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Competing Interests: Disclosure: There is no conflict of interest or other disclosures.

Background: This study aimed to compare the prediction performance of two-dimensional (2D) and three-dimensional (3D) semantic segmentation models for intracranial metastatic tumors with a volume ≥ 0.3 mL., Methods: We used postcontrast T1 whole-brain magnetic resonance (MR), which was collected from Taipei Veterans General Hospital (TVGH). Also, the study was approved by the institutional review board (IRB) of TVGH. The 2D image segmentation model does not fully use the spatial information between neighboring slices, whereas the 3D segmentation model does. We treated the U-Net as the basic model for 2D and 3D architectures., Results: For the prediction of intracranial metastatic tumors, the area under the curve (AUC) of the 3D model was 87.6% and that of the 2D model was 81.5%., Conclusion: Building a semantic segmentation model based on 3D deep convolutional neural networks might be crucial to achieve a high detection rate in clinical applications for intracranial metastatic tumors., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

The frameshift hypothesis is a widely accepted model of bird wing evolution. This hypothesis postulates a shift in positional values, or molecular-developmental identity, that caused a change in digit phenotype. The hypothesis synthesized developmental and paleontological data on wing digit homology. The "most anterior digit" (MAD) hypothesis presents an alternative view based on changes in transcriptional regulation in the limb. The molecular evidence for both hypotheses is that the MAD expresses Hoxd13 but not Hoxd11 and Hoxd12. This digit I "signature" is thought to characterize all amniotes. Here, we studied Hoxd expression patterns in a phylogenetic sample of 18 amniotes. Instead of a conserved molecular signature in digit I, we find wide variation of Hoxd11, Hoxd12, and Hoxd13 expression in digit I. Patterns of apoptosis, and Sox9 expression, a marker of the phalanx-forming region, suggest that phalanges were lost from wing digit IV because of early arrest of the phalanx-forming region followed by cell death. Finally, we show that multiple amniote lineages lost phalanges with no frameshift. Our findings suggest that the bird wing evolved by targeted loss of phalanges under selection. Consistent with our view, some recent phylogenies based on dinosaur fossils eliminate the need to postulate a frameshift in the first place. We suggest that the phenotype of the Archaeopteryx lithographica wing is also consistent with phalanx loss. More broadly, our results support a gradualist model of evolution based on tinkering with developmental gene expression., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

With the downscaling in device sizes, process-induced parameter variation has emerged as one of the most serious problems. In particular, the parameter fluctuation of the dynamic random access memory (DRAM) sense amplifiers causes an offset voltage, leading to sensing failure. Previous studies indicate that the threshold voltage mismatch between the paired transistors of a sense amplifier is the most critical factor. In this study, virtual wafers were generated, including statistical V T variation. Then, we numerically investigate the prediction accuracy and reliability of the offset voltage of DRAM wafers using test point measurement for the first time. We expect that this study will be helpful in strengthening the in-line controllability of wafers to secure the DRAM sensing margin.

Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. We enrolled patients with lung cancer ( n = 144) and healthy volunteers as the controls ( n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using enzyme-linked immunosorbent assay. Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC) and 19 had small cell lung cancer. The area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80-0.89) for differentiating lung cancer patients from controls. The levels of all the markers were significantly higher in NSCLC patients with stage IV than in those with stages I-III. A Kaplan-Meier survival analysis showed that NSCLC cancer patients with higher levels of all markers showed poorer survival than those with lower levels. In Cox multivariate analysis of patients with NSCLC, independent prognostic factors for overall survival were CXCL9 and CXCL11. CXCL9 was the only independent prognostic factor for cancer-specific survival. Serum IFN-γ-inducible chemokines may be useful as clinical markers of metastasis and prognosis in NSCLC, and CXCL9 levels showed the most significant results.

We evaluated new features from biosignals comprising diverse physiological response information to predict the outcome of weaning from mechanical ventilation (MV). We enrolled 89 patients who were candidates for weaning from MV in the intensive care unit and collected continuous biosignal data: electrocardiogram (ECG), respiratory impedance, photoplethysmogram (PPG), arterial blood pressure, and ventilator parameters during a spontaneous breathing trial (SBT). We compared the collected biosignal data's variability between patients who successfully discontinued MV ( n = 67) and patients who did not ( n = 22). To evaluate the usefulness of the identified factors for predicting weaning success, we developed a machine learning model and evaluated its performance by bootstrapping. The following markers were different between the weaning success and failure groups: the ratio of standard deviations between the short-term and long-term heart rate variability in a Poincaré plot, sample entropy of ECG and PPG, α values of ECG, and respiratory impedance in the detrended fluctuation analysis. The area under the receiver operating characteristic curve of the model was 0.81 (95% confidence interval: 0.70-0.92). This combination of the biosignal data-based markers obtained during SBTs provides a promising tool to assist clinicians in determining the optimal extubation time.

The diagnosis of brain metastasis (BM) is commonly observed in non-small cell lung cancer (NSCLC) with poor outcomes. Accordingly, developing an approach to early predict BM response to Gamma Knife radiosurgery (GKRS) may benefit the patient treatment and monitoring. A total of 237 NSCLC patients with BMs (for survival prediction) and 256 patients with 976 BMs (for prediction of local tumor control) treated with GKRS were retrospectively analyzed. All the survival data were recorded without censoring, and the status of local tumor control was determined by comparing the last MRI follow-up in patients' lives with the pre-GKRS MRI. Overall 1763 radiomic features were extracted from pre-radiosurgical magnetic resonance images. Three prediction models were constructed, using (1) clinical data, (2) radiomic features, and (3) clinical and radiomic features. Support vector machines with a 30% hold-out validation approach were constructed. For treatment outcome predictions, the models derived from both the clinical and radiomics data achieved the best results. For local tumor control, the combined model achieved an area under the curve (AUC) of 0.95, an accuracy of 90%, a sensitivity of 91%, and a specificity of 89%. For patient survival, the combined model achieved an AUC of 0.81, an accuracy of 77%, a sensitivity of 78%, and a specificity of 80%. The pre-radiosurgical radiomics data enhanced the performance of local tumor control and survival prediction models in NSCLC patients with BMs treated with GRKS. An outcome prediction model based on radiomics combined with clinical features may guide therapy in these patients.

Objective: Growth hormone (GH) treatment is known to be effective in increasing stature in children with a short stature born small for gestational age (SGA). This multicentre, randomized, open-label, comparative, phase III study aimed to evaluate the efficacy and safety of Growtropin-II (recombinant human GH) and to demonstrate that the growth-promoting effect of Growtropin-II is not inferior to that of Genotropin in children with SGA (NCT ID: NCT02770157)., Methods: Seventy five children who met the inclusion criteria were randomized into 3 groups in a ratio of 2:2:1 (the study group [Growtropin-II, n = 30], control group [Genotropin, n = 30], and 26-week non-treatment group [n = 15]). The study and control groups received subcutaneous injections of Growtropin-II and Genotropin, respectively for 52 weeks, whereas the non-treatment group underwent a non-treatment observation period during weeks 0 to 26 and a dosing period during weeks 27 to 52 and additional dosing till week 78 only in re-consenting children., Results: No significant differences in demographic and baseline characteristics between the groups were observed. The mean ± standard deviation change difference in annualized height velocity (aHV) (study group - control group) was 0.65 ±2.12 cm/year (95% confidence interval [CI], -0.53 to 1.83), whereas the lower limit for the 2-sided 95% CI was -0.53 cm/year. Regarding safety, treatment-emergent adverse events (TEAEs) occurred in 53.33% children in the study group and 43.33% children in the control group; the difference in the incidence of TEAEs between the 2 treatment groups was not statistically significant (P  = .4383). A total of 17 serious adverse events (SAEs) occurred in 13.33% children in the treatment groups, and no significant difference in incidence between groups (P  = .7065) was seen. Two cases of adverse drug reaction (ADR) occurred in 2 children (3.33%): 1 ADR (injection site swelling or pain) occurred in 1 child (3.33%) each in the study and control groups., Conclusions: This study demonstrates that the change in aHV from the baseline till 52 weeks with Growtropin-II treatment is non-inferior to that with Genotropin treatment in children with short stature born SGA. Growtropin-II is well-tolerated, and its safety profile is comparable with that of Genotropin over a 1-year course of treatment., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The diagnosis of tuberculous lymphadenitis (TB-LAP) is challenging. We evaluated the role of blood CXC chemokine receptor 3 (CXCR3) ligands in its diagnosis. A total of 65 lymphadenopathy patients were enrolled and lymph node sampling was performed. We also recruited 113 control subjects, consisting of 27 with positive results and 86 with negative results, in the interferon (IFN)-γ release assay (IGRA). In all study subjects, whole-blood samples were collected using the IGRA methodology. After incubation, plasma levels of IFN-γ and two CXCR3 ligands, IFN-inducible T-cell a chemoattractant (I-TAC) and monokine induced by IFN-γ (MIG), were measured using immunoassay. Fifty-three TB-LAP patients were enrolled. TB antigen-stimulated IFN-γ, I-TAC, and MIG levels were all significantly higher in the TB-LAP patients than in the controls and non-TB-LAP patients. The levels of I-TAC and MIG, but not IFN-γ, showed significant differences between the TB-LAP patients and IGRA-positive controls. Area under the receiver operating characteristic curves (AUROCs) of IFN-γ, I-TAC, and MIG were 0.955, 0.958, and 0.959, respectively, for differentiating TB-LAP from control group, and were 0.912, 0.956, and 0.936, respectively, for differentiating TB-LAP from non-TB-LAP. In conclusion, the TB antigen-stimulated MIG and I-TAC could be useful biomarkers in the diagnosis of TB-LAP.

In this research, we develop an affective computing method based on machine learning for emotion recognition using a wireless protocol and a wearable electroencephalography (EEG) custom-designed device. The system collects EEG signals using an eight-electrode placement on the scalp; two of these electrodes were placed in the frontal lobe, and the other six electrodes were placed in the temporal lobe. We performed experiments on eight subjects while they watched emotive videos. Six entropy measures were employed for extracting suitable features from the EEG signals. Next, we evaluated our proposed models using three popular classifiers: a support vector machine (SVM), multi-layer perceptron (MLP), and one-dimensional convolutional neural network (1D-CNN) for emotion classification; both subject-dependent and subject-independent strategies were used. Our experiment results showed that the highest average accuracies achieved in the subject-dependent and subject-independent cases were 85.81% and 78.52%, respectively; these accuracies were achieved using a combination of the sample entropy measure and 1D-CNN. Moreover, our study investigates the T8 position (above the right ear) in the temporal lobe as the most critical channel among the proposed measurement positions for emotion classification through electrode selection. Our results prove the feasibility and efficiency of our proposed EEG-based affective computing method for emotion recognition in real-world applications.

Introduction: Plantar fasciitis is one of the common foot complaints that is chronic and can induce dysfunction. Total contact insole (TCI) is simple but effective in treating plantar fasciitis. Despite its effect, the cost and long duration for production have been the major flaws. Therefore, we developed a newly designed three-spike insole (TSI) that can be commercially productive and compared its clinical outcomes to TCI., Methods: Patients with plantar fasciitis refractory to conservative treatment for more than 6 weeks were candidates. We produced insoles with hardness of 58 ± 5 Shore-A. Twenty-eight patients were randomized with equal allocation to either TSI or TCI. The following assessment tools were used: visual analog scale (VAS), American Orthopaedic Foot and Ankle score, Foot and Ankle Outcome Score, Karlsson-Peterson (KP) score, Short Form-36 for quality of life, and Foot Function Index. Non-inferiority was declared if VAS was within the statistical variability of minimal important difference. A blinded assessor evaluated the groups at baseline and after 6, 12, and 24 weeks., Results: The groups were homogenous for majority of variables at baseline. Overall patient-reported satisfaction showed improvement from mean 5.2 (range, 1-12) weeks of wearing and all clinical outcome scores showed significant improvements in both groups over time on Friedman test (p ≤.032). TSI showed non-inferiority to TCI at each time point. Post hoc analysis revealed that many scales showed significant superiority of TSI at 3 month (p ≤.008) and KP score at 6 month (p < .001)., Conclusion: We reaffirmed that semi-rigid insole is effective in refractory plantar fasciitis and showed TSI restores pedal function more rapidly than TCI. TSI can be not only effective in deriving better clinical outcomes but also be manufactured for popularization to lower the price and producing time of orthosis., Competing Interests: The authors have declared that no competing interests exist.

The most common genetic backgrounds of hereditary paraganglioma and pheochromocytoma (PPGL) are SDHx germline mutations. Given the fact that the immunohistochemistry (IHC) result for SDHB is always negative regardless of the type of SDHx mutation, we aimed to evaluate the efficacy of using SDHB IHC for screening SDHx mutations in PPGL cases. In total, 52 patients who underwent surgery for PPGL treatment between 2006 and 2020 and underwent genetic analysis at diagnosis were included. Tissue microarrays (TMAs) were constructed with PPGL tissues and IHC for SDHB was performed on TMA sections. All 10 patients with SDHB-negative IHC contained SDHB or SDHD mutations. The genetic test results of patients with SDHB-weakly positive IHC varied (one SDHB , two RET , one VHL , and three unknown gene mutations). There were no SDHx mutations in the SDHB-positive IHC group. Six patients with weakly positive SDHB IHC with primarily unknown genetic status were re-called and underwent next-generation sequencing. None of them had SDHx mutations. In conclusion, SDHB-negative IHC is a cost-effective and reliable method to predict SDHx mutations. However, in the case of weakly positive SDHB staining, an additional gene study should be considered.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.

In this paper, we propose a bio-molecular algorithm with O( n 2 + m ) biological operations, O( 2 n ) DNA strands, O( n ) tubes and the longest DNA strand, O( n ), for solving the independent-set problem for any graph G with m edges and n vertices. Next, we show that a new kind of the straightforward Boolean circuit yielded from the bio-molecular solutions with m NAND gates, ( m +n × ( n + 1 )) AND gates and (( n × ( n + 1 ))/2) NOT gates can find the maximal independent-set(s) to the independent-set problem for any graph G with m edges and n vertices. We show that a new kind of the proposed quantum-molecular algorithm can find the maximal independent set(s) with the lower bound Ω ( 2 n/2 ) queries and the upper bound O( 2 n/2 ) queries. This work offers an obvious evidence for that to solve the independent-set problem in any graph G with m edges and n vertices, bio-molecular computers are able to generate a new kind of the straightforward Boolean circuit such that by means of implementing it quantum computers can give a quadratic speed-up. This work also offers one obvious evidence that quantum computers can significantly accelerate the speed and enhance the scalability of bio-molecular computers. Next, the element distinctness problem with input of n bits is to determine whether the given 2 n real numbers are distinct or not. The quantum lower bound of solving the element distinctness problem is Ω ( 2 n×(2/3) ) queries in the case of a quantum walk algorithm. We further show that the proposed quantum-molecular algorithm reduces the quantum lower bound to Ω (( 2 n/2 )/( [Formula: see text]) queries. Furthermore, to justify the feasibility of the proposed quantum-molecular algorithm, we successfully solve a typical independent set problem for a graph G with two vertices and one edge by carrying out experiments on the backend ibmqx4 with five quantum bits and the backend simulator with 32 quantum bits on IBM's quantum computer.

Background: Laparoscopic adrenalectomy is widely used for treating various adrenal tumors. Posterior retroperitoneoscopic adrenalectomy was introduced after transperitoneal laparoscopic adrenalectomy. The comparability and superiority of posterior retroperitoneoscopic adrenalectomy have been widely investigated. We aimed to compare the outcomes of posterior retroperitoneoscopic adrenalectomy and transperitoneal laparoscopic adrenalectomy using 10 years' data. The changes in outcomes over time were also analyzed., Methods: This was a retrospective observational study. A total of 505 patients who underwent laparoscopic adrenalectomy between 2009 and 2018 were included. The patients were divided into two groups: transperitoneal (n=114) and retroperitoneal (n=391) groups. Patients who underwent posterior retroperitoneoscopic adrenalectomy were further classified into sub-groups (sub-group 1: 2009-2012; sub-group 2: 2013-2015; and sub-group 3: 2016-2018) based on time periods. Clinicopathological factors and postoperative outcomes were retrospectively reviewed and analyzed., Results: The retroperitoneal group showed significantly shorter operation time, diet initiation time, and hospital stay compared to the transperitoneal group (P=0.000, 0.000 and 0.000, respectively). Analgesics were used less frequently in the retroperitoneal group than in the transperitoneal group (P=0.048). In the retroperitoneal group, the time to postoperative diet initiation shortened over time (P=0.000)., Conclusions: Posterior retroperitoneoscopic adrenalectomy is a favorable surgical method that results in patient outcomes that are comparable to those of conventional transperitoneal laparoscopic adrenalectomy, without compromising patient safety., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-178). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Thyroid cancer in children is very uncommon. For pediatric thyroid cancer, robotic surgery has served as a minimally invasive surgical alternative to conventional open surgery. Our study aimed to evaluate the results of robotic versus open surgical treatment for patients with thyroid cancer younger than 20 years of age at the time of diagnosis. This retrospective review included 161 pediatric patients who underwent robotic transaxillary or conventional open thyroidectomy at our institution from 2008 to 2019. Of these patients, 99 comprised the robotic group and 62 the open group. Patient demographics, surgical outcomes, and disease-free survival rates were compared between the two groups. Patients in the open group were more likely to have advanced stage diseases with a larger tumor size and higher tumor-node-metastasis stage than those in the robotic group. Operation time and follow-up period were similar in both groups. Patients in the robotic group had a lower rate of postoperative complications and a shorter length of hospital stay, but they also had a lower average number of retrieved central lymph nodes. However, there were no significant between group differences in recurrence rates and disease-free survival. In the hands of an experienced surgeon, robotic thyroidectomy is a feasible and safe option for pediatric patients.

Hyperparathyroidism is not a rare disease; if a parathyroid adenoma is confirmed, the treatment of choice is the surgical resection. Diagnostic use of fine-needle aspiration biopsy (FNAB) for histological confirmation in patients with hyperparathyroidism is controversial. And spontaneous remission of hyperparathyroidism caused by bleeding or infarction of the adenoma rarely occurs. Here we have reported two cases of hyperparathyroidism in which spontaneous remission occurred due to the use of FNAB for diagnosis. The remission was confirmed after surgical removal and pathological review of the adenoma. The first patient diagnosed with primary hyperparathyroidism (PHPT) had neck pain and severe swelling 4 days after FNAB, and spontaneous remission due to intracapsular hemorrhage was confirmed after surgery. In the second patient receiving hemodialysis treatment for end-stage renal disease, hyperparathyroidism spontaneously resolved after FNAB and the parathyroid hormone (PTH) levels normalized after surgery. The first patient maintained a normal level of PTH for 6 years, and the second patient received kidney transplantation 6 years after surgery, and the normal level of PTH was confirmed for 13 years. Caution is needed while performing FNAB for diagnosis of hyperparathyroidism and during decision making regarding whether to observe the patient or perform surgery after spontaneous remission due to bleeding or infarction., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-6). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Objective: Hypothalamic obesity is common among patients with craniopharyngioma. This study examined whether precise stereotactic radiosurgery reduces the risk of hypothalamic obesity in cases of craniopharyngioma with expected long-term survival., Methods: This cohort study included 40 patients who had undergone Gamma Knife radiosurgery (GKRS; n = 22) or fractionated radiotherapy (FRT; n = 18) for residual or recurrent craniopharyngioma. Neurological presentations, tumor volume changes, and BMI values were meticulously reviewed. The median clinical follow-up durations were 9.7 years in the GKRS group and 10.8 years in the FRT group., Results: The median ages at the time of GKRS and FRT were 9.0 years and 10.0 years, respectively. The median margin dose of GKRS was 12.0 Gy (range 10.0-16.0 Gy), whereas the median dose of FRT was 50.40 Gy (range 44.1-56.3 Gy). Prior to GKRS or FRT, the median BMI values were 20.5 kg/m2 in the GKRS cohort and 20.0 kg/m2 in the FRT cohort. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. In the FRT cohort, BMI curves rapidly increased beyond the 85th percentile of the upper limit of the general population. BMI curves in the GKRS cohort increased more gradually, and many of the patients merged into the normal growth curve after adolescence. However, the observed difference was not statistically significant (p = 0.409)., Conclusions: The study compared the two adjuvant radiation modalities most commonly used for recurrent and residual craniopharyngioma. The authors' results revealed that precise radiosurgery dose planning can mediate the subsequent increase in BMI. There is every indication that meticulous GKRS treatment is an effective approach to treating craniopharyngioma while also reducing the risk of hypothalamic obesity.

Introduction: Psychological factors such as anxiety and confidence that students have in the patient care situation are important in that this affects the actual clinical performance. Students who are just starting clinical practice have a lack of clinical knowledge, skill proficiency, and patient communication skills, so they experience anxiety and lack of confidence in clinical setting. Practice in a safe environment, such as simulation education, can help students perform more settled and competently in patient care. The purpose of this study was to analyze the effect of high-fidelity simulation experience on anxiety and confidence in medical students., Materials and Methods: This study enrolled 37 5th-year students at Ajou University School of Medicine in 2020. Two simulation trainings were implemented, and a survey was conducted to measure students' level of anxiety and confidence before and after each simulation. Based on the research data, a paired t-test was conducted to compare these variables before and after the simulation, and whether this was their first or second simulation experience., Results: Students had a significantly lower level of anxiety and a significantly higher level of confidence after the simulation than before. In addition, after one simulation experience, students had less anxiety and more confidence before the second simulation compared to those without simulation experience., Conclusions: We confirmed that medical students need to be repeatedly exposed to simulation education experiences in order to have a sense of psychological stability and to competently deliver medical treatment in a clinical setting. There is a practical limitation in that medical students do not have enough opportunities to meet the patients during clinical practice in hospitals. Therefore, in order to produce excellent doctors, students should have the expanded opportunities to experience simulation education so they can experience real-world medical conditions., Competing Interests: The authors have declared that no competing interests exist.

Nursing assistants (NAs) working in nursing homes (NHs) are at higher risk for work-related musculoskeletal symptoms (WRMSs) than their counterparts working in other health care settings. Worldwide, NAs have ranked shoulders in the top three body parts at risk of WRMSs. However, factors associated with their shoulder WRMSs are currently unknown. The aim of this study was to identify these associated risk factors among NAs working in NHs. 440 NAs from 47 nursing homes (with 60-90% response rate from each nursing home), recruited by convenience sampling, participated in this cross-sectional study in 2014-2015. A validated and reliable questionnaire was used for data collection. Information on demographic, job content questionnaire (JCQ), perceived physical exertion (PE), workstyle, ergonomic and manual handling knowledge and other work-related factors was collected using a self-administered questionnaire. 53% of the participants reported experiencing with WRMSs in their shoulders. Nine associated factors of shoulder WRMSs were identified using bivariate analysis. With the adjustment of age and gender using multivariable logistic regression, body mass index (OR = .931, 95% CI [.874-.991]), job title of health workers (OR = 2.72, 95% CI [1.18-6.25]) and workstyle-working through pain (OR = 1.06, 95% CI [1.01-1.11]) remained as predictors. Effort should be directed at integrating "workstyle intervention" into lifestyle physical activity training for NAs., Competing Interests: The authors declare there are no competing interests., (©2021 Cheung et al.)

Mutations of phosphatidylinositol glycan biosynthesis class T ( PIGT ), which encodes a subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, can lead to multiple anomalies, including seizures, intellectual disabilities, facial dysmorphism, and various congenital malformations. We performed whole-exome sequencing in a patient with seizures, intellectual disabilities, truncal ataxia, facial dysmorphism, and persistent hypophosphatasia without rickets or bone mineralization defects, and identified two heterozygous mutations in PIGT , c.250G>T (p.Glu84*) and c.1582G>A (p.Val528Met). GPI-linked protein analyses found no abnormalities. Although the patient's hypophosphatasia persists, no skeletal, urological, or dental abnormalities were found. The seizures disappeared after administering antiepileptic drugs. PIGT mutations should be considered in patients with multiple congenital symptoms and persistent hypophosphatasia., (© 2021 by the Association of Clinical Scientists, Inc.)

It is well-known that microbiota dysbiosis is closely associated with numerous diseases in the human body. The oral cavity and gut are the two largest microbial habitats, playing a major role in microbiome-associated diseases. Even though the oral cavity and gut are continuous regions connected through the gastrointestinal tract, the oral and gut microbiome profiles are well-segregated due to the oral-gut barrier. However, the oral microbiota can translocate to the intestinal mucosa in conditions of the oral-gut barrier dysfunction. Inversely, the gut-to-oral microbial transmission occurs as well in inter- and intrapersonal manners. Recently, it has been reported that oral and gut microbiomes interdependently regulate physiological functions and pathological processes. Oral-to-gut and gut-to-oral microbial transmissions can shape and/or reshape the microbial ecosystem in both habitats, eventually modulating pathogenesis of disease. However, the oral-gut microbial interaction in pathogenesis has been underappreciated to date. Here, we will highlight the oral-gut microbiome crosstalk and its implications in the pathogenesis of the gastrointestinal disease and cancer. Better understanding the role of the oral-gut microbiome axis in pathogenesis will be advantageous for precise diagnosis/prognosis and effective treatment.

Hydroxychloroquine has recently received attention as a treatment for COVID-19. However, it may prolong the QTc interval. Furthermore, when hydroxychloroquine is administered concomitantly with other drugs, it can exacerbate the risk of QT prolongation. Nevertheless, the risk of QT prolongation due to drug-drug interactions (DDIs) between hydroxychloroquine and concomitant medications has not yet been identified. To evaluate the risk of QT prolongation due to DDIs between hydroxychloroquine and 118 concurrent drugs frequently used in real-world practice, we analyzed the electrocardiogram results obtained for 447,632 patients and their relevant electronic health records in a tertiary teaching hospital in Korea from 1996 to 2018. We repeated the case-control analysis for each drug. In each analysis, we performed multiple logistic regression and calculated the odds ratio (OR) for each target drug, hydroxychloroquine, and the interaction terms between those two drugs. The DDIs were observed in 12 drugs (trimebutine, tacrolimus, tramadol, rosuvastatin, cyclosporin, sulfasalazine, rofecoxib, diltiazem, piperacillin/tazobactam, isoniazid, clarithromycin, and furosemide), all with a p value of < 0.05 (OR 1.70-17.85). In conclusion, we found 12 drugs that showed DDIs with hydroxychloroquine in the direction of increasing QT prolongation.

Background: Children with nephrotic syndrome (NS) are at an increased risk of acute kidney injury (AKI) and the incidence of AKI in this population is reportedly increasing. This study aimed to investigate the incidence, clinical profiles, and risk factors of AKI in hospitalized children with NS through a nationwide study., Methods: This retrospective multicenter study included 14 pediatric nephrology centers in Korea. From 2013 to 2017, a total of 814 patients with idiopathic NS were cared for at participating centers. Among them, 363 patients were hospitalized for NS and investigated in this study., Results: A total of 363 children with NS were hospitalized 574 times. AKI occurred in 93 admissions (16.2%) of 89 patients: 30 (32.3%) stage 1; 24 (25.8%) stage 2; and 39 (41.9%) stage 3. Multivariate logistic regression analysis showed that longer disease duration, lower albumin level, and methylprednisolone pulse treatment were significantly associated with AKI development in hospitalized children with NS. AKI was associated with a longer hospital stay than non-AKI (median 10 vs. 7 days, P = 0.001). Among 93 admissions, 85 (91.4%) episodes recovered from AKI without complication, whereas 6 (6.5%) progressed to advanced chronic kidney disease (CKD)., Conclusions: AKI is not uncommon in hospitalized children with NS, and its incidence in this nationwide study was 16.2%. Risk factors for AKI in hospitalized children with NS include longer disease duration, lower albumin level, and methylprednisolone pulse therapy. Pediatric NS patients with these characteristics should be under more strict scrutiny for the occurrence of AKI. Graphical abstract.

Background: Postoperative transient hypocalcemia (TH) is a common complication of total thyroidectomy. This retrospective study evaluated the clinical utility of preoperative vitamin D3 injection for the prevention of TH after total thyroidectomy., Methods: We included 2294 patients who underwent total thyroidectomy from January 2015 until October 2018 and retrospectively analyzed their data by complete chart review at our hospital. The patients were divided into two groups: vitamin D3 injection (VDI; n  = 342) and vitamin D3 noninjection (VDN; n  = 1952). TH was defined as serum calcium <8.2 mg/dL and signs or symptoms of hypocalcemia., Results: The mean preoperative serum 25-hydroxyvitamin D (25-OHD) levels of the VDI group were significantly lower than those of the VDN group (16.5 ± 6.9 ng/mL vs 19.4 ± 8.7 ng/mL, p  < 0.001). Multivariate analysis indicated that the significant risk factors of TH include vitamin D noninjection (hazard ratio (HR): 1.717, 95% confidence interval (CI): 1.282-2.300, p  < 0.001), male gender (HR: 1.427, 95% CI: 1.117-1.822, p  = 0.004), and capsular extension (HR: 1.273, 95% CI: 1.011-1.603, p  = 0.040)., Conclusions: Preoperative vitamin D3 injection significantly contributed to the prevention of TH after total thyroidectomy. Further prospective or multicenter studies must be conducted to determine the effect of vitamin D3 injection., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Kwangsoon Kim et al.)

Artificial intelligence (AI) has been applied with considerable success in the fields of radiology, pathology, and neurosurgery. It is expected that AI will soon be used to optimize strategies for the clinical management of patients based on intensive imaging follow-up. Our objective in this study was to establish an algorithm by which to automate the volumetric measurement of vestibular schwannoma (VS) using a series of parametric MR images following radiosurgery. Based on a sample of 861 consecutive patients who underwent Gamma Knife radiosurgery (GKRS) between 1993 and 2008, the proposed end-to-end deep-learning scheme with automated pre-processing pipeline was applied to a series of 1290 MR examinations (T1W+C, and T2W parametric MR images). All of which were performed under consistent imaging acquisition protocols. The relative volume difference (RVD) between AI-based volumetric measurements and clinical measurements performed by expert radiologists were + 1.74%, - 0.31%, - 0.44%, - 0.19%, - 0.01%, and + 0.26% at each follow-up time point, regardless of the state of the tumor (progressed, pseudo-progressed, or regressed). This study outlines an approach to the evaluation of treatment responses via novel volumetric measurement algorithm, and can be used longitudinally following GKRS for VS. The proposed deep learning AI scheme is applicable to longitudinal follow-up assessments following a variety of therapeutic interventions.

Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of disorders with variable growth failure and skeletal impairments affecting the spine and long bone epiphyses and metaphyses. Here we report on four unrelated families with SEMD in which we identified two monoallelic missense variants and one monoallelic splice site variant in RPL13, encoding the ribosomal protein eL13. In two out of four families, we observed autosomal dominant inheritance with incomplete penetrance and variable clinical expressivity; the phenotypes of the mutation-positive subjects ranged from normal height with or without hip dysplasia to severe SEMD with severe short stature and marked skeletal dysplasia. In vitro studies on patient-derived dermal fibroblasts harboring RPL13 missense mutations demonstrated normal eL13 expression, with proper subcellular localization but reduced colocalization with eL28 (p < 0.001). Cellular functional defects in fibroblasts from mutation-positive subjects indicated a significant increase in the ratio of 60S subunits to 80S ribosomes (p = 0.007) and attenuated global translation (p = 0.017). In line with the human phenotype, our rpl13 mutant zebrafish model, generated by CRISPR-Cas9 editing, showed cartilage deformities at embryonic and juvenile stages. These findings extend the genetic spectrum of RPL13 mutations causing this novel human ribosomopathy with variable skeletal features. Our study underscores for the first time incomplete penetrance and broad phenotypic variability in SEMD-RPL13 type and confirms impaired ribosomal function. Furthermore, the newly generated rpl13 mutant zebrafish model corroborates the role of eL13 in skeletogenesis. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).., (© 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Patients with oral squamous cell carcinoma (OSCC) bone invasion are surgically treated with bone resection, which results in severe physical and psychological damage. Here, we investigated the potential of fractalkine (CX3CL1), which is regulated by transforming growth factor (TGF-β), as a novel biomarker for correct prediction and early detection of OSCC-associated bone invasion. TGF-β knockdown and treatment with a TGF-β-neutralizing antibody decreased the level of fractalkine in the culture media of HSC-2 and YD10B OSCC cells. Treatment with a fractalkine-neutralizing antibody reduced TGF-β-stimulated invasion by HSC-2 and YD10B cells. Fractalkine treatment increased the viability, invasion, and uPA secretion of both OSCC cell lines. Furthermore, OSCC cell bone invasion was assessed following subcutaneous inoculation of wild-type or TGF-β knockdown OSCC cells in mouse calvaria. TGF-β knockdown prevented erosive bone invasion, reduced the number of osteoclasts at the tumor-bone interface, and downregulated fractalkine expression in mouse tumor tissues. Our results indicate that the production of fractalkine is stimulated by TGF-β and mediates TGF-β-induced cell invasion in several OSCC cell lines showing an erosive pattern of bone invasion. Fractalkine may be a useful predictive marker and therapeutic target for OSCC-induced bone destruction., (© 2021 European Journal of Oral Sciences.)

We need to be able to learn new behaviour, but also be capable of changing existing routines, when they start conflicting with our long-term goals. Little is known about to what extent blank-slate learning of new and adjustment of existing behavioural routines rely on different neural and bodily mechanisms. In the current study, participants first acquired novel stimulus-response contingencies, which were subsequently randomly changed to create the need for flexible adjustments. We measured midfrontal theta oscillations via EEG as an indicator of neural conflict processing, as well as heart rate as a proxy of autonomic activity. Participants' trial-wise learning progress was estimated via computation modelling. Theta power and heart rate significantly differed between correct and incorrect trials. Differences between correct and incorrect trials in both neural and cardiac feedback processing were more pronounced for adjustments compared to blank-slate learning. This indicates that both midfrontal and cardiac processing are sensitive to changes in stimulus-response contingencies. Increases in individual learning rates predicted lower impact of performance feedback on midfrontal theta power, but higher impact on heart rate. This suggests that cardiac and midfrontal reactivity are partially reflective of different mechanisms related to feedback learning. Our results shed new light on the role of neural and autonomic mechanisms for learning and behavioural adjustments., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Gamma Knife radiosurgery (GKRS) is a safe and effective treatment modality with a long-term tumor control rate over 90% for vestibular schwannoma (VS). However, numerous tumors may undergo a transient pseudoprogression during 6-18 months after GKRS followed by a long-term volume reduction. The aim of this study is to determine whether the radiomics analysis based on preradiosurgical MRI data could predict the pseudoprogression and long-term outcome of VS after GKRS., Materials and Methods: A longitudinal dataset of patients with VS treated by single GKRS were retrospectively collected. Overall 336 patients with no previous craniotomy for tumor removal and a median of 65-month follow-up period after radiosurgery were finally included in this study. In total 1763 radiomic features were extracted from the multiparameteric MRI data before GKRS followed by the machine-learning classification., Results: We constructed a two-level machine-learning model to predict the long-term outcome and the occurrence of transient pseudoprogression after GKRS separately. The prediction of long-term outcome achieved an accuracy of 88.4% based on five radiomic features describing the variation of T2-weighted intensity and inhomogeneity of contrast enhancement in tumor. The prediction of transient pseudoprogression achieved an accuracy of 85.0% based on another five radiomic features associated with the inhomogeneous hypointensity pattern of contrast enhancement and the variation of T2-weighted intensity., Conclusion: The proposed machine-learning model based on the preradiosurgical MR radiomics provides a potential to predict the pseudoprogression and long-term outcome of VS after GKRS, which can benefit the treatment strategy in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker., Methods: LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results., Results: LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages., Conclusion: LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

Antimicrobial resistance (AMR) threatens the effective prevention and treatment of a wide range of infections. Governments around the world are beginning to devote effort for innovative treatment development to treat these resistant bacteria. Systems biology methods have been applied extensively to provide valuable insights into metabolic processes at system level. Genome-scale metabolic models serve as platforms for constraint-based computational techniques which aid in novel drug discovery. Tools for automated reconstruction of metabolic models have been developed to support system level metabolic analysis. We discuss features of such software platforms for potential users to best fit their purpose of research. In this work, we focus to review the development of genome-scale metabolic models of Gram-negative pathogens and also metabolic network approach for identification of antimicrobial drugs targets.

Background: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS)., Objectives: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes., Methods: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS., Results: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS., Conclusions: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs., (© 2020 S. Karger AG, Basel.)

Oral squamous cell carcinoma (OSCC) frequently invades nearby bone and bone involvement determines the prognosis of patients. Growth factors, stored in the bone matrix and released during bone destruction, are known as key components in the bone-tumor interaction. However, the coordination of growth factor signals and the precise mechanism of bone destruction in oral cancer are still unclear. In the study, we investigated the differential cytokine expression profile of oral cancer cells by TGF-β treatment and the function of altered expression of cytokines on the osteoclast differentiation. We established TGFBR2-knockdown cells using small hairpin RNA. TGF-β was treated to both TGFBR2 expressing and knockdown cells and the culture supernatants were analyzed using a cytokine array kit. We found that the TGF-β inhibited IGFBP3 level and enhanced MMP9 level. We confirmed this regulation of IGFBP3 and MMP9 by TGF-β using ELISA and zymography, respectively. IGFBP3 is known as to modulate the bioavailability of IGF1, which is abundant in the bone microenvironment and regulates osteoclast differentiation. Therefore, we further analyzed the function of IGFBP3 on osteoclastogenesis. Although IGFBP3 increased the viability of murine bone marrow macrophages, the osteoclast differentiation of these cells was blocked by IGFBP3 in a dose-dependent manner. These results revealed a novel pathway for the regulation of osteoclastogenesis by oral cancer cells, which may be a new therapeutic target for osteolysis induced by oral cancer infiltrating into the bone., (Copyright © 2020. Published by Elsevier Inc.)

Background: The current position of robotic surgery in the field of minimally invasive surgery remains ambiguous. We evaluated long-term trends of robotic general surgery and the future direction of its development., Methods: Data on robotic cancer surgeries between 2005 and 2014 were retrospectively collected by volunteer institutions in the Republic of Korea. Spearman's correlation and logistic regression analyses were used to compare robotic and laparoscopic surgery trends in general surgery., Results: The odds that robotic surgery was performed instead of laparoscopic surgery significantly decreased in the fields of colorectal, stomach, and hepato-biliary-pancreatic surgery (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.93-0.97; OR: 0.90, 95% CI: 0.88-0.92; and OR: 0.71, 95% CI: 0.65-0.78, respectively), except for thyroid surgery (OR: 1.28, 95% CI: 1.25-1.30). Of the total numbers of each procedure, proportions of robotic intersphincteric resections, abdominoperineal resections, and pylorus-preserving surgery performed significantly increased (r = 0.98, P < .001; r = 0.78, P = .01; and r = 0.86, P = .007, respectively)., Conclusions: The use of robotic surgery failed to preponderate that of laparoscopic surgery, except for thyroid surgery. Robotic surgery is increasingly preferred for limited fields or complex surgeries, but the use of robotics in simple surgeries has decreased., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Taiwan LLC.)

Background: The initial response to islet transplantation and the subsequent acute inflammation is responsible for significant attrition of islets following both autologous and allogenic procedures. This multicentre study compares this inflammatory response using cytokine profiles and complement activation., Methods: Inflammatory cytokine and complement pathway activity were examined in two cohorts of patients undergoing total pancreatectomy followed either by autologous (n=11) or allogenic (n=6) islet transplantation. Two patients who underwent total pancreatectomy alone (n=2) served as controls., Results: The peak of cytokine production occurred immediately following induction of anaesthesia and during surgery. There was found to be a greater elevation of the following cytokines: TNF-alpha (P<0.01), MCP-1 (P=0.0013), MIP-1α (P=0.001), MIP-1β (P=0.00020), IP-10 (P=0.001), IL-8 (P=0.004), IL-1α (P=0.001), IL-1ra (0.0018), IL-10 (P=0.001), GM-CSF (P=0.001), G-CSF (P=0.0198), and Eotaxin (P=0.01) in the allogenic group compared to autografts and controls. Complement activation and consumption was observed in all three pathways, and there were no significant differences in between the groups although following allogenic transplantation ∆IL-10 and ∆VEGF levels were significantly elevated those patients who became insulin-independent compared with those who were insulin-dependent., Conclusions: The cytokine profiles following islet transplantation suggests a significantly greater acute inflammatory response following allogenic islet transplantation compared with auto-transplantation although a significant, non-specific inflammatory response occurs following both forms of islet transplantation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3519). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Growth hormone (GH) treatment preference and adherence are affected by delivery device convenience, injection-site pain, confidence in correct dose administration, and device satisfaction. This survey investigated if switching device to NordiFlex® improved treatment experience in pediatric patients in South Korea., Design and Methods: Patients aged 4-≤18 years were surveyed. Participants were NordiFlex® users who previously used NordiLet®/other devices. Participants compared preference, self-reported adherence, satisfaction, perceived ease of use, and device subjective benefits (across four domains: ease of use, self-efficacy, minimal disruption of daily life, positive feelings about injections ) of NordiFlex® vs. previous device., Results: Ninety-four patients were enrolled, of which 91.5% previously used NordiLet®. Significantly more patients preferred, and were more satisfied with NordiFlex® vs. previous device; mean score: 0.65 (95% confidence interval [CI]:0.41;0.88) and 0.61 (95% CI:0.36;0.85), respectively. Participants reported greater perceived ease of use (0.49 [95% CI:0.26;0.72]) and fewer missed injections (0.20 [95% CI:0.06;0.34], with NordiFlex® vs. previous device. Bivariate analysis showed significant associations between preference for NordiFlex® and higher scores on self-efficacy, ease of use, minimal disruption of daily life , and positive feelings about injection (all p < 0.001)., Conclusion: These results suggest that improvements in device features could be associated with improved treatment experience.

Purpose: To investigate the reproducibility of quantitative digital subtraction angiography (QDSA) measurements and their associations with brain arteriovenous malformation (BAVM) hemorrhage., Methods: From 2011-2019, 37 patients with BAVMs who had undergone both diagnostic and stereotactic DSA were divided into hemorrhagic and nonhemorrhagic groups. QDSA analysis was performed on the 2 DSA exams. The inter-exam reliabilities of QDSA measurements across the diagnostic and stereotactic DSA were tested using intraclass correlation coefficients (ICCs). Demographics, BAVM characteristics, and QDSA results for the hemorrhagic and nonhemorrhagic groups were compared., Results: Fifteen of 37 (40.5 %) patients presented with hemorrhage were associated with smaller BAVM volume and the presence of intranidal aneurysm and exclusive deep venous drainage. The median interval between the diagnostic and stereotactic DSA was 49 days and did not differ between the groups. In both groups, the inter-exam QDSA measurements were more reliable for drainage veins and transnidal time (ICCs ranged from 0.38-0.93) than for feeding arteries (ICCs ranged from 0.01-0.74). Among the venous parameters, the hemorrhagic group had lower peak density, area under the curve, inflow gradient, and outflow gradient on both DSA exams and larger full width at half maximum and stasis index on the stereotactic DSA exam than the nonhemorrhagic group., Conclusions: In BAVMs, the QDSA measurements for veins are more reliable than those for arteries. QDSA analysis reflecting stagnant venous drainage is associated with BAVM hemorrhage, but may be confounded by the acute hemodynamic change after hemorrhage., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Angiogenesis plays a crucial role in tumor growth and metastasis. Vascular endothelial growth factor (VEGF)-stimulated endothelial cell proliferation and migration are critical steps in tumor angiogenesis. Here, we investigated the anti-angiogenic activity of xanthorrhizol, a sesquiterpenoid isolated from the Indonesian medicinal plant Curcuma xanthorrhiza. Xanthorrhizol at noncytotoxic concentrations inhibited the proliferation, migration, and formation of capillary-like tubes in VEGF-treated human umbilical vein endothelial cells (HUVECs). Xanthorrhizol inhibited the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) and the expression of vascular cell adhesion molecule (VCAM)-1 and E-selectin in VEGF-treated HUVECs. The expression and transcriptional activity of NF-[Formula: see text]B were downregulated by xanthorrhizol in VEGF-treated HUVECs. Furthermore, xanthorrhizol significantly inhibited VEGF-induced angiogenesis in the chorioallantoic membrane of fertilized eggs and Matrigel plugs subcutaneously injected into mice. Xanthorrhizol inhibited tumor volume and tumor-derived angiogenesis in mice inoculated with breast cancer cells. The in vitro and in vivo anti-angiogenic activities of xanthorrhizol were as potent as those of curcumin, a well-known anticancer agent derived from C. longa . Taken together, xanthorrhizol inhibits VEGF-induced angiogenesis of endothelial cells by blocking the activation of the PI3K/Akt/eNOS axis and subsequent upregulation of adhesion molecules induced by the transcriptional activation of NF-[Formula: see text]B. Xanthorrhizol is a promising anti-angiogenic agent and can serve as a beneficial agent to enhance anticancer treatments.

Aims: We compared long-term clinical outcomes between patients treated with Orsiro sirolimus-eluting stent (O-SES) and those treated with durable biocompatible polymer Resolute Integrity zotarolimus-eluting stent (R-ZES)., Methods and Results: The ORIENT trial was a randomized controlled noninferiority trial to compare angiographic outcomes between O-SES and R-ZES. We performed a post hoc analysis of 3-year clinical outcomes and included 372 patients who were prospectively enrolled and randomly assigned to O-SES (n = 250) and R-ZES (n = 122) groups in a 2:1 ratio. The primary endpoint was target lesion failure defined as a composite of cardiac death, nonfatal myocardial infarction, and target lesion revascularization. At 3 years, target lesion failure occurred in 4.7% and 7.8% of O-SES and R-ZES groups, respectively (hazard ratio, 0.58; 95% confidence intervals, 0.24-1.41; p = .232 by log-rank test). Secondary endpoints including cardiac death, myocardial infarction, and target lesion revascularization showed no significant differences between the groups. Stent thrombosis occurred in two patients in R-ZES group (0.0% vs. 1.6%, p = .040)., Conclusion: This study confirms long-term safety and efficacy of the two stents. We found a trend for lower target lesion failure with O-SES compared to R-ZES, although statistically insignificant., (© 2019 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.)

Objectives/hypothesis: Papillary thyroid carcinoma (PTC) tends to metastasize rather early to local lymph nodes (LNs). Incidences of cystic LN metastases is relatively rare compared with that of solid LN metastases. Few studies have attempted to assess the characteristics in these patients. This study aimed to compare the clinicopathologic characteristics and surgical outcomes between patients with cystic LN metastases and those with solid LN metastases., Study Design: Retrospective cohort study., Methods: We retrospectively reviewed the data of 1,028 patients with N1b PTC who underwent bilateral total thyroidectomy with central compartment neck dissection and modified radical neck dissection between January 2005 and September 2011. Of these, 136 (13.2%) had cystic LN metastases and 892 (86.8%) had solid LN metastases. Clinicopathologic characteristics and surgical outcomes were compared between these two patient groups., Results: The proportion of patients with thyroid tumor multifocality was relatively higher in the cystic node cohort (19.9% vs. 12.7%, P = .048). The number of total metastatic LNs and positive lateral LNs was slightly higher in the cystic node cohort (11.3 ± 8.9 vs. 9.7 ± 7.5, P = .029 and 6.9 ± 6.3 vs. 5.5 ± 4.6, P = .018, respectively). The proportion of patients with recurrence was higher in the cystic node cohort (14.0% vs. 3.0%, P < .001). Multivariate analysis indicated that cystic nodes were a significant risk factor for recurrence (hazard ratio: 5.265, 95% confidence interval: 2.898-9.563)., Conclusions: This study demonstrates that cystic lateral LN metastases are associated with aggressive tumor behavior in PTC patients. and that their presence is a significant independent prognostic factor for disease-free survival., Level of Evidence: 2b Laryngoscope, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Longitudinal bone growth is primarily mediated by the growth plate, which is a specialized cartilaginous structure. Aggrecan, encoded by ACAN, is a primary proteoglycan component of the extracellular matrix in both the growth plate and articular cartilage. Aggrecanopathies have emerged as a phenotype of genetic skeletal disease in humans. A heterozygous ACAN mutation causes short stature, premature growth cessation, and accelerated bone age maturation. We report the case of a 15-year-old boy with familial short stature, with height of 149 cm (Korean standard deviation score [SDS] of -3.6) and weight of 50.5 kg (-1.48 SDS). He presented with mild midfacial hypoplasia, frontal bossing, a broad chest, and a short neck. The father's and mother's heights were 150 cm (-4.8 SDS) and 153 cm (-1.69 SDS), respectively. The patient's bone age was 2-3 years more advanced than his chronological age, and no endocrine abnormalities were detected. Wholeexome sequencing followed by Sanger sequencing revealed a heterozygous ACAN mutation, c.512C>T (p.Ala171Val), in both the proband and his father. Short stature is generally associated with a delayed bone age, and this case suggests that ACAN mutations may be the most likely etiology among patients with short stature and an advanced bone age and should warrant early treatment.

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves' disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.

Purpose: Paragangliomas (PGL) are rare neuroendocrine tumors derived from chromaffin cells of the autonomic nervous system. We aim to describe our experience and the long-term outcome of abdominal PGL over the last decade., Methods: A retrospective review of patients diagnosed with PGL in our hospital between November 2005 and June 2017 was conducted. All nonabdominal PGL were excluded and the clinicopathological features and long-term outcomes of the patients were analyzed., Results: A total of 46 patients were diagnosed with abdominal PGL. The average age of diagnosis was 55.4 years and there was no sex predilection. The average tumor size was 5.85 cm and they were predominantly located in the infrarenal position (50%). The mean follow-up period was 42 months (range, 1.8-252 months). All patients with metastases had Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) of ≥4. One patient presented with synchronous metastases while 2 developed local recurrence and distant metastases. One presented with only local recurrence. One patient died 5 years after diagnosis., Conclusion: Abdominal PGL is a rare tumor with excellent long-term prognosis. Recurrence although uncommon, can occur decades after initial diagnosis. Long-term follow-up is therefore recommended for all patients with PGL, especially in patients with PASS of ≥4., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2020, the Korean Surgical Society.)

A new tactile sensing module was proposed to sense the contact force and location of an object on a robot hand, which was attached on the robot finger. Three air pressure sensors are installed at the tip of the finger to detect the contacting force at the points. To obtain a nominal contact force at the finger from data from the three air pressure sensors, a force estimation was developed based upon the learning of a deep neural network. The data from the three air pressure sensors were utilized as inputs to estimate the contact force at the finger. In the tactile module, the arrival time of the air pressure sensor data has been utilized to recognize the contact point of the robot finger against an object. Using the three air pressure sensors and arrival time, the finger location can be divided into 3 × 3 block locations. The resolution of the contact point recognition was improved to 6 × 4 block locations on the finger using an artificial neural network. The accuracy and effectiveness of the tactile module were verified using real grasping experiments. With this stable grasping, an optimal grasping force was estimated empirically with fuzzy rules for a given object.

Sign language was designed to allow hearing-impaired people to interact with others. Nonetheless, knowledge of sign language is uncommon in society, which leads to a communication barrier with the hearing-impaired community. Many studies of sign language recognition utilizing computer vision (CV) have been conducted worldwide to reduce such barriers. However, this approach is restricted by the visual angle and highly affected by environmental factors. In addition, CV usually involves the use of machine learning, which requires collaboration of a team of experts and utilization of high-cost hardware utilities; this increases the application cost in real-world situations. Thus, this study aims to design and implement a smart wearable American Sign Language (ASL) interpretation system using deep learning, which applies sensor fusion that "fuses" six inertial measurement units (IMUs). The IMUs are attached to all fingertips and the back of the hand to recognize sign language gestures; thus, the proposed method is not restricted by the field of view. The study reveals that this model achieves an average recognition rate of 99.81% for dynamic ASL gestures. Moreover, the proposed ASL recognition system can be further integrated with ICT and IoT technology to provide a feasible solution to assist hearing-impaired people in communicating with others and improve their quality of life.