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This study utilized the Early Growth and Development Study (N = 561 adoptive children; 57.2% male, 55.3% White), a study of children adopted at birth, to examine heritable (birth parent psychopathology) and prenatal risk (prenatal maternal distress and smoking during pregnancy), infant negative affectivity, adoptive parent over-reactivity and warmth as independent predictors of childhood externalizing symptoms. The current study evaluated if: (1) infant negative affectivity and over-reactive parenting are candidate mediators for the effects of heritable and prenatal risk on externalizing symptoms and (2) parental warmth weakens the influence of heritable risk, prenatal risk, negative affectivity, and over-reactive parenting on externalizing symptoms. There were main effects of heritable risk, infant negative affectivity, and over-reactive parenting on child externalizing symptoms. The study found no support for the hypothesized mediation and moderation effects, suggesting that targeting parental over-reactivity rather than warmth would be more effective in reducing risk for childhood externalizing symptoms., Competing Interests: Conflict of interest disclosure. The authors have no conflicts of interests to disclose.

Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the association between prepregnancy or perinatal risk factors and the NDD of offspring. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002 to 2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression of interaction and non-linearity terms, 79% versus 50% (MDD), 82% versus 52% (CDD) and 74% versus 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring., (© 2024. The Author(s).)

This study introduces a thermally responsive smart hydrogel with enhanced electrical properties achieved through volume switching. This advancement was realized by incorporating multiscale liquid metal particles (LMPs) into the PNIPAM hydrogel during polymerization, using their inherent elasticity and conductivity when deswelled. Unlike traditional conductive additives, LMPs endow the PNIPAM hydrogel with a remarkably consistent volume switching ratio, significantly enhancing electrical switching. This is attributed to the minimal nucleation effect of LMPs during polymerization and their liquid-like behavior, like vacancies in the polymeric hydrogel under compression. The PNIPAM/LMP hydrogel exhibits the highest electrical switching, with an unprecedented switch of 6.1 orders of magnitude. Even after repeated swelling/deswelling cycles that merge some LMPs and increase the conductivity when swelled, the hydrogel consistently maintains an electrical switch exceeding 4.5 orders of magnitude, which is still the highest record to date. Comprehensive measurements reveal that the hydrogel possesses robust mechanical properties, a tissue-like compression modulus, biocompatibility, and self-healing capabilities. These features make the PNIPAM/LMP hydrogel an ideal candidate for long-term implantable bioelectronics, offering a solution to the mechanical mismatch with dynamic human tissues.

Objectives: Difficulties in interpersonal relationships intensify negative emotions and act as risk and maintenance factors for eating pathology in eating disorders. Rejection sensitivity refers to the tendency to react sensitively to a rejection. Patients with eating disorders experience difficulties in interpersonal relationships because of their high sensitivity to rejection. Cognitive bias modification interpretation (CBM-I) is a treatment developed to correct interpretation bias for social and emotional stimuli. In this review, we searched for research characteristics and trends through a systematic literature analysis of CBM-I for eating disorders., Methods: Five papers that met the selection and exclusion criteria were included in the final literature review and analyzed according to detailed topics (participant characteristics, design, and results)., Results: The literature supports the efficacy of the CBM-I in reducing negative interpretation bias and eating disorder psychopathology in patients with eating disorders. CBM-I targets emotional dysregulation in adolescent patients with eating disorders and serves as an additional strengthening psychotherapy to alleviate eating disorder symptoms., Conclusion: The current findings highlight the potential of CBM-I as an individualized adjunctive treatment for adolescents with eating disorders and social functioning problems., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Academy of Child and Adolescent Psychiatry.)

Some insertion sequence (IS) elements were actively transposed using oxidative stress conditions, including gamma irradiation and hydrogen peroxide treatment, in Deinococcus geothermalis , a radiation-resistant bacterium. D. geothermalis wild-type (WT), sigma factor gene-disrupted (∆ dgeo _0606), and LysR gene-disrupted (∆ dgeo _1692) mutants were examined for IS induction that resulted in non-pigmented colonies after gamma irradiation (5 kGy) exposure. The loss of pigmentation occurred because dgeo _0524, which encodes a phytoene desaturase in the carotenoid pathway, was disrupted by the transposition of IS elements. The types and loci of the IS elements were identified as IS Dge2 and IS Dge6 in the ∆ dgeo _0606 mutant and IS Dge5 and IS Dge7 in the ∆ dgeo _1692 mutant, but were not identified in the WT strain. Furthermore, 80 and 100 mM H 2 O 2 treatments induced different transpositions of IS elements in ∆ dgeo _0606 (IS Dge5 , IS Dge6 , and IS Dge7 ) and WT (IS Dge6 ). However, no IS transposition was observed in the ∆ dgeo _1692 mutant. The complementary strain of the ∆ dgeo _0606 mutation showed recovery effects in the viability assay; however, the growth-delayed curve did not return because the neighboring gene dgeo _0607 was overexpressed, probably acting as an anti-sigma factor. The expression levels of certain transposases, recognized as pivotal contributors to IS transposition, did not precisely correlate with active transposition in varying oxidation environments. Nevertheless, these findings suggest that specific IS elements integrated into dgeo _0524 in a target-gene-deficient and oxidation-source-dependent manner.

Objectives: Growing evidence suggests that intuitive eating is associated with numerous positive mental health and well-being constructs. Understanding factors that predict intuitive eating is necessary for identifying practical targets to enhance this style of eating, yet research identifying such predictors is scarce. Self-compassion is one variable that could enhance intuitive eating because it involves the practice of healthy emotion regulation skills that may disrupt the tendency to turn to food to cope during distressing situations. The present study tested for a longitudinal association between self-compassion and intuitive eating. We also tested whether this association was mediated by indices of emotion regulation (i.e., global emotion regulation skill scores and body image flexibility)., Method: Adult women (n = 3039) were invited to completed study measures at baseline (T1), 4-month follow-up (T2), and 8-month follow-up (T3). Path analyses were computed to test hypothesized indirect effects., Results: A direct path from T1 self-compassion to T3 intuitive eating emerged, such that higher self-compassion levels predicted increased intuitive eating over time. However, this association was not mediated by T2 emotion regulation skills nor body image flexibility., Conclusion: Findings suggest that self-compassion may facilitate an intuitive eating style, which does not appear to be explained by certain emotion regulation skills., (© 2023 The Authors. Journal of Clinical Psychology published by Wiley Periodicals LLC.)

G-protein-coupled receptor 119 (GPR119) has great potential as a therapeutic target for the treatment of type II diabetes. Novel thieno[3,2-d]pyrimidine derivatives were discovered as GPR119 agonists through a bioisosteric replacement strategy. The sulfonylphenyl thieno[3,2-d] pyrimidine scaffold was introduced, and its derivatives exhibited potent agonistic activity for GPR119 in cell-based assays. The representative derivative 43 displayed excellent pharmacokinetic profiles in rodents and significantly improved glucose tolerance in vivo. In OGTT study, compound 43 reduced significantly blood glucose levels in both mice and rats., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kyung Hoon Min, Minjung Kim, Kyujin Oh, and Sohee Lee report-that financial support was provided by National Research Foundation of Korea (NRF), Republic of Korea Hee Cheol Kim has patent #WO 2012/093809 A2 issued to HANMI PHARM CO., LTD., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Active surveillance (AS) has become an alternative treatment approach for papillary thyroid microcarcinoma (PTMC). The purpose of this study is to uncover the clinicopathological factors associated with high-risk nodal disease in order to select proper candidates for AS of PTMC., Methods: We retrospectively reviewed 5,329 patients with PTMC without extrathyroidal extension (ETE) who underwent thyroidectomy with central compartment neck dissection (CCND) between 2007 and 2021 at Seoul St. Mary's Hospital. Patients with more than five metastatic lymph nodes (MLNs) (higher-risk N1 disease) and/or lateral neck node metastases (N1b disease) were defined as having high-risk nodal disease. The clinicopathological factors associated with high-risk nodal disease were analyzed., Results: A total of 415 (7.8%) patients had higher-risk N1 disease. These patients were younger on average, included a higher proportion of males, and had a larger tumor size and more frequent capsular invasion and multifocality compared with other patients. For the tumor size, a cutoff value of 0.65 cm was the best predictor of nodal risk groups. In a multivariate analysis, the independent risk factors associated with higher-risk N1 disease were younger age, male sex, tumor size >0.65 cm, and the presence of capsular invasion and/or multifocality. A total of 246 (4.6%) patients had N1b disease at initial diagnosis. In a multivariate analysis, the independent risk factors associated with N1b disease were younger age, male sex, tumor size >0.65 cm, and the presence of capsular invasion and/or multifocality., Conclusions: Young age, male sex, tumor size >0.65 cm, and presence of capsular invasion and/or multifocality can be considered risk factors for high-risk nodal disease in PTMC. Therefore, cautious observation is necessary for AS of patients with these characteristics., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-256/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Background: Papillary thyroid carcinoma (PTC) located in the isthmus generally has been known to have more extrathyroidal extension (ETE), lymph node involvement, and multifocality. The purpose of this study was to determine the clinical significance of an isthmic location of PTC., Methods: The records of 160 patients who underwent a total thyroidectomy due to a single, dominant isthmic PTC were retrospectively reviewed. The characteristics of isthmic cancer were compared with those of unilateral-lobar cancer in a PTC cohort at Seoul St. Mary's hospital. After propensity score matching for age, sex, and tumor size, 160 isthmic PTCs and 800 unilateral-lobar PTCs were compared. The clinicopathologic characteristics were analyzed to evaluate the prognostic significance of an isthmic tumor location., Results: The isthmic group was significantly older (49.6 vs . 46.8 years, P=0.007) and had a smaller mean tumor size (0.8±0.4 vs . 1.0±0.7 cm, P<0.001) than the unilateral-lobar group. After propensity score matching, tumor size categories, ETE, multifocality, nodal metastasis and proportion of patients with more than five metastatic lymph nodes were similar in both groups. However, N1b cases were more frequent in the unilateral-lobar group both before and after propensity score matching. In multivariate analysis, isthmic location was not correlated with gross ETE, multifocality, and higher-risk N1 disease. Younger age and more than five metastatic nodes increased the risk of PTC recurrence. However, isthmic tumor location was not significantly correlated with recurrence-free survival., Conclusions: Isthmic location is not an independent risk factor for aggressive clinicopathologic features and is not related to PTC recurrence., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-56/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Background: It remains controversial whether prophylactic central compartment neck dissection (pCCND) is necessary in cases of stage T1-T2 cN0 papillary thyroid carcinoma (PTC). Some studies have demonstrated the benefits of pCCND on oncologic outcomes, whereas others reported that any advantages were insignificant. The purpose of this study was to investigate the effects of pCCND on cancer recurrence and its pattern in patients with T1-T2 cN0 PTC., Methods: We retrospectively reviewed 2,902 patients with PTC who had undergone thyroidectomy between 2006 and 2012 at Seoul St. Mary's Hospital: 2,099 patients had undergone pCCND and thyroidectomy (pCCND group), whereas 803 did not undergo pCCND (non-pCCND group). We investigated the effects of pCCND on cancer recurrence by comparing these two groups. Recurrence was classified according to the location of the recurrence., Results: The mean follow-up period was 112 months. The mean patient age was significantly younger in the pCCND group than in the non-pCCND group. There were no statistically significant differences in the distribution of sex, tumor size, or thyroidectomy extension between the groups. In the pCCND group, 883 (42%) patients showed evidence of N1a disease, and the mean number of metastatic lymph nodes was 1.26±2.2. Recurrence occurred in 67 (2.3%) patients in the total cohort. Recurrence was observed in 20 (2.5%) and 47 (2.2%) patients in the non-pCCND and pCCND groups, respectively, but there were no significant differences between the groups (P=0.687). When analyzed by the site of recurrence, 50% and 4.3% of recurrent disease in the non-pCCND and pCCND groups, respectively, occurred in the central compartment (P<0.001). There were no differences between the two groups in recurrent disease at other sites. The 15-year cumulative central compartment recurrence-free survival (RFS) rates of patients in the non-pCCND and pCCND groups were 99% and 100%, respectively (P<0.001). In the multivariate analysis, not performing pCCND was the only independent risk factor related to central compartment RFS, and the hazard ratio was 13.362 [95% confidence interval (CI): 2.928-60.986; P<0.001]., Conclusions: The omission of pCCND was found to be an independent risk factor for recurrence in the central compartment in patients with T1-T2 cN0 PTC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-550/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Background: Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) are used to treat patients with asymptomatic or mildly symptomatic gallstone disease. This study was conducted to evaluate the efficacy of gallbladder (GB) stone dissolution by UDCA/CDCA and the impact of treatment on gut microbial profiles. Methods: Fifteen treatment-naive patients with GB stones were initially included, but two dropped out during the treatment period. UDCA/CDCA was administered for 6 months. Abdominal ultrasonography was performed to evaluate response to treatment. In addition, fecal samples were collected before and after treatment for gut microbiome profiling. Then, 16S ribosomal RNA gene sequencing was carried out on fecal samples obtained before and after treatment, and results were compared with those of forty healthy controls. Results: Eight (62%) of the thirteen evaluable patients treated with UDCA/CDCA responded to treatment (four achieved complete GB stone resolution and four partial dissolution). Taxonomic compositions of fecal samples at the phylum level showed a significantly lower relative abundance of the Proteobacteria phylum in the pre-UDCA/CDCA group than in the healthy control group ( p = 0.024). At the genus level, the relative abundances of five bacteria ( Faecalibacterium , Roseburia , Lachnospira , Streptococcus , and Alistipes ) differed in the control and pre-UDCA/CDCA group. Interestingly, the abundance of Roseburia was restored after 6 months of UDCA/CDCA treatment. Conclusion: Gut microbial dysbiosis was observed in GB stone patients and partially reversed by UDCA/CDCA treatment, which also effectively dissolved GB stones.

Background: Common bile duct (CBD) stone recurrence is a common late adverse event after CBD stone treatment. In this preliminary study, we compared the bile fluid and duodenum microbial profiles of patients with or without recurrent CBD stones to identify risk factors associated with recurrence., Methods: Bile fluid samples of 47 consecutive patients who underwent ERCP for biliary diseases were subjected to microbiome analysis. Nineteen patients were stone-recurrent (SR), and 28 patients were non-stone-recurrent (NSR). Paired samples (duodenum biopsy tissue and bile fluid samples) from five SR patients were used to compare microbiome compositions in the biliary system and duodenum. In addition, we compared the microbiome compositions of these duodenal tissue samples with those 12 controls (gastric ulcer patients without recurrent CBD stones)., Results: Enterococcaceae&#95;unclassified and enterococcus were more abundant in bile fluid in the SR group than in the NSR group ( p = 0.002 and p = 0.003, respectively). A comparison of the microbiome compositions of duodenum tissue and bile fluid samples of the five recurrent CBD stone patients revealed proteobacteria compositions were almost identical from the phylum to genus level. In these five patients, alpha and beta diversities were no different in bile fluid and duodenal tissues. Furthermore, a comparison of the microbiome compositions of duodenal mucosa in patients with recurrent CBD stone patients ( n = 5) and controls ( n = 12) revealed significant differences between microbiome compositions., Conclusions: Enterococcus seems to contribute to CBD stone development. Furthermore, our results indicate that retrograde migration of the duodenal microbiome may contribute to bile microbiome alterations. We recommend that more research be conducted to confirm this hypothesis.

Introduction: MegaShield® is a newly developed temperature-sensitive anti-adhesive containing micronized acellular dermal matrix. The aim of this study was to investigate the efficacy and safety of MegaShield® compared with Guardix-SG® in the prevention of adhesions in patients undergoing bilateral total thyroidectomy., Method: We conducted a multicenter trial between October 2018 and March 2020 in patients undergoing total thyroidectomy. The patients were randomly assigned to either the MegaShield® group or the Guardix-SG® group. The primary outcome was the esophageal movement using marshmallow six weeks after the surgery and the secondary outcome was the assessed adhesion score. The safety assessment was also evaluated., Results: The study included 70 patients each in the MegaShield® and control (Guardix-SG®) groups. Baseline clinical characteristics, the mean score of marshmallow esophagography, and the sum of adhesion scores were not statistically different between the two groups. Inferiority test demonstrated that the efficacy of MegaShield® is not inferior to that of Guardix-SG®. There were no device-related complications in both groups., Conclusion: The efficacy and safety of MegaShield® were not inferior than those of Guardix-SG®. MegaShield® demonstrated the potential of ADM as a potential future anti-adhesive agent., Trial Registration: The name of trial registry CRIS (Clinical Research Information Service) https://cris.nih.go.kr/cris/index.jsp. (The full trial protocol can be accessed) Registration number: KCT0003204., Competing Interests: The authors of this manuscript have read the journal’s policy and declare the following competing interests: this study’s protocol and test devices were sponsored by L&C bio; however, a grant was finally sponsored by the Ministry of Health & Welfare. There are no patents, products in development, or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

In order to counteract the COVID-19 pandemic by wearing face masks, we examine washable fabric-based triboelectric nanogenerators (FTENGs). We applied the flash-spun nonwoven fabric (FS fabric) into the FTENGs, comparing the melt-blown nonwoven fabric (MB fabric) based FTENGs, which is conventionally studied in the field of energy harvesting. For reusability, all our proposed FTENGs are systematically investigated by controlling the washing conditions. After washing, the degradation ratio of the obtained output voltage is found to be only 12.5% for FS FTENGs, compared to the ratio of about 50% for the typical MB FTENGs. A rather small degradation ratio for FS fabric cases has resulted from less changed fabric structure after washing due to more dense fabric nature. Additionally, in order to improve the electrical characteristics of FS FTENGs. Note that the output voltage of FTENGs exhibits as much as 600 V.

Due to its semiconducting nature, controlled growth of large-area chemical vapor deposition (CVD)-grown two-dimensional (2D) molybdenum disulfide (MoS 2 ) has a lot of potential applications in photodetectors, sensors, and optoelectronics. Yet the controllable, large-area, and cost-effective growth of highly crystalline MoS 2 remains a challenge. Confined-space CVD is a very promising method for the growth of highly crystalline MoS 2 in a controlled manner. Herein, we report the large-scale growth of MoS 2 with different morphologies using NaCl as a seeding promoter for confined-space CVD. Changes in the morphologies of MoS 2 are reported by variation in the amount of seeding promoter, precursor ratio, and the growth temperature. Furthermore, the properties of the grown MoS 2 are analyzed using optical microscopy, scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDX), and atomic force microscopy (AFM). The electrical properties of the CVD-grown MoS 2 show promising performance from fabricated field-effect transistors. This work provides new insight into the growth of large-area MoS 2 and opens the way for its various optoelectronic and electronic applications., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

This study aimed to enzymatically prepare structured monogalactosyldiacylglycerols (MGDGs) with different hydrophile-lipophile balance (HLB) values for use as emulsifiers. Acidolysis of Perilla frutescens-derived MGDGs with capric acid (10:0) was conducted to obtain structured MGDGs containing 10:0. Lewatit VP OC 1600-immobilized Rhizomucor miehei lipase was used as the biocatalyst. Structured MGDGs (HLB value = 2.95-7.17) containing 13.0-70.6 mol% 10:0 were obtained from P. frutescens MGDGs (HLB value = 1.93). A quadratic regression equation (R 2  = 0.920) to predict the 10:0 content of the structured MGDGs under the given conditions was established using response surface methodology. Using a linear regression equation (R 2  = 0.999) to predict the HLB value by 10:0 content, structured MGDGs containing 27.1-54.6 mol% 10:0 were predicted to have an HLB value of 4-6, indicating their potential applicability as hydrophobic emulsifiers. Structured MGDGs with a purity of ∼ 43% w/w were obtained from the reaction products using silica column chromatography., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pancreatic cancer (PC) is a leading cause of cancer death and its incidence and mortality have shown an increasing trend. Despite improvements in outcomes, another treatment option is required for PC. Laser ablation (LA) has been evaluated for the treatment of various types of cancer. The aim of this study was to assess the safety and feasibility of a novel cylindrical light diffuser in a xenograft model of PC. This study was performed using a customized high-power laser system. PANC-1 cells and BALB/c mice were used for experiments at a laser power of 5 W for 40 to 200 s at five different energy levels (n = 30). There was no acute bleeding or major complication. Using the cylindrical light diffuser, tumors were irradiated with similar size in each energy group. A correlation between laser dose and tumor necrosis was observed. Pearson's correlation for the relation between the amount of necrosis area and laser ablation energy on day 3 was 0.78 (p < 0.01). No statistical difference of necrosis area was exhibited when the necrosis area of each harvested tumor analyzed by dividing into 5 specimens for each energy. The study demonstrates that LA treatment using a cylindrical light diffuser induced remarkable tumor necrosis at histopathologic examinations. Laser ablation dosage and tumor response were strongly correlated, and the ablation procedure resulted in homogeneous tissue necrosis. No adverse event was encountered. These findings suggest that the devised cylindrical light diffuser offers a safe and effective means of treating pancreatic cancer., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The coronavirus disease 2019 (COVID-19) outbreak became a worldwide pandemic in 2020. Social distancing measures, such as self-quarantine, lockdowns, and school closures, which have proven efficacy in various pandemic situations, remain in use in Korea. These measures prevented viral transmission to some extent; however, adverse effects have also resulted. First, the negative effect of social isolation on mental health is evident. This influences the psychiatric milieu of parents and children directly and indirectly. The most stressful factor among Korean youth was the restriction of outdoor activities. Increasing parenting burden result in increased screen time among youth, and social isolation created depressive mood with symptoms similar to those of attention deficit hyperactivity disorder and anxiety. Second, symptoms of posttraumatic stress disorder (PTSD) and somatization are prevalent among children and adolescents. The sense of threatened health and life during the pandemic, one symptom of PTSD, is a strong risk factor for somatization. Finally, the increased pattern of child abuse in pandemic indicates increased levels of emotional/psychological abuse and nonmedical neglect. Social isolation makes people less aware of these events. Because pediatricians evaluate pediatric patients and their families, they should regularly assess emotional/stress factors, especially when somatization is prominent during the pandemic, and cautiously recommend that families seek advice from mental health professionals when warranted. Primary physicians must understand the characteristics and aspects of child abuse in the COVID-19 pandemic, make efforts to identify signs of child abuse, and deliver accurate information and preventive strategies for child abuse to caregivers, thereby functioning as a professional guardian. To promote the mental health of parents and children during the COVID-19 pandemic, more research and cooperation among health professionals, families, governments, and schools are needed in the future.

This study sought to identify adulterated red pepper powder (RPP) containing undeclared ingredients, such as salts, glucose, Monascus red pigments, and other plant ingredients (e.g., wheat flour, garlic powder, onion powder) using element and sugar analysis methods. Analytical data were obtained for 66 samples of authentic RPP and 12 samples of adulterated RPP. The variables selected to identify the authenticity of RPP include Na, Cl, K, maltohexaose, and maltoheptaose, which partly or totally originate from RPP, salts, or Monascus red pigments. All the 12 samples of commercial seasoned RPP used as models of adulterated RPP and all the 20 blind samples containing ≥10% (w/w) of commercial seasoned RPP were correctly identified by applying the range of the five variables found for the authentic RPP samples. Our findings suggest that combined analyses of the above five constituents could be used to identify adulterated RPP containing undeclared ingredients. PRACTICAL APPLICATION: Adulteration of high-priced spice products, including red pepper powder (RPP), has increasingly become a public concern worldwide as it endangers consumer health and represents economic fraud. This study provides analytical methods that can accurately determine the authenticity of RPP. They would become effective means for protecting producers and suppliers against unfair competition and consumers against health threats., (© 2022 Institute of Food Technologists®.)

The gene amplification of human epidermal growth factor receptor 2 (HER2) plays an essential role in the proliferation and progression of several cancers. However, HER2 inhibitors such as lapatinib strongly suppress wild-type EGFR, resulting in severe adverse effects. Therefore, there is an unmet need for highly selective HER2 inhibitors. In this study, we describe the design and synthesis of novel quinazoline derivatives that exhibit enhanced selectivity for HER2 over wild-type EGFR. Structure-activity relationship analysis indicated that the selectivity for HER2 over EGFR depends on the aniline moiety at C-4 and the substituents at C-6 in the quinazoline derivatives. Compound 7c with an IC 50 of 8 nM for HER2 exhibited significantly higher selectivity for HER2 over EGFR, with a 240-fold improvement over lapatinib. In addition, the synthesized compounds exhibited anti-proliferative activity in the nanomolar range against SKBR3, a human breast cancer cell line that overexpresses HER2., (© 2022. The Pharmaceutical Society of Korea.)

Introduction: Recently, automated detection has been a new approach to address the risks posed by prescribing errors. This study focused on prescription errors and utilized real medical data to supplement the Drug Utilization Review (DUR)-based rules, the current prescription error detection method. We developed a new hybrid method through artificial intelligence for prescription error prediction by utilizing actual detection accuracy improvement to reduce 'warning fatigue' for doctors and improve medical care quality., Object: This study was conducted in the Department of Pediatrics, targeting children sensitive to drugs to develop a prescription error detection system. Based on the DUR prescription history, 15,281 patient-level observations of children from Konyang University Hospital (KYUH)'s common data model (CDM) and DUR were collected and analyzed retrospectively., Method: Among the CDM data, inspection information was interlocked with DUR and reflected as standard information for model development; this included outpatient prescriptions from January 1 to December 31, 2018. Through consultation with pediatric clinicians, rule definitions and model development were conducted for 35 drugs, with 137,802 normal and 1609 prescription errors., Results: We developed a novel hybrid method of error detection in the form of an advanced rule-based deep neural network (ARDNN), which showed the expected performance (precision: 72.86, recall: 81.01, F1 score: 76.72) and reduced alarm pop-up alert fatigue to below 10%. We also created an ARDNN-based comprehensive dashboard that allows doctors to monitor prescription errors with alarm pop-ups when prescribing medications., Conclusion: These results can advance the existing rule-based model by developing a prescription error detection model using deep learning. This method can improve overall medical efficiency and service quality by reducing doctors' fatigue., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The mechanisms of action responsible for the reported hypolipidemic activity of barley sprouts have yet to be elucidated. The objective of this study was to compare the content of saponarin (the sole flavonoid present in barley sprout leaves), hypolipidemic activity between barley sprout water extract (BSW) and barley sprout ethanol extract (BSE), and the associated relevance to hypolipidemic activity in 3T3-L1 preadipocytes. BSW elicited superior antiadipogenic effects when compared with BSE in MDI mixture [IBMX 0.5 mM + dexamethasone 1  μ M + insulin 1  μ g/mL]-treated 3T3-L1 preadipocytes. BSW attenuated MDI-mediated triacylglycerol (TAG) accumulation by inhibiting fatty acid synthase (FAS). FAS protein expression was markedly and dose dependently attenuated by BSW, with higher doses suppressing expression to a level equivalent to the controls. BSW also significantly attenuated MDI-mediated increases in the expression of genes involved in TAG synthesis as well as FAS in 3T3-L1 preadipocytes. High-performance liquid chromatography analysis indicated that BSW contains more than four times more saponarin than BSE. Further investigation of saponarin-mediated hypotriacylglycerolemic activity and related gene expression revealed that saponarin significantly inhibited TAG accumulation, which was attributed to reductions in TAG synthesis-related gene expression. Taken together, these findings provide a basis for further development of barley sprout extract for functional health food purposes.

Using a prospective design, we investigated possible bi-directional relationships between intuitive eating and four empirically distinct components of negative body image: overvaluation (judgements of self-worth contingent upon weight/shape), dissatisfaction (general discontent with weight/shape), preoccupation (ruminative thinking about weight/shape), and fear of weight gain. We assessed adult women at baseline (T1) and four-month follow-up (T2), as prior work has demonstrated that this time lag is sufficient to detect change in intuitive eating scores. After adjusting for T1 intuitive eating scores and demographic confounds, higher T1 dissatisfaction was the only body image component to significantly predict lower T2 intuitive eating scores in both univariate and multivariate models. Higher T1 intuitive eating scores also significantly predicted lower scores on each of the four negative body image components at T2. Findings suggest that general body discontent may be one of the more important body image variables that lead to decreases in intuitive eating principles. Present findings also add to a growing body of evidence demonstrating the potentially adaptive role of intuitive eating on psychological health indices., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pathological maternal inflammation and abnormal placentation contribute to several pregnancy-related disorders, including preterm birth, intrauterine growth restriction, and preeclampsia. TANK-binding kinase 1 (TBK1), a serine/threonine kinase, has been implicated in the regulation of various physiological processes, including innate immune response, autophagy, and cell growth. However, the relevance of TBK1 in the placental pro-inflammatory environment has not been investigated. In this study, we assessed the effect of TBK1 inhibition on lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation and its underlying mechanisms in human trophoblast cell lines and mouse placenta. TBK1 phosphorylation was upregulated in the trophoblasts and placenta in response to LPS. Pharmacological and genetic inhibition of TBK1 in trophoblasts ameliorated LPS-induced NLRP3 inflammasome activation, placental inflammation, and subsequent interleukin (IL)-1 production. Moreover, maternal administration of amlexanox, a TBK1 inhibitor, reversed LPS-induced adverse pregnancy outcomes. Notably, TBK1 inhibition prevented LPS-induced NLRP3 inflammasome activation by targeting the mammalian target of rapamycin complex 1 (mTORC1). Thus, this study provides evidence for the biological significance of TBK1 in placental inflammation, suggesting that amlexanox may be a potential therapeutic candidate for treating inflammation-associated pregnancy-related complications., 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 Lee, Shin, Kim, Shin, Lee and Park.)

The biomedical field is currently reaping the benefits of research on biomimetic nanoparticles (NPs), which are synthetic nanoparticles fabricated with natural cellular materials for nature-inspired biomedical applications. These camouflage NPs are capable of retaining not only the physiochemical properties of synthetic nanoparticles but also the original biological functions of the cellular materials. Accordingly, NPs coated with cell-derived membrane components have achieved remarkable growth as prospective biomedical materials. Particularly, bacterial outer membrane vesicle (OMV), which is a cell membrane coating material for NPs, is regarded as an important molecule that can be employed in several biomedical applications, including immune response activation, cancer therapeutics, and treatment for bacterial infections with photothermal activity. The currently available cell membrane-coated NPs are summarized in this review. Furthermore, the general features of bacterial OMVs and several multifunctional NPs that could serve as inner core materials in the coating strategy are presented, and several methods that can be used to prepare OMV-coated NPs (OMV-NPs) and their characterization are highlighted. Finally, some perspectives of OMV-NPs in various biomedical applications for future potential breakthrough are discussed. This in-depth review, which includes potential challenges, will encourage researchers to fabricate innovative and improvised, new-generation biomimetic materials through future biomedical applications.

Purpose: To determine prevalence, clinicopathological characteristics, initial treatments, and outcomes associated with low estrogen receptor (ER)-expressing invasive breast cancer., Methods: This retrospective, non-interventional database study included patients undergoing surgery with curative intent for invasive ductal or lobular breast cancer. Patients were treated between January 2003-December 2012. Demographics, clinicopathological characteristics, initial treatments, and outcomes were abstracted from patient records. Patients were categorized using immunohistochemistry to determine ER, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) levels. ER-positive patients were subclassified as ER-low (1% to 10%) and ER-high (> 10%) according to the Allred Proportion Score. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups by log-rank test., Results: 5930 patients were included (median follow-up, 80.9 months). Of all patients included, 117 (2.0%) had ER-low tumors: 63 (53.8%) of whom had HER2- tumors and 54 (46.2%) HER2+ tumors. Five-year DFS and OS were highest in the ER-high/HER2- cohort (94.0% and 98.6%, respectively) and lowest in the triple-negative breast cancer (TNBC; 81.3% and 90.1%) and ER-low/HER2- (85.7% and 92.1%) cohorts. Menopausal status, elevated Ki-67, higher nuclear grade, higher tumor stage, presence of lymphovascular invasion, greater regional lymph node involvement, and larger tumor size were all potential prognostic factors for shorter DFS and OS., Conclusion: Patients with ER-low/HER2- breast cancer had similar clinicopathological characteristics, treatments, and outcomes as patients with TNBC irrespective of disease setting. Further research is needed to understand predictive and prognostic factors associated with ER-low/HER2- disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The treatment for papillary thyroid cancer (PTC) has become more conservative, but still no specific guidelines exist for managing isthmic PTC. This study analyzed the outcomes from isthmusectomy in single isthmic PTC and compared it with those for patients who previously had undergone a total thyroidectomy., Methods: An isthmusectomy with prophylactic central compartment neck dissection (pCCND) was planned for a single isthmic PTC between 2014 and 2018 (isthmusectomy group). For cases with gross extrathyroidal extension (ETE) or multiple nodal metastasis, the procedure was converted to a total thyroidectomy. The study analyzed the characteristics and outcomes of the isthmusectomy group. Additionally, the results were compared with those of the isthmusectomy-feasible group who met the eligibility criteria for isthmusectomy among total thyroidectomies performed between 2009 and 2013., Results: Of the 90 patients in the isthmusectomy group, 81 received isthmusectomy and 9 had conversion to a total thyroidectomy. Microcarcinoma occurred in 72 cases and gross ETE in 3 cases. One patient showed occult satellite cancer, and seven patients showed more than five metastatic nodes. Transient hypocalcemia developed in five and patients and permanent hypocalcemia in one patient with total thyroidectomy. Of 46 patients who began hormone replacement postoperatively, 13 completely stopped taking medication during the follow-up period. Metachronous PTC was diagnosed for one patient 12 months after isthmusectomy. The isthmusectomy group and the isthmusectomy-feasible group showed similar clinicopathologic properties including multifocality, ETE, and nodal metastasis. However, the isthmusectomy group showed significantly less transient or permanent hypocalcemia and thyroid hormone dependency., Conclusions: Isthmusectomy with pCCND may be a feasible alternative for properly selected isthmic PTC, resulting in a better quality of life than total thyroidectomy., (© 2021. Society of Surgical Oncology.)

Follicular-patterned tumors of the thyroid in the adult population frequently harbor RAS mutations or PAX8-PPARG rearrangement, but little is known about molecular profiles in the pediatric patients with thyroid tumors, which is rare. To identify the molecular profile of pediatric follicular-patterned tumors, we enrolled 41 pediatric patients with follicular-patterned tumors from two institutions. We did next-generation sequencing using a mutation panel targeting 49 thyroid-tumor-related genes and a fusion panel targeting 88 types of thyroid-related gene fusions. We identified nonsynonymous mutations in at least one target gene in most of the tumors (28/41, 68%). Somatic DICER1 mutations (22%, n = 9) were the most common genetic alteration, followed by mutations of NRAS (15%), FGFR3 (15%), PTEN (12%), and STK11 (10%). Infrequent genetic alterations (≤ 5% of all cases) included mutations of HRAS, APC, TSHR, CTNNB1, TP53, EIF1AX, FGFR4, GNAS, RET, and SOS1, and gene fusion of THADA-IGF2BP3. DICER1 and RAS mutations were mutually exclusive. No patients had tumors related to the DICER1 syndrome or the Cowden syndrome. There was no significant difference in total mutation burden or distribution between follicular adenoma and follicular carcinoma. In the literature, the DICER1 mutation has been reported in 20 to 53% of pediatric patients with follicular-patterned tumors. In conclusion, our study reinforces the role of the DICER1 mutation in the development of pediatric thyroid tumors. Gene fusions rarely occur in pediatric follicular-patterned tumors. Mutation or gene fusion alone could not distinguish benign from malignant follicular-patterned tumors in pediatric patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The interactions between proteins and nanoparticles need to be fully characterized as the immobilization of proteins onto various nanoplatforms in the physiological system often results in the change of surface of the protein molecules to avoid any detrimental issues related to their biomedical applications. Hence, in this article, the successful low-temperature synthesis of a BP-based γ-Fe 2 O 3 (IB) nanocomposite and its interactive behavior with bovine serum albumin (BSA)-a molecule with chemical similarity and high sequence identity to human serum albumin-are described. To confirm the formation of γ-Fe 2 O 3 and the IB nanocomposite, X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy analyses of the materials were performed. Additionally, the physical interaction between BSA and the IB nanocomposite was confirmed via UV-Vis and photoluminescence spectral analyses. Finally, the biocompatibility of the BSA-immobilized IB nanocomposite was verified using an in vitro cytotoxicity assay with HCT-15 colon cancer cells. Our findings demonstrate that this newly developed nanocomposite has potential utility as a biocompatible nanoplatform for various biomedical applications.

Background: There is an increased use of endoscopic thyroidectomy (ET), including robotic-assisted thyroidectomy (RT), to avoid postoperative scars on the anterior neck. The objective of this study was to compare the surgical and oncologic outcomes between ET and conventional open thyroidectomy (COT) for differentiated thyroid carcinoma (DTC)., Methods: We reviewed 4129 patients with DTC who underwent thyroid lobectomy at Seoul St. Mary's Hospital (Seoul, Korea) from January 2009 to December 2014. Patients were categorized according to the type of surgery and statistically compared using propensity score matching analysis., Results: The mean operation time was significantly longer in the ET group than in the OT group (101.2 ± 26.2 min vs. 86.4 ± 27.0 min, p < 0.001). The number of harvested lymph nodes was significantly lower in the ET group than in the OT group (5.5 ± 4.2 vs. 8.3 ± 6.2, p < 0.001). There was no significant difference in the recurrence rate between the two groups (p = 0.879). Kaplan-Meier analysis revealed no significant difference in the disease-free survival after propensity score matching (p = 0.811). The mean follow-up duration was 90.4 ± 21.0 months., Conclusions: Transaxillary ET including RT for DTC is a safe and feasible alternative to COT with a cosmetically desirable outcome. Further studies are required to confirm our results.

Purpose: Digital interventions that consider end-user needs, preferences, and concerns may address suboptimal rates of e-health uptake, usage, and engagement. We explored target-user perspectives of e-health treatment and prevention programs for eating disorders (EDs), with a focus on investigating (1) perceived advantages and barriers of e-health; (2) help-seeking intentions; and (3) preferences for different digital functionality, device types, and content-delivery formats., Methods: Survey data were analysed from 722 community-based participants. Participants were categorized into one of four groups based on symptom presentation and severity, ranging from low risk to probable bulimia nervosa or binge-eating disorder., Results: e-health advantages that received the highest endorsement (~ 84%) were "always there in times of need" and "travel not required". e-health barriers that received the highest endorsement (~ 50%) were concerns about data privacy and the accuracy of content presented. Nearly three-quarters reported an intention to use an e-health platform for preventing or treating EDs. Preference ratings were highest for programs to be available on all digital devices (relative to restricting the program to one type of device) and for content to be presented via graphics and video tutorials (rather than audio-based). e-health functionality that received highest preference ratings (~ 80%) were added clinician support, tailored feedback, strategies to change unhelpful ED thoughts, screening scales to assess symptoms, ED psychoeducation, and just-in-time intervention prompts. Preference and intention ratings were strikingly similar across all subgroups., Conclusion: Findings may inform the development and design of e-health platforms that meet the needs of people at different stages of an ED., Level of Evidence: Level V, cross-sectional descriptive study.

Resistance to polymyxins when treating multidrug-resistant (MDR) Gram-negative bacterial infections limit therapeutic options. Here, we report the synthesis of a nickel (Ni) doped Zinc oxide (NZO) combined with black phosphorus (BP) (NZB) nanocomposite and its synergistic action with polymyxin B (PolB) against polymyxin-resistant Escherichia coli harboring mobilized colistin resistance ( mcr-1 ) gene. NZB and PolB combination therapy expressed a specific and strong synergy against Mcr-1 expressing E. coli cells. The underlying mechanism of the synergy is the charge neutralization of the E. coli cell surface by NZB, resulting in a more feasible incorporation of PolB to E. coli . The synergistic concentration of NZB with PolB was proved biocompatible. Thus, the NZB is the first biocompatible nano-adjuvant to polymyxins against polymyxin-resistant E. coli cells, recognizing the physical status of bacteria instead of known adjuvants targeting cellular gene products. Therefore, NZB has the potential to revive polymyxins as leading last-resort antibiotics to combat polymyxin-resistant Gram-negative bacterial infections.

Antibiotic therapy is the gold standard for bacterial infections treatment. However, the rapid increase in multidrug-resistant (MDR) bacterial infections and its recent use for secondary bacterial infections in many COVID-19 patients has considerably weakened its treatment efficacy. These shortcomings motivated researchers to develop new antibacterial materials, such as nanoparticle-based antibacterial platform with the ability to increase the chances of killing MDR strains and prevent their drug resistance. Herein, we report a new black phosphorus (BP)-based non-damaging near-infrared light-responsive platform conjugated with ZnO and Au nanoparticles as a synergistic antibacterial agent against Staphylococcus aureus species. First, BP nanosheets containing Au nanoparticles were assembled in situ with the ZnO nanoparticles prepared by a low-temperature solution synthesis method. Subsequently, the antibacterial activities of the resulting Au-ZnO-BP nanocomposite against the non-resistant, methicillin-resistant, and erythromycin-resistant S. aureus species were determined, after its photothermal efficacy was assessed. The synthesized nanocomposite exhibited excellent anti- S. aureus activity and good photothermal characteristics. The non-resistant S. aureus species did not produce drug-resistant bacteria after the treatment of multiple consecutive passages under the pressure of the proposed nanoantibiotic, but rapidly developed resistance to erythromycin. This work clearly demonstrates the excellent photothermal antibacterial properties of Au-ZnO-BP nanocomposite against the MDR S. aureus species.

Background: Although most differentiated thyroid carcinomas (DTCs) have indolent behavior, DTCs with distant metastasis have a poor prognosis. However, there are no validated markers that predict the risk of distant metastasis and the prognosis of DTC. We aimed to develop a genetic classifier for predicting the outcomes of DTC patients with distant metastases. Methods: Targeted deep sequencing of 157 cancer-related genes was performed for 61 DTCs with distant metastases. A candidate mutation was validated with independent thyroid cancer samples using digital polymerase chain reaction. Results: The most frequently mutated gene in the 61 DTCs was BRAF ( n  = 31, 51%), followed by TERT promoter ( n  = 28, 46%), NRAS ( n  = 13, 11%), PLEKHS1 promoter ( n  = 6, 10%), and STK11 ( n  = 6, 10%) mutations. PLEKHS1 promoter mutations were more common in the radioactive iodine (RAI)-refractory cases ( p  = 0.003). Losses of 9q and 11q were associated with RAI-refractory disease ( p  = 0.002) and cancer-specific mortality ( p  = 0.028), respectively. In multivariate analysis, bone metastasis (adjusted odds ratio [aOR] = 15.17, 95% confidence interval [CI 3.38-68.06], p  < 0.001) and at least one mutation in the TERT promoter, the PLEKHS1 promoter, or TP53 (aOR = 7.64 [CI 1.78-32.76], p  = 0.006) remained significant factors associated with RAI-refractoriness. In independently collected papillary thyroid carcinomas without initial distant metastasis ( n  = 75), a PLEKHS1 promoter mutation was only found in one case that developed distant metastasis during the follow-up period. We developed a genetic classifier consisting of BRAF , RAS , the TERT promoter, the PLEKHS1 promoter, and TP53 for categorizing the prognosis of patients with DTC with distant metastasis. In the poor-prognosis group, 61% of the patients were RAI-refractory and death occurred in 21% during the follow-up. In the intermediate-prognosis group, 29% were RAI-refractory, but no death occurred. In the good-prognosis group, all patients were RAI-responsive and no death occurred. Conclusions: Mutations in the PLEKHS1 promoter are a novel genetic marker of aggressive DTC. Our genetic classifier can be useful for predicting RAI-refractory disease and poor prognosis in DTC patients with distant metastases.

Background: Distant metastases from well-differentiated thyroid carcinoma (WDTC) occasionally occur over a wide range of time intervals after primary thyroid surgery. The prognostic impact of the timing of distant metastasis onset remains unclear., Methods: We retrospectively reviewed the clinicopathologic features and clinical outcomes of 57 patients with WDTC and distant metastases, and evaluated the mutational profiles of BRAF , RAS , and TERT promoter genes. All patients underwent thyroidectomy and radioactive iodine (RAI) ablation using the same treatment protocol. Synchronous distant metastases were defined as those detected within 12 months of the primary WDTC diagnosis. Metachronous metastases were considered early- and late-onset diseases if detected 1-5 and ≥5 years after the primary diagnosis, respectively., Results: In all patients, the 5- and 10-year cancer-specific survival (CSS) rates after the diagnosis of distant metastasis were 86% and 57%, respectively. Late-onset (≥5 years) metachronous distant metastasis was associated with age of ≥55 years (P=0.043) and patients refractory to RAI therapy (P=0.026). TERT promoter mutations were associated with RAI refractivity (P=0.026). BRAF V600E and RAS mutations had no prognostic significance. Bone metastasis (P=0.002) and the onset time of distant metastasis (P=0.004) were associated with poor CSS. There was no significant difference in CSS between patients with synchronous distant metastases and those with early-onset (1-5 years) metachronous distant metastases. In the multivariate analysis, bone metastasis [hazard ratio (HR) =10.24; 95% confidence interval (CI): 1.25-83.74; P=0.030] and late-onset (≥5 years) metachronous distant metastasis (HR =5.20; 95% CI: 1.01-26.63; P=0.048) were independent predictors for worse CSS., Conclusions: The prognosis of patients with WDTC was poorer for late metachronously detected metastases than for synchronous or early metachronous metastases. Patients with distant metastasis occurring 5 years later after primary thyroid diagnosis should, therefore, be more carefully treated., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-416). The series “Asian and Western Practice in Thyroid Pathology: Similarities and Differences” was commissioned by the editorial office without any funding or sponsorship. CKJ serves as an unpaid editorial board member of Gland Surgery from Jul 2019 to Jun 2021. The authors have no other conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Nano-particles have been combined with antibiotics in recent studies to overcome multidrug-resistant bacteria. Here, we synthesized a nano-material in which Ag nano-particles were assembled with a ZnO nano-structure to form an Ag-ZnO (AZO) nano-composite at low temperature. This material was combined with erythromycin (Ery), an antibiotic effective towards gram-positive bacteria, using three different approaches (AZO + Ery (AZE) [centrifuged (AZE1), used separately after 1-h gap (AZE2), without centrifugation (AZE3)]) to prepare a nano-antibiotic against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). X-ray diffraction analysis and transmission electron microscopy confirmed the presence of Ag nano-particles and ZnO nano-structure. The elemental and chemical state of the elements present in the AZO nano-composite were assessed by X-ray photoelectron spectroscopy. The antibacterial activity of AZE samples against both Escherichia coli and S. aureus strains including MRSA was evaluated in antibacterial and morphological analyses. The AZE3 sample showed greater antibacterial activity than the other samples and was comparable to erythromycin. AZE3 was ~20-fold less prone to developing bacterial resistance following multiple exposures to bacteria compared to erythromycin alone. The AZE3 nano-composite showed good biocompatibility with 293 human embryonic kidney cells. Our newly synthesized nano-platform antibiotics may be useful against multidrug-resistant gram-positive bacteria.

gBRCA1/2 mutations increase the incidence of breast cancer by interrupting the homologous recombination repair (HRR) pathway. Although gBRCA1 and gBRCA2 breast cancer have similar clinical profiles, different molecular characteristics have been observed. In this study, we conducted comprehensive genomic analyses and compared gBRCA1/2 breast cancer. Sanger sequencing to identify gBRCA1/2 mutations was conducted in 2,720 patients, and gBRCA1 ( n = 128) and gBRCA2 ( n = 126) mutations were analyzed. Within this population, deep target sequencing and matched whole-transcriptome sequencing (WTS) results were available for 46 and 34 patients, respectively. An internal database of patients with breast cancer with wild-type gBRCA was used to compile a target sequencing ( n = 195) and WTS ( n = 137) reference dataset. Three specific mutation sites, p.Y130X ( n = 14) and p.1210Afs ( n = 13) in gBRCA1 and p.R294X ( n = 22) in gBRCA2, were comparably frequent. IHC subtyping determined that the incidence of triple-negative breast cancer was higher among those with a gBRCA1 mutation (71.9%), and estrogen receptor-positive breast cancer was dominant in those with a gBRCA2 mutation (76.2%). gBRCA1/2 mutations were mutually exclusive with PIK3CA somatic mutations ( P < 0.05), and gBRCA1 frequently cooccurred with TP53 somatic mutations ( P < 0.05). The median tumor mutation burden was 6.53 per megabase (MB) in gBRCA1 and 6.44 per MB in gBRCA2. The expression of AR, ESR1 , and PGR was significantly upregulated with gBRCA2 mutation compared with gBRCA1 mutation. gBRCA1 and gBRCA2 breast cancer have similar clinical characteristics, but they have different molecular subtypes, coaltered somatic mutations, and gene expression patterns. IMPLICATIONS: Even though gBRCA1 and gBRCA2 mutations both alter HRR pathways, our results suggest that they generate different molecular characteristics and different mechanisms of carcinogenesis., (©2020 American Association for Cancer Research.)

Electrically enhanced triboelectric nanogenerators (TENGs) using 3D fabrics and polydimethylsiloxane (PDMS) are suggested for next-generation wearable electronics. TENGs with fabric-fabric- fabric (FFF) and PDMS-fabric-PDMS (PFP) structures were fabricated with ordinary 2D fabrics and honeycomb-like 3D fabrics. A 3D fabric TENG with an FFF structure showed an output voltage of 7 V, 7 times higher than a 2D fabric FFF structured TENG. Interestingly, an extremely high output voltage of 240 V was achieved by a 3D fabric PFP structured TENG. This was attributed to the high surface frictional triboelectric effect between fabric and PDMS and also marginal 3D structure in the 3D fabric active layer.

Antimicrobial resistance (AMR) is widely acknowledged as a global health problem, yet the available solutions to this problem are limited. Nanomaterials can be used as potential nanoweapons to fight against this problem. In this study, we report an easy one-pot low-temperature synthesis of Ag-ZnO nanoparticles (AZO NPs) and their targeted antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains. The physical properties of the samples were characterized by X-ray diffractometry (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). Furthermore, minimum inhibitory concentration (MIC), zone of inhibition (ZOI), and scanning electron microscopy (SEM) images for morphological characterization of bacteria were assessed to evaluate the antibacterial activity of AZO NPs against both Gram-negative [ Escherichia coli ( E. coli ) and Acinetobacter baumannii ( A. baumannii ) standard and AMR strains] and Gram-positive ( S. aureus , MRSA3, and MRSA6) bacteria. The AZO NPs showed comparatively better antibacterial activity against S. aureus and MRSA strains than Gram-negative bacterial strains. This cost-effective and simple synthesis strategy can be used for the development of other metal oxide nanoparticles, and the synthesized nanomaterials can be potentially used to fight against MRSA., (Copyright © 2020 Naskar, Lee and Kim.)

Protein import across the endoplasmic reticulum membrane is physiologically regulated in a substrate-selective manner to ensure the protection of stressed ER from the overload of misfolded proteins. However, it is poorly understood how different types of substrates are accurately distinguished and disqualified during translocational regulation. In this study, we found poorly assembled translocon-associated protein (TRAP) complexes in stressed ER. Immunoaffinity purification identified calnexin in the TRAP complex in which poor assembly inhibited membrane insertion of the prion protein (PrP) in a transmembrane sequence-selective manner, through translocational regulation. This reaction was induced selectively by redox perturbation, rather than calcium depletion, in the ER. The liberation of ERp57 from calnexin appeared to be the reason for the redox sensitivity. Stress-independent disruption of the TRAP complex prevented a pathogenic transmembrane form of PrP (ctmPrP) from accumulating in the ER. This study uncovered a previously unappreciated role for calnexin in assisting the redox-sensitive function of the TRAP complex and provided insights into the ER stress-induced reassembly of translocon auxiliary components as a key mechanism by which protein translocation acquires substrate selectivity.

Infections by multidrug-resistant (MDR) bacteria are one of the most threatening concerns for public health. For this purpose, nanomaterials have emerged with great potential for antibacterial activity. In this paper, we report the synthesis of new Ni 2+ -doped zinc oxide (Ni-ZnO or NZO) nanostructures as targeted antibacterial agents for Gram-negative bacteria. A one-pot low-temperature solution process was used with varying compositions containing 2 or 5% Ni 2+ relative to Zn 2+ , resulting in 2NZO or 5NZO, respectively. X-ray diffractometry, transmission electron microscopy, and X-ray photoelectron spectroscopy were used for material characterization. Further, the antibacterial activity against both Gram-negative [ Escherichia coli ( E. coli ) and Acinetobacter baumannii ( A. baumannii ) strains including standard, MDR, and clinical isolates associated with mcr-1 gene] and Gram-positive ( Staphylococcus aureus and Staphylococcus epidermidis ) bacteria were evaluated through analysis of zone of inhibition, minimum inhibitory concentration (MIC), and scanning electron microscopy images. Among the prepared nanostructures, the 5NZO sample showed excellent antibacterial activity against MDR strains of A. baumannii and E. coli . In addition, samples of NZO generated approximately 7 to 16 times more reactive oxygen species (ROS) in E. coli compared to ZnO. Our synthesized nanomaterials have the potential to fight MDR and colistin-resistant Gram-negative bacteria., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Regulating protein import across the endoplasmic reticulum (ER) membrane occasionally results in the synthesis of topologically unnatural variants, and their accumulation often leads to proteotoxicity. However, since this is a regulated process, it is questionable whether the topological rearrangement really has adverse consequences. In the present study, we provide an insight into the functional benefit of translocational regulation by illustrating mutant-selective topologic conversion (MSTC) and demonstrate that MSTC contributes to selective degradation of a membrane-anchored prion protein isoform (ctmPrP). We find that ctmPrP is inherently short-lived and topologically competent for degradation rather than accumulation. MSTC achieves, cotranslationally, the unique topology of ctmPrP during translocation, facilitating selective ctmPrP degradation from the ER via the proteasome-dependent pathway before entering the secretory pathway. At this time, the N-terminal polycationic cluster is essential for MSTC, and its cytosolic exposure acquires "ERAD-degron"-like activity for ctmPrP. Bypassing MSTC delays ctmPrP degradation, thus increasing prion proteotoxicity. Thus, topological rearrangement is used for the MSTC as a part of the protein quality control pathway to ensure the safety of the secretory pathway from misfolded PrP.

Engineered polymeric hydrogels have been extensively utilized in tissue engineering and regenerative medicine because of their biocompatibility, tunable properties, and structural similarity in their native extracellular microenvironment. The native extracellular matrix (ECM) has been implicated as a crucial factor in the regulation of cellular behaviors and their fate. The emerging trend in the design of hydrogels involves the development of advanced materials to precisely recapitulate the native ECM or to stimulate the surrounding tissues via physical, chemical, or biological stimuli. The ECM presents various parameters such as ECM components, soluble factors, cell-to-cell and cell-to-matrix interactions, physical forces, and physicochemical environments. Among these environmental factors, oxygen is considered as an essential signaling molecule. In particular, abnormal oxygen tension such as a lack of oxygen (defined as hypoxia) and an excess supply of oxygen (defined as hyperoxia) plays a pivotal role during early vascular development, tissue regeneration and repair, and tumor progression and metastasis. In this chapter, we discuss how engineered polymeric hydrogels serve as either an artificial extracellular microenvironment to create engineered tissues or as an acellular matrix to stimulate the native tissues for a wide range of biomedical applications including tissue engineering and regenerative medicine, wound healing, and engineered disease models. Specifically, we focus on emerging technologies to create advanced polymeric hydrogel materials that accurately mimic or stimulate the native ECM.

Background: Active surveillance is an alternative management for patents with low-risk papillary thyroid microcarcinoma (PTMC); however, there is an absence of specific molecular markers that predict its progression. We compared gene expression patterns between PTMC with lateral neck-node metastasis (N1b) and PTMC-lacking nodal metastasis (N0)., Methods: We performed oligonucleotide microarray analysis in three PTMCs without cervical lymph-node metastases (N0), and five PTMCs with lateral neck-node metastasis (N1b) at initial diagnosis, using an Illumina HumanHT-12 v4.0 Expression BeadChip. Quantitative real-time PCR (qPCR) and western blot analysis confirmed microarray data. We performed immunohistochemistry (IHC) to confirm protein overexpression in samples from 20 N0 and 24 N1b PTMC patients who underwent thyroidectomy., Results: Microarray analyses identified 52 probes corresponding to 45 genes. Expression of these genes differed significantly between the two PTMC groups. Forty genes were significantly upregulated and five genes were downregulated in N1b PTMC compared to N0. Four genes related to epithelial-to-mesenchymal transition (EMT) and stem cell markers, including ALDH1A3, TM4SF1, PROM1, and CAV1 were significantly upregulated in N1b PTMCs. Real-time qPCR confirmed this expression and western blot analysis confirmed higher expression of ALDH1A3, TM4SF1, PROM1, and CAV1 in N1b than in N0 PTMCs. IHC indicated overexpression of ALDH1A3 and CAV1 in N1b compared to N0 PTMCs., Conclusions: Genes related to EMT and thyroid cancer stem cell-like properties are upregulated in early extensive lymphatic spread of PTMC., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The Body Image Acceptance and Action Questionnaire (BI-AAQ), a measure designed to assess body image flexibility, was originally developed for and psychometrically investigated with nonclinical populations, but it has been recently administered to people with binge-eating disorder (BED) symptomatology. Tests of measurement invariance are needed to understand whether the BI-AAQ operates in the same way for BED and non-BED populations, thereby ensuring meaningful comparison across these groups. We thus tested the measurement invariance of the BI-AAQ in participants with and without clinically significant BED symptomatology. Data were analyzed from 358 community-based participants. Participants were either classified as with (n = 179) or without (n = 179) "probable BED" based on self-reported symptom frequency. An unacceptable model fit was found across both groups, indicating that the unidimensional structure of the BI-AAQ was not replicated. We then sought to confirm the unidimensional structure of a recently proposed five-item version of the BI-AAQ. A unidimensional structure of this abbreviated version was replicated, and tests of measurement variance were upheld. Internal consistency, convergent validity, and incremental validity were documented for both the original and abbreviated BI-AAQ across individuals with and without BED symptomatology. Present findings provide further psychometric support for an abbreviated five-item BI-AAQ, although it is important for future research to replicate both the full and abbreviated BI-AAQ in more diverse samples. Overall, an abbreviated BI-AAQ may be an attractive alternative for researchers studying body image flexibility. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

In this study, amine functionalized carbon black (ABCB) was synthesized using 4-aminobenzoic acid in a phosphoric acid (PPA)/phosphorus pentoxide (P 2 O 5 ) medium, and silver-attached carbon black (Ag-ABCB) was prepared by reducing AgNO 3 with NaBH 4 in the presence of ABCB in ethanol. Elemental, thermogravimetric, and Fourier transform-infrared analyses showed that carbon black (CB) had a well-functionalized 4-aminobenzoic acid. In addition, X-ray photoelectron spectroscopy and X-ray diffraction were used to examine the crystal structure of Ag nanoparticles. Conductive fibers were prepared by melt-spinning using ABCB, Ag-ABCB as a conductive filler, and polyethylene terephthalate (PET) as a polymer matrix. Results confirmed that the fiber that had Ag-ABCB as a conductive filler exhibited the best electrical conductivity. The dispersibility and morphology of the conductive filler in the PET matrix were confirmed through scanning electron microscopy analysis, and Ag-ABCB was the most uniformly dispersed filler in the PET matrix, with good structure.

Rapid endoplasmic reticulum (ER) stress-induced export (RESET) is undoubtedly beneficial in that it eliminates misfolded prion protein (PrP) from a stressed ER. Considering that RESET induces rapid endocytosis of misfolded PrP for degradation, it is questionable whether RESET is beneficial when its product amount overwhelms the capacity of subsequent clearance pathways. We require a strategy to monitor the endocytic flux rate of misfolded PrPs. Here, we stabilized misfolded PrPs by inserting red fluorescent protein (RFP) and indirectly determined this rate by monitoring the lysosomal free RFP. We discovered a surveillance mechanism that limits endocytosis of misfolded PrPs through plasma membrane quality control (pmQC). pmQC was regulated by the thiol-disulfide status of misfolded PrPs and consequently accumulates nonpathogenic PrP variants at the plasma membrane. This variant alleviated prion proteotoxicity induced by persistent RESET. Thus, PrP endocytosis is regulated by pmQC to ensure the safety of endolysosomal pathway from persistent internalization of misfolded PrP.-Lee, D., Lee, S., Shin, Y., Song, Y., Kang, S.-W. Thiol-disulfide status regulates quality control of prion protein at the plasma membrane.

Background: The incidence of a secondary solid malignancy after hematopoietic cell transplantation (HCT) is increasing in long-term survivors., Objective: The aim of this study was to compare the clinicopathological characteristics of HCT recipients with secondary thyroid cancer (STC), with those of non-HCT thyroid cancer patients., Methods: We retrospectively investigated 5184 patients who received HCT between 1983 and 2016. Of these, 18 patients developed STC and underwent thyroidectomy due to differentiated thyroid cancer. We compared the clinicopathological characteristics of post-HCT thyroid cancer patients (post-HCT group) with those of a primary differentiated thyroid carcinoma cohort (cohort group) from Seoul St. Mary's Hospital., Results: The mean ages at HCT and thyroidectomy after HCT were 22.0 and 31.8 years, respectively, and the median time interval between HCT and thyroidectomy was 5 years (range 1-16). Compared with the cohort group, the post-HCT group was younger at cancer onset and frequently had a palpable mass at initial diagnosis. The post-HCT group had more aggressive features, including larger tumor size, frequent extrathyroidal extension, lymphatic invasion, perineural invasion, and frequent lateral neck node metastasis and distant metastasis, relative to the cohort group; however, most patients (83.2%) in the post-HCT group were stage I or II. Additionally, BRAF V600E mutation was less frequent in the post-HCT group., Conclusions: We found that STC after HCT showed younger presentation and more aggressive clinical presentation. Therefore, a policy of regular screening, including neck ultrasound examination, may promote early detection and treatment in HCT recipients.

The present study deals with the potential application of chitosan nonwoven for biomedical textiles based on enzyme immobilization. For this, chitosan nonwoven was first cross-linked with glutaraldehyde to introduce aldehyde groups at optimal conditions. To immobilize the enzyme trypsin onto glutaraldehyde-pre-activated chitosan nonwoven, several parameters such as pH, enzyme concentration, and reaction times were investigated. In addition, the pH, thermal stability, storage stability, and reusability of immobilized trypsin were examined. We found that the optimal immobilization conditions for trypsin were pH 8.5, enzyme concentration of 8% (owf), and treatment time of 30 min. Trypsin was immobilized at 25 °C efficiently. The immobilized trypsin showed lower pH stability and better thermal stability than free trypsin. The immobilized trypsin showed 50% of its initial activity after being used 15 times and 80% of that after 20 days of storage at 4 °C. SEM analysis also confirmed that trypsin was immobilized on chitosan nonwoven., Competing Interests: The authors declare no conflict of interest.

A comparative study of the electrical performance of triboelectric nanogenerators (TENGs) with plain- and 2/1 twill-woven cotton textiles was conducted. Furthermore, the microstructures of the cotton fiber surfaces were examined to understand the fundamental mechanical interaction among the cotton fibers in the TENGs. The TENG with 2/1 twill-woven cotton textiles exhibited higher output voltages compared to that with plain-woven cotton textiles. The difference in the output voltage between the two types of TENGs resulted from the difference in triboelectric charge generation between the constituent cotton textiles. The higher output voltage of the TENG with 2/1 twill-woven cotton textiles was attributed to the higher density in triboelectric interactions among the cotton fiber molecules.