• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.155-164
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• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• Journal of Biomedical Engineering Research
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• v.43 no.5
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• pp.341-352
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• 2022

Medical image segmentation is the most important task in radiation therapy. Especially, when segmenting medical images, the liver is one of the most difficult organs to segment because it has various shapes and is close to other organs. Therefore, automatic segmentation of the liver in computed tomography (CT) images is a difficult task. Since tumors also have low contrast in surrounding tissues, and the shape, location, size, and number of tumors vary from patient to patient, accurate tumor segmentation takes a long time. In this study, we propose a method algorithm for automatically segmenting the liver and tumor for this purpose. As an advantage of setting the boundaries of the tumor, the liver and tumor were automatically segmented from the CT image using the 2D CoordConv DeepLab V3+ model using the CoordConv layer. For tumors, only cropped liver images were used to improve accuracy. Additionally, to increase the segmentation accuracy, augmentation, preprocess, loss function, and hyperparameter were used to find optimal values. We compared the CoordConv DeepLab v3+ model using the CoordConv layer and the DeepLab V3+ model without the CoordConv layer to determine whether they affected the segmentation accuracy. The data sets used included 131 hepatic tumor segmentation (LiTS) challenge data sets (100 train sets, 16 validation sets, and 15 test sets). Additional learned data were tested using 15 clinical data from Seoul St. Mary's Hospital. The evaluation was compared with the study results learned with a two-dimensional deep learning-based model. Dice values without the CoordConv layer achieved 0.965 ± 0.01 for liver segmentation and 0.925 ± 0.04 for tumor segmentation using the LiTS data set. Results from the clinical data set achieved 0.927 ± 0.02 for liver division and 0.903 ± 0.05 for tumor division. The dice values using the CoordConv layer achieved 0.989 ± 0.02 for liver segmentation and 0.937 ± 0.07 for tumor segmentation using the LiTS data set. Results from the clinical data set achieved 0.944 ± 0.02 for liver division and 0.916 ± 0.18 for tumor division. The use of CoordConv layers improves the segmentation accuracy. The highest of the most recently published values were 0.960 and 0.749 for liver and tumor division, respectively. However, better performance was achieved with 0.989 and 0.937 results for liver and tumor, which would have been used with the algorithm proposed in this study. The algorithm proposed in this study can play a useful role in treatment planning by improving contouring accuracy and reducing time when segmentation evaluation of liver and tumor is performed. And accurate identification of liver anatomy in medical imaging applications, such as surgical planning, as well as radiotherapy, which can leverage the findings of this study, can help clinical evaluation of the risks and benefits of liver intervention.

• The Korean Society of Law and Medicine
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• v.23 no.1
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• pp.121-148
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• 2022

CRISPR-Cas9 is one of the gene-editing technologies that infinite potential. It may provide human beings with many benefits or cause unanticipated challenges. The governance as standards setting or regulation of gene-editing technologies can contribute to keeping a balance between scientific value and ethical commitments. Guaranteeing public participation provides an additional opportunity to think about ethical and moral considerations: For whose benefit the internationally discussed governance of gene-editing technologies is directed at? There is a doubt regarding whether the governance justifies scientific researchers' gene-editing research. Suppose that governance promotes the advancement of CRISPR-Cas9, it should also encourage greater research responsibility. If not, there may be tragedies brought about by the misconduct of researchers. Thus, the essential matter on the governance for the research of CRISPR-Cas9 is the researchers' responsibility.

• The Korea Journal of Herbology
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• v.35 no.1
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• pp.57-68
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• 2020

Objective : The aim of present study was to clarify the effect of Areca Semen and Toosendan Fructus Mixture (AT-mix) on chronic reflux esophagitis (CRE) in rats. Methods : The antioxidant activity of AT-mix was measured through DPPH and ABTS radical scavenging activities in vitro. CRE was induced in SD rats (5 weeks, male) by ligating the border forestomach and granular portion with 2-0 silk and the duodenum near the pyloric portion was covered with 2-mm wide piece of 18-Fr Nélaton catheter. And then rats were treated AT-mix 200 mg/kg one daily for 14 days. The anti-oxidant and inflammatory protein levels were evaluated using western blotting. Results : Gross lesion of esophageal mucosa after AT-mix treatment showed a superior enhancement compared with that of CRE control rats. AT-mix treatment strongly reduced both DPPH and ABTS radical scavenging activities (DPPH, IC₅₀ 8.15±0.14 ㎍/mL; ABTS, IC₅₀ 24.69±0.03 ㎍/mL, repspectively). Levels of the NADPH oxidase subunit including NOX4 and p22^phox increased in CRE control rats. Otherwise, AT-mix treatment significantly reduced. The activation of Nuclear factor-erythroid 2-related factor 2 (Nrf2) led to significantly the up-regulation of HO-1. The inhibition of IκBα phosphorylation led to NF-κB inactivation. Subsequently, NF-κB inactivation significantly induced the decrease of COX-2, iNOS, TNF-α, and IL-6 protein expressions. Conclusion : Taken together, these results suggest that AT-mix treatment can attenuate the esophageal mucosal ulcer though inhibiting NF-κB pathway and enhancing Nrf2/HO-1 pathway. Thus, the additional mechanism study about AT-mix would need for the development as a safe herbal therapy for CRE.

• Nuclear Engineering and Technology
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• v.55 no.8
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• pp.2935-2940
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• 2023

A polystyrene phantom was developed following the guidance of the International Atomic Energy Association (IAEA) for gamma knife (GK) quality assurance. Its performance was assessed by measuring the absorbed dose rate to water and dose distributions. The phantom was made of polystyrene, which has an electron density (1.0156) similar to that of water. The phantom included one outer phantom and four inner phantoms. Two inner phantoms held PTW T31010 and Exradin A16 ion chambers. One inner phantom held a film in the XY plane of the Leksell coordinate system, and another inner phantom held a film in the YZ or ZX planes. The absorbed dose rate to water and beam profiles of the machine-specific reference (msr) field, namely, the 16 mm collimator field of a GK Perfexion^TM or Icon^TM, were measured at seven GK sites. The measured results were compared to those of an IAEA-recommended solid water (SW) phantom. The radius of the polystyrene phantom was determined to be 7.88 cm by converting the electron density of the plastic, considering a water depth of 8 g/cm². The absorbed dose rates to water measured in both phantoms differed from the treatment planning program by less than 1.1%. Before msr correction, the PTW T31010 dose rates (PTW Freiberg GmbH, New York, NY, USA) in the polystyrene phantom were 0.70 (0.29)% higher on average than those in the SW phantom. The Exradin A16 (Standard Imaging, Middleton, WI, USA) dose rates were 0.76 (0.32)% higher in the polystyrene phantom. After msr correction factors were applied, there were no statistically significant differences in the A16 dose rates measured in the two phantoms; however, the T31010 dose rates were 0.72 (0.29)% higher in the polystyrene phantom. When the full widths at half maximum and penumbras of the msr field were compared, no significant differences between the two phantoms were observed, except for the penumbra in the Y-axis. However, the difference in the penumbra was smaller than variations among different sites. A polystyrene phantom developed for gamma knife dosimetry showed dosimetric performance comparable to that of a commercial SW phantom. In addition to its cost effectiveness, the polystyrene phantom removes air space around the detector. Additional simulations of the msr correction factors of the polystyrene phantom should be performed.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.366-386
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• 2023

Objective: In this study, a questionnaire survey was conducted for doctors and patients to obtain basic data necessary for the development of an integrated medical system for idiopathic pulmonary fibrosis (IPF). Methods: Questionnaires were developed separately for doctors and patients through an expert group meeting. The survey subjects were recruited online and offline, and finally, responses from 231 doctors and 59 patients were used for statistical analysis. Results: The most important parts in the treatment of IPF for both doctors and patients were the "improvement of respiratory symptoms," "improvement of quality of life," and "prevention of disease progression." Antifibrotic agents were prescribed at a high rate, and 100% of the specialists in Western medicine (WM) and 45.8% of patients reported experiencing side effects. As for the additional payment costs that patients considered as affordable for an integrated medical system, "under 50,000 won (about 38$)" was reported the most in both doctor and patient groups. With regard to the reasons for their reluctance to recommend an integrated medical system for IPF, specialists in WM responded highly to "uncertain evidence for treatment effectiveness." Regarding complementary and alternative medicine therapies that can be beneficial in patients with IPF, "lifestyle management," "diet management," "herb," "relaxation therapy," and "psychotherapy" were ranked high in both doctor and patient groups. Conclusions: In this study, a questionnaire survey on IPF was conducted to review actual treatment status, analyze shortcomings, and identify considerations for the development of an integrated medical system for IPF in the future.

• KIPS Transactions on Software and Data Engineering
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• v.12 no.7
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• pp.315-324
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• 2023

A simple and accurate whole body rehabilitation interaction technology using immersive digital content is needed for elderly patients with steadily increasing age-related diseases. In this study, we introduce whole-body interaction technology using HoloLens and Kinect for this purpose. To achieve this, we propose three coordinate transformation methods: mesh feature point-based transformation, AR marker-based transformation, and body recognition-based transformation. The mesh feature point-based transformation aligns the coordinate system by designating three feature points on the spatial mesh and using a transform matrix. This method requires manual work and has lower usability, but has relatively high accuracy of 8.5mm. The AR marker-based method uses AR and QR markers recognized by HoloLens and Kinect simultaneously to achieve a compliant accuracy of 11.2mm. The body recognition-based transformation aligns the coordinate system by using the position of the head or HMD recognized by both devices and the position of both hands or controllers. This method has lower accuracy, but does not require additional tools or manual work, making it more user-friendly. Additionally, we reduced the error by more than 10% using RANSAC as a post-processing technique. These three methods can be selectively applied depending on the usability and accuracy required for the content. In this study, we validated this technology by applying it to the "Thunder Punch" and rehabilitation therapy content.

• Journal of Periodontal and Implant Science
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• v.54 no.1
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• pp.13-24
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• 2024

Purpose: This study investigated the adjunctive effect of light-emitting diodes (LEDs) in the treatment of experimental periodontitis. Methods: Experimental periodontitis was induced by placing ligatures around the mandibular second, third, and fourth premolars of 6 beagles for 3 months. After ligature removal, periodontitis progressed spontaneously for 2 months. The animals' hemimandibles were allocated among the following 3 groups: 1) no treatment (control), 2) scaling and root planing (SRP), and 3) SRP with LED irradiation at 470-nm and 630-nm wavelengths (SRP/LED). The probing pocket depth (PPD) and gingival recession (GR) were measured at baseline, 6 weeks, and 12 weeks. The clinical attachment level (CAL) was calculated. After 12 weeks, histological and histomorphometric assessments were performed. The distances from the gingival margin to the apical extent of the junctional epithelium (E) and to the connective tissue (CT) attachment were measured, as was the total length of soft tissue (ST). Results: PPD and CAL increased at 12 weeks compared with baseline in the control group (6.31±0.43 mm to 6.93±0.50 mm, and 6.46±0.60 mm to 7.61±0.78 mm, respectively). PPD and CAL decreased at 12 weeks compared with baseline in the SRP group (6.01±0.59 to 4.81±0.65 mm, and 6.51±0.98 to 5.39±0.93 mm, respectively). PPD and CAL decreased at 12 weeks compared with baseline in the SRP/LED group (6.03±0.39 to 4.46±0.47 mm, and 6.11±0.47 to 4.78±0.57 mm, respectively). The E/ST and CT/ST ratios significantly differed among the 3 groups (P<0.05). The clinical parameters and histologic findings demonstrated that 470-nm and 630-nm wavelength LED irradiation accompanying SRP could improve treatment results. Conclusions: Within the study limitations, 470 nm and 630 nm wavelength LED irradiation might provide additional benefits for periodontitis treatment.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.152-158
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• 2023

Staphylococcus aureus (SA) is a common cause of skin and soft tissue infections. Panton-Valentine leukocidin (PVL) toxin-producing strain of SA has been discovered worldwide and is known to cause serious infections. However, reports of neonatal infections caused by PVL-positive SA are rare. Here, we report a case of severe skin and soft tissue infection caused by PVL-positive SA in a 7-day-old neonate. The patient was admitted to the emergency room with a history of fever for one day, tenderness, and sensation of buttocks heating. The infant presented with fever, tachycardia, poor general health, progressive tenderness, and edema of the buttocks on the day of admission. Ultrasonography and magnetic resonance imaging revealed necrotizing fasciitis involving the skin, soft tissue, and muscles. Specimens drained from the buttock lesions confirmed the presence of PVL-positive methicillin-resistant SA (MRSA), and there was no bacteremia. She recovered after one month of intravenous antibiotics and surgical drainages. One month after discharge, she was rehospitalized for otitis externa and was infected with MRSA again. Considering the PVL-positive strain, the patient was treated with intravenous linezolid and dressing. The patient underwent decolonization therapy in a 0.5% chlorhexidine bath and recovered completely without sequelae. This case suggests that aggressive drainage and antibiotic treatment are essential for PVL-producing MRSA infections, and additional decolonization is needed to prevent recurrence and community spread.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.24 no.1
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• pp.1-9
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• 2024

Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episode (MELAS) is a rare maternally inherited disorder primarily caused by mutations in mitochondrial DNA, notably the m.3243A>G mutation in the MT-TL1 gene. This mutation impairs mitochondrial function crucial for cellular energy production, particularly in high-energy-demanding organs such as the brain and muscles. MELAS manifests as recurrent stroke-like episodes, seizures, diabetes mellitus, cardiomyopathy, and other multisystemic symptoms that are often present in childhood. The diagnosis combines genetic testing, clinical evaluation, and neuroimaging, with elevated lactate levels and characteristic magnetic resonance imaging (MRI) findings as key indicators. Treatment focuses on symptomatic management and enhancement of mitochondrial function through L-arginine, coenzyme Q10, high-dose vitamins, and taurine supplementation. Studies have identified additional genetic variants linked to MELAS, including mutations in POLG and other mitochondrial genes, further complicating the genetic landscape. Emerging therapies, particularly gene therapy and mitochondria-targeting drugs, offer promising avenues for addressing the underlying genetic defects and improving mitochondrial functioning. Furthermore, ongoing studies continue to enhance our understanding and management of MELAS, with the aim of reducing its burden and improving patient outcomes and quality of life. This review summarizes the current knowledge on the genetics, clinical features, diagnosis, and treatment of MELAS, highlighting the latest advancements and future directions for therapeutic interventions.