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Purpose Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitor (TKI) inhibitors. However, it is not clear whether other treatment modalities are involved in the histologic changes. Materials and methods We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available. Results Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined adenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non-small cell carcinomas. Only surgical treatment might induce histologic change. Three patients experienced two histologic changes, which the changed tumors returned to its original state or changed to a combined tumor after treatments. Four cases showed combined histology in first or second change. Two SqCas were changed to SCC. Conclusion The histology of non-small cell carcinoma can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occurred regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

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

Halide perovskites attract enormous attention as promising light absorption and emission materials for photovoltaics and optoelectronic applications. Here we report ternary diagrams of the phase, optical bandgap energy (Eg) and photoluminescence intensity of methylammonium lead halide (MAPbX3, where X = I, Br and Cl) perovskites, with three vertices of MAPbI3, MAPbBr3 and MAPbCl3. All the compositions were synthesized via a facile mechanochemical reaction at room temperature, to ensure the desired stoichiometries of the final products. Through structural study on MAPbX3, the phase diagram comprising a single phase region and two multi-phase regions was obtained. In the single phase region, the a-axis lattice constant increases almost linearly with increasing the average size of the X site ions. Interestingly, Eg decreases almost linearly with increasing the average size of the X site ions, giving negligible deviation from Vegard's law. As the result, a certain bandgap value, in the range of 1.55 - 2.9 eV, can be easily designed with infinite numbers of compositions. For the last, the ternary diagram of the photoluminescence intensity reveals the effective compositions for red, green and blue light emission. The comprehensive structural and optical information reported in this study is useful for designing halide perovskites for various applications. In addition, our approach for compositional mapping various characteristics using a solid-state reaction is an efficient and robust way to studying halide perovskites.

Objective The aim of this study was to identify clinicopathological factors that affect the number of lymph nodes (LNs) (12 or more) retrieved from patients with colorectal cancer (CRC), particularly those with pathologic T1 (pT1) disease. Methods From 429 CRC patients, 75 pT1 cancers were identified and digitally scanned. Binary logistic regression analysis was performed to identify the clinicopathological factors affecting the number of LNs retrieved from all 429 patients and from the subset of patients with pT1 CRC. Results For the 429 patients, the mean number of harvested LNs per specimen was 20 (median, 19). The number of retrieved LNs was independently associated with maximum tumor diameter > 2.3 cm and right-sided tumor location. The mean number of LNs retrieved from the 75 patients with pT1 CRC was 14 (median, 15); retrieval of 12 or more LNs from this group was independently associated with maximum tumor diameter > 14.1 mm. Conclusion The number of LNs retrieved from patients with CRC was associated with maximum tumor diameter and right-sided tumor location. For patients with pT1 CRC, maximum tumor diameter was independently associated with the harvesting of 12 or more LNs.

Background: The persistent vitelline vein is a portal venous system malformation arising during the embryonic period. These abnormal blood vessels frequently thrombose and can lead superior mesenteric vein obstruction or portal hypertension. Case report: We visualized a fetal intra-abdominal cystic mass with turbulent flow on prenatal ultrasound at 28 weeks' gestation. Initially diagnosed as an umbilical vein varix, it was later determined to be an extrahepatic persistent vitelline vein with an internal thrombus by postnatal ultrasound. It was successfully surgically excised. Conclusion: When an abnormal abdominal vascular structure near the umbilicus is found during prenatal ultrasonography, the persistent vitelline vein should be included in the differential diagnosis to allow prompt evaluation and treatment after birth.

Sebacic acid (SA) is an aliphatic ten-carbon dicarboxylic acid (1,10-decanedioic acid) with a variety of industrial applications, including the production of plasticizers, lubricants, cosmetics, and plastics. Currently, SA is produced exclusively from alkaline pyrolysis of castor oil. Herein, we present an environmentally friendly green route of SA production from plant oil-derived sources by microbial ω-oxidation. We genetically engineered β-oxidation-blocked diploid yeast Candida tropicalis, and created an effective microbial cell factory with an increase of 46% in SA production by overexpression of genes involved in ω-oxidation of hydrocarbons compared to the original strain. A biotransformation process of SA production from decanoic acid methyl ester was developed to overcome the challenges of high-density cell culture, substrate feed, substrate/intermediate toxicity, and foam generation. Fed-batch production of engineered C. tropicalis resulted in a molar yield of above 98%, a productivity of 0.57 g L−1 h−1, and a final titre of 98.3 g L−1 in a 5-litre fermenter and the results were successfully reproduced using a larger scale 50-litre fermenter. The produced SAs were successfully purified to >99.8% using acid precipitation and recrystallization. Finally, bio-nylon 610 was successfully synthesized by polymerization of the purified SA with hexamethylenediamine and showed thermal properties very similar to those of commercially available nylon 610. The processes developed and described in this study can be employed to produce and isolate SA for the synthesis of bio-nylons, using environmentally friendly procedures based on microbial biotransformation with potential industrial applications.

This letter proposes a CMOS divide-by-6 injection-locked frequency divider (ILFD) with a divide-by-2 current-mode logic (CML) stacked on a capacitive cross-coupled oscillator used as an LC divide-by-3 ILFD. The divide-by-6 ILFD in the TSMC 0.18 μm 1P6M CMOS process has a measured locking range 1.7 GHz from 8.4 GHz to 10.1 GHz at the power consumption of 10.6 mW. The divide-by-6 ILFD uses the CML FD with wide locking range to track the input frequency from the LC sub-ILFD output, and occupies a die area of $1.2\times 1.2$ mm2. The LC sub-ILFD uses a dual-resonance resonator with two resonant frequencies, which can be used to extend the locking range.

This letter studies the RF performance of wideband divide-by-2 injection-locked frequency dividers (ILFDs) with various inductor layouts in the 0.18 µm CMOS process. The ILFDs use an inductor composite in shunt with parasitic capacitors as the resonator, and they also use capacitive cross-coupled pairs to generate negative resistance for start-up oscillation. The gate biases of capacitive cross-coupled pairs are used to tune the free-running ILFD oscillation frequency. The first designed ILFD uses two octagonal inductors, the inductors in other two ILFDs use a twisted configuration and the ILFDs have low EM radiation level and less sensitive to received EM noise. These ILFDs have wide locking range because no varactors is in shunt with injection FETs.

This letter designs a class-D oscillator with frequency doubler implemented in the TSMC standard 0.18 µm BiCMOS processes. The die area is 1x1 mm2. At the supply voltage of 0.4 V below the nominal threshold voltage, the n-core oscillator outputs a frequency source at 2.80 GHz. This class-D oscillator with frequency doubler is made of a parallel LC resonator and a capacitive cross-coupled MOSFET pair with inductive gate voltage booting, which enables the class-D mode operation by switching the FETs to deep cut-off region in shorter time.

Colorectal large-cell neuroendocrine carcinomas (NECs) are extremely rare and have very poor prognosis compared to adenocarcinomas. A 74-year-old man presented with abdominal pain, diarrhea and hematochezia. The histopathologic report of colonoscopic biopsy performed at a local clinic was a poorly differentiated carcinoma. An abdominopelvic computed scan revealed irregularly enhanced wall thickening at the sigmoid colon with regional fat stranding and lymphnode enlargement. He underwent a laparoscopic high anterior resection with selective peritonectomy for peritoneal carcinomatosis, intraoperative peritoneal irrigation chemotherapy, and early postoperative intraperitoneal chemotherapy for 5 days. The tumor had a high proliferation rate (mitotic count > 50/10 HPFs and 90% of the Ki-67 index) and lymph-node metastases had occurred. On immunohistochemistry, the tumor cells expressed CD56 and synaptophysin. Large-cell NEC was confirmed. Systemic chemotherapy with cisplatin/etoposide was done. The patient is still alive after 3 years with no evidence of recurrence.

The effect of In doping on the sintering behaviors and electrical properties of Gd 0.1 Ce 0.9 O 1.95 (Gd-doped ceria, or GDC) was investigated. The solubility limit of In in GDC was determined to be ~2 at%, and the lattice parameter of GDC was found to decrease from 5.417(7) A to 5.416(5) A with 2 at% In dopant. The mean grain size of the sintered body decreased with increasing In content. The concentration of In did not significantly affect the conductivity of the samples; however, undoped GDC showed the highest conductivity. Cole-Cole plots showed that the activation energies of the grain boundaries and grain interiors decreased and increased, respectively, as the In concentration increased to 1 at%. The decreased grain-boundary activation energy is attributed to the segregation of the negatively charged dopant at the grain boundaries, while the increased activation energy of the grain interiors is attributed to the decreases in both the lattice parameters and binding energies with In doping.

Severe eating disorders characterized by repetitive episodes of purging and vomiting can occasionally trigger acute kidney injury. However, interstitial nephritis induced by episodes of repeated vomiting has rarely been reported, and the pathophysiology of this entity remains unknown. A 26-year-old man was admitted to our hospital because of known hypokalemia. His serum electrolyte profile showed: sodium 133 mEq/L, potassium 2.6 mEq/L, chloride 72 mEq/L, total carbon dioxide 50 mEq/L, blood urea nitrogen/creatinine ratio (BUN/Cr) 21.9/1.98 mg/dL, and magnesium 2.0 mg/dL. Arterial blood gas analysis showed: pH 7.557, partial pressure of carbon dioxide 65.8 mmHg, and bicarbonate 58.5 mEq/L. His urinary potassium concentration was 73.2 mEq/L, and Cr was 111 mg/dL. Renal biopsy revealed acute tubular necrosis and tubulointerstitial nephritis with a few shrunken glomeruli. Repeated psychogenic vomiting may precipitate acute kidney injury and interstitial nephritis secondary to volume depletion and hypokalemia. Serum electrolyte levels and renal function should be carefully monitored in patients diagnosed with eating disorders to prevent tubular ischemia and interstitial nephritis.

Tenosynovial giant cell tumor of diffuse type is a locally aggressive neoplasm that most commonly arises in the lower extremities. Herein, we report for the first time a case of an extra-articular tenosynovial giant cell tumor of diffuse type in the temporal region with brain parenchymal invasion. Imaging studies revealed an intracranial expansile mass in the temporal bone without involvement of the temporomandibular joint. The unusual location of the tumor without involvement of the joint and the presence of brain parenchymal invasion made this case challenging to diagnose.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays an important role in lung cancer progression. Here, we examined the therapeutic efficacy of CEACAM6 gene silencing using an siRNA delivery platform targeting the acidic tumour microenvironment in a lung adenocarcinoma xenograft mouse model. An siRNA delivery vector was constructed by tethering the peptide nucleic acid form of an siRNA targeting CEACAM6 (siCEACAM6) to a peptide with a low pH-induced transmembrane structure (pHLIP) to transport siRNAs across the plasma membrane. Specific binding of the pHLIP-siCEACAM6 conjugate to A549 lung adenocarcinoma cells at low pH was demonstrated by flow cytometry. A549 cells incubated with pHLIP-siCEACAM6 at an acidic pH showed downregulated expression of endogenous CEACAM6 protein and reduced cell viability. The in vivo tumour-suppressing effects of pHLIP-siCEACAM6 in lung adenocarcinoma were assessed in a xenograft model generated by injecting BALB/c nude mice with A549 cells. pHLIP-siCEACAM6 treatment alone resulted in tumour growth inhibition of up to 35.5%. When combined with cisplatin treatment, pHLIP-siCEACAM6 markedly enhanced tumour growth inhibition by up to 47%. In conclusion, the delivery of siCEACAM6 to lung adenocarcinoma using the pHLIP peptide has therapeutic potential as a unique cancer treatment approach.

The sintering behavior of Li-doped yttria-stabilized zirconia (YSZ) was investigated. Li doping in YSZ reduced the densification temperature and enhanced grain growth, as a result of the formation of a lithium-zirconate-related eutectic liquid during sintering. For 5 at% Li doping, the sample developed a duplex microstructure consisting of small grains with second phase particles in the inner region and large grains with pores in the surface region. The second phase of Li 2 ZrO 3 near the surface of the sample decomposed into Li 2 O and ZrO 2 , followed by the evaporation of Li 2 O during sintering, leaving behind large pores in the microstructure.

Image binarization is divided into global algorithm and local algorithm. Global binarization algorithms have a problem to describe objects that have similar brightness with a single threshold. Local binarization algorithms make boundary lines because these algorithms split the image into a specific size of blocks. Therefore, in this paper, we propose a binarization method to complement these problems. The proposed method uses triangular fuzzy membership function to classify the image into obvious regions and ambiguous regions. Obvious regions are binarized by using global binarization algorithm. Whereas ambiguous regions are binarized by using improved local algorithm. Experimental results show the proposed method binarizes the image with less information loss. Moreover, binarized image describes the object in more detail than global binarization methods and more natural than local binarization method.

The sintering behavior and electrical properties of Gd-doped CeO 2 (GDC), with and without Li 2 O as a sintering additive, were examined. With increasing Li 2 O content, the grain growth of GDC was enhanced because of an increase in the duration for which a Li-rich liquid phase existed during sintering. The migration of Li ions led to an increase in the electrical conductivity of the Li-doped GDC. When the Li-doped GDC was sintered at a high temperature of 1400 °C, the Li evaporated, resulting in a decrease in the electrical conductivity.

Background: Malignant pleural effusion (MPE) is a common complication of cancer cell metastasis to the pleura. Discrimination between MPE and benign pleural effusion is necessary to design treatment strategies. Cytology is important for the diagnosis of MPE. Carcinoembryonic antigen (CEA) is an epithelial biomarker with a strong staining pattern in adenocarcinomas. Here, the diagnostic performances of liquid-based cytology (LBC), cell block (CB) preparation, and CEA immunostaining for the detection of malignancy in effusion cytology were compared in a large case series. Methods: In a single institution, 1,014 cytology samples from 862 patients were retrospectively collected and reviewed between January 2013 and November 2015. Ethanol-fixed, paraffin embedded CB of pleural effusions was analyzed by CEA immunostaining. Diagnostic values were compared among LBC, CB, CEA immunostaining, and the combination of two methods. Results: The sensitivity and specificity of the CB preparation were 94.3% and 98.7%, respectively, compared with 81.3% and 99.4% for LBC preparations, respectively. Combination of LBC and CB increased sensitivity by 98.3%. Although the accuracy of CEA staining itself was moderate (sensitivity, 89.8%), the combined use of CB and CEA tumor marker increased the detection rate of malignancy (sensitivity, 100%; specificity, 100%), compared with that of cytology (LBC or CB) alone. Conclusions: The sensitivity and specificity for the diagnosis of MPE could be improved by integrating the CB and CEA staining into LBC in routine clinical practice to improve diagnostic accuracy.

Supplementary Material for Clinicopathological characteristics of costal hemangiomas: a case report and literature review by Chang Gok Woo, Ho-Chang Lee, Seung-Myoung Son, Jong-Myeon Hong and Ok-Jun Lee in Journal of International Medical Research

Image binarization is a process to divide the image into objects and backgrounds, widely applied to the fields of image analysis and its recognition. In the existing method of binarization, there is some uncertainty when there is insufficient brightness gap between objects and backgrounds in setting threshold. The method of fuzzy binarization has improved the features of objects efficiently. However, since this method sets ⍺-cut value statically, there remain some problems that important features of objects can be lost during binarization. Therefore, in this paper, we propose a binarization method which does not set α-cut value statically. The proposed method uses fuzzy membership functions calculated by thresholds of mean, iterative, and Otsu binarization. Experiment results show the proposed method binaries various images with less loss than the existing methods. 키워드 : 영상처리, 퍼지 이진화, 퍼지 로직, 퍼지 수리 연산, 영상 개선 Key word : Image Processing, Fuzzy Binarization, Fuzzy Logic, Fuzzy Arithmetic Operation , Image EnhancementJournal of the Korea Institute of Information andCommunication Engineering

Turner syndrome is the most common chromosomal disorder in girls. Various phenotypic features show depending upon karyotype from normal female through ambiguous genitalia to male. Usually, Turner girls containing 45,X/46,XY mosaicism, or sex-determining region Y (SRY) gene may have mixed gonadal dysgenesis with various external sexual differentiation. We experienced a short statured 45,X Turner girl with normal external genitalia. Because SRY gene was positive, laparoscopic gonadectomy was performed. The dysgenetic gonads revealed bilateral ovotesticular tissues. The authors report a mixed gonadal dysgenesis case found in clinical 45,X Turner patient with positive SRY gene. Screening for SRY gene should be done even the karyotype is 45,X monosomy and external genitalia is normal.

Polymer electrolyte membrane fuel cells (PEMFCs) are an up-and-coming technology for green and efficient power generation and offer a clean alternative to current technologies that use hydrocarbon fuel sources. In this paper, a reinforcing membrane was fabricated by Polyethylenimine polymer. Oxidized multiwalled carbon nanotube was dispersed into the PEI/Nafion membranes to achieve additional strength. The membranes were acidified via absorption of phosphoric acid from aqueous solution to make semi-interpenetrating polymer network (s-IPNs) which increases the proton conductivity by producing proton channel in the membrane. The PEI/Nafion/ox-MWCNT composite membranes show excellent phosphoric acid retention and high humidity, which impart a high ion exchange capacity (IEC) as well as improved proton conductivity. The surface morphologies and cross-sections of the resulting H3PO4 treated PEI/Nafion/ox-MWCNT composite membranes were observed using optical microscopy and scanning electron microscopy (SEM). The improvements in the thermal properties of the prepared PEI/Nafion/ox-MWCNT composite membranes were determined using thermogravimetric analysis (TGA). These performance results combined with the low inexpensive synthetic approach substantiate the potential for the new membrane to be used in PEMFCs.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays a crucial role in tumorigenesis of lung cancer. However, the therapeutic potential for anti CEACAM6 monoclonal antibody (mAb) has only been limitedly explored. Here, we evaluate the therapeutic potential of naked anti CEACAM6 mAb against lung adenocarcinoma. Clone 8F5, recognizing B domain of CEACAM6, is established by immunizing A549 cells and screening for clones double positive for A549 and CEACAM6-Fc recombinant protein. We found that 85.7% of 70 resected lung adenocarcinoma tissue sections were positive for CEACAM6, whereas all squamous cell carcinoma examined were negative. A549 cells with high levels of CEACAM6 demonstrated more aggressive growth nature and showed increased paclitaxel chemosensitivity upon 8F5 binding. Treatment with 8F5 to A549 decreased cellular CEACAM6 expression and reversed anoikis resistance. 8F5 also decreased cellular status of Akt phosphorylation and increased apoptosis via caspase activation. In a mouse model of lung adenocarcinoma with xenotransplanted A549 cells, 8F5 treatment alone demonstrated 40% tumor growth inhibition. When combined with paclitaxel treatment, 8F5 markedly enhanced tumor growth inhibition, up to 80%. In summary, we demonstrate that anti CEACAM6 mAb is an effective therapeutic treatment for lung adenocarcinoma whose effect is further enhanced by combined treatment with paclitaxel.