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1. Deep and Superficial Debridement Techniques in Lower Extremity Split-thickness Skin Grafting

Author: Rachel N. Rohrich, BS, Karen R. Li, BBA, Christian X. Lava, MS, Sami Alahmadi, MS, Henry L. Stanton, BS, Victoria H. Kim, MS, Daisy L. Spoer, MS, Karen K. Evans, MD, John S. Steinberg, DPM, and Christopher E. Attinger, MD
Subjects: Surgery, RD1-811
Abstract: Background:. Patients with nonhealing lower extremity (LE) wounds often require a split-thickness skin graft (STSG) for closure. Nonviable tissue must be debrided before STSG inset. Our study aimed to compare differences in debridement depth on STSG outcomes. Methods:. Chronic, atraumatic LE wounds receiving STSG from December 2014 to December 2022 at a single institution were reviewed. Demographics, wound characteristics, operative details, and outcomes were collected. Superficially debrided wounds were compared with wounds receiving deep debridement (DD), defined by debriding to the level of white tissue underlying the granulation tissue. Subanalysis was performed on wounds that had a negative and positive postdebridement culture. Primary outcome was graft failure. Results:. Overall, 244 wounds in 168 patients were identified. In total, 158 (64.8%) wounds were superficially debrided and 86 (35.3%) received DD. The cohort had a median Charlson Comorbidity Index of 4 [interquartile range (IQR): 3]. Diabetes (56.6%) and peripheral artery disease (36.9%) were prevalent. The only statically significant demographic difference between groups was congestive heart failure (SD: 14.9% versus DD: 3.0%, P = 0.017). Wound size, depth, and all microbiology results were similar between groups. Postoperatively, the DD group demonstrated significantly less graft failure (10.5% versus 22.2%, P = 0.023). In a multivariate regression, DD was independently associated with lower odds of graft failure (OR: 0.0; CI, 0.0–0.8; P = 0.034). Sub-analysis of graft failure supported this finding in culture-positive wounds (DD: 7.6% versus DD: 22.1%, P = 0.018) but not in culture-negative wounds (13.6% versus 22.2%, P = 0.507). Conclusions:. The DD technique demonstrates improved outcomes in chronic, culture-positive LE wounds receiving STSG.
Published: 2024
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2. Personalized Deep Learning Model for Clinical Target Volume on Daily Cone Beam Computed Tomography in Breast Cancer Patients

Author: Joonil Hwang, MS, Jaehee Chun, PhD, Seungryong Cho, PhD, Joo-Ho Kim, MS, Min-Seok Cho, MS, Seo Hee Choi, MD, and Jin Sung Kim, PhD
Subjects: Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Purpose: Herein, we developed a deep learning algorithm to improve the segmentation of the clinical target volume (CTV) on daily cone beam computed tomography (CBCT) scans in breast cancer radiation therapy. By leveraging the Intentional Deep Overfit Learning (IDOL) framework, we aimed to enhance personalized image-guided radiation therapy based on patient-specific learning. Methods and Materials: We used 240 CBCT scans from 100 breast cancer patients and employed a 2-stage training approach. The first stage involved training a novel general deep learning model (Swin UNETR, UNET, and SegResNET) on 90 patients. The second stage used intentional overfitting on the remaining 10 patients for patient-specific CBCT outputs. Quantitative evaluation was conducted using the Dice Similarity Coefficient (DSC), Hausdorff Distance (HD), mean surface distance (MSD), and independent samples t test with expert contours on CBCT scans from the first to 15th fractions. Results: IDOL integration significantly improved CTV segmentation, particularly with the Swin UNETR model (P values < .05). Using patient-specific data, IDOL enhanced the DSC, HD, and MSD metrics. The average DSC for the 15th fraction improved from 0.9611 to 0.9819, the average HD decreased from 4.0118 mm to 1.3935 mm, and the average MSD decreased from 0.8723 to 0.4603. Incorporating CBCT scans from the initial treatments and first to third fractions further improved results, with an average DSC of 0.9850, an average HD of 1.2707 mm, and an average MSD of 0.4076 for the 15th fraction, closely aligning with physician-drawn contours. Conclusion: Compared with a general model, our patient-specific deep learning-based training algorithm significantly improved CTV segmentation accuracy of CBCT scans in patients with breast cancer. This approach, coupled with continuous deep learning training using daily CBCT scans, demonstrated enhanced CTV delineation accuracy and efficiency. Future studies should explore the adaptability of the IDOL framework to diverse deep learning models, data sets, and cancer sites.
Published: 2024
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3. Deep Learning Assisted Imaging Methods to Facilitate Access to Ophthalmic Telepathology

Author: Andrew W. Browne, MD, PhD, Geunwoo Kim, MS, Anderson N. Vu, MD, Josiah K. To, MD, Don S. Minckler, MD, Maria Del Valle Estopinal, MD, Narsing A. Rao, MD, Christine A. Curcio, PhD, and Pierre F. Baldi, PhD
Subjects: Deep learning, Telepathology, Diffusion model, Artificial intelligence, Ophthalmology, RE1-994
Abstract: Purpose: To investigate the use of super-resolution imaging techniques to enable telepathology using low-cost commercial cameras. Design: Experimental study. Participants: A total of 139 ophthalmic pathology slides obtained from the Ophthalmic Pathology service at the University of California, Irvine. Methods: Denoising Diffusion Probabilistic Model (DDPM) was developed to predict super-resolution pathology slide images from low-resolution inputs. The model was pretrained using 150 000 images randomly sampled from the ImageNet dataset. Patch aggregation was used to generate large images with DDPM. The performance of DDPM was evaluated against that of generative adversarial networks (GANs) and Robust UNet, which were also trained on the same dataset. Main Outcome Measures: The performance of models trained to generate super-resolution output images from low-resolution input images can be evaluated by using the mean squared error (MSE) and Structural Similarity Index Measure (SSIM), as well as subjective grades provided by expert pathologist graders. Results: In total, our study included 110 training images, 9 validation images, and 20 testing images. The objective performance scores were averaged over patches generated from 20 test images. The DDPM-based approach with pretraining produced the best results, with an MSE score of 1.35e-5 and an SSIM score of 0.8987. A qualitative analysis of super-resolution images was conducted by expert 3 pathologists and 1 expert ophthalmic microscopist, and the average accuracy of identifying the correct ground truth images ranged from 25% to 70% (with an average accuracy of 46.5%) for widefield images and 25% to 60% (with an average accuracy of 38.25%) for individual patches. Conclusions: The DDPM-based approach with pretraining is assessed to be effective at super-resolution prediction for ophthalmic pathology slides both in terms of objective and subjective measures. The proposed methodology is expected to decrease the reliance on costly slide scanners for acquiring high-quality pathology slide images, while also streamlining clinical workflow and expanding the scope of ophthalmic telepathology. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Published: 2024
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4. Early Physiologic Numerical and Waveform Characteristics of Simulated Hemorrhagic Events With Healthy Volunteers Donating Blood

Author: Joo Heung Yoon, MD, Jueun Kim, MS, Theodore Lagattuta, RN, Michael R. Pinsky, MD, MCCM, Marilyn Hravnak, RN, PhD, and Gilles Clermont, MD, MS
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: OBJECTIVES:. Early signs of bleeding are often masked by the physiologic compensatory responses delaying its identification. We sought to describe early physiologic signatures of bleeding during the blood donation process. SETTING:. Waveform-level vital sign data including electrocardiography, photoplethysmography (PPG), continuous noninvasive arterial pressure, and respiratory waveforms were collected before, during, and after bleeding. SUBJECTS:. Fifty-five healthy volunteers visited blood donation center to donate whole blood. INTERVENTION:. After obtaining the informed consent, 3 minutes of resting time was given to each subject. Then 3 minutes of orthostasis was done, followed by another 3 minutes of resting before the blood donation. After the completion of donating blood, another 3 minutes of postbleeding resting time, followed by 3 minutes of orthostasis period again. MEASUREMENTS AND MAIN RESULTS:. From 55 subjects, waveform signals as well as numerical vital signs (heart rate [HR], respiratory rate, blood pressure) and clinical characteristics were collected, and data from 51 subjects were analyzable. Any adverse events (AEs; dizziness, lightheadedness, nausea) were documented. Statistical and physiologic features including HR variability (HRV) metrics and other waveform morphologic parameters were modeled. Feature trends for all participants across the study protocol were analyzed. No significant changes in HR, blood pressure, or estimated cardiac output were seen during bleeding. Both orthostatic challenges and bleeding significantly decreased time domain and high-frequency domain HRV, and PPG amplitude, whereas increasing PPG amplitude variation. During bleeding, time-domain HRV feature trends were most sensitive to the first 100 mL of blood loss, and incremental changes of different HRV parameters (from 300 mL of blood loss), as well as a PPG morphologic feature (from 400 mL of blood loss), were shown with statistical significance. The AE group (n = 6) showed decreased sample entropy compared with the non-AE group during postbleed orthostatic challenge (p = 0.003). No significant other trend differences were observed during bleeding between AE and non-AE groups. CONCLUSIONS:. Various HRV-related features were changed during rapid bleeding seen within the first minute. Subjects with AE during postbleeding orthostasis showed decreased sample entropy. These findings could be leveraged toward earlier identification of donors at risk for AE, and more broadly building a data-driven hemorrhage model for the early treatment of critical bleeding.
Published: 2024
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5. 111. Deep Debridement Method For Split Thickness Skin Graft Success In 316 Patients With Lower Extremity Wounds

Author: Rachel N. Rohrich, BS, Karen R. Li, BBA, Christian X. Lava, MS, Sami Alahmadi, MS, Henry L. Stanton, BS, Victoria H. Kim, MS, Karen K. Evans, MD, John S Steinberg, DPM, Kenneth L. Fan, MD, and Christopher E. Attinger, MD
Subjects: Surgery, RD1-811
Published: 2024
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6. Feasibility of Customized Thermoplastic Patient-Specific Helmet Bolus for Scalp Irradiation Using Volumetric-Modulated Arc Therapy Planning

Author: Heesoo Kim MS, Jeong-Woo Lee PhD, and Semie Hong PhD
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Introduction: In this study, we sought to develop a thermoplastic patient-specific helmet bolus that could deliver a uniform therapeutic dose to the target and minimize the dose to the normal brain during whole-scalp treatment with a humanoid head phantom. Methods: The bolus material was a commercial thermoplastic used for patient immobilization, and the holes in the netting were filled with melted paraffin. We compared volumetric-modulated arc therapy treatment plans with and without the bolus for quantitative dose distribution analysis. We analyzed the dose distribution in the region of interest to compare dose differences between target and normal organs. For quantitative analysis of treatment dose, OSLD chips were attached at the vertex (VX), posterior occipital (PO), right (RT), and left temporal (LT) locations. Results: The average dose in the clinical target volume was 6553.8 cGy (99.3%) with bolus and 5874 cGy (89%) without bolus, differing by more than 10% from the prescribed dose (6600 cGy) to the scalp target. For the normal brain, it was 3747.8 cGy (56.8%) with bolus and 5484.6 cGy (83.1%) without bolus. These results show that while the dose to the treatment target decreased, the average dose to the normal brain, which is mostly inside the treatment target, increased by more than 25%. With the bolus, the OSLD measured dose was 102.5 ± 1.2% for VX and 101.5 ± 1.9%, 95.9 ± 1.9%, and 81.8 ± 2.1% for PO, RT, and LT, respectively. In addition, the average dose in the treatment plan was 102%, 101%, 93.6%, and 80.7% for VX, PO, RT, and LT. When no bolus was administered, 59.6 ± 2.4%, 112.6 ± 1.8%, 47.1 ± 1.6%, and 53.1 ± 2.3% were assessed as OSLD doses for VX, PO, RT, and LT, respectively. Conclusion: This study proposed a method to fabricate patient-specific boluses that are highly reproducible, accessible, and easy to fabricate for radiotherapy to the entire scalp and can effectively spare normal tissue while delivering sufficient surface dose.
Published: 2024
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7. Feasibility of a Self-directed Upper Extremity Training Program to Promote Actual Arm Use for Individuals Living in the Community With Chronic Stroke

Author: Grace J. Kim, PhD, Amanda Gahlot, MS, Camile Magsombol, OTD, Margaret Waskiewicz, OTD, Nettie Capasso, MS, Stephen Van Lew, PhD, Hayejin Kim, MS, Avinash Parnandi, PhD, Victoria Vaughan Dickson, PhD, and Yael Goverover, PhD
Subjects: Self-directed training, Actual arm use, Shared decision-making, Stroke, Upper extremity, Medicine (General), R5-920
Abstract: Objective: To determine the feasibility of a self-directed training protocol to promote actual arm use in everyday life. The secondary aim was to explore the initial efficacy on upper extremity (UE) outcome measures. Design: Feasibility study using multiple methods. Setting: Home and outpatient research lab. Participants: Fifteen adults (6 women, 9 men, mean age=53.08 years) with chronic stroke living in the community. There was wide range of UE functional levels, ranging from dependent stabilizer (limited function) to functional assist (high function). Intervention: Use My Arm-Remote protocol. Phase 1 consisted of clinician training on motivational interviewing (MI). Phase 2 consisted of MI sessions with participants to determine participant generated goals, training activities, and training schedules. Phase 3 consisted of UE task-oriented training (60 minutes/day, 5 days/week, for 4 weeks). Participants received daily surveys through an app to monitor arm training behavior and weekly virtual check-ins with clinicians to problem-solve challenges and adjust treatment plans. Outcome Measures: Primary outcome measures were feasibility domains after intervention, measured by quantitative study data and qualitative semi-structured interviews. Secondary outcomes included the Canadian Occupational Performance Measure (COPM), Motor Activity Log (MAL), Fugl-Meyer Assessment (FMA), and accelerometry-based duration of use metric measured at baseline, discharge, and 4-week follow-up. Results: The UMA-R was feasible in the following domains: recruitment rate, retention rate, intervention acceptance, intervention delivery, adherence frequency, and safety. Adherence to duration of daily practice did not meet our criteria. Improvements in UE outcomes were achieved at discharge and maintained at follow-up as measured by COPM-Performance subscale (F[1.42, 19.83]=17.72, P
Published: 2024
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8. Comprehensive Evaluation of Traditional Herbal Medicine Combined With Adjuvant Chemotherapy on Post-Surgical Gastric Cancer: A Systematic Review and Meta-Analysis

Author: Soo-Dam Kim PhD, Jong-Hee Kim PhD, Dong-Hyun Kim MS, Ji-Hye Park KMD, PhD, Yabin Gong PhD, Chengbing Sun PhD, Hwa-Seung Yoo KMD, PhD, and So-Jung Park KMD, PhD
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients. Methods: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment. Results: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated. Conclusion: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings. Registration:PROSPERO CRD 42022354133
Published: 2024
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9. A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study

Author: Ji-Su Shim, MD, PhD, Hyunkyoung Kim, MS, Jae-Woo Kwon, MD, PhD, So-Young Park, MD, PhD, Sujeong Kim, MD, PhD, Byung-Keun Kim, MD, PhD, Young-Hee Nam, MD, PhD, Min-Suk Yang, MD, PhD, Mi-Yeong Kim, MD, PhD, Sae-Hoon Kim, MD, PhD, Byung-Jae Lee, MD, PhD, Taehoon Lee, MD, PhD, Sang-Ha Kim, MD, PhD, So Young Park, MD, PhD, Young-Joo Cho, MD, PhD, Chan Sun Park, MD, PhD, Jae-Woo Jung, MD, PhD, Han-Ki Park, MD, PhD, Joo-Hee Kim, MD, PhD, Jeong-Hee Choi, MD, PhD, Ji-Yong Moon, MD, PhD, Ian Adcock, MD, PhD, Kian Fan Chung, MD, PhD, Min-Hye Kim, MD, PhD, and Tae-Bum Kim, MD, PhD
Subjects: Asthma-COPD overlap, Asthma, Biologics, Monoclonal antibodies, Treatment response, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) 10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (−117.50 ± 94.38 vs. −115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (−18.62 ± 24.68 vs. −14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (−3.40 ± 10.60 vs. −14.48 ± 24.01 %, P = 0.065), blood eosinophils (−36.47 ± 517.02 vs. −363.22 ± 1294.59, P = 0.013), and exacerbation frequency (−3.07 ± 4.42 vs. −3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.
Published: 2023
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10. Clinical Trial and Real-World Outcomes of Patients With Metastatic NSCLC in the Post-Platinum–Based Chemotherapy Failure Setting

Author: Yu Yang Soon, MBBS, Wesley Furnback, BA, Jin Kim, MS, Po-Ya Chuang, MHA, Gordon Chavez, BA, Christina Proescholdt, MD, and Cloe Ying Chee Koh, MS
Subjects: NSCLC, Literature review, Response, Real-world evidence, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Introduction: A literature review was undertaken to identify clinical trials and real-world studies of patients with stage IV NSCLC who had progressed on or after treatment with platinum-based chemotherapy. Methods: The EMBASE and MEDLINE databases were used to search for English-language studies published between September 28, 2017, and September 28, 2021. Studies were included in the review if they (1) were clinical trials or real-world analyses of one or more treatment regimens for patients with stage IV NSCLC who had progressed on or after treatment with platinum-based chemotherapy, (2) contained an end point including efficacy, effectiveness, or safety, and (3) included 45 or more patients. Results: In total, there were 15 publications (nine unique trials and three real-world studies) included. Sample size ranged from 49 to 1253 patients. At least one treatment arm in eight of the nine clinical trials reported an overall response rate of ≥15%. Median progression-free survival (PFS) and overall survival ranged from 1.9 to 5.2 months and 5.4 to 15.4 months in clinical trials and 4.4 to 6.8 months and 8.3 to 18.0 months in real-world studies, respectively. Within studies reporting median PFS, a median PFS of more than or equal to 3 months was reported in eight of 11 clinical trials and both real-world studies. Discontinuation due to adverse events ranged from 1.9% to 18% across all included studies. Conclusions: Patients with stage IV NSCLC had limited response and a high burden of adverse events during treatment after progression on platinum-containing chemotherapy. There remains a pressing unmet need for additional, effective, and tolerable treatment options in this setting.
Published: 2023
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11. Highly sensitive noninvasive early lung cancer detection using DNA methylation topology in sputum-derived epithelial cellsCentral MessagePerspective

Author: Harmik J. Soukiasian, MD, Alexander Leung, MD, Taryne Imai, MD, Shika Bose, MD, Sungjin Kim, MS, Zab Mosenifar, MD, Nirdesh K. Gupta, PhD, and Jian Tajbakhsh, PhD
Subjects: DNA methylation, noninvasive test, non–small cell lung cancer, screening, sputum, Diseases of the circulatory (Cardiovascular) system, RC666-701, Surgery, RD1-811
Abstract: Objective: Sputum is a source of exfoliated respiratory epithelial cells transformed early in lung carcinogenesis. Malignant cells are hypomethylated and contain less genomic 5-methylcytosine (5mC). Validating a test that recognizes and quantifies aberrantly hypomethylated cells in sputum, we assessed its potential as a screening tool for detecting early-stage non–small cell lung cancer. Methods: Cells extracted from sputum were immunofluorescence labeled with an anti-5-methylcytosine antibody and counterstained with 4′,6-diamidino-2-phenylindole (DAPI) delineating global nuclear DNA (gDNA). Via confocal scanning and 3-dimensional image analysis, fluorescence 5mC and DAPI signals were measured in segmented cell nuclei, and a 5mC/DAPI co-distribution map was generated for each imaged cell. Cells were classified as hypomethylated based on 5mC load and 5mC/DAPI co-distribution. The proportion of hypomethylated epithelial cells in the sputum determines whether a patient has lung cancer. Results: A total of 88 subjects were enrolled: 12 healthy subjects; 34 high-risk subjects with benign chronic lung disorders (10 with chronic obstructive pulmonary disease, 24 with idiopathic pulmonary fibrosis), and 43 subjects with non–small cell lung cancer (27 with stage I-II and 16 with stage III-IV). The test identified early-stage non–small cell lung cancer and distinguished it from the high-risk group with 95.8% (95% confidence interval, 78.9-99.9) sensitivity and 41.2% (95% confidence interval, 24.6-59.3) specificity applying only 5mC, 95.8% (95% confidence interval, 78.9-99.9) sensitivity and 26.5% (95% confidence interval, 12.9-44.4) specificity using solely 5mC/DAPI index, and 100% (95% confidence interval, 98.7-100) sensitivity and 26.1% (95% confidence interval, 26.2-27.8) specificity with the combined parameters. Conclusions: We tested and validated a novel, noninvasive, highly sensitive screening test for non–small cell lung cancer. With the use of sputum, our test may impact lung cancer screening, evaluation of pulmonary nodules, and cancer surveillance algorithms.
Published: 2023
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12. Effect of Traditional Korean Medicine Oncotherapy on the Survival, Quality of Life, and Telomere Length: A Prospective Cohort Study

Author: Su-Jung Ha PhD, Eunbin Kwag MS, Soodam Kim MS, Ji-Hye Park PhD, So-Jung Park PhD, and Hwa-Seung Yoo PhD
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: A 4-year prospective cohort study on patients with lung, gastric, hepatic, colorectal, breast, uterine, and ovarian cancer was conducted at the East-West Cancer Center (EWCC) of Daejeon Korean Medicine Hospital in Daejeon, Korea. We divided patients into 2 groups based on how long they had been receiving TKM oncotherapy and compared event-free survival (EFS), telomere length change, and quality of life (QoL). The study collected data on 83 patients from October 2016 to June 2020 and discovered no statistical differences in EFS based on the duration of TKM oncotherapy. In the analysis of changes in QoL outcomes, there were no statistically significant group differences between the groups. After controlling for covariates that could affect telomere length, the long-term TKM oncotherapy group had a higher daily telomere attrition rate. The study of the relationship between telomere length and prognostic factors discovered that patients with advanced N stage at the time of diagnosis and who had previously received radiotherapy had shorter telomere length. When examining associations between SNP genotype and percentile score of telomere length, this study was able to confirm an association between telomere length and rs4387287. This study is significant because it is the first to assess the effects of TKM oncotherapy and investigate telomere length-related factors. To assess the effects of TKM oncotherapy on cancer patients’ survival and QoL, a longer-term observational study with a larger sample size is required.
Published: 2023
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13. Coordinated Health Care Interventions for Childhood Asthma Gaps in Outcomes (CHICAGO) plan

Author: Jerry A. Krishnan, MD, PhD, Helen Margellos-Anast, MPH, Rajesh Kumar, MD, Joel J. Africk, JD, Michael Berbaum, PhD, Nina Bracken, MSN, NP, Yi-Fan Chen, PhD, Julie DeLisa, MA, Kim Erwin, MDes, Stacy Ignoffo, MSW, Sai Dheeraj Illendula, MS, Hajwa Kim, MS, Cortland Lohff, MD, MPH, Tom MacTavish, MLIS, Molly A. Martin, MD, MAPP, Giselle S. Mosnaim, MD, MS, Hannah Nguyen, MPH, Sarah Norell, MDes, MFA, Sharmilee M. Nyenhuis, MD, S. Margaret Paik, MD, Zachary Pittsenbarger, MD, Valerie G. Press, MD, MPH, Jennifer Sculley, MDes, Trevonne M. Thompson, MD, Leslie Zun, MD, MBA, Lynn B. Gerald, PhD, MSPH, Michael McDermott, MD, Sana Ali, Janet Flores, Shahina Gantiwala, Carmen Goralski, Rajesh Kumar, Jacqueline Ortega, Zachary Pittsenbarger, Isabelle Wilson, Cortland Lohff, Michael McDermott, Kim Erwin, Thomas MacTavish, Sarah Norell, Maureen Damitz, David Massaquoi, Kenneth Soyemi, Thomas Senko, Trevonne Thompson, Kate McMahon, Joel Africk, Amy O’Rourke, Christopher Codispoti, Jane Kramer, Rabia Malik, Pamela Manning, Giselle Mosnaim, Jeanette Avila, Helen Margellos-Anast, Fatima Padron, Jessica Ramsay, Nazia Saiyed, Tala Schwindt, Gloria Seals, Leslie Zun, Susannah Butters, Ashley Hull, John Kim, S. Margaret Paik, Valerie Press, Crystal Stevenson, Nicole Twu, Nicole Woodrick, Michael Berbaum, Nina Bracken, Jennifer Buenrostro, Lauren Castro, Yi-Fan Chen, Julie DeLisa, David De La Torre-Dorado, Dameka Edwards, Alexander Frye, Maciej Grabarek, Sai Dheeraj Illendula, Hajwa Kim, Jerry Krishnan, Molly Martin, Melissa Morales- Perez, Hannah Nguyen, Sharmilee Nyenhuis, Jennifer Sculley, Bruce Bender, PhD, Francine Ducharme, MD, Sheri Hurdle, Xue Li, PhD, and Sande Okelo, MD, PhD
Subjects: Pragmatic clinical trial, asthma, community health worker, emergency department, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Evidence-based strategies to improve outcomes in minority children with uncontrolled asthma discharged from the emergency department (ED) are needed. Objectives: This multicenter pragmatic clinical trial was designed to compare an ED-only intervention (decision support tool), an ED-only intervention and home visits by community health workers for 6 months (ED-plus-home), and enhanced usual care (UC). Methods: Children aged 5 to 11 years with uncontrolled asthma were enrolled. The change over 6 months in the Patient-Reported Outcomes Measurement Information System Asthma Impact Scale score in children and Satisfaction with Participation in Social Roles score in caregivers were the primary outcomes. The secondary outcomes included guideline-recommended ED discharge care and self-management. Results: Recruitment was significantly lower than expected (373 vs 640 expected). Of the 373 children (64% Black and 31% Latino children), only 63% completed the 6-month follow-up visit. In multivariable analyses that accounted for missing data, the adjusted odds ratios and 98% CIs for differences in Asthma Impact Scores or caregivers’ Satisfaction with Participation in Social Roles scores were not significant. However, guideline-recommended ED discharge care was significantly improved in the intervention groups versus in the UC group, and self-management behaviors were significantly improved in the ED-plus-home group versus in the ED-only and UC groups. Conclusions: The ED-based interventions did not significantly improve the primary clinical outcomes, although the study was likely underpowered. Although guideline-recommended ED discharge care and self-management did improve, their effect on clinical outcomes needs further study.
Published: 2023
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14. Design of Montelukast Nanocrystalline Suspension for Parenteral Prolonged Delivery

Author: Park JS, Kim MS, Joung MY, Park HJ, Ho MJ, Choi JH, Seo JH, Song WH, Choi YW, Lee S, Choi YS, and Kang MJ
Subjects: montelukast, parenteral prolonged release delivery, crystallinity, nanocrystalline suspension, bead-milling, pharmacokinetics, local tolerability, Medicine (General), R5-920
Abstract: Jun Soo Park,1 Min Seop Kim,1 Min Yeong Joung,1 Hyun Jin Park,1 Myoung-Jin Ho,1 Jun Hyuk Choi,1 Jae Hee Seo,1 Woo Heon Song,1 Young Wook Choi,2 Sangkil Lee,3 Yong Seok Choi,1 Myung Joo Kang1 1College of Pharmacy, Dankook University, Cheonan, Republic of Korea; 2College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 3College of Pharmacy, Keimyung University, Daegu, Republic of KoreaCorrespondence: Myung Joo Kang, College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, 31116, Republic of Korea, Tel +82 41 550 1446, Fax +82 41 550 7899, Email kangmj@dankook.ac.krBackground: Montelukast (MTK), a representative leukotriene receptor antagonist, is currently being investigated as a potential candidate for treating Alzheimer’s disease. For potent and effective dosing in elderly patients, a parenteral prolonged delivery system is favored, with improved medication adherence with reduced dosage frequency.Purpose: This study aimed to design a nanocrystalline suspension (NS)-based MTK prolonged delivery system and evaluate its pharmacokinetics profile and local tolerability following subcutaneous administration.Methods: To decelerate the dissolution rate, the amorphous MTK raw material was transformed into a crystalline state using a solvent-mediated transformation method and subsequently formulated into NS using a bead-milling technique. The MTK NSs were characterized by morphology, particle size, crystallinity, and in vitro dissolution profiles. The pharmacokinetic profile and local tolerability at the injection site following subcutaneous injection of MTK suspension were evaluated in rats.Results: Microscopic and physical characterization revealed that the amorphous MTK powder was lucratively transformed into a crystalline form in acidic media (pH 4). MTK crystalline suspensions with different diameters (200 nm, 500 nm, and 3 μm) were uniformly prepared using bead-milling technology, employing polysorbate 80 as suspending agent. Prepared crystalline suspensions exhibited analogous crystallinity (melting point, 150°C) and size-dependent in vitro dissolution profiles. MTK NSs with particle sizes of 200 nm and 500 nm provided a protracted pharmacokinetic profile for up to 4 weeks in rats, with a higher maximum drug concentration in plasma than the 3 μm-sized injectable suspensions. Histopathological examination revealed that MTK NS caused chronic granulomatous inflammation at the injection site, which resolved after 4 weeks.Conclusion: The MTK parenteral NS delivery system is expected to be a valuable tool for treating Alzheimer’s disease with extended dose intervals.Graphical Abstract: Keywords: montelukast, parenteral prolonged release delivery, crystallinity, nanocrystalline suspension, bead-milling, pharmacokinetics, local tolerability
Published: 2022

15. Alterations and Prediction of Functional Profiles of Gut Microbiota After Fecal Microbiota Transplantation for Iranian Recurrent Clostridioides difficile Infection with Underlying Inflammatory Bowel Disease: A Pilot Study

Author: Azimirad M, Jo Y, Kim MS, Jeong M, Shahrokh S, Aghdaei HA, Zali MR, Lee S, Yadegar A, and Shin JH
Subjects: fecal microbiota transplantation, clostridioides difficile infection, inflammatory bowel disease, gut microbiome, functional profiles, gut dysbiosis, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract: Masoumeh Azimirad,1,&ast; YoungJae Jo,2,&ast; Min-Sueng Kim,2 Minsoo Jeong,2 Shabnam Shahrokh,3 Hamid Asadzadeh Aghdaei,4 Mohammad Reza Zali,3 Seungjun Lee,5 Abbas Yadegar,1 Jae-Ho Shin2 1Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea; 3Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Food Science and Nutrition, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Abbas Yadegar; Jae-Ho Shin Tel +98-21-22432518; +82 53-950-5716Fax +98-21-22432527; +82 53-953-7233Email babak_y1983@yahoo.com; jhshin@knu.ac.krBackground and Purpose: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT.Patients and Methods: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis.Results: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors.Conclusion: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.Keywords: fecal microbiota transplantation, Clostridioides difficile infection, inflammatory bowel disease, gut microbiome, functional profiles, gut dysbiosis
Published: 2022

16. Analyzing adverse drug reaction using statistical and machine learning methods

Author: Hae Reong Kim, MS, MinDong Sung, MD, Ji Ae Park, MS, Kyeongseob Jeong, BS, Ho Heon Kim, MS, Suehyun Lee, PhD, and Yu Rang Park, PhD
Subjects: Medicine
Abstract: Abstract. Background:. Adverse drug reactions (ADRs) are unintended negative drug-induced responses. Determining the association between drugs and ADRs is crucial, and several methods have been proposed to demonstrate this association. This systematic review aimed to examine the analytical tools by considering original articles that utilized statistical and machine learning methods for detecting ADRs. Methods:. A systematic literature review was conducted based on articles published between 2015 and 2020. The keywords used were statistical, machine learning, and deep learning methods for detecting ADR signals. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. Results:. We reviewed 72 articles, of which 51 and 21 addressed statistical and machine learning methods, respectively. Electronic medical record (EMR) data were exclusively analyzed using the regression method. For FDA Adverse Event Reporting System (FAERS) data, components of the disproportionality method were preferable. DrugBank was the most used database for machine learning. Other methods accounted for the highest and supervised methods accounted for the second highest. Conclusions:. Using the 72 main articles, this review provides guidelines on which databases are frequently utilized and which analysis methods can be connected. For statistical analysis, >90% of the cases were analyzed by disproportionate or regression analysis with each spontaneous reporting system (SRS) data or electronic medical record (EMR) data; for machine learning research, however, there was a strong tendency to analyze various data combinations. Only half of the DrugBank database was occupied, and the k-nearest neighbor method accounted for the greatest proportion.
Published: 2022
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17. High-Payload Nanosuspension of Centella asiatica Extract for Improved Skin Delivery with No Irritation

Author: Kim EA, Park JS, Kim MS, Jeong MY, Park HJ, Choi JH, Seo JH, Choi YS, and Kang MJ
Subjects: centella asiatica, asiatic acid, madecassic acid, asiaticoside, nanocrystal suspension, bead-milling, dissolution, skin absorption, skin irritation, Medicine (General), R5-920
Abstract: Eun A Kim, Jun Soo Park, Min Seop Kim, Min Young Jeong, Hyun Jin Park, Jun Hyuk Choi, Jae Hee Seo, Yong Seok Choi, Myung Joo Kang College of Pharmacy, Dankook University, Cheonan, Chungnam, 330-714, KoreaCorrespondence: Myung Joo KangCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, 330-714, KoreaTel +82 41 550 1446Fax +82 41 550 7899. Email kangmj@dankook.ac.krBackground: The titrated extract of Centella asiatica (CA) has received much attention as a cosmeceutical ingredient owing to its anti-wrinkle effect. However, due to the low solubility and high molecular weight of pharmacologically active constituents, including asiatic acid (AA), madecassic acid (MA), and asiaticoside (AS), it is challenging to fabricate high-payload topical preparations of CA with satisfactory skin absorption profiles.Purpose: This study aimed to design a high-payload topical preparation of CA using nanocrystallization technique and to evaluate its skin absorption profile and local tolerability.Methods: High-payload nanocrystal suspensions (NSs) were prepared using lab-scale bead-milling technology, by adjusting the type and amount of suspending agent, CA content, type of vehicle, and milling speed. CA-loaded NSs were characterized in terms of morphology, particle size, crystallinity, and in vitro dissolution pattern. Skin absorption of CA nanocrystals was evaluated using a vertical Franz diffusion cell mounted with porcine skin. In vivo skin irritation following topical application of high-payload NS was assessed in normal rats.Results: The optimized NS system, composed of 10% (w/v) CA, 0.5% polyvinylpyrrolidone (PVP) K30 as steric stabilizer, and 89.5% of distilled water, was characterized as follows: spherical or elliptical in shape, 200 nm in size, with low crystallinity. The in vitro dissolution of AA or MA from NSs was markedly faster compared to raw material, under sink condition. Penetration of AA, MA, and AS in the porcine skin was markedly elevated using the high-payload NS formula, providing 5-, 4-, and 4.5-fold higher accumulation in skin layer, compared to that of the marketed cream formula (CA 1%, Madeca cream). Moreover, topical application of high-payload NS was tolerable, showing neither erythema nor oedema in normal rats.Conclusion: The novel NS system is expected to be a virtuous approach for offering a better skin absorption of CA, without using an excess quantity of solubilizers.Keywords: Centella asiatica, asiatic acid, madecassic acid, asiaticoside, nanocrystal suspension, bead-milling, dissolution, skin absorption, skin irritation
Published: 2021

18. Is positive histologic surgical margin associated with overall survival in patients with resectable gallbladder cancer?

Author: Michael J Littau, BA, Sujay Kulshrestha, MD, Corinne Bunn, MD, Preston Kim, MS, Fred A. Luchette, MD, MSc, and Marshall S. Baker, MD, MBA
Subjects: Surgery, RD1-811
Abstract: Background: Achieving microscopically negative (R0) surgical margins in gallbladder cancer often requires a partial hepatectomy with associated risk of morbidity and potential to delay adjuvant therapy. Prior studies on the importance of margin status in resectable gall bladder cancer include small numbers of patients with positive (R1) resection margins and are underpowered. Methods: We queried the National Cancer Database to identify patients undergoing resection of gallbladder adenocarcinoma between 2004 and 2015. Patients presenting with metastatic disease, those who received neoadjuvant therapy, and those with fewer than 3 lymph nodes assessed were excluded. 1:1 propensity score matching was used to develop cohorts undergoing either R0 or R1 resection, matched for demographic, pathologic, and facility characteristics. Kaplan–Meier analysis was used to assess the association between margin status and overall survival. Results: A total of 1,439 patients met inclusion criteria; 1,285 underwent R0 and 154 underwent R1 resection. On Kaplan–Meier analysis of propensity-matched cohorts, patients undergoing R0 resection had a median overall survival that was 18 months longer than those undergoing R1 resection (34.6 ± 2.0 months vs 16.3 ± 1.7 months, P
Published: 2021
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19. Dexamethasone Intravitreal Implant for the Treatment of Macular Edema Following Retinal Vein Occlusion: Post Hoc Analysis of Post-Marketing Surveillance Data in the Real-World Setting in Korea

Author: Kim MS, Choi J, Lee HD, and Woo SJ
Subjects: retinal vein occlusion, dexamethasone, intravitreal, implant, post-marketing, real world, Ophthalmology, RE1-994
Abstract: Min Seok Kim,1 Jasmine Choi,2 Hyeong Du Lee,3 Se Joon Woo1 On behalf of the Korea Ozurdex Post-Marketing Surveillance Study Group1Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 2Allergan, an AbbVie Company, Irvine, CA, USA; 3Allergan, an AbbVie Company, Seoul, KoreaCorrespondence: Se Joon WooDepartment of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of KoreaTel +82-31-787-7377Fax +82-31-787-4057Email sejoon1@snu.ac.krPurpose: To supplement established efficacy and safety data, this analysis evaluated the real-world use of dexamethasone (DEX) intravitreal implant 700 μg for retinal vein occlusion (RVO)-related macular edema in an Asian population and baseline factors potentially associated with DEX implant efficacy.Patients and Methods: A prospective, observational, post-marketing surveillance study was conducted at 38 sites in South Korea in patients consecutively presenting with macular edema following branch or central RVO (BRVO, CRVO), and administered a first DEX implant. Follow-up visits and subsequent DEX or other therapies conformed with local practice. Outcome measures included best-corrected visual acuity (BCVA), change in BCVA from baseline, responder rates, and adverse events. Associations between baseline characteristics and BCVA gains were evaluated. Month-1, -2, -4, and -6 visit analysis windows were established.Results: In all, 700 patients (79.1% BRVO, 20.9% CRVO) received 1.12 DEX implants (mean) and were followed for 101.5 days (standard deviation, 51.7); 90% received a single implant. Among patients with analyzable data, mean BCVA improved from baseline with peak changes in Month 2 of − 0.193 and − 0.212 LogMAR, (P < 0.0001) and remained significant in the BRVO subgroup at the Month 4 and 6 windows (P < 0.0001 and P = 0.0039, respectively). Treatment-naïve patients experienced greater BCVA increases. The proportion of patients with stable/improved BCVA tended to decrease after Month 2 through Month 6 and the decline was greater in the CRVO subgroup. At the Month-2 window, ≥ 1-, 2- and 3-line increases were positively associated with younger age, worse baseline BCVA, and treatment naivety. The most common adverse event was increased intraocular pressure.Conclusion: In the real-world clinical setting in South Korea, DEX implant improved visual acuity and had a favorable safety profile similar to that reported in randomized controlled trials and observational European and North American studies. These data further support the value of DEX implant as a treatment option for RVO.ClinicalTrials.gov Identifier: NCT01976650. Date of registration: November 6, 2013.Keywords: retinal vein occlusion, dexamethasone, intravitreal, implant, post-marketing, real world
Published: 2021

20. Korean medicine registry of herbal medicine for weight loss

Author: Mi Mi Ko, PhD, Bo-Young Kim, MS, Mi Ju Son, KMD, PhD, Kyung Hwan Jegal, KMD, PhD, Won-Seok Chung, KMD, PhD, and Sungha Kim, KMD, PhD
Subjects: Medicine
Abstract: Abstract. Introduction:. In South Korea, the prevalence of obesity has continuously increased over the last decade, and the burden of social and economic costs has also increased immensely. The purpose of this study is to investigate the clinical characteristics and current status of patients receiving herbal medicine (HM) treatment for weight loss in Korean medicine (KM) by constructing a multi-institutional prospective registry. Methods and analysis:. This is a prospective, observational, multi-center registry, including patients visiting the KM clinics in South Korea for weight loss. This study will collaborate with 15 KM clinics and recruit patients into the registry between October 2021 and October 2022. The study population will include patients visiting the KM clinics for weight loss. A total of 1000 eligible patients visiting the KM clinics for weight loss who decide to undergo HM treatment will be enrolled in the registry. After enrollment, we will collect the individual characteristics of each patient, such as body mass index, body composition test, liver and kidney function tests, and information on prescribed HM. We will also record the adverse events at each visit. Discussion:. This study is the first prospective, multicenter registry of HM for weight loss in KM clinics. The results of this registry may show the current status of patients who receive HM treatments for weight loss and provide evidence for reasonable decision-making on KM healthcare policy for obese patients in the future.
Published: 2022
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21. Design, synthesis, and biological evaluation of histone deacetylase inhibitor with novel salicylamide zinc binding group

Author: Ji Hyun Kim, MS, Khan Hashim Ali, MS, Yong Jin Oh, PhD, Young Ho Seo, PhD, and Chang Chen.
Subjects: Medicine
Abstract: Abstract. Introduction:. Histone deacetylases (HDACs) have emerged as important therapeutic targets for various diseases, such as cancer and neurological disorders. Although a majority of HDAC inhibitors use hydroxamic acids as zinc binding groups, hydroxamic acid zinc-binding groups suffer from poor bioavailability and nonspecific metal-binding properties, necessitating a new zinc-binding group. Salicylic acid and its derivatives, well-known for their therapeutic value, have also been reported to chelate zinc ions in a bidentate fashion. This drew our attention towards replacing hydroxamic acid with salicylamide as a zinc-binding group. Methods:. In this study, for the first time, compound 5 possessing a novel salicylamide zinc-binding group was synthesized and evaluated biologically for its ability to inhibit various HDAC isoforms and induce acetylation upon α-tubulin and histone H3 among MDA-MB-231 cells. Results:. Compound 5 exhibits selective inhibition against class I HDAC isoforms (HDAC1, 2, and 3) over class II and IV HDAC isoforms (HDAC4, 6, and 11). The exposure of MDA-MB-231 cells to compound 5 efficiently induced the acetylation of more histone H3 than α-tubulin, suggesting that compound 5 is a class I selective HDAC inhibitor. Moreover, the molecular docking study indicated that the salicylamide zinc-binding group of compound 5 coordinates the active zinc ion of class I HDAC2 in a bidentate fashion. Conclusion:. Overall, salicylamide represents a novel zinc-binding group for the development of class I selective HDAC inhibitors. Graphical abstract:.
Published: 2022
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22. Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design

Author: Goo YT, Sa CK, Choi JY, Kim MS, Kim CH, Kim HK, and Choi YW
Subjects: revaprazan, supersaturation, solid micelle, box-behnken design, dissolution, oral bioavailability, Medicine (General), R5-920
Abstract: Yoon Tae Goo,1,* Cheol-Ki Sa,1,* Ji Yeh Choi,2 Min Song Kim,1 Chang Hyun Kim,1 Hyeon Kyun Kim,1 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 2Department of Psychology, York University, Toronto, Ontario, Canada*These authors contributed equally to this workCorrespondence: Young Wook ChoiCollege of Pharmacy, Chung-Ang University, 84 Heuksuk-Ro, Dongjak-Gu, Seoul, 06974, KoreaTel +82 2 820 5609Email ywchoi@cau.ac.krPurpose: To enhance the oral bioavailability of revaprazan (RVP), a novel solid, supersaturable micelle (SSuM) was developed.Methods: Surfactants and solid carriers were screened based on a solubility and a flowability test, respectively. Supersaturating agents, including Poloxamer 407 (P407), were screened. The SSuM was optimized using a Box-Behnken design with three independent variables, including Gelucire 44/14:Brij L4 (G44/BL4; X1) and the amounts of Florite PS-10 (FLO; X2) and Vivapur 105 (VP105; X3), and three response variables, ie, dissolution efficiency at 30 min (Y1), dissolution enhancing capacity (Y2), and Carr’s index (Y3). The solid state property was evaluated, and a dissolution test was conducted. RVP, Revanex®, solid micelle (P407-free from the composition of SSuM), and SSuM were orally administrated to rats (RVP 20 mg equivalent/kg) for in vivo pharmacokinetic study.Results: G44 and BL4 showed great solubility, with a critical micelle concentration range of 119.2– 333.0 μg/mL. P407 had an excellent supersaturating effect. FLO and VP105 were selected as solid carriers, with a critical solidifying ratio (g/mL) of 0.30 and 0.91, respectively. With optimized values of X1 (– 0.41), X2 (0.31), and X3 (– 0.78), RVP (200 mg)-containing SSuM consisting of G44 (253.8 mg), BL4 (106.2 mg), FLO (99.3 mg), VP105 (199.8 mg), and P407 (40 mg) was developed, resulting in Y1 (40.3%), Y2 (0.008), and Y3 (12.3%). RVP existed in an amorphous state in the optimized SSuM, and the SSuM formed a nanosized dispersion in the aqueous phase, with approximately 71.7% dissolution at 2 h. The optimized SSuM improved the relative bioavailability of RVP in rats by approximately 478%, 276%, and 161% compared to raw RVP, Revanex®, and solid micelle, respectively.Conclusion: The optimized SSuM has great potential for the development of solidified formulations of poorly water-soluble drugs with improved oral absorption.Keywords: revaprazan, supersaturation, solid micelle, Box-Behnken design, dissolution, oral bioavailability
Published: 2021

23. Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial

Author: Ahn, HK, Cho, EK, Park, IH, Lee, KS, Sim, SS, Hong, SJ, Chang, MH, Kim, JH, Kim, YJ, Kim, SH, Suh, KJ, Park, YH, Park, WY, Choi, YL, Yu, JH, Im, YH, Ahn, JS, Hur, JY, Park, SH, Kim, JY, Nam, SJ, Lee, JE, Kim, SW, Lee, SK, Im, SA, Kim, MS, Kim, TY, Oh, DY, Lee, KH, Lee, DW, Kim, HJ, Jung, KH, Kim, SB, Ahn, JH, Kim, JE, Jung, JH, Kang, SY, Ahn, MS, Choi, YW, Kim, GM, Sohn, JH, Kim, MH, Koh, SJ, Cheon, JK, Lee, JI, Lim, ST, Hyun, SY, Lee, KE, Lee, MH, Cho, JH, Lim, JH, Park, Yeon Hee, Kim, Tae-Yong, Kim, Gun Min, Kang, Seok Yun, Park, In Hae, Kim, Jee Hyun, Lee, Kyoung Eun, Ahn, Hee Kyung, Lee, Moon Hee, Kim, Hee-Jun, Kim, Han Jo, Lee, Jong In, Koh, Su-Jin, Kim, Ji-Yeon, Lee, Kyung-Hun, Sohn, Joohyuk, Kim, Sung-Bae, Ahn, Jin-Seok, Im, Young-Hyuck, Jung, Kyung Hae, and Im, Seock-Ah
Published: 2019
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24. A novel GPR119 agonist DA-1241 preserves pancreatic function via the suppression of ER stress and increased PDX1 expression

Author: Mi-Kyung Kim, Ph.D, Ye Hwang Cheong, Ph.D, Seung Ho Lee, Ph.D, Tae Hyoung Kim, MS, Il Hoon Jung, MS, Yuna Chae, MS, Jeong-Ha Lee, MS, Eun Kyoung Yang, MS, Hansu Park, MS, Jae-Sung Yang, Ph.D, and Ki Whan Hong, Ph.D
Subjects: β-cell, DA-1241, ER stress, GPR119 agonist, PDX1, Type 2 diabetes, Therapeutics. Pharmacology, RM1-950
Abstract: DA-1241 is a novel small molecule G protein-coupled receptor 119 (GPR119) agonist in early clinical development for type 2 diabetic patients. This study aimed to elucidate the pharmacological characteristics of DA-1241 for its hypoglycemic action. DA-1241 potently and selectively activated GPR119 with enhanced maximum efficacy. DA-1241 increased intracellular cAMP in HIT-T15 insulinoma cells (EC50, 14.7 nM) and increased insulin secretion (EC50, 22.3 nM) in association with enhanced human insulin promoter activity. Accordingly, postprandial plasma insulin levels were increased in mice after single oral administration of DA-1241. Postprandial glucose excursion was significantly reduced by single oral administration of DA-1241 in wild-type mice but not in GPR119 knockout mice. GLP-1 secretion was increased by DA-1241 treatment in mice. Thus, upon combined sitagliptin and DA-1241 treatment in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice, plasma active GLP-1 levels were synergistically increased. Accordingly, blood glucose and triglyceride levels were significantly lowered both by DA-1241 and sitagliptin alone and in combination. Immunohistochemical analysis revealed that β-cell mass with reduced PDX1 levels in the islets from HFD/STZ diabetic mice was significantly preserved by DA-1241, whereas increased glucagon and BiP levels were significantly suppressed. In HIT-T15 insulinoma cells subjected to ER stress, decreased cell viability was significantly rescued by treatment with DA-1241. Additionally, increased apoptosis was largely attenuated by DA-1241 by inhibiting BiP and CHOP expression through suppression of p38 MAPK. In conclusion, these studies provide evidence that DA-1241 can be a promising antidiabetic drug by potentially preserving pancreatic functions through suppressing ER stress and increasing PDX1 expression.
Published: 2021
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25. Ankle Proprioception Deficit Is the Strongest Factor Predicting Balance Impairment in Patients With Chronic Stroke

Author: Ji-Eun Cho, PT, PhD and Hogene Kim, MS, PhD
Subjects: Ankle, Balance, Berg balance scale, Proprioception, Rehabilitation, Stroke, Medicine (General), R5-920
Abstract: Objective: To determine the main factor that predicts balance impairment in patients with chronic stroke. Design: Cross-sectional study. Setting: Inpatient rehabilitation hospital and research laboratory. Participants: A total of 57 patients (42 men, 15 women; mean age 55.7±12.2 years) with chronic symptoms after stroke. Interventions: Not applicable. Main Outcome Measures: Primary outcomes were ankle functions, including strength, range of motion, and proprioception, and balance, including Berg Balance Scale score and Timed Up and Go test values. Secondary outcomes included gait kinematics, Fugl-Meyer Scale score, and Fall Efficacy Scale score. Results: According to the cutoff score
Published: 2021
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26. Effects of Steady Low-Intensity Exercise on High-Fat Diet Stimulated Breast Cancer Progression Via the Alteration of Macrophage Polarization

Author: Min Kyoon Kim MD, PhD, Yesl Kim MS, SeungHwa Park MS, Eunju Kim PhD, Yerin Kim MS, Yuri Kim PhD, and Jung-Hyun Kim PhD
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Physical inactivity and high-fat diet, especially high saturated fat containing diet are established risk factors for breast cancer that are amenable to intervention. High-fat diet has been shown to induce tumor growth and metastasis by alteration of inflammation but steady exercise has anti-tumorigenic effects. However, the mechanisms underlying the effects of physical activity on high-fat diet stimulated breast cancer initiation and progression are currently unclear. In this study, we examined how the intensity of physical activity influences high fat diet-stimulated breast cancer latency and progression outcomes, and the possible mechanisms behind these effects. Five-week-old female Balb/c mice were fed either a control diet or a high-fat diet for 8 weeks, and then 4T1 mouse mammary tumor cells were inoculated into the mammary fat pads. Exercise training occurred before tumor cell injection, and tumor latency and tumor volume were measured. Mice with a high-fat diet and low-intensity exercise (HFLE) had a longer tumor latency period, slower tumor growth, and smaller tumor volume in the final tumor assessment compared with the control, high-fat diet control (HFDC), and high-fat diet with moderate-intensity exercise (HFME) groups. Steady low- and moderate-intensity exercise had no effect on cell proliferation but induced apoptosis by activating caspase-3 through the alteration of Bcl-2, Bcl-xL, and Bax expression. Furthermore, steady exercise reduced M2 macrophage polarization in breast tumor tissue, which has been linked to tumor growth. The myokine, myostatin, reduced M2 macrophage polarization through the inhibition of the JAK-STAT signaling pathway. These results suggest that steady low-intensity exercise could delay breast cancer initiation and growth and reduce tumor volume through the induction of tumor cell apoptosis and the suppression of M2 macrophage polarization.
Published: 2020
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27. Deep-learning-based cardiovascular risk stratification using coronary artery calcium scores predicted from retinal photographs

Author: Tyler Hyungtaek Rim, MD, Chan Joo Lee, MD, Yih-Chung Tham, PhD, Ning Cheung, MD, Marco Yu, PhD, Geunyoung Lee, BS, Youngnam Kim, MS, Daniel S W Ting, MD, Crystal Chun Yuen Chong, BS, Yoon Seong Choi, MD, Tae Keun Yoo, MD, Ik Hee Ryu, MD, Su Jung Baik, MD, Young Ah Kim, MD, Sung Kyu Kim, MD, Sang-Hak Lee, ProfMD, Byoung Kwon Lee, ProfMD, Seok-Min Kang, ProfMD, Edmund Yick Mun Wong, FRCSEd, Hyeon Chang Kim, ProfMD, Sung Soo Kim, ProfMD, Sungha Park, ProfMD, Ching-Yu Cheng, ProfMD, and Tien Yin Wong, ProfMD
Subjects: Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Summary: Background: Coronary artery calcium (CAC) score is a clinically validated marker of cardiovascular disease risk. We developed and validated a novel cardiovascular risk stratification system based on deep-learning-predicted CAC from retinal photographs. Methods: We used 216 152 retinal photographs from five datasets from South Korea, Singapore, and the UK to train and validate the algorithms. First, using one dataset from a South Korean health-screening centre, we trained a deep-learning algorithm to predict the probability of the presence of CAC (ie, deep-learning retinal CAC score, RetiCAC). We stratified RetiCAC scores into tertiles and used Cox proportional hazards models to evaluate the ability of RetiCAC to predict cardiovascular events based on external test sets from South Korea, Singapore, and the UK Biobank. We evaluated the incremental values of RetiCAC when added to the Pooled Cohort Equation (PCE) for participants in the UK Biobank. Findings: RetiCAC outperformed all single clinical parameter models in predicting the presence of CAC (area under the receiver operating characteristic curve of 0·742, 95% CI 0·732–0·753). Among the 527 participants in the South Korean clinical cohort, 33 (6·3%) had cardiovascular events during the 5-year follow-up. When compared with the current CAC risk stratification (0, >0–100, and >100), the three-strata RetiCAC showed comparable prognostic performance with a concordance index of 0·71. In the Singapore population-based cohort (n=8551), 310 (3·6%) participants had fatal cardiovascular events over 10 years, and the three-strata RetiCAC was significantly associated with increased risk of fatal cardiovascular events (hazard ratio [HR] trend 1·33, 95% CI 1·04–1·71). In the UK Biobank (n=47 679), 337 (0·7%) participants had fatal cardiovascular events over 10 years. When added to the PCE, the three-strata RetiCAC improved cardiovascular risk stratification in the intermediate-risk group (HR trend 1·28, 95% CI 1·07–1·54) and borderline-risk group (1·62, 1·04–2·54), and the continuous net reclassification index was 0·261 (95% CI 0·124–0·364). Interpretation: A deep learning and retinal photograph-derived CAC score is comparable to CT scan-measured CAC in predicting cardiovascular events, and improves on current risk stratification approaches for cardiovascular disease events. These data suggest retinal photograph-based deep learning has the potential to be used as an alternative measure of CAC, especially in low-resource settings. Funding: Yonsei University College of Medicine; Ministry of Health and Welfare, Korea Institute for Advancement of Technology, South Korea; Agency for Science, Technology, and Research; and National Medical Research Council, Singapore.
Published: 2021
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28. Subjective Perception of Individuals with Physical Disabilities Regarding Exercise Equipment Use

Author: Song Yi Lee PhD, Jung Ah Lee PT, PhD, Hee Jung Chung PhD, Hyun-Jin Kim OT, PhD, Yu Cheon Kim MS, and Hogene Kim PhD
Subjects: Public aspects of medicine, RA1-1270
Abstract: Rehabilitation exercise is effective for improving the health of persons with physical disabilities. However, there are limited studies on their perception of exercise equipment use. The purpose of this study was to investigate the subjectivity to understand the types of perceptions of individuals with physical disabilities regarding the use of exercise equipment in South Korea. This study used Q-methodology. A literature review and focus group interviews with individuals with physical disabilities were conducted to construct Q-Population. Q-statements were selected from the Q-population, after which Q-sorting was executed by P-sample. The results indicated 4 perception types: (1) “Independent user,” (2) “Practical user,” (3) “Motivational user,” and (4) “Convenience user.” Recommendations were provided for developing exercise equipment for use by individuals with physical disabilities. This study revealed 4 perception categories and the findings have strong potential to contribute to the development of proper services and the effective utilization of exercise equipment for individuals with physical disabilities.
Published: 2021
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29. Treatment strategies and clinical outcomes of locally advanced pancreatic cancer patients treated at high-volume facilities and academic centers

Author: John M. David, MD, Sungjin Kim, MS, Veronica R. Placencio-Hickok, PhD, Arman Torosian, BS, Andrew Hendifar, MD, and Richard Tuli, MD, PhD
Subjects: Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Purpose: Locally advanced pancreatic cancer (LAPC) treatment has varying practice patterns with poor outcomes. We investigated treatment using single-agent chemotherapy and multiagent chemotherapy (MAC) with or without radiation therapy (RT) at high-volume facilities (HVFs) and academic centers (ACs). Methods and Materials: The National Cancer Database was used to obtain data on 10,139 patients with LAPC. HVF was defined as the top 5% of facilities per number of patients treated at each facility. Univariate and multivariable (MVA) analysis Cox regressions were performed to identify the impact of HVF, AC, MAC, and RT on overall survival (OS). Results: The median age of patients was 66 years (range, 22-90); 50.1% were male and 49.9% female. Of the patients, 46.1% received MAC, 53.8% received single-agent chemotherapy, 45.7% received RT, 54.3% did not receive RT, and 5% underwent surgical resection. The median follow-up was 48.8 months. On MVA, treatment at HVFs and ACs remained significantly associated with improved OS, with a hazard ratio (HR) of 0.84 (P
Published: 2019
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30. A Population-Based Investigation of Health-Care Needs and Preferences in American Adults With Multiple Sclerosis

Author: Chungyi Chiu PhD, Malachy Bishop PhD, Bradley McDaniels MRC, CRC, Byung-Jin Kim MS, and Lebogang Tiro MRC, CRC
Subjects: Medicine (General), R5-920
Abstract: Background: Comprehensive and effective multiple sclerosis (MS) health care requires understanding of patients’ needs, preferences, and priorities. Objective: To evaluate priorities of patients with MS for their MS care. Methods: Participants included 3003 Americans with MS recruited through the National MS Society and the North American Research Committee on Multiple Sclerosis patient registry. Participants completed a comprehensive questionnaire on aspects of their health-care experiences. Results: Participants identified the top 3 health-care priorities as (1) the affordability of MS health care, (2) ensuring that non-MS health-care providers have more education about MS and how it can interact with other conditions, and (3) access to an MS center or specialized MS clinic with MS health-care professionals together in one place. Participants receiving care in an MS center rated the quality and their satisfaction with care higher than those receiving care in other settings. Although having the opportunity to evaluate their health-care quality was important to the participants, only 36.4% had been provided the opportunity in the past year. Conclusions: This study identifies health-care priorities and concerns for Americans with MS.
Published: 2020
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31. Lack of association between airflow limitation and recurrence of venous thromboembolism among cancer patients with pulmonary embolism

Author: Shin SH, Kang D, Cho J, Chang H, Kim MS, Lee SY, Lee H, Kim H, Kim DK, Kim EK, and Park HY
Subjects: chronic obstructive pulmonary disease, cancer, pulmonary embolism, recurrence, venous thromboembolism, Diseases of the respiratory system, RC705-779
Abstract: Sun Hye Shin,1 Danbee Kang,2 Juhee Cho,2 Haseong Chang,3 Min Sun Kim,3 Su Yeon Lee,3 Hyun Lee,1 Hojoong Kim,1 Duk-Kyung Kim,3 Eun Kyoung Kim,3,* Hye Yun Park1,* 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 2Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea; 3Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea *These authors contributed equally to this work Background: COPD is a well-known risk factor for venous thromboembolism (VTE) development. However, recent data showed that it was not associated with VTE recurrence risk, which excluded cancer patients. This study investigated the association of airflow limitation and VTE recurrence in cancer patients with pulmonary embolism (PE). Methods: This is a retrospective cohort study of cancer patients with newly diagnosed PE at a university hospital. PE was confirmed using contrast-enhanced computed tomography scan. Airflow limitation was defined as pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC)
Published: 2018

32. Abstract 131: Dynamic Self-regenerating Cartilage Construct For Cartilage Repair In The Hand

Author: Yingfang Fan, MD, PhD, Samuel D. Zarfos, BS, Gem Runyan, MS, Jongkil Kim, MS, Stephen Sloan, MS, Bonassar Lawrence, PhD, Mark A. Randolph, MAS, and Robert W. Redmond, PhD
Subjects: Surgery, RD1-811
Published: 2020
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33. Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

Author: Kim MS, Yeom DW, Kim SR, Yoon HY, Kim CH, Son HY, Kim JH, Lee S, and Choi YW
Subjects: Chitosan, colon-specific delivery, acidification, microflora, factorial design, controlled release, Therapeutics. Pharmacology, RM1-950
Abstract: Min Soo Kim,1,* Dong Woo Yeom,1,* Sung Rae Kim,1 Ho Yub Yoon,1 Chang Hyun Kim,1 Ho Yong Son,1 Jin Han Kim,1 Sangkil Lee,2 Young Wook Choi1 1College of Pharmacy, Chung-Ang University, Seoul, 2College of Pharmacy, Keimyung University, Daegu, South Korea *These authors contributed equally to this work Abstract: A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. Keywords: chitosan, colon-specific delivery, acidification, microflora, factorial design, controlled release
Published: 2016

34. Inhibitory Effects of HangAmDan-B1 (HAD-B1) Combined With Afatinib on H1975 Lung Cancer Cell–Bearing Mice

Author: Hwa Jeong Kang MS, Jeehye Kim MS, Seong Hyeok Cho MS, So-Jung Park OMD, Hwa-Seung Yoo OMD, and In-Cheol Kang PhD
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Epidermal growth factor receptor mutation-positive non–small cell lung cancer is cared for mainly by target therapeutics in the clinical treatment at present. We investigated the antitumor effect of HangAmDan-B1 (HAD-B1) combined with afatinib on H1975 (L858R/T790M double mutation) lung cancer cells. The combined treatment of HAD-B1 with afatinib inhibited the proliferation of H1975 cells in a dose-dependent manner compared with the treatment of afatinib or HAD-B1 alone. The combined treatment group significantly induced early apoptosis and cell cycle arrest of the cells compared with afatinib- or HAD-B1-treated control group. Profile analysis of cell cycle proteins in H1975 cells treated with the combination of HAD-B1 and afatinib using InnoPharmaScreen antibody microarray showed downregulation of pERK1/2 and upregulation of p16 in the cells. In vivo tumor growth assay in xenograft animal model of human H1975 lung cancer cells revealed that the mean tumor volume in the group treated with the combination of HAD-B1 and afatinib showed a significant reduction compared with the control groups.
Published: 2019
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35. Effects of combined Adeli suit and neurodevelopmental treatment in children with spastic cerebral palsy with gross motor function classification system levels I and II

Author: Mi-Ra Kim, MS, PT, Byoung-Hee Lee, PhD, and Dae-Sung Park, PT, PhD
Subjects: Adeli suit, balance, gait, Gross Motor Function Measure, spastic cerebral palsy, Therapeutics. Pharmacology, RM1-950
Abstract: Background: Children with cerebral palsy (CP) exhibit diverse gait patterns depending on their neurological deficits and musculoskeletal problems. The Adeli suit treatment (AST) has been proposed as an intensive exercise protocol in the management of CP. Objectives: The aim of this study was to compare the effects of a 6-week programme of combined AST and neurodevelopment treatment (NDT) with those of NDT alone on Gross Motor Function Measure (GMFM), balance, and gait in children with CP. Methods: Twenty children with CP of Gross Motor Function Classification System levels I and II were randomly assigned to one of the following two groups: (1) NDT or (2) AST/NDT. The participants were assessed using the GMFM, Pediatric Balance Scale (PBS), Timed Up and Go (TUG) test, and spatiotemporal gait parameters. Results: The GMFM, PBS, and TUG test for both groups showed a statistically significant increase (p
Published: 2016
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36. Decision-making deficits in patients with chronic schizophrenia: Iowa Gambling Task and Prospect Valence Learning model

Author: Kim MS, Kang BN, and Lim JY
Subjects: Decision-making, Iowa Gambling Task, PVL model, Schizophrenia, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Myung-Sun Kim,1 Bit-Na Kang,1 Jae Young Lim2 1Department of Psychology, Sungshin Women’s University, Seoul, Republic of Korea; 2Department of Psychiatry, Keyo Medical Foundation, Keyo Hospital, Uiwang, Republic of Korea Purpose: Decision-making is the process of forming preferences for possible options, selecting and executing actions, and evaluating the outcome. This study used the Iowa Gambling Task (IGT) and the Prospect Valence Learning (PVL) model to investigate deficits in risk-reward related decision-making in patients with chronic schizophrenia, and to identify decision-making processes that contribute to poor IGT performance in these patients. Materials and methods: Thirty-nine patients with schizophrenia and 31 healthy controls participated. Decision-making was measured by total net score, block net scores, and the total number of cards selected from each deck of the IGT. PVL parameters were estimated with the Markov chain Monte Carlo sampling scheme in OpenBugs and BRugs, its interface to R, and the estimated parameters were analyzed with the Mann–Whitney U-test.Results: The schizophrenia group received significantly lower total net scores compared to the control group. In terms of block net scores, an interaction effect of group × block was observed. The block net scores of the schizophrenia group did not differ across the five blocks, whereas those of the control group increased as the blocks progressed. The schizophrenia group obtained significantly lower block net scores in the fourth and fifth blocks of the IGT and selected cards from deck D (advantageous) less frequently than the control group. Additionally, the schizophrenia group had significantly lower values on the utility-shape, loss-aversion, recency, and consistency parameters of the PVL model. Conclusion: These results indicate that patients with schizophrenia experience deficits in decision-making, possibly due to failure in learning the expected value of each deck, and incorporating outcome experiences of previous trials into expectancies about options in the present trial. Keywords: IGT, PVL model, risk-reward related decision-making
Published: 2016

37. Addendum to: Measurement and QCD analysis of double-differential inclusive jet cross sections in proton-proton collisions at $$ \sqrt{\textrm{s}} $$ = 13 TeV

Author: Tumasyan, A, Adam, W, Andrejkovic, JW, Bergauer, T, Chatterjee, S, Damanakis, K, Dragicevic, M, Escalante Del Valle, A, Frühwirth, R, Jeitler, M, Krammer, N, Cankocak, K, Ehataht, K, Tannenwald, B, Kim, J, Kalinowski, A, White, S, Wolfe, E, Poudyal, N, Guerrero, D, Black, K, Pétré, L, Jang, W, Pant, LM, Bose, T, Caillol, C, Dasu, S, De Bruyn, I, Everaerts, P, Kadastik, M, Konecki, M, Fienga, F, Galloni, C, Komurcu, Y, Joshi, BM, Shukla, P, He, H, Herndon, M, Hervé, A, Hussain, U, Lanaro, A, Loeliger, A, Loveless, R, Madhusudanan Sreekala, J, Sen, S, Krolikowski, J, Nandan, S, Aziz, T, Mejia Guisao, J, Mallampalli, A, Mohammadi, A, Pinna, D, Savin, A, Shang, V, Sharma, V, Chen, M, Smith, WH, Teague, D, Trembath-Reichert, S, Dugad, S, Araujo, M, Kim, M, Vetens, W, Nielsen, C, CMS Collaboration, Pata, J, Cerci, S, Raidal, M, Makarenko, V, Tani, L, Veelken, C, Volkov, S, Eerola, P, Forthomme, L, Koenig, E, Bargassa, P, Kirschenmann, H, Hos, I, Osterberg, K, Voutilainen, M, Bharthuar, S, Brücken, E, Garcia, F, Kumar, M, Darwish, MR, Havukainen, J, Kim, MS, Konigsberg, J, Ivanov, A, Kinnunen, R, Rebello Teles, P, Lampén, T, Lassila-Perini, K, Lehti, S, Lindén, T, Niedziela, M, Lotti, M, Martikainen, L, Myllymäki, M, Kaynak, B, De Wolf, EA, Korytov, A, Ott, J, Siikonen, H, Bastos, D, Tuominen, E, Tuominiemi, J, Banerjee, S, Luukka, P, Petrow, H, Ozkorucuklu, S, Tuuva, T, Amendola, C, Besancon, M, Lo, KH, Couderc, F, Janssen, T, Dejardin, M, Boletti, A, Chudasama, R, Denegri, D, Tiwari, PC, Saha, P, Faure, JL, Ferri, F, Ganjour, S, Gras, P, Hamel de Monchenault, G, Matchev, K, Jarry, P, Lenzi, B, Locci, E, Mills, C, Sunar Cerci, D, Kello, T, Faccioli, P, Malcles, J, Rander, J, Rosowsky, A, Sahin, MÖ, Savoy-Navarro, A, Valencia Palomo, L, Titov, M, Yu, GB, Zorbilmez, C, Karasavvas, D, Guchait, M, Ahuja, S, Beaudette, F, Bonanomi, M, Gallinaro, M, Lelek, A, Buchot Perraguin, A, Busson, P, Cappati, A, Grynyov, B, Menendez, N, Charlot, C, Karmakar, S, Davignon, O, Diab, B, Falmagne, G, Ghosh, S, Granier de Cassagnac, R, Lee, J, Hollar, J, Kang, DY, Hakimi, A, Rejeb Sfar, H, Mitselmakher, G, Kumar, S, Kucher, I, Motta, J, Nguyen, M, Ochando, C, Paganini, P, Rembser, J, Levchuk, L, Salerno, R, Sarkar, U, Leonardo, N, Sauvan, JB, Majumder, G, Muthirakalayil Madhu, A, Sirois, Y, Van Mechelen, P, Tarabini, A, Zabi, A, Anthony, D, Zghiche, A, Agram, J-L, Andrea, J, Apparu, D, Bloch, D, Mazumdar, K, Niknejad, T, Rawal, N, Bourgatte, G, Brom, J-M, Bhal, E, Chabert, EC, Van Putte, S, Collard, C, Darej, D, Fontaine, J-C, Goerlach, U, Mukherjee, S, Grimault, C, Le Bihan, A-C, Ramirez, F, Iemmi, F, Pisano, M, Nibigira, E, Van Hove, P, Asilar, E, Beauceron, S, Van Remortel, N, Bernet, C, Vorobyev, A, Boudoul, G, Camen, C, Kaadze, K, Carle, A, Rosenzweig, D, Chanon, N, Seixas, J, Contardo, D, Depasse, P, El Mamouni, H, Fay, J, Alpana, K, Gascon, S, Sanchez Cruz, S, Bologna, S, Blekman, F, Gouzevitch, M, Ille, B, Rosenzweig, S, Laktineh, IB, Lattaud, H, Toldaiev, O, Lesauvage, A, Lethuillier, M, Dube, S, Elkafrawy, T, Mirabito, L, Perries, S, Shchablo, K, Sordini, V, Bols, ES, Rotter, J, Torterotot, L, Touquet, G, Vander Donckt, M, Santoro, A, Cavanaugh, R, Roskas, C, Viret, S, Lomidze, I, Toriashvili, T, Tsamalaidze, Z, Botta, V, Feld, L, Shi, K, Klein, K, D’Hondt, J, Brooke, JJ, Lipinski, M, Oh, YD, Oh, G, Meuser, D, Varela, J, Pauls, A, Röwert, N, Schulz, J, Teroerde, M, Dodonova, A, Bundock, A, Sturdy, J, Eliseev, D, Erdmann, M, Kansal, B, Fackeldey, P, Delcourt, M, Fischer, B, Afanasiev, S, Hebbeker, T, Clement, E, Hoepfner, K, Ivone, F, Ayala, G, Mastrolorenzo, L, Laha, A, Merschmeyer, M, Meyer, A, Mocellin, G, Mondal, S, El Faham, H, Cussans, D, Budkouski, D, Noll, D, Novak, A, Wang, J, Pandey, S, Pook, T, Pozdnyakov, A, Rath, Y, Reithler, H, Flacher, H, Roemer, J, Schmidt, A, Schuler, SC, Lee, SW, Golutvin, I, Lowette, S, Rane, A, Yigitbasi, E, Sharma, A, Vigilante, L, Kang, Y, Wiedenbeck, S, Zaleski, S, Dziwok, C, Flügge, G, Haj Ahmad, W, Hlushchenko, O, Kress, T, Rastogi, A, Gorbunov, I, Zuo, X, Goldstein, J, Nowack, A, Moortgat, S, Pistone, C, Pooth, O, Roy, D, Sert, H, Stahl, A, Ziemons, T, Sharma, S, Zotz, A, Schweiger, K, Heath, GP, Aarup Petersen, H, Adams, T, Karjavine, V, Aldaya Martin, M, Asmuss, P, Morton, A, Baxter, S, Bayatmakou, M, Behnke, O, Bakhshiansohi, H, Heath, HF, Bermúdez Martínez, A, Bhattacharya, S, Bin Anuar, AA, Askew, A, Borras, K, Korenkov, V, Brunner, D, Campbell, A, Cardini, A, Müller, D, Vazquez Valencia, F, Andreev, Y, Cheng, C, Colombina, F, Consuegra Rodríguez, S, Correia Silva, G, Ruiz Alvarez, JD, Danilov, V, De Silva, M, Lanev, A, Didukh, L, Sur, N, Eckerlin, G, Khazaie, E, Eckstein, D, Eren, E, Sahasransu, AR, Estevez Banos, LI, Filatov, O, Habibullah, R, Gallo, E, Gao, J, Kreczko, L, Geiser, A, Malakhov, A, Hohlmann, M, Zeinali, M, Giraldi, A, Grohsjean, A, Guthoff, M, Jafari, A, Jomhari, NZ, Tavernier, S, Kapoor, A, Hagopian, V, Jung, H, Kasem, A, Kasemann, M, Godinovic, N, Kaveh, H, Matveev, V, Kleinwort, C, Krücker, D, Lange, W, Krikler, B, Lidrych, J, Lipka, K, Johnson, KF, Lohmann, W, Van Doninck, W, Chenarani, S, Mäkelä, T, Mankel, R, Melzer-Pellmann, I-A, Silva Do Amaral, SM, Paramesvaran, S, Mendizabal Morentin, M, Metwally, J, Meyer, AB, Meyer, M, Khurana, R, Mnich, J, Samalan, A, Mussgiller, A, Otarid, Y, Beghin, D, Seif El Nasr-Storey, S, Pérez Adán, D, Pitzl, D, Palichik, V, Raspereza, A, Ribeiro Lopes, B, Rübenach, J, Castilla-Valdez, H, Etesami, SM, Saggio, A, Saibel, A, Smith, VJ, Savitskyi, M, Scham, M, Scheurer, V, Bilin, B, Schnake, S, Perelygin, V, Schütze, P, Schwanenberger, C, Khakzad, M, Kolberg, T, Pitters, FM, Stylianou, N, Shchedrolosiev, M, Sosa Ricardo, RE, Stafford, D, Tonon, N, Van De Klundert, M, Walsh, R, Walter, D, Clerbaux, B, Moon, CS, Mohammadi Najafabadi, M, Da Costa, EM, Savina, M, Martinez, G, Wen, Y, Wichmann, K, Wiens, L, Wissing, C, Wuchterl, S, Zlebcik, R, Aggleton, R, Albrecht, S, Walkingshaw Pass, 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S, Monroy, J, Damarseckin, S, Patterson, JR, Quach, D, Priyanka, P, Reichert, J, Reid, M, Bin Norjoharuddeen, N, Ryd, A, Sun, W, Thom, J, Kim, B, Demiroglu, ZS, Wittich, P, Okawa, H, Zou, R, Ranjan, K, Albrow, M, Alyari, M, Apollinari, G, Apresyan, A, Wan Abdullah, WAT, Apyan, A, Mal, P, Uribe Estrada, C, Bauerdick, LAT, Berry, D, Shah, A, Berryhill, J, Bhat, PC, Burkett, K, Butler, JN, Dolek, F, Canepa, A, Yusli, MN, Cerati, GB, Cali, IA, Cheung, HWK, Kyriakis, A, Bharti, M, Chlebana, F, Di Petrillo, KF, Elvira, VD, Dumanoglu, I, Feng, Y, Lin, Z, Freeman, J, Gecse, Z, Gray, L, Zolkapli, Z, Bhattacharya, R, Green, D, Grünendahl, S, Eskut, E, Gutsche, O, Harris, RM, Heller, R, Herwig, TC, Hirschauer, J, Xiao, M, Jayatilaka, B, Jindariani, S, D’Alfonso, M, Williams, J, Fonseca De Souza, S, Johnson, M, Joshi, U, Klijnsma, T, Klima, B, Kwok, KHM, Lammel, S, Lincoln, D, Lipton, R, Bhowmik, D, Chapon, E, Avila, C, Eysermans, J, Liu, T, Freer, C, Gomez Ceballos, G, O’Dell, V, Goncharov, M, Harris, P, Hu, M, Starodumov, A, Seo, H, Dutta, S, Lechner, L, Klute, M, Kovalskyi, D, Krupa, J, Lee, Y-J, Mironov, C, Papadimitriou, V, Paus, C, Rankin, D, Guler, Y, Roland, C, Gerber, CE, Roland, G, Shi, Z, Mota Amarilo, K, Susa, T, Stephans, GSF, Wang, Z, Pedro, K, Gurpinar Guler, E, Wyslouch, B, Chatterjee, RM, Knolle, J, Evans, A, Hiltbrand, J, Krohn, M, Mijuskovic, J, Kubota, Y, Wulz, C-E, Isik, C, Attikis, A, Pena, C, Mans, J, Revering, M, Rusack, R, Saradhy, R, Schroeder, N, Strobbe, N, Wadud, MA, Kara, O, Raicevic, N, Bloom, K, Bryson, M, Prokofyev, O, Sosnov, D, Christoforou, K, Claes, DR, Fangmeier, C, Finco, L, Mishra, T, Golf, F, Joo, C, Kravchenko, I, Krofcheck, D, Musich, M, Gomber, B, Ravera, F, Reed, I, Siado, JE, Snow, GR, Kayis Topaksu, A, Erodotou, E, Tabb, W, Yan, F, Zecchinelli, AG, Agarwal, G, Bandyopadhyay, H, Loukas, D, Maity, M, Butler, PH, Reinsvold Hall, A, Kiminsu, U, Hay, L, Iashvili, I, Kharchilava, A, McLean, C, Nguyen, D, Ioannou, A, Pekkanen, J, Rappoccio, S, Palit, P, Williams, A, Onengut, G, Alverson, G, Ristori, L, Ahmad, A, Barberis, E, Haddad, Y, Hortiangtham, A, Li, J, Madigan, G, Marzocchi, B, Rout, PK, Ozdemir, K, Kole, G, Morse, DM, Nguyen, V, Sexton-Kennedy, E, Orimoto, T, Asghar, MI, Parker, A, Skinnari, L, Tishelman-Charny, A, Wamorkar, T, Brigljevic, V, Saha, G, Wang, B, Wisecarver, A, Wood, D, Kolosova, M, León Coello, M, Bueghly, J, Awais, A, Chen, Z, Polatoz, A, Gilbert, A, Sahu, B, Gunter, T, Hahn, KA, Liu, Y, Odell, N, Schmitt, MH, Smith, N, Velasco, M, Konstantinou, S, Simsek, AE, Band, R, Kim, DH, Sarkar, S, Awan, MIM, Bucci, R, Cremonesi, M, Das, A, Dev, N, Goldouzian, R, Florez, C, Yang, UK, Hildreth, M, Hurtado Anampa, K, Jessop, C, Hangal, DA, Lannon, K, Mousa, J, Hoorani, HR, Lawrence, J, Loukas, N, Lutton, D, Chen, GM, Marinelli, N, Soha, A, Mcalister, I, McCauley, T, Sharan, M, Mcgrady, C, Mohrman, K, Moore, C, Musienko, Y, Khan, WA, Tali, B, Nicolaou, C, Ruchti, R, Siddireddy, P, Spalding, WJ, Townsend, A, Singh, B, Wayne, M, Wightman, A, Zarucki, M, Zygala, L, Muraleedharan Nair Bindhu, VK, Bylsma, B, Cardwell, B, Mundim, L, Durkin, LS, Ptochos, F, Spiegel, L, Lambrecht, L, Francis, B, Hill, C, Nunez Ornelas, M, Tok, UG, Wei, K, Winer, BL, Yates, BR, Addesa, FM, Bonham, B, Shah, MA, Das, P, Stakia, A, Sulimov, V, Stoynev, S, Turkcapar, S, Dezoort, G, Chekhovsky, V, Razis, PA, Elmer, P, Frankenthal, A, Greenberg, B, Haubrich, N, Higginbotham, S, Kalogeropoulos, A, Thakur, S, Zorbakir, IS, Shoaib, M, Strait, J, Kopp, G, Kwan, S, Lange, D, Marlow, D, Rykaczewski, H, Mei, K, Ojalvo, I, Olsen, J, Isildak, B, Behera, PK, Stickland, D, Tully, C, Taylor, L, Waqas, M, Norberg, S, Bakshi, AS, Barnes, VE, Chawla, R, Karapinar, G, Saka, H, Behera, SC, Das, S, Gutay, L, Jones, M, Tkaczyk, S, Jung, AW, Avati, V, Karmarkar, S, Kondratyev, D, Wilson, G, Liu, M, Negro, G, Kalbhor, P, Neumeister, N, Paspalaki, G, Finger, M, Piperov, S, Tran, NV, Purohit, A, Schulte, JF, Ocalan, K, Grzanka, L, Stojanovic, M, Thieman, J, Muhammad, A, Wang, F, Xiao, R, Xie, W, Dolen, J, Parashar, N, Murillo Quijada, JA, Yalvac, M, Baty, A, Carnahan, T, Malawski, M, Pradhan, R, Decaro, M, Dildick, S, Ecklund, KM, Freed, S, Gardner, P, Akgun, B, Geurts, FJM, Uplegger, L, Li, W, Kveton, A, Hofman, DJ, Padley, BP, Kim, GN, Bialkowska, H, Redjimi, R, Yoon, I, Shi, W, Stahl Leiton, AG, Vaandering, EW, Zhang, L, Pujahari, PR, Bodek, A, de Barbaro, P, Demina, R, Murzin, V, Ayala, E, Bluj, M, Dulemba, JL, Fallon, C, Ferbel, T, Fraga, J, Galanti, M, Garcia-Bellido, A, Hindrichs, O, Atakisi, IO, Khukhunaishvili, A, Ranken, E, Taus, R, Chiarito, B, Boimska, B, Carrera Jarrin, E, Chou, JP, Weber, HA, Diamantopoulou, M, Sikdar, AK, Chen, HS, Gandrakota, A, Gershtein, Y, Halkiadakis, E, Hart, A, Heindl, M, Karacheban, O, Laflotte, I, Lath, A, Górski, M, Montalvo, R, Gülmez, E, Dutta, D, Acosta, D, Assran, Y, Nash, K, Osherson, M, Salur, S, Schnetzer, S, Somalwar, S, Stone, R, Thayil, SA, Kaya, M, Thomas, S, Uvarov, L, Nogima, H, Avery, P, Wang, H, Acharya, H, Ellithi Kamel, A, Delannoy, AG, Fiorendi, S, Spanier, S, Kaya, O, Bouhali, O, Dalchenko, M, Mestdach, G, Delgado, A, Eusebi, R, Bourilkov, D, Kazana, M, Gilmore, J, Huang, T, Kamon, T, Özçelik, Ö, Litomin, A, Mahmoud, MA, Jha, V, Luo, S, Malhotra, S, Mueller, R, Cadamuro, L, Overton, D, Szleper, M, Duric, S, Rathjens, D, Safonov, A, Akchurin, N, Damgov, J, Kumar, V, Hegde, V, Mohammed, Y, Kunori, S, Lamichhane, K, Cherepanov, V, Tekten, S, Mengke, T, Zalewski, P, Muthumuni, S, Peltola, T, Mishra, DK, Volobouev, I, Whitbeck, A, Appelt, E, Yetkin, EA, Bhowmik, S, Errico, F, Greene, S, Gurrola, A, Johns, W, Bunkowski, K, Naskar, K, Melo, A, Ni, H, Padeken, K, Cakir, A, Romeo, F, Sheldon, P, Tuo, S, Sehrawat, A, Velkovska, J, Dewanjee, RK, Arenton, MW, Merrit, AH, Cox, B, Doroba, K, Nayak, A, Cummings, G, Hakala, J, Hirosky, R, Joyce, M, Ledovskoy, A, Field, RD, Li, A, Neu, C, Netrakanti, PK, and Perez Lara, CE
Subjects: Nuclear and High Energy Physics
Abstract: ArXiv ePrint: 2111.10431 (https://arxiv.org/abs/2111.10431). Copyright © 2022 The Authors. The QCD analysis at NNLO is repeated by using the NNLO interpolation grids for the double-differential inclusive jet cross section [1], which were released after the journal publication of the original analysis. The NNLOJET calculation used to derive these grids is based on the leading-colour and leading-flavour-number approximation and does not include the most recent subleading colour contributions. However, these contributions were reported in ref. [2] to be very small in inclusive jet production, in particular for a jet size of R = 0.7. The grids also contain an estimate of the numerical integration uncertainty of around 1% or less. To account for point-to-point fluctuations, this uncertainty, after consultation with the authors of NNLOJET, has been increased by a factor of two; however, its impact in the fit is negligible. A comparison of the measurement with predictions using various PDFs is shown in figure 1. Although the PDF parametrisation remains identical, higher precision in PDF and QCD parameters is expected by using NNLO grids consistently in the QCD analysis. These new results supersede those obtained by using the k-factor technique. SCOAP3.
Published: 2022

38. Chrysin Increases the Therapeutic Efficacy of Docetaxel and Mitigates Docetaxel-Induced Edema

Author: Hyun-Kyung Lim MS, Kyoung Mee Kim MS, Seong-Yun Jeong PhD, Eun Kyung Choi PhD, MD, and Joohee Jung PhD
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Docetaxel (DTX) is an effective commercial anticancer agent for chemotherapy in non–small cell lung cancer (NSCLC), breast cancer, gastric cancer, and prostate cancer, but its adverse effects including edema, neurotoxicity, and hair loss limit its application. To improve the chemotherapeutic efficacy of DTX and reduce adverse effects, combination therapy is one of the alternative methods. So chrysin, which has various biological activities including anticancer effects, was considered. In vitro, the combination of chrysin and DTX was investigated in A549 cells. Increased cytotoxicity, suppressed cellular proliferation, and induced apoptosis were observed with posttreatment of chrysin following DTX treatment. In vivo, chrysin enhanced the tumor growth delay of DTX and increased DTX-induced apoptosis in the A549-derived xenograft model. Furthermore, chrysin prevented DTX-induced edema in ICR mouse. These results indicated that chrysin strengthened the therapeutic efficacy of DTX and diminished the adverse effect of DTX, suggesting chrysin could be exploited as an adjuvant therapy for NSCLC.
Published: 2017
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39. β-Lapachone Inhibits Lung Metastasis of Colorectal Cancer by Inducing Apoptosis of CT26 Cells

Author: Ji-Ye Kee PhD, Yo-Han Han MS, Jinbong Park KMD, Dae-Seung Kim MS, Jeong-Geon Mun BS, Kwang Seok Ahn PhD, Hyun-Jung Kim PhD, Jae-Young Um PhD, and Seung-Heon Hong PhD
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: β-Lapachone is a quinone-containing compound found in red lapacho ( Tabebuia impetiginosa , syn. T avellanedae ) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. Methods: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription–polymerase chain reaction were performed to examine the effects of β-lapachone on metastatic phenotypes and molecular mechanisms. The effect of β-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. Results: We found that the inhibition of proliferation of the colon cancer cell lines by β-lapachone was due to the induction of apoptosis and cell cycle arrest. β-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of β-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, β-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, β-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, β-lapachone significantly inhibited the lung metastasis of CT26 cells. Conclusions: Our results demonstrated the inhibitory effect of β-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.
Published: 2017
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40. From Servicescape to Loyalty in the Medical Tourism Industry: A Medical Clinic’s Service Perspective

Author: Minseong Kim MS, Dong-Woo Koo PhD, Dong-Jin Shin MS, and Sae-Mi Lee PhD
Subjects: Public aspects of medicine, RA1-1270
Abstract: Medical tourism organizations have increasingly recognized that loyalty makes a medical clinic a marketing success. To increase understanding of the importance of medical clinics, this study examined the roles of servicescapes, emotions, and satisfaction in the development of customer loyalty toward medical clinics and destination. Data were collected among international medical tourists visiting Korea. Results identified that dimensions of medical clinics’ servicescape (ie, medical clinic environment, medical treatment, staff, and doctor) influenced emotions and satisfaction among international medical tourists. Also, positive emotions and the 2 dimensions of satisfaction with a medical clinic and doctor mediate the influence of medical clinics’ servicescapes on 2 types of loyalty (the medical clinic and Korea for medical care). Overall, these findings indicate that the interrelationship of servicescapes, positive emotion, and satisfaction is essential in influencing international medical tourists’ loyalty to a medical clinic.
Published: 2017
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41. Erratum to: Measurement of exclusive Υ photoproduction from protons in pPb collisions at √sNN=5.02TeV

Author: Sirunyan, AM, Tumasyan, A, Adam, W, Ambrogi, F, Asilar, E, Bergauer, T, Brandstetter, J, Brondolin, E, Dragicevic, M, Ero, J, Del Valle, AE, Flechl, M, Friedl, M, Fruhwirth, R, Ghete, VM, Grossmann, J, Hrubec, J, Jeitler, M, Konig, A, Krammer, N, Kratschmer, I, Liko, D, Madlener, T, Mikulec, I, Pree, E, Rad, N, Rohringer, H, Schieck, J, Schofbeck, R, Spanring, M, Spitzbart, D, Taurok, A, Waltenberger, W, Wittmann, J, Wulz, CE, Zarucki, M, Chekhovsky, V, Mossolov, V, Gonzalez, JS, De Wolf, EA, Di Croce, D, Janssen, X, Lauwers, J, Pieters, M, Van De Klundert, M, Van Haevermaet, H, Van Mechelen, P, Van Remortel, N, Abu Zeid, S, Blekman, F, D'Hondt, J, De Bruyn, I, De Clercq, J, Deroover, K, Flouris, G, Lontkovskyi, D, Lowette, S, Marchesini, I, Moortgat, S, Moreels, L, Python, Q, Skovpen, K, Tavernier, S, Van Doninck, W, Van Mulders, P, Van Parijs, I, Beghin, D, Bilin, B, Brun, H, Clerbaux, B, De Lentdecker, G, Delannoy, H, Dorney, B, Fasanella, G, Favart, L, Goldouzian, R, Grebenyuk, A, Kalsi, AK, Lenzi, T, Luetic, J, Seva, T, Starling, E, Vander Velde, C, Vanlaer, P, Vannerom, D, Yonamine, R, Cornelis, T, Dobur, D, Fagot, A, Gul, M, Khvastunov, I, Poyraz, D, Roskas, C, Trocino, D, Tytgat, M, Verbeke, W, Vermassen, B, Vit, M, Zaganidis, N, Bakhshiansohi, H, Bondu, O, Brochet, S, Bruno, G, Caputo, C, Caudron, A, David, P, De Visscher, S, Delaere, C, Delcourt, M, Francois, B, Giammanco, A, Krintiras, G, Lemaitre, V, Magitteri, A, Mertens, A, Musich, M, Piotrzkowski, K, Quertenmont, L, Saggio, A, Marono, MV, Wertz, S, Zobec, J, Alda, WL, Alves, FL, Alves, GA, Brito, L, Silva, GC, Hensel, C, Moraes, A, Pol, ME, Teles, PR, Das Chagas, EBB, Carvalho, W, Chinellato, J, Coelho, E, Da Costa, EM, Da Silveira, GG, Damiao, DD, De Souza, SF, Malbouisson, H, Jaime, MM, De Almeida, MM, Herrera, CM, Mundim, L, Nogima, H, Rosas, LJS, Santoro, A, Sznajder, A, Thiel, M, Manganote, EJT, De Araujo, FTD, Pereira, AV, Ahuja, S, Bernardes, CA, Calligaris, L, Tomei, TRFP, Gregores, EM, Mercadante, PG, Novaes, SF, Padula, SS, Abad, DR, Vargas, JCR, Aleksandrov, A, Hadjiiska, R, Iaydjiev, P, Marinov, A, Misheva, M, Rodozov, M, Shopova, M, Sultanov, G, Dimitrov, A, Litov, L, Pavlov, B, Petkov, P, Fang, W, Gao, X, Yuan, L, Ahmad, M, Bian, JG, Chen, GM, Chen, HS, Chen, M, Chen, Y, Jiang, CH, Leggat, D, Liao, H, Liu, Z, Romeo, F, Shaheen, SM, Spiezia, A, Tao, J, Wang, C, Wang, Z, Yazgan, E, Zhang, H, Zhao, J, Ban, Y, Chen, G, Li, J, Li, Q, Liu, S, Mao, Y, Qian, SJ, Wang, D, Xu, Z, Wang, Y, Avila, C, Cabrera, A, Montoya, CAC, Sierra, LFC, Florez, C, Hernandez, CFG, Delgado, MAS, Courbon, B, Godinovic, N, Lelas, D, Puljak, I, Cipriano, PMR, Sculac, T, Antunovic, Z, Kovac, M, Brigljevic, V, Ferencek, D, Kadija, K, Mesic, B, Starodumov, A, Susa, T, Ather, MW, Attikis, A, Mavromanolakis, G, Mousa, J, Nicolaou, C, Ptochos, F, Razis, PA, Rykaczewski, H, Finger, M, Jarrin, EC, Khalil, S, Mahmoud, MA, Mohammed, Y, Bhowmik, S, Dewanjee, RK, Kadastik, M, Perrini, L, Raidal, M, Veelken, C, Eerola, P, Kirschenmann, H, Pekkanen, J, Voutilainen, M, Havukainen, J, Heikkila, JK, Jarvinen, T, Karimaki, V, Kinnunen, R, Lampen, T, Lassila-Perini, K, Laurila, S, Lehti, S, Linden, T, Luukka, P, Maenpaa, T, Siikonen, H, Tuominen, E, Tuominiemi, J, Tuuva, T, Besancon, M, Couderc, F, Dejardin, M, Denegri, D, Faure, JL, Ferri, F, Ganjour, S, Ghosh, S, Givernaud, A, Gras, P, de Monchenault, GH, Jarry, P, Leloup, C, Locci, E, Machet, M, Malcles, J, Negro, G, Rander, J, Rosowsky, A, Sahin, MO, Titov, M, Abdulsalam, A, Amendola, C, Antropov, I, Baffioni, S, Beaudette, F, Busson, P, Cadamuro, L, Charlot, C, de Cassagnac, RG, Jo, M, Kucher, I, Lisniak, S, Lobanov, A, Blanco, JM, Nguyen, M, Ochando, C, Ortona, G, Paganini, P, Pigard, P, Salerno, R, Sauvan, JB, Sirois, Y, Leiton, AGS, Yilmaz, Y, Zabi, A, Zghiche, A, Agram, JL, Andrea, J, Bloch, D, Brom, JM, Chabert, EC, Collard, C, Conte, E, Coubez, X, Drouhin, F, Fontaine, JC, Gele, D, Goerlach, U, Jansova, M, Juillot, 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Subjects: Erratum
Abstract: Erratum to: Eur. Phys. J. C (2019) 79:277 https://doi.org/10.1140/epjc/s10052-019-6774-8 In this article the author name Luigi Calligaris was incorrectly written as A. Calligaris. The original article has been corrected.
Published: 2022

42. Measurement of the inclusive t(t)over-bar production cross section in proton-proton collisions at √s = 5.02 TeV

Author: Tumasyan, A, Adam, W, Andrejkovic, JW, Bergauer, T, Chatterjee, S, Dragicevic, M, Del Valle, AE, Fruhwirth, R, Krammer, N, Lechner, L, Liko, D, Mikulec, I, Paulitsch, P, Pitters, FM, Schieck, J, Schofbeck, R, Spanring, M, Templ, S, Waltenberger, W, Wulz, CE, Chekhovsky, V, Litomin, A, Makarenko, V, Darwish, MR, De Wolf, EA, Janssen, T, Kello, T, Lelek, A, Sfar, HR, Van Mechelen, P, Van Putte, S, Van Remortel, N, Blekman, F, Bols, ES, D'Hondt, J, Delcourt, M, El Faham, H, Lowette, S, Moortgat, S, Morton, A, Muller, D, Sahasransu, AR, Tavernier, S, Van Doninck, W, Van Mulders, P, Stylianou, N, Beghin, D, Bilin, B, Clerbaux, B, De Lentdecker, G, Favart, L, Grebenyuk, A, Kalsi, AK, Lee, K, Mahdavikhorrami, M, Makarenko, I, Moureaux, L, Petre, L, Popov, A, Postiau, N, Starling, E, Thomas, L, Vanden Bemden, M, Vander Velde, C, Vanlaer, P, Vannerom, D, Wezenbeek, L, Gao, X, Cornelis, T, Dobur, D, Knolle, J, Lambrecht, L, Mestdach, G, Niedziela, M, Roskas, C, Samalan, A, Skovpen, K, Tytgat, M, Verbeke, W, Vermassen, B, Vit, M, Bethani, A, Bruno, G, Bury, F, Caputo, C, David, P, Delaere, C, Donertas, IS, Giammanco, A, Jaffel, K, Jain, S, Lemaitre, V, Mondal, K, Prisciandaro, J, Taliercio, A, Teklishyn, M, Tran, TT, Vischia, P, Wertz, S, Alves, GA, Hensel, C, Moraes, A, Alda, WL, Pereira, MAG, Ferreira, MB, Malbouisson, HB, Carvalho, W, Chinellato, J, Da Costa, EM, Da Silveira, GG, Damiao, DD, De Souza, SF, Figueiredo, DM, Herrera, CM, Amarilo, KM, Mundim, L, Nogima, H, Teles, PR, Santoro, A, Do Amaral, SMS, Sznajder, A, Thiel, M, De Araujo, FTD, Pereira, AV, Bernardes, CA, Calligaris, L, Tomei, TRFP, Gregores, EM, Lemos, DS, Mercadante, PG, Novaes, SF, Padula, SS, Aleksandrov, A, Antchev, G, Hadjiiska, R, Iaydjiev, P, Misheva, M, Rodozov, M, Shopova, M, Sultanov, G, Dimitrov, A, Ivanov, T, Litov, L, Pavlov, B, Petkov, P, Petrov, A, Cheng, T, Guo, Q, Javaid, T, Mittal, M, Wang, H, Yuan, L, Ahmad, M, Bauer, G, Dozen, C, Hu, Z, Martins, J, Wang, Y, Yi, K, Chapon, E, 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Osterberg, K, Voutilainen, M, Bharthuar, S, Brucken, E, Garcia, F, Havukainen, J, Kim, MS, Kinnunen, R, Lampen, T, Lassila-Perini, K, Lehti, S, Linden, T, Lotti, M, Martikainen, L, Myllymaki, M, Ott, J, Siikonen, H, Tuominen, E, Tuominiemi, J, Luukka, P, Petrow, H, Tuuva, T, Amendola, C, Besancon, M, Couderc, F, Dejardin, M, Denegri, D, Faure, JL, Ferri, F, Ganjour, S, Givernaud, A, Gras, P, de Monchenault, GH, Jarry, P, Lenzi, B, Locci, E, Malcles, J, Rander, J, Rosowsky, A, Sahin, MO, Savoy-Navarro, A, Titov, M, Yu, GB, Mijuskovic, J, Ahuja, S, Beaudette, F, Bonanomi, M, Perraguin, AB, Busson, P, Cappati, A, Charlot, C, Davignon, O, Diab, B, Falmagne, G, Ghosh, S, de Cassagnac, RG, Hakimi, A, Kucher, I, Motta, J, Nguyen, M, Ochando, C, Paganini, P, Rembser, J, Salerno, R, Sauvan, JB, Sirois, Y, Tarabini, A, Zabi, A, Zghiche, A, Agram, JL, Andrea, J, Apparu, D, Bloch, D, Bourgatte, G, Brom, JM, Chabert, EC, Collard, C, Darej, D, Fontaine, JC, Goerlach, U, Grimault, C, Le Bihan, AC, 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Delannoy, AG, Fiorendi, S, Spanier, S, Bouhali, O, Dalchenko, M, Delgado, A, Eusebi, R, Gilmore, J, Huang, T, Luo, S, Malhotra, S, Mueller, R, Overton, D, Rathjens, D, Safonov, A, Akchurin, N, Damgov, J, Hegde, V, Kunori, S, Lamichhane, K, Mengke, T, Muthumuni, S, Peltola, T, Volobouev, I, Whitbeck, A, Appelt, E, Greene, S, Gurrola, A, Johns, W, Melo, A, Ni, H, Padeken, K, Romeo, F, Sheldon, P, Tuo, S, Velkovska, J, Arenton, MW, Cox, B, Cummings, G, Hakala, J, Hirosky, R, Joyce, M, Ledovskoy, A, Li, A, Neu, C, Tannenwald, B, White, S, Wolfe, E, Poudyal, N, Black, K, Bose, T, Caillol, C, Dasu, S, De Bruyn, I, Everaerts, P, Fienga, F, Galloni, C, He, H, Herndon, M, Herve, A, Hussain, U, Lanaro, A, Loeliger, A, Loveless, R, Sreekala, JM, Mallampalli, A, Mohammadi, A, Pinna, D, Savin, A, Shang, V, Smith, WH, Teague, D, Trembath-Reichert, S, Vetens, W, and Jeitler, M
Subjects: Hadron-Hadron Scattering, Top Physics
Abstract: The top quark pair production cross section is measured in proton-proton collisions at a center-of-mass energy of 5.02 TeV. The data were collected in a special LHC low-energy and low-intensity run in 2017, and correspond to an integrated luminosity of 302 pb(-1). The measurement is performed using events with one electron and one muon of opposite charge, and at least two jets. The measured cross section is 60.7 +/- 5.0 (stat) +/- 2.8 (syst) +/- 1.1 (lumi) pb. A combination with the result in the single lepton + jets channel, based on data collected in 2015 at the same center-of-mass energy and corresponding to an integrated luminosity of 27.4 pb(-1), is then performed. The resulting measured value is 63.0 +/- 4.1 (stat) +/- 3.0 (syst+lumi) pb, in agreement with the standard model prediction of 66.8(-3.1)(+2.9) pb.
Published: 2022

43. Colon-targeted delivery of piceatannol enhances anti-colitic effects of the natural product: potential molecular mechanisms for therapeutic enhancement

Author: Yum S, Jeong S, Lee S, Nam J, Kim W, Yoo JW, Kim MS, Lee BL, and Jung Y
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Soohwan Yum, Seongkeun Jeong, Sunyoung Lee, Joon Nam, Wooseong Kim, Jin-Wook Yoo, Min-Soo Kim, Bok Luel Lee, Yunjin Jung College of Pharmacy, Pusan National University, Busan, Republic of Korea Abstract: Piceatannol (PCT), an anti-colitic natural product, undergoes extensive Phase II hepatic metabolism, resulting in very low bioavailability. We investigated whether colon-targeted delivery of PCT could enhance anti-colitic effects and how therapeutic enhancement occurred at the molecular level. Molecular effects of PCT were examined in human colon carcinoma cells and inflamed colons. The anti-colitic effects of PCT in a colon-targeted capsule (colon-targeted PCT) were compared with PCT in a gelatin capsule (conventional PCT) in a trinitrobenzene sulfonic acid-induced rat colitis model. Colon-targeted PCT elicited greatly enhanced recovery of the colonic inflammation. In HCT116 cells, PCT inhibited nuclear factor kappaB while activating anti-colitic transcription factors, nuclear factor-erythroid 2 (NF-E2) p45-related factor 2, and hypoxia-inducible factor-1. Colon-targeted PCT, but not conventional PCT, modulated production of the target gene products of the transcription factors in the inflamed colonic tissues. Rectal administration of PCT, which simulates the therapeutic action of colon-targeted PCT, also ameliorated rat colitis and reproduced the molecular effects in the inflamed colonic tissues. Colon-targeted delivery increased therapeutic efficacy of PCT against colitis, likely resulting from multitargeted effects exerted by colon-targeted PCT. The drug delivery technique may be useful for therapeutic optimization of anti-colitic lead compounds including natural products. Keywords: piceatannol, colitis, colon-targeted delivery, multitarget, polypharmacology
Published: 2015

44. Evaluation of glycine-bearing celecoxib derivatives as a colon-specific mutual prodrug acting on nuclear factor-κB, an anti-inflammatory target

Author: Lee S, Lee Y, Kim W, Nam J, Jeong S, Yoo JW, Kim MS, Moon HR, and Jung Y
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Sunyoung Lee,1,* Yonghyun Lee,1,2,* Wooseong Kim,1 Joon Nam,1 Seongkeun Jeong,1 Jin-Wook Yoo,1 Min-Soo Kim,1 Hyung Ryong Moon,1 Yunjin Jung11College of Pharmacy, Pusan National University, Busan, 2Bio-Nanomedicine Lab, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea*These authors contributed equally to this workAbstract: In an inflammatory state where HOCl is generated, glycine readily reacts with HOCl to produce glycine chloramine, an anti-inflammatory oxidant. Colonic delivery of celecoxib elicits anticolitic effects in a trinitrobenzene sulfonic acid-induced rat colitis model. Glycine-bearing celecoxib derivatives were prepared and evaluated as a colon-specific mutual prodrug acting on nuclear factor-κB (NFκB), an anticolitic target. Glycylcelecoxib (GC), N-glycylaspart-1-ylcelecoxib (N-GA1C), and C-glycylaspart-1-ylcelecoxib (C-GA1C) were synthesized and their structures identified using infrared and proton nuclear magnetic resonance spectrometer. The celecoxib derivatives were chemically stable in pH 6.8 and 1.2 buffers. GC and C-GA1C were resistant to degradation in the small intestinal contents, while N-GA1C was substantially cleaved to release celecoxib. In contrast, all the celecoxib derivatives were degraded to liberate celecoxib in the cecal content. These results suggest that GC and C-GA1C could be delivered to and liberate celecoxib and glycine in the large intestine. In human colon carcinoma HCT116 and murine macrophage RAW264.7 cells, combined celecoxib–glycine chloramine treatment additively suppressed the production of proinflammatory NFκB target gene products. Collectively, our data suggest that C-GA1C is a potential colon-specific mutual prodrug acting against NFκB.Keywords: colon-specific drug delivery, mutual prodrug, celecoxib, glycine chloramine, nuclear factor kappa-B
Published: 2015

45. Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process

Author: Ha ES, Kim JS, Baek I, Yoo JW, Jung Y, Moon HR, and Kim MS
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Eun-Sol Ha,1 Jeong-Soo Kim,2 In-hwan Baek,3 Jin-Wook Yoo,1 Yunjin Jung,1 Hyung Ryong Moon,1 Min-Soo Kim1 1College of Pharmacy, Pusan National University, 2Dong-A ST Co Ltd, Yongin, 3College of Pharmacy, Kyungsung University, Busan, South Korea Abstract: In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was 95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0–24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate. Keywords: bioavailability, megestrol acetate, dissolution, supercritical technology
Published: 2015

46. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

Author: Naeem M, Cao J, Choi M, Kim WS, Moon HR, Lee BL, Kim MS, Jung Y, and Yoo JW
Subjects: Medicine (General), R5-920
Abstract: Muhammad Naeem, Jiafu Cao, Moonjeong Choi, Woo Seong Kim, Hyung Ryong Moon, Bok Luel Lee, Min-Soo Kim, Yunjin Jung, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. Keywords: azo-polyurethane, methacrylate copolymer, budesonide, colon-targeted nanoparticles, colitis
Published: 2015

47. Colon-targeted delivery of budesonide using dual pH- and time-dependent polymeric nanoparticles for colitis therapy

Author: Naeem M, Choi MJ, Cao J, Lee Y, Ikram M, Yoon S, Lee J, Moon HR, Kim MS, Jung YJ, and Yoo JW
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Muhammad Naeem,1 Moonjeong Choi,1 Jiafu Cao,1 Yujeong Lee,1 Muhammad Ikram,2 Sik Yoon,2 Jaewon Lee,1 Hyung Ryong Moon,1 Min-Soo Kim,1 Yunjin Jung,1 Jin-Wook Yoo11College of Pharmacy, Pusan National University, Busan, 2Pusan National University School of Medicine, Yangsan, South KoreaAbstract: Single pH-dependent drug delivery systems have been widely used for colon-targeted delivery, but their efficiency is often hampered by the variation in gut pH. To overcome the limitation of single pH-dependent delivery systems, in this study, we developed and evaluated the therapeutic potential of budesonide-loaded dual pH/time-dependent nanoparticles (NPs) for the treatment of colitis. Eudragit FS30D was used as a pH-dependent polymer, and Eudragit RS100 as a time-dependent controlled release polymer. Single pH-dependent NPs (pH_NPs), single time-dependent NPs (Time_NPs), and dual pH/time-dependent NPs (pH/Time_NPs) were prepared using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these NPs in gastrointestinal (GI) tract conditions were investigated. The therapeutic potential and in vivo distribution of the NPs were evaluated in a dextran sulfate sodium (DSS)-induced colitis mice model. The pH/Time_NPs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the mice GI tract demonstrated that pH/Time_NPs were more efficiently delivered to the inflamed colon than pH_NPs were. Compared to the single pH_NPs-treated group, the pH/Time_NPs-treated group showed increased body weight and colon length and markedly decreased disease activity index, colon weight/length ratios, histological damage, and inflammatory cell infiltration in colon tissue. Our results demonstrate that the dual pH/time-dependent NPs are an effective oral colon-targeted delivery system for colitis therapy.Keywords: colon-specific delivery, dual-sensitive delivery, budesonide, inflammatory bowel disease
Published: 2015

48. Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery

Author: Lee Y, Kim J, Kim W, Nam J, Jeong S, Lee S, Yoo JW, Kim MS, and Jung Y
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Yonghyun Lee,1,2,* Jungyun Kim,1,* Wooseong Kim,1,* Joon Nam,1,* Seongkeun Jeong,1 Sunyoung Lee,1 Jin-Wook Yoo,1 Min-Soo Kim,1 Yunjin Jung1 1College of Pharmacy, Pusan National University, Busan, 2Bio-Nanomedicine Laboratory, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran–glutamic acid–celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD]) was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F1α, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages. Keywords: colon-specific drug delivery, dextran, celecoxib, prodrug, cardiovascular toxicity
Published: 2015

49. Improving dissolution and oral bioavailability of pranlukast hemihydrate by particle surface modification with surfactants and homogenization

Author: Ha ES, Baek I, Yoo JW, Jung Y, and Kim MS
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Eun-Sol Ha,1 In-hwan Baek,2 Jin-Wook Yoo,1 Yunjin Jung,1 Min-Soo Kim1 1College of Pharmacy, Pusan National University, 2College of Pharmacy, Kyungsung University, Busan, Republic of Korea Abstract: The present study was carried out to develop an oral formulation of pranlukast hemihydrate with improved dissolution and oral bioavailability using a surface-modified microparticle. Based on solubility measurements, surface-modified pranlukast hemihydrate microparticles were manufactured using the spray-drying method with hydroxypropylmethyl cellulose, sucrose laurate, and water and without the use of an organic solvent. The hydrophilicity of the surface-modified pranlukast hemihydrate microparticle increased, leading to enhanced dissolution and oral bioavailability of pranlukast hemihydrate without a change in crystallinity. The surface-modified microparticles with an hydroxypropylmethyl cellulose/sucrose laurate ratio of 1:2 showed rapid dissolution of up to 85% within 30 minutes in dissolution medium (pH 6.8) and oral bioavailability higher than that of the commercial product, with approximately 2.5-fold and 3.9-fold increases in area under the curve (AUC0→12 h) and peak plasma concentration, respectively. Therefore, the surface-modified microparticle is an effective oral drug delivery system for the poorly water-soluble therapeutic pranlukast hemihydrate. Keywords: solubility, wettability, sucrose laurate, cellulose
Published: 2015

50. Design of a gelatin microparticle-containing self-microemulsifying formulation for enhanced oral bioavailability of dutasteride

Author: Baek I, Ha ES, Yoo JW, Jung Y, and Kim MS
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: In-hwan Baek,1,* Eun-Sol Ha,2,* Jin-Wook Yoo,2 Yunjin Jung,2 Min-Soo Kim21College of Pharmacy, Kyungsung University, 2College of Pharmacy, Pusan National University, Busan, Republic of Korea*These authors contributed equally to this workAbstract: In this study, a gelatin microparticle-containing self-microemulsifying formulation (SMF) was developed using a spray-drying method to enhance the oral delivery of the poorly water-soluble therapeutic dutasteride. The effect of the amount of gelatin and the type and amount of hydrophilic additives, namely, Gelucire® 44/14, poloxamer 407, sodium lauryl sulfate, Soluplus®, Solutol™ HS15, and D-α-tocopheryl polyethylene glycol 1000 succinate, on the droplet size, dissolution, and oral absorption of dutasteride from the SMF was investigated. Upon dispersion of the gelatin microparticle-containing SMF in water after spray-drying, the mean droplet size of the aqueous dispersion was in the range of 110–137 nm. The in vitro dissolution and recrystallization results showed that gelatin could be used as a solid carrier and recrystallization inhibitor for the SMF of dutasteride. Furthermore, combination of the gelatin microparticle-containing SMF and Soluplus enhanced the dissolution properties and oral absorption of dutasteride. The results of our study suggest that the gelatin microparticle-containing SMF in combination with Soluplus could be useful to enhance the oral absorption of dutasteride.Keywords: dissolution, solubility, bioavailability, dutasteride
Published: 2015

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