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Purpose: To investigate the clinical results of vitrectomy alone as the primary treatment for rhegmatogenous retinal detachment (RD) in patients with atopic dermatitis (AD).Methods: The medical records of patients with AD treated for rhegmatogenous retinal detachment (RD) were retrospectively reviewed. We investigated the characteristics of retinal breaks and detachments, applied surgical methods, and results.Results: Twenty eyes of 14 patients with AD who presented with rhegmatogenous RD and treated by vitrectomy were included in this analysis. Sixteen eyes (80%) were treated with vitrectomy, either alone or in combination with cataract surgery, and the retina was successfully attached to 94% of the eyes. There were four cases in which vitrectomy was combined with encircling. Reoperation was needed in half of the eyes that received vitrectomy with encircling, which presented nearly total detachment, severe proliferative vitreoretinopathy, and pseudophakia.Conclusions: Vitrectomy alone, in combination with cataract surgery, may be sufficient to treat rhegmatogenous RD in patients with AD. Additional encircling or buckling should still be considered in complicated cases.

Primary cilia, antenna-like cellular sensor structures, are generated from the mother centriole in the G0/G1 cell-cycle phase under control by cellular signaling pathways involving Wnt, hedgehog, and platelet-derived growth factor. Although primary ciliary dynamics have been reported to be closely related to ciliopathy and tumorigenesis, the molecular basis for the role of primary cilia in human disease is lacking. To clarify how Wnt3a affects primary ciliogenesis in anticancer drug-resistant cells, we derived specific drug-resistant subcell lines from A549 human lung cancer cells using anticancer drugs doxorubicin, dasatinib, and paclitaxel (A549/Dox, A549/Das, and A549/Pac, respectively). The primary cilia-containing cell population and primary cilia length increased in the A549/Dox and A549/Pac subcell lines under increased MDR1 expression, when compared to those in the parental A549 cells. In the A549/Das subcell line, primary cilia length increased but the cell population was not affected. In addition, Wnt3a increased primary cilia-containing cell population and primary cilia length in A549/Dox, A549/Das, and A549/Pac cells, without change of cell growth. Abnormal shapes of primary cilia were frequently observed by anticancer drug resistance and Wnt3a stimulation. Taken together, our results indicate that anticancer drug resistance and Wnt3a affect primary ciliogenesis synergistically, suggesting a potential new strategy for overcoming anticancer drug resistance.

Protein arginylation is a critical regulator of a variety of biological processes. The ability to uncover the global arginylation pattern and its associated signaling pathways would enable us to identify novel disease targets. Here, we report the development of a tool able to capture the N-terminal arginylome. This tool, termed R-catcher, is based on the ZZ domain of p62, which was previously shown to bind N-terminally arginylated proteins. Mutating the ZZ domain enhanced its binding specificity and affinity for Nt-Arg. R-catcher pulldown coupled to LC–MS/MS led to the identification of 59 known and putative arginylated proteins. Among these were a subgroup of novel ATE1-dependent arginylated ER proteins that are linked to diverse biological pathways, including cellular senescence and vesicle-mediated transport as well as diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease. This study presents the first molecular tool that allows the unbiased identification of arginylated proteins, thereby unlocking the arginylome and provide a new path to disease biomarker discovery. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-03805-x.

Objective We report the results of pharmacogenomics-based antidepressant treatment (PGXt) results in treating treatment-resistant major depressive disorder (TRD) patients in real practice. Methods Nine patients were prescribed NeuropharmagenⓇ for selection of antidepressants for individual patient and their clinical outcomes were followed. Results After treatment by PGXt results from current antidepressants, substantial reduction of depressive symptoms was observed at some point and maintained during observation period in six patients. Conclusion Our case series potentially shows the clinical utility and benefit of PGXt for treatment of TRD patients.

Research and development of smart vessels has progressed significantly in recent years, and ships have become high-value technology-intensive resources. These ships entail high production costs and long-life cycles. Thus, modernized technical design, professional training, and aggressive maintenance are important factors in the efficient management of ships. With the continuing digital revolution, the industrial shipbuilding applicability of augmented reality (AR) and virtual reality (VR) technologies as well as related 3D system modeling and processes has increased. However, resolving the differences between AR/VR and real-world models remains burdensome. This problem is particularly evident when mapping various texture characteristics to virtual objects. To mitigate the burden and improve the performance of such technologies, it is necessary to directly define various texture characteristics or to express them using expensive equipment. The use of deep-learning-based CycleGAN, however, has gained attention as a method of learning and automatically mapping real-object textures. Thus, we seek to use CycleGAN to improve the immersive capacities of AR/VR models and to reduce production costs for shipbuilding. However, when applying CycleGAN’s textures to pipe structures, the performance is insufficient for direct application to industrial piping networks. Therefore, this study investigates an improved CycleGAN algorithm that can be specifically applied to the shipbuilding industry by combining a modified object-recognition algorithm with a double normalization method. Thus, we demonstrate that basic knowledge on the production of AR industrial pipe models can be applied to virtual models through machine learning to deliver low-cost and high-quality textures. Our results provide an on-ramp for future CycleGAN studies related to the shipbuilding industry.

Objective : To test clinical effectiveness and tolerability of Korean Red Ginseng augmentation (RGA) in major depressive disorder (MDD) patients with difficult-to-treat. Methods Thirty six patients were enrolled in this 6 weeks, prospective, clinical trial. Rating scales were MontgomeryAsberg Depression Rating Scale (MADRS), Patient Health Questionnaire-15, Clinical Global Impression-improvement (CGI-I), and Patient Satisfaction Score. The primary endpoint was a remission rate measured by MADRS score at the end of study (≤ 10). Clinical outcomes and tolerability were assessed at baseline, week 2, and week 6. Results Among 36 patients, 26 patients completed the study and 28 patients had post-baseline visit data. The remission rate by MADRS score was 39.3% (11/28) and 57.1% by CGI-I scores of 1 or 2 at the end of the study. The mean change of MADRS score was significantly decreased by 44.4% from baseline to the end of study. The most frequent adverse events were headache (7/28, 25.0%) during the study. Conclusion Our study indicates the putative effectiveness and tolerability of RGA for treating MDD with difficult-to-treat in clinical practice. However, adequately powered, randomized, controlled trials will be needed to confirm these results.

Objective There has been a lack of data regarding the usefulness and clinical characteristic between patients-treated with and without antidepressants (Pw/Pwo ADs). Methods One hundred and eighty inpatients were recruited and observed for a 6-month. The depressive, cognitive, daily activity, and motor symptoms were evaluated at baseline and tracked at month 6, with the use of rating scales including Beck Depression Inventory (BDI), Mini Mental State Examination (MMSE), Global Deterioration Scale (GDS), modified Rankin Scale (MRS), modified Barthel Index (MBI), and Berg Balance Scale (BBS). Results Among 178 patients, 84 (47.2%) were treated with ADs. PwAD had numerically or significantly higher depressive cognitive, and motor symptoms along with daily activity impairment (8.3 point higher in BDI score, p < 0.001; 3.6 point lower in MMSE, p = 0.003; 0.8 point higher in GDS score, p = nonsignificant; 8.2 point lower in BBS score, p = 0.053, and 0.4 point higher in MBI score, p = nonsignificant) than PwoAD. Psychiatric consultation was also significantly higher in PwAD than in PwoAD (p < 0.001). The numbers need to treat for good clinical outcomes between PwAD and PwoAD were 5.8, 6.0, and 7.5, respectively, by MRS, MBI, and BBS scores. Conclusion Our findings suggest the potential utility of AD treatment and different clinical parameters between patients- treated with and without ADs. Adequately-powered and well-controlled further studies are mandatory to confirm and fully elaborate such association.

The importance of operations and maintenance (O&M) and piping inspection in shipbuilding and offshore plant industries has significantly increased recently. Therefore, this study proposes a system that uses augmented reality (AR) to support these operations. AR in O&M and inspection systems can increase work comprehension and efficiency by utilizing 3D graphics, instead of drawings, to describe specific work functions. To realize this improvement, the augmented model should correspond to the reality; if accurate registration is not achieved, it can disrupt the work functions. Therefore, marker-based AR is used to generate specific recognition objects and correct the location of the augmented model. However, owing to certain characteristics of the shipbuilding and offshore plant industries, the markers are likely to be damaged, and thus the cameras fail to clearly detect them. In this study, a 3D camera was used to generate a point cloud based on 3D image information. Accordingly, the area around the model to be detected was designated as the region of interest (ROI). Furthermore, it is difficult to support a high-end device environment because it is tested as a portable device that can be used in a working environment; therefore, superfluous data were removed by detecting the 3D edges in the ROI, thereby minimizing data operation. The scalability of this work was enhanced using the computer-aided design (CAD) file information extracted from the CAD tool (used in the shipbuilding industry) and converting it into a point cloud. The proposed system is expected to eliminate the issues related to understanding the O&M work by addressing registration errors that might occur in constrained environments and to improve the torsional phenomenon of the augmented models.

According to the Korea Radioactive Waste Agency’s (KORAD’s) medium and low level radioactive waste management implementation plan, the Domestic 3rd Step Landfill Disposal Facility has planned to accept a total of 104,000 drums (2 trenches) of very low level radioactive waste (VLLW), from the decommissioning site from April 2019 - February 2026 (total budget: 224.6 billion Won). Subsequently, 260,000 drums (5 trenches) will be disposed in a 34,076 m2. Accordingly, KORAD is preparing a waste acceptance criteria (WAC) for this facility. Every disposal facility for VLLW in other countries such as France and Spain, operate their WAC for each VLLW facility with a reasonable application approach, This, paper focuses on analyzing the WAC conditions in VLLW sites in the USA and discusses whether these can be met in domestic VLLW WAC. It also helps in the preparation of WAC for the 3rd Step Landfill Disposal Site in Gyeongju, since the USA has prior experience on decommissioning nuclear waste.

C5b-9 plays an important role in the pathogenesis of immunoglobin A nephropathy (IgAN). We evaluated C5b-9 as a prognostic marker for IgAN. We prospectively enrolled 33 patients with biopsy-proven IgAN. We analyzed the correlation between baseline urinary C5b-9 levels, posttreatment changes in their levels, and clinical outcomes, including changes in proteinuria, estimated glomerular filtration rate (eGFR), and treatment response. Baseline urinary C5b-9 levels were positively correlated with proteinuria (r = 0.548, p = 0.001) at the time of diagnosis. Changes in urinary C5b-9 levels were positively correlated with changes in proteinuria (r = 0.644, p < 0.001) and inversely correlated with changes in eGFR (r = −0.410, p = 0.018) at 6 months after treatment. Changes in urinary C5b-9 levels were positively correlated with time-averaged proteinuria during the follow-up period (r = 0.461, p = 0.007) but were not correlated with the mean annual rate of eGFR decline (r = −0.282, p = 0.112). Baseline urinary C5b-9 levels were not a significant independent factor that could predict the treatment response in logistic regression analyses (odds ratio 0.997; 95% confidence interval, 0.993 to 1.000; p = 0.078). Currently, urinary C5b-9 is not a promising prognostic biomarker for IgAN, and further studies are needed.

Background and Objectives: We investigated and compared the efficacy of three and five monthly loading regimens of an intravitreal aflibercept injection (IVA) in patients with diabetic macular edema (DME). Materials and Methods: This was a retrospective study that included patients diagnosed with DME and treated with an either three or five monthly aflibercept loading regimen from July 2018 to March 2022. Information on clinical characteristics and changes in the central retinal thickness (CRT) were obtained from medical records. Results: In total, 44 eyes of 44 patients with DME treated with IVA were included in this study, with 30 eyes treated with 3-monthly loadings (three-loading group) and 14 eyes with 5-monthly loadings (five-loading group). The mean CRT significantly decreased from the baseline one month after loading in both the three-loading and five-loading groups (p < 0.001). Four cases were refractory to treatment in the three-loading group, while there were no cases of refractory DME in the five-loading group. The stability rate was significantly higher in the five-loading group at three months after loading (p = 0.033). Conclusions: Five-monthly loading regimens of IVA might be favorable for DME considering the rate of refractory cases, stable duration, and the importance of early responsiveness to IVA in DME.

Background To investigate the safety of vitrectomy with laser photocoagulation in eyes with small peripheral retinal breaks without air or gas tamponade. Methods Among patients who underwent vitrectomy for various retinal disorders, those with small peripheral retinal breaks treated by laser photocoagulation without air or gas tamponade were included in this study. Their medical records were assessed retrospectively, and we investigated the characteristics of small peripheral retinal breaks and the incidence of postoperative retinal detachment (RD). Results Thirty-one eyes of 31 patients who presented with small peripheral retinal breaks requiring endolaser photocoagulation during vitrectomy were included in this analysis. There were two cases of iatrogenic retinal breaks that occurred during vitrectomy, while others were preexisting lesions, including retinal tears, atrophic retinal holes, and retinal holes with lattice degeneration. There were no cases of RD during the follow-up period of at least 6 months. Conclusions Adequate laser treatment without gas or air tamponade may be sufficient during vitrectomy in cases with small peripheral retinal breaks without concurrent RD, along with complete removal of vitreoretinal traction.

We hypothesized that minimal change disease (MCD) pathogenesis may be associated with mitochondrial injury, and that the degree of mitochondrial injury at the time of diagnosis may serve as a valuable prognostic marker. We compared urinary mitochondrial DNA (mtDNA) at the time of diagnosis in patients with MCD and age- and sex-matched healthy controls (MHC) (n = 10 each). We analyzed the site and signal intensity of immunohistochemical (IHC) staining of stimulator of interferon genes (STING) using kidney tissues at the time of diagnosis in patients with MCD. Patients with MCD were divided into high (n = 6) and low-intensity (n = 14) subgroups according to the signal intensity. Urinary mtDNA levels were elevated in the MCD groups more than in the MHC group (p < 0.001). Time-averaged proteinuria and frequency of relapses during the follow-up period were higher in the high-intensity than in the low-intensity subgroup (1.18 ± 0.54 vs. 0.57 ± 0.45 g/day, p = 0.022; and 0.72 ± 0.60 vs. 0.09 ± 0.22 episodes/year, p = 0.022, respectively). Mitochondrial injury may be associated with MCD pathogenesis, and the signal intensity of STING IHC staining at the time of diagnosis could be used as a valuable prognostic marker in MCD.

β‐Catenin is a multifunctional protein and participates in numerous processes required for embryonic development, cell proliferation, and homeostasis through various molecular interactions and signaling pathways. To date, however, there is no direct evidence that β‐catenin contributes to cytokinesis. Here, we identify a novel p‐S60 epitope on β‐catenin generated by Plk1 kinase activity, which can be found at the actomyosin contractile ring of early telophase cells and at the midbody of late telophase cells. Depletion of β‐catenin leads to cytokinesis‐defective phenotypes, which eventually result in apoptotic cell death. In addition, phosphorylation of β‐catenin Ser60 by Plk1 is essential for the recruitment of Ect2 to the midbody, activation of RhoA, and interaction between β‐catenin, Plk1, and Ect2. Time‐lapse image analysis confirmed the importance of β‐catenin phospho‐Ser60 in furrow ingression and the completion of cytokinesis. Taken together, we propose that phosphorylation of β‐catenin Ser60 by Plk1 in cooperation with Ect2 is essential for the completion of cytokinesis. These findings may provide fundamental knowledge for the research of cytokinesis failure‐derived human diseases., Phosphorylation of β‐catenin Ser60 by Plk1 in cooperation with Ect2 induces RhoA activation and mediates the progression of furrow ingression and subsequent cytokinesis steps.

The initiation of centrosome duplication is regulated by the Plk4/STIL/hsSAS-6 axis; however, the involvement of other centrosomal proteins in this process remains unclear. In this study, we demonstrate that Cep131 physically interacts with Plk4 following phosphorylation of residues S21 and T205. Localizing at the centriole, phosphorylated Cep131 has an increased capability to interact with STIL, leading to further activation and stabilization of Plk4 for initiating centrosome duplication. Moreover, we found that Cep131 overexpression resulted in centrosome amplification by excessive recruitment of STIL to the centriole and subsequent stabilization of Plk4, contributing to centrosome amplification. The xenograft mouse model also showed that both centrosome amplification and colon cancer growth were significantly increased by Cep131 overexpression. These findings demonstrate that Cep131 is a novel substrate of Plk4, and that phosphorylation or dysregulated Cep131 overexpression promotes Plk4 stabilization and therefore centrosome amplification, establishing a perspective in understanding a relationship between centrosome amplification and cancer development.

Simple Summary Cancer-associated fibroblasts (CAF) arise from normal fibroblasts within the tumor microenvironment (TME) and promote tumorigenesis through metabolic reprograming and secretion of tumor promoting molecules such as transforming growth factor beta (TGFβ). Here, we show that autophagy plays a key role in CAF activation. During CAF activation, fibroblasts induce the mRNA expression of p62, and resulting p62 targets Keap1 for lysosomal degradation, which allows the nuclear translocation of Nrf2 and transcriptional induction of antioxidant responses. The transcriptional targets of Nrf2 include ATF6, which mediates ER stress responses. Taken together, normal fibroblasts are differentiated into CAFs as protective responses to stresses under TME via the p62-Nrf2 pathway. Abstract Cancer-associated fibroblasts (CAFs) are important in tumor progression. The autophagy adaptor protein, p62/SQSTM1/Sequestosome-1, is up-regulated in tumors, but down-regulated in CAFs in the early stages of lung adenocarcinoma. We investigated whether p62-induced autophagy might control CAF activation. Under CAF-inducing conditions, like hypoxia or cancer cell co-cultures, p62 ablation or autophagy inhibition with hydroxychloroquine (HCQ) impaired CAF activation and reduced transforming growth factor beta (TGFβ) production, which impeded tumor growth. During CAF activation, p62-induced autophagy up-regulated the expression of the anti-oxidant signaling protein, nuclear factor erythroid 2-related factor 2 (Nrf2), and the ER-stress response regulator, activating transcription factor 6 (ATF6). Genetically or pharmacologically inhibiting the Nrf2-ATF6 pathway totally blocked CAF activation and tumor progression. These results demonstrate that p62 is a key modulator of primary lung adenocarcinoma progression. Thus, targeting the p62-Nrf2 autophagy signaling pathway might be a novel, stroma-focused, cancer prevention and/or treatment strategy.

Background and Objectives: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker used to predict heart failure and evaluate volume status in hemodialysis (HD) patients. However, it is difficult to determine the cutoff value for NT-proBNP in HD patients. In this study, we analyzed whether NT-proBNP helps predict heart function and volume status in HD patients. Materials and Methods: This prospective observational study enrolled 96 end-stage kidney disease patients with HD. All patients underwent echocardiography and bioimpedance spectroscopy (BIS) after an HD session. Overhydration (OH) was measured by BIS. Laboratory data were obtained preHD, while serum NT-proBNP was measured after HD. Interventions for blood pressure control and dry weight control were performed, and NT-proBNP was re-assessed after a month. Results: There was an inverse correlation between NT-proBNP and ejection fraction (EF) (β = −0.34, p = 0.001). OH (β = 0.331, p = 0.001) and diastolic dysfunction (β = 0.226, p = 0.027) were associated with elevated NT-proBNP. In a subgroup analysis of diastolic dysfunction grade, NT-proBNP increased according to dysfunction grade (normal, 4177 pg/mL [2637–10,391]; grade 1, 9736 pg/mL [5471–21,110]; and grades 2–3, 26,237 pg/mL [16,975–49,465]). NT-proBNP showed a tendency toward a decrease in the ‘reduced dry weight’ group and toward an increase in the ‘increased dry weight’ group compared to the control group (ΔNT-proBNP, −210 pg/mL [−12,899 to 3142], p = 0.104; 1575 pg/mL [−113 to 6439], p = 0.118). Conclusions: We confirmed that NT-proBNP is associated with volume status as well as heart function in HD patients.

Protein arginylation is a critical regulator of a variety of biological processes. The ability to uncover the global arginylation pattern and its associated signaling pathways would enable us to identify novel disease targets. Here, we report the development of a tool able to capture the N-terminal arginylome. This tool, termed R-catcher, is based on the ZZ domain of p62, which was previously shown to bind N-terminally arginylated proteins. Mutating the ZZ domain enhanced its binding specificity and affinity for Nt-Arg. R-catcher pulldown coupled to LC-MS/MS led to the identification of 59 known and putative arginylated proteins. Among these were a subgroup of novel ATE1-dependent arginylated ER proteins that are linked to diverse biological pathways, including cellular senescence and vesicle-mediated transport as well as diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer's disease. This study presents the first molecular tool that allows the unbiased identification of arginylated proteins, thereby unlocking the arginylome and provide a new path to disease biomarker discovery.

Purpose: The objective of this study was to improve the three-dimensional (3D) understanding of optimal lateral cortical hinge in medial open-wedge high tibial osteotomy (MOWHTO) via a computational cadaveric simulation of actual size. Methods: The computed tomography data of 117 adult cadavers were imported into Mimics® software to design 3D models of tibia and fibula. To simulate the MOWTHO, a virtual cutting plane was developed inside the safe zone based on established landmarks. After splitting and distracting through the cutting plane, the 10-mm cylinder (Ø 30 mm; height 10 mm) was placed vertically to be occupied properly in the nonosteotomized lateral cortex. The cross points between the round cylinder and cutting plane represented the anterior and posterior hinge points, which were used to validate the 3D position and direction of cortical hinge. Results: A 10-mm cylinder did not violate the proximal tibiofibular joint (PTFJ) and the protruding segment of the condylar area was less than 2 mm in 115 models. The connecting line between anterior and posterior hinge points was an average of 12.1° (range 0–24.1°, SD 4.64) to the lateral side. In the nonoverlapping anteroposterior projection between proximal fibula and tibia, the posterior hinge point was laid over the PTFJ as close as possible. Based on free 360° rotation and magnification without any tilt, no posterior cortical disruption of PTFJ was observed while securing a minimum width of 10 mm. Conclusion: If the posterior hinge point was placed immediately above the PTFJ without involvement, the nonosteotomized portion carried sufficient width greater than 10 mm, despite lateral rotation at an average hinge direction of 12.1°.

We developed a simple and rapid method for analyzing nonproteinogenic amino acids that does not require conventional chromatographic equipment. In this technique, nonproteinogenic amino acids were first converted to a proteinogenic amino acid through in vitro metabolism in a cell extract. The proteinogenic amino acid generated from the nonproteinogenic precursors were then incorporated into a reporter protein using a cell-free protein synthesis system. The titers of the nonproteinogenic amino acids could be readily quantified by measuring the activity of reporter proteins. This method, which combines the enzymatic conversion of target amino acids with translational analysis, makes amino acid analysis more accessible while minimizing the cost and time requirements. We anticipate that the same strategy could be extended to the detection of diverse biochemical molecules with clinical and industrial implications.

The primary cilium is a non-motile microtubule-based structure, which functions as an antenna-like cellular sensing organelle. The primary cilium is assembled from the basal body, a mother centriole-based structure, during interphase or a quiescent cell stage, and rapidly disassembles before entering mitosis in a dynamic cycle. Defects in this ciliogenesis dynamics are associated with human diseases such as ciliopathy and cancer, but the molecular mechanisms of the ciliogenesis dynamics are still largely unknown. To date, various cellular signaling pathways associated with primary cilia have been proposed, but the main signaling pathways regulating primary cilia assembly/disassembly remain enigmatic. This review describes recent findings in Wnt-induced primary cilia assembly/disassembly and potential future directions for the study of the cellular signaling related to the primary ciliogenesis dynamics.

IMPORTANCE: The incidence of gallstones has been reported to increase after gastrectomy. However, few studies have been conducted on the prevention of gallstone formation in patients who have undergone gastrectomy. OBJECTIVE: To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing gallstone formation after gastrectomy in patients with gastric cancer. DESIGN, SETTING, AND PARTICIPANTS: The PEGASUS-D study (Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study) was a randomized, double-blind, placebo-controlled clinical trial conducted at 12 institutions in the Republic of Korea. Adults (aged ≥19 years) with a diagnosis of gastric cancer who underwent total, distal, or proximal gastrectomy were enrolled between May 26, 2015, and January 9, 2017; follow-up ended January 8, 2018. Efficacy was evaluated by both the full analysis set, based on the intention-to-treat principle, and the per-protocol set; full analysis set findings were interpreted as the main results. INTERVENTIONS: Eligible participants were randomly assigned to receive 300 mg of UDCA, 600 mg of UDCA, or placebo at a ratio of 1:1:1. Ursodeoxycholic acid and placebo were administered daily for 52 weeks. MAIN OUTCOMES AND MEASURES: Gallstone formation was assessed with abdominal ultrasonography every 3 months for 12 months. Randomization and allocation to trial groups were carried out by an interactive web-response system. The primary end point was the proportion of patients developing gallstones within 12 months after gastrectomy. RESULTS: A total of 521 patients (175 received 300 mg of UDCA, 178 received 600 mg of UDCA, and 168 received placebo) were randomized. The full analysis set included 465 patients (311 men; median age, 56.0 years [interquartile range, 48.0-64.0 years]), with 151 patients in the 300-mg group, 164 patients in the 600-mg group, and 150 patients in the placebo group. The proportion of patients developing gallstones within 12 months after gastrectomy was 8 of 151 (5.3%) in the 300-mg group, 7 of 164 (4.3%) in the 600-mg group, and 25 of 150 (16.7%) in the placebo group. Compared with the placebo group, odds ratios for gallstone formation were 0.27 (95% CI, 0.12-0.62; P = .002) in the 300-mg group and 0.20 (95% CI, 0.08-0.50; P

Background and Aims Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. Method We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with IgA nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time×group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Results Compared to the MHC group, the MGA and IgAN groups displayed differences in the time×group effects of eGFR (Figure 1), higher mean annual rates of eGFR decline (Table), and higher urinary mtDNA copy numbers (Figure 2); however, these groups did not significantly differ from each other. Conclusion The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

The phenotypic heterogeneity of psoriasis is suspected to reflect differences in its pathogenesis, but not yet completely elucidated. Studies of the Th1 and Th17 cytokines associated with different phenotypes of psoriasis have yielded inconsistent results.To investigate the tissue expression levels of Th1 and Th17 cytokines among patients with chronic plaque psoriasis, acute guttate psoriasis, and healthy control.A total of 20 patients with psoriasis (10 with chronic plaque type and 10 with acute guttate type) and 5 healthy controls were enrolled. The tissue mRNA and protein levels of following cytokines were measured: interleukin (IL)-12, IL-2, interferon (IFN)-γ, IL-23, IL-17A, and IL-22.The tissue mRNA levels of IL-12, IFN-γ, IL-23, IL-17A, IL-22 and the protein levels of IL-12, IL-2, IFN-γ, IL-17A, IL-22 were significantly increased in the psoriasis patients compared with the healthy controls. In comparisons of the subtypes, the tissue mRNA level of IFN-γ was increased in acute guttate psoriasis, whereas the protein levels of IL-12 and IL-17A were significantly increased in chronic plaque psoriasis. The cytokine ratios of IL-17A/IL-2 and IL-22/IL-2 were significantly higher in chronic plaque psoriasis than in acute guttate psoriasis.We confirmed that the tissue levels of Th1 and Th17 cytokines were increased in psoriasis patients compared with healthy controls. The increased IFN-γ mRNA level in acute guttate psoriasis and increased IL-12 and IL-17A protein levels in chronic plaque psoriasis suggest that an imbalance between Th1 and Th17 cytokines may play a role in the phenotypic transition of psoriasis.

Elevated expression of human enhancer filamentation 1 (HEF1; also known as NEDD9 or Cas-L) is an essential stimulus for the metastatic process of various solid tumors. This process requires HEF1 localization to focal adhesions (FAs). Although the association of HEF1 with FAs is considered to play a role in cancer cell migration, the mechanism targeting HEF1 to FAs remains unclear. Moreover, up-regulation of Polo-like kinase 1 (Plk1) positively correlates with human cancer metastasis, yet how Plk1 deregulation promotes metastasis remains elusive. Here, we report that casein kinase 1δ (CK1δ) phosphorylates HEF1 at Ser-780 and Thr-804 and that these phosphorylation events promote a physical interaction between Plk1 and HEF1. We found that this interaction is critical for HEF1 translocation to FAs and for inducing migration of HeLa cells. Plk1-docking phosphoepitopes were mapped/confirmed in HEF1 by various methods, including X-ray crystallography, and mutated for functional analysis in HeLa cells. In summary, our results reveal the role of a phosphorylation-dependent HEF1–Plk1 complex in HEF1 translocation to FAs to induce cell migration. Our findings provide critical mechanistic insights into the HEF1–Plk1 complex–dependent localization of HEF1 to FAs underlying the metastatic process and may therefore contribute to the development of new cancer therapies.

Current strategy of hepatocellular carcinoma (HCC) surveillance evaluates individual risks of HCC for defining candidates for surveillance, but estimated risks are not utilized for clinical decision-making during actual screening. We sought to determine whether consideration of individual risks improve the performance of ultrasound (US)-based HCC screening in a real-world chronic hepatitis B (CHB) cohort. This single center retrospective cohort study analyzed 27,722 screening US tests from 4,175 consecutive CHB patients. Logistic regression analysis was performed to identify independent parameters predicting presence of HCC. A nomogram was built based on the independent predictors of HCC and compared with US-only screening by receiver operating characteristics analysis. The cost-effectiveness of the nomogram was assessed by decision curve analysis. HCC developed in 222 patients with the incidence of 0.769 per 1000 person-year during the median follow-up of 63 months. Age, sex, presence of cirrhosis, serum alpha-fetoprotein (AFP) levels and positive US test results were independent predictors of HCC presence. A nomogram based on these predictors showed higher C-statistics compared to US-only screening (0.960 vs. 0.731 and 0.935 vs. 0.691 for derivation and validation cohort, respectively; p < 0.001). Decision curve analysis showed higher net benefit of the HCC nomogram-guided screening model compared to US-only screening in the risk threshold range between 0 and 0.3. A nomogram composed of age, sex, presence of cirrhosis, serum AFP levels and US findings better predicted the presence of HCC compared to US-only screening in CHB on surveillance.