conclusion@#The newly proposed low-density lipoprotein cholesterol estimation equation showed significantly improved performance compared to the 12 existing estimation equations. The use of representative samples and external verification is required for more sophisticated estimates in the future.
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Lung cancer ranks first in cancer mortality in Korea and cancer incidence in Korean men. More than half of Korean lung cancer patients undergo chemotherapy, including adjuvant therapy. Cytotoxic agents, targeted therapy, and immune checkpoint inhibitors are used in chemotherapy according to the biopsy and genetic test results. Among chemotherapy, the one that has developed rapidly is targeted therapy. The National Comprehensive Cancer Network (NCCN) guidelines have been updated recently for targeted therapy of multiple gene mutations, and targeted therapy is used not only for chemotherapy but also for adjuvant therapy. While previously targeted therapies have been developed for common genetic mutations, recently targeted therapies have been developed to overcome uncommon mutations or drug resistance that have occurred since previous targeted therapy. Therefore, this study describes recent, rapidly developing targeted therapies.
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Purpose@#This study aimed to identify the influence of effort-reward imbalance and job satisfaction on turnover intention among hospital nurses. @*Methods@#Data were collected from January 28 to February 10, 2022, from 237 nurses from five hospitals including clinics, general hospitals, and tertiary care hospitals located in B city. The collected data were analyzed using descriptive statistics, t-test, ANOVA, the Scheffé test, Pearson’s correlation coefficients, and multiple linear regression analysis, using SPSS/WIN 26.0. @*Results@#The average of the effort-reward ratio, an indicator of effort-reward imbalance, was 1.67±0.66, and 86.5% of the participants had a value of 1 or more. The mean job satisfaction and turnover intention were 3.32±0.48 and 3.69±0.89 on a 5-point scale, respectively. Multiple regression revealed that factors affecting turnover intention among hospital nurses included effort-reward imbalance (β=.30,p<.001) and job satisfaction (β=-.32, p<.001), and these variables explained 29.0% of turnover intention. @*Conclusion@#These findings indicate that effort-reward imbalance and job satisfaction are associated with turnover intention. Therefore, to decrease the turnover intention of hospital nurses, interventions and policies should be prepared to resolve the nurse's effort-reward imbalance and increase job satisfaction at regional or national level hospitals.
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Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics.
Subject(s)
Cell Differentiation , Cell Proliferation , Cells, Cultured , Dental Pulp/metabolism , Lysophospholipids , Osteogenesis , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Sphingosine/analogs & derivatives , Stem CellsABSTRACT
Purpose@#The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). @*Materials and Methods@#In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). @*Results@#Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). @*Conclusion@#The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.
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Purpose@#We investigated the clinicopathological features and management for superficial nonampullary duodenal tumors (SNADTs). The safety and feasibility of laparoscopic management, especially laparoscopic endoscopic cooperative surgery (LECS), were evaluated. @*Methods@#A total of 59 patients with SNADTs who underwent operations from January 2009 to December 2018 at all 8 institutions of the Catholic Medical Center were identified in our comprehensive multi-institutional database. Clinicopathological and surgical data on the 4 anatomical regions of the duodenum were collected and compared.Characteristics of laparoscopic procedure (laparoscopy-only) and LECS procedures were also compared. @*Results@#There were significantly more asymptomatic patients with tumors in the first and second vs. third and fourth duodenal regions. Gastrointestinal stromal tumors (GISTs), carcinoids, and ectopic pancreatic tumors were identified in 32, 12, and 5 cases, respectively. Forty-two patients (71.2%) underwent laparoscopy. Of patients undergoing laparoscopy, the LECS group exhibited significantly more endophytic features and smaller tumor sizes (P < 0.001 and P < 0.001, respectively). Although no significant difference in the wedge resection or postoperative complication rate was seen between the 2 groups (P = 0.096 and P = 0.227, respectively), the wedge resection rate was higher, and the complication rate lower, in the LECS group than the conventional laparoscopic surgery group. @*Conclusion@#Most of the SNADTs located in proximal duodenum were detected incidentally. GISTs were the most common diagnoses of SNADTs in all locations. In treating these tumors, laparoscopic resection is safe and feasible. Especially, LECS may be ideal for treating small endophytic tumors, minimizing over-resection and postoperative complications.
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Restless legs syndrome (RLS) is a common neurological illness marked by a strong desire to move one’s legs, usually in association with uncomfortable sensations. Recent studies have investigated brain networks and connectivity in RLS. The advent of network analysis has greatly improved our understanding of the brain and various neurological disorders. A few studies have investigated alterations in functional connectivity in patients with RLS. This article reviews functional connectivity studies of patients with RLS, which have identified significant alterations relative to healthy controls in several brain networks including thalamic, salience, default-mode, and small-world networks. In addition, network changes related to RLS treatment have been found, including to repetitive transcranial magnetic stimulation, transcutaneous spinal cord direct-current stimulation, and dopaminergic drugs. These findings suggest that the underlying pathogenesis of RLS includes alterations in the functional connectivity in the brain and that RLS is a network disorder.
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Purpose@#Tumor radioresistance and dose-limiting toxicity restrict the curative potential of radiotherapy, requiring novel approaches to overcome the limitations and augment the efficacy. Here, we investigated the effects of signal transducer and activator of transcription 3 (STAT3) activation and autophagy induction by irradiation on antiapoptotic proteins and the effectiveness of the BH3 mimetic ABT-737 as a radiosensitizer using K-ras mutant non-small cell lung cancer (NSCLC) cells and a Kras G12D :p53 fl/fl mouse (KP mouse) model. @*Materials and Methods@#A549 and H460 cells were irradiated, and the expression of Bcl-2 family proteins, JAK/STAT transcriptional pathway, and autophagic pathway were evaluated by immunoblotting. The radiosensitizing effects of ABT-737 were evaluated using A549 and H460 cell lines with clonogenic assays and also by a KP mouse model with microcomputed tomography and immunohistochemistry. @*Results@#In A549 and H460 cells and mouse lung tissue, irradiation-induced overexpression of the antiapoptotic molecules BclxL, Bcl-2, Bcl-w, and Mcl-1 through JAK/STAT transcriptional signaling induced dysfunction of the autophagic pathway. After treatment with ABT-737 and exposure to irradiation, the number of surviving clones in the cotreatment group was significantly lower than that in the group treated with radiation or ABT-737 alone. In the KP mouse lung cancer model, cotreatment with ABT-737 and radiation-induced significant tumor regression; however, body weight changes in the combination group were not significantly different, suggesting that combination treatment did not cause systemic toxicity. @*Conclusion@#These findings supported the radiosensitizing activity of ABT-737 in preclinical models, and suggested that clinical trials using this strategy may be beneficial in K-ras mutant NSCLC.
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Objective@#We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer’s disease study (BICWALZS) participants. @*Methods@#A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. @*Results@#The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer’s dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer’s disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. @*Conclusion@#The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.