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1. Efficacy, Safety, and Economic Feasibility of Dokhwalgisaeng-Tang for Degenerative Knee Osteoarthritis: Protocol for a Multicenter, Randomized, Assessor Blinded, Controlled Trial

Author

Kim W, Park YC, Goo B, Kim JH, Nam D, Kim E, Lee HJ, Pyun DH, Suh HS, Lee Y, Kim MS, Seo BK, and Baek YH

Subjects
degenerative joint disease, dokhwalgisaeng-tang, noninferiority trial, randomized controlled trial, Medicine (General), R5-920
Abstract

Wonnam Kim,1,* Yeon-Cheol Park,2,3,* Bonhyuk Goo,2 Jung-Hyun Kim,2 Dongwoo Nam,3,4 Eunseok Kim,5,6 Hyun-Jong Lee,7 Dong-Hyun Pyun,8,9 Hae Sun Suh,8– 10 Yoonsung Lee,11 Man S Kim,11 Byung-Kwan Seo,2,3 Yong-Hyeon Baek2,3 1Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 2Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 3Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 4Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 5Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 6Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 7Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 8Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea; 9Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul, Republic of Korea; 10College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; 11Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Yong-Hyeon Baek, Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea, Tel +82 2 440 6099, Fax +82 2 440 714, Email byhacu@khu.ac.krPurpose: Knee osteoarthritis (KOA) is one of the most prevalent degenerative joint diseases worldwide. The herbal decoction, Dokhwalgisaeng-tang (DHGST), has been commonly used in East Asia to treat osteoarthritis. However, there is insufficient evidence to draw clear conclusions concerning its effectiveness and safety for patients with KOA. We aim to determine the efficacy, safety, and economic feasibility of DHGST compared with Celecoxib, an oral COX-2 inhibitor, for patients with degenerative KOA.Trial Design and Methods: This multicenter, randomized, noninferiority trial, involving 160 participants who will be randomized using block randomization with 1:1 allocation, will compare DHGST and Celecoxib. The total trial period is 24 weeks after random allocation, comprising 12 weeks of treatment and 12 weeks of follow-up. Participants with KOA will be administered 200 mg of DHGST (treatment group) or Celecoxib capsules (control group) for 12 weeks. Efficacy and safety evaluations will be conducted at weeks 0, 4, 8, and 12, and 24. The primary outcome measurement is the Korean Western Ontario McMaster score at week 12. Changes in pain intensity using a 100 mm visual analog scale, changes in quality of life using a EuroQol 5-dimension 5-level self-report survey, and patient satisfaction will also be measured to evaluate effectiveness between the two groups. A trial-based economic feasibility evaluation will be conducted to analyze treatment cost-effectiveness from societal and healthcare system perspectives. Drug safety will be assessed through adverse reactions and laboratory test findings.Discussion: This trial protocol has the following limitations. Applying a double-dummy design is not possible, as the tablet and granule forms can easily be distinguished visually, and achieving participant blinding is challenging. The trial findings are intended to inform participants, physicians, and other stakeholders in determining whether DHGST could be used as an alternative therapeutic option for KOA.Trial Registration Number: KCT0008424 (Clinical Research Information Service of the Republic of Korea), registered on 12 May 2023.Keywords: degenerative joint disease, Dokhwalgisaeng-tang, noninferiority trial, randomized controlled trial

Published
2024

2. 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

3. 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,* YoungJae Jo,2,* 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*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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. Toxicity of colloidal silica nanoparticles administered orally for 90 days in rats

Author

Kim YR, Lee SY, Lee EJ, Park SH, Seong NW, Seo HS, Shin SS, Kim SJ, Meang EH, Park MK, Kim MS, Kim CS, Kim SK, Son SW, Seo YR, Kang BH, Han BS, An SSA, Lee BJ, and Kim MK

Subjects
Medicine (General), R5-920
Abstract

Yu-Ri Kim,1,* Seung-Young Lee,3,* Eun Jeong Lee,1 Sung Ha Park,4 Nak-won Seong,3 Heung-Sik Seo,3 Sung-Sup Shin,3 Seon-Ju Kim,3 Eun-Ho Meang,3 Myeong-Kyu Park,3 Min-Seok Kim,3 Cheol-Su Kim,5 Soo-Ki Kim,5 Sang Wook Son,2 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Beom-Jun Lee,10 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, 2Department of Dermatology, Korea University Medical School and College, 3General Toxicology Team, Korea Testing and Research Institute, Seoul, Republic of Korea; 4Department of Biochemistry, University of Bath, Bath, UK; 5Department of Microbiology, Wonju College of Medicine, Yonsei University, Gangwon, 6Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, 7Nonclinical Research Institute, Chemon Inc, Gyeonggi, 8Toxicological Research Center, Hoseo University, Chungnam, 9Department of Bionanotechnology, Gachon University, Gyeonggi, 10College of Veterinary Medicine, Chungbuk National University, Chungbuk, Republic of Korea *These authors contributed equally to this work Abstract: This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO2EN,20(-) (20 nm) or SiO2EN,100(-) (100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2 particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2EN,20(-) (20 nm) or SiO2EN,100(-) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO2EN,20(-) and SiO2EN,100(-) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex. Keywords: silica nanoparticles, particle size, 90-day oral dose toxicity, no observed adverse effect level

Published
2014

18. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

Author

Kim YR, Park JI, Lee EJ, Park SH, Seong NW, Kim JH, Kim GY, Meang EH, Hong JS, Kim SH, Koh SB, Kim MS, Kim CS, Kim SK, Son SW, Seo YR, Kang BH, Han BS, An SSA, Yun HI, and Kim MK

Subjects
Medicine (General), R5-920
Abstract

Yu-Ri Kim,1,* Jong-Il Park,2,* Eun Jeong Lee,1 Sung Ha Park,3 Nak-won Seong,2 Jun-Ho Kim,2 Geon-Yong Kim,2 Eun-Ho Meang,2 Jeong-Sup Hong,2 Su-Hyon Kim,2 Sang-Bum Koh,2 Min-Seok Kim,2 Cheol-Su Kim,4 Soo-Ki Kim,4 Sang Wook Son,5 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Hyo-In Yun,9 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 2General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 3Department of Biochemistry, University of Bath, Bath, UK; 4Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon, Korea; 5Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea; 6Nonclinical Research Institute, Chemon Inc., Yongin, Gyeonggi, Korea; 7Toxicological Research Center, Hoseo University, Ansan, Chungnam, Korea; 8Department of Bionanotechnology, Gachon University, Seongnam, Gyeonggi, Korea; 9College of Veterinary Medicine, Chungnam National University, Daejon, Korea *These authors contributed equally to this work Abstract: Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[-]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(-) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. Keywords: zinc oxide nanoparticles, surface charge, 90-day oral dose toxicity, no observed adverse effect level

Published
2014

19. Prenatal development toxicity study of zinc oxide nanoparticles in rats

Author

Hong JS, Park MK, Kim MS, Lim JH, Park GJ, Maeng EH, Shin JH, Kim MK, Jeong J, Park JA, Kim JC, and Shin HC

Subjects
Medicine (General), R5-920
Abstract

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. Keywords: developmental toxicity, maternal toxicity, nanotoxicology, teratogenicity

Published
2014

20. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days

Author

Ryu HJ, Seong NW, So BJ, Seo HS, Kim JH, Hong JS, Park MK, Kim MS, Kim YR, Cho KB, Seo MY, Kim MK, Maeng EH, and Son SW

Subjects
Medicine (General), R5-920
Abstract

Hwa Jung Ryu,1,* Nak-won Seong,2,* Byoung Joon So,1 Heung-sik Seo,2 Jun-ho Kim,2 Jeong-Sup Hong,2 Myeong-kyu Park,2 Min-Seok Kim,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Mu yeb Seo,2 Meyoung-Kon Kim,3 Eun Ho Maeng,2 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, South Korea; 2Korea Testing and Research Institute, Gyunggi-Do, South Korea; 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea; 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, South Korea *These authors contributed equally to this work Abstract: Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. Keywords: silica nanoparticles, toxicity, dermal route

Published
2014

21. Preparation and evaluation of cyclosporin A-containing proliposomes: a comparison of the supercritical antisolvent process with the conventional film method

Author

Karn PR, Jin SE, Lee BJ, Sun BK, Kim MS, Sung JH, and Hwang SJ

Subjects
Medicine (General), R5-920
Abstract

Pankaj Ranjan Karn,1 Su-Eon Jin,2 Benjamin Joon Lee,1,2 Bo Kyung Sun,1,2 Min-Soo Kim,3 Jong-Hyuk Sung,1,2 Sung-Joo Hwang1,2 1Yonsei Institute of Pharmaceutical Sciences, 2College of Pharmacy, Yonsei University, Yeonsu-gu, Incheon, Republic of Korea; 3College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea Objectives: The objectives of this study were to prepare cyclosporin A (CsA)-containing proliposomes using the supercritical antisolvent (SAS) process and the conventional thin film method for the comparative study of proliposomal formulations and to evaluate the physicochemical properties of these proliposomes.Methods: CsA-containing proliposomes were prepared by the SAS process and the conventional film method, composed of natural and synthetic phospholipids. We investigated particle size, polydispersity index, and zeta potential of CsA-containing proliposomes. In addition, both production yield and entrapment efficiency of CsA in different proliposomes were analyzed. Physicochemical properties of CsA-containing proliposomes were also evaluated, using differential scanning calorimetry and X-ray diffraction. The morphology and size of ­CsA-containing proliposomes were confirmed, using scanning electron microscopy. We checked the in vitro release of CsA from CsA-containing proliposomes prepared by different preparation methods, comparing them with Restasis® as a positive control and the stability of SAS-mediated proliposomes was also studied.Results: CsA-containing proliposomes formed by the SAS process had a relatively smaller particle size, with a narrow size distribution and spherical particles compared with those of conventionally prepared proliposomes. The yield and entrapment efficiency of CsA in all proliposomes varied from 85% to 92% and from 86% to 89%, respectively. Differential scanning calorimetry and X-ray diffraction studies revealed that the anhydrous lactose powder used in this formulation retained its crystalline form and that CsA was present in an amorphous form. Proliposome powders were rapidly converted to liposomes on contact with water. The in vitro release study of proliposomal formulations demonstrated a similar pattern to Restasis®. The SAS-mediated CsA-containing proliposomes were stable on storage, with no significant changes in particle size, polydispersity index, and entrapment efficiency.Conclusion: These results show promising features of CsA-containing proliposomal formulations, using the SAS process for the large-scale industrial application. Keywords: proliposomes, cyclosporin A, supercritical antisolvent process, thin film method, Restasis®

Published
2014

22. Fabrication and evaluation of valsartan–polymer–surfactant composite nanoparticles by using the supercritical antisolvent process

Author

Kim MS and Baek IH

Subjects
Medicine (General), R5-920
Abstract

Min-Soo Kim,1 In-hwan Baek21College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea; 2College of Pharmacy, Kyungsung University, Daeyeon-dong, Nam-gu, Busan, Republic of KoreaAbstract: The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan–hydroxypropyl methylcellulose–poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan–hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.Keywords: supersaturation, bioavailability, solid dispersion, dissolution, supercritical fluid

Published
2014

23. Influence of hydrophilic additives on the supersaturation and bioavailability of dutasteride-loaded hydroxypropyl- β-cyclodextrin nanostructures

Author

Kim MS

Subjects
Medicine (General), R5-920
Abstract

Min-Soo KimDepartment of Pharmaceutical Engineering, Inje University, Gimhae, Gyeongnam, Republic of KoreaAbstract: The objectives of this study were to develop a novel solid dutasteride formulation with improved physicochemical properties and oral bioavailability, and to examine the correlation between its in vitro dissolution and in vivo pharmacokinetic parameters. Hydroxypropyl-β-cyclodextrin (HP-β-CD) nanostructures with or without hydrophilic additives were manufactured using the supercritical antisolvent process. The dutasteride-loaded HP-β-CD nanoparticles formed aggregates with a mean particle size of less than 160 nm and a specific surface area greater than 100 m2/g. Increases in the supersaturation and dissolution rate for dutasteride were dependent on the type of additive; increases in maximum solubility and extended supersaturation were observed in dutasteride-loaded HP-β-CD nanostructures with hydroxypropylmethyl cellulose, whereas the dissolution rate was the highest for nanostructures containing d-α-tocopheryl polyethylene glycol 1000 succinate. In rats, the oral bioavailability of dutasteride increased with the supersaturation induced by the HP-β-CD nanostructures. In addition, compared with the in vitro drug release rate, the in vivo pharmacokinetic parameters were more closely correlated with in vitro parameters related to supersaturation (solubility). Further, the bioavailability of the dutasteride-loaded HP-β-CD nanostructures with hydroxypropylmethyl cellulose was similar to that of the commercially available soft gelatin capsule (Avodart®). In conclusion, preparation of dutasteride-loaded HP-β-CD nanostructures using the supercritical antisolvent process affords a viable alternative solid dosage form for dutasteride.Keywords: solubility, bioavailability, dutasteride, nanostructure, supercritical antisolvent

Published
2013

24. Optimized formulation of solid self-microemulsifying sirolimus delivery systems

Author

Cho W, Kim MS, Kim JS, Park J, Park HJ, Cha KH, Park JS, and Hwang SJ

Subjects
Medicine (General), R5-920
Abstract

Wonkyung Cho,1,2 Min-Soo Kim,3 Jeong-Soo Kim,2 Junsung Park,1,2 Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Jeong-Sook Park,2 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea Background: The aim of this study was to develop an optimized solid self-microemulsifying drug delivery system (SMEDDS) formulation for sirolimus to enhance its solubility, stability, and bioavailability. Methods: Excipients used for enhancing the solubility and stability of sirolimus were screened. A phase-separation test, visual observation for emulsifying efficiency, and droplet size analysis were performed. Ternary phase diagrams were constructed to optimize the liquid SMEDDS formulation. The selected liquid SMEDDS formulations were prepared into solid form. The dissolution profiles and pharmacokinetic profiles in rats were analyzed. Results: In the results of the oil and cosolvent screening studies, Capryol™ Propylene glycol monocaprylate (PGMC) and glycofurol exhibited the highest solubility of all oils and cosolvents, respectively. In the surfactant screening test, D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was determined to be the most effective stabilizer of sirolimus in pH 1.2 simulated gastric fluids. The optimal formulation determined by the construction of ternary phase diagrams was the T32 (Capryol™ PGMC:glycofurol:vitamin E TPGS = 30:30:40 weight ratio) formulation with a mean droplet size of 108.2 ± 11.4 nm. The solid SMEDDS formulations were prepared with Sucroester 15 and mannitol. The droplet size of the reconstituted solid SMEDDS showed no significant difference compared with the liquid SMEDDS. In the dissolution study, the release amounts of sirolimus from the SMEDDS formulation were significantly higher than the raw sirolimus powder. In addition, the solid SMEDDS formulation was in a more stable state than liquid SMEDDS in pH 1.2 simulated gastric fluids. The results of the pharmacokinetic study indicate that the SMEDDS formulation shows significantly greater bioavailability than the raw sirolimus powder or commercial product (Rapamune® oral solution). Conclusion: The results of this study suggest the potential use of a solid SMEDDS formulation for the delivery of poorly water-soluble drugs, such as sirolimus, through oral administration. Keywords: sirolimus, solubility, stability, bioavailability, self-emulsifying drug delivery systems, microemulsion

Published
2013

25. The comparative immunotoxicity of mesoporous silica nanoparticles and colloidal silica nanoparticles in mice

Author

Lee S, Kim MS, Lee D, Kwon TK, Khang D, Yun HS, and Kim SH

Subjects
Medicine (General), R5-920
Abstract

Soyoung Lee,1,* Mi-Sun Kim,1,* Dakeun Lee,2 Taeg Kyu Kwon,3 Dongwoo Khang,4 Hui-Suk Yun,5 Sang-Hyun Kim11CMRI, Laboratory of Immunotoxicology, Department of Pharmacology,School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 3Department of Immunology, School of Medicine, Keimyung University, Daegu, Republic of Korea; 4School of Nano and Advanced Materials Science and Engineering, Gyeongsang National University, Jinju, Republic of Korea; 5Engineering Ceramics Department, Powder and Ceramics Division, Korea Institute of Materials Science, Changwon, Republic of Korea*These authors contributed equally to this workBackground: Mesoporous silica (MPS) nanoparticles (NPs), which have a unique pore structure and extremely large surface area and pore volume, have received much attention because of their biomedical application potential. Using MPS NPs for biomedical devices requires the verification of their biocompatibility because the surface area of NPs is one of the most important determinants of toxicity, including the cellular uptake and immune response. We have previously reported that the cytotoxicity and inflammation potential of MPS NPs have been shown to be lower than those of general amorphous colloidal silica (Col) NPs in macrophages, but the low cytotoxicity does not guarantee high biocompatibility in vivo. In this study, we compared the in vivo immunotoxicity of MPS and Col NPs in the mouse model to define the effects of pore structural conditions of silica NPs.Materials and methods: Both MPS and Col NPs (2, 20, and 50 mg/kg/day) were intraperitoneally administered in female BALB/c mice for 4 weeks, and clinical toxicity, lymphocyte population, serum IgG/IgM levels, and histological changes were examined.Results: There was no overt sign of clinical toxicity in either MPS- or Col-treated mice. However, MPS NPs led to significant increases in liver and spleen weight and splenocyte proliferation. Mice treated with MPS NPs showed altered lymphocyte populations (CD3+, CD45+, CD4+, and CD8+) in the spleen, increased serum IgG and IgM levels, and histological changes. Despite slight changes in lymphocyte populations in the spleen, Col NPs did not alter other immunological factors.Conclusion: The results indicate that in vivo exposure to MPS NPs caused more damage to systemic immunity than that of Col NPs through the dysregulation of the spleen. The results for in vivo data are inconsistent with those for in vitro data, which show lower cytotoxicity for MPS NPs. These results suggest the importance of verifying biocompatibility both in vitro and in vivo during the design of new nanomaterials.Keywords: immunotoxicity, mesoporous silica nanoparticle, colloidal silica nanoparticle, spleen

Published
2013

26. Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

Author

Cha KH, Cho KJ, Kim MS, Kim JS, Park HJ, Park J, Cho W, Park JS, and Hwang SJ

Subjects
Medicine (General), R5-920
Abstract

Kwang-Ho Cha,1,3 Kyung-Jin Cho,3 Min-Soo Kim,4 Jeong-Soo Kim,3 Hee Jun Park,1,3 Junsung Park,1,3 Wonkyung Cho,1,3 Jeong-Sook Park,3 Sung-Joo Hwang1,21Yonsei Institute of Pharmaceutical Sciences, 2College of Pharmacy, Yonsei University, Incheon, Republic of Korea; 3College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 4Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of KoreaBackground: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO2.Methods: Fenofibrate was loaded onto Neusilin® UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO2. For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate formulations prepared were characterized by differential scanning calorimetry, powder x-ray diffractometry, specific surface area, pore size distribution, scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro dissolution and in vivo bioavailability were also investigated.Results: Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced crystal formation following adsorption. Supercritical CO2 facilitated the introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw fenofibrate, fenofibrate from the prepared powders showed a significantly increased dissolution rate and better bioavailability. In particular, the area under the drug concentration-time curve and maximal serum concentration of the powders prepared using supercritical CO2 were 4.62-fold and 4.52-fold greater than the corresponding values for raw fenofibrate.Conclusion: The results of this study highlight the usefulness of the melt-adsorption method using supercritical CO2 for improving the bioavailability of fenofibrate.Keywords: fenofibrate, melt adsorption, supercritical CO2, bioavailability

Published
2012

27. Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process

Author

Kim MS, Kim JS, Park HJ, Cho WK, Cha KH, and Hwang SJ

Subjects
Medicine (General), R5-920
Abstract

Min-Soo Kim1, Jeong-Soo Kim1, Hee Jun Park1, Won Kyung Cho1,3, Kwang-Ho Cha1,3, Sung-Joo Hwang2,31College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea, 2College of Pharmacy, 3Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of KoreaBackground: The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS) process.Methods: First, excipients for enhancing the stability and solubility of sirolimus were screened. Second, using the SAS process, solid dispersions of sirolimus-polyvinylpyrrolidone (PVP) K30 nanoparticles were prepared with or without surfactants such as sodium lauryl sulfate (SLS), tocopheryl propylene glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52. A mean particle size of approximately 250 nm was obtained for PVP K30-sirolimus nanoparticles. Solid state characterization, kinetic solubility, powder dissolution, stability, and pharmacokinetics were analyzed in rats.Results: X-ray diffraction, differential scanning calorimetry, and high-pressure liquid chromatography indicated that sirolimus existed in an anhydrous amorphous form within a solid dispersion of nanoparticles and that no degradation occurred after SAS processing. The improved supersaturation and dissolution of sirolimus as a solid dispersion of nanoparticles appeared to be well correlated with enhanced bioavailability of oral sirolimus in rats. With oral administration of a solid dispersion of PVP K30-SLS-sirolimus nanoparticles, the peak concentration and AUC0→12h of sirolimus were increased by approximately 18.3-fold and 15.2-fold, respectively.Conclusion: The results of this study suggest that preparation of PVP K30-sirolimus-surfactant nanoparticles using the SAS process may be a promising approach for improving the bioavailability of sirolimus.Keywords: sirolimus, solubility, bioavailability, supercritical antisolvent, nanoparticles

Published
2011

28. Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in Nc/Nga mice

Author

Kang MJ, Eum JY, Jeong MS, Park SH, Moon KY, Kang MH, Kim MS, Choi SE, Lee MW, Lee DI, Bang H, Lee CS, Joo SS, Li K, Lee M-K, Seo SJ, and Choi YW

Subjects
Medicine (General), R5-920
Abstract

Myung Joo Kang1, Jae Yoon Eum1, Mi Sook Jeong2, Sang Han Park1, Ki Young Moon1, Mean Hyung Kang1, Min Soo Kim1, Sun Eun Choi1, Min Won Lee1, Do Ik Lee1, Hyoweon Bang2, Chung Soo Lee2, Seong Soo Joo3, Kapsok Li2, Mi-Kyung Lee2, Seong Jun Seo2, Young Wook Choi11College of Pharmacy, ChungAng University, Heuksuk-dong, Dongjak-gu, Seoul, 2College of Medicine, Chung-Ang University, Heuksukdong, Dongjak-gu, Seoul, 3Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung, South KoreaBackground: The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T).Methods: HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed.Results: EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils.Conclusion: A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD.Keywords: hirsutenone, elastic liposomes, atopic dermatitis, NC/Nga mice, Tat peptide

Published
2011

29. Updated estimates of eligibility for and response to genome-targeted oncology drugs among US cancer patients, 2006-2020.

Author

Haslam, A, Kim, MS, and Prasad, V

Subjects
Humans, Neoplasms, Antineoplastic Agents, Pharmaceutical Preparations, Drug Approval, United States Food and Drug Administration, United States, eligibility, genome-targeted therapy, response, Genetics, Digestive Diseases, Human Genome, Cancer, Development of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPrior studies have evaluated the percentage of cancer patients with advanced or metastatic cancer who are eligible for and respond to genome-targeted therapy, but since that publication, the number of Food and Drug Administration (FDA) approvals for drugs targeting genetic indications has grown rapidly. We sought to update the estimates of both eligibility for and response to genome-targeted and genome-informed therapies in US cancer patients for FDA-approved drugs to reflect estimates as of 2020.Materials and methodsWe used mortality data from the American Cancer Society to estimate eligibility for these drugs, based on prevalence statistics from the published literature. We then multiplied eligibility by the response rate in the FDA label to generate an estimate for the percentage of US cancer patients who respond.ResultsFor genome-targeted therapy, we estimate that the eligibility increased from 5.13% in 2006 to 13.60% in 2020. For genome-targeted therapy, we estimate that the response increased from 2.73% in 2006 to 7.04% in 2020.ConclusionsThe percentage of US cancer patients who are eligible for and respond to genome-targeted therapy has increased over time. Most of the increase in eligibility for genome-targeted therapies was seen after 2018, whereas most of the increase in response was seen before 2018.

Published
2021

30. 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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31. 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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32. 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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33. 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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34. 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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35. Burden of disease scenarios for 204 countries and territories, 2022-2050: a forecasting analysis for the Global Burden of Disease Study 2021

Author

Vollset, SE, Ababneh, HS, Abate, YH, Abbafati, C, Abbasgholizadeh, R, Abbasian, M, Abbastabar, H, Abd Al Magied, AHA, Abd ElHafeez, S, Abdelkader, A, Abdelmasseh, M, Abd-Elsalam, S, Abdi, P, Abdollahi, M, Abdoun, M, Abdullahi, A, Abebe, M, Abiodun, O, Aboagye, RG, Abolhassani, H, Abouzid, M, Aboye, GB, Abreu, LG, Absalan, A, Abualruz, H, Abubakar, B, Abukhadijah, HJJ, Addolorato, G, Adekanmbi, V, Adetunji, CO, Adetunji, JB, Adeyeoluwa, TE, Adha, R, Adhikary, RK, Adnani, QES, Adzigbli, LA, Afrashteh, F, Afzal, MS, Afzal, S, Agbozo, F, Agodi, A, Agrawal, A, Agyemang-Duah, W, Ahinkorah, BO, Ahlstrom, AJ, Ahmad, A, Ahmad, F, Ahmad, MM, Ahmad, S, Ahmed, A, Ahmed, H, Ahmed, S, Ahmed, SA, Akinosoglou, K, Akkaif, MA, Akrami, AE, Akter, E, Al Awaidy, S, Al Hasan, SM, Al Mosa, AS, Al Ta'ani, O, Al Zaabi, OAM, Alahdab, F, Alajlani, MM, Al-Ajlouni, Y, Alalalmeh, SO, Al-Aly, Z, Alam, K, Alam, N, Alam, T, Alam, Z, Al-Amer, RM, Alanezi, FM, Alanzi, TM, Albakri, A, Aldhaleei, WA, Aldridge, RW, Alemohammad, SY, Alemu, YM, Al-Gheethi, AAS, Al-Hanawi, MK, Ali, A, Ali, I, Ali, MU, Ali, R, Ali, SSS, Ali, VE, Ali, W, Al-Ibraheem, A, Alicandro, G, Alif, SM, Aljunid, SM, Alla, F, Almazan, JU, Al-Mekhlafi, HM, Alqutaibi, AY, Alrawashdeh, A, Alrousan, SM, Al-Sabah, SK, Alsabri, MA, Altaany, Z, Al-Tammemi, AB, Al-Tawfiq, JA, Altirkawi, KA, Aluh, DO, Alvis-Guzman, N, Al-Wardat, MS, Al-Worafi, YM, Aly, H, Alyahya, MS, Alzoubi, KH, Al-Zyoud, W, Amani, R, Ameyaw, EK, Amin, TT, Amindarolzarbi, A, Amiri, S, Amirzade-Iranaq, MH, Amu, H, Amugsi, DA, Ancuceanu, R, Anderlini, D, Anderson, DB, Andrade, PP, Andrei, CL, Andrei, T, Andrews, EA, Anil, A, Anil, S, Anoushiravani, A, Antony, CM, Antriyandarti, E, Anuoluwa, BS, Anvari, S, Anyasodor, AE, Appiah, F, Aquilano, M, Arab, JP, Arabloo, J, Arafa, EA, Arafat, M, Aravkin, AY, Ardekani, A, Areda, D, Aregawi, BB, Aremu, A, Ariffin, H, Arkew, M, Armani, K, Artamonov, AA, Arumugam, A, Asghari-Jafarabadi, M, Ashbaugh, C, Astell-Burt, T, Athari, SS, Atorkey, P, Atout, MMW, Aujayeb, A, Ausloos, M, Awad, H, Awotidebe, AW, Ayatollahi, H, Ayuso-Mateos, JL, Azadnajafabad, S, Azeez, FK, Azevedo, RMS, Badar, M, Baghdadi, S, Bagheri, M, Bagheri, N, Bai, R, Baker, JL, Bako, AT, Balakrishnan, S, Balcha, WF, Baltatu, OC, Barchitta, M, Bardideh, E, Barker-Collo, SL, Barnighausen, TW, Barqawi, HJ, Barteit, S, Basiru, A, Basso, JD, Bastan, M-M, Basu, S, Bauckneht, M, Baune, BT, Bayati, M, Bayileyegn, NS, Behnoush, AH, Behzadi, P, Beiranvand, M, Bello, OO, Belo, L, Beloukas, A, Bemanalizadeh, M, Bensenor, IM, Benzian, H, Beran, A, Berezvai, Z, Bernstein, RS, Bettencourt, PJG, Beyene, KA, Beyene, MG, Bhagat, DS, Bhagavathula, AS, Bhala, N, Bhandari, D, Bharadwaj, R, Bhardwaj, N, Bhardwaj, P, Bhargava, A, Bhaskar, S, Bhat, V, Bhattacharjee, NV, Bhatti, GK, Bhatti, JS, Bhatti, MS, Bhuiyan, MA, Bisignano, C, Biswas, B, Bjorge, T, Bodolica, V, Bodunrin, AO, Hashemi, MB, Basara, BB, Borhany, H, Bosoka, SA, Carvajal, AB, Bouaoud, S, Boufous, S, Boxe, C, Boyko, EJ, Brady, OJ, Braithwaite, D, Brauer, M, Brazo-Sayavera, J, Brenner, H, Brown, CS, Browne, AJ, Brugha, T, Bryazka, D, Bulamu, NB, Buonsenso, D, Burkart, K, Burns, RA, Busse, R, Bustanji, Y, Butt, ZA, dos Santos, FLC, Barsbay, MC, Calina, D, Campos, LA, Cao, S, Capodici, A, Cardenas, R, Carreras, G, Carugno, A, Carvalho, M, Castaldelli-Maia, JM, Castelpietra, G, Cattaruzza, MS, Caye, A, Cegolon, L, Cembranel, F, Cenko, E, Cerin, E, Chadban, SJ, Chadwick, J, Chakraborty, C, Chakraborty, S, Chalek, J, Chan, JSK, Chandika, RM, Chandy, S, Charan, J, Chaudhary, AA, Chaurasia, A, Chen, A-T, Chen, H, Chen, MX, Chen, S, Cherbuin, N, Chi, G, Chichagi, F, Chimed-Ochir, O, Chimoriya, R, Ching, PR, Chirinos-Caceres, JL, Chitheer, A, Cho, DY, Cho, WCS, Choi, D-W, Chong, B, Chong, CL, Chopra, H, Chu, D-T, Chung, E, Chutiyami, M, Clayton, JT, Cogen, RM, Cohen, AJ, Columbus, A, Comfort, H, Conde, J, Connolly, JT, Cooper, EEK, Cortese, S, Cruz-Martins, N, da Silva, AG, Dadras, O, Dai, X, Dai, Z, Dalton, BE, Damiani, G, Dandona, L, Dandona, R, Das, JK, Das, S, Dash, NR, Davletov, K, De la Hoz, FP, De Leo, D, Debopadhaya, S, Delgado-Enciso, I, Denova-Gutierrez, E, Dervenis, N, Desai, HD, Devanbu, VGC, Dewan, SMR, Dhama, K, Dhane, AS, Dhingra, S, da Silva, DD, Diaz, D, Diaz, LA, Diaz, MJ, Dima, A, Ding, DD, Do, THP, Do Prado, CB, Dodangeh, M, Doegah, PT, Dohare, S, Dong, W, D'Oria, M, Doshi, R, Dowou, RK, Dsouza, HL, Dsouza, V, Dube, J, Dumith, SC, Duncan, BB, Duraes, AR, Duraisamy, S, Durojaiye, OC, Dushpanova, A, Dutta, S, Dzianach, PA, Dziedzic, AM, Eboreime, E, Ebrahimi, A, Kalan, ME, Edinur, HA, Efendi, F, Eikemo, TA, Eini, E, Ekundayo, TC, El Arab, RA, El Sayed, I, Elamin, O, Elemam, NM, ElGohary, GMT, Elhadi, M, Elmeligy, OAA, Elmoselhi, AB, Elshaer, M, Elsohaby, I, Eltahir, ME, Emeto, TI, Eshrati, B, Eslami, M, Esmaeili, Z, Fabin, N, Fagbamigbe, AF, Fagbule, OF, Falzone, L, Fareed, M, Farinha, CSES, Faris, MEM, Faro, A, Fasihi, K, Fatehizadeh, A, Fauk, NK, Fazylov, T, Feigin, VL, Fekadu, G, Feng, X, Fereshtehnejad, S-M, Ferrara, P, Ferreira, N, Firew, BS, Fischer, F, Fitriana, I, Flavel, J, Flor, LS, Folayan, MO, Foley, KM, Fonzo, M, Force, LM, Foschi, M, Freitas, A, Fridayani, NKY, Fukutaki, KG, Furtado, JM, Fux, B, Gaal, PA, Gadanya, MA, Gallus, S, Ganesan, B, Ganiyani, MA, Gautam, RK, Gebi, TG, Gebregergis, MW, Gebrehiwot, M, Getacher, L, Getahun, GKA, Gething, PW, Ghadimi, DJ, Ghadirian, F, Ghafarian, S, Ghailan, KY, Ghasemi, M, Dabaghi, GG, Ghazy, RM, Ghoba, S, Gholami, E, Gholamrezanezhad, A, Gholizadeh, N, Ghorbani, M, Vajargah, PG, Ghotbi, E, Gil, AU, Gill, TK, Girmay, A, Glasbey, JC, Glushkova, EV, Gnedovskaya, EV, Gobolos, L, Goldust, M, Goleij, P, Golinelli, D, Gopalani, SV, Goulart, AC, Gouravani, M, Goyal, A, Grivna, M, Grosso, G, Guarducci, G, Gubari, MIM, Guicciardi, S, Guimaraes, RA, Gulati, S, Gulisashvili, D, Gunawardane, DA, Guo, C, Gupta, AK, Gupta, R, Gupta, S, Gupta, VK, Haakenstad, A, Hadi, NR, Haep, N, Hafiz, A, Haghmorad, D, Haile, D, Ali, AH, Ali, HA, Haj-Mirzaian, A, Halboub, ES, Haller, S, Halwani, R, Abdullah, KH, Hamdy, NM, Hamoudi, R, Hanifi, N, Hankey, GJ, Haq, ZA, Haque, MR, Harapan, H, Hargono, A, Haro, JM, Hasaballah, AI, Hasan, SMM, Hasanian, M, Hasnain, MS, Hassan, A, Haubold, J, Hay, SI, Hebert, JJ, Hegazi, OE, Heidari, M, Hemmati, M, Henson, CA, Herrera-Serna, BY, Herteliu, C, Heydari, M, Hezam, K, Hidayana, I, Hiraike, Y, Hoan, NQ, Holla, R, Hoogar, P, Horita, N, Hossain, MM, Hosseinzadeh, H, Hosseinzadeh, M, Hostiuc, M, Hostiuc, S, Hu, C, Huang, J, Hultstrom, M, Hundie, TG, Hunt, AJ, Hushmandi, K, Hussain, J, Hussain, MA, Hussein, NR, Huynh, H-H, Hwang, B-F, Ibitoye, SE, Iftikhar, PM, Ikiroma, AI, Ikwegbue, PC, Ilic, IM, Ilic, MD, Immurana, M, Isa, MA, Islam, MR, Islam, SMS, Ismail, F, Ismail, NE, Isola, G, Iwagami, M, Iyamu, IO, Jacob, L, Jacobsen, KH, Jafarinia, M, Jahankhani, K, Jahanmehr, N, Jain, N, Jairoun, AA, Mani, DRJ, Jamil, S, Jamora, RDG, Jatau, AI, Javadov, S, Javaheri, T, 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Abstract

BACKGROUND: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. METHODS: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects m

Published
2024

36. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Author

Brauer, M, Roth, GA, Aravkin, AY, Zheng, P, Abate, KH, Abate, YH, Abbafati, C, Abbasgholizadeh, R, Abbasi, MA, Abbasian, M, Abbasifard, M, Moradi, Y, Bensenor, IM, Benzian, H, Beran, A, Abouzid, M, Berezvai, Z, Bernabe, E, Bernstein, RS, Bettencourt, PJG, Bhagavathula, AS, Bhala, N, Moraga, P, Bhandari, D, Bhardwaj, N, Bhardwaj, P, Bhaskar, S, Aboye, GB, Bhat, AN, Bhat, V, Bhatti, GK, Bhatti, JS, Bhatti, MS, Morawska, L, Bhatti, R, Bhuiyan, MA, Bhutta, ZA, Bikbov, B, Bishai, JD, Abreu, LG, Bisignano, C, Biswas, A, Biswas, B, Biswas, RK, Moreira, RS, Bjørge, T, Boachie, MK, Boakye, H, Bockarie, MJ, Bodolica, V, Bodunrin, AO, Abualruz, H, Bogale, EK, Bolla, SR, Boloor, A, Morovatdar, N, Bonakdar Hashemi, M, Boppana, SH, Bora Basara, B, Borhany, H, Botero Carvajal, A, Bouaoud, S, Boufous, S, Abubakar, B, Bourne, R, Boxe, C, Morrison, SD, Braithwaite, D, Brant, LC, Brar, A, Breitborde, NJK, Breitner, S, Brenner, H, Briko, AN, Britton, G, Abu-Gharbieh, E, Brown, CS, Morze, J, Browne, AJ, Brunoni, AR, Bryazka, D, Bulamu, NB, Bulto, LN, Buonsenso, D, Burkart, K, Burns, RA, Busse, R, Abukhadijah, HJJ, Mosaddeghi Heris, R, Bustanji, Y, Butt, NS, Butt, ZA, Caetano dos Santos, FL, Cagney, J, Cahuana-Hurtado, L, Calina, D, Cámera, LA, Campos, LA, Campos-Nonato, IR, Mossialos, E, Aburuz, S, Cao, C, Cao, F, Cao, Y, Capodici, A, Cárdenas, R, Carr, S, Carreras, G, Carrero, JJ, Carugno, A, Motappa, R, Carvalho, F, Abu-Zaid, A, Carvalho, M, Castaldelli-Maia, JM, Castañeda-Orjuela, CA, Castelpietra, G, Catalá-López, F, Catapano, AL, Cattaruzza, MS, Caye, A, Alemayohu, MA, Ali, BA, Cederroth, CR, Cegolon, L, Adane, MM, Cenderadewi, M, Cercy, KM, Cerin, E, Chadwick, J, Chakraborty, C, Chakraborty, PA, Chakraborty, S, Mougin, V, Chan, JSK, Chan, RNC, Chandan, JS, Addo, IY, Chandika, RM, Chaturvedi, P, Chen, A-T, Chen, CS, Chen, H, Chen, MX, Mousavi, P, Chen, M, Chen, S, Cheng, C-Y, Cheng, ETW, Addolorato, G, Cherbuin, N, Chi, G, Chichagi, F, Chimed-Ochir, O, Chimoriya, R, Msherghi, A, Ching, PR, Chirinos-Caceres, JL, Chitheer, A, Cho, WCS, Chong, B, Adedoyin, RA, Chopra, H, Chowdhury, R, Christopher, DJ, Chu, D-T, Mubarik, S, Chukwu, IS, Chung, E, Chung, S-C, Chutiyami, M, Cioffi, I, Cogen, RM, Adekanmbi, V, Cohen, AJ, Columbus, A, Conde, J, Muccioli, L, Corlateanu, A, Cortese, S, Cortesi, PA, Costa, VM, Costanzo, S, Criqui, MH, Cruz, JA, Aden, B, Cruz-Martins, N, Culbreth, GT, Mueller, UO, da Silva, AG, Dadras, O, Dai, X, Dai, Z, Daikwo, PU, Dalli, LL, Damiani, G, D'Amico, E, Adetunji, JB, D'Anna, L, Mulita, F, Darwesh, AM, Das, JK, Das, S, Dash, NR, Dashti, M, Dávila-Cervantes, CA, Davis Weaver, N, Davitoiu, DV, De la Hoz, FP, Adeyeoluwa, TE, Mullany, EC, de la Torre-Luque, A, De Leo, D, Debopadhaya, S, Degenhardt, L, Del Bo', C, Delgado-Enciso, I, Delgado-Saborit, JM, Demoze, CK, Denova-Gutiérrez, E, Dervenis, N, Munjal, K, Adha, R, Dervišević, E, Desai, HD, Desai, R, Devanbu, VGC, Dewan, SMR, Dhali, A, Dhama, K, Dhane, AS, Dhimal, ML, Marx, W, Murillo-Zamora, E, Dhimal, M, Adibi, A, Dhingra, S, Dhulipala, VR, Dhungana, RR, Dias da Silva, D, Diaz, D, Diaz, LA, Diaz, MJ, Dima, A, Abbasi-Kangevari, M, Ding, DD, Dinu, M, Adnani, QES, Djalalinia, S, Do, TC, Do, THP, do Prado, CB, Dodangeh, M, Dohare, S, Dokova, KG, Ali, I, Dong, W, Dongarwar, D, D'Oria, M, Adzigbli, LA, Dorostkar, F, Dorsey, ER, Doshi, R, Doshmangir, L, Dowou, RK, Driscoll, TR, Murlimanju, BV, Dsouza, AC, Dsouza, HL, Dumith, SC, Duncan, BB, Afolabi, AA, Duraes, AR, Duraisamy, S, Dushpanova, A, Dzianach, PA, Dziedzic, AM, Musina, A-M, Ebrahimi, A, Echieh, CP, Ed-Dra, A, Edinur, HA, Edvardsson, D, Afolabi, RF, Edvardsson, K, Efendi, F, Eftekharimehrabad, A, Eini, E, Mustafa, G, Ekholuenetale, M, Ekundayo, TC, El Arab, RA, El Sayed Zaki, M, El-Dahiyat, F, Elemam, NM, Afshin, A, Elgar, FJ, ElGohary, GMT, Elhabashy, HR, Muthu, S, Elhadi, M, Elmehrath, AO, Elmeligy, OAA, Elshaer, M, Elsohaby, I, Emeto, TI, Esfandiari, N, Afyouni, S, Eshrati, B, Eslami, M, Muthupandian, S, Esmaeili, SV, Estep, K, Etaee, F, Fabin, N, Fagbamigbe, AF, Fagbule, OF, Fahimi, S, Falzone, L, Afzal, MS, Fareed, M, Muthusamy, R, Farinha, CSES, Faris, MEM, Faris, PS, Faro, A, Fasina, FO, Fatehizadeh, A, Fauk, NK, Fazylov, T, Feigin, VL, Afzal, S, Muzaffar, M, Feng, X, Fereshtehnejad, S-M, Feroze, AH, Ferrara, P, Ferrari, AJ, Ferreira, N, Fetensa, G, Feyisa, BR, Filip, I, Fischer, F, Maryam, S, Myung, W, Agampodi, SB, Fitriana, I, Flavel, J, Flohr, C, Flood, D, Flor, LS, Foigt, NA, Folayan, MO, Force, LM, Fortuna, D, Nafei, A, Foschi, M, Agbozo, F, Franklin, RC, Freitas, A, Friedman, SD, Fux, B, G, S, Gaal, PA, Gaihre, S, Gajdács, M, Nagarajan, AJ, Galali, Y, Gallus, S, Aghamiri, S, Gandhi, AP, Ganesan, B, Ganiyani, MA, Garcia, V, Gardner, WM, Garg, RK, Gautam, RK, Ali, L, Gebi, TG, Gebregergis, MW, Gebrehiwot, M, Agodi, A, Gebremariam, TBB, Gebremeskel, TG, Gerema, U, Getacher, L, Getahun, GKA, Getie, M, Nagaraju, SP, Ghadirian, F, Ghafarian, S, Ghaffari Jolfayi, A, Ghailan, KY, Agrawal, A, Ghajar, A, Ghasemi, M, Ghasempour Dabaghi, G, Ghasemzadeh, A, Ghassemi, F, Nagel, G, Ghazy, RM, Gholami, A, Gholamrezanezhad, A, Gholizadeh, N, Ghorbani, M, Agyemang-Duah, W, Gil, AU, Gil, GF, Gilbertson, NM, Gill, PS, Naghavi, M, Gill, TK, Gindaba, EZ, Girmay, A, Glasbey, JC, Gnedovskaya, EV, Göbölös, L, Ahinkorah, BO, Godinho, MA, Goel, A, Golechha, M, Naghavi, P, Goleij, P, Golinelli, D, Gomes, NGM, Gopalani, SV, Gorini, G, Goudarzi, H, Goulart, AC, Ahmad, A, Gouravani, M, Goyal, A, Naik, GR, Graham, SM, Grivna, M, Grosso, G, Guan, S-Y, Guarducci, G, Gubari, MIM, Guha, A, Guicciardi, S, Ahmad, D, Gulati, S, Naik, G, Gulisashvili, D, Gunawardane, DA, Guo, C, Gupta, AK, Gupta, B, Gupta, M, Gupta, R, Gupta, RD, Ahmad, F, Mathangasinghe, Y, Nainu, F, Gupta, S, Gupta, VB, Gupta, VK, Habibzadeh, F, Habibzadeh, P, Hadaro, TS, Hadian, Z, Haep, N, Haghi-Aminjan, H, Nair, TS, Ahmad, N, Haghmorad, D, Hagins, H, Haile, D, Hailu, A, Hajj Ali, A, Halboub, ES, Halimi, A, Hall, BJ, Haller, S, Najdaghi, S, Halwani, R, Ahmad, S, Hamadeh, RR, Hamdy, NM, Hameed, S, Hamidi, S, Hammoud, A, Hanif, A, Hanifi, N, Haq, ZA, Nakhostin Ansari, N, Haque, MR, Harapan, H, Ahmad, T, Hargono, A, Haro, JM, Hasaballah, AI, Hasan, I, Hasan, MJ, Hasan, SMM, Hasani, H, Ali, MU, Hasanian, M, Hashmeh, N, Hasnain, MS, Ahmed, A, Hassan, A, Hassan, I, Hassan Zadeh Tabatabaei, MS, Hassani, S, Hassanipour, S, Hassankhani, H, Nanavaty, DP, Haubold, J, Havmoeller, RJ, Hay, SI, Hebert, JJ, Hegazi, OE, Hegena, TY, Heidari, G, Heidari, M, Helfer, B, Nangia, V, Hemmati, M, Henson, CA, Herbert, ME, Herteliu, C, Heuer, A, Hezam, K, Hinneh, TK, Hiraike, Y, Hoan, NQ, Narasimha Swamy, S, Holla, R, Hon, J, Hoque, ME, Horita, N, Hossain, S, Hosseini, SE, Ahmed, LA, Hosseinzadeh, H, Hosseinzadeh, M, Hostiuc, M, Narimani Davani, D, Hostiuc, S, Hoven, H, Hsairi, M, Hsu, JM, Hu, C, Huang, J, Huda, MN, Ahmed, MB, Hulland, EN, Hultström, M, Nascimento, BR, Hushmandi, K, Hussain, J, Hussein, NR, Huynh, CK, Huynh, H-H, Ibitoye, SE, Idowu, OO, Ihler, AL, Ahmed, S, Ikeda, N, Mathioudakis, AG, Nascimento, GG, Ikuta, KS, Ilesanmi, OS, Ilic, IM, Ilic, MD, Imam, MT, Immurana, M, Inbaraj, LR, Irham, LM, Isa, MA, Ahmed, SA, Nashwan, AJ, Islam, MR, Ismail, F, Ismail, NE, Iso, H, Isola, G, Iwagami, M, Iwu, CCD, Iwu-Jaja, CJ, J, V, Jaafari, J, Natto, ZS, Ajami, M, Jacob, L, Jacobsen, KH, Jadidi-Niaragh, F, Jahankhani, K, Jahanmehr, N, Jahrami, H, Jain, A, Jain, N, Jairoun, AA, Nauman, J, Jaiswal, A, Akalu, GT, Jakovljevic, M, Jalilzadeh Yengejeh, R, Jamora, RDG, Jatau, AI, Javadov, S, Javaheri, T, Jayaram, S, Jeganathan, J, Navaratna, SNK, Jeswani, BM, Jiang, H, Akara, EM, Johnson, CO, Jokar, M, Jomehzadeh, N, Jonas, JB, Joo, T, Joseph, A, Joseph, N, Ali, R, Joshi, V, Joshua, CE, Jozwiak, JJ, Akbarialiabad, H, Jürisson, M, Kaambwa, B, Kabir, A, Kabir, Z, Kadashetti, V, Kahn, EM, Naveed, M, Kalani, R, Kaliyadan, F, Kalra, S, Kamath, R, Akhlaghi, S, Kanagasabai, T, Kanchan, T, Kandel, H, Kanmiki, EW, Kanmodi, KK, Nayak, BP, Kansal, SK, Kapner, DJ, Kapoor, N, Karagiannidis, E, Karajizadeh, M, Akinosoglou, K, Karakasis, P, Karanth, SD, Karaye, IM, Karch, A, Nayak, VC, Karim, A, Karimi, H, Karmakar, S, Kashoo, FZ, Kasraei, H, Kassahun, WD, Akinyemiju, T, Kassebaum, NJ, Kassel, MB, Katikireddi, SV, Ndejjo, R, Kauppila, JH, Kawakami, N, Kaydi, N, Kayode, GA, Kazemi, F, Keiyoro, PN, Kemmer, L, Akkaif, MA, Kempen, JH, Kerr, JA, Matozinhos, FP, Nduaguba, SO, Kesse-Guyot, E, Khader, YS, Khafaie, MA, Khajuria, H, Khalaji, A, Khalil, M, Khalilian, A, Khamesipour, F, Akkala, S, Khan, A, Negash, H, Khan, MN, Khan, M, Khan, MJ, Khan, MAB, Khanmohammadi, S, Khatab, K, Khatatbeh, H, Khatatbeh, MM, Khatib, MN, Akombi-Inyang, B, Negoi, I, Khavandegar, A, Khayat Kashani, HR, Khidri, FF, Khodadoust, E, Khormali, M, Khorrami, Z, Khosla, AA, Khosrowjerdi, M, Khreis, H, Khusun, H, Negoi, RI, Al Awaidy, S, Kifle, ZD, Kim, K, Kim, MS, Kim, YJ, Kimokoti, RW, Kisa, A, Kisa, S, Knibbs, LD, Knudsen, AKS, Nejadghaderi, SA, Koh, DSQ, Al Hasan, SM, Kolahi, A-A, Kompani, F, Kong, J, Koren, G, Korja, M, Korshunov, VA, Korzh, O, Kosen, S, Nejjari, C, Kothari, N, Koul, PA, Alahdab, F, Koulmane Laxminarayana, SL, Krishan, K, Krishnamoorthy, V, Krishnamoorthy, Y, Krishnan, B, Krohn, KJ, Kuate Defo, B, Ali, SSS, Kucuk Bicer, B, Kuddus, MA, Kuddus, M, AL-Ahdal, TMA, Kugbey, N, Kuitunen, I, Kulimbet, M, Kulkarni, V, Kumar, A, Kumar, N, Nematollahi, MH, Kumar, V, Kundu, S, Kurmi, OP, Kusnali, A, Alalalmeh, SO, Kusuma, D, Kutluk, T, La Vecchia, C, Ladan, MA, Laflamme, L, Nepal, S, Lahariya, C, Lai, DTC, Lal, DK, Lallukka, T, Lám, J, Alalwan, TA, Lan, Q, Lan, T, Landires, I, Lanfranchi, F, Neupane, S, Langguth, B, Lansingh, VC, Laplante-Lévesque, A, Larijani, B, Larsson, AO, Lasrado, S, Al-Aly, Z, Lauriola, P, Le, H-H, Le, LKD, Mattumpuram, J, Ng, M, Le, NHH, Le, TTT, Leasher, JL, Ledda, C, Lee, M, Lee, PH, Lee, SW, Alam, K, Lee, SWH, Lee, YH, Nguefack-Tsague, G, LeGrand, KE, Leigh, J, Leong, E, Lerango, TL, Lescinsky, H, Leung, J, Li, M-C, Li, W-Z, Alam, N, Li, W, Ngunjiri, JW, Li, Y, Li, Z, Ligade, VS, Lim, L-L, Lim, SS, Lin, R-T, Lin, S, Liu, C, Liu, G, Alanezi, FM, Nguyen, DH, Liu, J, Liu, RT, Liu, S, Liu, W, Liu, X, Livingstone, KM, Llanaj, E, Lohiya, A, Nguyen, NNY, Alanzi, TM, López-Bueno, R, Lopukhov, PD, Lorkowski, S, Lotufo, PA, Lozano, R, Lubinda, J, Lucchetti, G, Luo, L, lv, H, Nguyen, PT, M Amin, HI, Albakri, A, Ma, ZF, Maass, KL, Mabrok, M, Machairas, N, Machoy, M, Mafhoumi, A, Magdy Abd El Razek, M, Maghazachi, AA, Mahadeshwara Prasad, DR, Maharaj, SB, AlBataineh, MT, Mahmoud, MA, Mahmoudi, E, Majeed, A, Makram, OM, Makris, KC, Malasala, S, Maled, V, Ali, W, Malhotra, K, Malik, AA, Malik, I, Aldhaleei, WA, Malinga, LA, Malta, DC, Mamun, AA, Manda, AL, Manla, Y, Mansour, A, Nguyen, VT, Mansouri, B, Mansouri, P, Mansourian, M, Mansournia, MA, Aldridge, RW, Mantovani, LG, Manu, E, Marateb, HR, Maravilla, JC, Marsh, E, Nguyen Tran Minh, D, Martinez, G, Martinez-Piedra, R, Martini, S, Martins-Melo, FR, Martorell, M, Maugeri, A, Niazi, RK, Nicholson, SI, Nie, J, Nikoobar, A, Nikpoor, AR, Ningrum, DNA, Nnaji, CA, Noman, EA, Alicandro, G, Nomura, S, Maulik, PK, Noroozi, N, Norrving, B, Noubiap, JJ, Nri-Ezedi, CA, Ntaios, G, Ntsekhe, M, Nunemo, MH, Nurrika, D, Nutor, JJ, Alif, SM, Mayeli, M, Oancea, B, O'Connell, EM, Odetokun, IA, O'Donnell, MJ, Oduro, MS, Ogunfowokan, AA, Ogunkoya, A, Oh, I-H, Okati-Aliabad, H, Okeke, SR, Mazidi, M, Aljunid, SM, Okekunle, AP, Okonji, OC, Olagunju, AT, Olasupo, OO, Olatubi, MI, Oliveira, AB, Oliveira, GMM, Olorukooba, AA, Olufadewa, II, Alemu, YM, Olusanya, BO, Alla, F, Olusanya, JO, Oluwafemi, YD, Omar, HA, Omar Bali, A, Omer, GL, Ong, KL, Ong, S, Onwujekwe, OE, Mazzotti, A, Onyedibe, KI, Oppong, AF, Abd ElHafeez, S, Al-Marwani, S, Ordak, M, Orish, VN, Ornello, R, Orpana, HM, Ortiz, A, Ortiz-Prado, E, McGrath, JJ, Osman, WMS, Ostroff, SM, Osuagwu, UL, Otoiu, A, Al-Mekhlafi, HM, Otstavnov, N, Otstavnov, SS, Ouyahia, A, Owolabi, MO, Oyeyemi, IT, McKee, M, Oyeyemi, OT, P A, MP, Pacheco-Barrios, K, Padron-Monedero, A, Padubidri, JR, Almustanyir, S, Pal, PK, Palicz, T, Pan, F, Pan, H-F, McKowen, ALW, Pana, A, Panda, SK, Panda-Jonas, S, Pandey, A, Pandi-Perumal, SR, Pangaribuan, HU, Alomari, MA, Pantazopoulos, I, Pantea Stoian, AM, Papadopoulou, P, McLaughlin, SA, Parent, MC, Parija, PP, Parikh, RR, Park, S, Parsons, N, Pashaei, A, Alonso, J, Pasovic, M, Passera, R, McPhail, MA, Patil, S, Patoulias, D, Patthipati, VS, Paudel, U, Pawar, S, Pazoki Toroudi, H, Peden, AE, Pedersini, P, Alqahtani, JS, Peng, M, McPhail, SM, Pensato, U, Pepito, VCF, Peprah, EK, Peprah, P, Peres, MFP, Perianayagam, A, Perico, N, Perna, S, Pesudovs, K, Alqutaibi, AY, Mechili, EA, Petcu, I-R, Petermann-Rocha, FE, Pham, HT, Philip, AK, Phillips, MR, Pickering, BV, Pierannunzio, D, Pigeolet, M, Pigott, DM, Piracha, ZZ, Mehmood, A, Al-Raddadi, RM, Piradov, MA, Pisoni, E, Piyasena, MP, Plass, D, Plotnikov, E, Poddighe, D, Polkinghorne, KR, Poluru, R, Pond, CD, Mehmood, K, Popovic, DS, Alrawashdeh, A, Porru, F, Postma, MJ, Poudel, GR, Pour-Rashidi, A, Pourshams, A, Pourtaheri, N, Prabhu, D, Prada, SI, Al-Fatly, B, Pradhan, J, Pradhan, PMS, Al-Rifai, RH, Prasad, M, Prates, EJS, Purnobasuki, H, Purohit, BM, Puvvula, J, Qasim, NH, Qattea, I, Mehrabani-Zeinabad, K, Qazi, AS, Qian, G, Qiu, S, Abd-Elsalam, S, Alrousan, SM, Rabiee Rad, M, Radfar, A, Radhakrishnan, RA, Radhakrishnan, V, Raeisi Shahraki, H, Mehrabi Nasab, E, Rafferty, Q, Rafiei, A, Raggi, A, Raghav, PR, Raheem, N, Al-Sabah, SK, Rahim, F, Rahim, MJ, Rahimifard, M, Rahimi-Movaghar, V, Meier, T, Rahman, MO, Rahman, MA, Rahmani, AM, Rahmani, B, Rahmanian, M, Rahmanian, N, Alshahrani, NZ, Rahmanian, V, Rahmati, M, Rahmawaty, S, Mejia-Rodriguez, F, Raimondo, D, Rajaa, S, Rajendran, V, Rajput, P, Ramadan, MM, Ramasamy, SK, Ramasubramani, P, Altaany, Z, Ramazanu, S, Ramteke, PW, Mekene Meto, T, Rana, J, Rana, K, Ranabhat, CL, Rane, A, Rani, U, Ranta, A, Rao, CR, Rao, M, Altaf, A, Rao, PC, Mekonnen, BD, Rao, SJ, Rasella, D, Rashedi, S, Rashedi, V, Rashidi, M, Rashidi, M-M, Rasouli-Saravani, A, Ratan, ZA, Rathnaiah Babu, G, Al-Tawfiq, JA, Menezes, RG, Rauniyar, SK, Rautalin, I, Rawaf, DL, Rawaf, S, Rawassizadeh, R, Razo, C, Reda, ZFF, Reddy, MMRK, Redwan, EMM, Reifels, L, Mengist, B, Altirkawi, KA, Reitsma, MB, Remuzzi, G, Reshmi, B, Resnikoff, S, Restaino, S, Reyes, LF, Rezaei, M, Rezaei, N, Mensah, GA, Rezaeian, M, Aluh, DO, Rhee, TG, Riaz, MA, Ribeiro, ALP, Rickard, J, Robinson-Oden, HE, Rodrigues, CF, Rodrigues, M, Rodriguez, JAB, Mensah, LG, Roever, L, Romadlon, DS, Alvis-Guzman, N, Ronfani, L, Rosauer, JJ, Roshandel, G, Rostamian, M, Rotimi, K, Rout, HS, Roy, B, Al-Gheethi, AAS, Roy, N, Rubagotti, E, Ruela, GDA, Alvis-Zakzuk, NJ, Rumisha, SF, Runghien, T, Russo, M, Ruzzante, SW, S N, C, Saad, AMA, Mentis, A-FA, Saber, K, Saber-Ayad, MM, Sabour, S, Sacco, S, Abdi, P, Alwafi, H, Sachdev, PS, Sachdeva, R, Saddik, B, Saddler, A, Meo, SA, Sadee, BA, 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Mithra, P, Angappan, D, Tolani, MA, Tolossa, T, Tonelli, M, Topor-Madry, R, Topouzis, F, Touvier, M, Tovani-Palone, MR, Trabelsi, K, Tran, JT, Mittal, C, Tran, MTN, Angus, C, Tran, NM, Trico, D, Trihandini, I, Troeger, CE, Tromans, SJ, Truyen, TTTT, Tsatsakis, A, Tsermpini, EE, Moazen, B, Tumurkhuu, M, Udoakang, AJ, Anil, A, Udoh, A, Ullah, A, Ullah, S, Umair, M, Umakanthan, S, Unim, B, Moberg, ME, Unnikrishnan, B, Upadhyay, E, Urso, D, Anil, S, Usman, JS, Vaithinathan, AG, Vakili, O, Valenti, M, Valizadeh, R, Van den Eynde, J, Mocciaro, G, van Donkelaar, A, Varga, O, Vart, P, Varthya, SB, Anjum, A, Vasankari, TJ, Vasic, M, Vaziri, S, Venketasubramanian, N, Verghese, NA, Mohamadkhani, A, Verma, M, Veroux, M, Verras, G-I, Vervoort, D, Villafañe, JH, Anoushiravani, A, Villalobos-Daniel, VE, Villani, L, Villanueva, GI, Vinayak, M, Alhassan, RK, Violante, FS, Vlassov, V, Vo, B, Vollset, SE, Volovat, SR, Vos, T, Antonazzo, IC, Vujcic, IS, Waheed, Y, Wang, C, Mohamed, AZ, Wang, F, Wang, S, Wang, Y, Wang, Y-P, Wanjau, MN, Waqas, M, Ward, P, Abdulah, DM, Antony, CM, Waris, A, Mohamed, AI, Wassie, EG, Weerakoon, KG, Weintraub, RG, Weiss, DJ, Weiss, EJ, Weldetinsaa, HLL, Wells, KM, Wen, YF, Wiangkham, T, Antriyandarti, E, Mohamed, J, Wickramasinghe, ND, Wilkerson, C, Willeit, P, Wilson, S, Wong, YJ, Wongsin, U, Wozniak, S, Wu, C, Wu, D, Wu, F, Mohamed, MFH, Anuoluwa, BS, Wu, Z, Xia, J, Xiao, H, Xu, S, Xu, X, Xu, YY, Yadav, MK, Yaghoubi, S, Yamagishi, K, Mohamed, NS, Yang, L, Anvari, D, Yano, Y, Yaribeygi, H, Yasufuku, Y, Ye, P, Yesodharan, R, Yesuf, SA, Yezli, S, Yi, S, Mohammadi, E, Yiğit, A, Yigzaw, ZA, Anvari, S, Yin, D, Yip, P, Yismaw, MB, Yon, DK, Yonemoto, N, You, Y, Younis, MZ, Mohammadi, S, Yousefi, Z, Yu, C, Yu, Y, Anwar, S, Zadey, S, Zadnik, V, Zakham, F, Zaki, N, Zakzuk, J, Zamagni, G, Mohammadian-Hafshejani, A, Zaman, SB, Zandieh, GGZ, Zanghì, A, Zar, HJ, Anwar, SL, Zare, I, Zarimeidani, F, Zastrozhin, MS, Zeng, Y, Zhai, C, Mohammadifard, N, Zhang, AL, Zhang, H, Zhang, L, Zhang, M, Zhang, Y, Anwer, R, Zhang, Z, Zhang, Z-J, Zhao, H, Zhao, JT, Mohammed, H, Zhao, X-JG, Zhao, Y, Zhong, C, Zhou, J, Anyabolo, EE, Zhou, S, Zhu, B, Zhu, L, Ali, A, Zhu, Z, Ziaeian, B, Ziafati, M, Zielińska, M, Zimsen, SRM, Zoghi, G, Zoller, T, Anyasodor, AE, Zumla, A, Zyoud, SH, Mohammed, M, Murray, CJL, Gakidou, E, Abdullahi, A, Apostol, GLC, Arabloo, J, Arabzadeh Bahri, R, Arafat, M, Areda, D, Aregawi, BB, Mohammed, S, Aremu, A, Armocida, B, Arndt, MB, Ärnlöv, J, Abebe, M, Arooj, M, Artamonov, AA, Artanti, KD, Aruleba, IT, Arumugam, A, Asbeutah, AM, Asgary, S, Asgedom, AA, Ashbaugh, C, Ashemo, MY, Abedi, A, Ashraf, T, Askarinejad, A, Assmus, M, Astell-Burt, T, Mokdad, AH, Athar, M, Athari, SS, Atorkey, P, Atreya, A, Aujayeb, A, Ausloos, M, Avila-Burgos, L, Awoke, AA, Ayala Quintanilla, BP, Monasta, L, Ayatollahi, H, Ayestas Portugal, C, Ayuso-Mateos, JL, Azadnajafabad, S, Azevedo, RMS, Azhar, GS, Azizi, H, Abegaz, TM, Azzam, AY, Backhaus, IL, Mondello, S, Badar, M, Badiye, AD, Bagga, A, Baghdadi, S, Bagheri, N, Bagherieh, S, Bahrami Taghanaki, P, Bai, R, Abeldaño Zuñiga, RA, Baig, AA, Moni, MA, Baker, JL, Bakkannavar, SM, Balasubramanian, M, Baltatu, OC, Bam, K, Bandyopadhyay, S, Banik, B, Banik, PC, Banke-Thomas, A, Abiodun, O, Moodi Ghalibaf, A, Bansal, H, Barchitta, M, Bardhan, M, Bardideh, E, Barker-Collo, SL, Bärnighausen, TW, Barone-Adesi, F, Barqawi, HJ, Barrero, LH, Barrow, A, Moore, CE, Abiso, TL, Barteit, S, Basharat, Z, Basiru, A, Basso, JD, Bastan, M-M, Basu, S, Batchu, S, Batra, K, Batra, R, Moradi, M, Baune, BT, Aboagye, RG, Bayati, M, Bayileyegn, NS, Beaney, T, Behnoush, AH, Beiranvand, M, Béjot, Y, Bekele, A, Belgaumi, UI, Bell, AW, Bell, ML, Abolhassani, H, Bello, MB, Bello, OO, Belo, L, Beloukas, A, Bendak, S, Bennett, DA, and Bennitt, FB

Published
2024

37. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Author

Naghavi, M, Ong, KL, Aali, A, Ababneh, HS, Abate, YH, Abbafati, C, Abbasgholizadeh, R, Abbasian, M, Abbasi-Kangevari, M, Abbastabar, H, Abd ElHafeez, S, Abdelmasseh, M, Abd-Elsalam, S, Abdelwahab, A, Abdollahi, M, Abdollahifar, M-A, Abdoun, M, Abdulah, DM, Abdullahi, A, Abebe, M, Abebe, SS, Abedi, A, Abegaz, KH, Abhilash, ES, Abidi, H, Abiodun, O, Aboagye, RG, Abolhassani, H, Abolmaali, M, Abouzid, M, Aboye, GB, Abreu, LG, Abrha, WA, Abtahi, D, Abu Rumeileh, S, Abualruz, H, Abubakar, B, Abu-Gharbieh, E, Abu-Rmeileh, NME, Aburuz, S, Abu-Zaid, A, Accrombessi, MMK, Adal, TG, Adamu, AA, Addo, IY, Addolorato, G, Adebiyi, AO, Adekanmbi, V, Adepoju, AV, Adetunji, CO, Adetunji, JB, Adeyeoluwa, TE, Adeyinka, DA, Adeyomoye, OI, Admass, BAA, Adnani, QES, Adra, S, Afolabi, AA, Afzal, MS, Afzal, S, Agampodi, SB, Agasthi, P, Aggarwal, M, Aghamiri, S, Agide, FD, Agodi, A, Agrawal, A, Agyemang-Duah, W, Ahinkorah, BO, Ahmad, A, Ahmad, D, Ahmad, F, Ahmad, MM, Ahmad, S, Ahmad, T, Ahmadi, K, Ahmadzade, AM, Ahmed, A, Ahmed, H, Ahmed, LA, Ahmed, MS, Ahmed, MB, Ahmed, SA, Ajami, M, Aji, B, Akara, EM, Akbarialiabad, H, Akinosoglou, K, Akinyemiju, T, Akkaif, MA, Akyirem, S, Al Hamad, H, Al Hasan, SM, Alahdab, F, Alalalmeh, SO, Alalwan, TA, Al-Aly, Z, Alam, K, Alam, M, Alam, N, Al-amer, RM, Alanezi, FM, Alanzi, TM, Al-Azzam, S, Albakri, A, Albashtawy, M, AlBataineh, MT, Alcalde-Rabanal, JE, Aldawsari, KA, Aldhaleei, WA, Aldridge, RW, Alema, HB, Alemayohu, MA, Alemi, S, Alemu, YM, Al-Gheethi, AAS, Alhabib, KF, Alhalaiqa, FAN, Al-Hanawi, MK, Ali, A, Ali, L, Ali, MU, Ali, R, Ali, S, Ali, SSS, Alicandro, G, Alif, SM, Alikhani, R, Alimohamadi, Y, Aliyi, AA, Aljasir, MAM, Aljunid, SM, Alla, F, Allebeck, P, Al-Marwani, S, Al-Maweri, SAA, Almazan, JU, Al-Mekhlafi, HM, Almidani, L, Almidani, O, Alomari, MA, Al-Omari, B, Alonso, J, Alqahtani, JS, Alqalyoobi, S, Alqutaibi, AY, Al-Sabah, SK, Altaany, Z, Altaf, A, Al-Tawfiq, JA, Altirkawi, KA, Aluh, DO, Alvis-Guzman, N, Alwafi, H, Al-Worafi, YM, Aly, 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BA, Starnes, JR, Starodubova, AV, Stein, C, Stein, DJ, Steinbeis, F, Steiner, C, Steinmetz, JD, Steiropoulos, P, Stevanović, A, Stockfelt, L, Stokes, MA, Stortecky, S, Subramaniyan, V, Suleman, M, Suliankatchi Abdulkader, R, Sultana, A, Sun, HZ, Sun, J, Sundström, J, Sunkersing, D, Sunnerhagen, KS, Swain, CK, Szarpak, L, Szeto, MD, Szócska, M, Tabaee Damavandi, P, Tabarés-Seisdedos, R, Tabatabaei, SM, Tabatabaei Malazy, O, Tabatabaeizadeh, S-A, Tabatabai, S, Tabish, M, TADAKAMADLA, J, Tadakamadla, SK, Taheri Abkenar, Y, Taheri Soodejani, M, Taiba, J, Takahashi, K, Talaat, IM, Talukder, A, Tampa, M, Tamuzi, JL, Tan, K-K, Tandukar, S, Tang, H, Tang, HK, Tarigan, IU, Tariku, MK, Tariqujjaman, M, Tarkang, EE, Tavakoli Oliaee, R, Tavangar, SM, Taveira, N, Tefera, YM, Temsah, M-H, Temsah, RMH, Teramoto, M, Tesler, R, Teye-Kwadjo, E, Thakur, R, Thangaraju, P, Thankappan, KR, Tharwat, S, Thayakaran, R, Thomas, N, Thomas, NK, Thomson, AM, Thrift, AG, Thum, CCC, Thygesen, LC, Tian, J, Tichopad, A, Ticoalu, JHV, Tillawi, T, Tiruye, TY, Titova, MV, Tonelli, M, Topor-Madry, R, Toriola, AT, Torre, AE, Touvier, M, Tovani-Palone, MR, Tran, JT, Tran, NM, Trico, D, Tromans, SJ, Truyen, TTTT, Tsatsakis, A, Tsegay, GM, Tsermpini, EE, Tumurkhuu, M, Tung, K, Tyrovolas, S, Uddin, SMN, Udoakang, AJ, Udoh, A, Ullah, A, Ullah, I, Ullah, S, Umakanthan, S, Umeokonkwo, CD, Unim, B, Unnikrishnan, B, Unsworth, CA, Upadhyay, E, Urso, D, Usman, JS, Vahabi, SM, Vaithinathan, AG, Valizadeh, R, Van de Velde, SM, Van den Eynde, J, Varga, O, Vart, P, Varthya, SB, Vasankari, TJ, Vasic, M, Vaziri, S, Vellingiri, B, Venketasubramanian, N, Verghese, NA, Verma, M, Veroux, M, Verras, G-I, Vervoort, D, Villafañe, JH, Villanueva, GI, Vinayak, M, Violante, FS, Viskadourou, M, Vladimirov, SK, Vlassov, V, Vo, B, Vollset, SE, Vongpradith, A, Vos, T, Vujcic, IS, Vukovic, R, Wafa, HA, Waheed, Y, Wamai, RG, Wang, C, Wang, N, Wang, S, Wang, Y, Wang, Y-P, Waqas, M, Ward, P, Wassie, EG, Watson, S, Watson, SLW, Weerakoon, KG, Wei, MY, Weintraub, RG, Weiss, DJ, Westerman, R, Whisnant, JL, Wiangkham, T, Wickramasinghe, DP, Wickramasinghe, ND, Wilandika, A, Wilkerson, C, Willeit, P, Wilson, S, Wojewodzic, MW, Woldegebreal, DH, Wolf, AW, Wolfe, CDA, Wondimagegene, YA, Wong, YJ, Wongsin, U, Wu, A-M, Wu, C, Wu, F, Wu, X, Wu, Z, Xia, J, Xiao, H, Xie, Y, Xu, S, Xu, W-D, Xu, X, Xu, YY, Yadollahpour, A, Yamagishi, K, Yang, D, Yang, L, Yano, Y, Yao, Y, Yaribeygi, H, Ye, P, Yehualashet, SS, Yesiltepe, M, Yesuf, SA, Yezli, S, Yi, S, Yigezu, A, Yiğit, A, Yiğit, V, Yip, P, Yismaw, MB, Yismaw, Y, Yon, DK, Yonemoto, N, Yoon, S-J, You, Y, Younis, MZ, Yousefi, Z, Yu, C, Yu, Y, Yuh, FH, Zadey, S, Zadnik, V, Zafari, N, Zakham, F, Zaki, N, Zaman, SB, Zamora, N, Zand, R, Zangiabadian, M, Zar, HJ, Zare, I, Zarrintan, A, Zeariya, MGM, Zeinali, Z, Zhang, H, Zhang, J, Zhang, L, Zhang, Y, Zhang, Z-J, Zhao, H, Zhong, C, Zhou, J, Zhu, B, Zhu, L, Ziafati, M, Zielińska, M, Zitoun, OA, Zoladl, M, Zou, Z, Zuhlke, LJ, Zumla, A, Zweck, E, Zyoud, SH, Wool, EE, and Murray, CJL

Published
2024

38. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Author

Ferrari, AJ, Santomauro, DF, Aali, A, Abate, YH, Abbafati, C, Abbastabar, H, Abd ElHafeez, S, Abdelmasseh, M, Abd-Elsalam, S, Abdollahi, A, Abdullahi, A, Abegaz, KH, Abeldaño Zuñiga, RA, Aboagye, RG, Abolhassani, H, Abreu, LG, Abualruz, H, Abu-Gharbieh, E, Abu-Rmeileh, NME, Ackerman, IN, Addo, IY, Addolorato, G, Adebiyi, AO, Adepoju, AV, Adewuyi, HO, Afyouni, S, Afzal, S, Agodi, A, Ahmad, A, Ahmad, D, Ahmad, F, Ahmad, S, Ahmed, A, Ahmed, LA, Ahmed, MB, Ajami, M, Akinosoglou, K, Akkaif, MA, Al Hasan, SM, Alalalmeh, SO, Al-Aly, Z, Albashtawy, M, Aldridge, RW, Alemu, MD, Alemu, YM, Alene, KA, Al-Gheethi, AAS, Alharrasi, M, Alhassan, RK, Ali, MU, Ali, R, Ali, SSS, Alif, SM, Aljunid, SM, Al-Marwani, S, Almazan, JU, Alomari, MA, Al-Omari, B, Altaany, Z, Alvis-Guzman, N, Alvis-Zakzuk, NJ, Alwafi, H, Al-Wardat, MS, Al-Worafi, YM, Aly, S, Alzoubi, KH, Amare, AT, Amegbor, PM, Ameyaw, EK, Amin, TT, Amindarolzarbi, A, Amiri, S, Amugsi, DA, Ancuceanu, R, Anderlini, D, Anderson, DB, Andrade, PP, Andrei, CL, Ansari, H, Antony, CM, Anwar, S, Anwar, SL, Anwer, R, Anyanwu, PE, Arab, JP, Arabloo, J, Arafat, M, Araki, DT, Aravkin, AY, Arkew, M, Armocida, B, Arndt, MB, Arooj, M, Artamonov, AA, Aruleba, RT, Arumugam, A, Ashbaugh, C, Ashemo, MY, Ashraf, M, Asika, MO, Askari, E, Astell-Burt, T, Athari, SS, Atorkey, P, Atout, MMW, Atreya, A, Aujayeb, A, Ausloos, M, Avan, A, Awotidebe, AW, Awuviry-Newton, K, Ayala Quintanilla, BP, Ayuso-Mateos, JL, Azadnajafabad, S, Azevedo, RMS, Babu, AS, Badar, M, Badiye, AD, Baghdadi, S, Bagheri, N, Bah, S, Bai, R, Baker, JL, Bakkannavar, SM, Bako, AT, Balakrishnan, S, Bam, K, Banik, PC, Barchitta, M, Bardhan, M, Bardideh, E, Barker-Collo, SL, Barqawi, HJ, Barrow, A, Barteit, S, Barua, L, Bashiri Aliabadi, S, Basiru, A, Basu, S, Bathini, PP, Batra, K, Baune, BT, Bayileyegn, NS, Behnam, B, Behnoush, AH, Beiranvand, M, Bejarano Ramirez, DF, Bell, ML, Bello, OO, Beloukas, A, Bensenor, IM, Berezvai, Z, Bernabe, E, Bernstein, RS, Bettencourt, PJG, Bhagavathula, AS, Bhala, N, Bhandari, D, Bhargava, A, Bhaskar, S, Bhat, V, Bhatti, GK, Bhatti, JS, Bhatti, MS, Bhatti, R, Bhutta, ZA, Bikbov, B, Bishai, JD, Bisignano, C, Bitra, VR, Bjørge, T, Bodolica, V, Bodunrin, AO, Bogale, EK, Bonakdar Hashemi, M, Bonny, A, Bora Basara, B, Borhany, H, Boxe, C, Brady, OJ, Bragazzi, NL, Braithwaite, D, Brant, LC, Brauer, M, Breitner, S, Brenner, H, Brown, J, Brugha, T, Bulamu, NB, Buonsenso, D, Burkart, K, Burns, RA, Busse, R, Bustanji, Y, Butt, ZA, Byun, J, Caetano dos Santos, FL, Calina, D, Cámera, LA, Campos-Nonato, IR, Cao, C, Capodici, A, Carr, S, Carreras, G, Carugno, A, Carvalho, M, Castaldelli-Maia, JM, Castañeda-Orjuela, CA, Castelpietra, G, Catapano, AL, Cattaruzza, MS, Caye, A, Cegolon, L, Cembranel, F, Cenderadewi, M, Cerin, E, Chakraborty, PA, Chan, JSK, Chan, RNC, Chandika, RM, Chandrasekar, EK, Charalampous, P, Chattu, VK, Chatzimavridou-Grigoriadou, V, Chen, AW, Chen, A-T, Chen, CS, Chen, H, Chen, NM, Cheng, ETW, Chimed-Ochir, O, Chimoriya, R, Ching, PR, Cho, WCS, Choi, S, Chong, B, Chong, YY, Choudhari, SG, Chowdhury, R, Christensen, SWM, Chu, D-T, Chukwu, IS, Chung, E, Chutiyami, M, Claassens, MM, Cogen, RM, Columbus, A, Conde, J, Cortesi, PA, Cousin, E, Criqui, MH, Cruz-Martins, N, Dadras, O, Dai, S, Dai, X, Dai, Z, Dalaba, MA, Damiani, G, Das, JK, Das, S, Dashti, M, Dávila-Cervantes, CA, Davletov, K, De Leo, D, Debele, AT, Debopadhaya, S, DeCleene, NK, Deeba, F, Degenhardt, L, Del Bo', C, Delgado-Enciso, I, Demetriades, AK, Denova-Gutiérrez, E, Dervenis, N, Desai, HD, Desai, R, Deuba, K, Dhama, K, Dharmaratne, SD, Dhingra, S, Dias da Silva, D, Diaz, D, Diaz, LA, Diaz, MJ, Dima, A, Ding, DD, Dirac, MA, Do, THP, do Prado, CB, Dohare, S, Dominguez, R-MV, Dong, W, Dongarwar, D, D'Oria, M, Dorsey, ER, Doshmangir, L, Dowou, RK, Driscoll, TR, Dsouza, HL, Dsouza, V, Dube, J, Dumith, SC, Duncan, BB, Duraes, AR, Duraisamy, S, Durojaiye, OC, Dzianach, PA, Dziedzic, AM, Eboreime, E, Ebrahimi, A, Edinur, HA, Edvardsson, D, Eikemo, TA, Eini, E, Ekholuenetale, M, Ekundayo, TC, El Sayed, I, El Tantawi, M, Elbarazi, I, Elemam, NM, ElGohary, GMT, Elhadi, M, Elmeligy, OAA, ELNahas, G, Elshaer, M, Elsohaby, I, Engelbert Bain, L, Erkhembayar, R, Eshrati, B, Estep, K, Fabin, N, Fagbamigbe, AF, Falzone, L, Fareed, M, Farinha, CSES, Faris, MEM, Faro, A, Farrokhi, P, Fatehizadeh, A, Fauk, NK, Feigin, VL, Feng, X, Fereshtehnejad, S-M, Feroze, AH, Ferreira, N, Ferreira, PH, Fischer, F, Flavel, J, Flood, D, Flor, LS, Foigt, NA, Folayan, MO, Force, LM, Fortuna, D, Foschi, M, Franklin, RC, Freitas, A, Fukumoto, T, Furtado, JM, Gaal, PA, Gadanya, MA, Gaidhane, AM, Gaihre, S, Galali, Y, Ganbat, M, Gandhi, AP, Ganesan, B, Ganie, MA, Ganiyani, MA, Gardner, WM, Gebi, TG, Gebregergis, MW, Gebrehiwot, M, Gebremariam, TBB, Gebremeskel, TG, Gela, YY, Georgescu, SR, Getachew Obsa, A, Gething, PW, Getie, M, Ghadiri, K, Ghadirian, F, Ghailan, KY, Ghajar, A, Ghasemi, M, Ghasempour Dabaghi, G, Ghasemzadeh, A, Ghazy, RM, Gholamrezanezhad, A, Ghorbani, M, Ghotbi, E, Gibson, RM, Gill, TK, Ginindza, TG, Girmay, A, Glasbey, JC, Göbölös, L, Godinho, MA, Goharinezhad, S, Goldust, M, Golechha, M, Goleij, P, Gona, PN, Gorini, G, Goulart, AC, Grada, A, Grivna, M, Guan, S-Y, Guarducci, G, Gubari, MIM, Gudeta, MD, Guha, A, Guicciardi, S, Gulati, S, Gulisashvili, D, Gunawardane, DA, Guo, C, Gupta, AK, Gupta, B, Gupta, I, Gupta, M, Gupta, R, Gupta, VB, Gupta, VK, Gutiérrez, RA, Habibzadeh, F, Habibzadeh, P, Haddadi, R, Hadi, NR, Haep, N, Hafezi-Nejad, N, Hafiz, A, Hagins, H, Halboub, ES, Halimi, A, Haller, S, Halwani, R, Hamilton, EB, Hankey, GJ, Hannan, MA, Haque, MN, Harapan, H, Haro, JM, Hartvigsen, J, Hasaballah, AI, Hasan, I, Hasanian, M, Hasnain, MS, Hassan, A, Haubold, J, Havmoeller, RJ, Hay, SI, Hayat, K, Hebert, JJ, Hegazi, OE, Heidari, G, Helfer, B, Hemmati, M, Hendrie, D, Henson, CA, Hezam, K, Hiraike, Y, Hoan, NQ, Holla, R, Hon, J, Hossain, MM, Hosseinzadeh, H, Hosseinzadeh, M, Hostiuc, M, Hostiuc, S, Hsu, JM, Huang, J, Hugo, FN, Hushmandi, K, Hussain, J, Hussein, NR, Huynh, CK, Huynh, H-H, Hwang, B-F, Iannucci, VC, Ihler, AL, Ikiroma, AI, Ikuta, KS, Ilesanmi, OS, Ilic, IM, Ilic, MD, Imam, MT, Immurana, M, Irham, LM, Islam, MR, Islam, SMS, Islami, F, Ismail, F, Ismail, NE, Isola, G, Iwagami, M, Iwu, CCD, Iyer, M, Jaafari, J, Jacobsen, KH, Jadidi-Niaragh, F, Jafarinia, M, Jaggi, K, Jahankhani, K, Jahanmehr, N, Jahrami, H, Jain, A, Jain, N, Jairoun, AA, Jaiswal, A, Jakovljevic, M, Jatau, AI, Javadov, S, Javaheri, T, Jayapal, SK, Jayaram, S, Jee, SH, Jeganathan, J, Jeyakumar, A, Jha, AK, Jiang, H, Jin, Y, Jonas, JB, Joo, T, Joseph, A, Joseph, N, Joshua, CE, Jozwiak, JJ, Jürisson, M, K, V, Kaambwa, B, Kabir, A, Kabir, Z, Kadashetti, V, Kalani, R, Kalankesh, LR, Kaliyadan, F, Kalra, S, Kamenov, K, Kamyari, N, Kanagasabai, T, Kandel, H, Kanmanthareddy, AR, Kanmodi, KK, Kantar, RS, Karaye, IM, Karim, A, Karimi, SE, Karimi, Y, Kasraei, H, Kassel, MB, Kauppila, JH, Kawakami, N, Kayode, GA, Kazemi, F, Kazemian, S, Keikavoosi-Arani, L, Keller, C, Kempen, JH, Kerr, JA, Keshtkar, K, Kesse-Guyot, E, Keykhaei, M, Khajuria, H, Khalaji, A, Khalid, A, Khalid, N, Khalilian, A, Khamesipour, F, Khan, A, Khan, I, Khan, M, Khan, MAB, Khanmohammadi, S, Khatab, K, Khatami, F, Khatatbeh, MM, Khater, AM, Khayat Kashani, HR, Khidri, FF, Khodadoust, E, Khormali, M, Khorrami, Z, Kifle, ZD, Kim, MS, Kimokoti, RW, Kisa, A, Kisa, S, Knudsen, AKS, Kocarnik, JM, Kochhar, S, Koh, HY, Kolahi, A-A, Kompani, F, Koren, G, Korzh, O, Kosen, S, Koulmane Laxminarayana, SL, Krishan, K, Krishna, V, Krishnamoorthy, V, Kuate Defo, B, Kuddus, MA, Kuddus, M, Kuitunen, I, Kulkarni, V, Kumar, M, Kumar, N, Kumar, R, Kurmi, OP, Kusuma, D, Kyu, HH, La Vecchia, C, Lacey, B, Ladan, MA, Laflamme, L, Lafranconi, A, Lahariya, C, Lai, DTC, Lal, DK, Lalloo, R, Lallukka, T, Lám, J, Lan, Q, Lan, T, Landires, I, Lanfranchi, F, Langguth, B, Laplante-Lévesque, A, Larijani, B, Larsson, AO, Lasrado, S, Lauriola, P, Le, H-H, Le, LKD, Le, NHH, Le, TDT, Leasher, JL, Ledda, C, Lee, M, Lee, PH, Lee, S-W, Lee, SW, Lee, W-C, Lee, YH, LeGrand, KE, Lenzi, J, Leong, E, Leung, J, Li, M-C, Li, W, Li, X, Li, Y, Lim, L-L, Lim, SS, Lindstrom, M, Linn, S, Liu, G, Liu, R, Liu, S, Liu, W, Liu, X, Llanaj, E, Lo, C-H, López-Bueno, R, Loreche, AM, Lorenzovici, L, Lozano, R, Lubinda, J, Lucchetti, G, Lunevicius, R, Lusk, JB, lv, H, Ma, ZF, Machairas, N, Madureira-Carvalho, ÁM, Magaña Gómez, JA, Maghazachi, AA, Maharjan, P, Mahasha, PW, Maheri, M, Mahjoub, S, Mahmoud, MA, Mahmoudi, E, Majeed, A, Makris, KC, Malakan Rad, E, Malhotra, K, Malik, AA, Malik, I, Malta, DC, Manla, Y, Mansour, A, Mansouri, P, Mansournia, MA, Mantilla Herrera, AM, Mantovani, LG, Manu, E, Marateb, HR, Mardi, P, Martinez, G, Martinez-Piedra, R, Martini, D, Martins-Melo, FR, Martorell, M, Marx, W, Maryam, S, Marzo, RR, Mathangasinghe, Y, Mathieson, S, Mathioudakis, AG, Mattumpuram, J, Maugeri, A, Mayeli, M, Mazidi, M, Mazzotti, A, McGrath, JJ, McKee, M, 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R, Misganaw, A, Mishra, AK, Mitchell, PB, Mittal, C, Moazen, B, Moberg, ME, Mohamed, J, Mohamed, MFH, Mohamed, NS, Mohammadi, E, Mohammadi, S, Mohammed, H, Mohammed, S, Mohr, RM, Mokdad, AH, Molinaro, S, Momtazmanesh, S, Monasta, L, Mondello, S, Moodi Ghalibaf, A, Moradi, M, Moradi, Y, Moradi-Lakeh, M, Moraga, P, Morawska, L, Moreira, RS, Morovatdar, N, Morrison, SD, Morze, J, Mosapour, A, Mosser, JF, Mossialos, E, Motappa, R, Mougin, V, Mouodi, S, Mrejen, M, Msherghi, A, Mubarik, S, Mueller, UO, Mulita, F, Munjal, K, Murillo-Zamora, E, Murlimanju, BV, Mustafa, G, Muthu, S, Muzaffar, M, Myung, W, Nagarajan, AJ, Naghavi, P, Naik, GR, Nainu, F, Nair, S, Najmuldeen, HHR, Nangia, V, Naqvi, AA, Narayana, AI, Nargus, S, Nascimento, GG, Nashwan, AJ, Nasrollahizadeh, A, Natto, ZS, Nayak, BP, Nayak, VC, Nduaguba, SO, Negash, H, Negoi, I, Negoi, RI, Nejadghaderi, SA, Nesbit, OD, Netsere, HB, Ng, M, Nguefack-Tsague, G, Ngunjiri, JW, Nguyen, DH, Nguyen, HQ, Niazi, RK, Nikolouzakis, TK, Nikoobar, A, Nikoomanesh, F, Nikpoor, AR, Nnaji, CA, Nnyanzi, LA, Noman, EA, Nomura, S, Norrving, B, Nri-Ezedi, CA, Ntaios, G, Ntsekhe, M, Nurrika, D, Nzoputam, CI, Nzoputam, OJ, Oancea, B, Odetokun, IA, O'Donnell, MJ, Oguntade, AS, Oguta, JO, Okati-Aliabad, H, Okeke, SR, Okekunle, AP, Okonji, OC, Olagunju, AT, Olasupo, OO, Olatubi, MI, Oliveira, GMM, Olufadewa, II, Olusanya, BO, Olusanya, JO, Omar, HA, Omer, GL, Omonisi, AEE, Onie, S, Onwujekwe, OE, Ordak, M, Orish, VN, Ortega-Altamirano, DV, Ortiz, A, Ortiz-Brizuela, E, Osman, WMS, Ostroff, SM, Osuagwu, UL, Otoiu, A, Otstavnov, N, Otstavnov, SS, Ouyahia, A, Ouyang, G, Owolabi, MO, P A, MP, Padron-Monedero, A, Padubidri, JR, Palicz, T, Palladino, C, Pan, F, Pandi-Perumal, SR, Pangaribuan, HU, Panos, GD, Panos, LD, Pantea Stoian, AM, Pardhan, S, Parikh, RR, Pashaei, A, Pasovic, M, Passera, R, Patel, J, Patel, SK, Patil, S, Patoulias, D, Patthipati, VS, Pawar, S, Pazoki Toroudi, H, Pease, SA, Peden, AE, Pedersini, P, Peng, M, Pensato, U, Pepito, VCF, Peprah, EK, Peprah, P, Perdigão, J, Pereira, MO, Perianayagam, A, Perico, N, Pesudovs, K, Petermann-Rocha, FE, Petri, WA, Pham, HT, Philip, AK, Phillips, MR, Pigeolet, M, Pigott, DM, Pillay, JD, Piracha, ZZ, Pirouzpanah, S, Plass, D, Plotnikov, E, Poddighe, D, Polinder, S, Postma, MJ, Pourtaheri, N, Prada, SI, Pradhan, PMS, Prakash, V, Prasad, M, Prates, EJS, Priscilla, T, Pritchett, N, Puri, P, Puvvula, J, Qasim, NH, Qattea, I, Qazi, AS, Qian, G, Rabiee Rad, M, Radhakrishnan, RA, Radhakrishnan, V, Raeisi Shahraki, H, Rafferty, Q, Raggi, A, Raghav, PR, Rahim, MJ, Rahman, MM, Rahman, MHU, Rahman, M, Rahman, MA, Rahmani, S, Rahmanian, M, Rahmawaty, S, Rajaa, S, Ramadan, MM, Ramasamy, SK, Ramasubramani, P, Ramazanu, S, Rana, K, Ranabhat, CL, Rancic, N, Rane, A, Rao, CR, Rao, K, Rao, M, Rao, SJ, Rashidi, M-M, Rathnaiah Babu, G, Rauniyar, SK, Rawaf, DL, Rawaf, S, Razo, C, Reddy, MMRK, Redwan, EMM, Reifels, L, Reiner Jr, RC, Remuzzi, G, Renzaho, AMN, Reshmi, B, Reyes, LF, Rezaei, N, Rezaei Hachesu, P, Rezaeian, M, Rickard, J, Rodrigues, CF, Rodriguez, JAB, Roever, L, Ronfani, L, Roshandel, G, Rotimi, K, Rout, HS, Roy, B, Roy, N, Roy, P, Rubagotti, E, S N, C, Saad, AMA, Saber-Ayad, MM, Sabour, S, Sacco, S, Sachdev, PS, Saddik, B, Saddler, A, Sadee, BA, Sadeghi, E, Sadeghi, M, Saeb, MR, Saeed, U, Safi, SZ, Sagar, R, Sagoe, D, Saif, Z, Sajid, MR, Sakshaug, JW, Salam, N, Salami, AA, Salaroli, LB, Saleh, MA, Salem, MR, Salem, MZY, Sallam, M, Samadzadeh, S, Samargandy, S, Samodra, YL, Samy, AM, Sanabria, J, Sanna, F, Santos, IS, Santric-Milicevic, MM, Sarasmita, MA, Sarikhani, Y, Sarmiento-Suárez, R, Sarode, GS, Sarode, SC, Sarveazad, A, Sathian, B, Sathyanarayan, A, Satpathy, M, Sawhney, M, Scarmeas, N, Schaarschmidt, BM, Schmidt, MI, Schneider, IJC, Schumacher, AE, Schwebel, DC, Schwendicke, F, Sedighi, M, Senapati, S, Senthilkumaran, S, Sepanlou, SG, Sethi, Y, Setoguchi, S, Seylani, A, Shadid, J, Shafie, M, Shah, H, Shah, NS, Shah, PA, Shahbandi, A, Shahid, S, Shahid, W, Shahwan, MJ, Shaikh, MA, Shakeri, A, Shalash, AS, Sham, S, Shamim, MA, Shamshirgaran, MA, Shamsi, MA, Shanawaz, M, Shankar, A, Shannawaz, M, Sharath, M, Sharifan, A, Sharifi-Rad, J, Sharma, M, Sharma, R, Sharma, S, Sharma, U, Sharma, V, Shastry, RP, Shavandi, A, Shayan, AM, Shayan, M, Shehabeldine, AME, Shetty, PH, Shibuya, K, Shifa, JE, Shiferaw, D, Shiferaw, WS, Shigematsu, M, Shiri, R, Shitaye, NA, Shittu, A, Shivakumar, KM, Shivarov, V, Shokati Eshkiki, Z, Shool, S, Shrestha, S, Shuval, K, Sibhat, MM, Siddig, EE, Sigfusdottir, ID, Silva, DAS, Silva, JP, Silva, LMLR, Silva, S, Simpson, CR, Singal, A, Singh, A, Singh, BB, Singh, H, Singh, JA, Singh, M, Singh, P, Skou, ST, Sleet, DA, Slepak, ELN, Solanki, R, Soliman, SSM, Song, S, Song, Y, Sorensen, RJD, Soriano, JB, Soyiri, IN, Spartalis, M, Sreeramareddy, CT, Stark, BA, Starodubova, AV, Stein, C, Stein, DJ, Steiner, C, Steiner, TJ, Steinmetz, JD, Steiropoulos, P, Stockfelt, L, Stokes, MA, Subedi, NS, Subramaniyan, V, Suemoto, CK, Suleman, M, Suliankatchi Abdulkader, R, Sultana, A, Sundström, J, Swain, CK, Szarpak, L, Tabaee Damavandi, P, Tabarés-Seisdedos, R, Tabatabaei Malazy, O, Tabatabaeizadeh, S-A, Tabatabai, S, Tabche, C, Tabish, M, Tadakamadla, SK, Taheri Abkenar, Y, Taheri Soodejani, M, Taherkhani, A, Taiba, J, Talaat, IM, Talukder, A, Tampa, M, Tamuzi, JL, Tan, K-K, Tandukar, S, Tang, H, Tavakoli Oliaee, R, Tavangar, SM, Teimoori, M, Temsah, M-H, Teramoto, M, Thangaraju, P, Thankappan, KR, Thapar, R, Thayakaran, R, Thirunavukkarasu, S, Thomas, N, Thomas, NK, Thum, CCC, Tichopad, A, Ticoalu, JHV, Tillawi, T, Tiruye, TY, Tobe-Gai, R, Tonelli, M, Topor-Madry, R, Torre, AE, Touvier, M, Tovani-Palone, MR, Tran, JT, Tran, MTN, Tran, NM, Tran, N-H, Trico, D, Tromans, SJ, Truyen, TTTT, Tsatsakis, A, Tsegay, GM, Tsermpini, EE, Tumurkhuu, M, Tyrovolas, S, Udoh, A, Umair, M, Umakanthan, S, Umar, TP, Undurraga, EA, Unim, B, Unnikrishnan, B, Unsworth, CA, Upadhyay, E, Urso, D, Usman, JS, Vahabi, SM, Vaithinathan, AG, Van den Eynde, J, Varga, O, Varma, RP, Vart, P, Vasankari, TJ, Vasic, M, Vaziri, S, Vellingiri, B, Venketasubramanian, N, Veroux, M, Verras, G-I, Vervoort, D, Villafañe, JH, Violante, FS, Vlassov, V, Vollset, SE, Volovat, SR, Vongpradith, A, Waheed, Y, Wang, C, Wang, F, Wang, N, Wang, S, Wang, Y, Wang, Y-P, Ward, P, Wassie, EG, Weaver, MR, Weerakoon, KG, Weintraub, RG, Weiss, DJ, Weldemariam, AH, Wells, KM, Wen, YF, Whisnant, JL, Whiteford, HA, Wiangkham, T, Wickramasinghe, DP, Wickramasinghe, ND, Wilandika, A, Wilkerson, C, Willeit, P, Wimo, A, Woldegebreal, DH, Wolf, AW, Wong, YJ, Woolf, AD, Wu, C, Wu, F, Wu, X, Wu, Z, Wulf Hanson, S, Xia, Y, Xiao, H, Xu, X, Xu, YY, Yadav, L, Yadollahpour, A, Yaghoubi, S, Yamagishi, K, Yang, L, Yano, Y, Yao, Y, Yaribeygi, H, Yazdanpanah, MH, Ye, P, Yehualashet, SS, Yesuf, SA, Yezli, S, Yiğit, A, Yiğit, V, Yigzaw, ZA, Yismaw, Y, Yon, DK, Yonemoto, N, Younis, MZ, Yu, C, Yu, Y, Yusuf, H, Zahid, MH, Zakham, F, Zaki, L, Zaki, N, Zaman, BA, Zamora, N, Zand, R, Zandieh, GGZ, Zar, HJ, Zarrintan, A, Zastrozhin, MS, Zhang, H, Zhang, N, Zhang, Y, Zhao, H, Zhong, C, Zhong, P, Zhou, J, Zhu, Z, Ziafati, M, Zielińska, M, Zimsen, SRM, Zoladl, M, Zumla, A, Zyoud, SH, Vos, T, and Murray, CJL

Published
2024

40. 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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41. 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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42. 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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43. Spatiotemporal network motif reveals the biological traits of developmental gene regulatory networks in Drosophila melanogaster

Author

Kim, MS, Kim, JR, Kim, D, Lander, AD, and Cho, KH

Abstract

Background: Network motifs provided a " conceptual tool" for understanding the functional principles of biological networks, but such motifs have primarily been used to consider static network structures. Static networks, however, cannot be used to reveal time- and region-specific traits of biological systems. To overcome this limitation, we proposed the concept of a " spatiotemporal network motif," a spatiotemporal sequence of network motifs of sub-networks which are active only at specific time points and body parts.Results: On the basis of this concept, we analyzed the developmental gene regulatory network of the Drosophila melanogaster embryo. We identified spatiotemporal network motifs and investigated their distribution pattern in time and space. As a result, we found how key developmental processes are temporally and spatially regulated by the gene network. In particular, we found that nested feedback loops appeared frequently throughout the entire developmental process. From mathematical simulations, we found that mutual inhibition in the nested feedback loops contributes to the formation of spatial expression patterns.Conclusions: Taken together, the proposed concept and the simulations can be used to unravel the design principle of developmental gene regulatory networks. © 2012 Kim et al.; licensee BioMed Central Ltd.

Published
2012

44. The Effects of Approximate Multiplication on Convolutional Neural Networks

Author

Kim, MS, Kim, MS, Del Barrio, AA, Kim, HJ, Bagherzadeh, N, Kim, MS, Kim, MS, Del Barrio, AA, Kim, HJ, and Bagherzadeh, N

Abstract

This article analyzes the effects of approximate multiplication when performing inferences on deep convolutional neural networks (CNNs). The approximate multiplication can reduce the cost of the underlying circuits so that CNN inferences can be performed more efficiently in hardware accelerators. The study identifies the critical factors in the convolution, fully-connected, and batch normalization layers that allow more accurate CNN predictions despite the errors from approximate multiplication. The same factors also provide an arithmetic explanation of why bfloat16 multiplication performs well on CNNs. The experiments are performed with recognized network architectures to show that the approximate multipliers can produce predictions that are nearly as accurate as the FP32 references, without additional training. For example, the ResNet and Inception-v4 models with Mitch-ww6 multiplication produces Top-5 errors that are within 0.2 percent compared to the FP32 references. A brief cost comparison of Mitch-ww6 against bfloat16 is presented where a MAC operation saves up to 80 percent of energy compared to the bfloat16 arithmetic. The most far-reaching contribution of this article is the analytical justification that multiplications can be approximated while additions need to be exact in CNN MAC operations.

Published
2022

45. Gabapentin for Pain in Pediatric Palliative Care.

Author

Drake, R, Prael, G, Phyo, Y, Chang, S, Hunt, J, Herbert, A, Mott, C, Hynson, J, Phillips, M, Cossich, M, Mherekumombe, M, Kim, MS, Chong, PH, Abitz, M, Bernada, M, Avery, M, Doogue, M, Rowett, D, Currow, D, Drake, R, Prael, G, Phyo, Y, Chang, S, Hunt, J, Herbert, A, Mott, C, Hynson, J, Phillips, M, Cossich, M, Mherekumombe, M, Kim, MS, Chong, PH, Abitz, M, Bernada, M, Avery, M, Doogue, M, Rowett, D, and Currow, D

Abstract

OBJECTIVE: Gabapentin is commonly used to treat pain in children receiving pediatric palliative care. This study describes the real-world use of gabapentin and the associated benefits and adverse effects/events (AEs). METHODS: A prospective, multicenter cohort of standardized data collection after a clinical decision was made to use gabapentin for managing neuropathic or nociplastic pain in children attended on by a pediatric palliative care service. It was conducted across 11 sites in seven countries including hospital, inpatient, and outpatient services. Clinical outcomes were graded using pain scales validated for age and cognitive ability and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) at baseline, 14 days, 28 days, six weeks and 12 weeks after initiation of gabapentin. Ad-hoc safety reporting continued throughout the study. RESULTS: Data were collected from 127 children with a median age of 4.7 years (IQR 0.1-17.9); 61% had a neurological disorder, 21% advanced cancer and the cohort had a high level of disability (Lansky/Karnofsky performance score 37.1). Gabapentin was prescribed at standard pediatric doses. On average, 76% of children had a reduction in pain and 42% experienced a potential AE. The mean pain score decreased from 6.0 (SD 2.6) at baseline to 3.3 (SD 2.4) at 14 days and 1.8 (SD 1.8) after 12-weeks of gabapentin therapy. Ten percent had increased pain at each time point. AEs did not increase when individual changes over time were accounted for except for somnolence (7%). Serious AEs attributable to gabapentin were possible or probable in 3% of children. CONCLUSIONS: Gabapentin prescribed at standard doses for advanced cancer and severe neurological injury in children under a pediatric palliative care service was associated with generally improved pain intensity at previously described levels of adverse effects.

Published
2023

46. 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, K, Grunewald, M, Bein, S, Benato, L, Prosper, H, Seitova, D, De Lentdecker, G, Connor, P, De Leo, K, Eich, M, Feindt, F, White, R, Fröhlich, A, Abbrescia, M, Garbers, C, Garutti, E, Gunnellini, P, Schiber, C, Hajheidari, M, Shalaev, V, Haller, J, Favart, L, Swain, SK, Hinzmann, A, Kasieczka, G, Aly, R, Klanner, R, Kogler, R, Kramer, T, Kutzner, V, Viazlo, O, Lange, J, Lange, T, Ngadiuba, J, Shmatov, S, Lobanov, A, Malara, A, Zarubin, A, Dermenev, A, Grebenyuk, A, Nigamova, A, Pena Rodriguez, KJ, Rieger, O, Schleper, P, Kim, D, Yohay, R, Schröder, M, Schwandt, J, Sonneveld, J, Shulha, S, Aruta, C, Stadie, H, Steinbrück, G, Tews, A, Kalsi, AK, Bell, KW, Zoi, I, Bechtel, J, Salazar González, CA, Brommer, S, Burkart, M, Butz, E, Madrid, C, Caspart, R, Smirnov, V, Chwalek, T, Belyaev, A, De Boer, W, Dierlamm, A, Droll, A, Lee, K, Zhang, J, El Morabit, K, Faltermann, N, Roy, T, Giffels, M, Gosewisch, JO, Brew, C, Gottmann, A, Teryaev, O, Hartmann, F, Heidecker, C, Husemann, U, Keicher, P, Baarmand, MM, Koppenhöfer, R, Colaleo, A, Mahdavikhorrami, M, Martins, J, Leggat, D, Maier, S, Metzler, M, Mitra, S, Müller, T, Voytishin, N, Neukum, M, Nürnberg, A, Quast, G, Butalla, S, Creanza, D, Brown, RM, Rabbertz, K, Rauser, J, Savoiu, D, Makarenko, I, Schnepf, M, Seith, D, Shvetsov, I, Sznajder, A, Simonis, HJ, Ulrich, R, Cockerill, DJA, De Filippis, N, De La Cruz-Burelo, E, Van Der Linden, J, Von Cube, RF, Wassmer, M, Weber, M, Wieland, S, Moureaux, L, Wolf, R, Wozniewski, S, Cooke, C, Yuldashev, BS, Skovpen, K, Wunsch, S, De Palma, M, Di Florio, A, Karathanasis, G, Di Pilato, A, Elmetenawee, W, Fiore, L, Gninenko, S, Ellis, KV, Alves Gallo Pereira, M, Gelmi, A, Gul, M, Iaselli, G, Ince, M, Lezki, S, Kontaxakis, P, Tytgat, M, Maggi, G, Maggi, M, Vats, D, Margjeka, I, Mastrapasqua, V, Mora Herrera, C, Golubev, N, My, S, Nuzzo, S, Pellecchia, A, Koraka, CK, Pompili, A, Pugliese, G, Kim, S, Ramos, D, Vermassen, B, Ranieri, A, Selvaggi, G, Rudrabhatla, S, Silvestris, L, Radburn-Smith, BC, Torres Da Silva De Araujo, F, Manousakis-Katsikakis, A, Simone, FM, Harder, K, Venditti, R, Verwilligen, P, Abbiendi, G, Battilana, C, Bonacorsi, D, Borgonovi, L, Tonjes, MB, Wezenbeek, L, Brigliadori, L, Panagiotou, A, Maravin, Y, Campanini, R, Karneyeu, A, Capiluppi, P, Castro, A, Cavallo, FR, Cuffiani, M, Dallavalle, GM, Diotalevi, T, Varelas, N, Fabbri, F, Harper, S, Papavergou, I, Fanfani, A, Benecke, A, Giacomelli, P, Kirpichnikov, D, Giommi, L, Grandi, C, Guiducci, L, Lo Meo, S, Lunerti, L, Senger, M, Holmberg, M-L, Viinikainen, J, Saoulidou, N, Marcellini, S, Masetti, G, Navarria, FL, Perrotta, A, Bethani, A, Kirsanov, M, Primavera, F, Rossi, AM, Linacre, J, Rovelli, T, Siroli, GP, Theofilatos, K, Wang, X, Albergo, S, Costa, S, Di Mattia, A, Potenza, R, Tricomi, A, Tuve, C, Manolopoulos, K, Krasnikov, N, Bruno, G, Barbagli, G, Tziaferi, E, Cassese, A, Wu, Z, Ceccarelli, R, Ciulli, V, Civinini, C, D’Alessandro, R, Newbold, DM, Focardi, E, Latino, G, Lenzi, P, Pashenkov, A, Kumar Verma, R, Lizzo, M, Bury, F, Ye, Z, Meschini, M, Paoletti, S, Schieck, J, Seidita, R, Sguazzoni, G, Viliani, L, Benussi, L, Bianco, S, Popov, A, Piccolo, D, Pivovarov, G, Bozzo, M, Maeshima, K, Liao, H, Alhusseini, M, Ferro, F, Caputo, C, Mulargia, R, Robutti, E, Tosi, S, Zhizhin, I, Benaglia, A, Boldrini, G, Brivio, F, Vanlaer, P, Cetorelli, F, Toropin, A, Dilsiz, K, De Guio, F, Dinardo, ME, Dini, P, David, P, Vellidis, K, Gennai, S, Ghezzi, A, Olaiya, E, Govoni, P, Guzzi, L, Lucchini, MT, Malberti, M, Lelas, D, Epshteyn, V, Malvezzi, S, Massironi, A, Vourliotis, E, Menasce, D, Petyt, D, Moroni, L, Delaere, C, Paganoni, M, Pedrini, D, Pinolini, BS, Ragazzi, S, Lopez-Fernandez, R, Redaelli, N, Gavrilov, V, Bakas, G, Ko, B, Tabarelli de Fatis, T, Valsecchi, D, Zuolo, D, Buontempo, S, Carnevali, F, Donertas, IS, Cavallo, N, De Iorio, A, Gandrajula, RP, Fabozzi, F, Takahashi, Y, Mitchell, T, Kousouris, K, Iorio, AOM, Barroso Ferreira Filho, M, Lychkovskaya, N, Lista, L, Meola, S, Paolucci, P, Rossi, B, Sciacca, C, Azzi, P, Reis, T, Köseyan, OK, Papakrivopoulos, I, Giammanco, A, Bacchetta, N, Bisello, D, Bortignon, P, Vilela Pereira, A, Bragagnolo, A, Carlin, R, Checchia, P, Schuh, T, Dorigo, T, Dosselli, U, Tsipolitis, G, Merlo, J-P, Gasparini, F, Gasparini, U, Jaffel, K, Grosso, G, Hoh, SY, Nikitenko, A, Shepherd-Themistocleous, CH, Layer, L, Lusiani, E, Margoni, M, Zacharopoulou, A, Meneguzzo, AT, Mestvirishvili, A, Pazzini, J, Ronchese, P, Rossin, R, Simonetto, F, Tomalin, IR, Jain, S, Strong, G, Popov, V, Tosi, M, Adamidis, K, Yarar, H, Zanetti, M, Nachtman, J, Zotto, P, Zucchetta, A, Williams, T, Zumerle, G, Aimè, C, Braghieri, A, Calzaferri, S, Lemaitre, V, Noonan, D, Stepennov, A, Fiorina, D, Montagna, P, Ogul, H, Bainbridge, R, Ratti, SP, Re, V, Riccardi, C, Salvini, P, Vai, I, Vitulo, P, Bestintzanos, I, Asenov, P, Bilei, GM, Toms, M, Bansal, S, Mondal, K, Mantilla, C, Onel, Y, Ciangottini, D, Fanò, L, Lariccia, P, Magherini, M, Evangelou, I, Mantovani, G, Mariani, V, Bloch, P, Menichelli, M, Moscatelli, F, Piccinelli, A, Vlasov, E, Penzo, A, Presilla, M, Prisciandaro, J, Rossi, A, Gavrilov, G, Santocchia, A, Bonomally, S, Spiga, D, Tedeschi, T, Azzurri, P, Bagliesi, G, Bertacchi, V, Bianchini, L, Snyder, C, Zhokin, A, Boccali, T, Postiau, N, Adloff, C, Liu, Z-A, Bossini, E, Taliercio, A, Castaldi, R, Ciocci, MA, D’Amante, V, Dell’Orso, R, Di Domenico, MR, Donato, S, Tiras, E, Giassi, A, Borg, J, Foudas, C, Aushev, T, Ligabue, F, Manca, E, Mandorli, G, Teklishyn, M, Matos Figueiredo, D, Messineo, A, Palla, F, Parolia, S, Modak, A, Mondragon Herrera, CA, Gianneios, P, Ramirez-Sanchez, G, Rizzi, A, Chadeeva, M, Rolandi, G, Roy Chowdhury, S, Scribano, A, Shafiei, N, Tran, TT, Lee, JSH, Spagnolo, P, Tenchini, R, Katsoulis, P, Waltenberger, W, Tonelli, G, Turini, N, Venturi, A, Sekmen, S, Oskin, A, Verdini, PG, Breeze, S, Barria, P, Campana, M, Cavallari, F, Kokkas, P, Del Re, D, Puljak, I, Vischia, P, Di Marco, E, Diemoz, M, Longo, E, Buchmuller, O, Meridiani, P, Parygin, P, Organtini, G, Pandolfi, F, Manthos, N, Paramatti, R, Quaranta, C, Amram, O, Rahatlou, S, Rovelli, C, Cepaitis, V, Wertz, S, Santanastasio, F, Soffi, L, Tramontano, R, Liko, D, Papadopoulos, I, Amapane, N, Arcidiacono, R, Argiro, S, Blumenfeld, B, Chahal, GS, Arneodo, M, Bartosik, N, Bellan, R, Bellora, A, Alves, GA, Berenguer Antequera, J, Rahmani, M, Biino, C, Bernardes, CA, Cartiglia, N, Beri, SB, Cometti, S, Corcodilos, L, Costa, M, Covarelli, R, Demaria, N, Kiani, B, Legger, F, Strologas, J, Mariotti, C, Hensel, C, Colling, D, Maselli, S, Popova, E, Migliore, E, Mason, D, Davis, J, Monteil, E, Monteno, M, Obertino, MM, Csanad, M, Ortona, G, Oh, BH, Dauncey, P, Pacher, L, Pastrone, N, Pelliccioni, M, Pinna Angioni, GL, Moraes, A, Rusinov, V, Eminizer, M, Ruspa, M, Shchelina, K, Farkas, K, Davies, G, Siviero, F, Sola, V, Solano, A, Soldi, D, Staiano, A, Tornago, M, Trocino, D, Vagnerini, A, Gritsan, AV, Selivanova, D, Della Negra, M, Golovtcov, V, Aldá Júnior, WL, Belforte, S, Candelise, V, Casarsa, M, Cossutti, F, Da Rold, A, Della Ricca, G, Sorrentino, G, Vazzoler, F, Fayer, S, Kyriacou, S, Gadallah, MMA, Dogra, S, Andreev, V, Huh, C, Azarkin, M, Dremin, I, Yang, YC, Kirakosyan, M, Terkulov, A, Nam, K, Boos, E, Starling, E, Maksimovic, P, Calligaris, L, Dubinin, M, Dudko, L, Ershov, A, Klyukhin, V, Kodolova, O, Milosevic, V, Kim, H, Lokhtin, I, Lukina, O, Lökös, S, Obraztsov, S, Perez Navarro, DA, Petrushanko, S, Savrin, V, Fernandez Perez Tomei, TR, Snigirev, A, Lee, Y, Blinov, V, Dimova, T, Kardapoltsev, L, Moon, DH, Major, P, Kozyrev, A, Ovtin, I, Roskes, J, Radchenko, O, Skovpen, Y, Fedi, G, Azhgirey, I, Bayshev, I, Gregores, EM, Elumakhov, D, Kachanov, V, Mandal, K, Konstantinov, D, Francois, B, Mandrik, P, Swartz, M, Hall, G, Petrov, V, Ryutin, R, Slabospitskii, S, Sobol, A, Troshin, S, Tyurin, N, Mehta, A, Lemos, DS, Uzunian, A, Volkov, A, Bhatnagar, V, Kim, TJ, Antunovic, Z, Babaev, A, Okhotnikov, V, Borshch, V, Ivanchenko, V, Tcherniaev, E, Yumiceva, F, Adzic, P, Dordevic, M, Kuo, CM, Hassanshahi, MH, Milenovic, P, Mercadante, PG, Milosevic, J, Vámi, TÁ, Park, J, Aguilar-Benitez, M, Alcaraz Maestre, J, Álvarez Fernández, A, Pasztor, G, Bachiller, I, Iles, G, Barrio Luna, M, Bedoya, CF, Carrillo Montoya, CA, Cepeda, M, Cerrada, M, McBride, P, Abreu, A, Novaes, SF, Cho, S, Rádl, AJ, Langford, J, Colino, N, De La Cruz, B, Delgado Peris, A, Fernández Ramos, JP, Flix, J, Fouz, MC, Gonzalez Lopez, O, Goy Lopez, S, Anguiano, J, Hernandez, JM, Lyons, L, Surányi, O, Josa, MI, Choi, S, Padula, SS, León Holgado, J, Moran, D, Navarro Tobar, Á, Perez Dengra, C, Pérez-Calero Yzquierdo, A, Puerta Pelayo, J, Magnan, A-M, Baldenegro Barrera, C, Veres, GI, Redondo, I, Romero, L, Sánchez Navas, S, Go, Y, Urda Gómez, L, Aleksandrov, A, Willmott, C, de Trocóniz, JF, Malik, S, Reyes-Almanza, R, Alvarez Gonzalez, B, Ivanov, Y, Baringer, P, Cuevas, J, Erice, C, Fernandez Menendez, J, Folgueras, S, Brandao Malbouisson, H, Gonzalez Caballero, I, Rebassoo, F, González Fernández, JR, Antchev, G, Palencia Cortezon, E, Bartók, M, Ramón Álvarez, C, Bean, A, Rodríguez Bouza, V, Soto Rodríguez, A, Trapote, A, Trevisani, N, Martelli, A, Vico Villalba, C, Hong, B, Brochero Cifuentes, JA, Cabrillo, IJ, Bencze, G, Calderon, A, Mikulec, I, Bylinkin, A, Hadjiiska, R, Duarte Campderros, J, Monk, DG, Fernandez, M, Fernandez Madrazo, C, Fernández Manteca, PJ, García Alonso, A, Thomas, L, Gomez, G, Martinez Rivero, C, Martinez Ruiz del Arbol, P, Sánchez Hernández, A, Merlin, JA, Matorras, F, Matorras Cuevas, P, Iaydjiev, P, Piedra Gomez, J, Prieels, C, Rodrigo, T, Hajdu, C, Ruiz-Jimeno, A, Lee, KS, Scodellaro, L, Nahn, S, Chaudhary, G, Vila, I, Flowers, Z, Vizan Garcia, JM, Jayananda, MK, Kailasapathy, B, Sonnadara, DUJ, Misheva, M, Horvath, D, Wickramarathna, DDC, Dharmaratna, WGD, Monti, F, Liyanage, K, Lim, J, Perera, N, Isidori, T, Wickramage, N, Aarrestad, TK, Abbaneo, D, Alimena, J, Adams, MR, Auffray, E, Nash, J, Auzinger, G, Rodozov, M, Baechler, J, Baillon, P, Khalil, S, Barney, D, Bendavid, J, Bianco, M, Sikler, F, Pesaresi, M, Bocci, A, Camporesi, T, Capeans Garrido, M, Cerminara, G, Chernyavskaya, N, Shopova, M, Chhibra, SS, Merkel, P, Kovac, M, Park, SK, Raymond, DM, Veszpremi, V, Cipriani, M, Cristella, L, d’Enterria, D, Dabrowski, A, David, A, De Roeck, A, Defranchis, MM, Deile, M, Dobson, M, Richards, A, King, J, Czellar, S, Sultanov, G, Yoo, J, Dünser, M, Dupont, N, Elliott-Peisert, A, Emriskova, N, Fallavollita, F, Fasanella, D, Rose, A, Florent, A, Franzoni, G, Karancsi, J, Krintiras, G, Funk, W, Giani, S, Goh, J, Dimitrov, A, Gigi, D, Gill, K, Scott, E, Glege, F, Gouskos, L, Haranko, M, Molnar, J, Hegeman, J, Kropivnitskaya, A, Innocente, V, James, T, Janot, P, Gurtu, A, Ferencek, D, Kaspar, J, Ivanov, T, Kieseler, J, Komm, M, Kim, V, Kratochwil, N, Lange, C, Lazarovits, M, Laurila, S, Lecoq, P, Seez, C, Lintuluoto, A, Long, K, Kim, HS, Lourenço, C, Maier, 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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

47. 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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48. 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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50. 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, P, Le Bihan, AC, Tonon, N, Van Hove, P, Gadrat, S, Beauceron, S, Bernet, C, Boudoul, G, Chanon, N, Chierici, R, Contardo, D, Depasse, P, El Mamouni, H, Fay, J, Finco, L, Gascon, S, Gouzevitch, M, Grenier, G, Ille, B, Lagarde, F, Laktineh, IB, Lattaud, H, Lethuillier, M, Mirabito, L, Pequegnot, AL, Perries, S, Popov, A, Sordini, V, Vander Donckt, M, Viret, S, Zhang, S, Toriashvili, T, Tsamalaidze, Z, Autermann, C, Feld, L, Kiesel, MK, Klein, K, Lipinski, M, Preuten, M, Rauch, MP, Schomakers, C, Schulz, J, Teroerde, M, Wittmer, B, Zhukov, V, Albert, A, Duchardt, D, Endres, M, Erdmann, M, Erdweg, S, Esch, T, Fischer, R, Guth, A, Hebbeker, T, Heidemann, C, Hoepfner, K, Knutzen, S, Merschmeyer, M, Meyer, A, Millet, P, Mukherjee, S, Pook, T, Radziej, M, Reithler, H, Rieger, M, Scheuch, F, Teyssier, D, Thuer, S, Flugge, G, Kargoll, B, Kress, T, Kunsken, A, Muller, T, Nehrkorn, A, Nowack, A, Pistone, C, Pooth, O, Stahl, A, Martin, MA, Arndt, T, Asawatangtrakuldee, C, Beernaert, K, Behnke, O, Behrens, U, Martinez, AB, Anuar, AAB, Borras, K, Botta, V, Campbell, A, Connor, P, Contreras-Campana, C, Costanza, F, Danilov, V, De Wit, A, Pardos, CD, Damiani, DD, Eckerlin, G, Eckstein, D, Eichhorn, T, Elwood, A, Eren, E, Gallo, E, Garcia, JG, Geiser, A, Luyando, JMG, Grohsjean, A, Gunnellini, P, Guthoff, M, Harb, A, Hauk, J, Hempel, M, Jung, H, Kasemann, M, Keaveney, J, Kleinwort, C, Knolle, J, Korol, I, Krucker, D, Lange, W, Lelek, A, Lenz, T, Lipka, K, Lohmann, W, Mankel, R, Melzer-Pellmann, IA, Meyer, AB, Meyer, M, Missiroli, M, Mittag, G, Mnich, J, Mussgiller, A, Pitzl, D, Raspereza, A, Savitskyi, M, Saxena, P, Shevchenko, R, Stefaniuk, N, Tholen, H, Van Onsem, GP, Walsh, R, Wen, Y, Wichmann, K, Wissing, C, Zenaiev, O, Aggleton, R, Bein, S, Blobel, V, Vignali, MC, Dreyer, T, Garutti, E, Gonzalez, D, Haller, J, Hinzmann, A, Hoffmann, M, Karavdina, A, Kasieczka, G, Klanner, R, Kogler, R, Kovalchuk, N, Kurz, S, Kutzner, V, Lange, J, Marconi, D, Multhaup, J, Niedziela, M, Nowatschin, D, Peiffer, T, Perieanu, A, Reimers, A, Scharf, C, Schleper, P, Schmidt, A, Schumann, S, Schwandt, J, Sonneveld, J, Stadie, H, Steinbruck, G, Stober, FM, Stover, M, Troendle, D, Usai, E, Vanhoefer, A, Vormwald, B, Akbiyik, M, Barth, C, Baselga, M, Baur, S, Butz, E, Caspart, R, Chwalek, T, Colombo, F, De Boer, W, Dierlamm, A, Faltermann, N, Freund, B, Friese, R, Giffels, M, Harrendorf, MA, Hartmann, F, Heindl, SM, Husemann, U, Kassel, F, Kudella, S, Mildner, H, Mozer, MU, Plagge, M, Quast, G, Rabbertz, K, Schroder, M, Shvetsov, I, Sieber, G, Simonis, HJ, Ulrich, R, Wayand, S, Weber, M, Weiler, T, Williamson, S, Wohrmann, C, Wolf, R, Anagnostou, G, Daskalakis, G, Geralis, T, Kyriakis, A, Loukas, D, Topsis-Giotis, I, Karathanasis, G, Kesisoglou, S, Panagiotou, A, Saoulidou, N, Tziaferi, E, Kousouris, K, Papakrivopoulos, I, Evangelou, I, Foudas, C, Gianneios, P, Katsoulis, P, Kokkas, P, Mallios, S, Manthos, N, Papadopoulos, I, Paradas, E, Strologas, J, Triantis, FA, Tsitsonis, 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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

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