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Background: With a growing understanding of biomechanical disadvantages following medial meniscus posterior root tear (MMPRT), recent studies have focused on surgical repair of MMPRT. Because not all tears are repairable, surgical indications can be properly established when the outcomes of conservative treatments are revealed. This study tried to identify risk factors for osteoarthritis progression after conservative treatments for isolated MMPRT., Materials & Methods: Patients who had conservative treatments for isolated MMPRT during 2013-2016 were retrospectively reviewed. To evaluate osteoarthritis progression, those who were followed up for ≤3 years and those who already showed advanced osteoarthritis of Kellgren--Lawrence (K-L) grade 4 at the time of diagnosis were excluded. Because patients with varus malalignment were candidates for realignment osteotomy, conservative treatments for MMPRT were applied to patients with well-aligned knees. Osteoarthritis progression was determined based on the K-L grading system, and risk factors including age, sex, body mass index, lower limb alignment, preoperative K-L grade, meniscal extrusion, and the presence of subchondral bone marrow lesion (BML) were analyzed using logistic regression analyses., Results: A total of 42 patients were followed up for 57.4 ± 26.8 months. During that period, osteoarthritis progression was noted in 17 (40.5%) patients. Based on univariate analyses for each risk factor, age, meniscal extrusion, and the presence of subchondral BML were included in the multivariate logistic regression analysis. The results showed that age ( p = 0.028, odds ratio = 0.87) and meniscal extrusion ( p = 0.013, odds ratio = 9.65) were significant risk factors. A receiver operating characteristic curve found that the cutoff age was 63.5 years, with the area under the curve being 0.72 (sensitivity, 68.0%; specificity, 70.6%)., Conclusions: About two-fifths of patients who had conservative treatments for MMPRT underwent osteoarthritis progression in the mid to long term. Age and meniscal extrusion were determining factors of osteoarthritis progression. The risk for osteoarthritis progression was decreased when the age of patients was over 63.5 years.

Orientation sensitivity is a fundamental property of the visual system, but not all orientations are created equal. For instance, radially oriented stimuli, aligned with a line intersecting the center of gaze, produce greater activity throughout the visual cortex and are associated with greater perceptual sensitivity compared with other orientations. Here, we discuss a robust visual illusion that is likely related to this preference. Using a continuous response measure, participants ( N = 36 adults) indicated the gap position in a peripheral Landolt C placed in one of eight orientations and eight locations along four meridians (vertical, horizontal, 45°, 135°). The error distributions revealed that the perceived gap was attracted toward the radial axis. For instance, the gap in a regular C would often be wrongly perceived as tilted 45° corresponding to the oblique meridian where it was placed. These findings demonstrate an unsuspected early-vision influence on the perceived orientation of an object.

The loss of vascular integrity is a cardinal feature of acute inflammatory responses evoked by activation of the TLR4 inflammatory cascade. Utilizing in vitro and in vivo models of inflammatory lung injury, we explored TLR4-mediated dysregulated signaling that results in the loss of endothelial cell (EC) barrier integrity and vascular permeability, focusing on Dock1 and Elmo1 complexes that are intimately involved in regulation of Rac1 GTPase activity, a well recognized modulator of vascular integrity. Marked reductions in Dock1 and Elmo1 expression was observed in lung tissues (porcine, rat, mouse) exposed to TLR4 ligand-mediated acute inflammatory lung injury (LPS, eNAMPT) in combination with injurious mechanical ventilation. Lung tissue levels of Dock1 and Elmo1 were preserved in animals receiving an eNAMPT-neutralizing mAb in conjunction with highly significant decreases in alveolar edema and lung injury severity, consistent with Dock1/Elmo1 as pathologic TLR4 targets directly involved in inflammation-mediated loss of vascular barrier integrity. In vitro studies determined that pharmacologic inhibition of Dock1-mediated activation of Rac1 (TBOPP) significantly exacerbated TLR4 agonist-induced EC barrier dysfunction (LPS, eNAMPT) and attenuated increases in EC barrier integrity elicited by barrier-enhancing ligands of the S1P1 receptor (sphingosine-1-phosphate, Tysiponate). The EC barrier-disrupting influence of Dock1 inhibition on S1PR1 barrier regulation occurred in concert with: 1) suppressed formation of EC barrier-enhancing lamellipodia, 2) altered nmMLCK-mediated MLC2 phosphorylation, and 3) upregulation of NOX4 expression and increased ROS. These studies indicate that Dock1 is essential for maintaining EC junctional integrity and is a critical target in TLR4-mediated inflammatory lung injury., Competing Interests: Declaration of competing interest Joe GN Garcia, MD is CEO and founder of Aqualung Therapeutics Corporation. All other authors declare no competing financial interests., (Copyright © 2022. Published by Elsevier B.V.)

Obesity by itself is a factor in the development of gallstone disease, and periods of weight loss after bariatric surgery further increase the risk of gallstone formation. In patients with obesity, hypersecretion of cholesterol may increase the risk of gallstone formation, which is approximately five-fold higher than that in the general population. The incidence of gallstone formation after bariatric surgery is 10-38% and often associated with a proportional increase in the risk of developing biliary complications. Routine postoperative administration of ursodeoxycholic acid (UDCA) is recommended to prevent gallstone formation. Several randomized trials have indicated that UDCA can effectively prevent gallstones and reduce the risk of cholecystectomy after bariatric procedures. The effective daily dose of UDCA in each study ranged from 500 to 1,200 mg, and it may be considered at least during the period of rapid weight loss (first 3-6 months postoperatively) to decrease the incidence of symptomatic gallstones., Competing Interests: Conflict of Interest: None of the authors have any conflict of interest., (Copyright © 2022, The Korean Society for Metabolic and Bariatric Surgery.)

The importance of probiotics in pig production is widely recognized. However, the precise role of probiotics in regulating the gut microbiota of piglets has not been assessed extensively. Therefore, we intend to examine whether suckling pigs ingesting with synthetic milk (SM) and probiotics along with mother milk has a carryover effect on its growth and gut health at the post-weaning stage. A total of 40 [Duroc× (Yorkshire× Landrace)] neonates with an initial BW of 1.49 ± 0.28 kg were assigned to one of two treatments groups: control (CON) and treatment (TRT). Control group piglets were nourished with synthetic milk, while TRT group piglets were nourished SM with (1 × 10 9 CFU/g) Lactobacillus sp. probiotics. The treatment group piglets showed higher ( p < 0.05) body weight and daily gain at week 3 than the CON group piglets. 16S metagenome sequencing showed average demultiplexed reads and denoised reads counts of 157,399 and 74,945, respectively. The total ASV taxonomy number classified with a confidence threshold > 70% (default) on sequence alignment with the SILVA v138 reference database was 4,474. During week 1, Escherichia-Shigella, Clostridium sensu stricto 1 , and Bacteroides were confirmed as the major dominant bacterial genera in both the groups at the genus level. However, during week 2, the relative proportion of Escherichia-Shigella, Clostridium sensu stricto 1 , and Proteobacteria was decreased, while that of Lactobacillus and Bacteroidota was increased in pigs receiving the probiotic supplement. During weeks 2 and 3, Firmicutes, Proteobacteria , and Bacteroidota phyla were dominant in both groups. During week 6, the relative proportion of Proteobacteria was slightly increased in both groups. Furthermore, Prevotella was confirmed as the major dominant bacterial genus in both groups during weeks 3 and 6. This study suggests that nourishing neonatal piglets with synthetic milk and Lactobacillus sp. probiotics from birth to 21 days would be beneficial to enhance the gut health of piglets and to overcome post-weaning mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sampath, Song, Jeong, Mun, Han and Kim.)

Background and Objectives: Previous studies regarding tranexamic acid (TXA) in total knee arthroplasty (TKA) investigated only symptomatic deep vein thrombosis (DVT), or did not include high risk patients. The incidence of DVT including both symptomatic and asymptomatic complications after applying topical TXA has not been evaluated using ultrasonography. Materials and Methods: The medical records of 510 patients who underwent primary unilateral TKA between July 2014 and December 2017 were retrospectively reviewed. Because TXA was routinely applied through the topical route, those who had a history of venous thromboembolism, myocardial infarction, or cerebral vascular occlusive disease, were not excluded. Regardless of symptom manifestation, DVT was examined at 1 week postoperatively for all patients using ultrasonography, and the postoperative transfusion rate was investigated. The study population was divided according to the use of topical TXA. After the two groups were matched based on the propensity scores, the incidence of DVT and the transfusion rate were compared between the groups. Results: Of the 510 patients, comprising 298 patients in the TXA group and 212 patients in the control group, DVT was noted in 22 (4.3%) patients. Two patients had DVT proximal to the popliteal vein. After propensity score matching (PSM), 168 patients were allocated to each group. In all, 11 patients in the TXA group and seven patients in the control group were diagnosed with DVT, which did not show a significant difference (p = 0.721). However, the two groups differ significantly in the transfusion rate (p < 0.001, 50.0% in the TXA group, 91.7% in the control group). Conclusions: The incidence of DVT, whether symptomatic or asymptomatic, was not affected by the use of topical TXA. The postoperative transfusion rate was reduced in the TXA group. Topical TXA could be applied safely even in patients who had been known to be at high risk.

Background: The prevalence of dry eye, which is a common lacrimal disease, is steadily increasing in modern society. However, fundamental treatment for it has not yet been established. This study aims to assess the efficacy and safety of a novel medical device, the biodegradable microneedle acupuncture (BMA), using a traditional intradermal acupuncture needle as the control acupuncture for dry eye., Method: This study will be an investigator-initiated, assessor-blinded, comparative, superiority pilot randomized controlled trial. A total of 30 patients with dry eye will be randomly assigned to the experimental or the control group in equal proportion. For the experimental group, the BMA will be applied to both sides of 5 acupoints including BL2, GB14, TE23, EX-HN5, and ST1. For the control group, conventional intradermal acupuncture will be applied to the same acupoints. The needles will be attached for 4 hours. Over 4 weeks, both the interventions will be performed 12 times in total. The primary outcome would be the ocular surface disease index. The secondary outcomes would be the visual analog scale for subjective symptoms, quality of life, Schirmer I test, and general assessment., Discussion: The findings of this study on the efficacy and safety of the BMA would be helpful for patients with dry eye in clinical practice. Further, these results would provide for the foundation of a large-scale BMA study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This Mendelian randomization (MR) study aimed to investigate the causal relationship between osteoarthritis (OA) and cardiovascular disease (CVD)., Methods: From a genome-wide association study of European ancestry, we selected single nucleotide polymorphisms for two types of OA, knee osteoarthritis (KOA) and hip osteoarthritis (HOA), as instrumental variables. We evaluated three types of CVD: coronary heart disease (CHD), heart failure (HF), and stroke. We used the traditional inverse variance weighting (IVW) method and other methods to estimate causality. Heterogeneity and sensitivity tests were also applied. Finally, we conducted a MR analysis in the opposite direction to investigate reverse causality., Results: IVW analysis showed that HOA significantly affected the incidence of HF [odds ratio (OR): 1.0675; 95% confidence interval (CI): 0.0182-0.1125, P = 0.0066]. HOA significantly affected the incidence of stroke (OR: 1.1368; 95% CI: 1.0739-1.2033, P = 9.9488e-06). CHD could dramatically affect the incidence of KOA (OR: 0.9011; 95% CI: 0.8442-0.9619, P = 0.0018). The rest of the results were negative., Conclusions: Our results revealed a potential causal relationship between HOA and risk of HF, and a potential causal relationship between HOA and risk of stroke. Our findings also suggested that CHD has a significant causal relationship with the risk of KOA. This paper may provide new ideas for the treatment of OA and CVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Kang, Xu, Zhang, Song, Wang, Yuan, Lee, Zhang, Wang, Sun and Fan.)

Background: Workers in logistics centers are always pressed for time to collect and pack products. They also participate in high-intensity manual labor in which various musculoskeletal hazards exist. In the case of logistic center labor, it is estimated that there is a high risk of presenteeism due to the above characteristics which can cause deterioration of workers' mental health. However, there is insufficient research on this topic., Methods: Workers in a logistic center were surveyed using an Internet questionnaire. The survey items included demographic characteristics, labor intensity and work-related factors, and mental health aspects such as depression and anxiety. The survey was conducted for about a month from July 26, 2021 and a total of 353 people were analyzed. Through the χ 2 test and t-test, the characteristics of workers who experienced presenteeism were examined and the prevalence ratios (PRs) of depression and anxiety experiences were calculated by multivariable Poisson regression. Afterwards, stratification analysis considering gender, the type of contract, and labor intensity was implemented., Results: In the group that experienced presenteeism, the number of working days per week was higher and fixed-term workers, high labor intensity, and sleep deprivation were more common. In the multi-Poisson regression analysis conducted by adjusting the demographic characteristics, working hours, and work-related factors, the PRs of depression and anxiety were 1.98 (95% confidence interval: 1.24-3.18) and 1.81 (1.22-2.68), respectively. In particular, the p -value for interactions was significant when stratified with the type of contract., Conclusions: As a result of the study, presenteeism and mental health were associated in logistic center workers. To prevent mental health issues of logistic center workers, management of presenteeism is necessary and a prospective study is needed., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2022 Korean Society of Occupational & Environmental Medicine.)

Reinforced concrete (RC) structures with non-seismic reinforcement details are vulnerable to earthquakes. This experimental study evaluates the efficiency of three techniques to alleviate the dynamic responses of existing structures: glass fiber-reinforced polyurea (GFRPU) reinforcement, a lever-typed tuned mass damper (LTMD) system, and a hybrid system of GFRPU and LTMD reinforcements. The lateral-resisting capacity and ductility of the GFRPU reinforcement specimen were enhanced by the material characteristics, and the dynamic responses were alleviated. The LTMD control specimen controlled the dynamic responses by the passive control system of the tuned mass damper (TMD), and the control forces to sustain its geometric motion were exerted on the specimen. The hybrid system was designed to control the dynamic responses by the GFRPU reinforcement and the LTMD control system. Four specimens, including an unreinforced specimen, were tested under external excitations, including the El Centro earthquake. The vibrations were more controlled in the order of the GFRPU reinforcement specimen, the LTMD control specimen, and the hybrid control specimen. The hybrid system was evaluated as excellent for seismic reinforcement, such as preventing abrupt failure with the lateral-resisting capacity and ductility of GFRPU and improving the dynamic control capacity by LTMD.

Background: Whether lateral hinge fracture (LHF) after open-wedge high tibial osteotomy (OWHTO) is associated with the change in tibial posterior slope (PS) has not been determined. Risk factors for PS increase are still unknown., Hypothesis: There will be no difference in patient characteristics and radiographic factors when stratified by change in tibial PS (ΔPS)., Study Design: Cohort study; Level of evidence, 3., Methods: We reviewed the records of 148 patients who underwent OWHTO with locking-plate fixation from 2010 to 2016. Included were those with a minimum 2-year follow-up and true lateral radiographs before and at 1 year after surgery. ΔPS was defined as a difference between preoperative and 1-year postoperative PS, with positive values indicating PS increase. ΔPS was classified into <3°, 3° to <6°, and ≥6°. Any LHFs were grouped by Takeuchi classification as stable (type 1) or unstable (types 2 and 3). Risk factors for PS increase were evaluated using ordinal logistic regression analyses. Clinical outcomes according to ΔPS were evaluated using the Hospital for Special Surgery score., Results: There were 79 (53.4%) patients with ΔPS <3°, 44 (29.7%) with 3° ≤ ΔPS < 6°, and 25 (16.9%) with ΔPS ≥6°. LHFs were observed in 41 (27.7%) patients: 32 with type 1 and 7 and 2 with types 2 and 3, respectively. Results of the multivariate ordinal logistic regression analysis indicated that ΔPS was associated with unstable LHF ( P = .005, exp[β] = 6.34), preoperative PS ( P = .028, exp[β] = 0.90), and correction angle ( P = .037, exp[β] = 1.09). ΔPS ≥6° was seen in 4 of 9 (44.4%) patients with unstable LHF, 9 of 32 (28.1%) with stable LHF, and 12 of 107 (11.2%) with no LHF ( P = .017). The mean correction angle was 11.3° ± 3.6° in patients with ΔPS ≥6°, 9.4° ± 4.6° in cases of 3° ≤ ΔPS < 6°, and 8.8° ± 3.6° in cases of ΔPS <3° ( P = .019). Hospital for Special Surgery scores did not differ according to ΔPS., Conclusion: LHF type and correction angle were associated with ΔPS after OWHTO, and unstable LHF and large correction angle were risk factors for PS increase. There was no significant difference in clinical outcomes according to ΔPS., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Children diagnosed with attention deficit hyperactivity disorder (ADHD) require early intervention and sustained treatment. This study used a game-based digital treatment planning NeuroWorld DTx to analyze the impact on attention and cognitive function in children with ADHD. Thirty children diagnosed with ADHD were recruited and subjected to a four-week NeuroWorld DTx digital treatment. To assess the impact of the digital therapeutic therapy on children's attention, we used the comprehension attention test (CAT) and Korean ADHD Rating Scale (K-ARS). Clinical global impression (CGI) and the Korean-child behavior checklist (K-CBCL 6-18) were used to examine the degree of improvement in ADHD. After four weeks, significant differences in the sensitivity and response style indices were noted, as compared with the baseline in the CAT test; in the case of K-ARS and CGI, a moderate decrease in ADHD was confirmed. The study achieved better results for the "total behavior problems" belonging to the K-CBCL assessment. Game-based digital therapy intervention can be a treatment method that elicits interest and satisfaction in children with ADHD and can be used as an adjunct to drug therapy to improve the quality of life and strengthen attention in children with symptoms of ADHD.

Background: Clonorchis sinensis requires bile acid transporters as this fluke inhabits bile juice-filled biliary ducts, which provide an extreme environment. Clonorchis sinensis sodium-bile acid co-transporter (CsSBAT) is indispensable for the fluke's survival in the final host, as it circulates taurocholate and prevents bile toxicity in the fluke; hence, it is recognized as a useful drug target., Methodology and Principal Findings: In the present study, using structure-based virtual screening approach, we presented inhibitor candidates targeting a bile acid-binding pocket of CsSBAT. CsSBAT models were built using tertiary structure modeling based on a bile acid transporter template (PDB ID: 3zuy and 4n7x) and were applied into AutoDock Vina for competitive docking simulation. First, potential compounds were identified from PubChem (holding more than 100,000 compounds) by applying three criteria: i) interacting more favorably with CsSBAT than with a human homolog, ii) intimate interaction to the inward- and outward-facing conformational states, iii) binding with CsSBAT preferably to natural bile acids. Second, two compounds were identified following the Lipinski's rule of five. Third, other two compounds of molecular weight higher than 500 Da (Mr > 500 Da) were presumed to efficiently block the transporter via a feasible rational screening strategy. Of these candidates, compound 9806452 exhibited the least hepatotoxicity that may enhance drug-likeness properties., Conclusions: It is proposed that compound 9806452 act as a potential inhibitor toward CsSBAT and further studies are warranted for drug development process against clonorchiasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Yoo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the development of wearable devices and soft electronics, the demand for stretchable piezoelectric energy harvesters (SPEHs) has increased. Energy harvesting can provide energy when large batteries or power sources cannot be employed, and stretchability provides a user-friendly experience. However, the performance of SPEHs remains low, which limits their application. In this study, a wearable SPEH is developed by adopting a kirigami structure on a polyvinylidene fluoride film. The performance of the SPEH is improved by rearranging the stress distribution throughout the film. This is conducted using two approaches: topological depolarization, which eliminates the opposite charge generation by thermal treatment, and optimization of the neutral axis, which maximizes the stress applied at the surface of the piezoelectric film. The SPEH performance is experimentally measured and compared with that of existing SPEHs. Using these two approaches, the stress was rearranged in both the x-y plane and z-direction, and the output voltage increased by 21.57% compared with that of the original film with the same stretching motion. The generated energy harvester was successfully applied to smart transmittance-changing contact lenses., (© 2022. The Author(s).)

Although effort required to complete spirometry is known to differ by age, no studies have addressed this issue. The present study aimed to identify the difference in the effort required to complete spirometry by age in children and adolescents. Data from 707 children (mean age, 10.2 years; range, 4-25 years) from 6 medical centers were analyzed. In addition to demographics, we obtained information on the time required for as well as the number of demonstrations and spirometry demonstrations and trials from the patients' electronic medical records. A total of 398 (56.3%) male participants were included, and 300 (42.4%) participants had no prior experience receiving spirometry. The mean time required for spirometry demonstration was 2.7 minutes (standard deviation [SD], 2.1 minutes), whereas that for spirometry trial was 5.9 minutes (SD, 5.1 minutes). The total mean time required for spirometry was 8.6 minutes (SD, 6.5 minutes). Significant negative associations were observed between age and effort required to complete spirometry with respect to the time and number of demonstrations and trials. The results of the present study suggest that age may affect the degree of effort required to complete spirometry, with a pattern of increasing effort with decreasing age. This finding provides important evidence for the establishment of health care policies especially regarding lung diseases that can benefit from spirometry., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Endoscopic submucosal dissection (ESD) application for patients with tumors beyond the expanded indication for ESD is inconclusive. This study aimed to identify the preoperative clinical features that can be curatively treated with ESD in patients with early gastric cancer (EGC) beyond the indication of ESD., Methods: From 2006 to 2016, 673 patients who underwent gastrectomy for EGC beyond the expanded indication for ESD based on preoperative assessments were retrospectively reviewed. We identified tumors curatively resected by ESD based on the postoperative pathologic findings. We also analyzed the clinical and pre-treatment features to determine the risk factors associated with curative resection of ESD., Results: 39% of the patients (263/673) who had undergone gastrectomy had tumors of endoscopic curability A or B (eCuraA/B) that could be treated by ESD alone. In multivariate analysis, tumor size ≤ 10 mm (OR 0.240; 95% CI = 0.12-0.46), no ulceration (OR 0.500; 95% CI = 0.29-0.87), differentiated histology (OR 0.599; 95% CI = 0.43-0.84), and location in the distal two-thirds of the stomach (OR 0.499; 95% CI = 0.28-0.88) in pre-treatment assessment were identified as independent predictors of eCuraA/B. Considering the risk factors, 63.6% (7/11)/61.3% (19/31) of patients with a differentiated/undifferentiated tumor size ≤ 10 mm located in distal two-third of the stomach without ulceration were deemed as eCuraA/B., Conclusions: This study suggests that patients with EGC indicated for surgery can be treated by ESD by adding tumor locations in the indication for ESD. Thus, ESD can be applied for patients with a tumor size ≤ 10 mm located in the lower/middle stomach without ulceration., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rice false smut caused by the filamentous fungus Ustilaginoidea virens is a devastating grain disease in rice. Fungicides have been an important measure for the control of this disease. In this study, baseline sensitivities of 179 isolates of U. virens to the quinone outside inhibitor (QoI) fungicides azoxystrobin and pyraclostrobin were established. The distribution of the 50% effective concentration (EC 50 ) values of each fungicide was unimodal. The frequency distribution of logarithmically transformed EC 50 values fit or fit closer to a normal distribution. The ranges of EC 50 values for azoxystrobin and pyraclostrobin were 0.001 to 0.864 and 0.001 to 0.569 μg/ml, with means and standard errors of the mean values of 0.203 ± 0.012 and 0.079 ± 0.006 μg/ml, respectively. There was a statistically significant and moderately positive correlation ( n = 100, r = 0.469, P = 0.001) in sensitivity between these two fungicides. No cross-resistance was found between azoxystrobin, pyraclostrobin, and carbendazim or sterol demethylation inhibitor fungicides. Each fungicide had a significantly higher mean preventive efficacy compared with its curative efficacy. Field assays showed that the control efficacy of pyraclostrobin against rice false smut was greater than that of azoxystrobin. Pyraclostrobin had the best control of rice false smut in three rice varieties, with the control efficacy ranging from 81.5 to 95.5%, whereas azoxystrobin decreased the disease index by 64.1 to 69.2% under the same conditions. These results provide us a reference point in the management of U. virens and future QoI fungicide resistance monitoring programs.

BACKGROUND. Washout CT is commonly used to evaluate indeterminate adrenal nodules, although its diagnostic performance is poorly established in true adrenal incidentalomas. OBJECTIVE. The purpose of this study was to compare, in patients without a known malignancy history, the prevalence of malignancy for incidental adrenal nodules with unenhanced attenuation more than 10 HU that do and do not show absolute washout of 60% or more, thereby determining the diagnostic performance of washout CT for differentiating benign from malignant incidental adrenal nodules. METHODS. This retrospective six-institution study included 299 patients (mean age, 57.3 years; 180 women, 119 men) without known malignancy or suspicion for functioning adrenal tumor who underwent washout CT, which showed a total of 336 adrenal nodules with a short-axis diameter of 1 cm or more, homogeneity, and unenhanced attenuation over 10 HU. The date of the first CT ranged across institutions from November 1, 2003, to January 1, 2017. Washout was determined for all nodules. Reference standard was pathology ( n = 54), imaging follow-up (≥ 1 year) ( n = 269), or clinical follow-up (≥ 5 years) ( n = 13). RESULTS. Prevalence of malignancy among all nodules, nodules less than 4 cm, and nodules 4 cm or more was 1.5% (5/336; 95% CI, 0.5-3.4%), 0.3% (1/317; 95% CI, 0.0-1.7%), and 21.1% (4/19; 95% CI, 6.1-45.6%), respectively. Prevalence of malignancy was not significantly different for nodules smaller than 4 cm with (0% [0/241]; 95% CI, 0.0-1.2%) and without (1.3% [1/76]; 95% CI, 0.0-7.1%) washout of 60% or more ( p = .08) or for nodules 4 cm or larger with (16.7% [1/6]; 95% CI, 0.4-64.1%) and without (23.1% [3/13]; 95% CI, 5.0-53.8%) washout of 60% or more ( p = .75). Washout of 60% or more was observed in 75.5% (243/322; 95% CI, 70.4-80.1%) of benign nodules (excluding pheochromocytomas), 20.0% (1/5; 95% CI, 0.5-71.6%) of malignant nodules, and 33.3% (3/9; 95% CI, 7.5-70.1%) of pheochromocytomas. For differentiating benign nodules from malignant nodules and pheochromocytomas, washout of 60% or more had 77.5% sensitivity, 70.0% specificity, 98.8% PPV, and 9.2% NPV among nodules smaller than 4 cm. CONCLUSION. Prevalence of malignancy is low among incidental homogeneous adrenal nodules smaller than 4 cm with unenhanced attenuation more than 10 HU and does not significantly differ between those with and without washout of 60% or more; wash-out of 60% or more has suboptimal performance for characterizing nodules as benign. CLINICAL IMPACT. Washout CT has limited utility in evaluating incidental adrenal nodules in patients without known malignancy.

Gastrectomy is the main treatment option for gastric cancer patients. Laparoscopic approach has become popular as an alternative to open method during the last decades, and clinical trials have revealed safety and feasibility in the short- and long-term outcomes of laparoscopic gastrectomy. The aim of this review is to summarize the results of prospective clinical trials and propose future perspectives for laparoscopic gastrectomy., (Copyright ©2022 Chinese Journal of Cancer Research. All rights reserved.)

Background: The aim of this study was to investigate whether the use of three-dimensional (3-D) computed tomography (CT)-based head-lesser trochanter distance (HLD) could reduce leg length discrepancy (LLD) more than the use of a two-dimensional (2-D) plain film method in primary bipolar hemiarthroplasty. Methods: Propensity score matching (PSM) analysis was used to adjust the confounding factors. A retrospective comparative analysis of 128 patients was performed. In the control group, the leg length was equalized using the 2-D, plain film-based HLD. In the study group, primary bipolar hemiarthroplasty was performed using the 3-D CT-based HLD method. Postoperative LLDs were compared between the two groups using the method of Ranawat. In addition, the Harris hip score (HHS) was evaluated and compared at one year after surgery. Results: A significant difference was observed in mean postoperative LLD between the 2-D HLD group and the 3-D CT HLD group: 1.6 ± 1.2 mm (range, 0.1−6.0 mm) and 1.1 ± 1.2 mm (range, 0.1−5.1 mm), respectively (p < 0.05). Additionally, a higher percentage of patients in the 3-D CT HLD group had an LLD of less than 2 mm. The mean HHS at one year after surgery showed no significant difference between the two groups. Conclusions: To minimize the occurrence of LLD, HLD measurement from a CT scanner may be more accurate than an X-ray. The 2-D and 3-D HLD differences in the 3-D CT HLD group were statistically significant. Using a 3-D, CT-based HLD method might decrease the possibility of an LLD over 2 mm.

The present study was aimed to investigate the effects of circRNA-0028171 on the apoptosis of vascular endothelial cells induced by arsenic trioxide (As 2 O 3 ). Human umbilical vein endothelial cells (HUVECs) were treated with 0-15 μmol/L As 2 O 3 for 24 h. Then, cellular viability was measured by MTT assay. The expression levels of circRNA-0028171, Bcl-2 and Bax mRNA were detected by real-time quantitative PCR. Bcl-2/Bax protein ratio was detected by Western blot. Whether circRNA-0028171 was involved in the regulation of HUVECs by As 2 O 3 was investigated by transfection with overexpression plasmid of circRNA-0028171 and siRNA. The results showed that compared with the control group, As 2 O 3 group showed decreased cellular viability, reduced Bcl-2/Bax mRNA and protein ratios, and significantly lower expression of circRNA-0028171. Overexpression of circRNA-0028171 inhibited apoptosis of HUVECs induced by As 2 O 3 . Knockdown of circRNA-0028171 by siRNA promoted As 2 O 3 -induced apoptosis in HUVECs. These results suggest that circRNA-0028171 is involved in the vascular endothelial cell apoptosis induced by As 2 O 3 .

(1) Background: The medial meniscus horizontal tear (MMHT) is known as a lesion that can be treated nonoperatively. However, some patients show persistent pain despite conservative treatments. In arthroscopic surgery for MMHT, surgeons often encounter unexpected unstable flaps, which can explain the intractable pain. This study aimed to determine whether preoperative factors could predict the hidden unstable flaps in MMHT. (2) Materials and Methods: Medical records of 65 patients who underwent arthroscopic partial meniscectomy (APM) for isolated MMHT during 2016-2020 were retrospectively reviewed. APM was indicated when there was no severe chondral degeneration and intractable localized knee pain in the medial compartment did not resolve despite conservative treatments. Unstable flap was confirmed based on arthroscopic images and operation notes. Each of the following preoperative factors were investigated using logistic regression analyses to determine whether they can predict an unstable flap: age, sex, body mass index, lower limb alignment, trauma history, mechanical symptoms, symptom duration, visual analogue scale (VAS), Lysholm score, cartilage wear of the medial compartment, and subchondral bone marrow lesion (BML). (3) Results: Hidden unstable flaps were noted in 45 (69.2%) patients. Based on univariate analyses for each preoperative factor, age, symptom duration, cartilage wear (of the femoral condyle and the tibial plateau), and subchondral BML were included in the multivariate logistic regression analysis. The results showed that symptom duration ( p = 0.026, odds ratio = 0.99) and high-grade cartilage wear of the medial femoral condyle ( p = 0.017, odds ratio = 0.06) were negatively associated with unstable flaps. A receiver operating characteristic curve was used to calculate the symptom duration at which the prediction of unstable flaps was maximized, and the cutoff point was 14.0 months. (4) Conclusions: More than two thirds of patients suffering intractable pain from MMHT had hidden unstable flaps. However, APM should not be considered when the symptom duration is more than 14 months or high-grade cartilage wear of the medial femoral condyle is noted.

This study quantitatively analyzed the gain of the six-dimensional (6D) cone-beam CT (CBCT) correction method compared with the conventional set-up method in 60 patients who underwent radiation treatment of head and neck and brain tumors. The correction gain of CBCT was calculated for the translational and rotational motion components separately and in combination to evaluate the individual and overall effects of these motion components. Using a statistical simulation mimicking the actual set-up correction process, the effective gain of periodic CBCT correction during the entire treatment fraction was analyzed by target size and CBCT correction period under two different correction scenarios: translation alone and full 6D corrections. From the analyses performed in this study, the gain of CBCT correction was quantitatively determined for each situation, and the appropriate CBCT correction strategy was suggested based on treatment purpose and target size., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hoon Sik Choi et al.)

As a novel cell type from eight-cell-stage embryos, extended pluripotent stem cells (EPSCs) are known for diverse differentiation potency in both extraembryonic and embryonic lineages, suggesting new possibilities as a developmental research model. Although various features of EPSCs have been defined, their ability to directly transfer extended pluripotency to differentiated somatic cells by cell fusion remains to be elucidated. Here, we derived EPSCs from eight-cell mouse embryos and confirmed their extended pluripotency at the molecular level and extraembryonic differentiation ability. Then, they were fused with OG2 +/- ROSA +/- neural stem cells (NSCs) by the polyethylene-glycol (PEG)-mediated method and further analyzed. The resulting fused hybrid cells exhibited pluripotential markers with upregulated EPSC-specific gene expression. Furthermore, the hybrid cells contributed to the extraembryonic and embryonic lineages in vivo and in vitro. RNA sequencing analysis confirmed that the hybrid cells showed distinct global expression patterns resembling EPSCs without parental expression of NSC markers, indicating the complete acquisition of extended pluripotency and the erasure of the somatic memory of NSCs. Furthermore, ultrastructural observation and metabolic analysis confirmed that the hybrid cells rearranged the mitochondrial morphology and bivalent metabolic profile to those of EPSCs. In conclusion, the extended pluripotency of EPSCs could be transferred to somatic cells through fusion-induced reprogramming.

The VOCs and metabolites in urine for exposed VOCs were evaluated for firefighters who participated in the actual fire fighting to determine whether firefighters were exposed to hazardous chemicals, which is the basic data on cancer risk of firefighters. When the fire extinguishing time is long, the concentration of benzene, PHEMA, and toluene among VOCs and metabolites in the case of fire suppression, rescue, and fire investigation work, which is estimated that the exposure of hazardous substances generated from the fire site at the time of fire suppression was large, significantly increased. In the case where the number of urination is 2 or less, the concentration of TZCA, toluene, and benzene among VOCs and metabolites was significantly increased compared to the number of urinating more than 2 times. In the concentration of VOCs and metabolites in urine corrected with creatinine, the concentrations of toluene and PHEMA in urine were significantly higher. The concentration of PHEMA in urine was higher in the group who participated in the fire suppression for more than 11 hours (long time) than the group who participated in the fire suppression for a short time.

The ability to manipulate light and liquids on integrated optofluidics chips has spurred a myriad of important developments in biology, medicine, chemistry and display technologies. Here we show how the convergence of optofluidics and metasurface optics can lead to conceptually new platforms for the dynamic control of light fields. We first demonstrate metasurface building blocks that display an extreme sensitivity in their scattering properties to their dielectric environment. These blocks are then used to create metasurface-based flat optics inside microfluidic channels where liquids with different refractive indices can be directed to manipulate their optical behaviour. We demonstrate the intensity and spectral tuning of metasurface colour pixels as well as on-demand optical elements. We finally demonstrate automated control in an integrated meta-optofluidic platform to open up new display functions. Combined with large-scale microfluidic integration, our dynamic-metasurface flat-optics platform could open up the possibility of dynamic display, imaging, holography and sensing applications., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The effects of perioperative blood transfusion on the prognosis of gastric cancer patients remain controversial. This study aimed to assess the association between perioperative blood transfusion and survival outcomes., Methods: The study included 2905 patients who underwent curative gastrectomy for stage II/III gastric cancer between 2006 and 2015 and were followed until 2018. Propensity-score matching was used to adjust for differences in baseline clinicopathologic characteristics between patients with or without blood transfusion., Results: Of 2905 patients, 543 (18.7%) received a perioperative blood transfusion. Patients with blood transfusion had significantly worse overall survival and recurrence-free survival than those without blood transfusion (p < 0.001 for both). Survival outcomes did not differ according to timing of transfusion (preoperative, intraoperative, or postoperative), transfused volume (1-2 units of packed red cells vs ≥ 3 units of packed red blood cells), and volume of intraoperative blood loss (≤300 mL vs > 300 mL). After propensity-score matching adjusting for risk factors associated with blood transfusion, 498 patients were included in each group. Long-term recurrence-free survival was not significantly different between patients with or without blood transfusion in the matched analysis (p = 0.808)., Conclusions: In propensity-score matched analysis, blood transfusion was not associated with recurrence-free survival. Clinical circumstances, including demographic, pathologic, and surgical characteristics, rather than blood transfusions, appear to be the main prognostic factors for recurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Oxidative stress is extensively involved in neurodegeneration. Clinical evidence shows that keeping the mind active through mentally-stimulating physical activities can effectively slow down the progression of neurodegeneration. With increased physical activities, more neurotransmitters would be released in the brain. In the present study, we investigated whether some of the released neurotransmitters might have a beneficial effect against oxidative neurodegeneration in vitro. Glutamate-induced, glutathione depletion-associated oxidative cytotoxicity in HT22 mouse hippocampal neuronal cells was used as an experimental model. We showed that norepinephrine (NE, 50 µM) or dopamine (DA, 50 µM) exerted potent protective effect against glutamate-induced cytotoxicity, but this effect was not observed when other neurotransmitters such as histamine, γ-aminobutyric acid, serotonin, glycine and acetylcholine were tested. In glutamate-treated HT22 cells, both NE and DA significantly suppressed glutathione depletion-associated mitochondrial dysfunction including mitochondrial superoxide accumulation, ATP depletion and mitochondrial AIF release. Moreover, both NE and DA inhibited glutathione depletion-associated MAPKs activation, p53 phosphorylation and GADD45α activation. Molecular docking analysis revealed that NE and DA could bind to protein disulfide isomerase (PDI). In biochemical enzymatic assay in vitro, NE and DA dose-dependently inhibited the reductive activity of PDI. We further revealed that the protective effect of NE and DA against glutamate-induced oxidative cytotoxicity was mediated through inhibition of PDI-catalyzed dimerization of the neuronal nitric oxide synthase. Collectively, the results of this study suggest that NE and DA may have a protective effect against oxidative neurodegeneration through inhibition of protein disulfide isomerase and the subsequent activation of the MAPKs‒p53‒GADD45α oxidative cascade., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Mesenchymal stem cells (MSCs) are considered a potential tool for regenerating damaged tissues due to their great multipotency into various cell types. Here, we attempted to find the appropriate conditions for neuronal differentiation of tonsil-derived MSCs (TMSCs) and expand the potential application of TMSCs for treating neurological diseases., Methods: The TMSCs were differentiated in DMEM/F-12 (Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12) supplemented with various neurotrophic factors for 7-28 days to determine the optimal neuronal differentiation condition for the TMSCs. The morphologies as well as the levels of the neural markers and neurotransmitters were assessed to determine neuronal differentiation potentials and the neuronal lineages of the differentiated TMSCs., Results: Our initial study demonstrated that DMEM/F12 supplemented with 50 ng/mL basic fibroblast growth factor with 10 μM forskolin was the optimal condition for neuronal differentiation for the TMSCs. TMSCs had higher protein expression of neuronal markers, including neuron-specific enolase (NSE), GAP43, postsynaptic density protein 95 (PSD95), and synaptosomal-associated protein of 25 kDa (SNAP25) compared to the undifferentiated TMSCs. Immunofluorescence staining also validated the increased mature neuron markers, NeuN and synaptophysin, in the differentiated TMSCs. The expression of glial fibrillar acidic protein and ionized calcium-binding adaptor molecule 1 the markers of astrocytes and microglia, were also slightly increased. Additionally, the differentiated TMSCs released a significantly higher level of acetylcholine, the cholinergic neurotransmitter, as analyzed by the liquid chromatography-tandem mass spectrometry and showed an enhanced choline acetyltransferase immunoreactivity compared to the undifferentiated cells., Conclusion: Our study suggests that the optimized condition favors the TMSCs to differentiate into cholinergic neuron-like phenotype, which could be used as a possible therapeutic tool in treating certain neurological disorders such as Alzheimer's disease., (© 2022. Korean Tissue Engineering and Regenerative Medicine Society.)

Two new species of Peucedanum (Apiaceae), P.miroense and P.tongkangense , from Gangwon Province, South Korea, are described. Both species are most similar to P.elegans and P.hakuunense because of their linear ultimate leaf segments. Peucedanummiroense was found on crevices of rocks in mountain summits and can be distinguished by its pubescent ovary, purple anthers, oblong schizocarp, and 1 or (2) vittae per vallecula and 4 on the commissural face. Peucedanumtongkangense was found in open areas on rocky cliffs along the Donggang River and can be distinguished by its glabrous ovary, whitish-yellow anthers, narrowly ellipsoid schizocarp, and 3 vittae per vallecula and 4 on the commissural face. Distinguishing characteristics, full descriptions, illustrations, photographs, taxonomic notes on geographical distribution, ecology, and phenology of the two species are presented. An identification key for all Korean species of Peucedanum is also provided. In addition, the mericarp surface of two new species and their close relatives are compared using micromorphological analysis., (Kyeonghee Kim, Hwa-Jung Suh, Jun-Ho Song.)

Therapeutic drug monitoring (TDM) is effective in optimizing the efficacy of infliximab in patients with inflammatory bowel disease (IBD). An affordable way of monitoring is in high demand. This study evaluated the analytical and clinical performances of the newly available Remsima monitor kits and compared them with the established enzyme-linked immunosorbent assay kits. The trough level of infliximab in patients with IBD treated with an infliximab originator (Remicade) or biosimilar compounds (Remsima and Remaloce) was measured using a Remsima® Monitor Drug Level (Remsima) kit at the Samsung Medical Center, Seoul, Korea. Twenty-six plasma samples were collected immediately before the infusion of infliximab from 18 patients with IBD (Remicade, n = 8; Remsima, n = 6; and Remaloce, n = 4). The intra-assay intraclass correlation coefficient (ICC) of the RIDA and Remsima kits was 0.951 (95% CI = 0.908-0.976) and 0.990 (95% CI = 0.981-0.995). The inter-assay ICC of infliximab trough level between the RIDA and Remsima kits was very high (R = 0.971; 95% CI = 0.935-0.987), and the mean difference between the kits was 1.458 (95% limits of agreement = -3.302 to 6.219). The intra- and inter-assay reliabilities of all types of infliximab did not show significant differences. Qualitative stratification revealed substantial similarities between the kits (weighted kappa = 0.798). This study indicated that the Remsima kit was reproducible and highly correlated with the RIDA kit., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Mosladadoensis (Lamiaceae), a new species from the southern islands of South Korea, is described and illustrated. The new species is morphologically similar to M.chinensis , but is distinguished from the latter by having two types of hairs on its stems, wider leaf blades, longer corolla length, and ellipsoid nutlets with a narrowly U-shaped extended area of abscission scar. Mosladadoensis is also distinguished from the Chinese narrow endemic M.hangchouensis by having an included pistil to the corolla, smaller ellipsoid nutlets, and later flowering and fruiting season. Phylogenetic analyses, based on two nuclear ribosomal (ETS, ITS) and three chloroplast ( rbc L, mat K, trn L-F) DNA regions, confirmed that the new species was constructed as monophyletic, and that M.dadoensis and M.hangchouensis form a sister group with robust support. We hereby provide a detailed morphological description of M.dadoensis with its corresponding geographical distributions, and comparison tables of related taxa., (Hyun-Do Jang, Kwi-Kwan Jeong, Myoung-Ja Nam, Jun-Ho Song, Hye-Kyoung Moon, Hyeok Jae Choi.)

As the demand for ocean exploration increases, studies are being actively conducted on autonomous underwater vehicles (AUVs) that can efficiently perform various missions. To successfully perform long-term, wide-ranging missions, it is necessary to apply fault diagnosis technology to AUVs. In this study, a system that can monitor the health of in situ AUV thrusters using a convolutional neural network (CNN) was developed. As input data, an acoustic signal that comprehensively contains the mechanical and hydrodynamic information of the AUV thruster was adopted. The acoustic signal was pre-processed into two-dimensional data through continuous wavelet transform. The neural network was trained with three different pre-processing methods and the accuracy was compared. The decibel scale was more effective than the linear scale, and the normalized decibel scale was more effective than the decibel scale. Through tests on off-training conditions that deviate from the neural network learning condition, the developed system properly recognized the distribution characteristics of noise sources even when the operating speed and the thruster rotation speed changed, and correctly diagnosed the state of the thruster. These results showed that the acoustic signal-based CNN can be effectively used for monitoring the health of the AUV's thrusters.

Phytic acid (PA) acts as an antinutrient substance in cereal grains, disturbing the bioavailability of micronutrients, such as iron and zinc, in humans, causing malnutrition. GmIPK1 encodes the inositol 1,3,4,5,6-penta kis phosphate 2-kinase enzyme, which converts myo -inopsitol-1,3,4,5,6-penta kis phosphate (IP 5 ) to myo -inositol-1,2,3,4,5,6-hexakisphosphate (IP 6 ) in soybean ( Glycine max L.). In this study, for developing soybean with low PA levels, we attempted to edit the GmIPK1 gene using the CRISPR/ Cas9 system to introduce mutations into the GmIPK1 gene with guide RNAs in soybean (cv. Kwangankong). The GmIPK1 gene was disrupted using the CRISPR/Cas9 system, with sgRNA-1 and sgRNA-4 targeting the second and third exon, respectively. Several soybean Gmipk1 gene-edited lines were obtained in the T 0 generation at editing frequencies of 0.1-84.3%. Sequencing analysis revealed various indel patterns with the deletion of 1-9 nucleotides and insertions of 1 nucleotide in several soybean lines (T 0 ). Finally, we confirmed two sgRNA-4 Gmipk1 gene-edited homozygote soybean T 1 plants (line #21-2: 5 bp deletion; line #21-3: 1 bp insertion) by PPT leaf coating assay and PCR analysis. Analysis of soybean Gmipk1 gene-edited lines indicated a reduction in PA content in soybean T 2 seeds but did not show any defects in plant growth and seed development.

Objective: To analyze the association between body mass index (BMI) and coronary heart disease. Methods: The data for the present study were from the prospective cohort study of China Kadoorie Biobank (CKB) in Qingdao, a total of 33 355 participants aged 30-79 years were included in the study. Cox regression analyses were performed to evaluate the association between BMI and coronary heart disease. Results: During the follow-up for an average 9.2 years, a total of 2 712 cases of ischemic heart disease (IHD) and 420 cases of major coronary events (MCE) were found. Multivariate Cox regression analysis showed that, compared with participants with normal BMI, the participants who were overweight had a 41% and 87% higher risk of IHD and MCE, the adjusted HR were 1.41 (95% CI : 1.27-1.56) and 1.87 (95% CI : 1.43-2.44), respectively. The participants who were obesity had 91% and 143% higher risk of IHD and MCE, the adjusted HR were 1.91 (95% CI : 1.72-2.13) and 2.43 (95% CI : 1.82-3.24), respectively. Conclusion: Overweight and obesity might increase the risk for IHD and MCE.

Hyperhomocysteinemia (HHcy) is considered a risk factor for cardiovascular disease (CVD), including chronic kidney disease (CKD). In this study, we investigated the association between levels of serum homocysteine (Hcy) and mortality, inferred from the presence of CKD. Our study included data of 9895 participants from the 1999 to 2016 National Health and Nutrition Examination Surveys (NHANES). Multivariable-adjusted Cox proportional hazard models using propensity-score, were used to examine dose-response associations between Hcy level and mortality. A total of 9895 participants, 1025 (10.3%) participants were diagnosed with CKD. In a multivariate Cox regression analysis including all participants, Hcy level was significantly associated with all-cause mortality in the nonCKD group, compared to the 1st quartile in the fully adjusted model (2nd quartile: hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.348-2.274, P < .001; 3rd quartile: HR 2.22, 95% CI 1.726-2.855, P < .001; 4th quartile: HR 3.77, 95% CI 2.952-4.830, P < .001). However, this finding was not observed in the CKD group. The observed pattern was similar after propensity score matching. In the nonCKD group, overall mortality increased in proportion to Hcy concentration (2nd quartile: HR 2.19, 95% CI 1.299-3.709, P = .003; 3rd quartile: HR 2.60, 95% CI 1.570-4.332, P < .001; 4th quartile: HR 3.72, 95% CI 2.254-6.139, P < .001). However, the risk of all-cause mortality according to the quartile of Hcy level, did not increase in the CKD group. This study found a correlation between the Hcy level and mortality rate only in the nonCKD group. These altered risk factor patterns may be attributed to protein-energy wasting or chronic inflammation status, that is accompanied by CKD., Competing Interests: The authors have no funding and conflict of interests to declare., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Metastatic prostate cancer in the bone induces bone-forming lesions that contribute to progression and therapy resistance. Prostate cancer-induced bone formation originates from endothelial cells (EC) that have undergone endothelial-to-osteoblast (EC-to-OSB) transition in response to tumor-secreted BMP4. Current strategies targeting prostate cancer-induced bone formation are lacking. Here, we show that activation of retinoic acid receptor (RAR) inhibits EC-to-OSB transition and reduces prostate cancer-induced bone formation. Treatment with palovarotene, an RARγ agonist being tested for heterotopic ossification in fibrodysplasia ossificans progressiva, inhibited EC-to-OSB transition and osteoblast mineralization in vitro and decreased tumor-induced bone formation and tumor growth in several osteogenic prostate cancer models, and similar effects were observed with the pan-RAR agonist all-trans-retinoic acid (ATRA). Knockdown of RARα, β, or γ isoforms in ECs blocked BMP4-induced EC-to-OSB transition and osteoblast mineralization, indicating a role for all three isoforms in prostate cancer-induced bone formation. Furthermore, treatment with palovarotene or ATRA reduced plasma Tenascin C, a factor secreted from EC-OSB cells, which may be used to monitor treatment response. Mechanistically, BMP4-activated pSmad1 formed a complex with RAR in the nucleus of ECs to activate EC-to-OSB transition. RAR activation by palovarotene or ATRA caused pSmad1 degradation by recruiting the E3-ubiquitin ligase Smad ubiquitination regulatory factor1 (Smurf1) to the nuclear pSmad1/RARγ complex, thus blocking EC-to-OSB transition. Collectively, these findings suggest that palovarotene can be repurposed to target prostate cancer-induced bone formation to improve clinical outcomes for patients with bone metastasis., Significance: This study provides mechanistic insights into how RAR agonists suppress prostate cancer-induced bone formation and offers a rationale for developing RAR agonists for prostate cancer bone metastasis therapy. See related commentary by Bhowmick and Bhowmick, p. 2975., (©2022 American Association for Cancer Research.)

Cancer cells utilize multiple nutrient scavenging mechanisms to support growth and survival in nutrient-poor, hypoxic tumor microenvironments. Among these mechanisms, macropinocytosis has emerged as an important pathway of extracellular nutrient acquisition in cancer cells, particularly in tumors with activated RAS signaling, such as pancreatic cancer. However, the absence of a clinically available inhibitor, as well as the gap of knowledge in macropinocytosis regulation, remain a hurdle for its use for cancer therapy. Here, we use the Informer set library to identify novel regulators of macropinocytosis-dependent growth in pancreatic cancer cells. Understanding how these regulators function will allow us to provide novel opportunities for therapeutic intervention.

Clinical studies have shown that subsets of patients with cancer achieve a significant benefit from Aurora kinase inhibitors, suggesting an urgent need to identify biomarkers for predicting drug response. Chromodomain helicase DNA binding protein 1 (CHD1) is involved in chromatin remodeling, DNA repair, and transcriptional plasticity. Prior studies have demonstrated that CHD1 has distinct expression patterns in cancers with different molecular features, but its impact on drug responsiveness remains understudied. Here, we show that CHD1 promotes the susceptibility of prostate cancer cells to inhibitors targeting Aurora kinases, while depletion of CHD1 impairs their efficacy in vitro and in vivo. Pan-cancer drug sensitivity analyses revealed that high expression of CHD1 was associated with increased sensitivity to Aurora kinase A (AURKA) inhibitors. Mechanistically, KPNA2 served as a direct target of CHD1 and suppressed the interaction of AURKA with the coactivator TPX2, thereby rendering cancer cells more vulnerable to AURKA inhibitors. Consistent with previous research reporting that loss of PTEN elevates CHD1 levels, studies in a genetically engineered mouse model, patient-derived organoids, and patient samples showed that PTEN defects are associated with a better response to AURKA inhibition in advanced prostate cancer. These observations demonstrate that CHD1 plays an important role in modulating Aurora kinases and drug sensitivities, providing new insights into biomarker-driven therapies targeting Aurora kinases for future clinical studies., Significance: CHD1 plays a critical role in controlling AURKA activation and promoting Aurora kinase inhibitor sensitivity, providing a potential clinical biomarker to guide cancer treatment., (©2022 American Association for Cancer Research.)

One of the brain's primary functions is to promote actions in dynamic, distracting environments. Because distractions divert attention from our primary goals, we must learn to maintain accurate actions under sensory and cognitive distractions. Visuomotor adaptation is a learning process that restores performance when sensorimotor capacities or environmental conditions are abruptly or gradually altered. Prior work showed that learning to counteract an abrupt perturbation under a particular single- or dual-task setting (i.e., attentional context) was associated with better recall under the same conditions. This suggested that the attentional context was encoded during adaptation and used as a recall cue. The current study investigated whether the attentional context (i.e., single vs. dual task) also affected adaptation and recall to a gradual perturbation, which limited awareness of movement errors. During adaptation, participants moved a cursor to a target while learning to counteract a visuomotor rotation that increased from 0° to 45° by 0.3° each trial, with or without performing a secondary task. Relearning was impaired when the attentional context was different between adaptation and recall ( experiment 1 ), even when the exposure to the attentional context was limited to the early or late half of adaptation ( experiment 2 ). Changing the secondary task did not affect relearning, indicating that the attentional context, rather than specific stimuli or tasks, was associated with better recall performance ( experiment 3 ). These findings highlight the importance of cognitive factors, such as attention, in visuomotor adaptation and have implications for learning and rehabilitation paradigms. NEW & NOTEWORTHY Adaptation acquired under single- or dual-task setting, which created an undivided or divided attentional context, respectively, was impaired when relearning occurred under different conditions (i.e., shifting from a dual to single task). Changes to the attentional context impaired relearning when the initial adaptation was to a gradual perturbation. Explicit awareness of the perturbation was not necessary for this effect to be robust, nor was the effect attributable to changes in the secondary task requirements.

Purpose: This study aims to investigate the incidence rate and risk factors of stroke in patients treated with bilateral TKA compared with patients with unilateral TKA., Methods: In this retrospective nationwide cohort study, we compared patients undergoing unilateral TKA or bilateral TKA using data from the Korean National Health Insurance claims database between January 1, 2009 and August 31, 2017 and included patients older than 40 years of age who underwent primary TKA by the index date as documented primary diagnosis and first additional diagnosis without a history of stroke during the preceding 1 year. We used matched Cox regression models to compare the incidence rate and risk factors of newly acquired stroke among patients treated with unilateral TKA or bilateral TKA after propensity score (PS) matching., Results: In the present study, 163,719 patients who received unilateral TKA were matched to 163,719 patients with bilateral TKA based on PS. The risk of stroke during the study period was lower in patients treated with bilateral TKA than in patients with unilateral TKA (adjusted hazard ratio [HR] 0.79). Patients who received bilateral TKA were at decreased risk of stroke when the following variables were present: advanced age (70-79 years, HR 0.76), female sex (HR 0.75), rural area (HR 0.77), small- or medium-sized hospital (HR 0.75), health insurance (HR 0.77), history of hypertension drug use (HR 0.75), congestive heart failure (HR 0.70), connective tissue disease (HR 0.71), diabetes (HR 0.77), and diabetes with complication (HR 0.76)., Conclusion: The risk of stroke was lower in patients treated with bilateral TKA than in patients with unilateral TKA. Patients treated with bilateral TKA were at decreased risk of stroke when the following variables were present: age (70-79 years), female sex, health insurance, history of hypertension drug use, and comorbidities, such as congestive heart failure, connective tissue disease, and diabetes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Osteoporosis is a well-known risk factor of screw loosening. Classically, dual-energy x-ray absorptiometry (DEXA) scan is an easy and cost-effective method of detecting bone mineral density (BMD). However, T-score on DEXA scan can be overestimated in patients with degenerative changes of the spine. Our objective was to identify correlation between Hounsfield unit (HU) measured by 3-dimensional computed tomography (3D-CT) and screw loosening., Methods: A total of 113 patients treated with lumbosacral spinal fusion were reviewed and categorized into a screw loosening group and a normal group to compare their average values of preoperative CT HU. Screw loosening was defined as radiolucent area around screw that was thicker than 1 mm with a "double halo sign"., Results: There were statistically significant differences in patient age and steroid use between screw loosening and non-loosening groups. There was no significant difference in BMD or T-score between the 2 groups. However, HU values measured in axial, coronal, and sagittal images were significantly different between the 2 groups. In the receiver operating characteristic for HU values measured in CT images, the greatest area under the curve was 0.774 and that was in case of Hounsfield unit measured by axial CT images from L1 to L4., Conclusions: Preoperative CT HU is associated with screw loosening. It can be a better predictor of screw loosening than DEXA scan. The best predictor of screw loosening in this study is the average value of HU from L1 to L4 in axial cut., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The number of elderly people living with HIV is increasing globally, and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection. However, the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear. Here, we used the simian immunodeficiency virus mac239 (SIVmac239) strain to infect six young and six old Chinese rhesus macaques (ChRMs) and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph nodes. The results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes, especially when a large number of CD8+ T cells infiltrated the follicles and germinal centers. STAT3 in these follicular CXCR5+CD8+ T cells was highly activated, with high expression of granzyme B, which might be caused by the severe inflammatory milieu in the follicles of old ChRMs. This study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues, affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+ cells., (© 2022. The Author(s), under exclusive licence to CSI and USTC.)

Background: When endoscopically resected specimens of early colorectal cancer (CRC) show high-risk features, surgery should be performed based on current guidelines because of the high-risk of lymph node metastasis (LNM). The aim of this study was to determine the utility of an artificial intelligence (AI) with deep learning (DL) of hematoxylin and eosin (H&E)-stained endoscopic resection specimens without manual-pixel-level annotation for predicting LNM in T1 CRC. In addition, we assessed AI performance for patients with only submucosal (SM) invasion depth of 1000 to 2000 μm known to be difficult to predict LNM in clinical practice., Methods: H&E-stained whole slide images (WSIs) were scanned for endoscopic resection specimens of 400 patients who underwent endoscopic treatment for newly diagnosed T1 CRC with additional surgery. The area under the curve (AUC) of the receiver operating characteristic curve was used to determine the accuracy of AI for predicting LNM with a fivefold cross-validation in the training set and in a held-out test set., Results: We developed an AI model using a two-step attention-based DL approach without clinical features (AUC, 0.764). Incorporating clinical features into the model did not improve its prediction accuracy for LNM. Our model reduced unnecessary additional surgery by 15.1% more than using the current guidelines (67.4% vs. 82.5%). In patients with SM invasion depth of 1000 to 2000 μm, the AI avoided 16.1% of unnecessary additional surgery than using the JSCCR guidelines., Conclusions: Our study is the first to show that AI trained with DL of H&E-stained WSIs has the potential to predict LNM in T1 CRC using only endoscopically resected specimens with conventional histologic risk factors., (© 2022. Japanese Society of Gastroenterology.)

Objectives: Vancomycin and teicoplanin are glycopeptides with activity against Enterococcus faecium. However, studies on the clinical efficacy of teicoplanin are limited. This study aimed to compare the therapeutic efficacy of teicoplanin and vancomycin in E. faecium bacteremia., Methods: We identified patients with bloodstream infections prospectively from July 2015 to December 2016 in 14 hospitals as part of a multicenter nationwide surveillance. Patients with E. faecium monomicrobial bacteremia were selected. Teicoplanin and vancomycin groups included patients treated with either agent for ≥48 hours. The primary outcome was 30-day all-cause in-hospital mortality. The Cox proportional hazards model with inverse probability weighting was used to account for the imbalance in baseline characteristics between the two groups., Results: Among 97 patients with E. faecium bacteremia, 33 (34%) were treated with teicoplanin and 64 (66%) with vancomycin. There were no significant differences in 30-day in-hospital mortality (18.2% vs 26.6%, P = 0.358) and 7-day mortality (6.1% vs 15.6%, P = 0.212). Furthermore, multivariable analysis confirmed that the use of teicoplanin was not significantly associated with mortality (adjusted odds ratio, 0.72; 95% confidence interval, 0.28-1.86; P = 0.494)., Conclusion: We found no significant differences in the clinical outcomes. These findings suggest teicoplanin as a useful alternative to vancomycin., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Structures constructed before seismic design standards in Korea were enacted are being seismically and structurally strengthened for structural performance. The jacket method has been used to enhance the shear load-carrying capacity and ductility of reinforced concrete columns. This study investigated the effect of glass fiber-reinforced polyurea (GFRPU) on the enhancement of shear strength and ductility. It was shown that the GFRPU spraying technique played an important role in enhancing the column because of the material characteristics of the GFRPU, that is, high-tensile strength and elongation. The reinforcement effect of GFRPU on the shear-span ratio and axial-force ratio of six reinforced concrete (RC) column specimens was evaluated. The experimental results demonstrated that the lateral-reinforcement effect and energy-dissipation capacity were improved. The H-series and S-series specimens reinforced by the GFRPU with an axial-load ratio of 0.1 exhibited higher shear strength, of about 30% and 18%, than the specimens without reinforcement. The shear-load-carrying capacity of the S-series specimen with the axial-load-force ratio of 0.2 increased by 4%. The design method representing the lateral-resistance ability of the GFRPU was represented by an empirical formula reflecting the experimental results.

A convenient and rapid detection method for methanol in ethanol remains a major challenge due to their indistinguishable physical properties. Herein, a novel fluorescence probe based on perovskite was successfully designed to overcome this bottleneck. We report a new zero-dimensional (0D) hybrid perovskite of [MP] 2 In x Sb 1-x Cl 7  ⋅ 6 H 2 O (MP=2-methylpiperazine) displaying an unusual green light emission with near-unity photoluminescence quantum yield. Remarkably, this 0D perovskite exhibits reversible methanol-response luminescence switching between green and yellow color but fail in any other organic vapors. Even for blended alcohol solutions, the luminescent probe exhibits excellent sensing performance with multiple superiorities of rapid response time (30 s) and ultra-low detection limit (40 ppm), etc. Therefore, this 0D perovskite can be utilized as a perfect fluorescence probe to detect traces of methanol from ethanol with ultrahigh sensitivity, selectivity and repeatability. To the best of our knowledge, this work represents the first perovskite as fluorescence probe for methanol with wide potential in environmental monitoring and methanol detection, etc., (© 2022 Wiley-VCH GmbH.)