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Introduction: Transaxillary robotic thyroidectomy is considered a technically feasible and safe treatment option for patients with low-risk papillary thyroid carcinoma (PTC). The aim of the present study was to determine the factors that contribute to the perioperative surgical outcomes of robotic thyroidectomy and to suggest guidelines for patient selection to be used by surgeons inexperienced in the technique. Method: We reviewed the records of 275 patients with PTC who underwent robotic total thyroidectomy using a gasless, transaxillary single-incision approach at Yonsei University Health System, South Korea, between January 2011 and May 2012. The association between surgical outcomes and clinicopathologic factors was assessed using linear and logistic regression analysis. Results: The contributing factors for surgical outcomes of robotic thyroidectomy were categorized as patient factors, including gender and body mass index (BMI), and thyroid-specific factors, including thyroid gland size, coexistent thyroiditis, tumor size, and serum anti-thyroglobulin antibody and anti-microsomal antibody titers. Of these, male gender, a large thyroid gland, and thyroiditis significantly increased the total operation time. Male gender, thyroiditis, and overweight BMI increased the working space time, and a large thyroid gland and overweight BMI affected the console time. A large thyroid gland and histological thyroiditis were associated with increased intraoperative blood loss. There was no association between postoperative complications and clinicopathologic parameters. Conclusion: Male gender, overweight BMI, a large thyroid gland, and coexistent thyroiditis adversely affected the surgical outcome of robotic thyroidectomy. Surgeons inexperienced in the technique should avoid or carefully approach individuals with these factors. [ABSTRACT FROM AUTHOR]

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.)

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.

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.)

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.)

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.)

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.

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: 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.

Chronic stress disrupts brain homeostasis and adversely affects the cerebro-vascular system. Even though the effects of chronic stress on brain system have been extensively studied, there are few in vivo dynamic studies on the effects of chronic stress on the cerebro-vascular system. In this study, the effects of chronic stress on cerebral vasculature and BBB permeability were studied using in vivo two-photon (2p) microscopic imaging with an injection of fluorescence-conjugated dextran. Our real-time 2p imaging results showed that chronic stress reduced the vessel diameter and reconstructed vascular volume, regardless of vessel type and branching order. BBB permeability was investigated with two different size of tracers. Stressed animals exhibited a greater BBB permeability to 40-kDa dextran, but not to 70-kDa dextran, which is suggestive of weakened vascular integrity following stress. Molecular analysis revealed significantly higher VEGFa mRNA expression and a reduction in claudin-5. In summary, chronic stress decreases the size of cerebral vessels and increases BBB permeability. These results may suggest that the sustained decrease in cerebro-vascular volume due to chronic stress leads to a hypoxic condition that causes molecular changes such as VEGF and claudin-5, which eventually impairs the function of BBB.

Background: Atopic dermatitis (AD) and psoriasis are the 2 most common chronic inflammatory skin diseases. There is an unmet medical need to overcome limitations for transcutaneous drug development posed by the skin barrier., Objective: We aimed to identify a novel transdermal delivery peptide and to develop a transcutaneously applicable immunomodulatory protein for treating AD and psoriasis., Methods: We identified and generated reporter proteins conjugated to astrotactin 1-derived peptide (AP), a novel transdermal delivery peptide of human origin, and analyzed the intracellular delivery efficiency of these proteins in mouse and human skin cells and tissues using multiphoton confocal microscopy. We also generated a recombinant therapeutic protein, AP-recombinant protein tyrosine phosphatase (rPTP), consisting of the phosphatase domain of the T-cell protein tyrosine phosphatase conjugated to AP. The immunomodulatory function of AP-rPTP was confirmed in splenocytes on cytokine stimulation and T-cell receptor stimulation. Finally, we confirmed the in vivo efficacy of AP-rPTP transdermal delivery in patients with oxazolone-induced contact hypersensitivity, ovalbumin-induced AD-like, and imiquimod-induced psoriasis-like skin inflammation models., Results: AP-conjugated reporter proteins exhibited significant intracellular transduction efficacy in keratinocytes, fibroblasts, and immune cells. In addition, transcutaneous administration of AP-dTomato resulted in significant localization into the dermis and epidermis in both mouse and human skin. AP-rPTP inhibited phosphorylated signal transducer and activator of transcription (STAT) 1, STAT3, and STAT6 in splenocytes and also regulated T-cell activation and proliferation. Transcutaneous administration of AP-rPTP through the paper-patch technique significantly ameliorated skin tissue thickening, inflammation, and cytokine expression in both AD-like and psoriasis-like dermatitis models., Conclusion: We identified a 9-amino-acid novel transdermal delivery peptide, AP, and demonstrated its feasibility for transcutaneous biologic drug development. Moreover, AP-rPTP is a novel immunomodulatory drug candidate for human dermatitis., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare thyroid neoplasm characterized by unique morphologic findings and association with familial adenomatous polyposis. The biologic behavior of this variant has been reported to behave similarly to classic PTC. We report a rare sporadic case of CMV-PTC occurring in a 45-year-old female with multiple lymph nodes and bone metastases, which were detected after total thyroidectomy and radioactive iodine remnant ablation. Molecular analyses of primary thyroid and metastatic tumor tissues revealed a telomerase reverse transcriptase (TERT) promoter mutation, but absence of BRAF, KRAS, NRAS, HRAS, and PIK3CA mutations. Over a 4-year follow-up period, structurally identifiable bone metastases were persistent, but serial post-operative serum thyroglobulin levels remained undetectable in the absence of thyroglobulin antibody. The literature was reviewed. This is the first case of aggressive CMV-PTC showing TERT promoter mutation. TERT promoter mutations may help in predicting aggressive clinical behavior in CMV-PTC. Postoperative serum thyroglobulin measurement may have no impact on clinical decision-making in this type of tumor.

We report an analytical assessment of an iron oxide (Fe2O3)/graphene (G) nanocomposite electrode used in combination with in situ plated bismuth (Bi) working as an electrochemical sensor for the determination of trace Zn(2+), Cd(2+), and Pb(2+). The as-synthesized nanocomposites were characterized by transmission electron microscopy, scanning electron microscopy, thermo-gravimetric analyzer, and X-ray diffraction. The electrochemical properties of the Fe2O3/G/Bi composite modified electrode were investigated. Differential pulse anodic stripping voltammetry was applied for the detection of metal ions. Due to the synergetic effect between graphene and the Fe2O3 nanoparticles, the modified electrode showed improved electrochemical catalytic activity high sensitivity toward trace heavy metal ions. Several parameters such as the preconcentration potential, bismuth concentration, preconcentration time, and pH were carefully optimized to determine the target metal ions. Under optimized conditions, the linear range of the electrode was 1-100μgL(-1) for Zn(2+), Cd(2+), and Pb(2+), and the detection limits were 0.11μgL(-1), 0.08μgL(-1), and 0.07μgL(-1), respectively (S/N =3). Repeatability (% RSD) was found to be 1.68% for Zn(2+), 0.92% for Cd(2+), and 1.69% for Pb(2+) for single sensor with 10 measurements and 0.89% for Zn(2+), 1.15% for Cd(2+), and 0.91% for Pb(2+) for 5 different electrodes. The Fe2O3/G/Bi composite electrode was successfully applied to the analysis of trace metal ions in real samples. The solventless thermal decomposition method applied to the simple and easy synthesis of nanocomposite electrode materials can be extended to the synthesis of nanocomposites and promising electrode materials for the determination of heavy metal ions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to investigate the efficacy of the combined balloon decompression with a balloon-inflatable catheter (ZiNeu) in addition to conventional epidural adhesiolysis, and to identify factors that predict patient responses., Study Design: An institutional single-armed prospective observational study., Subjects: Chronic refractory lumbar spinal stenosis., Methods: This study was performed in 61 patients with spinal stenosis who suffered from chronic (at least 3 months) lumbar radicular pain with or without lower back pain. Patients had failed to maintain improvement for more than 1 month with conventional epidural injection. The numeric rating scale (NRS) and Oswestry disability index (ODI) were each measured at 1, 3, 6, and 12 months after percutaneous epidural adhesiolysis and balloon decompression with a ZiNeu catheter., Results: The percentage of successful responders was 72.1%, 60.7%, 57.4%, and 36.1% of patients at 1, 3, 6, and 12 months, respectively. A single combined treatment of percutaneous epidural adhesiolysis and balloon decompression with a ZiNeu catheter provided sufficient pain relief and functional improvement in patients with chronic refractory lumbar spinal stenosis, and the improvement was maintained for 12 months (P < 0.001). Multivariate logistic regression analysis showed that absence of diabetes independently predicted successful response at 12 months after percutaneous epidural decompression and adhesiolysis with the balloon catheter (Odds ratio = 0.080; 95% confidence interval = 0.009-0.676; P = 0.020)., Conclusions: The combined epidural adhesiolysis and balloon decompression with a ZiNeu catheter led to significant pain relief and functional improvement in a subset of patients with refractory spinal stenosis., (© 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Using the da Vinci(®) robotic system, surgeons can complete secure thyroidectomy without noticeable neck scarring. This study compared the surgical completeness of transaxillary robotic thyroidectomy (RT) with conventional open procedures (OT) in treating papillary thyroid carcinoma (PTC) patients., Materials and Methods: From April 2009 through February 2011, 94 PTC patients underwent total thyroidectomy with central compartment neck dissection (CCND) at Yonsei University College of Medicine. All patients received 1.1 GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBS), and diagnostic WBS (DxWBS) 1 year later. We prospectively compared patient clinicopathologic characteristics and surgical completeness between the two groups., Results: Fifty-one patients underwent OT and 43 underwent RT. Mean age was significantly younger in the RT group. Tumor size, capsular-invasion frequency, multifocality, bilaterality, and central nodal metastasis were not different between the two groups. The number of retrieved nodes during CCND did not significantly differ between the groups. There was no significant difference between the OT and RT groups in stimulated thyroglobulin levels acquired during TxWBS and DxWBS. The RAI uptake ratios at TxWBS were significantly higher in the RT group compared with the OT group; however, follow-up DxWBS showed no difference in RAI uptake ratios. Also, the ablation success rate was similar between the two groups. There were no abnormal findings in follow-up neck ultrasonography in either group., Conclusion: Remnant thyroid tissue ablation after transaxillary RT was successfully managed by 1.1 GBq RAI. RT showed similar surgical completeness versus conventional OT, and provides a safe and feasible surgical option for PTC patients.

Background: Robotic applications have achieved safe and precise thyroidectomy with notable cosmetic and functional benefits. This study was designed to document the influence of body habitus on robotic thyroidectomy in papillary thyroid carcinoma (PTC) patients., Methods: From July 2009 to February 2010, 352 patients underwent robotic thyroidectomy using a gasless, transaxillary single-incision approach at Yonsei University Health System. Body habitus was described using body mass index category (normal weight, overweight, obese), neck length, shoulder width, and shoulder width to neck length ratios. The impact of body habitus on surgical outcomes was analyzed with respect to operation time, number of retrieved central nodes, bleeding amount, and postoperative complications., Results: Of the 352 patients, 217 underwent less than total thyroidectomy and 135 underwent total thyroidectomy. Operative variables (i.e. operation times, bleeding amounts, and numbers of retrieved central nodes) showed no significant differences between three BMI groups for less than total thyroidectomy. However, total operation and working space times were longer for obese patients during total thyroidectomy. In particular, shoulder width was positively correlated with total operation time, working space time, console time, and number of retrieved central nodes. On the other hand, postoperative complications were not significantly different in the three BMI groups and showed no significant correlation with the other indices of body habitus., Conclusions: Standardized robotic thyroidectomy can be performed safely and feasibly in patients with a large body habitus despite longer operation times.

Urinary proteins may provide clues regarding pathogenesis of kidney disease as well as providing markers of disease activity. We employed two-dimensional differential in-gel electrophoretic analysis (2-D DIGE) to assess multiple urine samples in patients with diabetic nephropathy. Patient samples were collected as timed overnight collections. All the patients had longstanding diabetes, impaired renal function, and overt proteinuria. Control and patient urinary protein were analyzed by 2-D DIGE and DeCyder analysis. Ninety-nine spots were significantly regulated in the urine proteome of the diabetic samples, with 63 up- and 36 down-regulated. One spot corresponding to a pI 5-6 and a molecular weight between 45 and 66 kDa was consistently up-regulated by 19-fold across individuals in the diabetic group. Surface-enhanced laser desorption/ionization-time of flight analysis of in-gel tryptic digest of this spot identified this protein as alpha 1 antitrypsin (AAT). ELISA of urine samples from a separate group of patients and controls confirmed a marked increase of AAT in diabetic patients. Immunostaining of human diabetic kidneys revealed up-regulation of AAT in areas of renal fibrosis. In conclusion, we developed a method to analyze numerous urine samples from patients and allowed for detection and identification of regulated urine protein spots.