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This study conducts a systematic review and meta-analysis of the randomized-controlled clinical trials (RCTs) of attachment- and relationship-based interventions in the NICU. A systematic search of the PubMed, MEDLINE, Embase (OVID), PsycINFO, and CINAHL databases and the Cochrane Database of Systematic Reviews was conducted in February 2021. Of the 32,904 studies examined, 15 were identified as relevant, and 10 RCTs were eligible for meta-analysis. Cochrane's risk of bias tool was used to assess the quality of the trial reporting. Interventions were categorized as (1) parent-infant interactions, (2) parent education, and/or (3) support through qualitative synthesis. The attachment- or relationship-based intervention was effective in relieving maternal traumatic stress, maternal depression, infant weight growth, and infant development. Subgroup analyses suggested that interventions significantly improved sub-domains of mothers' and children's interactive behavior. Tailored, staged interventions may contribute to better health outcomes in preterm infants and their families.

The present study was performed to investigate the validity of a wireless earbud-type inertial measurement unit (Ear-IMU) sensor used to estimate head angle during four workouts. In addition, relationships between head angle obtained from the Ear-IMU sensor and the angles of other joints determined with a 3D motion analysis system were investigated. The study population consisted of 20 active volunteers. The Ear-IMU sensor measured the head angle, while a 3D motion analysis system simultaneously measured the angles of the head, trunk, pelvis, hips, and knees during workouts. Comparison with the head angle measured using the 3D motion analysis system indicated that the validity of the Ear-IMU sensor was very strong or moderate in the sagittal and frontal planes. In addition, the trunk angle in the frontal plane showed a fair correlation with the head angle determined with the Ear-IMU sensor during a single-leg squat, reverse lunge, and standing hip abduction; the correlation was poor in the sagittal plane. Our results indicated that the Ear-IMU sensor can be used to directly estimate head motion and indirectly estimate trunk motion.

The tumor immune microenvironment (TIME) in high-grade glioma (HGG) exhibits high spatial heterogeneity. Though the tumor core and peripheral regions have different biological features, the cause of this spatial heterogeneity has not been clearly elucidated. Here, we examined the spatial heterogeneity of HGG using core and peripheral regions obtained separately from the patients with HGG. We analyzed infiltrating immune cells by flow cytometry from 34 patients with HGG and the transcriptomes by RNA-seq analysis from 18 patients with HGG. Peripheral region-infiltrating immune cells were in vitro cultured in hypoxic conditions and their immunophenotypes analyzed. We analyzed whether the frequencies of exhausted CD8 + T cells and immunosuppressive cells in the core or peripheral regions are associated with the survival of patients with HGG. We found that terminally exhausted CD8 + T cells and immunosuppressive cells, including regulatory T (T REG ) cells and M2 tumor-associated macrophages (TAMs), are more enriched in the core regions than the peripheral regions. Terminally exhausted and immunosuppressive profiles in the core region significantly correlated with the hypoxia signature, which was enriched in the core region. Importantly, in vitro culture of peripheral region-infiltrating immune cells in hypoxic conditions resulted in an increase in terminally exhausted CD8 + T cells, CTLA-4 + T REG cells, and M2 TAMs. Finally, we found that a high frequency of PD-1 + CTLA-4 + CD8 + T cells in the core regions was significantly associated with decreased progression-free survival of patients with HGG. The hypoxic condition in the core region of HGG directly induces an immunosuppressive TIME, which is associated with patient survival., Competing Interests: The authors declare no potential conflicts of interest., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Spinal cord injury (SCI) can cause motor, sensory, and autonomic dysfunctions and may affect the cerebral functions. However, the mechanisms of plastic changes in the brain according to SCI severity remain poorly understood. Therefore, in the current study, we compared the brain activity of the entire neural network according to severity of SCI using fractional amplitude of low-frequency fluctuations (fALFF) analysis in resting-state functional magnetic resonance imaging (rs-fMRI). A total of 59 participants were included, consisting of 19 patients with complete SCI, 20 patients with incomplete SCI, and 20 healthy individuals. Their motor and sensory functions were evaluated. The rs-fMRI data of low-frequency fluctuations were analyzed based on fALFF. Differences in fALFF values among complete-SCI patients, incomplete-SCI patients, and healthy controls were assessed using ANOVA. Then post hoc analysis and two-sample t-tests were conducted to assess the differences between the three groups. Pearson correlation analyses were used to determine correlations between clinical measures and the z-score of the fALFF in the SCI groups. Patients with SCI (complete and incomplete) showed lower fALFF values in the superior medial frontal gyrus than the healthy controls, and were associated with poor motor and sensory function (p < .05). Higher fALFF values were observed in the putamen and thalamus, and were negatively associated with motor and sensory function (p < .05). In conclusion, alterations in the neural activity of the motor- and sensory-related networks of the brain were observed in complete-SCI and incomplete-SCI patients. Moreover, plastic changes in these brain regions were associated with motor and sensory function., (© 2021 John Wiley & Sons, Ltd.)

Background: Cancer-related cognitive impairment (CRCI) is a significant problem for cancer patients, as the number of cancer survivors experiencing cognitive impairments is increasing in the absence of standard treatment. There have been attempts to improve the cognitive function of patients with cancer using acupuncture; however, no studies have been conducted using electroacupuncture. Thus, we designed a preliminary study to investigate the feasibility of a clinical trial using electroacupuncture in CRCI patients., Methods: We conducted a single-arm, pilot, clinical trial to investigate the feasibility of a study protocol for further large-scale clinical trials of electroacupuncture in CRCI patients. All participants were treated with electroacupuncture twice a week for 30 minutes at a time, for 8 weeks on acupoints GV20, GV24, EX-HN1, and GB20, HT7, PC6, and KI3. Both subjective and objective outcomes of cognitive function, quality of life (QoL), and psychological factors were measured in all participants at baseline, week 4, 8, and 12. For safety assessment, vital signs, laboratory examinations, and adverse events (AEs) were observed throughout the trial., Results: A total of 12 participants were enrolled at Daejeon and Dunsan Korean Medicine Hospital of Daejeon University from 21 April 2017 to 31 January 2018. After 8 weeks of treatment, electroacupuncture significantly improved both subjective and objective cognitive outcomes, including the perceived cognitive impairments scale of the Functional Assessment of Cancer Therapy-Cognitive Function, QoL scale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire-C30, Korean version of Montreal Cognitive Assessment, Boston Naming Test, Seoul Verbal Learning Test, and Rey Complex Figure Test. During the entire trial period, 19 AEs were observed, with no serious AEs. Additionally, it was found that all feasibility outcomes, including recruitment, completion, and adherence rates, achieved successful results as the ratio exceeded 0.8., Conclusion: Our study results revealed that electroacupuncture improved cognitive complaints in cancer patients, and we expect electroacupuncture to be a safe and effective management therapy for CRCI patients. These feasibility trial results will be used as preliminary data for future randomized controlled clinical trials., Trial Registration Number: Korean Clinical Trial Registry (KCT0002168).

Background: Seroprevalence studies of coronavirus disease 2019 (COVID-19) cases, including asymptomatic and past infections, are important to estimate the scale of the disease outbreak and to establish quarantine measures. We evaluated the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays available in Korea for use in seroprevalence studies., Methods: The sensitivity, specificity, cross-reactivity, and interference of five SARS-CoV-2 antibody assays were evaluated using the following: 398 serum samples from confirmed COVID-19 patients, 510 negative control samples from before 2018 (pre-pandemic), 163 serum samples from patients with SARS, Middle East respiratory syndrome (MERS), and other viral infections, and five samples for the interference study., Results: The sensitivities of the five assays ranged from 92.2% to 98%, and their specificities, including cross-reactivity and interference, ranged from 97.5% to 100%. The agreement rates were excellent (kappa >0.9). Adjustment of the cutoff values could be considered through ROC curve analysis. The positive predictive values of the individual assays varied from 3.5% to 100% at a 0.1% prevalence but were as high as ≥95% when two assays were combined., Conclusions: The prevalence of COVID-19 in Korea is considered to be exceptionally low at present; thus, we recommend using a combination of two or more SARS-CoV-2 antibody assays rather than a single assay. These results could help select SARS-CoV-2 antibody assays for COVID-19 seroprevalence studies in Korea.

Objectives: The Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide cross-sectional surveillance system that assesses the health and nutritional status of the Korean population. To evaluate the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the community, we investigated the prevalence of anti-SARS-CoV-2 antibodies in the sera of KNHANES participants., Methods: Subjects were recruited between April 24 and December 12, 2020. In total, 5,284 subjects aged 10-90 years from 17 regions participated. SARS-CoV-2 antibodies were screened using the Elecsys Anti-SARS-CoV-2 assay. Positive samples were verified using 4 different SARS-CoV-2 antibody assays and the plaque reduction neutralizing test. The final seropositivity criteria were a positive screening test and at least 1 positive result from the 5 additional tests., Results: Almost half (49.2%; 2,600/5,284) of participants were from metropolitan areas, 48.9% were middle-aged (40-69 years), and 20.5% were in their 20s or younger. The seropositivity rate was 0.09% (5/5,284). Three of the 5 antibody-positive subjects had a history of infection, of whom 2 were infected abroad and 1 was infected in a local cluster outbreak., Conclusions: The low SARS-CoV-2 antibody seroprevalence in Korea indicates that there have been few coronavirus disease 2019 (COVID-19) cases due to successful COVID-19 management measures (e.g., diagnostic tests for overseas arrivals, national social distancing, and strict quarantine measures). Moreover, asymptomatic infections were uncommon due to active polymerase chain reaction testing. However, hidden infections may exist in the community, requiring the continuation of quarantine and vaccination measures.

Objectives: After the third wave of coronavirus disease 2019 (COVID-19), by mid-February 2021, approximately 0.16% of the Korean population was confirmed positive, which appeared to be among the lowest rates worldwide at that time. However, asymptomatic transmission is challenging for COVID-19 surveillance. Therefore, a community-based serosurvey of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted to understand the effectiveness of Korea's strong containment strategy., Methods: We collected 5,002 residual sera samples from January 30 to March 3, 2021, from 265 medical facilities in Seoul, 346 in Gyeonggi Province, and 57 in Incheon. Sixty samples from tertiary institutions were excluded. We defined the sub-regions according to the addresses of the medical facilities where the specimens were collected. Elecsys Anti-SARS-CoV-2 was used for screening, and positivity was confirmed using the SARS-CoV-2 sVNT Kit. Prevalence was estimated using sampling weights and the Wilson score interval for a binomial proportion with a 95% confidence interval., Results: Among the 4,942 specimens, 32 and 25 tested positive for COVID-19 in the screening and confirmatory tests, respectively. The overall crude prevalence of SARS-CoV-2 antibodies was 0.51%. The population-adjusted overall prevalence was 0.55% in women and 0.38% in men. The region-specific estimation was 0.67% and 0.30% in Gyeonggi Province and Seoul, respectively. No positive cases were detected in Incheon., Conclusions: The proportion of undetected cases in Korea remained low as of early 2021. Therefore, an infection control strategy with exhaustive tracing and widespread pre-emptive testing appears to be effective in containing community spread of COVID-19.

Introduction: Lumbar spinal stenosis (LSS) is a pathological condition that causes a variety of neurological symptoms due to narrowing of the anatomical structures; usually, conservative treatment is recommended, rather than surgical treatment. Acupotomy combines conventional acupuncture with small scalpels; the procedure can be considered minimally invasive, and has recently received considerable attention in clinical practice. Still, there is a lack of data and randomized controlled trials regarding acupotomy related to LSS. Additional studies are necessary, considering the low methodological quality and small size of the study., Methods and Analysis: This is a pragmatic, pilot, randomized controlled trial. The trial comprises 8 weeks of treatment, with 16 visits and a 4-week follow-up period. Forty participants diagnosed with LSS will be randomly assigned to either the experimental or control groups; both groups will receive acupuncture and interferential current therapy twice a week for 8 weeks, while the experimental group will receive an additional acupotomy intervention once a week for 8 weeks. The primary outcome will be assessed using the visual analog scale; the secondary outcome will be measured by self-rated walking distance, Oswestry Disability Index, and short-form McGill Pain Questionnaire. Measurements will be obtained prior to the start of the clinical trial, 4 weeks after the interventional procedure, 8 weeks after the procedure, and 4 weeks after the end of the interventional procedure. Blood tests and adverse reactions will be performed to ensure safety of the treatments., Conclusion: We expect that this study will provide basic data for future large-scale acupotomy studies regarding LSS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Polydimethylsiloxane (PDMS) is an important viscoelastic material that finds applications in a large number of engineering systems, particularly lab-on-chip microfluidic devices built with a flexible substrate. Channels made of PDMS, used for transporting analytes, are integral to these applications. The PDMS viscoelastic nature can induce additional hydrodynamic contributions at the soft wall/fluid interface compared to rigid walls. In this research, we investigated the pressure drop within PDMS channels bounded by rigid tubes (cellulose tubes). The bulging effect of the PDMS was limited by the rigid tubes under flowing fluids. The PDMS viscoelasticity was modulated by changing the ratio of the base to the cross-linker from 10:1 to 35:1. We observed that the pressure drop of the flowing fluids within the channel decreased with the increased loss tangent of the PDMS in the examined laminar regime [Reynolds number ( Re ) ∼ 23-58.6 for water and Re ∼ 0.69-8.69 for glycerol solution]. The elastic PDMS 10:1 wall channels followed the classical Hagen Poiseuille's equation, but the PDMS walls with lower cross-linker concentrations and thicker walls decreased pressure drops. The friction factor ( f ) for the PDMS channels with the two working fluids could be approximated as f = 47/ Re . We provide a correlation between the pressure drop and PDMS viscoelasticity based on experimental findings. In the correlation, the loss tangent predominates; the larger the loss tangent, the smaller is the pressure drop. The research findings appear to be unexpected if only considering the energy dissipation of viscoelastic PDMS walls. We attributed the reduction in the pressure drop to a lubricating effect of the viscoelastic PDMS walls in the presence of the working fluids. Our results reveal the importance of the subtle diffusion of the residual oligomers and water from the bulk to the soft wall/fluid interface for the observed pressure drop in soft wall channels.

Alzheimer's disease (AD) is a degenerative brain disease that is the most common cause of dementia. The incidence of AD is rapidly rising because of the aging of the world population. Because AD is presently incurable, early diagnosis is very important. The disease is characterized by pathological changes such as deposition of senile plaques and decreased concentration of the amyloid-beta 42 (Aβ42) peptide in the cerebrospinal fluid (CSF). The concentration of Aβ42 in the CSF is a well-studied AD biomarker. The specific peptide probe was screened through four rounds of biopanning, which included the phage display process. The screened peptide showed strong binding affinity in the micromolar range, and the enzyme-linked peptide assay was optimized using the peptide we developed. This diagnostic method showed specificity toward Aβ42 in the presence of other proteins. The peptide-binding site was also estimated using molecular docking analysis. Finally, the diagnostic method we developed could significantly distinguish patients who were classified based on amyloid PET images.

Streptococcus gordonii, a Gram-positive commensal bacterium, is an opportunistic pathogen closely related to initiation and progression of various oral diseases, such as periodontitis and dental caries. Its biofilm formation is linked with the development of such diseases by enhanced resistance against antimicrobial treatment or host immunity. In the present study, we investigated the effect of short-chain fatty acids (SCFAs) on the biofilm formation of S. gordonii. SCFAs, including sodium acetate (NaA), sodium propionate (NaP), and sodium butyrate (NaB), showed an effective inhibitory activity on the biofilm formation of S. gordonii without reduction in bacterial growth. SCFAs suppressed S. gordonii biofilm formation at early time points whereas SCFAs did not affect its preformed biofilm. A quorum-sensing system mediated by competence-stimulating peptide (CSP) is known to regulate biofilm formation of streptococci. Interestingly, SCFAs substantially decreased mRNA expression of comD and comE, which are CSP-sensor and its response regulator responsible for CSP pathway, respectively. Although S. gordonii biofilm formation was enhanced by exogenous synthetic CSP treatment, such effect was not observed in the presence of SCFAs. Collectively, these results suggest that SCFAs have an anti-biofilm activity on S. gordonii through inhibiting comD and comE expression which results in negative regulation of CSP quorum-sensing system. SCFAs could be an effective anti-biofilm agent against S. gordonii for the prevention of oral diseases., (© 2021. The Microbiological Society of Korea.)

Shwachman-Diamond syndrome (SDS; OMIM #260400) is caused by variants in SBDS (Shwachman-Bodian-Diamond syndrome gene), which encodes a protein that plays an important role in ribosome assembly. Recent reports suggest that recessive variants in EFL1 are also responsible for SDS. However, the precise genetic mechanism that leads to EFL1-induced SDS remains incompletely understood. Here we present 3 unrelated Korean SDS patients who carry biallelic pathogenic variants in EFL1 with biased allele frequencies, resulting from a bone marrow-specific somatic uniparental disomy in chromosome 15. The recombination events generated cells that were homozygous for the relatively milder variant, allowing for the evasion of catastrophic physiologic consequences. However, the milder EFL1 variant was still solely able to impair 80S ribosome assembly and induce SDS features in cell line and animal models. The loss of EFL1 resulted in a pronounced inhibition of terminal oligopyrimidine element-containing ribosomal protein transcript 80S assembly. Therefore, we propose a more accurate pathogenesis mechanism of EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy., (© 2021 by The American Society of Hematology.)

Background: The World Health Organization declared COVID-19 a global pandemic on 11 March 2020, due to the number of newly reported confirmed cases and the rapid increase in deaths. Therefore, countries around the world limited their population to policies such as "social distancing" or "staying at home" to prevent the spread of the virus. The purpose of this study was to evaluate differences in lifestyle pre and post the outbreak COVID-19 among older adults in South Korea and to identify the impact of lifestyle differences on depression and quality of life., Methods: An online single questionnaire covering sociodemographic data, lifestyle details, depression status, and quality of life level was distributed using mailing lists and social media. To assess lifestyles differences in older people pre and post the outbreak of COVID-19 pandemic, the online single questionnaire was used post COVID-19 pandemic. Based on the participants' memories, they responded lifestyles at two time points (pre and post COVID-19 pandemic)., Results: The results showed that there was a significant decrease in physical activity and activity participation during the pandemic. In terms of nutrition, there was no statistically significant change pre and post the outbreak COVID-19, except for the intake of protein, fat, and vitamins. Additionally, the results showed that the resulting lifestyle differences seem to have had a negative impact on depression and quality of life among older adults in South Korea., Conclusion: There was a significant difference the lifestyle patterns among the participants in South Korea between the current period and pre COVID-19 pandemic. Additionally, it is observed that these differenced lifestyles were associated with depression and quality of life among the participants. Our findings may help to develop public health programs that support healthy lifestyles in pandemic conditions.

This work investigates the role of DNA binding by Runt in regulating the sloppy paired 1 ( slp1 ) gene and in particular two distinct cis -regulatory elements that mediate regulation by Runt and other pair-rule transcription factors during Drosophila segmentation. We find that a DNA-binding-defective form of Runt is ineffective at repressing both the distal (DESE) and proximal (PESE) early stripe elements of slp1 and is also compromised for DESE-dependent activation. The function of Runt-binding sites in DESE is further investigated using site-specific transgenesis and quantitative imaging techniques. When DESE is tested as an autonomous enhancer, mutagenesis of the Runt sites results in a clear loss of Runt-dependent repression but has little to no effect on Runt-dependent activation. Notably, mutagenesis of these same sites in the context of a reporter gene construct that also contains the PESE enhancer results in a significant reduction of DESE-dependent activation as well as the loss of repression observed for the autonomous mutant DESE enhancer. These results provide strong evidence that DNA binding by Runt directly contributes to the regulatory interplay of interactions between these two enhancers in the early embryo.

Background: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification., Methods: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier)., Results: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems., Conclusions: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Competing Interests: There are no conflicts of interest.

Regional Cardiocerebrovascular Centers (RCCs)-a Korean government initiative-seek to reduce medical gaps across regions, and their cardiac rehabilitation (CR) programs are expected to model post-acute care for the Korean CR program. Accordingly, this study aimed to evaluate the current status of CR programs in the RCCs. We distributed surveys on the CR condition, activity, and barriers to 12 RCCs in different provinces. The results revealed significant gaps in the annual number of acute myocardial infarction admissions, and CR candidates, capacity, and density across the 12 RCCs. The CR capacity (50-500) and density (0.42-7.36) indicated particularly large gaps. Twelve RCCs had the necessary facilities, equipment and personnel for CR assessments and management, with high CR referral (97%) and patient education (78%) rates. However, the inpatient CR exercise training (56%) participation rate was inadequate, with much lower enrollment (47%) and adherence (17%) rates to the outpatient CR program and large differences across centers. Therefore, this study's results will provide the evidence required to establish special national health strategies to overcome the CR barriers of patient, doctor/hospital, and policy factors for activating Korean CR programs.

Initiation and progression of oral infectious diseases are associated with streptococcal species. Bacterial infection induces inflammatory responses together with reactive oxygen species (ROS), often causing cell death and tissue damage in the host. In the present study, we investigated the effects of oral streptococci on cytotoxicity and ROS production in human periodontal ligament (PDL) cells. Streptococcus gordonii showed cell cytotoxicity in a dose- and time-dependent manner. The cytotoxicity might be due to apoptosis since S. gordonii increased annexin V-positive cells, and the cytotoxicity was reduced by an apoptosis inhibitor, Z-VAD-FMK. Other oral streptococci such as Streptococcus mitis , Streptococcus sanguinis , and Streptococcus sobrinus also induced apoptosis, whereas Streptococcus mutans did not. All streptococci tested except S. mutans triggered ROS production in human PDL cells. Interestingly, however, streptococci-induced apoptosis appears to be ROS-independent, as the cell death induced by S. gordonii was not recovered by the ROS inhibitor, resveratrol or n -acetylcysteine. Instead, hydrogen peroxide (H 2 O 2 ) appears to be important for the cytotoxic effects of streptococci since most oral streptococci except S. mutans generated H 2 O 2 , and the cytotoxicity was dramatically reduced by catalase. Furthermore, streptococcal lipoproteins are involved in cytotoxicity, as we observed that cytotoxicity induced by the lipoprotein-deficient S. gordonii mutant was less potent than that by the wild-type and was attenuated by anti-TLR2-neutralizing antibody. Indeed, lipoproteins purified from S. gordonii alone were sufficient to induce cytotoxicity. Notably, S. gordonii lipoproteins did not induce H 2 O 2 or ROS but cooperatively induced cell death when co-treated with H 2 O 2 . Taken together, these results suggest that most oral streptococci except S. mutans efficiently induce damage to human PDL cells by inducing apoptotic cell death with bacterial H 2 O 2 and lipoproteins, which might contribute to the progression of oral infectious diseases such as apical periodontitis., 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 © 2021 Park, Kim, So, Im, Ji, Ahn, Seo, Yun and Han.)

Numerous chemosensors have been developed for next-generation detection systems because of their ease of use and promising characteristics to distinguish signals between various analytes binding. However, given their typically poor emission response and arduous preparation methods, very few chemosensing probes have been commercialized to date. In this work, a simple, naphthoquinone-based mitochondria-targeting chemosensor (CIA) has been fabricated for the simultaneous detection of Cu 2+ and GSSG (glutathione oxidized) through an "on-off" mode in a buffered semi-aqueous solution. Significantly, the CIA chemosensor showed a sensitive detection response towards Cu 2+ and GSSG with low detection limits (0.309 μM, and 0.226 μM, respectively). In addition, the detection mechanism of CIA was thoroughly verified and confirmed using numerous analytical techniques. Furthermore, CIA was utilized as a sequential fluorescence biomarker to detect Cu 2+ in human cervical cancer cell lines. These findings indicate that the chemosensor CIA can discriminate human cancer cells from normal cells. The CIA was also confirmed to possess the ability to target mitochondria. More importantly, the present CIA chemosensor detected Cu 2+ in zebrafish larvae, indicating the probe has tissue penetration ability., 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 © 2021 Elsevier B.V. All rights reserved.)

The goal of the present work was to fabricate a new low-cost, easy-to-prepare, dual-channel fluorescence chemosensor comprised of acridine-diphenylacetyl moieties (NDA) to enable remarkable Sn 4+ detection in water and biological medium. The resulting NDA-Sn 4+ complex was utilized for the distinguished identification of Cr 2 O 7 2- ions from other anions and biomolecules. These investigations involve the absorption, fluorescence, and electrochemical methods for the detection of Sn 4+ and Cr 2 O 7 2- ions in pure water. The mechanism for NDA-mediated Sn 4+ detection was experimentally determined by FT-IR, NMR titrations, mass (ESI) analyses, and DFT calculations. The obtained results indicate that the NDA chemosensor possessed excellent performance characteristics including good water solubility and compatibility, quick response time (less than 10 s), high sensitivity (Sn 4+ = 0.268 μM and Cr 2 O 7 2- = 0.160 μM), and selectivity against coexisting metals, anions, amino acids, and peptides. The chemosensor NDA induced negligible toxicity in live cells and was successfully utilized as a biomarker for the tracking of Sn 4+ in human normal and cancer cells. More importantly, NDA demonstrates distinguished recognition of Sn 4+ in human cancer cells rather than in normal live cells. Additionally, NDA was shown to act as a mitochondria-targeted probe in FaDu cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of sensory-based feeding treatment for toddlers with food refusal compared with only providing nutrition education., Methods: Thirty-two toddlers with food refusal were randomly assigned to an intervention group or the control group. Toddlers in the intervention group received the sensory-based feeding intervention and the duration was for 1 hour for 5 days per week for 4 weeks, and then 1 hour, once a week for 8 weeks. Subjects in both the intervention and control groups received nutritional education once every 4 weeks for 12 weeks. The participants were evaluated at their entry into the study and 12 weeks later based on height, weight, behavior at mealtime using the Behavioral Pediatrics Feeding Assessment Scale (BPFAS), and sensory processing ability using the Infant/Toddler Sensory Profile., Results: Sixteen toddlers were included in each group. Two subjects in the intervention group and four toddlers in the control group were excluded from the final analysis. Significant improvements in child or parent subscales of the BPFAS were observed in the intervention group. In contrast, there were no significant improvements in any BPFAS scores in the control group., Conclusion: Sensory-based feeding intervention was effective for improving mealtime behavior in toddlers with food refusal. Therefore, a sensory-based feeding intervention could be considered as an intervention approach to address feeding disorders in toddlers.

Isolated pyramids, 30-80 nm wide and 3-20 nm tall, form during sputter-annealing cycles on the Ge (110) surface. Pyramids have four walls with {19 13 1} faceting and a steep mound at the apex. We used scanning tunneling microscopy (STM) under ultrahigh vacuum conditions to periodically image the surface at ion energies between 100 eV and 500 eV and incremental total flux. Pyramids are seen using Ar + between 200 eV and 400 eV, and require Ag to be present on the sample or sample holder. We suspect that the pyramids are initiated by Ag co-sputtered onto the surface. Growth of pyramids is due to the gathering of step edges with (16 × 2) reconstruction around the pyramid base during layer-by-layer removal of the substrate, and conversion to {19 13 1} faceting. The absence of pyramids using Ar + energies above 400 eV is likely due to surface damage that is insufficiently annealed.

Objectives: Emerging studies found the potential effects of acupuncture for treating chronic pain and mental disorders, namely, depressive and anxiety disorders. Acupuncture is widely used for treating culture-related anger syndrome, Hwa-byung. This pilot trial aimed to investigate the feasibility of a clinical trial testing acupuncture for the psychosomatic symptoms of Hwa-byung. Methods: A total of 26 patients with Hwa-byung planned to be randomly assigned to the acupuncture or sham acupuncture groups. About 10 treatment sessions were applied over 4 weeks. The 100-mm visual analog scale was used to measure the six major Hwa-byung symptoms: stuffiness in the chest, heat sensations, pushing-up in the chest, feeling a mass in the throat, feelings of unfairness, and hard feelings. The criteria for assessing the success of this pilot trial were defined as improvement in three or more of the six Hwa-byung symptoms after treatment, with an effect size >0.2. Results: A total of 15 patients were finally included and randomly assigned to the acupuncture group ( n = 7) or the sham acupuncture group ( n = 8). After 10 treatment sessions, the Cohen's d effect sizes for acupuncture compared to sham acupuncture were >0.2 for each one of the six major Hwa-byung symptoms, which met our a priori criteria for success. Also, the effect size for the somatic symptoms of "stuffiness in the chest" was 0.81 (95% CI -0.40, 2.20), referring to a large effect size. Conclusions: Our results suggest that acupuncture treatment would be regarded as an acceptable intervention for a full-scale study of psychosomatic symptoms in patients with Hwa-byung. Trial Registration: cris.nih.go.kr, identifier: KCT0001732., 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 © 2021 Choi, Park, Kim, Kwon, Kim, Park, Lee and Kim.)

Objective: This study aimed to analyze the factors affecting depression among South Korean middle-aged and older adults using data from the Korean Longitudinal Study of Aging. Methods: We analyzed data regarding demographic characteristics, lifestyle, quality of life, cognitive level, and depression. Cognitive level and depression were evaluated using the Korean-Mini-Mental Status Examination and Center for Epidemiological Studies Depression Scale, respectively. Results: Depression was correlated with age, gender, residential area, level of education, alcohol intake, regular exercise, life satisfaction, and cognitive level, but not smoking. Furthermore, depression was highly affected by age, residential area, regular exercise, life satisfaction, and cognitive level, with a prediction accuracy of 80.26% achieved through machine learning analysis. Conclusions: Various factors are associated with depression in middle-aged and older adults. Therefore, multifaceted interventions for preventing depression in these age groups are required.

A species-specific quantitative PCR (qPCR) assay using environmental DNA (eDNA) is a promising tool for both qualitative and quantitative analyses of target species directly from water samples. Despite its reliability, an eDNA-based qPCR assay pipeline has not yet developed to monitor salmon species inhabiting Korean waters, which have been rapidly decreasing. We designed species-specific primers for four Oncorhynchus species inhabiting the eastern coastal waters along the Korean Peninsula. These include primers for two native species ( Oncorhynchus keta and O. masou ) and two that were introduced ( O. mykiss and O. kisutch ). The limit of detection and limit of quantification for the four qPCR assays ranged from 4.11 to 10.38 copies and from 30 to 81 copies, respectively, indicating a high sensitivity and specificity across all four species. Following optimization, the qPCR assays were used for the quantitative analyses of the four Oncorhynchus species in the Yangyangnamdae River during the spawning and non-spawning seasons in the year 2019-2020, one of the main rivers where salmon migrate during the spawning season in Korea. The raw copy numbers in all of the examined samples were normalized by PCR inhibition rates to standardize and compare with other studies. Among the four Oncorhynchus species examined, the eDNA concentration of O. keta increased significantly (63.60-fold, p < 0.0001) during the spawning season (November) compared with that in the non-spawning season (March), suggesting that O. keta is the main salmon species migrating through the Yangyangnamdae River. In contrast, we did not detect any differences in eDNA concentration for the other three Oncorhynchus species between the spawning and non-spawning seasons, indicating that their presence does not alter during the year. Their eDNA concentration is also relatively low compared to O. keta , which suggests that small numbers of these three species are present in the river. Overall, these newly developed qPCR assays represent useful monitoring tools for the management of four salmon species in Korean waters.

Background: Danggwijagyaksan (DJS) has been one of the most widely used herbal medicines for gynecological disorders in traditional East Asian medicine. Several clinical studies about DJS have shown improvement in menopausal symptoms. This pilot study aimed to evaluate the efficacy, safety and feasibility of DJS for treating climacteric syndrome with a blood-deficiency-dominant pattern., Methods: This was a randomized, double-blind, placebo-controlled pilot trial. A group of 45-to 60-year-old women with climacteric syndrome were registered for the trial. The participants received treatment over a 4-week period and were then followed for 4 weeks. The primary outcome measure was the mean change in the Menopause Rating Scale (MRS). Secondary outcome measures included the World Health Organization Quality of Life-BREF (WHOQOL-BREF), the Blood-Deficiency Scoring System (BDSS), lean body mass, and serum hormone levels, including follicle-stimulating hormone (FSH) and estradiol (E 2 ) levels., Results: The MRS and BDSS scores decreased significantly in both groups, but the differences between two groups were not significant. The WHOQOL-BREF scores increased in the control group. No statistically meaningful differences in serum hormone levels or lean body mass were observed in both groups. There were no serious adverse events, and the laboratory tests were within the normal range. The recruitment rate, completion rate and medication adherence rate were over 90% in both groups, indicating high feasibility., Conclusions: DJS showed clinical effectiveness in the treatment of climacteric syndrome with a blood-deficiency-dominant pattern. Additionally, DJS was shown to be safe and feasible for a large-scale study to confirm the efficacy of the treatment. Trial registration: Clinical Research Information Service (CRIS, https://cris.nih.go.kr): KCT0002387., Competing Interests: The authors declare that they have no competing interests., (© 2021 Published by Elsevier B.V. on behalf of Korea Institute of Oriental Medicine.)

Background: The first treatment option for major depressive disorder (MDD) is antidepressants, however, there is substantial demand for alternative therapies due to its low compliance and remission rates. This study was aimed to explore the effectiveness, safety, and feasibility of electroacupuncture plus moxibustion therapy for MDD., Methods: Thirty adults with MDD were randomly assigned to the treatment group (TG) or control group (CG). The TG was treated with electroacupuncture plus moxibustion, and the CG received sham interventions at non-acupoints for 8 weeks. The primary outcome measure was the intergroup difference of the mean change of total score of the Hamilton rating scale for depression (HRSD) between baseline and week 9. Secondary outcome measures were Beck's depression inventory, insomnia severity index, the state-trait anxiety inventory, the EuroQol-5 dimension index, the measure yourself medical outcome profile version 2, and frontal alpha asymmetry measured by electroencephalography. Adverse events (AEs) were monitored for safety assessment., Results: The primary outcome measure was not significantly different between the two groups (p=0.2641), although the scores of HRSD in both groups improved significantly after treatment. No significant difference was identified between groups in secondary outcome measures. The incidence of AE was not significantly different between the two groups (p=0.1067)., Conclusion: A clinical trial using electroacupuncture plus moxibustion for MDD seems feasible. However, further studies with the larger size, adopting ideal controls are warranted to provide a confirmative conclusion to the efficacy and safety of electroacupuncture plus moxibustion for MDD., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier B.V. on behalf of Korea Institute of Oriental Medicine.)

Background: Postoperative patient-controlled analgesia provides pain relief, encourages early mobilization, and results in a shortened hospital stay. Patient-controlled analgesia involves the mixing of different types of drugs. When using patient-controlled analgesia, it is important to confirm the microbiological and physicochemical stability of each drug in a mixture to guarantee that the drug is delivered to the patient in an unaltered form., Objectives: To confirm the microbiological and physicochemical stability of various drug mixtures for intravenous patient-controlled analgesia., Study Design: An in vitro protocol to examine the microbiological and physicochemical stability of the most commonly used postoperative intravenous patient-controlled analgesia mixtures at our institution., Setting: In vitro laboratory study., Methods: Each mixture contained a total of 4 drugs: fentanyl 400 µg, ketorolac 30 mg, either hydromorphone 4 mg or oxycodone 10 mg, and either ramosetron 0.3 mg or ondansetron 10 mg. Each mixture was placed in a portable patient-controlled analgesia system containing 0.9% saline and stored at a constant temperature of 24°C for 96 hours. Physical properties (color, transparency, and sedimentation) were observed with the naked eye and optical microscopy. Sterility testing was performed to assess microbiological contamination in the drug mixture during the 96-hour study period. The pH of each mixture was evaluated for up to 96 hours after mixing. The concentration of each drug was evaluated by high-performance liquid chromatography every 24 hours until 96 hours after mixing., Results: All mixtures appeared visibly transparent, and no sediments were visible under the microscope. Bacterial or fungal growth was not observed in any of the samples after 14 days of incubation. The pH variations in all mixtures were maintained within 0.25 over the 96-hour study period. The concentration of drugs, except ketorolac, ranged from 90-110% of the initial concentration up to 96 hours after mixing. In the mixtures with a pH of 4.21-4.39, the concentration of ketorolac significantly decreased at 24 hours and 48 hours., Limitations: Confirmation of the stability of drugs in vitro does not automatically ensure that the pharmacokinetics and pharmacodynamics of the drugs are not altered in vivo., Conclusion: With the exception of ketorolac, the drugs used in the intravenous patient-controlled analgesia drug mixtures in this study were physicochemically stable up to 96 hours after mixing. The concentration of ketorolac decreased in more acidic mixtures.

Identifying the severity of carpal tunnel syndrome (CTS) is essential to providing appropriate therapeutic interventions. We developed and validated machine-learning (ML) models for classifying CTS severity. Here, 1037 CTS hands with 11 variables each were retrospectively analyzed. CTS was confirmed using electrodiagnosis, and its severity was classified into three grades: mild, moderate, and severe. The dataset was randomly split into a training (70%) and test (30%) set. A total of 507 mild, 276 moderate, and 254 severe CTS hands were included. Extreme gradient boosting (XGB) showed the highest external validation accuracy in the multi-class classification at 76.6% (95% confidence interval [CI] 71.2-81.5). XGB also had an optimal model training accuracy of 76.1%. Random forest (RF) and k-nearest neighbors had the second-highest external validation accuracy of 75.6% (95% CI 70.0-80.5). For the RF and XGB models, the numeric rating scale of pain was the most important variable, and body mass index was the second most important. The one-versus-rest classification yielded improved external validation accuracies for each severity grade compared with the multi-class classification (mild, 83.6%; moderate, 78.8%; severe, 90.9%). The CTS severity classification based on the ML model was validated and is readily applicable to aiding clinical evaluations., (© 2021. The Author(s).)

The activation of signal transducer and activator of transcription 3 (STAT3), as well as up-regulation of cytokines and growth factors to promote STAT3 activation, have been found in the epidermis of psoriatic lesions. Recently, a series of synthetic compounds possessing the Michael acceptor have been reported as STAT3 inhibitors by covalently binding to cysteine of STAT3. We synthesized a Michael acceptor analog, SKSI-0412, and confirmed the binding affinity between STAT3 and SKSI-0412. We hypothesized that the SKSI-0412 can inhibit interleukin (IL)-17A-induced inflammation in keratinocytes. The introduction of IL-17A increased the phosphorylation of STAT3 in keratinocytes, whereas the inactivation of STAT3 by SKSI-0412 reduced IL-17A-induced STAT3 phosphorylation and IκBζ expression. In addition, human β defensin-2 and S100A7, which are regulated by IκBζ, were significantly decreased with SKSI-0412 administration. We also confirmed that SKSI-0412 regulates cell proliferation, which is the major phenotype of psoriasis. Based on these results, we suggest targeting STAT3 with SKSI-0412 as a novel therapeutic strategy to regulate IL-17A-induced psoriatic inflammation in keratinocytes.

Gender differences have been recognized in several aspects of coronary artery disease (CAD). However, evidence for gender differences in long-term outcomes after left main coronary artery (LMCA) revascularization is limited. We sought to evaluate the impact of gender on outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for unprotected LMCA disease. We evaluated 4,320 patients with LMCA disease who underwent CABG (n = 1,456) or PCI (n = 2,864) from the Interventional Research Incorporation Society-Left MAIN Revascularization registry. The primary outcome was a composite of death, myocardial infarction (MI), or stroke. Among 4,320 patients, 968 (22.4%) were females and 3,352 (77.6%) were males. Compared to males, females were older, had a higher prevalence of hypertension and insulin-requiring diabetes, more frequently presented with acute coronary syndrome, but had less extensive CAD and less frequent left main bifurcation involvement. The adjusted risk for the primary outcome was not different after PCI or CABG in females and males (hazard ratio [HR] 1.09; 95% confidence interval [CI]: 0.73-1.63 and HR 0.97; 95% CI: 0.80-1.19, respectively); there was no significant interaction between gender and the revascularization strategy (P for interaction = 0.775). In multivariable analysis, gender did not appear to be an independent predictor for the primary outcome. In revascularization for LMCA disease, females and males had a comparable primary composite outcome of death, MI, or stroke with either CABG or PCI without a significant interaction of gender with the revascularization strategy., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A new colorimetric and ratiometric fluorescence chemosensor 4-((3-(octadecylthio)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino)benzenesulfonamide (4DBS) was synthesized and investigated for the selective detection of Hg 2+ in DMSO-H 2 O (9:1, v/v) solution. The chemosensor was efficiently synthesized in two steps via Michael-like addition and nucleophilic substitution reactions. The ratiometric fluorescence turn-on response was obtained towards Hg 2+ , and its fluorescence emission peak was red-shifted by 140 nm with an associated color change from light maroon to pale yellow due to the intramolecular charge transfer effect. The formed coordination metal complex was further evaluated by FT-IR, 1 H NMR, and quantum chemical analyses to confirm the binding mechanism. The detection process was sensitive/reversible, and the calculated limit of detection for Hg 2+ was 0.451 µM. Furthermore, 4DBS was effectively utilized as a bioimaging agent for detection of Hg 2+ in live cells and zebrafish larvae. Additionally, 4DBS showed distinguishing detection of Hg 2+ in cancer cells in comparison with normal cells. Thus, 4DBS could be employed as an efficient bioimaging probe for discriminative identification of human cancer cells., 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 © 2021 Elsevier B.V. All rights reserved.)

Several fluorescence and colorimetric chemosensory for Sn 2+ detection in an aqueous media have been reported, but applications remain limited for discriminative Sn 2+ detection in live human cells and zebrafish larvae. Herein, a mitochondria-targeted Sn 2+ "turn-on" colorimetric and fluorescence chemosensor, 2CTA, with an aggregation-induced emission (AIE) response was developed. The sensing of Sn 2+ was enabled by a reduction-enabled binding pathway, with the conversion of -C˭O groups to -C-OH groups at the naphthoquinone moiety. The color changed from light maroon to milky white in a buffered aqueous solution. The chemosensor 2CTA possessed the excellent characteristics of good water solubility, fast response (less than 10 s), and high sensitivity (79 nM) and selectivity for Sn 2+ over other metal ions, amino acids, and peptides. The proposed binding mechanism was experimentally verified by means of FT-IR and NMR studies. The chemosensor 2CTA was successfully employed to recognize Sn 2+ in live human cells and in zebrafish larvae. In addition, a colocalization study proved that the chemosensor had the ability to target mitochondria and overlapped almost completely with MitoTracker Red. Furthermore, a bioimaging study of live cells demonstrated the discriminative detection of Sn 2+ in human cancer cells and the practical applications of 2CTA in biological systems., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We previously demonstrated the safety and feasibility of mesenchymal stem cell (MSC) transplantation for bronchopulmonary dysplasia (BPD) in preterm infants in a phase I clinical trial. We thus investigated the therapeutic efficacy of MSCs for BPD in premature infants. A phase II double-blind, randomized, placebo-controlled clinical trial was conducted on preterm infants at 23 to 28 gestational weeks (GW) receiving mechanical ventilator support with respiratory deterioration between postnatal days 5 and 14. Infants were stratified by 23 to 24 GW and 25 to 28 GW and randomly allocated (1:1) to receive stem cells (1 × 10 7 cells/kg, n = 33) or placebo (n = 33). Although the inflammatory cytokines in the tracheal aspirate fluid were significantly reduced with MSCs, the primary outcome of death or severe/moderate BPD in the control group (18/33, 55%) was not significantly improved with MSC transplantation (17/33, 52%). In the subgroup analysis, the secondary outcome of severe BPD was significantly improved from 53% (8/15) to 19% (3/16) with MSC transplantation in the 23 to 24 GW group but not in the 25 to 28 GW subgroup. In summary, although MSC transplantation might be safe and feasible, this small study was underpowered to detect its therapeutic efficacy in preterm infants at 23 to 28 GW. Accordingly, we are now conducting an additional larger and controlled phase II clinical trial focusing on infants at 23 to 24 GW (NCT03392467). ClinicalTrials.gov identifier: NCT01828957., (© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Background: Tegoprazan is a novel, fast- and long-acting potassium-competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non-erosive reflux disease (NERD), a type of gastroesophageal reflux disease., Aim: To evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD., Methods: In this phase 3, double-blind, placebo-controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4-week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated., Results: Among all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn-free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P < 0.05 for all). No significant difference in the incidence of treatment-emergent adverse events were noted., Conclusions: Tegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with NERD. Registration number: ClinicalTrials.gov identifier NCT02556021., (© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Abstract: Variables derived from the cardiopulmonary exercise test (CPX) provide objective information regarding the exercise capacity of children with cerebral palsy (CP), which can be used as the basis for exercise recommendations. Performing maximal CPX might not be appropriate, safe, or practical for children with CP. In the present study, the safety and feasibility of symptom-limited CPX using the modified Naughton protocol, a submaximal protocol, were investigated in children with CP, Gross Motor Function Classification System (GMFCS) level I or II. The present study included 40 children aged 6 to 12 years with CP who underwent symptom-limited CPX. CPX was performed to measure cardiopulmonary fitness using a treadmill with a modified Naughton protocol. Motor capacity was assessed using the Gross Motor Function Measure (GMFM), Pediatric Balance Scale (PBS), Timed Up and Go (TUG) test, and 6-minute walk test. Thirty-seven children with CP successfully completed testing without any adverse events during or immediately after CPX (dropout rate 7.5%). The reason for test termination was dyspnea (51.4%) or leg fatigue (48.6%). Based on the respiratory exchange ratio (RER), 21 of 37 (56.8%) children chose premature termination. The relationship between the reason for test termination and RER was not statistically significant (Spearman rho = 0.082, P = .631). CPX exercise time was strongly correlated with GMFM (Spearman rho = 0.714) and moderate correlation with PBS (Spearman rho = 0.690) and TUG (Spearman rho = 0.537). Peak oxygen uptake during CPX showed a weak correlation with GMFM and a moderate correlation with PBS. This study revealed that symptom-limited CPX using the modified Naughton protocol was safe and feasible for children with CP and GMFCS level I or II., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The development of potential and novel proton exchange membranes (PEMs) is imperative for the further commercialization of PEM fuel cells (PEMFCs). In this work, phosphotungstic acid (PWA) and graphene oxide (GO) were integrated into sulfonated poly(arylene ether) (SPAE) through a solution casting approach to create a potential composite membrane for PEMFC applications. Thermal stability of membranes was observed using thermogravimetric analysis (TGA), and the SPAE/GO/PWA membranes exhibited high thermal stability compared to pristine SPAE membranes, owing to the interaction between SPAEK, GO, and PWA. By using a scanning electron microscope (SEM) and atomic force microscope (AFM), we observed that GO and PWA were evenly distributed throughout the SPAE matrix. The SPAE/GO/PWA composite membrane comprising 0.7 wt% GO and 36 wt% PWA exhibited a maximum proton conductivity of 186.3 mS cm -1 at 90 °C under 100% relative humidity (RH). As a result, SPAE/GO/PWA composite membrane exhibited 193.3 mW cm -2 of the maximum power density at 70 °C under 100% RH in PEMFCs.

Healthy living habits (healthy eating, regular physical activity, abstinence from smoking, restrictions on alcohol consumption, and stress management) can help prevent a significant number of diseases. The purpose of this study is to use a bibliometric analysis to analyze the relationships between countries, institutions and authors through lifestyle studies from 2016 to 2020 to find out the latest research trends. This study utilized bibliometric data collected through Scopus including thesis titles, authors, agencies, countries/regions, publication years, and keywords. Data were analyzed using the VOS viewer (Vers. 1.6.13; Leiden University, Leiden, The Netherlands) and the findings were used to visualize similarity mapping techniques. Publication of lifestyle-related research papers has steadily increased between 2016 and 2020. The country/region most actively conducting such research was the United States, also home to the majority of institutions conducting work in the field. PloS ONE published the most lifestyle-related research under the field of Medicine. Identified keywords were related to risk measures, psychosocial factors, prevention, health promotion, and risk factors. Lifestyle research is a promising field of research worldwide and has great potential to improve human health, the environment, and quality of life. The findings are expected to promote future research and give direction to the advancement of the field of research by comprehensively analyzing and summarizing lifestyle research trends.

Cancer-related fatigue (CRF) is one of the most common chronic symptoms experienced by cancer patients. As moxibustion is a popular traditional therapy for managing fatigue, it can be an alternative strategy to treat CRF as well. Therefore, we rigorously designed a full-scale, multicenter, assessor-blinded, randomized controlled trial to evaluate the efficacy and safety of moxibustion treatment for CRF. Ninety-six subjects suffering from CRF were recruited and randomly assigned to moxibustion group, sham moxibustion group, or usual care group. Both the moxibustion group and the sham group received moxibustion treatment for 8 weeks and the usual care group did not. Brief fatigue inventory (BFI) score and Functional Assessment of Cancer Therapy-Fatigue score were used to assess CRF at baseline and weeks 5, 9, and 13. Questionnaires for the assessment of cognitive impairment, quality of life, and Cold-Heat and Deficiency-Excess patterns were also evaluated. BFI scores significantly decreased in moxibustion group compared to the usual care group (mean difference of -1.92, p < 0.001 at week 9 and mean difference of -2.36, p < 0.001 at week 13). Although the sham group also showed significant improvement during the treatment period, only the moxibustion group showed improvement after 4 weeks of follow-up period (mean difference of -1.06, p < 0.001). There were no serious adverse events. Our findings confirmed the efficacy and safety of moxibustion for CRF compared to usual care. We also found that moxibustion has a prolonged treatment effect during 4 weeks of follow-up period., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures., Methods: The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications., Results: The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (p = 0.019), and T8 dominant group than T4 dominant group (p = 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps., Conclusions: Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.

Early (preclinical) diagnosis of Parkinson's disease (PD) is a major challenge in modern neuroscience. The objective of this study was to experimentally evaluate a diagnostic challenge test with monoiodotyrosine (MIT), an endogenous inhibitor of tyrosine hydroxylase. Striatal dopamine was shown to decrease by 34% 2 h after subcutaneous injection of 100 mg/kg MIT to intact mice, with the effect not being amplified by a further increase in the MIT dose. The selected MIT dose caused motor impairment in a neurotoxic mouse model of preclinical PD, but not in the controls. This was because MIT reduced striatal dopamine to the threshold of motor symptoms manifestation only in PD mice. Therefore, using the experimental mouse model of preclinical PD, we have shown that a MIT challenge test may be used to detect latent nigrostriatal dysfunction., (Copyright ® 2021 National Research University Higher School of Economics.)