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Background: The incidence and prevalence of endometriosis remain unclear due to diagnostic difficulties. Especially, there has been little information regarding the population-based epidemiology of endometriosis. The purpose of this study is to estimate the prevalence and incidence of endometriosis in Korea based on the health insurance claims data. Methods: This study is a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort, which correspond to approximately 1 million Korean populations from 2002 to 2013. Patients aged 15–54 years were selected, and the prevalence and incidence of endometriosis were estimated by time and age groups. Results: The age-adjusted prevalence rate of endometriosis also increased from 2.12 per 1,000 persons (95% confidence interval [CI], 2.01–2.24) in 2002 to 3.56 per 1,000 persons (95% CI, 3.40–3.71) in 2013. The average adjusted incidence showed no statistically significant increase. However, the age-specific incidence of the 15–19 and 20–24 years age groups increased significantly from 0.24 and 1.29 per 1,000 persons in 2003 to 2.73 and 2.71 per 1,000 persons in 2013 (R2 = 0.93 and 0.77, P < 0.001), while the incidence rate of the age group 40–44 and 45–49 years decreased from 2.36 and 1.72 per 1,000 persons in 2003 to 0.81 and 0.27 per 1,000 persons in 2013 (R2 = 0.83 and 0.89, P < 0.001). Conclusion: The prevalence and incidence of endometriosis in Korean women were lower than that of previous reports in high-risk population studies. Furthermore, we found a significant increase in the diagnosis of endometriosis in younger age groups.

Early prediction of treatment response in nasopharyngeal carcinoma is clinically relevant for optimizing treatment strategies. This meta-analysis was performed to evaluate whether apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can predict treatment response of patients with nasopharyngeal carcinoma. A systematic search of PubMed-MEDLINE and Embase was performed to identify relevant original articles until July 22, 2021. We included studies which performed DWI for predicting locoregional treatment response in nasopharyngeal carcinoma treated with neoadjuvant chemotherapy, definitive chemoradiation, or radiation therapy. Hazard ratios were meta-analytically pooled using a random-effects model for the pooled estimates of overall survival, local relapse-free survival, distant metastasis-free survival and their 95% CIs. ADC showed a pooled sensitivity of 87% (95% CI 72–94%) and specificity of 70% (95% CI 56–80%) for predicting treatment response. Significant between-study heterogeneity was observed for both pooled sensitivity (I2 = 68.5%) and specificity (I2 = 92.2%) (P

Asymmetric subcellular mRNA localization allows spatial regulation of gene expression and functional compartmentalization. In neurons, localization of specific mRNAs to neurites is essential for cellular functioning. However, it is largely unknown how transcript sorting works in a sequence-specific manner. Here, we combined subcellular transcriptomics and massively parallel reporter assays and tested ∼50 000 sequences for their ability to localize to neurites. Mapping the localization potential of >300 genes revealed two ways neurite targeting can be achieved: focused localization motifs and broadly encoded localization potential. We characterized the interplay between RNA stability and localization and identified motifs able to bias localization towards neurite or soma as well as the trans-acting factors required for their action. Based on our data, we devised machine learning models that were able to predict the localization behavior of novel reporter sequences. Testing this predictor on native mRNA sequencing data showed good agreement between predicted and observed localization potential, suggesting that the rules uncovered by our MPRA also apply to the localization of native full-length transcripts.

The hole density of individual copper sulfide nanocrystals (Cu2-xS NCs) is determined from the stoichiometric mismatch (x) between copper and sulfide atoms. Consequently, the electronic properties of the material vary over a range of x. To exploit Cu2-xS NCs in devices, assemblies of NCs are typically required. Herein, we investigate the influence of x, referred to as the stoichiometric doping effect, on the structural, optical, electrical, and thermoelectric properties of electronically coupled Cu2-xS NC assemblies. The doping process is done by immersing the solid NC assemblies into a solution containing a Cu(I) complex for different durations (0-10 min). As Cu+ gradually occupied the copper-deficient sites of Cu2-xS NCs, x could be controlled from 0.9 to less than 0.1. Consequently, the near-infrared (NIR) absorbance of Cu2-xS NC assemblies changes systematically with x. With increasing x, electrical conductivity increased and the Seebeck coefficient decreased systematically, leading to the maximal thermoelectric power factor from a film of Cu2-xS NCs at an optimal doping condition yielding x = 0.1. The physical characteristics of the Cu2-xS NC assemblies investigated herein will provide guidelines for exploiting this emerging class of nanocrystal system based on doping.

PURPOSE Thermal ablation is a novel treatment alternative for benign thyroid nodules, and one of the most promising thermal ablation techniques is radiofrequency ablation (RFA). Considering the increasing use of thyroid RFA, some scientific societies have proposed clinical practice guidelines. We systemically reviewed and compared these guidelines for thyroid RFA to identify a standard treatment strategy that represents the positions of most societies. METHODS We searched the MEDLINE and EMBASE databases for studies with human participants that were published in English between January 1, 2000 and August 2, 2019. Studies containing clinical practice guidelines for the RFA of benign thyroid nodules were included. We extracted data regarding indications, pre- and post-procedural evaluations, treatment techniques, and the need to obtain informed consent. RESULTS Of the 83 studies found, four studies were included, and one study was added after searching the bibliographies of those articles. The five included studies were guidelines developed by the Korean Society of Thyroid Radiology, a group of experts from Italian scientific societies, the Italian Working Group on Minimally Invasive Treatments of the Thyroid, the United Kingdom's National Institute for Health and Clinical Excellence, and a group of four professional Austrian thyroid associations. Indications, pre- and post-procedural evaluations, and techniques were similar across studies; however, differences in each of these categories were found. CONCLUSION While the reviewed guidelines are similar with regard to major categories, international guidelines for the RFA of benign thyroid nodules should be established in the future.

Glomangiopericytoma is a rare sinonasal mesenchymal tumor of borderline or low malignant potential. We reviewed the CT and MR imaging findings of head and neck glomangiopericytoma via a retrospective case series study and systematic review. Our study revealed that glomangiopericytoma is a well-defined lobulated avidly enhancing soft-tissue mass with erosive bony remodeling that is most commonly found in the sinonasal cavity. Typically, it is hyperintense on T2-weighted images with vascular signal voids, has a high mean ADC value, and a wash-in and washout pattern on dynamic contrast-enhanced MR imaging. Although the CT findings are nonspecific, typical MR imaging findings, including those on the ADC map and dynamic contrast-enhanced MR imaging, may be helpful for differentiating glomangiopericytomas from other hypervascular tumors in the head and neck.

The hole density of individual copper sulfide nanocrystals (Cu

e18627 Background: Timely radiographic studies are essential to oncology care. At our institution, a safety net hospital in a large metropolitan area, baseline assessment determined that the overwhelming majority of outpatient computed tomographic (CT) scans for oncology patients were overdue for scheduling. We applied the Lean Kaizen quality improvement model to improve on-time scheduling of CT scans in our hematology-oncology clinic. Lean Kaizen is centered around eliminating waste, improving productivity, and maintaining sustained improvement through collaborative efforts from multiple departments to analyze system workflow inefficiencies in a stepwise fashion. Methods: In collaboration with our Kaizen Promotion Office, we conducted a series of interdisciplinary meetings including staff from radiology, oncology, scheduling, and administration. All aspects of the scheduling workflow were critically reviewed and barriers to scheduling were identified using an Ishikawa root-cause diagram and the Kaizen principle of gemba (“go and see the work”). A new workflow was developed in which clinic staff scheduled patients for CT scans prior to clinic discharge. To implement the new workflow, we employed the principles of shojinka (“create flow”) and nagara (“eliminate waste”). We developed and distributed workflow guides, conducted simulation events, and provided one-on-one training to ensure a successful rollout. Three months after our initial meeting, the new workflow was launched. The workflow was refined based on feedback from daily pre-clinic team meetings. Results: Preliminary data were gathered approximately 3 weeks following implementation of our new workflow. Since our intervention, the percentage of CT scans overdue for scheduling decreased from 87% (65 of 75 CT scans) to 17% (9 of 53 CT scans). Conclusions: Our study showed that the Lean Kaizen QI model was successful in improving the rate of oncology patients scheduled for CT scans in a timely fashion. This study demonstrated the importance of interdepartmental collaboration and continuous monitoring for improvement. Given the success of this project, this workflow will be expanded to other services within our institution following the Kaizen principle of yokoten (“sharing knowledge”).

To determine reproducible MRI parameters predictive of molecular subtype and risk stratification in glioma and develop a structured reporting system. All study patients were initially diagnosed with glioma, 141 from the Cancer Genome Atlas and 131 from our tertiary institution, as training and validation sets, respectively. Images were analyzed by three neuroradiologists with 1–7 years of experience. MRI features including contrast enhancement pattern, necrosis, margin, edema, T2/FLAIR mismatch, internal cyst, and cerebral blood volume higher than normal cortex were reported using a structured reporting system. The pathology was stratified into five risk types: (1) oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, 1p19q co-deleted; (2) diffuse astrocytoma, IDH-mutant, grade II–III; (3) glioblastoma, IDH-mutant, grade IV; (4) diffuse astrocytoma, IDH-wild, grade II–III; and (5) glioblastoma, IDH-wild, grade IV. Significant predictors were selected using multivariate logistic regression, and diagnostic performance was tested using a validation set. Reproducible imaging parameters exhibiting > 50% agreement across readers included the presence of necrosis, T2/FLAIR mismatch, internal cyst, and predominant contrast enhancement. In the validation set, prediction of risk type 5 exhibited the highest diagnostic performance with AUCs of 0.92 (reader 1) and 0.93 (reader 2) with predominant enhancement, followed by risk type 2 with AUCs of 0.95 and 0.95 with T2/FLAIR mismatch sign and no necrosis, and risk type 1 with AUCs of 0.84 and 0.83 with internal cyst or necrosis. Risk types 3 and 4 were difficult to visually predict. Imaging parameters with high reproducibility enabling prediction of IDH-wild-type glioblastoma, IDH-mutant/1p19q co-deletion oligodendroglioma, and IDH-mutant diffuse astrocytoma were identified. • Reproducible MRI parameters for determining molecular subtypes of glioma included the presence of necrosis, T2/FLAIR mismatch, internal cyst, and predominant contrast enhancement. • IDH-wild type glioblastoma, IDH-mutant/1p19q co-deletion oligodendroglioma, and IDH-mutant low-grade astrocytoma were identified using MRI parameters with high inter-reader reproducibility. • Identification of IDH-wild type low-grade glioma and IDH-mutant glioblastoma was difficult by visual analysis.

Organ morphogenesis is driven by a wealth of tightly orchestrated cellular behaviors, which ensure proper organ assembly and function. Many of these cell activities involve cell-cell interactions and remodeling of the F-actin cytoskeleton. Here, we analyze the requirement for Rasip1 (Ras-interacting protein 1), an endothelial-specific regulator of junctional dynamics, during blood vessel formation. Phenotype analysis of rasip1 mutants in zebrafish embryos reveals distinct functions of Rasip1 during sprouting angiogenesis, anastomosis and lumen formation. During angiogenic sprouting, loss of Rasip1 causes cell pairing defects due to a destabilization of tricellular junctions, indicating that stable tricellular junctions are essential to maintain multicellular organization within the sprout. During anastomosis, Rasip1 is required to establish a stable apical membrane compartment; rasip1 mutants display ectopic, reticulated junctions and the apical compartment is frequently collapsed. Loss of Ccm1 and Heg1 function mimics the junctional defects of rasip1 mutants. Furthermore, downregulation of ccm1 and heg1 leads to a delocalization of Rasip1 at cell junctions, indicating that junctional tethering of Rasip1 is required for its function in junction formation and stabilization during sprouting angiogenesis., Development, 148 (15), ISSN:0950-1991, ISSN:1477-9129

Background: Although uterine leiomyoma causes many problems, including infertility, there are few studies that have investigated the epidemiologic characteristics of uterine leiomyoma in South Korea. The aim of this study is to estimate the prevalence and incidence of uterine leiomyoma in South Korea and analyze the treatment trends. Materials and Methods: Women of reproductive age (15-54 years) were selected from the Korean National Health Insurance Service (NHIS) sample cohort dataset, which was collected from 2002 to 2013. Patients with uterine leiomyoma were identified by ICD-10 (International Codes of Disease, 10th Edition) and intervention codes. Prevalence and incidence were calculated from the NHIS cohort dataset and the treatment trends were analyzed for diagnosed patients. Results: The prevalence in overall age groups increased from 0.96% in 2002 to 2.43% in 2013, and the 1-year incidences of all age groups increased. The 26-30 age group showed the highest rate of 1-year incidence increase (2.14-folds, 0.33% in 2003 to 0.70% in 2013). The proportion of myomectomy increased from 22% in 2002 to 49% in 2013, whereas the proportion of hysterectomy decreased from 78% to 45%. Conclusions: The prevalence and incidence of uterine leiomyoma are increasing in South Korea as time progresses, and the rate of incidence increase is higher in younger reproductive women. Overall trends in uterine leiomyoma treatment are shifting to the methods of the saving uterus.

Organ morphogenesis is driven by a wealth of tightly orchestrated cellular behaviors, which ensure proper organ assembly and function. Many of these cell activities involve cell-cell interactions and remodeling of the F-actin cytoskeleton. Here, we analyze the requirement for Rasip1 (Ras-interacting protein 1), an endothelial-specific regulator of junctional dynamics, during blood vessel formation. Phenotype analysis ofrasip1mutants in zebrafish embryos reveal distinct requirements for Rasip1 during sprouting angiogenesis, vascular anastomosis and lumen formation. During angiogenic sprouting, Rasip1 is required for efficient cell pairing, which is essential for multicellular tube formation. High-resolution time-lapse analyses show that these cell pairing defects are caused by a destabilization of tricellular junctions suggesting that tri-cellular junctions may serve as a counterfort to tether sprouting endothelial cells during morphogenetic cell rearrangements. During anastomosis, Rasip1 is required to establish a stable apical membrane compartment;rasip1mutants display ectopic, reticulated junctions and the apical compartment is frequently collapsed. Loss of Ccm1 and Heg1 function leads to junctional defects similar to those seen inrasip1mutants. Analysis ofradil-bsingle andrasip1/radil-bdouble mutants reveal distinct and overlapping functions of both proteins. While Rasip1 and Radil-b have similar functions during angiogenic sprouting, the junction formation during anastomosis may primarily depend on Rasip1.

Ovarian cancer has a high mortality rate and high resistance to chemotherapy. Thus, many studies are currently assessing the ability of natural products to induce ovarian cancer cell death. A coumarin derivative, 4-methylumbelliferone (4-MU), has been reported to have anti-cancer effects on various cancers, but its effects on ovarian cancer are not fully understood. In this study, we identified the intracellular mechanism underlying the effects of 4-MU on epithelial ovarian cancer cells. Decreased ovarian cancer cell proliferation and an accumulation of cells in the G2/M phase were observed following 4-MU treatment. Moreover, 4-MU interfered with calcium homeostasis, induced endoplasmic reticulum stress in both cell lines, inhibited AKT and S6 phosphorylation, and increased ERK1/2, P38, and JNK phosphorylation. Furthermore, 4-MU and pharmacological inhibitors showed synergic effects in suppressing cell proliferation. Collectively, our current data indicate that antitumor effects of 4-MU could be appropriate for use as a therapeutic agent against epithelial ovarian cancer cells.

Imaging plays a key role in the diagnosis and characterization of thyroid diseases, and the information provided by imaging studies is essential for management planning. A referral guideline for imaging studies may help physicians make reasonable decisions and minimize the number of unnecessary examinations. The Korean Society of Thyroid Radiology (KSThR) developed imaging guidelines for thyroid nodules and differentiated thyroid cancer using an adaptation process through a collaboration between the National Evidence-based Healthcare Collaborating Agency and the working group of KSThR, which is composed of radiologists specializing in thyroid imaging. When evidence is either insufficient or equivocal, expert opinion may supplement the available evidence for recommending imaging. Therefore, we suggest rating the appropriateness of imaging for specific clinical situations in this guideline.

BACKGROUND AND PURPOSE: Although olfactory dysfunction is a common cranial nerve disorder, there are no simple objective morphometric criteria to assess olfactory dysfunction. The aim of this study was to evaluate the diagnostic performance of MR imaging morphometric parameters for detecting olfactory dysfunction. MATERIALS AND METHODS: This prospective study enrolled patients from those presenting with olfactory symptoms who underwent both an olfactory function test and MR imaging. Controls without olfactory dysfunction were recruited during the preoperative work-up for pituitary adenoma. Two independent neuroradiologists measured the olfactory bulb in 3D and assessed olfactory bulb concavity on MR imaging while blinded to the clinical data. Diagnostic performance was assessed using receiver operating characteristic curve analysis. RESULTS: Sixty-four patients and 34 controls were enrolled. The patients were significantly older than the controls (mean age, 57.8 ± 11.9 years versus 47.1 ± 12.1 years; P < .001). Before age adjustment, the olfactory bulb height was the only olfactory bulb parameter showing a significant difference between patients and controls (1.6 ± 0.3 mm versus 2.0 ± 0.3 mm, P < .001). After age adjustment, all parameters and olfactory bulb concavity showed significant intergroup differences, with the olfactory bulb height having the highest area under the curve (0.85). Olfactory bulb height was confirmed to be the only significant parameter showing a difference in the detection of olfactory dysfunction in 22 pairs after matching for age and sex (area under the curve = 0.87, P < .001). Intraclass correlation coefficients revealed moderate-to-excellent degrees of inter- and intrareader agreement. CONCLUSIONS: MR imaging morphometric analysis can differentiate patients with olfactory dysfunction, with the olfactory bulb height having the highest diagnostic performance for detecting olfactory dysfunction irrespective of age.

Objective We compared the expression levels of Mullerian inhibiting substance (MIS)/anti-Mullerian hormone type II receptor (AMHRII) in uterine myoma and adenomyosis to evaluate the possibility of using MIS/anti-Mullerian hormone (AMH) as a biological regulator or therapeutic agent in patients with uterine leiomyoma and adenomyosis. Methods We studied normal uterine myometrium, leiomyoma, endometrial tissue, and adenomyosis from 57 patients who underwent hysterectomy for uterine leiomyoma (22 cases) or adenomyosis (28 cases) and myomectomy for uterine myoma (7 cases). Immunohistochemical staining was used to confirm the MIS/AMHRII protein expression level in each tissue. Reverse transcription-polymerase chain reaction was performed to quantify MIS/AMHRII mRNA expression. Results The MIS/AMHRII protein was more strongly expressed in uterine myoma (frequency of MIS/AMHRII expressing cells: 51.95%±13.96%) and adenomyosis (64.65%±4.85%) tissues than that in the normal uterine myometrium (3.15%±1.69%) and endometrium (31.10%±7.19%). In the quantitative analysis of MIS/AMHRII mRNA expression, MIS/AMHRII mRNA expression levels in uterine myoma (mean density: 4.51±0.26) and adenomyosis (6.84±0.20) tissues were higher than that in normal uterine myometrial tissue (0.08±0.09) and endometrial tissue (1.63±0.06). Conclusion This study demonstrated that MIS/AMHRII was highly and strongly expressed on uterine myoma and adenomyosis. Our data suggest that MIS/AMH may be evaluated as a biological modulator or therapeutic agent on MIS/AMHRII expressing uterine myoma and adenomyosis.

Uterine leiomyomas are one of the most common benign gynecologic tumors, but the exact causes are not completely understood. In 2011, through DNA sequencing, MED12 mutation was discovered in approximately 71% of uterine leiomyomas. Several recent studies confirmed the high frequency of MED12 mutation in uterine leiomyoma. Nevertheless, no study has been done on MED12 mutation in the case of patients with multiple leiomyomas in a patient. The purpose of this study was to investigate the frequency of MED12 mutations in uterine leiomyomas of South Korean patients. In addition, we examined MED12 mutation in multiple leiomyomas in the same patients. Uterine leiomyoma tissues were obtained from symptomatic women who underwent hysterectomy or myomectomy for medically indicated reasons. We collected 60 uterine leiomyomas from 41 women. Tumor size ranged from 1 to 12cm. Patients' ages ranged from 25 to 55 years with an average of 38.4 years. Of the 60 tumors, 40 (66.67%) displayed MED12 mutation. Among the 41 patients, 14 patients had multiple leiomyomas and we analyzed those multiple leiomyomas. Three of them had the same mutations. Five of them, each leiomyoma had a different mutation. Two of them did not have mutation. Four of them had both mutation-positive and mutation-negative leiomyomas. In conclusion, we confirmed the high frequency of the MED12 mutation in uterine leiomyomas of South Korean patients. We also identified various MED12 mutation status in patients with multiple leiomyomas. This suggests that in a given patient, different tumors may have arisen from different cell origins and therefore it is supposed that occurrence of multiple leiomyoma in a single patient may not be caused by intrauterine metastasis or dissemination.

The Mis18 proteins (Mis18α, Mis18β, and M18BP1) are pivotal to the deposition of CENP-A at the centromere during cell cycle progression and are indispensable for embryonic development. Here, we show that Mis18α is critical for the proliferation of keratinocytes and stratification of the epidermis. Mice lacking Mis18α in the epidermis died shortly after birth, showing skin abnormalities like thin and translucent skin and defective skin barrier functions. The epidermis of newborn Mis18α-deficient mice lacked distinct stratification and mature hair follicles, with a reduction in the number of proliferating cells and increased cell death in the basal layer. Earlier expression of the Cre recombinase from keratin-14 promoter in the ventral region resulted in earlier keratinocyte death in the ventral part compared with the dorsal part in the absence of Mis18α, leading to more severe malformation of the ventral epidermal layers. As observed in Mis18α-deficient mouse keratinocytes, knockdown of Mis18α in HaCaT cells caused marked loss of centromeric CENP-A dots and chromosomal misalignment. Overall, we propose that Mis18α is important for epidermal cell proliferation and stratification, because it is required for the deposition of CENP-A at the centromeric nucleosomes.

Background Although radiofrequency ablation (RFA) is a safe treatment for thyroid tumors, nerve damage is a frequent complication. A previous retrospective study suggested that an injection of cold 5% dextrose in water (5% DW) can reduce nerve damage during RFA. This study validated the efficacy of injecting cold 5% DW for management of nerve damage during RFA. Methods Between November 2017 and December 2018, 242 patients underwent 291 RFA sessions for treatment of benign thyroid nodules or recurrent thyroid cancers. Using a standardized technique, cold (0°C to 4°C) 5% DW was immediately injected around the damaged nerve into patients with any symptoms suggesting nerve damage. The incidence of nerve damage, the volume of 5% DW injected, symptom recovery time and the incidence of permanent nerve damage were evaluated. Results Nineteen patients experienced nerve damage symptoms related to 21 RFA sessions, including 17 patients during 19 sessions and two patients on the day after two sessions. Patients with nerve damage symptoms detected during RFA were treated by injection of a mean 41 mL (range, 3 to 260) cold 5% DW, but the two patients who experienced symptoms the next day did not receive cold 5% DW injections. Immediate recovery was observed after 15 RFA sessions in 14 patients. No patient experienced permanent nerve damage. Conclusion Injection of cold 5% DW is effective in managing nerve damage during RFA of thyroid lesions.

Enhancing light–matter interactions is essential to improving nanophotonic and optoelectronic device performance. In the present work, we developed a new design for 3D plasmonic nanostructures with enhanced near-field interactions among the plasmonic nanomaterials. The 3D plasmonic nanostructures consisted of multilayered bottom Ag/polydimethylsiloxane (PDMS) nanostructures, an alumina middle layer, and top Ag nanoparticles (NPs). High areal density PDMS nanoprotrusions were self-organized by a simple maskless plasma etching process. The conformal deposition of alumina using atomic layer deposition and Ag deposition produced 3D plasmonic nanostructures. These structures induced multiple near-field interactions between the ultrahigh-areal-density (1400 μm−2) top Ag NPs and the underlying Ag nanostructures, and among the top Ag NPs themselves. The high density of hot spots across the 3D space yielded highly efficient and widely tunable plasmonic responses across the entire visible range. The SERS signal enhancement measured at the 3D plasmonic nanostructures was 3.9 times the signal measured at the 2D multilayered structures and 48.0 times the signal measured at a Ag NP layer deposited onto a Si substrate. Finally, the 3D plasmonic nanostructures exhibited excellent uniformity with a variation of 6.8%, based on a microscale Raman mapping analysis. The excellent Raman signal uniformity can be attributed to the ultrahigh areal density of the Ag NPs and the uniform thickness of the alumina spacing layer.

Highly roughened Au-decorated 3D ZnO nano-structures were prepared using a combination of prism holographic lithography and atomic layer deposition techniques. Prism holographic lithography is a simple and rapid method for fabricating ordered 3D nanostructures using the optical interference effects of multiple beams derived from a specially designed prism. Highly ordered reproducible surface-enhanced Raman scattering (SERS) substrates are needed for the reliable calibration of target analyte concentrations. A high density of Au nanoparticles separated by nanoscale gaps was generated on the Au-coated ZnO inverse structures. The nanogaps may function as strong hot spots for highly sensitive SERS-based chemical/biological sensors. The optimized SERS intensity from the prepared Au-coated 3D ZnO inverse structures was 20 times the intensity obtained from an Au-coated flat glass control substrate. The surfaces could be reused after the photocatalytic degradation and removal of adsorbates in the presence of ZnO. The Au-coated 3D ZnO structures described here offer an alternative to traditional single-use SERS substrates.

Mullerian inhibiting substance/anti-Mullerian hormone (MIS/AMH) is a regulator of the female reproductive system, an indicator of ovarian reserve and a growth inhibitor of Mullerian duct-derived tumors in vivo and in vitro. The objective of the present study was to analyze MIS/AMH type II receptor (MIS/AMHRII) protein and mRNA expression in healthy human endometria compared with patients with endometrial hyperplasia and endometrial cancer, providing a foundation for MIS/AMH as a biological modifier for treatment of endometrial hyperplasia and endometrial cancer. The present study included healthy endometrial tissues (n=20), simple endometrial hyperplasia tissues without atypia (n=17), complex endometrial hyperplasia tissues without atypia (n=24) and endometrial cancer tissues (n=8). The location and variation of MIS/AMHRII protein expression was observed by immunohistochemistry. The expression was graded by two pathologists and was categorized as follows: Negative, weakly positive, moderately positive or strongly positive. Reverse transcription-quantitative polymerase chain reaction was used to quantify MIS/AMHRII mRNA expression. The expression of MIS/AMHRII protein was observed in the cytoplasm of healthy human endometria, endometrial hyperplasia and endometrial cancer cells. The frequency of MIS/AMHRII protein expression was 20.22±10.35% in the proliferative phase of the healthy endometrium and 24.09±11.73% in the secretory phase of the healthy endometrium. However, no differences were observed in the menstrual cycle phases. The frequency was 54.50±16.59% in endometrial hyperplasia without atypia, 55.10±15.87% in endometrial hyperplasia with atypia and 73.88±15.70% in endometrial cancer, indicating that expression was enhanced as the disease progressed from healthy to malignant status. In endometrial hyperplasia, MIS/AMHRII protein expression was significantly associated with histological complexity compared with atypia status. The present study demonstrated that MIS/AMHRII is present in healthy endometria, endometrial hyperplasia and endometrial cancer. The low expression frequency of MIS/AMHRII was not significantly different among normal endometrial tissues, however, the protein expression was elevated in endometrial hyperplasia and endometrial cancer. These findings indicated that the study of bioactive MIS/AMH, as a possible treatment for tumors expressing the MIS/AMH receptor, is essential.

IntroductionAdministrative data are widely used to estimate epidemiologic indicators. The look-back period is needed to define baseline population for the incidence. However, short look-back period is known to overestimate incidence of diseases misclassifying prevalent cases to incident cases. A short look-back period with longer observation period causes misclassification more inconsistent. Objectives and ApproachThe purpose of the study is to estimate the incidence rate of uterine leiomyoma by adjusting the misclassification error. We selected 319,608 women aged 15- 54 in 2002 from Korean National Health Insurance Service (KNHIS) cohort data. 34,445 cases were identified during 2002 - 2013. We applied 1-year look-back period as of 2003 and the actual look-back period increases with year, which incurs inconsistent misclassification error. Multiple regression model was used to estimate the number of incidence cases of the 11th look-back year for each year. Annual and adjusted annual incidence rates of uterine leiomyoma were calculated and compared. ResultsThe annual number of patients(X1) is linearly related with the number of misclassification cases, and the number of misclassification cases are logarithmically associated with the look-back periods(X2). The regression equation was 0.07217 (y= 0.07217+ 0.00003213* X1 + 0.07992*ln(X2), R2=94.3). Crude incidence rate of uterine leiomyoma during the study period was 11.7% (35,992 cases) and adjusted rate was 10.5% (32,477cases). The annual incidence and adjusted annual incidence increased by 2.29 times and 2.86 times between 2003 and 2013, respectively. With look-back period of 11 years, 4,588(53.8 %) patients with uterine leiomyoma were estimated to have prior history of the disease. Conclusion/ImplicationsWe proposed an adjustment for the misclassification error according to look-back periods. The method is applicable to estimate various healthcare events such as disease incidences and healthcare usage. Although the regression model showed very strong R-squared, follow-up study after several years is needed to validate the study results.

3D hybrid plasmonic nanomaterials are composed of 3D-stacked Ag nanowires and nanoparticles separated by a nanoscale-thick alumina interlayer. The 3D hybrid plasmonic nanostructures exhibit strong plasmonic coupling between the ultrahigh populations of plasmonic nanomaterials, overcoming the physical limitation of inefficient plasmonic coupling of the Ag nanowire stacks.

Angiogenesis and vascular remodeling are driven by a wide range of endothelial cell behaviors, such as cell divisions, cell movements, cell shape and polarity changes. To decipher the cellular and molecular mechanism of cell movements, we have analyzed the dynamics of different junctional components during blood vessel anastomosis in vivo. We show that endothelial cell movements are associated with oscillating lamellipodia-like structures, which are orientated in the direction of these movements. These structures emerge from endothelial cell junctions and we thus call them junction-based lamellipodia (JBL). High-resolution time-lapse imaging shows that JBL are formed by F-actin based protrusions at the front end of moving cells. These protrusions also contain diffusely distributed VE-cadherin, whereas the junctional protein ZO-1 (Zona occludens 1) remains at the junction. Subsequently, a new junction is formed at the front of the JBL and the proximal junction is pulled towards the newly established distal junction. JBL function is highly dependent on F-actin dynamics. Inhibition of F-actin polymerization prevents JBL formation, whereas Rac-1 inhibition interferes with JBL oscillations. Both interventions disrupt endothelial junction formation and cell elongation. To examine the role of VE-cadherin (encoded by cdh5 gene) in this process, we generated a targeted mutation in VE-cadherin gene (cdh5ubs25), which prevents VE-cad/F-actin interaction. Although homozygous ve-cadherin mutants form JBL, these JBL are less dynamic and do not promote endothelial cell elongation. Taken together, our observations suggest a novel oscillating ratchet-like mechanism, which is used by endothelial cells to move along or over each other and thus provides the physical means for cell rearrangements.

Mis18α, a component of Mis18 complex comprising of Mis18α, Mis18β, and M18BP1, is known to localize at the centromere from late telophase to early G1 phase and plays a priming role in CENP-A deposition. Although its role in CENP-A deposition is well established, the other function of Mis18α remains unknown. Here, we elucidate a new function of Mis18α that is critical for the proper progression of cell cycle independent of its role in CENP-A deposition. We find that Aurora B kinase phosphorylates Mis18α during mitosis not affecting neither centromere localization of Mis18 complex nor centromere loading of CENP-A. However, the replacement of endogenous Mis18α by phosphorylation-defective mutant causes mitotic defects including micronuclei formation, chromosome misalignment, and chromosomal bridges. Together, our data demonstrate that Aurora B kinase-mediated mitotic phosphorylation of Mis18α is a crucial event for faithful cell cycle progression through the enhanced recruitment of polo-like kinase 1 to the kinetochore.

Objective To determine whether a computer-aided diagnosis (CAD) system for the evaluation of thyroid nodules is non-inferior to radiologists with different levels of experience. Materials and Methods Patients with thyroid nodules with a decisive diagnosis of benign or malignant nodule were consecutively enrolled from November 2017 to September 2018. Three radiologists with different levels of experience (1 month, 4 years, and 7 years) in thyroid ultrasound (US) reviewed the thyroid US with and without using the CAD system. Statistical analyses included non-inferiority testing of the diagnostic accuracy for malignant thyroid nodules between the CAD system and the three radiologists with a non-inferiority margin of 10%, comparison of the diagnostic performance, and the added value of the CAD system to the radiologists. Results Altogether, 197 patients were included in the study cohort. The diagnostic accuracy of the CAD system (88.48%, 95% confidence interval [CI] = 82.65–92.53) was non-inferior to that of the radiologists with less experience (1 month and 4 year) of thyroid US (83.03%, 95% CI = 76.52–88.02; p < 0.001), whereas it was inferior to that of the experienced radiologist (7 years) (95.76%, 95% CI = 91.37–97.96; p = 0.138). The sensitivity and negative predictive value of the CAD system were significantly higher than those of the less-experienced radiologists were, whereas no significant difference was found with those of the experienced radiologist. A combination of US and the CAD system significantly improved sensitivity and negative predictive value, although the specificity and positive predictive value deteriorated for the less-experienced radiologists. Conclusion The CAD system may offer support for decision-making in the diagnosis of malignant thyroid nodules for operators who have less experience with thyroid US.

The purpose of this study was to explore the positive effects of Jian-Pi-Zhi-Dong Decoction (JPZDD) on Tourette syndrome (TS) by investigating the expression of gamma-aminobutyric acid (GABA) and its type A receptor (GABAAR) in the striatum of a TS mice model. The model was induced by 3,3′-iminodipropionitrile (IDPN) treatment; then mice were divided into 4 groups (n=22, each); control and IDPN groups were gavaged with saline and the remaining 2 groups were gavaged with tiapride and JPZDD. We recorded the stereotypic behaviors of TS mice and measured the content of GABA in striatum by HPLC and GABAAR expression by immunohistochemistry and real-time PCR. Our results showed that JPZDD inhibited the abnormal behaviors of TS model mice and decreased GABA levels and GABAAR protein and mRNA expression in the striatum of TS model mice. In brief, the mechanism by which JPZDD alleviates TS symptoms may be associated with GABAAR expression downregulation in striatum which may regulate GABA metabolism.

We report new 3D hybrid plasmonic nanostructures exhibiting highly sensitive SERS-based sensing performance, utilizing efficient plasmonic light absorption and analyte-enrichment effect. The hybrid plasmonic nanostructures composed of 3D-stacked Ag NWs and NPs separated by a thin hydrophobic dielectric interlayer. A hydrophobic polydimethylsiloxane (PDMS) interlayer provides dielectric nanogap between Ag NWs and NPs, and analyte-enrichment effect due to the inhibition of drop spreading. The 3D hybrid PDMS-interlayered Ag nanostructures showed hydrophobicity with initial contact angle of 137.6°. Utilizing the analyte-enrichment strategy, the PDMS-interlayered Ag nanostructures exhibited an enhanced sensitivity of methylene blue molecules by a factor of 10 (limit of detection, LOD of 1.5 nM), compared to the alumina-separated 3D hybrid Ag nanostructures.