The identification of effective tumor-suppressing neoantigens using a tumor-reactive TIL TCR-pMHC ternary complex.

Neoantigens are ideal targets for cancer immunotherapy because they are expressed de novo in tumor tissue but not in healthy tissue and are therefore recognized as foreign by the immune system. Advances in next-generation sequencing and bioinformatics technologies have enabled the quick identification and prediction of tumor-specific neoantigens; however, only a small fraction of predicted neoantigens are immunogenic. To improve the predictability of immunogenic neoantigens, we developed the in silico neoantigen prediction workflows VACINUSpMHC and VACINUSTCR: VACINUSpMHC incorporates physical binding between peptides and MHCs (pMHCs), and VACINUSTCR integrates T cell reactivity to the pMHC complex through deep learning-based pairing with T cell receptors (TCRs) of putative tumor-reactive CD8 tumor-infiltrating lymphocytes (TILs). We then validated our neoantigen prediction workflows both in vitro and in vivo in patients with hepatocellular carcinoma (HCC) and in a B16F10 mouse melanoma model. The predictive abilities of VACINUSpMHC and VACINUSTCR were confirmed in a validation cohort of 8 patients with HCC. Of a total of 118 neoantigen candidates predicted by VACINUSpMHC, 48 peptides were ultimately selected using VACINUSTCR. In vitro validation revealed that among the 48 predicted neoantigen candidates, 13 peptides were immunogenic. Assessment of the antitumor efficacy of the candidate neoepitopes using a VACINUSTCR in vivo mouse model suggested that vaccination with the predicted neoepitopes induced neoantigen-specific T cell responses and enabled the trafficking of neoantigen-specific CD8 + T cell clones into the tumor tissue, leading to tumor suppression. This study showed that the prediction of immunogenic neoantigens can be improved by integrating a tumor-reactive TIL TCR-pMHC ternary complex.

Impact of rumen cannulation surgery on rumen microbiota composition in Hanwoo steers.

Rumen cannulation is a surgical technique used to collect rumen contents from ruminants. However, rumen cannulation surgery may potentially impact the composition of the rumen microbiota. This study aimed to examine the longitudinal alterations in the rumen microbiota composition of Hanwoo steers after cannulation surgery. In this study, eight Hanwoo steers were used; four steers underwent rumen cannulation surgery (cannulation group), while the remaining four were left intact (control group). Rumen samples were collected from all eight steers using the stomach tubing method on the day before surgery (day 0) and on postoperative days 1, 4, 7, 10, 14, 17, 21, 24, and 28, resulting in 80 samples (10 timepoints × 8 animals). The microbiota of all 80 samples were analyzed using 16S rRNA gene amplicon sequencing with Quantitative Insights into Microbial Ecology version 2 (QIIME2). There were no significant differences (p > 0.05) in all major phyla and most major genera representing at least 0.5% of total sequences across all 80 samples between the control and cannulation groups on the preoperative and postoperative days. However, while the alpha diversity indices did not differ (p > 0.05) between the two groups on the preoperative day, they significantly differed (p < 0.05) between the two groups on the postoperative days. Further, the overall microbial distribution based on both unweighted and weighted principal coordinate analysis plots significantly differed (p < 0.05) between the two groups on both the preoperative and postoperative days. Orthogonal polynomial contrasts indicated that major genera and microbial diversity in the cannulation group decreased following surgery but returned to their initial states by postoperative day 28. In conclusion, this study demonstrates that rumen cannulation surgery affects some major taxa and microbial diversity, suggesting that the rumen cannulation method can alter the composition of rumen microbiota in Hanwoo steers.

Nickel-Catalyzed Hydrofluorination in Unactivated Alkenes: Regio- and Enantioselective C-F Bond Formation.

Catalytic formation of a regio- and enantioselective C-F bond chiral center from readily available alkenes is a crucial goal, yet it continues to pose significant challenges in organic synthesis. Here, we report the regioselective formation of C-F bonds facilitated by NiH catalysis and a coordination directing strategy that enables precise hydrofluorination of both terminal and internal alkenes. Notably, we have optimized this methodology to achieve high enantioselectivity in creating aliphatic C-F stereogenic centers especially with ß,γ-alkenyl substrates, using a tailored chiral Bn-BOx ligand. Another pivotal finding in our research is the identification of the (+)-nonlinear effect under optimized conditions, allowing for high enantioselectivity even with moderately enantiomerically enriched chiral ligands. Given the significant role of fluorine in pharmaceuticals and synthetic materials, this research offers essential insights into the regioselective and enantioselective formation of C-F bond chiral centers, paving the way for the efficient production of valuable fluorinated compounds.

Association between temporary employment and current smoking and change in smoking behaviors: A prospective cohort study from South Korea (2009-2018).

Background Previous studies have suggested that employment insecurity is associated with adverse health outcomes. We explored the association between temporary employment and smoking behaviors.Methods We analyzed 11,795 workers (51,867 observations) from the Korea Health Panel Study (2009-2018). Employment types were categorized as regular, fixed-term, or daily, based on the duration of labor contract. The outcomes were current smoking status and changes in smoking behavior (initiation or cessation) in the following year. Generalized estimating equations were used to estimate odds ratio (OR) and 95% confidence interval (CI).Results The proportions of fixed-term and daily workers were 41.2% and 16.4% for women and 23.6% and 12.4% for men, respectively. Temporary employment was associated with increased odds of current smoking, while also demonstrating prospective associations with changes in smoking behaviors. For instance, in prospective analyses, male workers with fixed-term and daily employments were associated with a decreased likelihood of smoking cessation (OR:0.77; 95% CI:0.65-0.91 for fixed-term employment and OR:0.66; 95% CI:0.52-0.83 for daily employment) in the following year compared to those with regular employment. Moreover, those experiencing consecutive temporary employment was most inversely associated with smoking cessation in both men (OR:0.56; 95% CI:0.44-0.71) and women (OR:0.37; 95% CI:0.16-0.85) compared to those experiencing consecutive regular employment. However, no clear association between temporary employment and smoking initiation was observed in both men and women.Conclusions Temporary employment is directly associated with current smoking and inversely associated with smoking cessation. Policies are needed to improve job insecurity among temporary employees.

Surgical Outcomes of Centrifugal Continuous-Flow Implantable Left Ventricular Assist Devices: Heartmate 3 versus Heartware Ventricular Assist Device.

Background: Left ventricular assist devices (LVADs) are widely employed as a therapeutic option for end-stage heart failure. We evaluated the outcomes associated with centrifugal-flow LVAD implantation, comparing 2 device models: the Heartmate 3 (HM3) and the Heartware Ventricular Assist Device (HVAD). Methods: Data were collected from patients who underwent LVAD implantation between June 1, 2015 and December 31, 2022. We analyzed overall survival, first rehospitalization, and early, late, and LVAD-related complications. Results: In total, 74 patients underwent LVAD implantation, with 42 receiving the HM3 and 32 the HVAD. A mild Interagency Registry for Mechanically Assisted Circulatory Support score was more common among HM3 than HVAD recipients (p=0.006), and patients receiving the HM3 exhibited lower rates of preoperative ventilator use (p=0.010) and extracorporeal membrane oxygenation (p=0.039). The overall early mortality rate was 5.4% (4 of 74 patients), with no significant difference between groups. Regarding early right ventricular (RV) failure, HM3 implantation was associated with a lower rate (13 of 42 [31.0%]) than HVAD implantation (18 of 32 [56.2%], p=0.051). The median rehospitalization-free period was longer for HM3 recipients (16.9 months) than HVAD recipients (5.3 months, p=0.013). Furthermore, HM3 recipients displayed a lower incidence of late hemorrhagic stroke (p=0.016). In the multivariable analysis, preoperative use of continuous renal replacement therapy (odds ratio, 22.31; p=0.002) was the only significant predictor of postoperative RV failure. Conclusion: The LVAD models (HM3 and HVAD) demonstrated comparable overall survival rates. However, the HM3 was associated with a lower risk of late hemorrhagic stroke.

Long-term results of atrial fibrillation surgery concomitant with mitral valve surgery: A propensity score-matched multicenter study.

OBJECTIVE: The aim of the study was to elucidate the long-term outcomes of atrial fibrillation surgery in patients with atrial fibrillation and mitral valve disease by comparing the patients who underwent mitral valve surgery with and without atrial fibrillation surgery. METHODS: Between 2005 and 2017, 2680 patients with atrial fibrillation who underwent mitral valve surgery (mitral valve surgery with atrial fibrillation surgery, n = 1841; mitral valve surgery without atrial fibrillation surgery, n = 839) at 5 centers were included. After propensity score matching, 1442 patients were extracted (atrial fibrillation surgery group, n = 721; non-atrial fibrillation surgery group, n = 721). All-cause mortality, cardiac mortality, major adverse cardiac and cerebrovascular events, stroke or transient ischemic attack, and permanent pacemaker implantation were compared between the atrial fibrillation surgery and non-atrial fibrillation surgery groups. RESULTS: Overall survivals at 5 and 10 years postoperatively were 91.0% and 80.7% in the atrial fibrillation surgery group and 86.5% and 75.9% in the non-atrial fibrillation surgery group, respectively (P = .013). Cardiac mortality-free survivals at 5 and 10 years postoperatively were 96.9% and 91.7% in the atrial fibrillation surgery group and 90.9% and 83.7% in the non-atrial fibrillation surgery group, respectively (P < .001). Cumulative incidence of reoperation, major adverse cardiac and cerebrovascular events, and stroke or transient ischemic attack was lower in the matched atrial fibrillation surgery group compared with the matched non-atrial fibrillation surgery group up to 15 years postoperatively (P = .010, P < .001, and P = .012, respectively). Cumulative incidence of permanent pacemaker implantation was higher in the matched atrial fibrillation surgery group compared with the matched non-atrial fibrillation surgery group (P < .001). CONCLUSIONS: In patients with atrial fibrillation and mitral valve disease, mitral valve surgery concomitant with atrial fibrillation surgery was associated with lower mortality, cardiac mortality, major adverse cardiac and cerebrovascular events, and stroke or transient ischemic attack up to 15 years after surgery when compared with mitral valve surgery without atrial fibrillation surgery.

Strategies to Minimize Sternal and Leg Wound Complications after Coronary Artery Bypass Grafting Using No-Touch Saphenous Vein Grafts.

PURPOSE: The aims of the present study were to examine sternal and saphenous vein (SV) harvest site wound complication rates, and to assess the strategies to minimize the sternal and leg wound complications after coronary artery bypass grafting using a no-touch (NT) SV. METHODS: Patients who underwent coronary artery bypass grafting (CABG) using internal thoracic artery (ITA) and/or NT SV grafts from March 2021 to June 2023 (N = 166) at a newly opened cardiac surgical program were included. We obeyed the current guidelines for the prevention of sternal wound infection. In addition, unilateral ITA was used in most of the patients and the sternal wound was meticulously closed using multiple sternal wires (≥7) and ZipFix. For the NT SV harvesting, the LigaSure device was used to minimize thermal injury, and the wound was meticulously closed. RESULTS: Sternal wound infections developed in 3/166 (1.8%) patients; all three patients showed superficial sternal wound infections. Leg wound complications were present in 2/153 (1.3%) patients, who recovered after secondary intention healing. CONCLUSION: Sternal wound complications after CABG could be minimized by the unilateral ITA usage, meticulous closure of the sternal wound in addition to compliance with the current guidelines. Wound complications after NT SV harvest may also be minimized by preoperative evaluation, careful harvesting, and meticulous wound closure.

Machine learning-based clinical decision support system for treatment recommendation and overall survival prediction of hepatocellular carcinoma: a multi-center study.

The treatment decisions for patients with hepatocellular carcinoma are determined by a wide range of factors, and there is a significant difference between the recommendations of widely used staging systems and the actual initial treatment choices. Herein, we propose a machine learning-based clinical decision support system suitable for use in multi-center settings. We collected data from nine institutions in South Korea for training and validation datasets. The internal and external datasets included 935 and 1750 patients, respectively. We developed a model with 20 clinical variables consisting of two stages: the first stage which recommends initial treatment using an ensemble voting machine, and the second stage, which predicts post-treatment survival using a random survival forest algorithm. We derived the first and second treatment options from the results with the highest and the second-highest probabilities given by the ensemble model and predicted their post-treatment survival. When only the first treatment option was accepted, the mean accuracy of treatment recommendation in the internal and external datasets was 67.27% and 55.34%, respectively. The accuracy increased to 87.27% and 86.06%, respectively, when the second option was included as the correct answer. Harrell's C index, integrated time-dependent AUC curve, and integrated Brier score of survival prediction in the internal and external datasets were 0.8381 and 0.7767, 91.89 and 86.48, 0.12, and 0.14, respectively. The proposed system can assist physicians by providing data-driven predictions for reference from other larger institutions or other physicians within the same institution when making treatment decisions.

Impact of inhalation exposure to cigarette smoke on the pathogenesis of pulmonary hypertension primed by monocrotaline in rats.

Extensive, long-term exposure to cigarette smoke (CS) was recently suggested to be a risk factor for pulmonary hypertension, although further validation is required. The vascular effects of CS share similarities with the etiology of pulmonary hypertension, including vascular inflammation and remodeling. Thus, we examined the influence of CS exposure on the pathogenesis of monocrotaline (MCT)-induced pulmonary hypertension, hypothesizing that smoking might accelerate the development of primed pulmonary hypertension. CS was generated from 3R4F reference cigarettes, and rats were exposed to CS by inhalation at total particulate matter concentrations of 100-300 µg/L for 4 h/day, 7 days/week for 4 weeks. Following 1 week of initial exposure, rats received 60 mg/kg MCT and were sacrificed and analyzed after an additional 3 weeks of exposure. MCT induced hypertrophy in pulmonary arterioles and increased the Fulton index, a measure of right ventricular hypertrophy. Additional CS exposure exacerbated arteriolar hypertrophy but did not further elevate the Fulton index. No significant alterations were observed in levels of endothelin-1 and vascular endothelial growth factor, or in hematological and serum biochemical parameters. Short-term inhalation exposure to CS exacerbated arteriolar hypertrophy in the lung, although this effect did not directly aggravate the overworked heart under the current experimental conditions.

Repeated intratracheal instillation of whole-cigarette smoke condensate to assess lung damage in a rat model.

Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.

Feasibility of fast, four-dimensional computed tomography-based O-ring LINAC plans for lung stereotactic body radiotherapy in patients with poor performance status.

Purpose: We aimed to retrospectively analyzed the feasibility of fast four-dimensional computed tomography (4DCT)-based O-ring LINAC treatment for patients with an average respiratory amplitude was< 0.5 cm and who cannot endure long treatment times due to poor performance status in lung 4D-stereotactic body radiotherapy (SBRT). Methods: This study included data of 38 patients who received lung 4D-SBRT and had average respiratory amplitude< 0.5 cm in the full phase. C-arm LINAC plans were based on 4DCT data obtained at phase values ranging from 20-70% using a C-arm LINAC. O-ring LINAC plans were retrospectively established based on 4DCT data obtained at phase values of 0-90% using an O-ring LINAC. The conformity index (CI), homogeneity index (HI), and gradient measurement of the planning target volumes (PTV) were analyzed to compare dosimetric data between C-arm LINAC and O-ring LINAC plans. Organs at risk were analyzed in accordance with the Radiation Therapy Oncology Group 0915 protocol. Treatment delivery time and total monitor units were analyzed to compare the efficiency of treatment delivery. Statistical comparisons were performed using the Wilcoxon signed-rank test (P< 0.05). Results: For the PTV, there was no significant difference in the CI or HI between C-arm LINAC and O-ring LINAC plans. For organs-at-risk, all plans met the criteria for dose constraint. There was a significant difference between C-arm LINAC and O-ring LINAC plans except in the spinal cord. Treatment delivery time was 92% longer for C-arm LINAC plans than for O-ring LINAC plans. The total MU value for C-arm LINAC plans was 9.6% higher than that for O-ring LINAC plans. Conclusion: We verified the feasibility of fast 4DCT-based O-ring LINAC treatment for patients with average respiratory amplitude< 0.5 cm and who cannot endure long treatment times due to poor performance status in lung 4D-SBRT.

Surgery-related anxiety regarding arthroscopic meniscectomy under general anesthesia: a retrospective observational study.

BACKGROUND: The prevalence of anxiety among patients undergoing arthroscopic surgery and its association with postoperative function has been well documented; however, the level of anxiety and anxiety-related characteristics remain unclear. As such, the present study investigated the characteristics of state anxiety in patients undergoing arthroscopic meniscectomy. METHODS: Data from 75 patients, who underwent arthroscopic partial meniscectomy under general anesthesia and completed an anxiety status questionnaire between April 2021 and March 2022, were retrospectively collected and reviewed. The State-Trait Anxiety Inventory (STAI)-X was used to measure state anxiety; a total score ≥ 52 was defined as clinically meaningful state anxiety. STAI score, main cause of preoperative anxiety, most anxious period, and most helpful factors for reducing perioperative anxiety were investigated. Patients were divided into 2 groups according to the main cause of preoperative anxiety; surgery or anesthesia (group I [n = 47]); and postoperative pain or rehabilitation (group II [n = 28]) Characteristics of state-anxiety between the two groups were compared using independent t-tests. RESULTS: The mean STAI score of the total population was 39.1 points (range, 20-60 points). The mean STAI score was significantly higher in group I than in group II (41.9 vs. 34.4 points, respectively; P < 0.001). The proportion of patients with clinically meaningful state anxiety was significantly higher in group I than in group II (23.4% vs. 3.6%, respectively, P = 0.02). Most patients (66.0% in group I and 50.0% in group II) responded that trust in medical staff was the most helpful factor in overcoming preoperative anxiety. In group I, 63.8% reported that the surgeon's explanation was the most helpful factor in reducing postoperative anxiety, whereas in group II, 71.4% reported that the natural course after surgery was the most helpful factor. CONCLUSIONS: Surgeons should be aware that anxiety related to arthroscopic meniscectomy differs according to patient characteristics, and a preoperative explanation of the postoperative process with the surgeon is important for patients who experience preoperative anxiety regarding anesthesia or the surgery itself.

Self-Esteem Trajectories After Occupational Injuries and Diseases and Their Relation to Changes in Subjective Health: Result From the Panel Study of Workers' Compensation Insurance (PSWCI).

BACKGROUND: Occupational injuries and diseases are life events that significantly impact an individuals' identity. In this study, we examined the trajectories of self-esteem among victims of occupational injury and disease and their relation to health. METHODS: The Panel Study of Workers' Compensation Insurance conducted annual follow-ups on workers who had experienced occupational injury or disease. A total of 2,000 participants, who had completed medical care, were followed from 2013 to 2017. Growth mixture modeling was utilized to identify latent classes in the self-esteem trajectory. Additionally, logistic regressions were conducted to explore the association between trajectory membership, baseline predictors, and outcomes. RESULTS: Three distinct trajectory classes were identified. Total 65.8% of the samples (n = 1,316) followed an increasing self-esteem trajectory, while 31.1% (n = 623) exhibited a constant trajectory, and 3.1% (n = 61) showed a decreasing trajectory. Individuals with an increasing trajectory were more likely to have a higher educational attainment (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.20-2.88), an absence of a moderate-to-severe disability rating (OR, 0.49; 95% CI, 0.25-0.96), no difficulty in daily living activities (OR, 0.81; 95% CI, 0.75-0.88), and were economically active (re-employed: OR, 2.46; 95% CI, 1.52-3.98; returned to original work: OR, 4.46; 9% CI, 2.65-7.50). Those with a decreasing self-esteem trajectory exhibited an increased risk of poor subjective health (OR, 1.89; 95% CI, 0.85-4.85 in 2013 to OR, 3.17; 95% CI, 1.04-13.81 in 2017), whereas individuals with an increasing trajectory showed a decreased risk (OR, 0.54; 95% CI, 0.43-0.68 in 2013 to OR, 0.44; 95% CI, 0.33-0.57 in 2017). CONCLUSION: Our findings emphasize the diversity of psychological responses to occupational injury or disease. Policymakers should implement interventions to enhance the self-esteem of victims.

Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse.

Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.

Epigenetic Regulation of the Expression of T Cell Stimulatory and Inhibitory Factors by Histone H3 Lysine Modification Enzymes and Its Prognostic Roles in Glioblastoma.

BACKGROUND: This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific co-stimulatory and co-inhibitory factors were investigated. METHODS: The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed. Immunohistochemical (IHC) staining for T cell co-stimulatory factors (CD27, CD28, CD137, OX40, and ICOS), T cell co-inhibitory factors (CTLA4, PD1, PD-L1, TIM3, and CD200R), and histone H3 lysine modification enzymes (MLL4, RIZ, EZH1, NSD2, KDM5c, JMJD1a, UTX, and JMJD5) was performed on archived paraffin-embedded tissues obtained by biopsy or resection. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed for specific factors, which demonstrated causal relationships, in order to validate the findings of the IHC examinations. RESULTS: The mean follow-up duration was 27.5 months (range, 4.1-43.5 months). During this period, 76 patients (90.5%) died, and the mean OS was 19.4 months (95% confidence interval, 16.3-20.9 months). Linear positive correlations were observed between the expression levels of CD28 and JMJD1a (R2 linear = 0.982) and those of CD137 and UTX (R2 linear = 1.528). Alternatively, significant negative correlations were observed between the expression levels of CTLA4 and RIZ (R2 linear = -1.746) and those of PD-L1 and EZH1 (R2 linear = -2.118); these relationships were confirmed by qRT-PCR. In the multivariate analysis, increased expression levels of CD28 (P = 0.042), and CD137 (P = 0.009), and decreased expression levels of CTLA4 (P = 0.003), PD-L1 (P = 0.020), and EZH1 (P = 0.040) were significantly associated with longer survival. CONCLUSION: These findings suggest that the expression of certain T cell co-stimulatory factors, such as CD28 and CD 137, and co-inhibitory factors, such as CTLA4 and PD-L1 are associated with prognosis of glioblastoma patients.

An integrated intelligent intersection control system for preventing rear-end and angled crashes: System design and deployment results.

In view of the dynamic all-red extension (DARE) system's effectiveness in preventing angled crashes (Park et al., 2018), this study has further enhanced its function to contend with rear-end collisions with dynamic green extension (DGE). With such a function, the enhanced Integrated Intelligent Intersection control system (III-CS) is capable of dynamically terminating the green at the interval of the lowest rear-end collision risk, so as to prevent undesirable "max-out" under actuated signal control which often traps some vehicles in the dilemma zone during high-volume traffic conditions. To ensure its effectiveness in practice, the proposed III-CS has been designed with the following new features: (i) executing the DGE within a customized time window of the green phase to ensure the signal's effective coordination with its neighboring intersections; (ii) adopting the comparison-based heuristic for the DGE's real-time risk prediction so as to circumvent the computing and communications delays. The results of two after-deployment assessments show that the system's DARE has perfectly detected all red-light runners; 66.7 percent of the decisions by the DGE module were observed to achieve the control objective during the first field assessment. The DGE's performance in making optimal decisions has improved over time and reached the level of 81.3% in the second field evaluation. Other measures of effectiveness, such as the number of vehicles trapped in the dilemma zone and the average deceleration rate of the driving populations approaching the target intersection, have also evolved to the anticipated trend after the deployment.

Association between job satisfaction and current smoking and change in smoking behavior: a 16-year longitudinal study in South Korea.

BACKGROUND AND AIMS: Previous studies have found that job satisfaction is closely associated with various health outcomes of workers. Our study measured the association between job satisfaction and current smoking and change in smoking behavior. DESIGN: Data from the longitudinal Korea Labor and Income Panel Study (KLIPS) that consist of nationally representative samples were used. The repeated measures analysis was conducted. SETTING: South Korea, 2005-2021. PARTICIPANTS: In total, 21 154 workers in Korea followed from 2005 to 2021 (145 120 observations) were included as study participants. MEASUREMENTS: The main predictor variable, job satisfaction, was assessed using a five-item general job satisfaction questionnaire. Job satisfaction was classified into 'dissatisfied', 'neutral' and 'satisfied', according to the tertiles of the sum of scores. The outcomes of interest were current smoking and initiation and cessation of smoking in the subsequent year. FINDINGS: Compared with those with a neutral level of job satisfaction, those who reported dissatisfaction with their job had an increased risk of smoking initiation [odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.01-1.22)]. Workers satisfied with their jobs were associated with a decreased likelihood of current smoking (OR = 0.96, 95% CI = 0.94-0.98) and smoking initiation (OR = 0.90, 95% CI = 0.81-0.99). There was a positive relationship between cumulative years of job dissatisfaction and smoking risk: > 4 years of experiencing job dissatisfaction was positively related to current smoking (OR = 1.14, 95% CI = 1.06-1.24) and smoking initiation (OR = 1.22, 95% CI = 1.00-1.49) and negatively related to smoking cessation (OR = 0.84, 95% CI = 0.72-0.99). CONCLUSIONS: In Korea, job dissatisfaction appears to be associated with an increased risk of smoking initiation.

Fully Automated Continuous Centrifugal Microfluidics Isolates Natural Killer Cells with High Performance and Minimal Stress.

Natural killer (NK) cells are a part of the innate immune system, providing the first line of defense against cancer cells and pathogens at an early stage. Hence, they are attracting attention as a valuable resource for allogeneic cell immunotherapy. However, NK cells exist with limited proportion in blood, and obtaining sufficient clinical-grade NK cells with highly viable and minimal stress is critical for successful immune cell therapy. Conventional purification methods via immunoaffinity or density gradient centrifugation had several limitations in yield, purity, and cellular stress, which might cause an increased risk for graft versus host disease and reduced efficacy due to NK cell malfunction, exhaustion, and apoptosis. Moreover, reducing the variations of isolation performance caused by the manual process is another unmet need for uniform quality of the living drug. Here, an automated system using an NK disc (NKD) based on continuous centrifugal microfluidics (CCM) technology was developed to isolate NK cells from whole blood with high yield, purity, reproducibility, and low stress. The CCM technology, which operates fluidic manipulation under disc rotation, enabled precise extraction of the ultra-thin target fluid layer generated by blood centrifugation. Compared to the conventional manual method, the CCM-NKD isolated NK cells with higher yield (recovery rate) and purity, while maintaining better reproducibility. Furthermore, since the CCM-NKD maintained substantially milder centrifugation conditions (120 ×g for 10 min) compared to the conventional approach (1200 ×g for 20 min), it showed reduced cellular stress and increased antioxidant capacity in the isolated NK cells. Based on the results, the CCM-NKD is expected to be a useful tool to provide highly intact and viable cell weapons for successful immune cell therapy.

First Report of Olive Mild Mosaic Virus in Imported Tulips (Tulipa gesneriana) in Korea.

Tulip cultivation in Korea primarily uses imported bulbs due to the absence of domestic production. To ensure safety and sustainability, Korean authorities have implemented strict phytosanitary measures for five viruses: arabis mosaic virus, tobacco necrosis virus, tobacco ringspot virus, tomato black ring virus, and tomato bushy stunt virus. In April 2021, 86 tulip plants presented symptoms such as chlorotic mottle, mosaic, streak, stripe, yellowing of the leaves, and color breaking on flowers. These samples were collected to investigate the incidence of viruses in four Korean provinces (Gangwon, Gyeongbuk, Gyeongnam, and Chungnam). The leaves and petals from each individual sample (10 mg each) were pooled and ground using liquid nitrogen. Total RNA was extracted using a Maxwell® 16 LEV Plant RNA Kit (Promega, Madison, USA). A cDNA library was constructed using TruSeq Standard Total RNA with Ribo - Zero (Illumina, San Diego, USA) and sequenced on an Illumina NovaSeq 6000 platform (Macrogen, Seoul, Korea) with 100-bp paired-end reads. Trinity software identified tulip breaking virus (TBV), tulip virus X (TVX), and lily symptomless virus (LSV), which are known to occur in Korea (Bak et al. 2023) by de novo assembly of 628 million reads into 498,795 contigs. The contigs were annotated as previously described (Bak et al. 2022). Moreover, a contig (ON758350) related to olive mild mosaic virus (OMMV; genus Alphanecrovirus, family Tombusviridae) was identified through BLASTn analysis. This contig had a 99.27% nucleotide (nt) identity to OMMV PPO-L190209 (KU641010), which was assembled from 201,346 reads and spanned 3,713 bp. To confirm the presence of OMMV, a primer pair (5'-GAATGTCTGGCGTTAAGCG-3'/5'-GTGTCCTGCGCATCATACAC-3') was designed to amplify a 797-bp fragment of the coat protein gene. In RT-PCR, 31.4% (27/86) of samples were positive for OMMV and coinfected with TBV or TBV+LSV. Coinfection with TBV led to chlorotic mottling and stripes, whereas triple coinfection with TBV+LSV produced distinct yellow streaks and mosaic within the lesion boundaries. In contrast, solely TBV infection did not produce such symptoms. The samples infected with OMMV were exclusively collected from Gangwon and Gyeongnam. In each province, an RT-PCR amplicon was cloned, and subsequently sequenced (Bioneer, Daejeon, Korea). The obtained sequences were named CC (OM243091) and GS (OM243092), and they shared 98.6% and 98.9% identity with PPO-L190209 (KU641010), respectively. A bioassay was conducted using a leaf infected with OMMV CC and TBV to inoculate 13 indicator species in triplicate, including Capsicum annuum, Chenopodium amaranticolor, C. quinoa, Cucumis sativus, Nicotiana benthamiana, N. clevelandii, N. glutinosa, N. occidentalis, N. rustica, N. tabacum, Solanum lycopersicum, Tetragonia tetragonioides, and Tulipa gesneriana. The RT-PCR revealed positivity only for OMMV in the upper leaves of N. clevelandii, while all other species were negative with no symptoms. To our knowledge, this is the first report of OMMV occurring in tulips grown from imported bulbs in Korea, with no other known natural hosts such as olive tree (Cardoso et al. 2004), spinach (Gratsia et al. 2012), and corn salad (Verdin et al. 2018). The Korean OMMV isolates exhibited a high nt identity with the foreign isolate, and the samples were collected from farms that rely entirely on bulb imports for cultivation. These suggest that the outbreak of OMMV was likely caused by imported bulbs.