Development of a Mature B Lymphocyte Probe through Gating-Oriented Live-Cell Distinction (GOLD) and Selective Imaging of Topical Spleen.

B lymphocytes play a pivotal role in the adaptive immune system by facilitating antibody production. Young B cell progenitors originate in the bone marrow and migrate to the spleen for antigen-dependent maturation, leading to the development of diverse B cell subtypes. Thus, tracking B cell trajectories through cell type distinction is essential for an appropriate checkpoint assessment. Despite its significance, monitoring specific B cell subclasses in live states has been hindered by a lack of suitable molecular tools. In this study, we introduce CDoB as the first mature B cell-selective probe, enabling real-time discrimination of three classified stages in B-cell development: progenitor, transitional, and mature B cells, through a single analysis using CyTOF. The selective mechanism of CDoB, elucidated as gating-oriented live-cell distinction (GOLD), targets SLC25A16, identified through systematic screening of SLC-CRISPRa and CRISPRi libraries. CDoB selectively brightens mature B cells in the mitochondrial area using SLC25A16 as the main gate, and the staining intensity correlates positively with the expression level of SLC25A16 along the B cell maturation continuum. In spleen tissues, CDoB demonstrates selective marking in mature B cell areas in live tissue status, representing the first performance achieved by a small-molecule fluorescent probe.

The Effects of Alexithymia and Confidence in Patient Safety Management on the Clinical Competence of Nursing Students: A Cross-Sectional Survey.

Nursing students frequently believe that they are clinically incompetent. The objective of this study was to identify the effects of alexithymia and patient safety management on the clinical competence of nursing students. A cross-sectional design was used to investigate these relationships among 167 nursing students from two universities in South Korea. A self-reported structured questionnaire was used for alexithymia, patient safety management confidence, and clinical competence. The factors influencing clinical competence were safety education (ß = -0.16, p = 0.022), alexithymia (ß = -0.14, p = 0.049), and confidence in patient safety management (ß = 0.52, p < 0.001). The explanatory power of these three factors was 37.1%, and confidence in patient safety management was found to have the greatest influence on clinical competence. Based on these results, the pursuit of patient safety and the delivery of high-quality care depend not only on the acquisition of clinical skills but also on the emotional competencies and patient safety management confidence of the nursing students.

Risk prediction model of peritoneal seeding in advanced gastric cancer: A decision tool for diagnostic laparoscopy.

BACKGROUND: Selective diagnostic laparoscopy in gastric cancer patients at high risk of peritoneal metastasis is essential for optimal treatment planning. In this study available clinicopathologic factors predictive of peritoneal seeding in advanced gastric cancer (AGC) were identified, and this information was translated into a clinically useful tool. METHODS: Totally 2833 patients underwent surgery for AGC between 2003 and 2013. The study identified clinicopathologic factors associated with the risk of peritoneal seeding for constructing nomograms using a multivariate logistic regression model with backward elimination. A nomogram was constructed to generate a numerical value indicating risk. Accuracy was validated using bootstrapping and cross-validation. RESULTS: The proportion of seeding positive was 12.7% in females and 9.6% in males. Of 2833 patients who underwent surgery for AGC, 300 (10.6%) were intraoperatively identified with peritoneal seeding. Multivariate analysis revealed the following factors associated with peritoneal seeding: high American Society of Anesthesiologists score, fibrinogen, Borrmann type 3 or 4 tumors, the involvement of the middle, anterior, and greater curvature, cT3 or cT4cN1 or cN2 or cN3, cM1, and the presence of ascites or peritoneal thickening or plaque or a nodule on the peritoneal wall on computed tomography. The bootstrap analysis revealed a robust concordance between mean and final parameter estimates. The area under the ROC curve for the final model was 0.856 (95% CI, 0.835-0.877), which implies good performance. CONCLUSIONS: This nomogram provides effective risk estimates of peritoneal seeding from gastric cancer and can facilitate individualized decision-making regarding the selective use of diagnostic laparoscopy.

A Study on the Effects of Gendered Social Norms on the Tradeoff Between Paid and Unpaid Work in Korea.

In this study, Korean time-use survey data for coupled households is analyzed to show that unpaid work time is endogenous in its relationship with paid work time because the views of traditional gender roles affect gender disparity in unpaid work time. The data not only includes time allocation between husbands and wives but also their views of traditional gender roles within their households, and this information can represent gendered social norms that can potentially explain the distribution of unpaid work between husbands and wives. The control function model is estimated to identify the tradeoff between unpaid work time and paid work time by solving the endogeneity problem. The results of this study show that wives' unpaid work is likely to be affected by gendered social norms and that the effect can be larger for those having children. In addition, only in the case of wives, unpaid work time is found to be negatively associated with whether to work full-time, showing that wives' burden of unpaid work could prevent them from working full time. The results indicate that it is crucial to recognize the need to change gendered social norms to address an asymmetric division of unpaid work between husbands and wives.

Tolerability and Effectiveness of Switching to Dulaglutide in Patients With Type 2 Diabetes Inadequately Controlled With Insulin Therapy.

Aims: Glucagon-like peptide 1 (GLP-1) receptor agonists have demonstrated strong glycemic control. However, few studies have investigated the effects of switching from insulin to GLP-1 receptor agonists. We aimed to investigate, using real-world data, whether switching to dulaglutide improves glycemic control in patients with type 2 diabetes mellitus (T2D) inadequately controlled with conventional insulin treatment. Materials and methods: We retrospectively evaluated 138 patients with T2D who were switched from insulin to dulaglutide therapy. We excluded 20 patients who dropped out during the follow-up period. The participants were divided into two groups according to whether they resumed insulin treatment at 6 months after switching to a GLP-1 receptor agonist (group I) or not (group II). A multiple logistic regression analysis was performed to evaluate the parameters associated with the risk of resuming insulin after replacement with dulaglutide. Results: Of 118 patients initiated on the GLP-1 receptor agonist, 62 (53%) resumed insulin treatment (group I), and 53 (47%) continued with GLP-1 receptor agonists or switched to oral anti-hypoglycemic agents (group II). Older age, a higher insulin dose, and lower postprandial glucose levels while switching to the GLP-1 receptor agonist were associated with failure to switch to the GLP-1 receptor agonist from insulin. Conclusions: A considerable proportion of patients with T2D inadequately controlled with insulin treatment successfully switched to the GLP-1 receptor agonist. Younger age, a lower dose of insulin, and a higher baseline postprandial glucose level may be significant predictors of successful switching from insulin to GLP-1 receptor agonist therapy.

First Report of Enterocytozoon hepatopenaei Infection in Pacific Whiteleg Shrimp (Litopenaeus vannamei) Cultured in Korea.

The consumption of cultured crustaceans has been steadily increasing, and Pacific whiteleg shrimp (Litopenaeus vannamei) are major cultivated invertebrates worldwide. However, shrimp productivity faces a variety of challenges, mainly related to outbreaks of lethal or growth retardation-related diseases. In particular, hepatopancreatic microsporidiosis caused by the microsporidian parasite Enterocytozoon hepatopenaei (EHP) is an important disease associated with growth retardation in shrimp. Here, we report the detection of EHP through histopathological, molecular and electron microscopy methods in the hepatopancreas of Pacific whiteleg shrimp with growth disorder in a South Korean farm. Phylogenetic analysis showed a clade distinct from the previously reported EHP strains isolated in Thailand, India, China and Vietnam. An EHP infection was not associated with inflammatory responses such as hemocyte infiltration. Although EHP infection has been reported worldwide, this is the first report in the shrimp aquaculture in Korea. Therefore, an EHP infection should be managed and monitored regularly for effective disease control and prevention.

Correcting signal biases and detecting regulatory elements in STARR-seq data.

High-throughput reporter assays such as self-transcribing active regulatory region sequencing (STARR-seq) have made it possible to measure regulatory element activity across the entire human genome at once. The resulting data, however, present substantial analytical challenges. Here, we identify technical biases that explain most of the variance in STARR-seq data. We then develop a statistical model to correct those biases and to improve detection of regulatory elements. This approach substantially improves precision and recall over current methods, improves detection of both activating and repressive regulatory elements, and controls for false discoveries despite strong local correlations in signal.

Athlete-Specific Neural Strategies under Pressure: A fNIRS Pilot Study.

(1) Background: Stress and pressure during competition and training impair athletes' performance in sports. However, the influence of mental stress on the prefrontal cortex (PFC) functioning in an athlete during the visual simulation task is unknown. The purpose of this pilot study was to investigate hemodynamic responses during the visual-simulation task that induces pressure and stress using functional near-infrared spectroscopy. (2) Methods: Ten archers and ten non-athlete collegiate students performed a visual-simulation task. Participants' current stress levels were collected using a visual analog scale before and after the task. Average oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (HbT) levels and their variability (standard deviation (SD) HbO, SD HbR, and SD HbT) were computed to compare the neural efficiency between athlete and non-athlete. (3) Results: In general, both groups exhibited increased stress levels after the simulation task, and there was no group difference in overall average hemodynamic response from PFC and dorsolateral prefrontal cortex (DLPFC). While the average hemodynamic response level did not differ between groups, variability in hemodynamic responses from the archer group showed a more stable pattern than the non-athlete group. (4) Conclusion: Under this experimental setting, decreasing the variability in hemodynamic responses during the visual simulation, potentially via stabilizing the fluctuation of PFC, was characterized by the stress-related compensatory neural strategy of elite archers.

"Coach Really Knew What I Needed and Understood Me Well as a Person": Effective Communication Acts in Coach-Athlete Interactions among Korean Olympic Archers.

The purpose of this study is to qualitatively explore situations in which athletes perceived communication with their coach to be important and determine the effect of this communication on the athletes. Literature on the communication process in sports emphasizes the distinct characteristics of each sports and its setting. However, previous research has not studied various settings in detail, and archery is yet to be explored. The qualitative process included an in-depth, semi-structured interview with eight Olympic archers. Thematic analysis was used to interpret the data. Athletes perceived communication with coaches to be important during their performance, while dealing with psychological crises, and during their training. Our analysis suggests that, depending on the communicative actions, a coach may positively or negatively impact an athlete's self-awareness, self-confidence, anxiety, autonomy, and motivation. A noteworthy finding of this study is that archers perceive communication with coaches about the selection and management of equipment as important. This study emphasizes the critical role of an athlete's communication with the coach in various situations and discusses the theoretical and practical implications in the context of sports performance.

Distinct immunoreactivity pattern to Bacillus mannanilyticus in a subgroup of anti-NMDA receptor encephalitis.

Over half of anti-NMDA receptor encephalitis (NMDARE) is unrelated to etiologies such as teratomas or herpes simplex encephalitis. Bacillus mannanilyticus nonribosomal peptide synthetase (NRPS) shares a protein sequence with GluN1. After confirming the anti-NRPS antibody immunoreactivity in an index patient by liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 24/57 (42%) patients with similar immunoreactivity patterns by western blotting. These patients mostly (20/24 [83%]) did not have ovarian teratomas, had fewer medial temporal (2/24 [8%]) and any (5/24 [21%]) brain lesions and less pleocytosis (13/24 [54%]). These results identified an anti-NMDARE subgroup with a distinct immunoreactivity pattern, which needs further investigation.

Bayesian estimation of genetic regulatory effects in high-throughput reporter assays.

MOTIVATION: High-throughput reporter assays dramatically improve our ability to assign function to noncoding genetic variants, by measuring allelic effects on gene expression in the controlled setting of a reporter gene. Unlike genetic association tests, such assays are not confounded by linkage disequilibrium when loci are independently assayed. These methods can thus improve the identification of causal disease mutations. While work continues on improving experimental aspects of these assays, less effort has gone into developing methods for assessing the statistical significance of assay results, particularly in the case of rare variants captured from patient DNA. RESULTS: We describe a Bayesian hierarchical model, called Bayesian Inference of Regulatory Differences, which integrates prior information and explicitly accounts for variability between experimental replicates. The model produces substantially more accurate predictions than existing methods when allele frequencies are low, which is of clear advantage in the search for disease-causing variants in DNA captured from patient cohorts. Using the model, we demonstrate a clear tradeoff between variant sequencing coverage and numbers of biological replicates, and we show that the use of additional biological replicates decreases variance in estimates of effect size, due to the properties of the Poisson-binomial distribution. We also provide a power and sample size calculator, which facilitates decision making in experimental design parameters. AVAILABILITY AND IMPLEMENTATION: The software is freely available from www.geneprediction.org/bird. The experimental design web tool can be accessed at http://67.159.92.22:8080. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Relationship between Perceived Coaching Behaviors, Competitive Trait Anxiety, and Athlete Burnout: A Cross-Sectional Study.

Athletes possibly experience a great deal of stress which may cause anxiety and burnout. Athletes' perceptions of their coaches' behaviors influence their performance and psychological well-being. The purpose of this study is to investigate the relationship between athletes' perception of their coaches' coaching behaviors and burnout, and also to examine the medication effects of competitive trait anxiety on the relationship. A total of 368 collegiate athletes participated in the study, and their ages ranged from 20 to 26 years old (Mage = 21.21 years, SD = 1.07 years). A cross-sectional research design was employed to collect the data. Descriptive statistics and structural equation modeling are utilized to analyze the data. Trait anxiety in athletes had a significant correlation with athlete burnout as well as significant pathways. Controlling coaching behaviors were significantly related to athletes' competitive trait anxiety, whereas autonomy-supportive coaching behaviors were not significantly related to trait anxiety. A significant positive pathway from controlling coaching to trait anxiety was observed. The bootstrapping results indicated a significant and indirect pathway from controlling coaching to athlete burnout via competitive trait anxiety. Given that controlling coaching behaviors affected trait anxiety and, in turn, burnout, it is concluded that coaches should provide less controlling coaching to reduce anxiety and burnout in athletes.

Visual Scanning Behavior and Attention Strategies for Shooting Among Expert Versus Collegiate Korean Archers.

This study analyzed differences in visual scanning behavior and resistance to distractions between Olympic and collegiate archers. The experiment required the participants to watch a test film comprising six stages corresponding to the phases of an archery performance. The recording emulated the archer's point of view. During initial phases of shooting, Olympic archers demonstrated more frequent and longer fixations than did their collegiate counterparts, whereas during the later phases of shooting, the groups' visual scanning patterns did not differ significantly. In a second experiment within this study, auditory and visual distractors led Olympic archers to exhibit fewer fixations of longer duration and less eye movement, regardless of the type of distraction. Thus, in each experiment, Korean national-team archers modified their attentional strategies more efficiently than collegiate archers, expanding and narrowing their focused attention based on task demands. These findings provide fundamental information on the nature of expert shooters' visual scanning patterns and have implications for developing training protocols for aspiring athletes.

Red ginseng monograph.

Ginseng has been traditionally used for several millennia in Asian countries, including Korea, China, and Japan, not only as a nourishing and tonifying agent but also as a therapeutic agent for a variety of diseases. In recent years, the various effects of red ginseng including immunity improvement, fatigue relief, memory improvement, blood circulation improvement, antioxidation, mitigation of menopausal women's symptoms, and anticancer an effect have been reported in clinical as well as basic research. Around the world, there is a trend of the rising consumption of health functional foods on the level of disease prevention along with increased interest in maintaining health because of population aging and the awareness of lifestyle diseases and chronic diseases. Red ginseng occupies an important position as a health functional food. But till now, international ginseng monographs including those of the World Health Organization have been based on data on white ginseng and have mentioned red ginseng only partly. Therefore, the red ginseng monograph is needed for component of red ginseng, functionality certified as a health functional food in the Korea Food and Drug Administration, major efficacy, action mechanism, and safety. The present red ginseng monograph will contribute to providing accurate information on red ginseng to agencies, businesses, and consumers both in South Korea and abroad.

Association between thyroid hormones and the components of metabolic syndrome.

BACKGROUND: Thyroid hormones are known to have direct and indirect effects on metabolism. Individuals with metabolic syndrome, a disease that is growing in incidence at a rapid rate, are at higher risk for cardiovascular disease, diabetes, and cancer. The aim of this study was to identify whether significant correlations exist between thyroid hormone levels and components of the metabolic syndrome in the general population of Korea. METHODS: The data were collected from the sixth Korea National Health and Nutrition Examination Surveys from 2013 to 2015. A total of 1423 participants were tested for thyroid function. The analysis of variance and multiple linear regression were performed to analyze the relationship between thyroid hormone level and components of the metabolic syndrome. RESULTS: A positive association between free thyroxine and fasting glucose level was observed in patients with high free thyroxine levels (≥1.70 ng/dL, ß = 15.992, p = < 0.0001), when compared with patients with normal-middle free thyroxine levels. Moreover, a negative association was observed between free thyroxine and triglyceride levels in patients with normal-high free thyroxine levels (ß = - 21.145, p = 0.0054) and those with high free thyroxine levels (ß = - 49.713, p = 0.0404). CONCLUSION: Free thyroxine shows a partially positive association with fasting glucose and a partially negative association with triglycerides in the Korean population. In patients with abnormal thyroid function, follow up tests for glucose levels and lipid profiling during treatment for thyroid dysfunction would be beneficial in terms of overlooking metabolic syndrome and to prevent related diseases.

Depletion of nerve growth factor in chemotherapy-induced peripheral neuropathy associated with hematologic malignancies.

OBJECTIVE: To investigate whether the depletion of nerve growth factor (NGF) is associated with the development of chemotherapy-induced peripheral neuropathy (CIPN) in patients with hematologic malignancy. METHODS: We prospectively enrolled hematologic cancer patients who had a plan to receive bortezomib, thalidomide, or vincristine. Baseline NGF levels were measured within one week before the start date of chemotherapy. Follow-up NGF levels were measured after four months from the start date of chemotherapy or the date when CIPN was initially diagnosed. RESULTS: Baseline and follow-up NGF pairs were measured in 45 patients (male/female = 27/18, median age = 63 years old). CIPN has developed in 28 patients. In the CIPN group, the level of NGF was significantly decreased after chemotherapy compared to the baseline (△NGF = -3.52 ±5.72; p-value = 0.003), while the NGF level of the no-CIPN group was not changed after chemotherapy. The differences in △NGF levels between the CIPN and no-CIPN group were more profound when analyzed in the subgroup of newly diagnosed multiple myeloma patients (△NGF = -4.14 ± 4.87 pg/ml for the CIPN group and +2.52 ± 8.39 pg/ml for the no-CIPN group; p-value = 0.043). CONCLUSIONS: This study shows that the depletion of NGF occurs during the development of CIPN, suggesting pathogenesis based on the role of NGF and therapeutic implications.

Decoy peptide targeted to Toll-IL-1R domain inhibits LPS and TLR4-active metabolite morphine-3 glucuronide sensitization of sensory neurons.

Accumulating evidence indicates that Toll-like receptor (TLR) signaling adapter protein interactions with Toll/Interleukin-1 Receptor (TIR) domains present in sensory neurons may modulate neuropathic pain states. Following ligand interaction with TLRs, TIR serves to both initiate intracellular signaling and facilitate recruitment of signaling adapter proteins to the intracytoplasmic domain. Although TLR TIR is central to a number of TLR signaling cascades, its role in sensory neurons is poorly understood. In this study we investigated the degree to which TLR TIR decoy peptide modified to include a TAT sequence (Trans-Activator of Transcription gene in HIV; TAT-4BB) affected LPS-induced intracellular calcium flux and excitation in sensory neurons, and behavioral changes due to TLR4 active metabolite, morphine-3-glucuronide (M3G) exposure in vivo. TAT-4BB inhibited LPS-induced calcium changes in a majority of sensory neurons and decreased LPS-dependent neuronal excitability in small diameter neurons. Acute systemic administration of the TAT-4BB reversed M3G-induced tactile allodynia in a dose-dependent manner but did not affect motor activity, anxiety or responses to noxious thermal stimulus. These data suggest that targeting TLR TIR domains may provide novel pharmacological targets to reduce or reverse TLR4-dependent pain behavior in the rodent.

Recent omics technologies and their emerging applications for personalised medicine.

A major objective of 'omics' technologies is to understand genetic causality of complex traits of human diseases. High-throughput omics technologies and their application to medicine open up remarkable opportunities for realising optimised medical treatment for individuals. Because many major breakthrough and discoveries in this field have been driven by the development of new omics technologies, in this review, the authors aim to provide an in-depth description of their underlying principles as a foundation of developing another new omics technology, and to introduce their emerging applications for personalised medicine. The systems biology approach is then introduced as a future direction towards actionable personalised medicine.

Effect of Intravenous Ferric Carboxymaltose on Hemoglobin Response Among Patients With Acute Isovolemic Anemia Following Gastrectomy: The FAIRY Randomized Clinical Trial.

IMPORTANCE: Acute isovolemic anemia occurs when blood loss is replaced with fluid. It is often observed after surgery and negatively influences short-term and long-term outcomes. OBJECTIVE: To evaluate the efficacy and safety of ferric carboxymaltose to treat acute isovolemic anemia following gastrectomy. DESIGN, SETTING, AND PARTICIPANTS: The FAIRY trial was a patient-blinded, randomized, phase 3, placebo-controlled, 12-week study conducted between February 4, 2013, and December 15, 2015, in 7 centers across the Republic of Korea. Patients with a serum hemoglobin level of 7 g/dL to less than 10 g/dL at 5 to 7 days following radical gastrectomy were included. INTERVENTIONS: Patients were randomized to receive a 1-time or 2-time injection of 500 mg or 1000 mg of ferric carboxymaltose according to body weight (ferric carboxymaltose group, 228 patients) or normal saline (placebo group, 226 patients). MAIN OUTCOMES AND MEASURES: The primary end point was the number of hemoglobin responders, defined as a hemoglobin increase of 2 g/dL or more from baseline, a hemoglobin level of 11 g/dL or more, or both at week 12. Secondary end points included changes in hemoglobin, ferritin, and transferrin saturation levels over time, percentage of patients requiring alternative anemia management (oral iron, transfusion, or both), and quality of life at weeks 3 and 12. RESULTS: Among 454 patients who were randomized (mean age, 61.1 years; women, 54.8%; mean baseline hemoglobin level, 9.1 g/dL), 96.3% completed the trial. At week 12, the number of hemoglobin responders was significantly greater for ferric carboxymaltose vs placebo (92.2% [200 patients] for the ferric carboxymaltose group vs 54.0% [115 patients] for the placebo group; absolute difference, 38.2% [95% CI, 33.6%-42.8%]; P = .001). Compared with the placebo group, patients in the ferric carboxymaltose group experienced significantly greater improvements in serum ferritin level (week 12: 233.3 ng/mL for the ferric carboxymaltose group vs 53.4 ng/mL for the placebo group; absolute difference, 179.9 ng/mL [95% CI, 150.2-209.5]; P = .001) and transferrin saturation level (week 12: 35.0% for the ferric carboxymaltose group vs 19.3% for the placebo group; absolute difference, 15.7% [95% CI, 13.1%-18.3%]; P = .001); but there were no significant differences in quality of life. Patients in the ferric carboxymaltose group required less alternative anemia management than patients in the placebo group (1.4% for the ferric carboxymaltose group vs 6.9% for the placebo group; absolute difference, 5.5% [95% CI, 3.3%-7.6%]; P = .006). The total rate of adverse events was higher in the ferric carboxymaltose group (15 patients [6.8%], including injection site reactions [5 patients] and urticaria [5 patients]) than the placebo group (1 patient [0.4%]), but no severe adverse events were reported in either group. CONCLUSION AND RELEVANCE: Among adults with isovolemic anemia following radical gastrectomy, the use of ferric carboxymaltose compared with placebo was more likely to result in improved hemoglobin response at 12 weeks. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01725789.