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Abstract High-energy impacts, like vehicle crashes or falls, can lead to pelvic ring injuries. Rapid diagnosis and treatment are crucial due to the risks of severe bleeding and organ damage. Pelvic radiography promptly assesses fracture extent and location, but struggles to diagnose bleeding. The AO/OTA classification system grades pelvic instability, but its complexity limits its use in emergency settings. This study develops and evaluates a deep learning algorithm to classify pelvic fractures on radiographs per the AO/OTA system. Pelvic radiographs of 773 patients with pelvic fractures and 167 patients without pelvic fractures were retrospectively analyzed at a single center. Pelvic fractures were classified into types A, B, and C using medical records categorized by an orthopedic surgeon according to the AO/OTA classification system. Accuracy, Dice Similarity Coefficient (DSC), and F1 score were measured to evaluate the diagnostic performance of the deep learning algorithms. The segmentation model showed high performance with 0.98 accuracy and 0.96–0.97 DSC. The AO/OTA classification model demonstrated effective performance with a 0.47–0.80 F1 score and 0.69–0.88 accuracy. Additionally, the classification model had a macro average of 0.77–0.94. Performance evaluation of the models showed relatively favorable results, which can aid in early classification of pelvic fractures.

The endotoxin test is based on the reaction between Limulus Amebocyte Lysate (LAL) and the lipopolysaccharides of Gram-negative bacteria. In this study, we sought to identify factors that interfere with the LAL testing of radiopharmaceuticals and evaluated acceptable ranges. A gel-clot LAL test and a chromogenic LAL test were used as endotoxin tests. We compared the performances of the EndosafeⓇ LAL and recombinant EndosafeⓇ Recombinant Cascade Reagent (rCR) cartridges for the chromogenic test. The factors that interfered with 68Ga-DOTATOC injection were pH, 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid (HEPES) buffer, and organic solvents, especially ethanol. However, interference by these factors was overcome by diluting the 68Ga-DOTATOC injection tenfold. In addition, no interference was observed at pH values between 4 and 8, at a HEPES concentration of 2,000 μg/mL, or an ethanol concentration of

Background Telmisartan is considered more potent than valsartan. Hemodynamic response during anesthesia induction may be influenced by anti-hypertension (HTN) medication. The present study compared the effect of anti-HTN medications on post-induction hypotension during noncardiac surgeries. Methods This observational study standardized the anesthetic regimen across patients, with hypotension defined as mean blood pressure (BP) of less than 65 mmHg. The hemodynamic changes within 5 min before and after endotracheal intubation, and within 10 min before and after surgical incision were measured. Transthoracic echocardiographic evaluation of the left ventricle (LV) during anesthesia induction was performed. The primary endpoint was the decline in mean BP after anesthetic administration in telmisartan and valsartan groups. Multivariate logistic regression analysis was used to identify predictors of post-induction hypotension. Results Data from 157 patients undergoing noncardiac surgery were analyzed. No significant differences were found in mean BP decline between the two groups during anesthesia induction. Hemodynamic changes and LV ejection fraction (EF) during anesthesia induction were similar between the groups. Age and preoperative initial mean BP in operation room (OR) were associated with post-induction hypotension in both groups. Conclusions The angiotensin receptor blocker (ARB) type did not influence post-induction hypotension during anesthesia induction. Age and preoperative initial mean BP in OR were associated with post-induction hypotension in patients taking ARBs.

Abstract With the recent increase in traffic accidents, pelvic fractures are increasing, second only to skull fractures, in terms of mortality and risk of complications. Research is actively being conducted on the treatment of intra-abdominal bleeding, the primary cause of death related to pelvic fractures. Considerable preliminary research has also been performed on segmenting tumors and organs. However, studies on clinically useful algorithms for bone and pelvic segmentation, based on developed models, are limited. In this study, we explored the potential of deep-learning models presented in previous studies to accurately segment pelvic regions in X-ray images. Data were collected from X-ray images of 940 patients aged 18 or older at Gachon University Gil Hospital from January 2015 to December 2022. To segment the pelvis, Attention U-Net, Swin U-Net, and U-Net were trained, thereby comparing and analyzing the results using five-fold cross-validation. The Swin U-Net model displayed relatively high performance compared to Attention U-Net and U-Net models, achieving an average sensitivity, specificity, accuracy, and dice similarity coefficient of 96.77%, of 98.50%, 98.03%, and 96.32%, respectively.

Background/Aims: Risk scoring systems for upper gastrointestinal (UGI) bleeding have not been well validated for tumor bleeding. This study aimed to identify risk factors for mortality in patients with UGI cancer bleeding and to develop a predictive model. Methods : Consecutive patients with UGI cancers who underwent esophagogastroduodenoscopy for suspected bleeding were retrospectively included. Patient characteristics, endoscopic findings and 30-day mortality were assessed. A predictive model was made based on risk factors for mortality using logistic regression, and the area under the curve (AUC) of this model was calculated. It was then compared with other risk scoring systems. Results : In a total of 264 patients, 193 had tumor bleeding. Among them, 108 (56.0%), 76 (39.4%), and nine (4.7%) patients received conservative treatment, endoscopic therapy, and non-endoscopic hemostasis, respectively. Rebleeding occurred in 23 (21.3%), 26 (34.2%), and one (11.1%) patient(s), respectively. Our new model is composed of altered mental status, renal failure, rebleeding, age older than 65 years, and low serum albumin (all p

[68Ga]Ga-FAPI-04 is a promising radiopharmaceutical that binds specifically to fibroblast activation protein, which is overexpressed in more than 90% of malignant epithelial tumors but not in normal healthy tissue. This study aimed to develop an efficient method for producing 68Ga-labelled FAPI-04 using a cassette-based automated synthesizer. [68Ga]GaCl3 was eluted from an Eckert & Ziegler Medical germanium-68/gallium-68 generator using 2.5 mL of 0.1 M HCl. The synthesis of the [68Ga]Ga-FAPI-04 was performed using different concentrations of HEPES (1~2.5 M; 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) in 3~10 minutes; amounts of FAPI-04 precursor (5~50 µg) and reaction temperature (25°C~100°C) were optimized on the BIKBoxⓇ synthesizer. The labeling efficiency of [68Ga]Ga-FAPI-04 was greater than 96% (decay corrected) using 25 µg FAPI-04 synthesized in 10 minutes at 100°C in 2 M HEPES (pH 3.85), and its stability was greater than 99% at 6 hours. The total synthesis time of [68Ga]Ga-FAPI-04 was 32.4 minutes, and the product met all quality control criteria. In this study, we developed and optimized a labeling method using [68Ga]Ga-FAPI-04 using a cassette-based synthesizer. The devised method is expected to be useful for supplying [68Ga]Ga-FAPI-04 for diagnosis in clinical practice.

Abstract Background The cause of early septic failure after two-stage exchange revision total knee arthroplasty (TKA) for chronic periprosthetic joint infection (PJI) and the factors affecting it are not well known. The purpose of this study was to determine the surgical outcomes and the risk factors for early septic failure after two-stage revision TKA for chronic PJI. Methods We identified a total of 246 adult patients who met the Musculoskeletal Infection Society (MSIS) diagnostic criteria for chronic PJI at two academic tertiary hospitals from March 2012 to December 2018. Finally, 151 patients who consecutively received two-stage exchange revision TKA for chronic PJI and who had a minimum 3-year follow-up were enrolled and retrospectively reviewed. Successful surgical treatment was evaluated for two-stage revision TKA and risk factors for early septic failure were identified. Results Early septic failures occurred within 3 years after reimplantation in 48 patients (31.8%). After accounting for potentially confounding variables, we found that male patient [odds ratio (OR): 2.753, 95% confidence interval (CI) 1.099–6.893, p = 0.031], fungus or mycobacterial infection (OR: 5.224, 95% CI 1.481–18.433, p = 0.01), and positive culture at reimplantation (OR: 4.407, 95% CI 1.255–15.480, p = 0.021) were independently associated with early septic failure after two-stage exchange revision TKA. Conclusion Male patients, fungus or mycobacterial infection, and positive culture at reimplantation were independently associated with an increased risk of early septic failure after two-stage exchange revision TKA despite normal C-reactive protein values prior to reimplantation. Further prospective and high-quality studies are needed to determine the risk factors of two-stage exchange revision TKA for chronic PJI. Level of evidence: level IV; retrospective comparison; treatment study.

[18F]Fluorocholine is a radiopharmaceutical used non-invasively in positron emission tomography to diagnose parathyroid adenoma, prostate cancer, and hepatocellular carcinoma by evaluating the choline metabolism. In this study, a radiolabeling method for [18F]fluorocholine was optimized using a solid phase extraction (SPE) cartridge. [18F]Fluorocholine was labeled in two steps using an automated synthesizer. In the first step, dibromomethane was reacted with [18F]KF/K2.2.2/K2CO3 to obtain the intermediate [18F]fluorobromomethane. In the second step, [18F]fluorobromomethane was passed through a Sep-PakⓇ Silica SPE cartridge to remove the impurities and then reacted with N,N-dimethylaminoethanol (DMAE) in a Sep-PakⓇ C18 SPE cartridge to label [18F]fluorocholine. The reaction conditions of [18F]fluorocholine were optimized. The synthesis yield was confirmed according to the number of silica cartridges and DMAE concentration. No statistically significant difference in the synthesis yield of [18F]fluorocholine was observed when using four or three silica cartridges (P＞0.05). The labeling yield was 11.5±0.5% (N=4) when DMAE was used as its original solution. On the other hand, when diluted to 10% with dimethyl sulfoxide, the radiochemical yield increased significantly to 30.1±5.2% (N=20). In conclusion, [18F]Fluorocholine for clinical use can be synthesized stably in high yield by applying an optimized synthesis method.

The germanium-68/gallium-68 (68Ge/68Ga) generator has high spatial utilization and requires little maintenance, making it economical and easy to produce. Thus, the frequency of use of 68Ga radiopharmaceuticals is rapidly increasing worldwide. Therefore, this study attempted to develop an automated synthesizer for the routine clinical application of 68Ga radiopharmaceuticals. The automated synthesizer was based on a fixed tubing system and the structure was designed after adjusting the position of the parts to reflect the synthesis method. Using various components that can be supplied in Korea, the automated synthesizer was manufactured at a much lower price cost than that of a commercialized automated synthesizer sold by companies. 68Ga-DOTA-[Tyr3]-octreotide (68Ga-DOTATOC) was synthesized to evaluate the performance of the automated synthesizer. 68Ga-DOTATOC could be synthesized with about 65% of non-decay corrected yield, and the synthesized 68Ga-DOTATOC met all quality control standards. We have synthesized 68Ga-DOTATOC more than 100 times, and only faced a few problems caused by mechanical errors. In this study, we successfully developed a simple automated synthesizer for 68Ga radiopharmaceuticals with high reproducibility. As various 68Ga radiopharmaceuticals have recently been developed, it is expected that the automated synthesizer developed in this study will be useful for routine clinical use.

Abstract Background The Rey Complex Figure Test (RCFT) has been widely used to evaluate the neurocognitive functions in various clinical groups with a broad range of ages. However, despite its usefulness, the scoring method is as complex as the figure. Such a complicated scoring system can lead to the risk of reducing the extent of agreement among raters. Although several attempts have been made to use RCFT in clinical settings in a digitalized format, little attention has been given to develop direct automatic scoring that is comparable to experienced psychologists. Therefore, we aimed to develop an artificial intelligence (AI) scoring system for RCFT using a deep learning (DL) algorithm and confirmed its validity. Methods A total of 6680 subjects were enrolled in the Gwangju Alzheimer’s and Related Dementia cohort registry, Korea, from January 2015 to June 2021. We obtained 20,040 scanned images using three images per subject (copy, immediate recall, and delayed recall) and scores rated by 32 experienced psychologists. We trained the automated scoring system using the DenseNet architecture. To increase the model performance, we improved the quality of training data by re-examining some images with poor results (mean absolute error (MAE) $$\ge$$ ≥ 5 [points]) and re-trained our model. Finally, we conducted an external validation with 150 images scored by five experienced psychologists. Results For fivefold cross-validation, our first model obtained MAE = 1.24 [points] and R-squared ( $${R}^{2}$$ R 2 ) = 0.977. However, after evaluating and updating the model, the performance of the final model was improved (MAE = 0.95 [points], $${R}^{2}$$ R 2 = 0.986). Predicted scores among cognitively normal, mild cognitive impairment, and dementia were significantly different. For the 150 independent test sets, the MAE and $${R}^{2}$$ R 2 between AI and average scores by five human experts were 0.64 [points] and 0.994, respectively. Conclusion We concluded that there was no fundamental difference between the rating scores of experienced psychologists and those of our AI scoring system. We expect that our AI psychologist will be able to contribute to screen the early stages of Alzheimer’s disease pathology in medical checkup centers or large-scale community-based research institutes in a faster and cost-effective way.

EGFRvIII is expressed only in tumor cells and strongly in glioblastoma and is considered a promising target in cancer diagnosis and therapy. Aptamers are synthetic single-stranded oligonucleotides that bind to biochemical target molecules with high binding affinity and specificity. This study examined the potential of the 68Ga-NOTA-EGFRvIII aptamer as a nuclear imaging probe for visualizing EGFRvIII-expressing glioblastoma by positron emission tomography (PET). EGFRvIII aptamer was selected using the SELEX technology, and flow cytometry and fluorescence microscopy verified the high binding affinity to EGFRvIII positive U87MG vIII 4.12 glioma cells but not to EGFRvIII negative U87MG cells. The EGFRvIII aptamer was conjugated with a chelator (1,4,7-triazanonane-1,4,7-triyl)triacetic acid (NOTA) for 68Ga-labeling. The 68Ga-NOTA-EGFRvIII aptamer was prepared using the preconcentration-based labeling method with a high radiolabeling yield at room temperature. Ex vivo biodistribution analyses confirmed the significantly higher tumor uptake of the 68Ga-NOTA-EGFRvIII aptamer in EGFRvIII-expressing xenograft tumors than that in EGFRvIII negative tumors, confirming the specific tumor uptake of the 68Ga-NOTA-EGFRvIII aptamer in vivo. PET imaging studies revealed a high retention rate of the 68Ga-NOTA-EGFRvIII aptamer in U87MG vIII 4.12 tumors but only low uptake levels in U87-MG tumors, suggesting that the 68Ga-NOTA-EGFRvIII aptamer may be used as a PET imaging agent for EGFRvIII-expressing glioblastoma.

Abstract Background Recent studies have shown that donor nephrectomy can induce renal function impairment. However, few meta-analysis studies about this have proceeded. Therefore, the objective of this systematic review and meta-analysis including all data of recent research studies was to determine whether living donor nephrectomy (LDN) could induce renal function impairment. Methods By November 2020, comprehensive literature searches were performed on PubMed, Embase, and Cochrane databases. Inclusion criteria were: (1) observational studies with data about overall end-stage renal disease (ESRD) or chronic kidney disease (CKD) of living kidney donors, (2) control group consisted of people without donor nephrectomy, and (3) outcomes of studies included long-term end-stage renal disease risks after living kidney donation. Risk of Bias in Non-randomized Studies of interventions (ROBINS-I) assessment tool was used to evaluate our methodological quality. Results The qualitative review included 11 studies and the meta-analysis included 5 studies. In the meta-analysis, the integrated overall ESRD risk was 5.57 (95% CI: 2.03—15.30). Regarding the overall risk of bias using ROBINS-I assessment tool, 0 studies was rated as "Low", 7 studies were rated as "moderate", 2 studies were rated as "Serious", and two studies were rated as "Critical". Conclusions Our study showed that LDN increased ESRD risk in LDN patients. However, in our meta-analysis, variables in included studies were not uniform and the number of included studies was small. To have a definite conclusion, meta-analyses of well-planned and detailed studies need to be conducted in the future.

Background/Aims Administrative databases provide valuable information for large-cohort studies. This study aimed to evaluate the diagnostic accuracy of an administrative database for resected gastric adenomas. Methods Data of patients who underwent endoscopic resection for benign gastric lesions were collected from three hospitals. Gastric adenoma cases were identified in the hospital database using International Classification of Diseases (ICD) 10-codes. The non-adenoma group included patients without gastric adenoma codes. The diagnostic accuracy for gastric adenoma was analyzed based on the pathological reports of the resected specimen. Results Among 5,095 endoscopic resections with codes for benign gastric lesions, 3,909 patients were included in the analysis. Among them, 2,831 and 1,078 patients were allocated to the adenoma and non-adenoma groups, respectively. Regarding the overall diagnosis of gastric adenoma with ICD-10 codes, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.7%, 88.5%, 95.2%, and 96.8%, respectively. There were no significant differences in these parameters between the tertiary and secondary centers. Conclusions Administrative codes of gastric adenoma, according to ICD-10 codes, showed good accuracy and can serve as a useful tool to study prognosis of these patients in real-world data studies in the future.

Depending on the degree of fracture, pelvic fracture can be accompanied by vascular damage, and in severe cases, it may progress to hemorrhagic shock. Pelvic radiography can quickly diagnose pelvic fractures, and the Association for Osteosynthesis Foundation and Orthopedic Trauma Association (AO/OTA) classification system is useful for evaluating pelvic fracture instability. This study aimed to develop a radiomics-based machine-learning algorithm to quickly diagnose fractures on pelvic X-ray and classify their instability. data used were pelvic anteroposterior radiographs of 990 adults over 18 years of age diagnosed with pelvic fractures, and 200 normal subjects. A total of 93 features were extracted based on radiomics:18 first-order, 24 GLCM, 16 GLRLM, 16 GLSZM, 5 NGTDM, and 14 GLDM features. To improve the performance of machine learning, the feature selection methods RFE, SFS, LASSO, and Ridge were used, and the machine learning models used LR, SVM, RF, XGB, MLP, KNN, and LGBM. Performance measurement was evaluated by area under the curve (AUC) by analyzing the receiver operating characteristic curve. The machine learning model was trained based on the selected features using four feature-selection methods. When the RFE feature selection method was used, the average AUC was higher than that of the other methods. Among them, the combination with the machine learning model SVM showed the best performance, with an average AUC of 0.75±0.06. By obtaining a feature-importance graph for the combination of RFE and SVM, it is possible to identify features with high importance. The AO/OTA classification of normal pelvic rings and pelvic fractures on pelvic AP radiographs using a radiomics-based machine learning model showed the highest AUC when using the SVM classification combination. Further research on the radiomic features of each part of the pelvic bone constituting the pelvic ring is needed.

Benign mediastinal cysts are challenging to diagnose. Although Endoscopic Ultrasound (EUS) and EUS-guided fine needle aspiration (FNA) can accurately diagnose mediastinal foregut cysts, little is known about their complications. This paper reports a rare case in which EUS-FNA performed on mediastinal hemangioma resulted in an aortic hematoma. A 29-year-old female patient was commissioned for EUS of an asymptomatic accidental mediastinal lesion. Chest CT revealed a 4.9×2.9×10.1 cm thin-walled cystic mass in the posterior mediastinum. EUS revealed a large, anechoic cystic lesion with a regular thin wall with negative Doppler. EUS-guided FNA was performed using a single-use 19-gauge aspiration needle (EZ Shot 3; Olympus, Tokyo, Japan), and approximately 70 cc of serous pinkish fluid was aspirated. The patient was in a stable condition with no signs of acute complication. One day after EUS-FNA, thoracoscopic resection for mediastinal mass was conducted. The purple and multi-loculated large cyst was removed. Upon removal, however, an aortic hematoma caused by a focal descending aortic wall injury was observed. After a few days of close observation, the patient was discharged upon stable 3D aorta angio CT findings. This paper reports a rare and severe complication of EUS-FNA, in which an aspiration needle caused a direct injury to the aorta. The injection must be performed carefully to avoid damaging the adjacent organs or digestive tract walls.

Abstract Purpose The aim of this study was to compare the anatomical structures of the acetabular rim around the anterior inferior iliac spine (AIIS) ridge that indicate anterior focal coverage of acetabulum between the sexes using a three-dimensional (3D) model. Methods 3D models of 71 adults (38 men and 33 women) with normal hip joints were used. Based on the location of the inflection point (IP) of the acetabular rim around the AIIS ridge, the patients were classified into anterior and posterior types, and the ratios thereof for each sex were compared. Coordinates for the IP, the most anterior point (MAP), and the most lateral point (MLP) were obtained and compared between the sexes and between anterior and posterior types. Results Coordinates for IPs in men were located anterior and inferior to those in women. MAP coordinates for men were located inferior to those for women, and MLP coordinates for men were located lateral and inferior to those for women. Comparing AIIS ridge types, we noted that coordinates for IPs of the anterior type were located medial, anterior, and inferior to those of the posterior type. Meanwhile, MAP coordinates of the anterior type were located inferior to those of the posterior type, and MLP coordinates of the anterior type were located lateral and inferior to those of the posterior type. Conclusion Anterior focal coverage of the acetabulum appears to differ between the sexes, and this difference may affect the development of pincer-type femoroacetabular impingement (FAI). Additionally, we found that anterior focal coverage differs according to anterior or posterior positioning of the bony prominence around the AIIS ridge, which may affect development of FAI.

Background/Aims Transcatheter arterial embolization (TAE) is useful for management of uncontrolled upper gastrointestinal (UGI) bleeding. We investigated clinical outcomes of TAE for non-variceal bleeding from benign UGI diseases uncontrolled with endoscopic intervention. Methods This retrospective study performed between 2017 and 2021 across four South Korean hospitals. Ninety-two patients (72 men, 20 women) who underwent angiography were included after the failure of endoscopic intervention for benign UGI disease- induced acute non-variceal bleeding. We investigated the factors associated with endoscopic hemostasis failure, the technical success rate of TAE, and post-TAE 30-day rebleeding and mortality rates. Results The stomach (52/92, 56.5%) and duodenum (40/92, 43.5%) were the most common sites of bleeding. Failure of endoscopic procedures was attributable to peptic ulcer disease (81/92, 88.0%), followed by pseudo-aneurysm (5/92, 5.4%), and angiodysplasia (2/92, 2.2%). Massive bleeding that interfered with optimal visualization of the endoscopic field was the most common indication for TAE both in the stomach (22/52, 42.3%) and duodenum (14/40, 35.0%). Targeted TAE, empirical TAE, and exclusive arteriography were performed in 77 (83.7%), nine (9.8%), and six patients (6.5%), respectively. The technical success rate, the post-TAE 30-day rebleeding rate, and the overall mortality rate were 100%, 22.1%, and 5.8%, respectively. On multivariate analysis, coagulopathy (OR, 5.66; 95% CI, 1.71~18.74; P=0.005) and empirical embolization (OR, 5.71; 95% CI, 1.14~28.65; P=0.034) were independent risk factors for post-TAE 30-day rebleeding episodes. Conclusions TAE may be useful for acute non-variceal UGI bleeding. Targeted embolization and correction of coagulopathy can improve clinical outcomes.

Hypoxia-induced neuronal death is a major cause of neurodegenerative diseases. Pyroptosis is a type of inflammatory programmed cell death mediated by elevated intracellular levels of reactive oxygen species (ROS). Therefore, we hypothesized that hypoxia-induced ROS may trigger pyroptosis via caspase-dependent gasdermin (GSDM) activation in neuronal cells. To test this, we exposed SH-SY5Y neuronal cells to cobalt chloride (CoCl2) to trigger hypoxia and then evaluated the cellular and molecular responses to hypoxic conditions. Our data revealed that CoCl2 induced cell growth inhibition and the expression of hypoxia-inducible factor-1α in SH-SY5Y cells. Exposure to CoCl2 elicits excessive accumulation of cytosolic and mitochondrial ROS in SH-SY5Y cells. CoCl2-induced hypoxia not only activated the intrinsic (caspases-3, -7, and -9) apoptotic pathway but also induced caspase-3/GSDME-dependent and NLRP3/caspase-1/GSDMD-mediated pyroptosis in SH-SY5Y cells. Importantly, inhibition of caspase-3 and -1 using selective inhibitors ameliorated pyroptotic cell death and downregulated GSDM protein expression. Additionally, treatment with a ROS scavenger significantly suppressed caspase- and pyroptosis-related proteins in CoCl2-treated SH-SY5Y cells. Our findings indicate that hypoxia-mediated ROS production plays an important role in the activation of both apoptosis and pyroptosis in SH-SY5Y neuronal cells, thus providing a potential therapeutic strategy for hypoxia-related neurological diseases.

Entosis is a process of cell cannibalism observed in cancer. Here, Sterling and colleagues report that entosis can also play a role in brain development and can contribute to the pathogenesis of microcephaly.

Collagenous gastroduodenitis is a rare gastrointestinal disease diagnosed histologically by subepithelial collagen deposition in the lamina propria. Its clinical presentation is diverse. The authors encountered a 17-year-old female patient who complained of epigastric pain. Endoscopy revealed several deep ulcers in the gastric body. The gastric mucosa around the ulcer showed diffuse fine nodularity in the shape of cobblestones with open-type atrophy. The duodenal mucosa showed nodular lesions similar to those of the gastric mucosa. The gastric ulcer healed completely with proton pump inhibitor treatment. The patient was followed up, showing no remarkable mucosal change of stomach or duodenum for several years. Collagenous gastroduodenitis was diagnosed by repeated histologic examinations. This paper reports a rare case of chronic collagen gastritis with deep gastric ulcer and its long-term clinical progress.

Toll-like receptor 3 (TLR3) plays an important role in double-stranded RNA recognition and triggers the innate immune response by acting as a key receptor against viral infections. Intracellular reactive oxygen species (ROS) are involved in TLR3-induced inflammatory responses during viral infections; however, their relationship with mitochondrial ROS (mtROS) remains largely unknown. In this study, we show that polyinosinic–polycytidylic acid (poly(I:C)), a mimic of viral RNA, induced TLR3-mediated nuclear factor-kappa B (NF-κB) signaling pathway activation and enhanced mtROS generation, leading to inflammatory cytokine production. TLR3-targeted small interfering RNA (siRNA) and Mito-TEMPO inhibited inflammatory cytokine production in poly(I:C)-treated BEAS-2B cells. Poly(I:C) recruited the TLR3 adaptor molecule Toll/IL-1R domain-containing adaptor, inducing IFN (TRIF) and activated NF-κB signaling. Additionally, TLR3-induced mtROS generation suppression and siRNA-mediated TRIF downregulation attenuated mitochondrial antiviral signaling protein (MAVS) degradation. Our findings provide insights into the TLR3-TRIF signaling pathway and MAVS in viral infections, and suggest TLR3-mtROS as a therapeutic target for the treatment of airway inflammatory and viral infectious diseases.

In the structural design of a roller-compacted concrete pavement (RCCP), it is crucial to estimate strain and stress developments in the RCCP slab realistically. Since the RCCP mix uses less cement and lower amount of water, shrinkage strain and concrete temperature during the hardening stage are expected to be reduced as compared to those of conventional concrete mixture, resulting in a reduction of the concrete early-age deformation and stress developments in the RCCP slab. In this paper, early-age concrete strain and stress developments in RCCP slab subjected to environmental loads were evaluated. A full-scale test section of RCCP under real climatic conditions was monitored. The early-age total strains, stress-independent strains, shrinkage strains, and coefficient of thermal expansion (CTE) of the RCCP were measured and analyzed. Using the results of measured strains, in-situ CTE and shrinkage strain, and temperature, the early-age concrete stress development is computed by incorporating a viscoelastic property of the early-age concrete. The results revealed that the shrinkage strain of the RCCP is quite low as compared to that of conventional concrete. The early-age stress developments in the RCCP slab are strongly governed by the thermal-induced stresses. Shrinkage-induced stresses were quite small and might be negligible in a preliminary estimation of early-age stress developments in the RCCP slab.

This paper introduces a machine learning based copy-move forgery (CMF) localization method. The basic convolutional neural network cannot be applied to CMF detection because CMF frequently involves rotation transformation. Therefore, we propose a rotation-invariant feature based on the root-mean squared energy using high-frequency wavelet coefficients. Instead of using three color image channels, two-scale energy features and low-frequency subband image are fed into the conventional VGG16 network. A correlation module is used by employing small feature patches generated by the VGG16 network to obtain the possible copied and moved patch pairs. The all-to-all similarity score is computed using the correlation module. To generate the final binary localization map, a simplified mask decoder module is introduced, which is composed of two simple bilinear upsampling and two batch-normalized-inception-based mask deconvolution followed by bilinear upsampling. We perform experiments on four test datasets and compare the proposed method with state-of-the-art tampering localization methods. The results demonstrate that the proposed scheme outperforms the existing approaches.

Aptamers have great potential for diagnostics and therapeutics due to high specificity to target molecules. However, studies have shown that aptamers are rapidly distributed and excreted from blood circulation due to nuclease degradation. To overcome this issue and to improve in vivo pharmacokinetic properties, inverted deoxythymidine (idT) incorporation at the end of aptamer has been developed. The goal of this study was to evaluate the biological characterization of 3'-idT modified ErbB2 aptamer and compare with that of unmodified aptamer via nuclear imaging. ErbB2-idT aptamer was labeled with radioisotope F-18 by base-pair hybridization using complementary oligonucleotide platform. The hyErbB2-idT aptamer demonstrated specific binding to targets in a ErbB2 expressing SK-BR-3 and KPL4 cells in vitro. Ex vivo biodistribution and in vivo imaging was studied in KPL4 xenograft bearing Balb/c nu/nu mice. 18F-hyErbB2-idT aptamer had significantly higher retention in the tumor (1.36 ± 0.17%ID/g) than unmodified 18F-hyErbB2 (0.98 ± 0.19%ID/g) or scrambled aptamer (0.79 ± 0.26% ID/g) at 1 h post-injection. 18F-hyErbB2-idT aptamer exhibited relatively slow blood clearance and delayed excretion by the renal and hepatobiliary system than 18F-hyErbB2 aptamer. In vivo PET imaging study showed that 18F-hyErbB2-idT aptamer had more stronger PET signals on KPL4 tumor than 18F-hyErbB2 aptamer. The results of this study demonstrate that attachment of idT at 3'-end of aptamer have a substantial influence on biological stability and extended blood circulation led to enhanced tumor uptake of aptamer.

Lesions diagnosed as gastric low-grade dysplasia (LGD) may be pathologically upgraded to early gastric cancer (EGC) or high-grade dysplasia (HGD) after endoscopic resection (ER). In this study, we investigated the risk factors for pathological upgrades after ER and assessed the reason for these upgrades by retrospectively analyzing ER data between January 1999 and December 2019. We enrolled patients with LGD confirmed by forceps biopsy; the patients were classified into pathologically concordant (LGD) and upgraded (HGD and EGC) groups according to the pathology of their resected specimen. To determine the risk factors for upgrade, we compared the endoscopic findings of the concordant and upgraded groups via 1:1 matched case-control design. To find the reasons for discordance, all upgraded cases were pathologically re-evaluated. Among 1,643 cases of LGD, pathological upgrades were observed in 423 (25.7%) resected specimens and EGC was found in 111 (6.7%) lesions. After matching the upgraded and concordant cases, lesion sizes exceeding 1.5 cm (odds ratio (OR): 1.8; 95% CI: 1.1-3.0), mucosal nodularity (OR: 10.8; 95% CI: 5.6-21.0), heterogeneous color (OR: 3.0; 95% CI: 1.7-5.3), presence of erosion (OR: 2.7; 95% CI: 1.8-5.3), and open-type gastric atrophy (OR: 2.9; 95% CI: 1.7-4.9) were noted to be significantly associated with upgraded pathology to EGC. Among the EGC cases, 99 (89.2%) were found to have pre-existing dysplasia. In conclusion, endoscopic evaluations should be performed because of possible pathological upgrades and co-existence of carcinomas in LGDs, especially when they exhibit surface nodularity, erosion, heterogeneous color, and large size.

Abstract Established genetic risk factors for Alzheimer’s disease (AD) account for only a portion of AD heritability. The aim of this study was to identify novel associations between genetic variants and AD-specific brain atrophy. We conducted genome-wide association studies for brain magnetic resonance imaging measures of hippocampal volume and entorhinal cortical thickness in 2643 Koreans meeting the clinical criteria for AD (n = 209), mild cognitive impairment (n = 1449) or normal cognition (n = 985). A missense variant, rs77359862 (R274W), in the SHANK-associated RH Domain Interactor (SHARPIN) gene was associated with entorhinal cortical thickness (p = 5.0 × 10−9) and hippocampal volume (p = 5.1 × 10−12). It revealed an increased risk of developing AD in the mediation analyses. This variant was also associated with amyloid-β accumulation (p = 0.03) and measures of memory (p = 1.0 × 10−4) and executive function (p = 0.04). We also found significant association of other SHARPIN variants with hippocampal volume in the Alzheimer’s Disease Neuroimaging Initiative (rs3417062, p = 4.1 × 10−6) and AddNeuroMed (rs138412600, p = 5.9 × 10−5) cohorts. Further, molecular dynamics simulations and co-immunoprecipitation indicated that the variant significantly reduced the binding of linear ubiquitination assembly complex proteins, SHPARIN and HOIL-1 Interacting Protein (HOIP), altering the downstream NF-κB signaling pathway. These findings suggest that SHARPIN plays an important role in the pathogenesis of AD.

Abstract Background To determine the 12-year incidence of and trends in rhegmatogenous retinal detachment (RRD) requiring surgery in Korea. Methods This was a nationwide, population-based, retrospective study. We identified 53,179 patients with incident RRD requiring surgery using the Korean National Health Claims Database from 2004 to 2015. We estimated the crude incidence rates and age- and sex-standardized incidence rates per 100,000 person-years in each year during the study period. A joinpoint regression analysis was performed to determine the trend. Results The average annual incidence rate was 9.78 (95% CI: 9.70–9.86). Male patients showed an incidence rate (10.68 [95% CI: 10.57–10.80]) 1.20 times that of female patients (8.87 [95% CI: 8.76–8.98]). The incidence showed a bimodal distribution; the highest peak was in the 60–64 year age group (23.77 [95% CI: 23.18–24.35]) and the second peak was in the 20–24 year age group (7.68 [95% CI: 7.41–7.95]). An increasing trend of RRD incidence was observed in the total population throughout the study period using joinpoint analysis (annual percentage change [APC], 2.05; 95% CI: 0.7–3.4). The increasing trend was more prominent among individuals aged under 50 years (APC, 3.44; 95% CI: 2.3–4.6), while among those aged 50 years or above, the increasing incidence was observed only in male patients. Conclusions In Korea, the incidence of RRD has increased recently. People in the

With the increasing availability of neuroimaging data from multiple modalities—each providing a different lens through which to study brain structure or function—new techniques for comparing, integrating, and interpreting information within and across modalities have emerged. Recent developments include hypothesis tests of associations between neuroimaging modalities, which can be used to determine the statistical significance of intermodal associations either throughout the entire brain or within anatomical subregions or functional networks. While these methods provide a crucial foundation for inference on intermodal relationships, they cannot be used to answer questions about where in the brain these associations are most pronounced. In this paper, we introduce a new method, called CLEAN-R, that can be used both to test intermodal correspondence throughout the brain and also to localize this correspondence. Our method involves first adjusting for the underlying spatial autocorrelation structure within each modality before aggregating information within small clusters to construct a map of enhanced test statistics. Using structural and functional magnetic resonance imaging data from a subsample of children and adolescents from the Philadelphia Neurodevelopmental Cohort, we conduct simulations and data analyses where we illustrate the high statistical power and nominal type I error levels of our method. By constructing an interpretable map of group-level correspondence using spatially-enhanced test statistics, our method offers insights beyond those provided by earlier methods.

Abstract Background Given that tau accumulation, not amyloid-β (Aβ) burden, is more closely connected with cognitive impairment in Alzheimer’s disease (AD), a detailed understanding of the tau-related characteristics of cognitive function is critical in both clinical and research settings. We investigated the association between phosphorylated tau (p-Tau) level and cognitive impairment across the AD continuum and the mediating role of medial temporal lobe (MTL) atrophy. We also developed a prediction model for abnormal tau accumulation. Methods We included participants from the Gwangju Alzheimer’s Disease and Related Dementia Cohort in Korea, who completed cerebrospinal fluid analysis and clinical evaluation, and corresponded to one of three groups according to the biomarkers of A and T profiles based on the National Institute on Aging and Alzheimer’s Association research framework. Multiple linear and logistic regression analyses were performed to examine the association between p-Tau and cognition and to develop prediction models. Receiver operating characteristic curve analysis was performed to examine the discrimination ability of the models. Results Among 185 participants, 93 were classified as A-T-, 23 as A+T-, and 69 as A+T+. There was an association between decreased visuospatial delayed memory performance and p-Tau level (B = − 0.754, β = − 0.363, p < 0.001), independent of other relevant variables (e.g., Aβ). MTL neurodegeneration was found to mediate the association between the two. Prediction models with visuospatial delayed memory alone (area under the curve [AUC] = 0.872) and visuospatial delayed memory and entorhinal thickness (AUC = 0.921) for abnormal tau accumulation were suggested and they were validated in an independent sample (AUC = 0.879 and 0.891, respectively). Conclusion It is crucial to identify sensitive cognitive measures that capture subtle cognitive impairment associated with underlying pathological changes. Preliminary findings from the current study might suggest that abnormal tau accumulation underlies episodic memory impairment, particularly visuospatial modality, in the AD continuum. Suggested models are potentially useful in predicting tau pathology, and might be utilized practically in the field.

Cnidium officinale Makino, a perennial crop in the Umbeliperae family, is one of Korea’s representative forest medicinal plants. However, the growing area of C. officinale has been reduced by plant disease and soil sickness caused by fusarium wilt. This study isolated rhizosphere bacteria from C. officinale, and their antagonistic activity was evaluated against Fusarium solani. Particularly, four isolated strains, namely, PT1, ST7, ST8, and SP4, showed a significant antagonistic activity against F. solani. An in planta test showed that the mortality rates of shoots were significantly low in the PT1-inoculated group. The fresh and dry weights of the inoculated plants were also higher than that of the other groups. The 16S rRNA gene sequencing identified the strain PT1 as Leclercia adecarboxylata, and downstream studies confirmed the production of antagonism-related enzymes such as siderophore and N-acetyl-β-glucosaminidase. The phosphorous solubilizing ability and secretion of related enzymes were also analyzed. The results showed that PT1 strain could be utilized as promising plant growth-promoting rhizobacteria (PGPR) and biocontrol agents (BCAs).

The present work deals with the high temperature deformation behavior of Fe-11.15Mn-5.6Al-0.07C (wt.%) triplex ferrite-based lightweight steel in the temperature range of 800–1100 °C under the strain rate of 0.001 to 0.1s−1. The compressive high temperature flow curves under the various thermomechanical conditions were accompanied by a considerable fractional softening. According to the detailed microstructural analysis, the observed flow softening was discussed relying on the occurrence of dynamic strain induced transformation and dynamic recrystallization. In this respect, a sine hyperbolic Arrhenius-type constitutive model was developed considering the three dimensional variation of the materials’ constant with strain, strain rate and temperature. This provided a proper condition for accurate assessment of the strain compensation mechanisms. The capability of the modified and un-modified constitutive models in prediction of the high temperature flow behavior of experimented low density steel were compared. According to the verified model, activation energy (Q) maps were developed and discussed in correlation with the characterized microstructure evolutions. The Q-plots were divided into three domains and a transition range was recognized at ~1100–1250 K, the extent of which decreased with increasing imposed strain. The low energy domains were attributed to the (i) activation of load transition as an effective strain compensation mechanism and the occurrence of dynamic austenite to ferrite transformation, and (ii) the high dislocation annihilation rate at high temperatures.

Abstract To evaluate the long-term outcomes of ranibizumab (RBZ) vs. aflibercept (AFL) in treatment-naïve eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). This multicenter, retrospective, matched-cohort analysis was conducted on data up to 4 years of follow-ups. The primary outcome was the visual acuity (VA) change from baseline. The secondary outcomes included the number of injections, proportion of eyes without a yearly injection, and the number of eyes with treatment switching. Subgroup analyses were performed for typical nAMD and PCV. Typical nAMD was defined as nAMD other than PCV. We included VA-matched 215 eyes of 209 patients (131 and 84 eyes with RBZ and AFL, respectively). The crude mean VA changes from baseline were + 6.7 vs. + 2.6, + 2.1 vs. − 0.4, − 1.3 vs. − 1.8, and − 2.2 vs. − 5.0 letters in the RBZ and AFL groups, at 1, 2, 3, and 4 years, respectively (p > 0.05). The adjusted predicted VA by linear mixed model, proportion of eyes stratified by VA, and the survival curve for significant vision loss were comparable during the 4-year follow-up (p > 0.05). The mean number of injections were similar between the RBZ and AFL groups (2.9 vs. 3.0, respectively, p = 0.692). The subgroup analysis for typical nAMD and PCV showed similar results between the groups. The visual outcomes did not differ between RBZ and AFL during 4 years with comparable numbers of injections. Our study reflects the long-term, real-world clinical practice and treatment pattern of two treatments for typical nAMD and PCV.

While clusterwise inference is a popular approach in neuroimaging that improves sensitivity, current methods do not account for explicit spatial autocorrelations because most use univariate test statistics to construct cluster-extent statistics. Failure to account for such dependencies could result in decreased reproducibility. To address methodological and computational challenges, we propose a new powerful and fast statistical method called CLEAN (Clusterwise inference Leveraging spatial Autocorrelations in Neuroimaging). CLEAN computes multivariate test statistics by modelling brain-wise spatial autocorrelations, constructs cluster-extent test statistics, and applies a refitting-free resampling approach to control false positives. We validate CLEAN using simulations and applications to the Human Connectome Project. This novel method provides a new direction in neuroimaging that paces with advances in high-resolution MRI data which contains a substantial amount of spatial autocorrelation.

Radiopharmaceuticals are drugs that contain radioisotopes and are used in the diagnosis, treatment, or investigation of diseases. Radiopharmaceuticals must be manufactured in compliance with good manufacturing practice regulations and subjected to quality control before they are administered to patients to ensure the safety of the drug. Radiopharmaceuticals for administration to humans need to be sterile and pyrogen-free. Hence, sterility tests and membrane filter integrity tests are carried out to confirm the asepticity of the finished drug product, and a bacterial endotoxin test conducted to assess contamination, if any, by pyrogens. The physical appearance and the absence of foreign insoluble substances should be confirmed by a visual inspection. The chemical purity, residual solvents, and pH should be evaluated because residual by-products and impurities in the finished product can be harmful to patients. The half-life, radiochemical purity, radionuclidic purity, and strength need to be assessed by analyzing the radiation emitted from radiopharmaceuticals to verify that the radioisotope contents are properly labeled on pharmaceuticals. Radiopharmaceuticals always carry the risk of radiation exposure. Therefore, the time taken for quality control tests should be minimized and care should be taken to prevent radiation exposure during handling. This review discusses the quality control procedures and acceptance criteria for a diagnostic radiopharmaceutical.

Objective To investigate the clinical factors associated with successful gastrostomy tube weaning in patients with prolonged dysphagia after stroke. Methods This study involved a retrospective medical chart review of patients diagnosed with prolonged dysphagia after stroke who underwent gastrostomy tube insertion between May 2013 and January 2020. Forty-seven patients were enrolled and consequently divided into gastrostomy tube sustaining and weaning groups. The numbers of patients in the sustaining and weaning groups were 31 and 16, respectively. The patients’ demographic data, Korean version of Mini-Mental State Examination (K-MMSE) score, Korean version of the Modified Barthel Index (K-MBI), Functional Dysphagia Scale (FDS) score, and Penetration-Aspiration Scale (PAS) score were compared between the two groups. A videofluoroscopic swallowing study was performed before making the decision of gastrostomy tube weaning. The clinical factors associated with gastrostomy tube weaning were then investigated. Results There were significant differences in age; history of aspiration pneumonia; K-MMSE, FDS, and PAS scores; and K-MBI between the groups. In the multiple logistic regression analysis, the FDS (odds ratio [OR]=0.791; 95% confidence interval [CI], 0.634–0.987) and PAS scores (OR=0.205; 95% CI, 0.059–0.718) were associated with successful gastrostomy tube weaning. In the receiver operating characteristic curve analysis, the FDS and PAS were useful screening tools for successful weaning, with areas under the curve of 0.911 and 0.918, respectively. Conclusion In patients with prolonged dysphagia, the FDS and PAS scores are the only factors associated with successful gastrostomy tube weaning. An evaluation of the swallowing function is necessary before deciding to initiate gastrostomy tube weaning.

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease, which causes high fever, thrombocytopenia, and death in humans and animals in East Asian countries. The pathogenicity of SFTS virus (SFTSV) remains unclear. We intraperitoneally infected three groups of mice: wild-type (WT), mice treated with blocking anti-type I interferon (IFN)-α receptor antibody (IFNAR Ab), and IFNAR knockout (IFNAR−/−) mice, with four doses of SFTSV (KH1, 5 × 105 to 5 × 102 FAID50). The WT mice survived all SFTSV infective doses. The IFNAR Ab mice died within 7 days post-infection (dpi) with all doses of SFTSV except that the mice were infected with 5 × 102 FAID50 SFTSV. The IFNAR−/− mice died after infection with all doses of SFTSV within four dpi. No SFTSV infection caused hyperthermia in any mice, whereas all the dead mice showed hypothermia and weight loss. In the WT mice, SFTSV RNA was detected in the eyes, oral swabs, urine, and feces at 5 dpi. Similar patterns were observed in the IFNAR Ab and IFNAR−/− mice after 3 dpi, but not in feces. The IFNAR Ab mice showed viral shedding until 7 dpi. The SFTSV RNA loads were higher in organs of the IFNAR−/− mice compared to the other groups. Histopathologically, coagulation necrosis and mononuclear inflammatory cell infiltration in the liver and white pulp atrophy in the spleen were seen as the main lesions in the IFN signaling lacking mice. Immunohistochemically, SFTSV antigens were mainly detected in the marginal zone of the white pulp of the spleen in all groups of mice, but more viral antigens were observed in the spleen of the IFNAR−/− mice. Collectively, the IFN signaling-deficient mice were highly susceptible to SFTSV and more viral burden could be demonstrated in various excreta and organs of the mice when IFN signaling was inhibited.

Objective To determine the immediate and short-term impact of the application of wearable balance compensation system (BCS) on balance impairment in patients with spinocerebellar ataxia (SCA). Methods The study enrolled 6 participants with SCA with varying degrees of balance impairment. After adjustment for individual fitting, wearable BCS with up to 3% body weight was placed in a garment on the trunk. Sway direction and magnitude were measured with sensors placed posteriorly at the lumbosacral junction, immediately before and after, and at day 1, day 2, and day 7 after wearing the BCS. Timed Up & Go test (TUG) and 25-foot timed walk test were performed, and static foot pressure was measured. Results A significant improvement in static and dynamic balance was found during the 25-foot timed walk and in static foot pressure measurement results after wearing the BCS, when compared with that at baseline (p=0.044 vs. p=0.011). Anterior and posterior sway showed improvements from baseline after wearing the BCS. Improvement in the lateral swaying movement control was also seen. Conclusion Application of the BCS might be beneficial in the improvement ofthe static and dynamic balance in patients with SCA. Further research on long-term effects and with a larger sample size is indicated.

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) strains are distinct from general Staphylococcus strains with respect to the composition of the membrane, ability to form a thicker biofilm, and, importantly, ability to modify the target of antibiotics to evade their activity. The agr gene is an accessory global regulator of gram-positive bacteria that governs virulence or resistant mechanisms and therefore an important target for the control of resistant strains. However, the mechanism by which agr impacts resistance to β-lactam antibiotics remains unclear. In the present study, we found the Δagr mutant strain having higher resistance to high concentrations of β-lactam antibiotics such as oxacillin and ampicillin. To determine the influence of variation in the microenvironment of cells between the parental and mutant strains, fatty acid analysis of the supernatant, total lipids, and phospholipid fatty acids were compared. The Δagr mutant strain tended to produce fewer fatty acids and retained lower amounts of C16, C18 fatty acids in the supernatant. Phospholipid analysis showed a dramatic increase in the hydrophobic longer-chain fatty acids in the membrane. To target membrane, we applied several surfactants and found that sorbitan monolaurate (Span20) had a synergistic effect with oxacillin by decreasing biofilm formation and growth. These findings indicate that agr deletion allows for MRSA to resist antibiotics via several changes including constant expression of mecA, fatty acid metabolism, and biofilm thickening.

Event sponsorship is considered as one major marketing strategy. Companies investing in sponsorship are growing rapidly. However, research on sponsorship has not been done in the depth management aspects of a sports organization and has been concentrated in specific areas. Thus, this research fills the gap by conducting the study to analyze the relationship between sponsor-event congruence on brand image, attitude toward the brand, and purchase intention in the context of sport sponsorship event in Indonesia. Questionnaires were distributed by applying a personally administered questionnaire to 200 respondents who participated in that event. Data were analyzed through structural equation modeling method. Results showed that there are 4 out of 6 hypotheses were supported. Those hypotheses are: there is a positive relationship between sponsor-event congruence and attitudes toward the brand; there is a positive relationship between attitudes toward the brand and purchase intention, there is a positive relationship between brand image and attitudes toward the brand, and there is a positive relationship between sponsor-event congruence and purchaseintention.

Abstract As more W replaced Mo in alumina-forming austenitic stainless steels, weight gain by oxidation decreased after 336 h at 1053 K. Electron microscopy revealed slower growth of scale in the presence of more numerous second phases by W addition. The retardation of oxidation was attributed to the necessary partitioning of W in front of the metal-oxide interface. The W-rich second phases interacted with growing oxides and finally transformed to fine particles of metallic W alloy within the scale.

Alzheimer’s disease is a neurodegenerative disease in which the degree of cortical atrophy in specific structures of the brain serves as a useful imaging biomarker. Recent approaches using linear mixed effects (LME) models in longitudinal neuroimaging have been powerful and flexible in investigating the temporal trajectories of cortical thickness. However, massive-univariate analysis, a simplified approach that obtains a summary statistic (e.g., a p-value) for every vertex along the cortex, is insufficient to model cortical atrophy because it does not account for spatial similarities of the signals in neighboring locations. In this article, we develop a permutation-based inference procedure to detect spatial clusters of vertices showing statistically significant differences in the rates of cortical atrophy. The proposed method, called SpLoc, uses spatial information to combine the signals adaptively across neighboring vertices, yielding high statistical power while controlling family-wise error rate (FWER) accurately. When we reject the global null hypothesis, we use a cluster selection algorithm to detect the spatial clusters of significant vertices. We validate our method using simulation studies and apply it to the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data to show its superior performance over existing methods. An R package for implementing SpLoc is publicly available.

Understanding the magnitude and causes of isotopic fractionation between organisms and their dietary resources is crucial for gaining knowledge on stable isotope ecology. However, little is known regarding the diet-tissue fractionation values of marine ciliates, which play a critical role in the reconstruction of microbial food webs. In the present study, we conducted experiments on two benthic (Pseudokeronopsis pararubra and Protocruzia labiata) and two pelagic (Strombidium sulcatum and Uronemella filificum) marine ciliates, where they were fed with isotopically constant foods (Chaetoceros calcitrans and Isochrysis galbana) under laboratory culture conditions to determine their carbon and nitrogen isotopic fractionation values (Δ13C and Δ15N). The stable isotope values (δ13C and δ15N) of ciliates for all experiments rapidly increased after the initial feeding, with half-lives ranging from 6.1 to 23.0h for δ13C and from 3.1 to 24.9h for δ15N. The Δ13C and Δ15N for all ciliates represented significantly positive enrichments, with overall mean fractionations of 0.6±0.2 and 1.2±0.4, respectively. Irrespective of the dietary type, both Δ13C and Δ15N were very similar for the same ciliate species. These results suggest that Δ13C and Δ15N for marine ciliates are similar to those found in common marine organisms with very little food-dependent variation. Overall, quantifying the specific isotopic fractionation of marine ciliates is expected to provide fundamental information on the trophic transfer of carbon, nitrogen, and energy flow through the microbial pathway in marine ecosystems.

Abstract The plasma proteins around nanoparticles (NPs) form an outer protein corona, significantly influencing the subsequent immune response. However, it was uncertain whether the protein corona around NPs influences immune response. This study clarified that the immune response mediated by the protein corona is greatly dependent on the type of plasma proteins surrounding the NPs. Structural changes in the unfolded protein corona elevated reactive oxygen species (ROS) levels and induced major proinflammatory cytokine release in both murine and human macrophage cell lines. In contrast, negligible structural changes in the protein corona provoke neither ROS production nor proinflammatory cytokine release. Furthermore, in vivo analysis confirms that a stimulated immune response by an unfolded protein corona triggers selective activation of innate and adaptive immunity in the spleen. Specifically, neutrophils, natural killer cells, and CD8+ T cells are overpopulated by unfolded protein corona structures surrounding nanotubes, whereas innate and adaptive immunologic responses are not triggered by a normal protein corona. In conclusion, highly unfolded protein corona structures are strongly correlated with subsequent activation of proinflammatory cytokines and innate immune responses; thus, the protein corona can be used in immune‐enhancing therapy.

In SmBa1-xCaxCo2O5+d (x = 0.01, 0.03, 0.1, and 0.2, SBCCO) oxide systems calcined at 1100°C for 8 h, the XRD patterns of the SBCCO single phase were maintained in the cases of SmBa0.97Ca0.03Co2O5+d (SBCCO-0.97) and SmBa0.99Ca0.01Co2O5+d (SBCCO-0.99) compositions. In SmBa0.8Ca0.2Co2O5+d (SBCCO-0.8) and SmBa0.9Ca0.1Co2O5+d (SBCCO-0.9), CaCoSmO4 existed with the pattern SBCCO. SBCCO structures were identified as orthorhombic crystal structures because they showed splitting of the X-ray diffraction (XRD) peaks at 23.4°, 47.9°, and 59.1°.Typical metallic conduction behaviors were found in all measured compositions except SBCCO-0.8, which showed a metal-insulator transition (MIT) behavior. Compared to other SmBa1-xCaxCo2O5+d compositions, SBCCO-0.8 showed the highest electrical conductivity of 460 S/cm at 500°C. In particular, SBCCO-0.9 was found to have an excellent ASR characteristic of about 0.077 Ωcm2 at 700°C. The activation energy of SBCCO-0.9 was the lowest among SBCCO oxide systems with a value of 0.77 eV.

When animals are faced with food depletion, food search-associated locomotion is crucial for their survival. Although food search-associated locomotion is known to be regulated by dopamine, it has yet to investigate the potential molecular mechanisms governing the regulation of genes involved in dopamine metabolism (e.g., cat-1, cat-2) and related behavioral disorders. During the studies of the pheromone ascaroside, a signal of starvation stress in C. elegans, we identified R02D3.7, renamed rcat-1 (regulator of cat genes-1), which had previously been shown to bind to regulatory sequences of both cat-1 and cat-2 genes. It was found that RCAT-1 (R02D3.7) is expressed in dopaminergic neurons and functions as a novel negative transcriptional regulator for cat-1 and cat-2 genes. When a food source becomes depleted, the null mutant, rcat-1(ok1745), exhibited an increased frequency of high-angled turns and intensified area restricted search behavior compared to the wild-type animals. Moreover, rcat-1(ok1745) also showed defects in state-dependent olfactory adaptation and basal slowing response, suggesting that the mutants are deficient in either sensing food or locomotion toward food. However, rcat-1(ok1745) has normal cuticular structures and locomotion genes. The discovery of rcat-1 not only identifies a new subtype of dopamine-related behaviors but also provides a potential therapeutic target in Parkinson’s disease.

Spinocerebellar ataxia (SCA) is a part of the cerebellar neurodegenerative disease group that is diverse in genetics and phenotypes. It usually shows autosomal dominant inheritance. SCAs, always together with the cerebellar degeneration, may exhibit clinical deficits in brainstem or eye, especially retina or optic nerve. Interestingly, autosomal dominant SCAs share a common genetic mechanism; the length of the glutamine chain is abnormally expanded due to the increase in the cytosine–adenine–guanine (CAG) repeats of the disease causing gene. Studies have suggested that the mutant ataxin induces alteration of protein conformation and abnormal aggregation resulting in nuclear inclusions, and causes cellular loss of photoreceptors through a toxic effect. As a result, these pathologic changes induce a downregulation of genes involved in the phototransduction, development, and differentiation of photoreceptors such as CRX, one of the photoreceptor transcription factors. However, the exact mechanism of neuronal degeneration by mutant ataxin restricted to only certain type of neuronal cell including cerebellar Purkinje neurons and photoreceptor is still unclear. The most common SCAs are types 1, 2, 3, 6, 7, and 17 which contain about 80% of autosomal dominant SCA cases. Various aspects of eye movement abnormalities are evident depending on the degree of cerebellar and brainstem degeneration in SCAs. In addition, certain types of SCAs such as SCA7 are characterized by both cerebellar ataxia and visual loss mainly due to retinal degeneration. The severity of the retinopathy can vary from occult macular photoreceptor disruption to extensive retinal atrophy and is correlated with the number of CAG repeats. The value of using optical coherence tomography in conjunction with electrodiagnostic and genetic testing is emphasized as the combination of these tests can provide critical information regarding the etiology, morphological evaluation, and functional significances. Therefore, ophthalmologists need to recognize and differentiate SCAs in order to properly diagnose and evaluate the disease. In this review, we have described and discussed SCAs showing ophthalmic abnormalities with particular attention to their ophthalmic features, neurodegenerative mechanisms, genetics, and future perspectives.

Abstract Background We propose a gene-level association test that accounts for individual relatedness and population structures in pedigree data in the framework of linear mixed models (LMMs). Our method data-adaptively combines the results across a class of score-based tests, only requiring fitting a single null model (under the null hypothesis) for the whole genome, thereby being computationally efficient. Results We applied our approach to test for association with the high-density lipoprotein (HDL) ratio of post- and pretreatments in GAW20 data. Using the LMM similar to that used by Aslibekyan et al. (PLos One, 7:48663, 2012), our method identified 2 nearly significant genes (APOA5 and ZNF259) near rs964184, whereas neither the other gene-level tests nor the standard test on each individual single-nucleotide polymorphism (SNP) detected any significant gene in a genome-wide scan. Conclusions Gene-level association testing can be a complementary approach to the SNP-level association testing and our method is adaptive and efficient compared to several other existing gene-level association tests.

Abstract DNA methylation plays an important role in normal human development and disease. In epigenome-wide association studies (EWAS), a univariate test for association between a phenotype and each cytosine-phosphate-guanine (CpG) site has been widely used. Given the number of CpG sites tested in EWAS, a stringent significance cutoff is required to adjust for multiple testing; in addition, multiple nearby CpG sites may be associated with the phenotype, which is ignored by a univariate test. These two factors may contribute to the power loss of a univariate test. As an alternative, we propose applying an adaptive gene-based test that is powerful in genome-wide association studies (GWAS), called aSPUw, to EWAS for simultaneous testing on multiple CpG sites within or near a gene. We show its application to the GAW20 methylation data set.