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Aims: The association between skeletal muscle mass and diabetes incidence/insulin resistance/glycated hemoglobin (HbA1C) is unknown. The aim of this study was to investigate such association in clinically apparently healthy males and females., Methods: A cross-sectional study of 372,399 Korean males and females who completed bioelectrical impedance analysis (BIA) in a health-screening programme was performed. Skeletal muscle index was used as an indicator of skeletal muscle mass. Skeletal muscle index (%) [appendicular skeletal muscle mass (kg)/body weight (kg)X100] was estimated using BIA. The study outcomes were diabetes incidence, homoeostasis model assessment of insulin resistance (HOMA-IR), and HbA1C., Results: The mean age of study participants was 38.92 ± 8.54 years. Multiple logistic regression analysis revealed a significant negative association between Skeletal muscle index and diabetes incidence/HOMA-IR/HbA1C after adjusting for various confounding factors. Odds ratios (95% confidence interval (CI)) of diabetes incidence in Q2, Q3, and Q4 compared to the lowest quantile (Q1) were 0.95 (0.85-1.05), 0.88 (0.78-0.99), and 0.79 (0.69-0.9), respectively. Beta coefficients (95% CI) of HOMA-IR in Q2, Q3, and Q3 with Q1 were 0.05 (0.03-0.07), -0.06 (-0.09∼-0.04), and -0.19 (-0.22∼-0.16), respectively. Beta coefficients (95% CI) of HbA1C in Q2, Q3, and Q4 with Q1 were 0.02 (0.01-0.03), -0.001 (-0.01∼0.01), and -0.02 (-0.03∼-0.01), respectively., Conclusions: This study demonstrated negative associations of skeletal muscle mass with diabetes incidence, insulin resistance, and HbA1C levels in healthy adults., (© 2023 John Wiley & Sons Ltd.)

New approach methods (NAMs) have been developed to predict a wide range of toxicities through innovative technologies. Liver injury is one of the most extensively studied endpoints due to its severity and frequency, occurring among populations that consume drugs or dietary supplements. In this review, we focus on recent developments of in silico modeling for liver injury prediction using deep learning and in vitro data based on adverse outcome pathways (AOPs). Despite these models being mainly developed using datasets generated from drug-like molecules, they were also applied to the prediction of hepatotoxicity caused by herbal products. As deep learning has achieved great success in many different fields, advanced machine learning algorithms have been actively applied to improve the accuracy of in silico models. Additionally, the development of liver AOPs, combined with big data in toxicology, has been valuable in developing in silico models with enhanced predictive performance and interpretability. Specifically, one approach involves developing structure-based models for predicting molecular initiating events of liver AOPs, while others use in vitro data with structure information as model inputs for making predictions. Even though liver injury remains a difficult endpoint to predict, advancements in machine learning algorithms and the expansion of in vitro databases with relevant biological knowledge have made a huge impact on improving in silico modeling for drug-induced liver injury prediction., Competing Interests: Declaration of competing interest None conflicted interest needs to be declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Selectively excited o -toluidine and α-methylbenzylamine have been studied with quasi-classical trajectory procedures to determine the extent and timescales of intramolecular energy flow. The initial excitation is in the stretching mode of the para -CH bond, and its flow is initiated by interaction with an argon atom. Energy flow to the NH stretching mode is the dominant relaxation pathway, and its effectiveness is enhanced strongly by the methyl-NH interaction. Energy flow characteristics in both molecules are similar, but the flow is more effective in o -toluidine than in α-methylbenzylamine because the methyl group bonded to the benzene ring exerts stronger perturbation on the energy-flow pathway than the group bonded to the side chain. The relaxation of the initially excited CH completes on a timescale of several picoseconds, but the main part of energy flow to the NH occurs on a subpicosecond scale. In o -toluidine, carbon-carbon overtone modes lead to ring-CC bonds gaining and transporting more energy than high-frequency CH bonds, but they all gain far less energy than the NH stretching mode.

Background: In multilevel posterior lumbar interbody fusion (PLIF) with posterior screw fixation, obtaining sufficient lumbar lordosis (LL) is difficult, especially in patients with osteoporosis. We performed intraoperative table modification (TM) using gravitational dropping of the patient's lumbar spine, to improve restoration of LL., Methods: We retrospectively reviewed the medical records of patients who underwent three- or four-level PLIF between 2005 and 2019. One hundred eleven patients were enrolled, with 96 patients receiving non-TM-PLIF and 15 patients receiving TM-PLIF. Radiological parameters, including segmental lordosis (SL), LL, sacral slope (SS), pelvic incidence, and pelvic tilt, were measured. Clinical outcomes were measured using a visual analogue scale (VAS) for the back and leg preoperatively and at the last follow-up. Additionally, the correlation between the bone mineral density (BMD) and the radiological parameters was calculated for TM-PLIF. We performed propensity score matching between the groups to control the baseline difference., Results: We found a statistically better correction between immediate and last follow-up postoperative SL (p = 0.04), as well as between preoperative and last follow-up SL (p < 0.01) in the TM-PLIF group compared to that in the non-TM-PLIF group. VAS for the back and leg were not significantly different between the two groups. Additionally, the efficacy of lordosis correction in the TM-PLIF group showed a statistically significant negative correlation between BMD and the SS change both before and after the surgery (rho = -0.60, p = 0.02)., Conclusion: Whilst further study is required to conclusively establish its efficacy, TM-PLIF (table modification using gravitational dropping) shows potential advantages for restoring and maintaining LL in multilevel lumbar fusion, particularly in cases with low BMD.

The indoor environment has been recognized as a crucial factor that can influence health and wellbeing of occupants. This is particularly true in hospital settings, where various environmental attributes can significantly affect patients' recovery and staff members' productivity. The present study aimed to investigate how occupants in hospitals perceived indoor environment, focusing specifically on COVID-19 hospitals across Republic of Korea. The study recruited two groups of participants: patients ( n = 100) who had been hospitalized in COVID-19 hospitals and staff members ( n = 103) who worked in COVID-19 hospitals. The data collected from the participants were analyzed using multiple regression models to determine which environmental attributes significantly affected their perception of the indoor environment. The study revealed that satisfaction with indoor acoustic environment and odor were significant predictors for how patients perceived the indoor environment as helpful for their recovery from COVID-19. On the other hand, odor was also the significant factor affecting staff members' perceived helpfulness for work. The results suggested that different environmental attributes can have a significant impact on the perception of the indoor environment, depending on the characteristics of occupancy. The study's findings provided insights into the certain environmental factors that COVID-19 hospitals can prioritize. These insights can help policymakers and hospital administrators to develop strategies to create hospital environments that meet the needs of both groups. The study also suggested that further research is needed to investigate additional factors affecting occupants' perception of the indoor environment in hospital settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Park, Shin and Kim.)

The coronavirus disease 2019 (COVID-19) pandemic has had a major influence on working patterns worldwide, given the various lockdown periods and the shift to remote working. As people's noise perception is known to be closely linked with their work performance and job satisfaction, investigating the noise perception in indoor spaces, especially in situations where people work from home, is crucial; however, studies on this aspect are limited. Thus, here, this study aimed to investigate the relationship between indoor noise perception and remote work during the pandemic. The study assessed how people who worked from home perceived indoor noise, and how it related with their work performance and job satisfaction. A social survey was conducted with respondents who worked from home during the pandemic in South Korea. A total of 1,093 valid responses were used for data analysis. Structural equation modeling was used as a multivariate data analysis method to simultaneously estimate multiple and interrelated relationships. The results showed that indoor noise disturbance significantly affected annoyance and work performance. Annoyance with indoor noise affected job satisfaction. Job satisfaction was found to have a significant impact on work performance, particularly on two dimensions of the work performance that are crucial for achieving organizations' goals. Moreover, one dimension of the work performance had a significant impact on annoyance. The study proposed that reducing negative perception of indoor noise and improvement of job satisfaction can lead to the maximization of one's work performance when working from home., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Injury to the genitourinary tract is rare, with an incidence of less than 1%. Younger men (mean age, approximately 30 years) are predominantly affected. We introduce an unusual case of a 25-year-old male patient with complete urethral injury combined with a severe open pelvic bone fracture. During the emergency surgery, the primary realignment of the posterior urethra could not be performed due to a large defect. With suprapubic cystostomy alone, follow-up voiding cystourethrography showed spontaneous recanalization of the transected urethra after four months. Suprapubic cystostomy is an efficient treatment option when primary realignment is not possible., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (© 2023 The Korean Society of Traumatology.)

Background: Enophthalmos is one of the most distressing complications of blowout orbital fractures. Although several studies have been conducted on the topic of indications of early surgical correction, none have been performed using a set of measurable parameters., Methods: The study quantitatively examined orbital fracture areas (OFA) and volumes (OFV) retrospectively of 242 patients with isolated medial orbital wall fractures that were treated conservatively during a 12-year period (from 2009 to 2021). Three plastic surgeons measured enophthalmos >6 months after trauma. The correlations between parameters and enophthalmos in the study cohort were analyzed. In addition, patients treated operatively, and nonoperatively were compared with assess the suitability of the predictive model., Results: Significant correlations were observed between several parameters and late enophthalmos. Total 2.59 cm 2 of OFA (ie, OFA >2.59 cm 2 ) or 1.45 cm 3 of OFV (ie, OFV >1.45 cm 3 ) corresponds to 2 mm of enophthalmos. Multiple regression analysis revealed the following coefficients: -0.208 is a constant ( P <0.001), with 0.695 and 0.372 for OFA and OFV, respectively ( P <0.001 for both OFA and OFV)., Conclusions: The study shows that enophthalmos can be more accurately predicted when OFA and OFV are simultaneously considered in patients with isolated medial wall fractures. Finally, an algorithm and a "blowout fracture coordinate plane" was proposed to aid treatment decision-making in isolated medial wall fractures., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Background: The regimen of prophylactic antibiotic for endoscopic endonasal skull base surgery (EE-SBS) varies considerably depending on surgeons and their institutes. The purpose of the present meta-analysis is to assess the effect of antibiotic regimens on EE-SBS surgery for anterior skull base tumor., Methods: The PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched through October 15, 2022., Results: The 20 included studies were all retrospective. The studies included a total of 10,735 patients who underwent EE-SBS for skull base tumor. The proportion of patients with postoperative intracranial infection across all 20 studies was 0.9% (95% confidence interval [CI] 0.5%-1.3%). The proportion of postoperative intracranial infection in the multiple antibiotics group did not show statistically significant difference to that of the single antibiotic agent group (proportion: 0.6%, 95% CI 0%-1.4% vs. proportion: 1%, 95% CI 0.6%-1.5%, respectively, P = 0.39). The ultra-short duration maintenance group showed lower incidence of postoperative intracranial infection, although it did not reach statistical significance (ultra-short group: 0.7%, 95% CI 0.5%-0.9%; short duration: 1.8%, 95% CI 0.5%-3%; and long duration: 1%, 95% CI 0.2%-1.9%, P = 0.22) The combination of the multiple antibiotics group did not show meaningful low incidence of postoperative intracranial infection (antibiotics combination group: 0.6%, 95% CI 0%-1.4%; cefazolin single group: 0.8%, 95% CI 0%-1.6%; and single antibiotics other than cefazolin: 1.2%, 95% CI 0.7%-1.7%, P = 0.22)., Conclusions: Multiple antibiotics did not show superiority compared with single antibiotic agent. Also, long maintenance duration of antibiotics did not reduce the incidence of postoperative intracranial infection., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Cheonwangbosim-dan is a traditional herbal prescription that is widely used to improve or treat physical and mental illnesses in East Asian countries.Aim of the study: The aim of the present study was to investigate the preventive and protective effects of a Cheonwangbosim-dan water extract (CBDW) against allergic inflammation using in vitro and in vivo models., Materials and Methods: BEAS-2B and MC/9 cells were treated with various concentrations of CBDW and stimulated with different inducers of inflammatory mediators. The production of various inflammatory mediators was subsequently evaluated. BALB/c mice were sensitized and challenged by repeated application of ovalbumin (OVA). CBDW was administered by oral gavage once daily for 10 consecutive days. We assessed the number of inflammatory cells and production of Th2 cytokines in bronchoalveolar lavage fluid (BALF), the plasma levels of total and OVA-specific immunoglobulin E (IgE), and histological changes in lung tissue., Results: Our findings showed that CBDW significantly decreased the levels of various inflammatory mediators (eotaxin-1, eotaxin-3, RANTES, LTC 4 , TNF-α, MMP-9, 5-LO, ICAM-1, and VCAM-1) in vitro , significantly reduced the accumulation of total inflammatory cells, the production of Th2 cytokines (IL-5 and IL-13), the levels of IgE (total and OVA-specific) in vivo , and remarkably inhibited histological changes (infiltration of inflammatory cells and goblet cell hyperplasia) in vivo ., Conclusions: These results suggest that CBDW possesses anti-inflammatory and anti-allergic properties by lowering allergic inflammation., 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 paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Toll-like receptors (TLRs) have a crucial role not only in triggering innate responses against microbes but in orchestrating an appropriate adaptive immunity. However, deregulated activation of TLR signaling leads to chronic inflammatory conditions such as inflammatory bowel disease (IBD). In this study, we evaluated the immunomodulatory potential of a TLR inhibitor in the form of a cell-penetrating peptide using an ulcerative colitis animal model. A peptide derived from the TIR domain of the TLR adaptor molecule TIRAP that was conjugated with a cell-penetrating sequence (cpTLR-i) suppressed the induction of pro-inflammatory cytokines such as TNF-α and IL-1β in macrophages. In DSS-induced colitis mice, cpTLR-i treatment ameliorated colitis symptoms, colonic tissue damage, and mucosal inflammation. Intriguingly, cpTLR-i attenuated the induction of TNF-α-expressing proinflammatory macrophages while promoting that of regulatory macrophages expressing arginase-1 and reduced type 17 helper T cell (Th17) responses in the inflamed colonic lamina propria. An in vitro study validated that cpTLR-i enhanced the differentiation of monocyte-driven macrophages into mature macrophages with a regulatory phenotype in a microbial TLR ligand-independent manner. Furthermore, the cocultivation of CD4 T cells with macrophages revealed that cpTLR-i suppressed the activation of Th17 cells through the functional modulation of macrophages. Taken together, our data show the immunomodulatory potential of the TLR inhibitor peptide and suggest cpTLR-i as a novel therapeutic candidate for the treatment of IBD., Competing Interests: Authors HS and SL are employed by Genesen 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 © 2023 Thapa, Pak, Chung, Shin, Lee and Lee.)

The etiology of attention-deficit hyperactivity disorder (ADHD) strongly suggests a genetic component as the main cause; however, environmental factors such as early adverse experiences in childhood may play an interactive role with the genetic susceptibility. Spontaneously hypertensive rats (SHRs), a genetic ADHD model, and control Wistar Kyoto rats (WKYs) were subjected to chronic unpredictable mild stress during the juvenile period. The behavioral characteristics were monitored, and dopamine-related factors in the core regions of dopaminergic pathways were measured. Higher ADHD symptom-related behaviors were observed in response to juvenile stress in male SHRs than control WKYs. For the SHRs subjected to juvenile stress, hyperactivity in males, recognition in females, and depressant potential in both sexes were markedly observed. In the expression of 17 dopamine-related genes and proteins, greater changes were detected in male SHRs subjected to juvenile stress, especially in dopamine metabolic factors. Dopamine clearance factors involved in dopamine degradation and transport, especially catechol-O-methyltransferase (COMT) and dopamine transporter (DAT), showed sex-specific differences induced by juvenile stress in dopamine metabolite assays. Moreover, stressed male SHRs treated with methylphenidate showed better improvement in behavior than the females, resulting in different levels of COMT and DAT amelioration. These results suggest that juvenile stress potentially increased the incidence of ADHD in a genetic rat model, which showed sex-specific differences based on the expression of COMT and DAT. Therefore, our results could help develop gender-specific diagnostics and healthcare options for juvenile stress in patients with ADHD., Competing Interests: Conflict of Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background/aim: Chronic cerebral hypoperfusion causes neuronal damage involving cognitive impairment and development of dementia. Permanent bilateral common carotid artery occlusion (BCCAO) in rat models is used to study chronic cerebral hypoperfusion. Pax6 is used as an early neurogenesis marker which affects the maturation of neuronal cells. However, the expression of PAX 6 after BCCAO is not well understood. In this study, we investigated the expression of PAX6 in the neurogenic zones after BCCAO to evaluate the effects of Pax6 on chronic hypoperfusion., Materials and Methods: Chronic hypoperfusion was induced by BCCAO. Common carotid artery was laid parallel to the vagus nerve and separated from it. Both arteries were occluded using 4-0 silk sutures. Rats who underwent bi-common carotid artery occlusion formed in the BCCAO group, while unoperated rats served as the control group. Brain samples were obtained on days 3 and 14 after BCCAO and subjected to immunohisto-chemistry with NeuN and western blotting for Pax6 and HIF1α., Results: Compared to the control, the expression of Pax6 increased three days after surgery but did not differ on day 14, while that of NeuN showed the opposite trend. The expression of HIF1α increased three days after surgery., Conclusion: Bilateral common carotid artery occlusion induced early neurogenesis at three days after BCCAO but this result was not maintained at fourteen days after BCCAO., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: As the significance of the early diagnosis of mild cognitive impairment (MCI) has emerged, it is necessary to develop corresponding screening tools with high ecological validity and feasible biomarkers. Virtual reality (VR)-based cognitive assessment program, which is close to the daily life of the older adults, can be suitable screening tools for MCI with ecological validity and accessibility. Meanwhile, dehydroepiandrosterone (DHEA) has been observed at a low concentration in the older adults with dementia or cognitive decline, indicating its potential as a biomarker of MCI. This study aimed to determine the efficacy and usability of a VR cognitive assessment program and salivary DHEA for screening MCI., Methods: The VR cognitive assessment program and the traditional Montreal Cognitive Assessment (MOCA) test were performed on 12 patients with MCI and 108 healthy older adults. The VR program operates in a situation of caring for a grandchild, and evaluates the memory, attention, visuospatial, and executive functions. An analysis of covariance (ANCOVA), a partial correlation analysis, and receiving operating characteristic (ROC) curve analysis were conducted for statistical analysis., Results: According to the ANCOVA, no significant difference in MOCA scores was found between the normal and MCI groups ( F = 2.36, p = 0.127). However, the VR total score of the MCI group was significantly lower than that of the normal group ( F = 8.674, p = 0.004). There was a significant correlation between the MOCA and VR scores in the total and matched subdomain scores. The ROC curve analysis also showed a larger area under the curve (AUC) for the VR test (0.765) than for the MOCA test (0.598), and the sensitivity and specificity of the VR program were 0.833 and 0.722, respectively. Salivary DHEA was correlated with VR total ( R 2 = 0.082, p = 0.01) and attention scores ( R 2 = 0.086, p = 0.009)., Conclusion: The VR cognitive test was as effective as the traditional MOCA test in the MCI classification and safe enough for older adults to perform, indicating its potential as a diagnostic tool. It has also been shown that salivary DHEA can be used as a biomarker for MCI., Competing Interests: J-HS was a professor at Yonsei University and the CEO of Minds.AI Co., Ltd., which was established in November 2019 as a research and development company for mental health in Republic of Korea. SJ, S-WC, I-YK, JK, J-YL, JR, and RA were employed by Research Institute of Minds.AI, Co., Ltd. HC and SK were employed by FNIKorea 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 © 2023 Jang, Choi, Son, Oh, Ha, Kim, Roh, Kim, Lee, Jung, Cha, Chae, Kang, Kwon, Kim, Lee, Shin, Ryu, Ahn, Hong and Seok.)

The role of a methyl group in intramolecular vibrational energy redistribution (IVR) of the hydrogen-bonded adenine-thymine base pair has been studied using classical dynamics procedures. Energy transferred to the doorway bond thymine-NH from the vibrationally excited H 2 O(v) efficiently redistributes among various bonds of the base pair through vibration-to-vibration coupling, depositing a large fraction of the available energy in the terminal bond adenine-NH. On the other hand, the extent of energy flow in the reverse direction from the excited adenine-NH to thymine-NH is insignificant, indicating IVR in adenine-thymine resulting from the intermolecular interaction with a vibrationally excited H 2 O molecule, is direction-specific. The unidirectional flow is due to the coupling of stretch-torsion vibrations of a methyl group with conjugated bonds on the thymine ring, when the methyl rotor is present and is adjacent to the vibrationally excited thymine-NH. The insignificance of energy flow from the terminal-to-terminal bond in the reverse direction is attributed to the absence of a methyl group on the adenine moiety, even though the molecule has many CC and CN bonds coupled to their neighbors.

Aim: To compare, and to analyze the clinical and radiological signs between bidirectional and unidirectional screw fixation in single level cervical discectomy and fusion surgery., Material and Methods: We retrospectively reviewed the data collected from 90 patients and divided them into the upper or lower spine fixation group (unidirectional) and the normal upper and lower spine fixation group (bidirectional). The patients' demographic data and preoperative and postoperative (24 months) clinical outcomes were collected. Pre- and postoperative (immediately and at 3, 6, 12, and 24 months) changes in the segmental angle in the operating field (SA), cervical lordosis, C2-7 sagittal vertical axis, and active disc height (aDH) were evaluated. We also compared the rate of fusion and muscle size change between the groups., Results: The operation time in the bidirectional screw fixation group was significantly longer than that in the unidirectional screw fixation group ( > 6 min; p=0.03). There was no significant difference between the two groups in radiographic parameters before and immediately after surgery. From 3 months postoperatively, the unidirectional group had significantly higher SA and aDH than the bidirectional group (p=0.03). The fusion rate was higher in the bidirectional screw fixation group than in the unidirectional group, but this was not statistically significant (97% vs. 88%, p=0.07)., Conclusion: The results of this study suggest that unidirectional screw fixation surgery can be useful as it has been associated with simple surgery, short surgery time, and maintenance of the lordotic curvature of SA and disc height.

Background: The association between size of ganglia or type of ganglia (intra-articular or extra-articular) and meniscal tears or severity of the osteoarthritis (OA) is not evaluated., Purpose: To evaluate the prevalence, size, and location of intra- and extra-capsular ganglia at the gastrocnemius origin and to assess their associations with meniscal injury and grades of OA., Material and Methods: This study included 301 consecutive patients who had knee pain and had undergone magnetic resonance imaging (MRI) of the knee. We evaluated presence of ganglia at the gastrocnemius muscle origin site and diagnosed whether it was an intra-capsular located or mixed-capsular located (intra-capsular and extra-capsular) and then measured the diameter of each ganglion. After two weeks, we evaluated whether articular cartilage injury existed. The presence of a meniscal tear was also recorded., Results: A total of 186 patients (93%) had intra- and extra-capsular ganglia. Intra-capsular ganglia were found in 183 cases (91%) and mixed-capsular ganglia were found in 16 cases (8%). In cases with intra- and extra-capsular ganglia, more meniscal tears were found ( P  = 0.029). Intra-capsular ganglia showed more meniscal tears ( P  = 0.021). Intra-capsular ganglia were more likely to have high-grade OA ( P  = 0.043). Patients who had a meniscal tear displayed larger-sized ganglia, especially of the intra-capsular type ( P  = 0.044)., Conclusion: Patients with intra- and extra-capsular ganglia, especially of the intra-capsular type, are more likely to have meniscal injury and more severe OA. Patients with a meniscal tear or OA are more likely to have larger intra- and extra-capsular ganglia, especially of the intra-capsular type.

Neurological disorders represent a substantial healthcare burden worldwide due to population aging. Acorus gramineus Solander (AG) and Acorus tatarinowii Schott (AT), whose major component is asarone, have been shown to be effective in neurological disorders. This review summarized current information from preclinical and clinical studies regarding the effects of extracts and active components of AG and AT (e.g., α-asarone and β-asarone) on neurological disorders and biomedical targets, as well as the mechanisms involved. Databases, including PubMed, Embase, and RISS, were searched using the following keywords: asarone, AG, AT, and neurological disorders, including Alzheimer's disease, Parkinson's disease, depression and anxiety, epilepsy, and stroke. Meta-analyses and reviews were excluded. A total of 873 studies were collected. A total of 89 studies were selected after eliminating studies that did not meet the inclusion criteria. Research on neurological disorders widely reported that extracts or active components of AG and AT showed therapeutic efficacy in treating neurological disorders. These components also possessed a wide array of neuroprotective effects, including reduction of pathogenic protein aggregates, antiapoptotic activity, modulation of autophagy, anti-inflammatory and antioxidant activities, regulation of neurotransmitters, activation of neurogenesis, and stimulation of neurotrophic factors. Most of the included studies were preclinical studies that used in vitro and in vivo models, and only a few clinical studies have been performed. Therefore, this review summarizes the current knowledge on AG and AT therapeutic effects as a basis for further clinical studies, and clinical trials are required before these findings can be applied to human neurological disorders., Competing Interests: CONFLICT OF INTEREST The authors have no conflicts of interest to declare., (© 2022 Korean Pharmacopuncture Institute.)

Deep-learning-based survival prediction can assist doctors by providing additional information for diagnosis by estimating the risk or time of death. The former focuses on ranking deaths among patients based on the Cox model, whereas the latter directly predicts the survival time of each patient. However, it is observed that survival time prediction for the patients, particularly with close observation times, possibly has incorrect orders, leading to low prediction accuracy. Therefore, in this paper, we present a whole slide image (WSI)-based survival time prediction method that takes advantage of both the risk as well as time prediction. Specifically, we propose to combine these two approaches by extracting the risk prediction features and using them as guides for the survival time prediction. Considering the high resolution of WSIs, we extract tumor patches from WSIs using a pre-trained tumor classifier and apply the graph convolutional network to aggregate information across these patches effectively. Extensive experiments demonstrate that the proposed method significantly improves the time prediction accuracy when compared with direct prediction of the survival times without guidance and outperforms existing methods., (© 2022. The Author(s).)

Purpose: Convolutional neural networks (CNNs) have rapidly emerged as one of the most promising artificial intelligence methods in the field of medical and dental research. CNNs can provide an effective diagnostic methodology allowing for the detection of early-staged diseases. Therefore, this study aimed to evaluate the performance of a deep CNN algorithm for apical lesion segmentation from panoramic radiographs., Materials and Methods: A total of 1000 panoramic images showing apical lesions were separated into training (n=800, 80%), validation (n=100, 10%), and test (n=100, 10%) datasets. The performance of identifying apical lesions was evaluated by calculating the precision, recall, and F1-score., Results: In the test group of 180 apical lesions, 147 lesions were segmented from panoramic radiographs with an intersection over union (IoU) threshold of 0.3. The F1-score values, as a measure of performance, were 0.828, 0.815, and 0.742, respectively, with IoU thresholds of 0.3, 0.4, and 0.5., Conclusion: This study showed the potential utility of a deep learning-guided approach for the segmentation of apical lesions. The deep CNN algorithm using U-Net demonstrated considerably high performance in detecting apical lesions., Competing Interests: Conflicts of Interest: The second author, Hak-Kyun Shin, invented the AI software model (called Deep Stack) and is still working for the company (DDH Inc., Seoul, South Korea) that developed it. The other authors have no conflict of interest to declare. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2022 by Korean Academy of Oral and Maxillofacial Radiology.)

Introduction: In this study, we developed a simplified artificial intelligence to support the clinical decision-making of medical personnel in a resource-limited setting., Methods: We selected seven infectious disease categories that impose a heavy disease burden in the central Vietnam region: mosquito-borne disease, acute gastroenteritis, respiratory tract infection, pulmonary tuberculosis, sepsis, primary nervous system infection, and viral hepatitis. We developed a set of questionnaires to collect information on the current symptoms and history of patients suspected to have infectious diseases. We used data collected from 1,129 patients to develop and test a diagnostic model. We used XGBoost, LightGBM, and CatBoost algorithms to create artificial intelligence for clinical decision support. We used a 4-fold cross-validation method to validate the artificial intelligence model. After 4-fold cross-validation, we tested artificial intelligence models on a separate test dataset and estimated diagnostic accuracy for each model., Results: We recruited 1,129 patients for final analyses. Artificial intelligence developed by the CatBoost algorithm showed the best performance, with 87.61% accuracy and an F1-score of 87.71. The F1-score of the CatBoost model by disease entity ranged from 0.80 to 0.97. Diagnostic accuracy was the lowest for sepsis and the highest for central nervous system infection., Conclusion: Simplified artificial intelligence could be helpful in clinical decision support in settings with limited resources., Competing Interests: Author HS was employed by company Acryl. Authors HL, BK and HS were employed by company FineHealthcare. 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, Lee, Shin, Lee, Kim and Kang.)

Open wounds are usually closed with suture. However, young patients often do not cooperate and prevent proper suture placement. Young patients are often terrified of mild pain and wholly uncooperative, which is why we introduce this timesaving, less painful, more aesthetic technique of placing and removing stitches. 104 patients with facial lacerations aged 5 to 15 years were treated at a single center from May 2019 to March 2021. Patients were randomly assigned equally to a simple interrupted suture group (the SI group) or a continuous locking with Steri-Strip group (the CS group). Suture times, times for stitch removal, pain scores at stitch removal and mature scar scores were evaluated. Suture and stitch removal times were significantly shorter, and pain scores at stitch removal and observer scar assessment scale scores were lower in the CS group. Patient scar assessment scale score was non-significantly lower in the SI group. This study shows that the novel continuous locking with the Steri-Strip technique is easier and quicker to perform, causes less pain when removing stitches, provides better aesthetic results than the simple interrupted suture technique and suggests the continuous locking with Steri-Strip technique would be very useful for uncooperative young patients., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Conventional thermosetting composites exhibit advantageous mechanical properties owing to the use of an autoclave; however, their wide usage is limited by high production costs and long molding times. In contrast, the fabrication of thermoplastic composites involves out-of-autoclave processes that use press equipment. In particular, induction-heating molding facilitates a quicker thermal cycle, reduced processing time, and improved durability of the thermoplastic polymers; thus, the process cost and production time can be reduced. In this study, carbon fiber/polyphenylene sulfide thermoplastic composites were manufactured using induction-heating molding, and the relationships among the process, structure, and mechanical properties were investigated. The composites were characterized using optical and scanning electron microscopy, an ultrasonic C-scan, and X-ray computed tomography. In addition, the composites were subjected to flammability tests. This study provides novel insights into the optimization of thermoplastic composite manufacturing and thermoset composite curing processes.

Summary: Drug-induced liver injury (DILI) is a challenging endpoint in predictive toxicology because of the complex reactive metabolites that cause liver damage and the wide range of mechanisms involved in the development of the disease. ToxSTAR provides structural similarity-based DILI analysis and in-house DILI prediction models that predict four DILI subtypes (cholestasis, cirrhosis, hepatitis and steatosis) based on drug and drug metabolite molecules., Availability and Implementation: ToxSTAR is freely available at https://toxstar.kitox.re.kr/., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Acute spinal cord injury (SCI) can result in debilitating motor, sensory, and autonomic dysfunction. As a treatment option, therapeutic hypothermia has been researched to inadequate pharmaceutical treatment, except for methylprednisolone. In this article, we systematically meta-analyzed to clarify the effect of hypothermia in acute SCI on neurological outcomes., Methods: The PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched until June 30, 2022. The proportion of cases with improved neurological status after hypothermia in acute SCI were pooled with a random-effects model. Subgroup analyses for the method of hypothermia and injury level were conducted., Results: Eight studies with a total of 103 patients were included. Hypothermia in acute SCI improved neurological function by 55.8% (95% confidence interval [CI]: 39.4%-72.1%). The subgroup analysis revealed that the pooled proportion of cases showing neurological improvement was higher with systemic hypothermia (70.9%) (95% CI, 14.9%-100%) than with local hypothermia (52.5%) (95% CI, 40.4%-64.5%), although the subgroup difference was not statistically significant (p = 0.53). Another subgroup analysis revealed that the proportion of cases with neurological improvement did not differ statistically between the cervical spine (61.4%) (95% CI, 42.2%-80.6%) and thoracic spine injury groups (59.4%) (95% CI, 34.8%-84.0%) (p = 0.90)., Conclusion: This meta-analysis identified that more than 50% of patients showed neurological improvement after hypothermia following acute SCI in general. A multicenter, randomized, double-blind study with larger sample size is necessary to validate the findings further.

Purpose: This study aimed to confirm the usefulness of surgery that avoids the cervicothoracic junction (CTJ) by comparing the clinical and radiographic outcomes after posterior cervical fusion at C5/6 with those at C7/T1., Methods: Patients who underwent laminectomy and posterior cervical instrument fusion for cervical spondylotic myelopathy (CSM) from 2012 to 2019 were retrospectively reviewed and divided according to whether the end level was at C5/6 (group 1) or C7/T1 (group 2). Demographic variables and incidence of distal junctional kyphosis (DJK) were compared between the groups. Clinical outcomes (visual analog scale [VAS] score for arm and neck pain and the Neck Disability Index value) and radiologic outcomes (T1 slope, cervical lordosis, segmental lordosis, C2-7 sagittal vertical axis, T1 slope-cervical lordosis mismatch) were compared over time., Results: Sixty-seven patients were included. There were 32 patients in group 1 and 35 in group 2. The VAS score for neck pain was significantly lower in group 1 than in group 2 at 2 years after surgery ( p = 0.03). The C2-7 sagittal vertical axis was significantly larger in group 2 than in group 1 at 1 year and 2 years postoperatively ( p = 0.04). The incidence of DJK was higher in group 2 than in group 1 (28.57% vs 9.37%, p = 0.04)., Conclusion: This study found that when CTJs are included in the posterior cervical long fusion surgery, although it would be better than preoperation, postoperative kyphosis and consequent neck pain may progress. The results of this study advocate the concept of avoiding CTJ fusion if possible.

Lyocell is a biodegradable filament yarn obtained by directly dissolving cellulose in a mixture of N -methylmorpholine- N -oxide and a non-toxic solvent. Therefore, herein, lyocell fabrics were employed as eco-friendly carbon-precursor substitutes for use as electromagnetic interference (EMI) shielding materials. First, a lyocell fabric treated with polyacrylamide via electron beam irradiation reported in a previous study to increase carbon yields and tensile strengths was carbonized by heating to 900, 1100, and 1300 °C. The carbonization transformed the fabric into a graphitic crystalline structure, and its electrical conductivity and EMI shielding effectiveness (SE) were enhanced despite the absence of metals. For a single sheet, the electrical conductivities of the lyocell-based carbon fabric samples at the different carbonization temperatures were 3.57, 5.96, and 8.91 S m -1 , leading to an EMI SE of approximately 18, 35, and 82 dB at 1.5-3.0 GHz, respectively. For three sheets of fabric carbonized at 1300 °C, the electrical conductivity was 10.80 S m -1 , resulting in an excellent EMI SE of approximately 105 dB. Generally, EM radiation is reduced by 99.9999% in instances when the EMI SE was over 60 dB. The EMI SE of the three lyocell-based carbon fabric sheets obtained at 1100 °C and that of all the sheets of the sample obtained at 1300 °C exceeded approximately 60 dB.

Glioblastoma multiforme (GBM) is the most frequently occurring malignant brain tumor in adults and is characterized by a high degree of vascularization. Glioblastoma cells communicate with their microenvironment and stimulate blood vessel formation to support tumor progression. It has previously been reported that isolinderalactone induces apoptosis in GBM cells and suppresses the growth of glioblastoma xenograft tumors in vivo . Furthermore, isolinderalactone has been shown to inhibit the hypoxia-driven upregulation of vascular endothelial growth factor (VEGF) in U-87 GBM cells and strongly reduce VEGF-triggered angiogenesis in vitro and in vivo . In the present study, the direct angiogenic effect of GBM and the effect of isolinderalactone on tumor angiogenesis were investigated. Culture supernatants were obtained from U-87 cells under normoxic or hypoxic conditions to provide normoxic conditioned medium (NCM) and hypoxic conditioned medium (HCM) respectively. The NCM and HCM were each used to treat to human brain microvascular endothelial cells (HBMECs), and their effects were observed using wounding migration and tube formation assays. HCM increased the migration and capillary-like tube formation of HBMECs when compared with NCM, and treatment with isolinderalactone suppressed the HCM-driven angiogenesis in vitro . Additionally, isolinderalactone decreased HCM-triggered angiogenic sprouting in HBMECs in a 3D microfluidic device after the application of an HCM-containing interstitial fluid flow. Furthermore, isolinderalactone strongly reduced HCM-triggered angiogenesis in an in vivo Matrigel plug assay in mice. These findings provide evidence of angiogenesis inhibition by isolinderalactone, and demonstrate the anti-angiogenic effect of isolinderalactone against the direct angiogenic effect of GBM tumor cells., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Lee et al.)

Ischemic stroke is the leading cause of immortal disability and death worldwide. For treatment in the acute phase, it is necessary to control excessive reactive oxygen species (ROS) damage during ischemia/reperfusion (I/R). Microglia are well known to be closely associated with excessive ROS response in the early stage of I/R. However, the precise roles of microglia associated with mitigating ROS damage, and molecular markers of heterogenetic microglia in the I/R damaged brain has not been clarified. Here, we identified a new type of microglia associated with stroke in the I/R injured brain. Single-cell RNA sequencing (scRNA-seq) was used to assess transcriptional changes of microglia and immune cells in the contralateral (CL) and ipsilateral (IL) hemispheres after transient middle cerebral artery occlusion (tMCAO) surgery to mimic ischemic stroke. We classified a unique type of microglia with enhanced antioxidant function and markers similar to those of disease-associated microglia (DAM), designated them as stroke-associated microglia (SAM). The representative antioxidant enzyme, Peroxiredoxin-1 (Prdx1), was predominantly expressed in SAM and mediated ROS defense genes, including Txn1, Srx1, Mt1, and Mt2. In the Prdx1 -/- I/R damaged brain, we observed significantly increased infarction, as assessed by TTC staining, and FACS analysis detected severe microglial cell death. Importantly, scRNA transcriptomics data showed that the SAM population was specifically decreased in Prdx1 -/- mice and that these mice exhibited decreased ROS damage resistance. Inflammatory responses which were detected by ELISA and qPCR, were also increased in Prdx1 -/- IL hemispheres. Finally, Prdx1-dependent antioxidative SAM were found to be essential for increasing the transcription levels of stroke-protective molecules, such as osteopontin and ferritin. A novel microglia type (SAM) is specifically activated in response to stroke I/R injury, and that Prdx1 expression is required for the activation and enhanced antioxidant function of SAM., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The incidence of spinal metastasis is increasing as cancer patients live longer owing to the improvement of cancer treatments. However, traditional surgery (TS) which fixates at least 2 levels above and 2 levels below the affected vertebrae is sometimes difficult to perform as it is burdensome to the patients. In this article, we introduce our experience and strategy in treating spinal metastasis, focusing particularly on challenging cases. We retrospectively reviewed the data of 110 patients who underwent spinal surgery for metastatic spinal tumors from April 2018 to March 2020. Among them, 5 patients who received anterior approach surgery were excluded. The remaining 105 patients were enrolled. In addition to TS, we also performed cervical pedicle screw, cervicothoracic junction fixation, thoracolumbar short fixation, and decompression surgery, depending on the characteristics of the tumor. The overall survival was analyzed, and the local tumor control rate was evaluated using magnetic resonance imaging. Perioperative clinical characteristics including Spine Oncology Study Group Outcomes Questionnaire, visual analog scale, Eastern Cooperative Oncology Group performance score, and Karnofsky Performance Score were also investigated. The overall survival rate was 57.9% at 1 year, and the local tumor control rate was 81.1% after surgery. There was a statistically significant difference according to the type of the tumor in the survival analysis: the overall survival rates were 72.7% for favorable tumors and 48.6% for unfavorable tumors at 12 months after surgery (P = .04). Spine Oncology Study Group Outcomes Questionnaire, visual analog scale, Eastern Cooperative Oncology Group performance score, and Karnofsky Performance Score was improved after surgery. All surgical methods, including TS, cervical pedicle screw, cervicothoracic junction fixation, thoracolumbar short fixation, and decompression surgery, showed good clinical and radiological outcomes. Optimized surgical methods show similarly good clinical outcomes in managing spinal metastasis as TS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Neural/glial antigen 2 (NG2)-expressing cells has multipotent stem cell activity under cerebral ischemia. Our study examined the effects of electroacupuncture (EA) therapy (2 Hz, 1 or 3 mA, 20 minutes) at the Sishencong acupoint on motor function after ischemic insult in the brain by investigating the rehabilitative potential of NG2-derived cells in a mouse model of ischemic stroke. EA stimulation alleviated motor deficits caused by ischemic stroke, and 1 mA EA stimulation was more efficacious than 3 mA EA stimulation or positive control treatment with edaravone, a free radical scavenger. The properties of NG2-expressing cells were altered with 1 mA EA stimulation, enhancing their survival in perilesional brain tissue via reduction of tumor necrosis factor alpha expression. EA stimulation robustly activated signaling pathways related to proliferation and survival of NG2-expressing cells and increased the expression of neurotrophic factors such as brain-derived neurotrophic factor, tumor growth factor beta, and neurotrophin 3. In the perilesional striatum, EA stimulation greatly increased the number of NG2-expressing cells double-positive for oligodendrocyte, endothelial cell, and microglia/macrophage markers (CC1, CD31, and CD68). EA therapy also greatly activated brain-derived neurotrophic factor/tropomyosin receptor kinase B and glycogen synthase kinase 3 beta signaling. Our results indicate that EA therapy may prevent functional loss at the perilesional site by enhancing survival and differentiation of NG2-expressing cells via the activation of brain-derived neurotrophic factor -induced signaling, subsequently ameliorating motor dysfunction. The animal experiments were approved by the Animal Ethics Committee of Pusan National University (approval Nos. PNU2019-2199 and PNU2019-2884) on April 8, 2019 and June 19, 2019., Competing Interests: None

Objective: This study analyzed the risk factors in patients who developed distal junctional kyphosis (DJK) after posterior cervical fusion., Methods: We retrospectively analyzed the clinical and radiographic outcomes of 64 patients, aged ≥18 years (51 and 13 male and female patients, respectively), who underwent single-staged multilevel (3-6 levels) posterior cervical fusion surgery due to multiple cervical spondylotic myelopathy. The surgeries were performed by a single spinal surgeon between January 2012 and December 2017. Demographic data, clinical outcomes, and radiological results were collected. We divided the patients into a DJK group and a non-DJK group according to the presence of DJK and investigated the risk factors by comparing the differences between the two groups., Results: Of the 64 patients, 13 developed DJK. No significant differences in clinical results were observed between the two groups before and immediately after the surgery. At the final follow-up, a higher visual analog score for neck pain was observed in the DJK group compared to the non-DJK group (p<0.01). The DJK group had a significantly lower T1 slope and a significantly higher C2-7 sagittal vertical axis (SVA) before surgery compared to the non-DJK group (p=0.03 and p<0.01, respectively). Immediately after surgery, the difference between the two groups decreased and no significant difference was observed. However, at the last followup, a significantly higher C2-7 SVA was observed in the DJK group (p<0.01). At the last follow up, there is no discrepancy in T1S-CL. In multiple logistic regression analysis, preoperative higher C2-7 SVA and preoperative lower T1 slope were identified as independent risk factors (p=0.03 and p<0.01, respectively). As a result, it was confirmed that DJK occurred along the process of returning to preoperative values., Conclusion: DJK can be considered to be caused by cervical misalignment due to excessive change in the surgical site in patients with low T1 slope and high C2-7 SVA before surgery. This also affects the clinical outcome after surgery. It is recommended to refrain from excessive segmental lordosis changes during multilevel cervical post fusion surgery, especially in patients with a small preoperative T1 slope and a large SVA value.

Siryung-tang (SRT) is a traditional herbal prescription containing Oryeong-san and Soshiho-tang that is used to treat digestive system diseases. We performed safety evaluations of SRT based on genotoxicity and developed an assay for quality control using high-performance liquid chromatography with a photodiode array detector. Genotoxicity was evaluated based on bacterial reverse mutation ( Salmonella typhimurium TA1535, TA98, TA100, and TA1537, and Escherichia coli WP2 uvrA), chromosomal aberration (Chinese hamster lung cells), and micronucleus (mouse) tests. Quality control analysis was conducted using a SunFire C 18 column and gradient elution with a distilled water-acetonitrile mobile phase system containing 0.1% ( v / v ) formic acid for 12 markers (5-(hydroxy-methyl)furfural, 3,4-dihydroxybenzaldehyde, liquiritin apioside, liquiritin, coumarin, baicalin, wogonoside, cinnamaldehyde, baicalein, glycyrrhizin, wogonin, and atractylenolide III). SRT showed no genotoxicity in three tests. Ames tests showed that SRT at 313-5000 μg/plate did not significantly increase the number of revertant colonies with or without metabolic activation among five bacterial strains. Moreover, in vivo micronucleus testing showed that SRT did not increase the frequency of bone marrow micronuclei. The number of chromosomal aberrations associated with SRT was similar to that observed in the negative controls. The 12 markers were detected at 0.04-16.86 mg/g in a freeze-dried SRT sample and completely eluted within 45 min. The extraction recovery was 95.39-104.319% and the relative standard deviation value of the precision was ≤2.09%. Our study will be used as basic data for the safety and standardization of SRT.

Cancer patients can develop visceral, somatic, and neuropathic pain, largely due to the malignancy itself and its treatments. Often cancer patients and survivors turn to the use of complementary and alternative medicine (CAM) to alleviate pain and fatigue. Thus, it is necessary to investigate how CAM therapies work as novel analgesics to treat cancer pain. Ojeok-san (OJS) is an herbal formula consisting of seventeen herbs. This herbal formula has been shown to possess anti-inflammatory, immunoregulatory, and analgesic properties. In this study, we examined the potential beneficial effects and mechanism of action of OJS in a preclinical model of colitis-associated colorectal cancer. Male and female C57BL/6J mice were exposed to the carcinogen, azoxymethane (AOM, 10 mg/kg) and a chemical inflammatory driver, dextran sulfate sodium (DSS1-2%), to promote tumorigenesis in the colorectum. OJS was given orally (500, 1000, and 2000 mg/kg) to determine its influence on disease activity, tumor burden, nociception, sedation, Erk signaling, and behavioral and metabolic outcomes. In addition, in vitro studies were performed to assess CT-26 cell viability, dorsal root ganglia (DRG) activation, and bone-marrow-derived macrophage (BMDM) inflammatory response to lipopolysaccharide stimulation after OJS treatment. We found that administration of 2000 mg/kg of OJS was able to mitigate mechanical somatic and visceral nociception via Erk signaling without affecting symptom score and polyp number. Moreover, we discovered that OJS has sedative properties and elicits prolonged total sleeping time in AOM/DSS mice. Our in vitro experiments showed that OJS has the capacity to reduce TNFα gene expression in LPS-stimulated BMDM, but no changes were observed in DRG spike number and CT-26 cell proliferation. Taken together, these data suggest that OJS ameliorates nociception in mice and warrants further examination as a potential CAM therapy to promote analgesia., Competing Interests: The authors have declared that no competing interests exist.

Oryeongsan (Wulingsan in China and Goreisan in Japan), a formula composed of five herbal medicines, has long been used for the treatment of imbalance of the body fluid homeostasis in Asian countries. However, the mechanism by which Oryeongsan (ORS) improves the impaired body fluid and salt metabolism is not clearly defined. The present study was performed to define the role of the cardiorenal humoral system in the ORS-induced changes in blood pressure and renal function in hypertension. Experiments were performed in normotensive and two-kidney, one-clip hypertensive rats. Changes in the fluid and salt balance were measured in rats individually housed in metabolic cages. Changes in the systemic and local renin-angiotensin system (RAS) and cardiac natriuretic peptide hormone system (NPS) were evaluated. ORS water extract was administered by oral gavage (100 mg/kg daily) for 3 weeks. ORS induced diuresis and natriuresis along with an increase in glomerular filtration rate and downregulation of the Na + /H + exchanger 3 (NHE3) and aquaporin 2 expression in the renal cortex and medulla, respectively. Furthermore, treatment with ORS significantly decreased systolic blood pressure with contraction of body sodium and water accumulation in hypertensive rats. ORS-induced changes were accompanied by modulation of the RAS and NPS, downregulation of the systemic RAS and cardiorenal expression of angiotensin-converting enzyme (ACE) and angiotensin II subtype 1 (AT 1 ) receptor, and upregulation of the plasma ANP concentration and cardiorenal expression of ANP, ACE2, Mas receptor, and AT 2 receptor. These findings indicate that ORS induces beneficial effects on the high blood pressure through modulation of the RAS and NPS of the cardiorenal system, suppression of the prohypertensive ACE-AT 1 receptor pathway and NHE3, accentuation of the antihypertensive ACE2-Mas axis/AT 2 receptor pathway in the kidney, suppression of the systemic RAS, and elevation of the plasma ANP levels and its synthesis in the heart. The present study provides a biological basis for the use of ORS in the treatment of impaired volume and pressure homeostasis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 You Mee Ahn et al.)

Objectives: To evaluate the efficacy and safety of tamsulosin and Hachimijiogan or Ryutanshakanto in patients with lower urinary tract symptoms due to benign prostatic hyperplasia., Methods: A prospective, randomized, double-blind method was used to determine the efficacy and safety of the combination or placebo at baseline and 4, 8, and 12 weeks of study. The International Prostate Symptom Score, quality of life index, complete voiding diary, and National Institutes of Health-Chronic Prostatitis Symptom Index were studied. Uroflowmetery and postvoid residual urine volume were measured and compared. Laboratory tests including prostate-specific antigen were performed., Results: In all groups, International Prostate Symptom Score and quality of life showed improvement, but no significant differences were shown among the groups. Prostate volume increased after treatment, and uroflowmetric parameters showed improvements after treatment without significance among the three groups. The total score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant improvement in all groups, without significant differences among the groups. Only the pain sub-score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant decrease in the tamsulosin with Ryutanshakanto group compared to the control group. A total of 11 adverse reactions occurred, but they were mild and not related to the study drugs., Conclusion: Ryutanshakanto can provide pain relief in patients with chronic prostatitis and chronic pelvic pain syndrome. If more research is conducted, Hachimijiogan and Ryutanshakanto may be applied as add-on treatments in patients with storage symptoms with alpha-blocker monotherapy., (© 2022 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Redistribution of vibrational energy in the adenine-uracil base pair is studied when the base pair undergoes an intermolecular interaction with an overtone-bending vibration excited H 2 O(2ν bend ) molecule. Energy transfer is calculated using the structural information obtained from density functional theory in the solution of the equations of motion. Intermolecular vibrational energy transfer (VET) from H 2 O(2ν bend ) to the uracil-NH stretching mode is efficient and rapidly followed by intramolecular vibrational energy redistribution (IVR) resulting from coupling between vibrational modes. An important pathway is IVR carrying energy to the NH-stretching mode of the adenine moiety in a subpicosecond scale, the energy build-up being sigmoidal, when H 2 O interacts with the uracil-NH bond. The majority of intermolecular hydrogen bonds between the base pair and H 2 O are weakened but unbroken during the ultrafast energy redistribution period. Lifetimes of intermolecular HB are on the order of 0.5 ps. The efficiency of IVR in the base pair is due to near-resonance between coupled CC and CN vibrations. The resonance also exists between the frequencies of H 2 O bend and NH stretch, thus facilitating VET. When H 2 O interacts with the NH bond at the adenine end of the base pair, energy flow in the reverse direction to the uracil-NH stretch is negligible, the unidirectionality discussed in terms of the effects of uracil CH stretches. The energy distributed in the CH bonds is found to be significant. The IVR process is found to be nearly temperature independent between 200 and 400 K.

Study Design: Retrospective study., Objective: To evaluate the absolute value of L4 trabecular region-of-interest (t-ROI) computed tomography (CT) attenuation, which can predict pedicle screw loosening, and determine the changes in value according to number of fused levels and sagittal balance in patients undergoing lumbar fusion surgery., Summary of Background Data: Although osteoporosis was not diagnosed in spinal dual x-ray absorptiometry preoperatively, we encountered several cases of screw loosening within 1 year of lumbar fusion surgery., Methods: We enrolled 478 patients and analyzed factors related to screw loosening. We evaluated the association between L4 t-ROI CT attenuation and screw loosening and determined the best cutoff value of t L4 t-ROI CT attenuation for predicting screw loosening., Results: The number of fused levels, postoperative C7-S1 sagittal vertical axis (SVA), and L4 t-ROI CT attenuation were independently correlated with screw loosening. According to number of fused level and postoperative C7-T1 SVA (≥36.9 mm or <36.9 mm), in patients with one-level fusion and C7-S1 SVA less than 36.9 mm, the optimal cutoff point of the L4 t-ROI CT attenuation predicting screw loosening was 106.5 Hounsfield unit (HU). L4 t-ROI attenuation did not change until two-level fusions. In patients with three-level fusions and C7-S1 SVA less than 36.9 mm, the optimal cutoff point of the L4 t-ROI CT attenuation predicting screw loosening was 159.0 HU. The optimal cutoff point of L4 t-ROI CT attenuation in patients with three-level fusions and C7-S1 SVA more than or equal to 36.9 mm was 191.0 HU., Conclusion: L4 t-ROI CT attenuation value considering number of fused levels and sagittal balance is an accurate measurement method to predict screw loosening. Spine surgeons should be aware of the L4 t-ROI attenuation before surgery to improve the fusion rate and reduce instrument-related complications of lumbar spine surgery in osteoporotic patients., Level of Evidence: 3., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Oncheong-eum (OCE) is a traditional herbal prescription made by combining Samul-tang and Hwangryunhaedok-tang. It is primarily used to treat gynecological disorders such as metrorrhagia and metrostaxis. In the present study, we focused on developing and validating a simultaneous assay for the quality control of OCE using 19 marker components (gallic acid, 5-(hydroxymethyl)furfural, chlorogenic acid, geniposide, coptisine chloride, jatrorrhizine chloride, paeoniflorin, berberine chloride, palmatine chloride, ferulic acid, nodakenin, benzoic acid, baicalin, benzoylpaeoniflorin, wogonoside, baicalein, wogonin, decursin, and decursinol angelate). This analysis was performed using high-performance liquid chromatography coupled with a diode array detector, and chromatographic separation of the 19 markers was carried out using a SunFire TM C 18 reversed-phase column and gradient elution conditions with two mobile phases (0.1% aqueous formic acid-0.1% formic acid in acetonitrile). The developed analytical method was validated through linearity, limits of detection and quantification, recovery, and precision. Under this assay, 19 markers in OCE samples were detected at not detected-9.62 mg/g. The analytical methods developed and validated in our research will have value as basic data for the quality control of related traditional herbal prescriptions as well as OCE.

Background: Therapeutic effects of transcranial alternating current stimulation (tACS) for treating Parkinson's disease (PD) are limited to modulating abnormally synchronized oscillations; however, long-lasting tACS effects may involve non-neuronal mechanisms like the regulation of neurotrophic factors., Objectives/hypothesis: We investigated whether tACS exerts neuroprotective effects on dopaminergic neurons in a mouse model of PD by regulating endogenous glial cell line-derived neurotrophic factor (GDNF)., Methods: Repeated high-definition tACS (HD-tACS, 20 min, 89.1 μA/mm 2 ) was administered over the primary motor cortex of C57BL/6J 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. Behavioral tests assessing motor function, immunohistochemistry, western blots, enzyme-linked immunosorbent assays, and flow cytometric analyses were performed to examine suitable tACS conditions and its underlying mechanisms., Results: Stimulation at representative frequencies (theta to gamma; 20-Hz beta frequency, in particular) attenuated motor dysfunction and protected the dopaminergic neurons with increased GDNF production. Beta-frequency (20 Hz) tACS application significantly attenuated motor deficits to levels comparable with those of levodopa treatment. Moreover, beta-frequency tACS induced the survival of dopaminergic neurons in the substantia nigra with upregulated production of endogenous GDNF in striatal parvalbumin-positive interneurons. An inhibitor of the GDNF receptor-associated rearranged during transfection (RET) kinase suppressed most aspects of the tACS-induced behavioral recovery, dopaminergic cell survival, and GDNF production. Beta-frequency tACS activated RET-related survival signaling for dopaminergic neurons in the substantia nigra., Conclusions: Application of tACS over the primary motor cortex may exert protective effects on dopaminergic neurons in the substantia nigra via activation of endogenous GDNF production by striatal parvalbumin-positive interneurons and its survival signaling., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Photobiomodulation (PBM) has received attention due to its potential for improving tissue function and enhancing regeneration in stroke. A lightweight, compact, and simple system of miniaturized electronic devices consisting of packaged light-emitting diodes (LEDs) that incorporates a flexible substrate for in vivo brain PBM in a mouse model is developed. Using this device platform, the preventive and therapeutic effects of PBM affixed to the exposed skull of mice in the photothrombosis and middle cerebral artery occlusion stroke model are evaluated. Among the wavelength range of 630, 850, and 940 nm LED array, the PBM with 630-nm LED array is proved to be the most effective for reducing the infarction volume and neurological impairment after ischemic stroke. Moreover, the PBM with 630 nm LED array remarkably improves the capability of spatial learning and memory in the chronic poststroke phase, attenuates AIM2 inflammasome activation and inflammasome-mediated pyroptosis, and modulates microglial polarization in the hippocampus and cortex 7 days following ischemic stroke. Thus, PBM may prevent tissue and functional damage in acute ischemic injury, thereby attenuating the development of cognitive impairment after stroke., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Membrane-free stem cell extract (MFSCE) of human adipose tissues possesses various biological activities. However, the effects of MFSCE on blood-brain barrier dysfunction and brain damage are unknown. In this study, we determined the role of MFSCE in an ischemic stroke mouse model. Mice were treated with MFSCE once daily for 4 days and 1 h before ischemic damage. Experimental ischemia was induced by photothrombosis. Pretreatment with MFSCE reduced infarct volume and edema and improved neurological, as well as motor functions. Evans blue leakage and water content in the brain tissue were reduced by MFSCE pretreatment relative to those in the vehicle group. MFSCE increased the expression of the tight junction proteins zonula occludens 1 and claudin-5, as well as vascular endothelial-cadherin, but decreased that of matrix metalloproteinase 9. Notably, MFSCE treatment decreased cell death and the level of NOD-like receptor protein 3 inflammasome, consistent with the downregulated expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 in the ischemic brain. These effects might have occurred via the suppression of the expression of Toll-like receptor 4 and activation of nuclear factor-κB. The results highlighted the potential of MFSCE treatment as a novel and preventive strategy for patients at a high risk of ischemic stroke.

To transform tall goldenrods, which are invasive alien plant that destroy the ecosystem of South Korea, into useful materials, cellulose fibers isolated from tall goldenrods are applied as EMI shielding materials in this study. The obtained cellulose fibers were blended with CNTs, which were used as additives, to improve the electrical conductivity. TGCF/CNT papers prepared using a facile paper manufacturing process with various weight percent ratios and thickness were carbonized at high temperatures and investigated as EMI shielding materials. The increase in the carbonization temperature, thickness, and CNT content enhanced the electrical conductivity and EMI SE of TGCF/CNT carbon papers. TGCF/CNT-15 papers, with approximately 4.5 mm of thickness, carbonized at 1300 °C exhibited the highest electrical conductivity of 6.35 S cm -1 , indicating an EMI SE of approximately 62 dB at 1.6 GHz of the low frequency band. Additionally, the obtained TGCF/CNT carbon papers were flexible and could be bent and wound without breaking.

Drug-induced liver injury (DILI) is one of the leading reasons for discontinuation of a new drug development project. Diverse machine learning or deep learning models have been developed to predict DILI. However, these models have not provided an adequate understanding of the mechanisms leading to DILI. The development of safer drugs requires novel computational approaches that enable the prompt understanding of the mechanism of DILI. In this study, the mechanisms leading to the development of cholestasis, steatosis, hepatitis, and cirrhosis were explored using a semi-automated approach for data gathering and associations. Diverse data from ToxCast, Comparative Toxicogenomic Database (CTD), Reactome, and Open TG-GATEs on reference molecules leading to the development of the respective diseases were extracted. The data were used to create biological networks of the four diseases. As expected, the four networks had several common pathways, and a joint DILI network was assembled. Such biological networks could be used in drug discovery to identify possible molecules of concern as they provide a better understanding of the disease-specific key events. The events can be target-tested to provide indications for potential DILI effects., Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00124-6., Competing Interests: Conflict of interestThe authors have no conflicts of interest to disclose., (© The Author(s) 2022.)

Background: Cervical pedicle screw (CPS) with O-arm-based intraoperative navigation has demonstrated satisfactory results in recent studies. In this article, we introduce our experience and discuss important considerations for CPS placement with O-arm navigation., Methods: We retrospectively reviewed the data of 51 patients with 156 pedicle screws who underwent O-arm navigated CPS from July 2020 to October 2021. The accuracy of each screw placement was evaluated at the initial screw location using intraoperative 3D reconstructed O-arm images and the final screw location using postoperative computed tomography (CT). The screw accuracy was assessed in the axial image., Results: The initial accuracy of screws on intraoperative 3D reconstructed O-arm images was 93.6% (146 of 156). The accuracies of the mid-cervical level (C3, C4, C5) were relatively low (83.3%-85.0%) compared with those of C2, C6, and C7 (93.3%-100.0%) at the initial screw due to the rotation of the vertebral body. Among 10 violated screws, 5 were converted to lateral mass screws or removed intraoperatively, and the other 5 were retained because the violations were minimal. After converting the screw, the final accuracy of the screws in postoperative CT was 96.7% (146 of 151)., Conclusions: CPS with O-arm navigation showed relatively low accuracy at the mid-cervical level due to vertebral rotation. However, the opportunity to convert the screw from intraoperative 3D reconstructed O-arm images is the advantage of the O-arm navigation, and it showed excellent accuracy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gungha-tang (GHT), a traditional herbal medicine, consists of nine medicinal herbs (Cnidii Rhizoma, Pinelliae Tuber, Poria Sclerotium, Citri Unshius Pericarpium, Citri Unshius Pericarpium Immaturus, Aurantii Fructus Immaturus, Atracylodis Rhizoma Alba, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens). It has been used for various diseases caused by phlegm. This study aimed to develop and verify the simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis method, using nine marker components (liquiritin apioside, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, liquiritigenin, glycyrrhizin, and 6-shogaol) for quality control of GHT. LC-MS/MS analysis was conducted using a Waters TQ-XS system. All marker analytes were separated on a Waters Acquity UPLC BEH C 18 column (2.1 × 100 mm, 1.7 μm) using gradient elution with a distilled water solution (containing 5 mM ammonium formate and 0.1% [ v / v ] formic acid)-acetonitrile mobile phase. LC-MS/MS multiple reaction monitoring (MRM) analysis was carried out in negative and positive ion modes of an electrospray ionization source. The developed LC-MS/MS MRM method was validated by examining the linearity, limits of detection and quantification, recovery, and precision. LOD and LOQ values of nine markers were calculated as 0.02-8.33 ng/mL and 0.05-25.00 ng/mL. The recovery was determined to be 89.00-118.08% and precision was assessed with a coefficient of variation value of 1.74-8.64%. In the established LC-MS/MS MRM method, all markers in GHT samples were detected at 0.003-16.157 mg/g. Information gathered during the development and verification of the LC-MS/MS method will be useful for the quality assessment of GHT and other herbal medicines.

Background: Although deep brain stimulation (DBS) is a relatively safe and effective surgery compared with ablative surgeries, intracerebral hemorrhage (ICH) is a serious complication during DBS that could result in a fatal prognosis. We retrospectively investigated whether ICH incidence differed between patients who underwent DBS in the subthalamic nucleus (STN) and in the globus pallidus interna (GPi), together with previously identified risk factors for ICH., Methods: We retrospectively reviewed the medical records of 275 patients (527 DBS targets) who received DBS for Parkinson's disease or dystonia from April 2001 to December 2020. In cases that developed intra- or postoperative ICH, patients were classified as asymptomatic, symptomatic with temporary neurological deficit or symptomatic with permanent neurological deficit, according to patient clinical status., Results: ICH occurred in 12 procedures (2.3%) among the 527 DBS procedures (275 patients) evaluated. In multivariable logistic regression analysis, the risk factor for all cases of ICH was systolic blood pressure (BP) during surgery (cut-off value 129.4 mmHg) (OR = 1.05, 95% CI = 1.01-1.09, P = 0.023). In addition, for ICH with permanent neurological deficit, STN target site (P = 0.024) and systolic BP during surgery (cut-off value: 148.3 mmHg) (P = 0.004) were identified as risk factors in univariable analyses., Conclusion: Even though the risk factor for all ICH in DBS was BP during surgery, when focused on ICH evoking permanent neurological deficit, the target location as well as systolic BP during surgery proved to be related., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Deep learning (DL) models in quantitative structure-activity relationship fed the molecular structure directly to the network without using human-designed descriptors by representing molecule as a graph or string (e.g., SMILES code). However, these two representations were oversimplification of real molecules to reflect chemical properties of molecular structures. Given that the choice of molecular representation determines the architecture of the DL model to apply, a novel way of molecular representation can open a way to apply diverse DL networks developed and used in other fields. A topological distance-based electron interaction (TDEi) tensor has been developed in this study inspired by the quantum mechanical model of the molecule, which defines a molecule with electrons and protons. In the TDEi tensor, the atomic orbital (AO) of each atom is represented by an electron configuration (EC) vector, which is a bit string based on the presence and absence of electrons in each AO according to spin indicated by positive and negative signs. Interactions between EC vectors were calculated based on the topological distance between atoms in a molecule. As a molecular structure was translated into 3D array, CNN models (modified VGGNet) were applied using a TDEi tensor to predict four physicochemical properties of drug-like compound datasets: MP (275,131), Lipop (4193), Esol (1127), and Freesolv (639). Models achieved good prediction accuracy. PCA showed that a stronger correlation was observed between the extracted features and the target endpoint as features were extracted from the deeper layer., Competing Interests: The author declares no competing financial interest., (© 2021 The Author. Published by American Chemical Society.)