Search

Atopic dermatitis (AD) is one of the most prevalent, chronic and persistent inflammatory skin diseases closely associated with intestinal microbiota. To evaluate the effect of D-galactose intake on AD, we orally administered D-galactose to BALB/c mice whose ears and skin were treated with 2,4-dinitrochlorobenzene (DNCB). D-galactose alleviated DNCB-induced AD-like phenotypes such as redness, scaling/dryness and excoriation. Ear thickness was also decreased by D-galactose administration. Histopathological analysis revealed decreased epidermal thickening, infiltration of immune cells, especially mast cells, in the dermis. Total levels of serum IgE representing the immunological response of AD were decreased by D-galactose administration. Microbiota analysis showed that D-galactose administration restored gut microbiota profiles, which were altered in AD mice, characterized by increased abundance of Bacteroidetes and decreased abundance of Firmicutes. The increased abundance of Bacteroides and the decreased abundance of Prevotella and Ruminococcus were reversed by D-galactose treatment, following improvement of AD. Our results suggest the possible use of D-galactose as a prebiotic to alleviate AD by altering gut microbiota., Competing Interests: H-EK, E-JR, and JS were employed by Quorum Bio Co., Ltd. The remaining 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 Kim, Jung, Song, Jang, Park, Ahn, Lee, Kim, Lee, Seo, Kim, Ryu, Sim and Park.)

Background: On tomato plants, the flowering truss is a group or cluster of smaller stems where flowers and fruit develop, while the growing truss is the most extended part of the stem. Because the state of the growing truss reacts sensitively to the surrounding environment, it is essential to control its growth in the early stages. With the recent development of information and artificial intelligence technology in agriculture, a previous study developed a real-time acquisition and evaluation method for images using robots. Furthermore, we used image processing to locate the growing truss to extract growth information. Among the different vision algorithms, the CycleGAN algorithm was used to generate and transform unpaired images using generated learning images. In this study, we developed a robot-based system for simultaneously acquiring RGB and depth images of the growing truss of the tomato plant., Results: The segmentation performance for approximately 35 samples was compared via false negative (FN) and false positive (FP) indicators. For the depth camera image, we obtained FN and FP values of 17.55 ± 3.01% and 17.76 ± 3.55%, respectively. For the CycleGAN algorithm, we obtained FN and FP values of 19.24 ± 1.45% and 18.24 ± 1.54%, respectively. When segmentation was performed via image processing through depth image and CycleGAN, the mean intersection over union (mIoU) was 63.56 ± 8.44% and 69.25 ± 4.42%, respectively, indicating that the CycleGAN algorithm can identify the desired growing truss of the tomato plant with high precision., Conclusions: The on-site possibility of the image extraction technique using CycleGAN was confirmed when the image scanning robot drove in a straight line through a tomato greenhouse. In the future, the proposed approach is expected to be used in vision technology to scan tomato growth indicators in greenhouses using an unmanned robot platform., (© 2022. The Author(s).)

Background/aim: Because there are ongoing efforts to identify and develop novel drugs in the treatment of refractory gastric cancer, it is necessary to develop effective preclinical studies. Here, the preclinical efficacy of gastric tumor xenograft (GTX)-derived cell line models for the personalized treatment of gastric cancer was investigated., Materials and Methods: Anti-cancer drugs were scanned with high-throughput screening (HTS) using pre-established GTX-derived cell lines. The efficacy of a selected drug (afatinib) was re-confirmed in vivo and intracellular signaling pathways were investigated in xenograft tumor cell lysates using western blotting. Validation studies, such as cell proliferation and caspase activity assays, were also conducted in vitro with GTX-derived cell lines., Results: HTS indicated that afatinib was effective in one of the five GTX-derived cell lines (GTX-087). A xenograft mouse model was established from GTX-087, and administration of afatinib at 1 mg/20 g body weight/day per oral resulted in tumor-suppressive activity in vivo. The RAS-ERK pathway was inactivated by an increase in Bax and cleaved caspase-3 in this xenograft model. In vitro cell proliferation assay also revealed that afatinib was able to suppress the growth of the GTX-087 cell line. Caspase activity assay confirmed that afatinib had an apoptotic role on GTX-087 and showed that caspase-3/7 activity increased in a time dependent manner., Conclusion: The GTX-derived cell line model might be useful for estimating novel drug responses and could be an alternative to patient-derived xenograft animal models., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: The detection of malignant cells in body fluids (BF) with an automated hematology analyzer has been proposed as an alternative to morphological examination owing to its various advantages; however, its limitations have also been highlighted. In this study, we devised a practical algorithm to screen for malignant cells in BFs using an automated hematology analyzer., Methods: A total of 558 BF samples, including 232 cerebrospinal fluid (CSF) samples and 326 non-CSF samples, were consecutively collected. Thereafter, the results obtained using the BF mode of Sysmex XN-350 (Sysmex, Kobe, Japan) were compared with the cytological diagnosis. A cutoff was also established to screen for malignant cells using receiver operating characteristic (ROC) curve analysis based on the final clinical judgment., Results: The automated hematology analyzer showed a moderate correlation or good agreement with the existing cytological diagnosis. Further, of the ROC curves for detecting malignant cells, the absolute value of highly fluorescent cells on BF (HF-BF) in total body fluids showed the highest area under the curve (0.85 [95% confidence interval 0.82-88], p < .0001, Youden index >7×10 6 /L, sensitivity 93%, and specificity 65%)., Conclusion: An automated hematology analyzer could function as a complement to cytological examination. We propose a practical and comprehensive algorithm for cytological examination that requires low- and high-resolution microscopy based on the absolute value of HF-BF in BF samples suspected of malignancy. This algorithm can more usefully detect malignant cells while taking advantage of the automated analyzer and cytological examination., (© 2022 John Wiley & Sons Ltd.)

The complex and evolving nature of clinical phenotypes have made genetically diagnosing pediatric patients with movement disorders difficult. Here, we describe this diverse complexity in the clinical and genetic features of a pediatric cohort examined by whole-exome sequencing (WES) and demonstrate the clinical benefit of WES as a diagnostic tool in a pediatric cohort. We evaluated 75 patients with diverse single or combined movement phenomenologies using WES. WES identified 42 variants in 37 genes (56.0%). The detection rate was highest in patients with dystonia (11/13, 84.6%), followed by ataxia (21/38, 55.3%), myoclonus (3/6, 50.0%), unspecified dyskinesia (1/4, 25.0%), tremor (1/1, 100%), respectively. Most genetically diagnosed patients (90.5%) were affected by other neurologic or systemic manifestations; congenital hypotonia (66.7%), and epilepsy (42.9%) were the most common phenotypes. The genetic diagnosis changed the clinical management for five patients (6.7%), including treatments targeting molecular abnormalities, and other systemic surveillance such as cancer screening. Early application of WES yields a high diagnostic rate in pediatric movement disorders, which can overcome the limitations of the traditional phenotype-driven strategies due to the diverse phenotypic and genetic complexity. Additionally, this early genetic diagnosis expands the patient's clinical spectrum and provides an opportunity for tailored treatment., Competing Interests: Author GS is employed by the company 3billion Inc. The remaining 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 Kim, Yum, Seo, Ko and Lee.)

Various near-atom-thickness two-dimensional (2D) van der Waals (vdW) crystals with unparalleled electromechanical properties have been explored for transformative devices. Currently, the availability of 2D vdW crystals is rather limited in nature as they are only obtained from certain mother crystals with intrinsically possessed layered crystallinity and anisotropic molecular bonding. Recent efforts to transform conventionally non-vdW three-dimensional (3D) crystals into ultrathin 2D-like structures have seen rapid developments to explore device building blocks of unique form factors. Herein, we explore a "peel-and-stick" approach, where a nonlayered 3D platinum sulfide (PtS) crystal, traditionally known as a cooperate mineral material, is transformed into a freestanding 2D-like membrane for electromechanical applications. The ultrathin (∼10 nm) 3D PtS films grown on large-area (>cm 2 ) silicon dioxide/silicon (SiO 2 /Si) wafers are precisely "peeled" inside water retaining desired geometries via a capillary-force-driven surface wettability control. Subsequently, they are "sticked" on strain-engineered patterned substrates presenting prominent semiconducting properties, i.e., p -type transport with an optical band gap of ∼1.24 eV. A variety of mechanically deformable strain-invariant electronic devices have been demonstrated by this peel-and-stick method, including biaxially stretchable photodetectors and respiratory sensing face masks. This study offers new opportunities of 2D-like nonlayered semiconducting crystals for emerging mechanically reconfigurable and stretchable device technologies.

Purpose: To investigate the relationship between the anatomical features of schizencephaly and characteristics of epilepsy., Methods: We retrospectively evaluated patients diagnosed with schizencephaly using brain magnetic resonance imaging. Seizure outcomes were evaluated as drug-resistant epilepsy and frequent seizures (more than once a month) during the previous year. Development of epilepsy, seizure outcomes, and clinical variables were compared according to the anatomical features of schizencephaly, such as cleft type, size, bilaterality, presence of cortical dysplasia, and temporal lobe involvement., Results: Of the 76 patients with schizencephaly-related epilepsy, 28 (36.8%) had open lip clefts, and 13 (17.1%) had bilateral clefts. The development of epilepsy was related to a larger cleft size and the presence of cortical dysplasia. The patients with medium-to-large clefts were younger at seizure onset than those with small clefts (9.7±7.8 vs. 20.8±10.4 years). Among the 64 patients whose outcomes were evaluated, 31 (48.4%) had drug-resistant epilepsy, and 21 (32.8%) met our definition of frequent seizures. In the univariate analysis, open lip, larger clefts, and the presence of cortical dysplasia were associated with poor seizure outcomes. Even after adjustment for covariates, open lip clefts were significantly related to drug-resistant epilepsy (odds ratio=13.036, P=0.001) and frequent seizures (odds ratio=7.682, P=0.008)., Conclusion: Open lip clefts were associated with poor seizure outcomes. Further, a larger cleft was related to an earlier development of epilepsy. The anatomical features of schizencephaly should be considered in the treatment of epilepsy., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the main procedure for mediastinal staging. However, long-term survival analyses according to clinical nodal stage diagnosed by EBUS-TBNA (eN stage) have not been reported. The value of EBUS-TBNA has not been assessed through an analysis of survival in false-negative EBUS-TBNA cases., Research Question: What is the prognostic impact of eN stage in non-small cell lung cancer (NSCLC)? What is the survival rate in false-negative EBUS-TBNA cases?, Study Design and Methods: We retrospectively (January 2006 to December 2011) reviewed the medical records of patients with NSCLC who underwent EBUS-TBNA (± transesophageal approach) for initial staging (N = 1,089). Mediastinoscopy was not performed for EBUS-TBNA-negative cases. We performed 5-year survival analyses according to eN stage and treatment modality. Survival in false-negative EBUS-TBNA cases was compared with that in patients with pN0-1, including 941 non-EBUS-TBNA cases, during the same period., Results: Among the 1,089 patients undergoing EBUS-TBNA (eN0-1: n = 681; eN2: n = 314; eN3: n = 94), we observed significant differences in survival between the eN stages (eN0-1 vs eN2: P < .0001; eN2 vs eN3: P = .0118; estimated 5-year overall survival [5YOS] rate: eN0-1 = 57.4%, eN2 = 23.2%, eN3 = 12.8%). Surgery cases had better survival than nonsurgery cases among patients with eN0-1 and eN2 (eN0-1/surgery vs eN0-1/no surgery: P < .0001; eN2/surgery vs eN2/no surgery: P < .0001). Among the patients with eN0-1, there were 55 false-negative cases (eN0-1/pN2-3, pN2: n = 54; pN3: n = 1). The 5YOS rates of patients with pN0, pN1, and eN0-1/pN2-3 were 76.4%, 56.0%, and 56.4%, respectively. Patients with eN0-1/pN2-3 had worse survival than patients with pN0 (P = .0061), whereas there was no significant difference compared with patients with pN1 (P = .9191)., Interpretation: Long-term survival significantly differed according to eN stage in NSCLC, highlighting the importance of EBUS-TBNA in NSCLC staging. False-negative EBUS-TBNA cases had favorable survival which was similar to that of patients with pN1, which may provide a rationale for performing surgery after negative EBUS-TBNA results., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Cancer cells are characterized by an abnormal cell cycle. Therefore, the cell cycle has been a potential target for cancer therapeutic agents. We developed a new lead compound, DGG200064 ( 7c ) with a 2-alkoxythieno [2,3- b ]pyrazine-3-yl)-4-arylpiperazine-1-carboxamide core skeleton. To evaluate its properties, compound DGG200064 was tested in vivo through a xenograft mouse model of colorectal cancer using HCT116 cells. The in vivo results showed high cell growth inhibition efficacy. Our results confirmed that the newly synthesized DGG200064 inhibits the growth of colorectal cancer cells by inducing G2/M arrest. Unlike the known cell cycle inhibitors, DGG200064 (GI 50 = 12 nM in an HCT116 cell-based assay) induced G2/M arrest by selectively inhibiting the interaction of FBXW7 and c-Jun proteins. Additionally, the physicochemical properties of the lead compounds were analyzed. Based on the results of the study, we suggested further development of DGG200064 as a novel oral anti-colorectal cancer drug.

The authors elucidated the relationship between temperature and mortality due to food competition in ant communities in forests. A field experiment was conducted using four bait types at six different oak forest sites with different mean annual temperatures in South Korea. The mortality rate due to food competition showed a hump-shaped trend, with temperature distribution being higher at study sites with intermediate temperatures and a linear trend increasing or decreasing with temperature along the temperature gradient. In most species, the mortality rate due to interspecific competition was higher than that due to intraspecific competition, but the dominant species, which were less affected by other species, had a higher mortality rate due to intraspecific competition. In subordinate species that are highly affected by other species, the mortality rate due to intraspecific competition increased as the mortality rate due to interspecific competition decreased. The results indicated that mortality due to inter- or intraspecific competition for food was associated by temperature, density of other species, and species characteristics (body size, dominance, feeding strategy, and aggressiveness). Given the relationship between temperature and mortality due to food competition, the authors expect that changes in competition due to climate warming will affect the fitness of ant species.

Objective: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM)., Methods: The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups., Results: A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD., Conclusions: PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Background: Previous studies have shown that different alcoholic beverage types impact prostate cancer (PCa) clinical outcomes differently. However, intake patterns of specific alcoholic beverages for PCa status are understudied. The study's objective is to evaluate intake patterns of total alcohol and the three types of beverage (beer, wine, and spirits) by the PCa risk and aggressiveness status., Method: This is a cross-sectional study using 10,029 men (4676 non-PCa men and 5353 PCa patients) with European ancestry from the PCa consortium. Associations between PCa status and alcohol intake patterns (infrequent, light/moderate, and heavy) were tested using multinomial logistic regressions., Results: Intake frequency patterns of total alcohol were similar for non-PCa men and PCa patients after adjusting for demographic and other factors. However, PCa patients were more likely to drink wine (light/moderate, OR = 1.11, p = 0.018) and spirits (light/moderate, OR = 1.14, p = 0.003; and heavy, OR = 1.34, p = 0.04) than non-PCa men. Patients with aggressive PCa drank more beer than patients with non-aggressive PCa (heavy, OR = 1.48, p = 0.013). Interestingly, heavy wine intake was inversely associated with PCa aggressiveness (OR = 0.56, p = 0.009)., Conclusions: The intake patterns of some alcoholic beverage types differed by PCa status. Our findings can provide valuable information for developing custom alcohol interventions for PCa patients.

Background: Mini-screws are widely used as temporary anchorages in orthodontic treatment, but have the disadvantage of showing a high failure rate of about 10%. Therefore, orthodontic mini-screws should have high biocompatibility and retention. Previous studies have demonstrated that the retention of mini-screws can be improved by imparting bioactivity to the surface. The method for imparting bioactivity proposed in this paper is to sequentially perform anodization, periodic pre-calcification, and heat treatments with a Ti-6Al-4V ELI alloy mini-screw., Materials and Methods: A TiO 2 nanotube-structured layer was formed on the surface of the Ti-6Al-4V ELI alloy mini-screw through anodization in which a voltage of 20 V was applied to a glycerol solution containing 20 wt% H 2 O and 1.4 wt% NH 4 F for 60 min. Fine granular calcium phosphate precipitates of HA and octacalcium phosphate were generated as clusters on the surface through the cyclic pre-calcification and heat treatments. The cyclic pre-calcification treatment is a process of immersion in a 0.05 M NaH 2 PO 4 solution and a saturated Ca(OH) 2 solution at 90 °C for 1 min each., Results: It was confirmed that the densely structured protrusions were precipitated, and Ca and P concentrations, which bind and concentrate endogenous bone morphogenetic proteins, increased on the surface after simulated body fluid (SBF) immersion test. In addition, the removal torque of the mini-screw fixed into rabbit tibias for 4 weeks was measured to be 8.70 ± 2.60 N cm., Conclusions: A noteworthy point in this paper is that the Ca and P concentrations, which provide a scaffold suitable for endogenous bone formation, further increased over time after SBF immersion of the APH group specimens. The other point is that our mini-screws have a significantly higher removal torque compared to untreated mini-screws. These results represent that the mini-screw proposed in this paper can be used as a mini-screw for orthodontics., (© 2022. The Author(s).)

Objective: To examine the modifying effect of body mass index (BMI) on the association between rehabilitation length of stay (LOS), severity of injury, and motor FIM (mFIM) improvement in patients with traumatic spinal cord injury (TSCI)., Design: Retrospective cohort study., Setting: Seventeen SCI Model Systems (SCIMS) centers in the United States., Participants: A total of 3413 patients (N=3413) who had a TSCI were admitted to an SCIMS between October 2011 and August 2018., Interventions: Not applicable., Main Outcome Measures: The mFIM (12 items) improvement by discharge. Four rehabilitation LOS groups split by quartiles were created for each neurologic severity of injury group (C1-C4 level with American Spinal Injury Association Impairment Scale [AIS] ABC, C5-C8 AIS ABC, T1-S3 AIS ABC, AIS DE). The interrelationship among rehabilitation LOS, BMI, and mFIM improvement were examined using multivariate linear regressions. A stratified analysis was performed to examine the association between rehabilitation LOS and mFIM improvement by BMI status (underweight or normal weight, overweight, obesity) and neurologic groups., Results: A total of 1099 (32.2%) and 821 (24.1%) patients were overweight and had obesity, respectively. Patients with obesity had less improvement in mFIM than those who were underweight or normal weight (unit of mFIM improvement, -3.71). After stratifying by BMI status, among patients with obesity, those with the longest rehabilitation LOS showed greater improvement in mFIM than those in the shortest LOS (unit of mFIM improvement=4.78)., Conclusions: Longer inpatient rehabilitation LOS may benefit patients with TSCI by increasing mFIM improvement by discharge. Obesity is negatively associated with mFIM improvement., (Published by Elsevier Inc.)

Aim: Bacteria naturally produce membrane vesicles (MVs), which have been shown to contribute to the spread of multi-drug resistant bacteria (MDR) by delivering antibiotic-resistant substances to antibiotic-susceptible bacteria. Here, we aim to show that MVs from Gram-positive bacteria are capable of transferring β-lactam antibiotic-resistant substances to antibiotic-sensitive Gram-negative bacteria., Materials and Methods: MVs were collected from a methicillin-resistant strain of Staphylococcus aureus (MRSA) and vesicle-mediated fusion with antimicrobial-sensitive Escherichia coli (RC85). It was performed by exposing the bacteria to the MVs to develop antimicrobial-resistant E. coli (RC85-T)., Results: The RC85-T exhibited a higher resistance to β-lactam antibiotics compared to the parent strain. Although the secretion rates of the MVs from RC85-T and the parent strain were nearly equal, the β-lactamase activity of the MVs from RC85-T was 12-times higher than that of MVs from the parent strain, based on equivalent protein concentrations. Moreover, MVs secreted by RC85-T were able to protect β-lactam-susceptible E. coli from β-lactam antibiotic-induced growth inhibition in a dose-dependent manner., Conclusion: MVs play a role in transferring substances from Gram-positive to Gram-negative bacteria, shown by the release of MVs from RC85-T that were able to protect β-lactam-susceptible bacteria from β-lactam antibiotics., Significance and Impact of Study: MVs are involved in the emergence of antibiotic-resistant strains in a mixed bacterial culture, helping us to understand how the spread of multidrug-resistant bacteria could be reduced., (© 2022 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.)

Family health history (FHH) can serve as an entry point for preventive medicine by providing risk estimations for many common health conditions. College is a critical time for young adults to begin to understand the value of FHH collection, and to establish healthy behaviors to prevent FHH-related diseases. This study seeks to develop an integrated theoretical framework to examine FHH collection behavior and associated factors among college students. A sample of 2670 college students with an average age of 21.1 years completed a web-based survey. Less than half (49.8%) reported actively seeking FHH information from their family members. Respondents' knowledge about FHH were generally low. Structural equation modeling findings suggested an adequate model fit between our survey data and the proposed integrated theoretical framework. Respondents who were members of racial/ethnic minority groups exhibited higher levels of anxiety and intention to obtain FHH information but had lower confidence in their ability to gather FHH information than non-Hispanic White respondents. Therefore, educational programs designed to enhance the level of young adults' FHH knowledge, efficacy, and behavior in FHH collection, and change subjective norms are critically needed in the future, especially for these who are members of racial/ethnic minority groups.

A memristor is defined as a non-volatile memory switching two-terminal resistor, and a memristor with digital switching characteristics is widely studied as a next-generation non-volatile memory because of its simple structure, high integration density, and low power consumption. Recently, analog memristors with gradual resistance switching (RS) characteristics have garnered great attention because of their potential to implement artificial synapses that can emulate the brain functions. Transition metal oxides are thought to be strong candidate materials for the RS. In particular, tantalum oxide (TaO x )-based memristive devices provide stable and durable switching characteristics. TaO x -based memristors utilize analog switching characteristics and have excellent durability and reliability, so they can be applied as artificial synaptic device. In this study, the characteristics of analog RS using Ta 2 O 5 -based memristive devices were investigated. The current level of the Pt/Ta 2 O 5 /Pt memristors was improved by adjusting the thickness of Ta 2 O 5 . In particular, when an indium-tin-oxide (ITO) buffer layer was added to Ta 2 O 5 forming a Pt/ITO/Ta 2 O 5 /Pt heterostructured double-layer device, it showed more symmetrical potentiation and depression characteristics under both polarities than a single-layer device without ITO layer. The symmetrical and linear potentiation and depression characteristics are essential for the development of efficient memristor-based neuromorphic systems. Insertion of the ITO buffer layer improves linearity, symmetry, and stability of the analog RS properties of Ta 2 O 5 -based memristors to artificial synapses., (© 2022 IOP Publishing Ltd.)

Diarrheal diseases due to foodborne Escherichia coli are the leading cause of illness in humans. Here, we performed pathogenic typing, molecular typing, and antimicrobial susceptibility tests on seventy-five isolates of E. coli isolated from stool samples of patients suffering from foodborne diseases in Busan, South Korea. All the isolates were identified as E. coli by both biochemical analysis (API 20E system) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The bacteria displayed entero-pathogenic E. coli (EPEC) (47.0%), entero-aggregative E. coli (EAEC) (33.3%), entero-toxigenic E. coli (ETEC) (6.6%), ETEC and EPEC (6.6%), EPEC and EAEC (4%), and ETEC and EAEC (2.7%) characteristics. The E. coli isolates were highly resistant to nalidixic acid (44.0%), tetracycline (41.3%), ampicillin (40%), ticarcillin (38.7%), and trimethoprim/sulfamethoxazole (34.7%); however, they were highly susceptible to imipenem (98.6%), cefotetan (98.6%), cefepime (94.6%), and chloramphenicol (94.6%). Although 52 strains (69.3%) showed resistance against at least 1 of the 16 antibiotics tested, 23 strains (30.7%) were susceptible to all the antibiotics. Nine different serotypes (O166, O8, O20, O25, O119, O159, O28ac, O127a, and O18), five genotypes (I to V, random-amplified polymorphic DNA), and four phenotypes (A to D, MALDI-TOF MS) were identified, showing the high level of heterogeneity between the E. coli isolates recovered from diarrheal patients in South Korea.

ARV-110, a novel proteolysis-targeting chimera (PROTAC), has been reported to show satisfactory safety and tolerability for prostate cancer therapy in phase I clinical trials. However, there is a lack of bioanalytical assays for ARV-110 determination in biological samples. In this study, we developed and validated an LC-MS/MS method for the quantitation of ARV-110 in rat and mouse plasma and applied it to pharmacokinetic studies. ARV-110 and pomalidomide (internal standard) were extracted from the plasma samples using the protein precipitation method. Sample separation was performed using a C18 column and a mobile phase of 0.1% formic acid in distilled water-0.1% formic acid in acetonitrile (30:70, v / v ). Multiple reaction monitoring was used to quantify ARV-110 and pomalidomide with ion transitions at m/z 813.4 → 452.2 and 273.8 → 201.0, respectively. The developed method showed good linearity in the concentration range of 2-3000 ng/mL with acceptable accuracy, precision, matrix effect, process efficiency, and recovery. ARV-110 was stable in rat and mouse plasma under long-term storage, three freeze-thaw cycles, and in an autosampler, but unstable at room temperature and 37 °C. Furthermore, the elimination of ARV-110 via phase 1 metabolism in rat, mouse, and human hepatic microsomes was shown to be unlikely. Application of the developed method to pharmacokinetic studies revealed that the oral bioavailability of ARV-110 in rats and mice was moderate (23.83% and 37.89%, respectively). These pharmacokinetic findings are beneficial for future preclinical and clinical studies of ARV-110 and/or other PROTACs.

The emergence of antimicrobial-resistant Staphylococcus aureus has become a grave concern worldwide. In this study, 95 strains of S. aureus isolated from stool samples were collected from Busan, South Korea to characterize their antimicrobial susceptibility, enterotoxin genes, and molecular typing using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and random amplification of polymorphic DNA (RAPD) assay. Only two strains showed no drug resistance, whereas resistance to three or more antibiotics was observed in 87.4% of strains. Ampicillin resistance was the most common at 90% and all strains were susceptible to vancomycin. The distribution of enterotoxin genes encoded in isolates was sea (32.6%), sec (11.6%), seg (19%), sea & sec (2.1%), and sec & seg (34.7%). Molecular typing using both MALDI-TOF MS and RAPD indicated that S. aureus exhibited diverse clonal lineages and no correlations were observed among the profiling of enterotoxin, MALDI-TOF MS, and RAPD. This investigation provides useful information on foodborne pathogenic S. aureus that has a significant public health impact in South Korea.

Gray mold disease is one of the most frequently occurring diseases in strawberries. Given that it spreads rapidly, rapid countermeasures are necessary through the development of early diagnosis technology. In this study, hyperspectral images of strawberry leaves that were inoculated with gray mold fungus to cause disease were taken; these images were classified into healthy and infected areas as seen by the naked eye. The areas where the infection spread after time elapsed were classified as the asymptomatic class. Square regions of interest (ROIs) with a dimensionality of 16 × 16 × 150 were acquired as training data, including infected, asymptomatic, and healthy areas. Then, 2D and 3D data were used in the development of a convolutional neural network (CNN) classification model. An effective wavelength analysis was performed before the development of the CNN model. Further, the classification model that was developed with 2D training data showed a classification accuracy of 0.74, while the model that used 3D data acquired an accuracy of 0.84; this indicated that the 3D data produced slightly better performance. When performing classification between healthy and asymptomatic areas for developing early diagnosis technology, the two CNN models showed a classification accuracy of 0.73 with regards to the asymptomatic ones. To increase accuracy in classifying asymptomatic areas, a model was developed by smoothing the spectrum data and expanding the first and second derivatives; the results showed that it was possible to increase the asymptomatic classification accuracy to 0.77 and reduce the misclassification of asymptomatic areas as healthy areas. Based on these results, it is concluded that the proposed 3D CNN classification model can be used as an early diagnosis sensor of gray mold diseases since it produces immediate on-site analysis results of hyperspectral images of leaves., Competing Interests: 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 manuscript., (Copyright © 2022 Jung, Kim, Kim, Lee, Kim and Park.)

Throughout the ages, hair has had psychological and sociological importance in framing the personality and general appearance of an individual. Despite efforts to solve this problem, no groundbreaking measures have been proposed. Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Three fractions (F1, F2 and F3) were obtained after separation and purification of GAGs from ascidian tunics. F1 was observed to contain a small amount of amino sugar while high contents of galactose and N-acetylglucosamine were noted in F2 and F3. 2-acetamido-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (∆Di-6S) and 2-acetamido-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (∆Di-4S) were the main disaccharide components. F3 exhibited the highest proliferation activity on human follicle dermal papilla (HFDP) cells. In addition, mixed samples (FFM) of F2 and F3 at different concentrations showed peak activities for five days. After cell culture at a concentration of 10 mg/mL and dihydrotestosterone (DHT), the inhibition effect was higher than that for Minoxidil. Application of 10 mg of FFM to the hair of mice for 28 days resulted in a hair growth effect similar to that of Minoxidil, a positive control.

Uncovering tumor markers of colorectal cancer is important for the early detection and prognosis of the patients. Spermine oxidase (SMOX) is upregulated in various cancers. The present study aims to explore the biologic function and expression patterns of SMOX in colorectal cancer (CRC), the third most common type of cancer worldwide. We used quantitative real-time PCR, Western blot, and in vitro functional studies in four CRC cell lines knocked down by SMOX siRNA and immunohistochemistry in 350 cases of CRC tissues. The results showed that SMOX was overexpressed in CRC cell lines and clinical samples. SMOX overexpression in tumor tissues was an independent prognostic factor, worsening overall survival ( p = 0.001). The knock-down of SMOX inhibited CRC cell proliferation, invasion, and soft agar colony formation, uncovering its carcinogenic functions. This study indicated that SMOX overexpression could be an important oncogene in CRC and might serve as a valuable prognostic marker and potential therapeutic target for CRC.

Titanium has a significant potential for the cryogenic industrial fields such as aerospace and liquefied gas storage and transportation due to its excellent low temperature properties. To develop and advance the technologies in cryogenic industries, it is required to fully understand the underlying deformation mechanisms of Ti under the extreme cryogenic environment. Here, we report a study of the lattice behaviour in grain families of Grade 2 CP-Ti during in-situ neutron diffraction test in tension at temperatures of 15-298 K. Combined with the neutron diffraction intensity analysis, EBSD measurements revealed that the twinning activity was more active at lower temperature, and the behaviour was complicated with decreasing temperature. The deviation of linearity in the lattice strains was caused by the load-redistribution between plastically soft and hard grain families, resulting in the three-stage hardening behaviour. The lattice strain behaviour further deviated from linearity with decreasing temperature, leading to the transition of plastically soft-to-hard or hard-to-soft characteristic of particular grain families at cryogenic temperature. The improvement of ductility can be attributed to the increased twinning activity and a significant change of lattice deformation behaviour at cryogenic temperature., (© 2022. The Author(s).)

Background: Gastric gastrointestinal stromal tumors (GISTs) exhibit various degrees of aggression and malignant potential. However, no systematic preoperative evaluation strategy to predict the malignancy potential of gastric GISTs has yet been developed. This study aimed to develop a reliable and easy-to-use preoperative risk-scoring model for predicting high malignancy potential (HMP) gastric GISTs., Methods: The data of 542 patients with pathologically confirmed gastric GISTs who underwent resection were reviewed. Multivariate logistic regression analysis was used to identify significant predictors of HMP. The risk-scoring system (RSS) was based on the predictive factors for HMP, and its performance was validated using a split-sample approach., Results: A total of 239 of 542 (44.1%) surgically resected gastric GISTs had HMP. Multivariate analysis demonstrated that tumor size, location, and surface changes were independent risk factors for HMP. Based on the accordant regression coefficients, the presence of surface ulceration was assigned 1 point. Tumor sizes of 4-6 cm and > 6 cm were assigned 2 and 5 points, respectively. Two points were assigned to cardia or fundus locations. A score of 3 points was the optimal cut-off value for HMP prediction. HMP were found in 19.8% and 82.7% of the low and high-risk groups of the RSS, respectively. The area under the receiver-operating characteristic curve for predicting HMP was 0.81 (95% confidence interval (CI) 0.75-0.86). Discrimination was good after validation (0.75, 95% CI 0.69-0.81)., Conclusion: This simple RSS could be useful for predicting the malignancy potential of gastric GISTs and may aid preoperative clinical decision making to ensure optimal treatment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study Design: Retrospective cohort study., Objective: Investigate the association between rehabilitation length of stay (LOS) and motor FIM ® (mFIM) between rehabilitation admission and discharge among patients with traumatic spinal cord injury (SCI)., Setting: Seventeen SCI Model Systems (SCIMS) centers in the United States., Methods: A total of 3386 patients with traumatic SCI enrolled in the SCIMS Database from 2011 to 2018. The main outcome measure was the mean change in mFIM (12 items) between rehabilitation admission and discharge by twelve neurological categories (C1-C4 American Spinal Injury Association impairment scale (AIS) A-B, AIS C, AIS D, and C5-C8 AIS A-B, AIS C, AIS D, and T1-T10 AIS A-B, AIS C, AIS D, and T11-S3 AIS A-B, C, D). Linear regression models were applied to estimate changes across rehabilitation LOS groups (shortest LOS, quarter2, quarter3, and longest LOS) after adjusting for covariables for each neurological category., Results: The mean age of study patients was 44.5 years. Patients were predominantly men (78.5%), non-Hispanic white (64.8%), and had private insurance (57.1%). The median LOS was 42 days across the entire sample. Longer LOS was associated with a higher mFIM score compared to the shortest LOS among patients with C1-C4 AIS D; C5-C8 AIS D; T1-T10 AIS A-B; and T11-S3 AIS A-B, C, and D after adjusting for demographics and clinical characteristics., Conclusion: Among patients with C1-C4 AIS D; C5-C8 AIS D; T1-T10 AIS A-B; and T11-S3 AIS A-B, C, and D injuries, those with longer rehabilitation stays tended to have more motor function improvement., (© 2021. The Author(s), under exclusive licence to International Spinal Cord Society.)

Brain-inspired computing enabled by memristors has gained prominence over the years due to the nanoscale footprint and reduced complexity for implementing synapses and neurons. The demonstration of complex neuromorphic circuits using conventional materials systems has been limited by high cycle-to-cycle and device-to-device variability. Two-dimensional (2D) materials have been used to realize transparent, flexible, ultra-thin memristive synapses for neuromorphic computing, but with limited knowledge on the statistical variation of devices. In this work, we demonstrate ultra-low-variability synapses using chemical vapor deposited 2D MoS 2 as the switching medium with Ti/Au electrodes. These devices, fabricated using a transfer-free process, exhibit ultra-low variability in SET voltage, RESET power distribution, and synaptic weight update characteristics. This ultra-low variability is enabled by the interface rendered by a Ti/Au top contact on Si-rich MoS 2 layers of mixed orientation, corroborated by transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS), and X-ray photoelectron spectroscopy (XPS). TEM images further confirm the stability of the device stack even after subjecting the device to 100 SET-RESET cycles. Additionally, we implement logic gates by monolithic integration of MoS 2 synapses with MoS 2 leaky integrate-and-fire neurons to show the viability of these devices for non-von Neumann computing.

mCardinal2 is a red fluorescent protein developed through the designs of mKate, mNeptune and mCardinal. Fluorescence spectrums of mCardinal2 and its five mutants (T143C, T143G, C158A, C158D and M160E) were measured with their quantum yields. C158A and C158D increased brightness with slight changes in fluorescence spectrums while T143C, T143G and M160E decreased brightness with blue shift in fluorescence spectrums, which resulted in green, cyan and green fluorescent proteins respectively. Crystal structures of all six variants were analyzed and compared together with those of mKate, LSS-mKate1, LSS-mKate2 and mCardinal. Around the Cα-Cβ bond of Tyr64 in the MYG chromophores, only C158A and C158D were in the trans conformation while all others were mostly in the cis conformation. Blue-shift brightness-decreased variants (T143C, T143G and M160E) showed the diminished hydrogen bonds while large-Stoke-shift brightness-increased variant C158D showed the enhanced hydrogen bonds around the chromophore., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tae-Sung Yoon reports financial support was provided by KRIBB. Tae-Sung Yoon reports a relationship with Korea Research Institute of Bioscience and Biotechnology that includes: employment and funding grants., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Several natural substances including protein produce sweet taste. Brazzein, derived from the plant Pentadipladra brazzeana, is one of the sweet proteins that bind to the taste receptor with stronger sweetness than sugar. Mutations of this protein affect its flavour, yielding higher sweetness in D29K and lower sweetness in R43A. To elucidate its sweet mechanism in the taste receptor, we determined the structures of two variants, D29K and R43A, to a resolution of 1.5 Å and 1.3 Å, respectively. Structures of the brazzein exhibit two α-helix and three β-sheets connected by four disulfide bonds with a significantly altered electrostatic distribution on the surface. Using the high-resolution structure data and models of the taste receptors T1R2 and T1R3 in the AlphaFold Protein Structure Database, we performed a docking calculation on the receptors and report that brazzein is bound between the two cysteine rich domains (CRDs) of the heterodimer protein complex. Substitution to lysine in D29K resulted in an increased number of hydrogen bonds in the T1R2 receptor, while substitution to alanine in R43A ablated a polar interaction in the T1R3 receptor. The significantly altered interaction of the variants at the interface is consistent with a change of the sweetness. The high-resolution structure and the docking model in this study may provide a structural basis to understand the flavour mechanism induced by the sweet protein., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Widely used in global households, fenugreek is well known for its culinary and medicinal uses. The various reported medicinal properties of fenugreek are by virtue of the different natural phytochemicals present in it. Regarded as a promising target, interleukin 2 receptor subunit alpha (IL2Rα) has been shown to influence immune responses. In the present research, using in silico techniques, we have demonstrated the potential IL2Rα binding properties of three polyphenol stilbenes (desoxyrhaponticin, rhaponticin, rhapontigenin) from fenugreek. As the first step, molecular docking was performed to assess the binding potential of the fenugreek phytochemicals with IL2Rα. All three phytochemicals demonstrated interactions with active site residues. To confirm the reliability of our molecular docking results, 100 ns molecular dynamics simulations studies were undertaken. As discerned by the RMSD and RMSF analyses, IL2Rα in complex with the desoxyrhaponticin, rhaponticin, and rhapontigenin indicated stability. The RMSD analysis of the phytochemicals alone also demonstrated no significant structural changes. Based on the stable molecular interactions and comparatively slightly better MM/PBSA binding free energy, rhaponticin seems promising. Additionally, ADMET analysis performed for the stilbenes indicated that all of them obey the ADMET rules. Our computational study thus supports further in vitro IL2Rα binding studies on these stilbenes, especially rhaponticin.

Objective: Pilocytic astrocytomas (PAs) have a generally favorable prognosis; however, progression or recurrence after resection is possible. The prognostic value of histopathological qualifiers (defined below) or BRAF alterations is not well understood. The aim of this study was to identify the prognostic value of genetic and histopathological features of pediatric PAs., Methods: Patients treated for a WHO grade I PA at a single institution were analyzed for histopathological and genetic features and outcomes. "Histopathological qualifier" refers to designations such as "WHO grade I PA with increased proliferative index." BRAF alterations include gene fusions and point mutations. Patients with neurofibromatosis type 1 were excluded., Results: A total of 222 patients were analyzed (51% female, mean age 9.6 years). Tumors were located in the cerebellum/fourth ventricle (51%), optic pathway/hypothalamus (15%), brainstem (12%), and cerebral cortex (11%). BRAF alterations were screened for in 77 patients and identified in 56 (73%). Histopathological qualifiers were present in 27 patients (14%). Resection was performed in 197 patients (89%), 41 (21%) of whom displayed tumor progression or recurrence after resection. Tumor progression or recurrence was not associated with histopathologic qualifiers (p = 0.36) or BRAF alterations (p = 0.77). Ki-67 proliferative indices were not predictive of progression or recurrence (p = 0.94). BRAF alterations, specifically KIAA1549 fusions, were associated with cerebellar/fourth ventricular tumor location (p < 0.0001) and younger patient age (p = 0.03). Patients in whom gross-total resection was achieved had lower rates of progression and recurrence (p < 0.0001)., Conclusions: Histopathological features/qualifiers and BRAF alterations were not associated with tumor recurrence/progression in pediatric PAs. The extent of resection was the only factor analyzed that predicted outcome.

The advantages of laparoscopic resection over open surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) are not conclusive. This study aimed to evaluate the postoperative and oncologic outcome of laparoscopic resection for gastric GIST, compared to open surgery. We retrospectively reviewed the prospectively collected database of 1019 patients with gastric GIST after surgical resection at 13 Korean and 2 Japanese institutions. The surgical and oncologic outcomes were compared between laparoscopic and open group, through 1:1 propensity score matching (PSM). The laparoscopic group (N = 318) had a lower rate of overall complications (3.5% vs. 7.9%, P = 0.024) and wound complications (0.6% vs. 3.1%, P = 0.037), shorter hospitalization days (6.68 ± 4.99 vs. 8.79 ± 6.50, P < 0.001) than the open group (N = 318). The superiority of the laparoscopic approach was also demonstrated in patients with tumors larger than 5 cm, and at unfavorable locations. The recurrence-free survival was not different between the two groups, regardless of tumor size, locational favorableness, and risk classifications. Cox regression analysis revealed that tumor size larger than 5 cm, higher mitotic count, R1 resection, and tumor rupture during surgery were independent risk factors for recurrence. Laparoscopic surgery provides lower rates of complications and shorter hospitalizations for patients with gastric GIST than open surgery., (© 2022. The Author(s).)

Herein, an unprecedented report is presented on the incorporation of size-dependent gold nanoparticles (AuNPs) with polyvinylpyrrolidone (PVP) capping into a conventional hole transport layer, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The hole transport layer blocks ion-diffusion/migration in methylammonium-lead-bromide (MAPbBr 3 )-based perovskite light-emitting diodes (PeLEDs) as a modified interlayer. The PVP-capped 90 nm AuNP device exhibited a seven-fold increase in efficiency (1.5%) as compared to the device without AuNPs (0.22%), where the device lifetime was also improved by 17-fold. This advancement is ascribed to the far-field scattering of AuNPs, modified work function and carrier trapping/detrapping. The improvement in device lifetime is attributed to PVP-capping of AuNPs which prevents indium diffusion into the perovskite layer and surface ion migration into PEDOT:PSS through the formation of induced electric dipole. The results also indicate that using large AuNPs (> 90 nm) reduces exciton recombination because of the trapping of excess charge carriers due to the large surface area., (© 2022. The Author(s).)

Background: The appropriate surgical approach for Siewert type II esophagogastric junction (EGJ) cancer remains under discussion. We compared surgical outcomes between transabdominal (TA) and transthoracic (TT) approaches for treating type II EGJ cancers., Materials and Methods: This retrospective study reviewed 397 type II EGJ cancer patients who underwent surgery from January 2001 to May 2019. We used a 1:3 propensity score-matching method for the analysis. The matching factors were age, sex, American Society of Anesthesiologists score, period of operation, and pathologic stage. Matching was performed using the MatchIt package of R 4.0.2., Results: A total of 46 patients in the TT group was matched to 126 patients in the TA group. R0 resection was achieved in both groups and was not statistically different between groups (p = 0.455). In the TA group, the operation time and in-hospital stay length were significantly shorter (p < 0.001) and the intraoperative estimated blood loss (EBL) was significantly lower than in the TT group (p = 0.011). The postoperative complication rate between the two groups was significantly different (p = 0.003). There was marginal difference in the five-year OS rate (p = 0.049) and significant difference in the five-year DFS (p = 0.039). However, surgical approach was not a significant prognostic factor in multivariate analysis of OS or DFS., Conclusions: There was no clear survival benefit of one approach over the other. However, less intraoperative bleeding, lower postoperative complication rate, shorter operation time, and reduced in-hospital stay length were correlated with the TA approach., Competing Interests: Declaration of competing interest The authors report no conflicts of interest related to this study., (Copyright © 2021. Published by Elsevier Ltd.)

Despite the essential roles of natural killer (NK) cells in cancer treatment, the physical barrier and biological cues of the tumor microenvironment (TME) may induce NK cell dysfunction, causing their poor infiltration into tumors. The currently available two-dimensional (2D) cancer-NK co-culture systems hardly represent the characteristics of TME and are not suitable for tracking the infiltration of immune cells and assessing the efficacy of immunotherapy. This study aims to monitor NK-mediated cancer cell killing using a polymer thin film-based, 3D assay platform that contains highly tumorigenic cancer spheroids. A poly(cyclohexyl methacrylate) (pCHMA)-coated surface enables the generation of tumorigenic spheroids from pancreatic cancer patient-derived cancer cells, showing considerable amounts of extracellular matrix (ECM) proteins and cancer stem cell (CSC)-like characteristics. The 3D spheroid-based assay platform allows rapid discovery of a therapeutic agent for synergistic NK-mediated cytotoxicity through imaging-based high-content screening. In detail, the small molecule C19, known as a multi-epithelial-mesenchymal transition pathway inhibitor, is shown to enhance NK activation and infiltration via modulation of the ECM, resulting in synergistic cytotoxicity against cancer spheroids. This 3D biomimetic co-culture assay platform provides promising applications for predicting patient-specific responses to immunotherapy through advanced therapeutic combinations involving a chemical drug and immune cells.

Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected TCR signaling strength in CD4 T cells. Results revealed that Erdr1 significantly enhanced the anti-TCR antibody-mediated activation and proliferation of T cells while failing to activate T cells in the absence of TCR stimulation. In addition, Erdr1 amplified Ca 2+ influx and the phosphorylation of PLCγ1 in CD4 T cells with the TCR stimuli. Furthermore, NFAT1 translocation into nuclei in CD4 T cells was also significantly promoted by Erdr1 in the presence of TCR stimulation. Taken together, our results indicate that Erdr1 positively modulates TCR signaling strength via enhancing the PLCγ1/Ca 2+ /NFAT1 signal transduction pathway.

Under certain conditions, numerous soluble proteins possess an inherent tendency to convert into insoluble amyloid aggregates, which are associated with several sporadic and genetic human diseases. Transthyretin (TTR) is one of the more than 30 human amyloidogenic proteins involved in conditions such as senile systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid cardiomyopathy. Considerable effort has been focused on identifying the native tetrameric TTR stabilizers to inhibit rate-limiting tetramer dissociation and, consequently, ameliorate TTR amyloidogenesis. Here, we describe the design and synthesis of quinolin-2(1H)-one derivatives that could be structurally complementary to the thyroxine-binding site within tetrameric TTR. Among these quinolin-2(1H)-one derivatives, compound 7a allowed 16.7% of V30M-TTR (3.6 μM) fibril formation at the same concentration and 49.6% at a concentration of 1.8 μM. Compound 7a exhibited much greater potency in complex biological samples like human plasma than that observed with tafamidis, the drug approved for the treatment of TTR amyloid cardiomyopathy for wild-type or hereditary TTR-mediated amyloidosis. Furthermore, the unique spectral properties of compound 7a demonstrated its high potential for TTR quantification, imaging sensors, and fluorescent tools to study the mechanism of TTR amyloidogenesis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: We describe the prevalence, thromboembolic risk factors, and neurologic outcomes in children with congenital heart disease (CHD) and arterial ischemic stroke (AIS)., Methods: We retrospectively analyzed the clinical data of children with CHD and AIS from 2000 to 2016. Demographics, procedural and postprocedural data, neuroimaging findings, details of antithrombotic treatment, and neurological status at last follow up were evaluated., Results: Patients with cyanotic CHD accounted for 24 of 30 cases with AIS. The majority of AIS (70%) was procedure related, and the mean time from procedure to diagnosis of stroke was 9.7 (range, 1-30) days. At the time of AIS, 14 (46.7%) patients revealed coexistence of additional thromboembolic causes of AIS. Three patients (10.0%) experienced recurrent AIS and six patients (20.0%) were diagnosed with post-stroke epilepsy. The unfavorable outcomes were found in 13 patients (43.3%), including four deaths. The unfavorable outcome was significantly associated with the main branch involvement of middle cerebral artery (OR = 10.296, 95% CI = 1.335-79.439) and hemorrhagic transformation (OR = 16.264, 95% CI = 1.359-194.690)., Conclusions: Additional thromboembolic risk factors such as systemic or cardiac thrombus, arrhythmia, and surgical procedures for cyanotic CHD were found in patients with CHD and AIS. The main branch involvement of middle cerebral artery and hemorrhagic transformation were significant predictors of unfavorable outcomes. Further studies are required to identify the target for stroke prevention and develop better prophylactic strategies to minimize AIS in patients with CHD., (© 2022 Japan Pediatric Society.)

Background: Trunk control ability is an important component of functional independence after the onset of stroke. Recently, it has been reported that robot-assisted functional training is effective for stroke patients. However, most studies on robot-assisted training have been conducted on upper and lower extremities., Objective: The purpose of this study was to evaluate the effects of robot-assisted trunk control training on trunk postural control and balance ability in stroke patients., Methods: Forty participants with hemiparetic stroke were recruited and randomly divided into two groups: the RT (robot-assisted trunk control training) group (n= 20) and the control group (n= 20). All participants underwent 40 sessions of conventional trunk stabilization training based on the Bobath concept (for 30 minutes, five-times per week for 8 weeks). After to each training session, 15 minutes of robotassisted trunk control training was given in the RT group, whereas the control group received stretching exercise for the same amount of time. Robot-assisted trunk control training was conducted in three programs: sitting balance, sit-to stand, and standing balance using a robot system specially designed to improve trunk control ability. To measure trunk postural control ability, trunk impairment scale (TIS) was used. Center of pressure (COP) distance, limits of stability (LOS), Berg Balance Scale (BBS) and functional reach test (FRT) were used to analyze balance abilities., Results: In TIS, COP distance, LOS, BBS and FRT, there were significant improvements in both groups after intervention. More significant changes were shown in the RT group than the control group (p< 0.05)., Conclusions: Our findings indicate that robot-assisted trunk control training is beneficial and effective to improve trunk postural control and balance ability in stroke patients. Therefore robot-assisted training may be suggested as an effective intervention to improve trunk control ability in patients with stroke.

Background and Purpose: This study was aimed to describe focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients., Methods: A total of 82 SCN1A mutation-positive patients were reviewed retrospectively (39 boys and 43 girls). Seizure type and electroencephalography (EEG) findings were investigated according to the stage, disease onset, and steady state (after age 2 years). Long-term video EEG data were used to classify the seizure type., Results: Focal seizures at onset and the steady state were found in 54.9% (45/82) and 90% (63/70) of patients, respectively. Afebrile focal seizures were an initial seizure in about one fourth of the patients (22/82, 26.8%). Of 48 seizures captured during long-term video EEG monitoring of 30 patients, 19 seizures were classified as focal onset (39.6%). Of the 19 focal seizures, 12 were either focal motor or focal non-motor seizures, and seven were focal onset bilateral tonic-clonic seizure. Focal epileptiform discharges were more frequent than generalized epileptiform discharges at seizure onset and during the clinical course on conventional EEG (3.7% vs. 0%, 52.9% vs. 32.9%, respectively)., Conclusions: Our study provides a comprehensive description of focal epilepsy features of SCN1A mutation-positive Dravet syndrome patients. Recognizing these features as defining the clinical spectrum of Dravet syndrome may lead to earlier genetic diagnosis and tailored management., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest., (Copyright © 2021 Korean Epilepsy Society.)