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Overweight and obesity among Israeli adolescents and the risk for serious morbidity in early young adulthood: a nationwide retrospective cohort study 以色列青少年的超重和肥胖与青年早期严重发病的风险:一项全国范围的回顾性队列研究
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-15 DOI: 10.1016/s2213-8587(24)00287-0
Yair Zloof, Maya Nitecki, Maya Simchoni, Ofek Adar, Avishai M Tsur, Estela Derazne, Dorit Tzur, Jacob Rotschield, Maya Braun, Orit Pinhas-Hamiel, Naomi Fliss Isakov, Hadar Milloh-Raz, Dan Nemet, Dror Dicker, Avi Moyal, Oded Scheuerman, Zivan Beer, Marius Braun, Arnon Afek, Hertzel C Gerstein, Gilad Twig

Background

Morbidities related to obesity are usually associated with its severity and duration. Yet, the onset of serious morbidities in early adulthood among otherwise healthy adolescents with obesity is understudied. We aimed to investigate the association between adolescent BMI and serious morbidities before age 25 years.

Methods

In this nationwide, retrospective cohort study, we included Israeli conscripts aged 17–21 years who underwent pre-recruitment medical evaluation between Jan 1, 1996, and Dec 31, 2017, were deemed medically eligible for military service, and were recruited to the Israeli Defense Forces between 1998 and 2018. Exclusion criteria were missing height or weight or service ineligibility for non-medical or medical reasons. Baseline BMI was converted into age-specific and sex-specific percentiles and classified using the US Centers for Disease Control and Prevention categories. The primary outcome was incidence of serious morbidity disqualifying individuals from completing mandatory service. Participants were followed from enlistment until end of service (3 years for males and 2 years for females), onset of serious morbidity, or Dec 31, 2021. Cox models with adjustment to various socio-economic confounders were applied to calculate the hazard ratio (HR) and 95% CI for serious morbidity for the BMI categories.

Findings

A total of 1 264 355 adolescents aged 16–20 years were assessed for military service. 145 702 were excluded; 144 705 were considered ineligible for service (133 112 for non-medical reasons and 11 593 for medical reasons), and 2867 had missing height or weight data. The study included 1 118 653 individuals (622 989 [55·7%] males and 495 664 [44·3%] females), with 23 347 cases of serious morbidity recorded over 2 534 873 person-years. Incidence of serious morbidity increased across BMI groups in both sexes. Among males, compared with those with normal BMI, the adjusted HRs were 0·89 (95% CI 0·83–0·95) for underweight, 1·21 (1·16–1·27) for overweight, 1·39 (1·32–1·47) for obesity class 1, 2·82 (2·60–3·06) for obesity class 2, and 5·14 (4·37–6·04) for obesity class 3. For females, the respective ratios were HR 0·95 (95% CI 0·84–1·09) for underweight, 1·27 (1·17–1·37) for overweight, 1·63 (1·45–1·82) for obesity class 1, 4·00 (3·46–4·61) for obesity class 2, and 7·30 (5·65–9·43) for obesity class 3. Results persisted in sensitivity analyses restricted to those with unimpaired health at baseline or those in civilian-equivalent office employments.

Interpretation

Obesity in otherwise healthy adolescents was linked with increased risk of serious morbidity before age 25 years. Reducing adolescent obesity will have substantial short-term and long-term health benefits in young adults.

Funding

Sheba Medical Center.
背景与肥胖有关的疾病通常与肥胖的严重程度和持续时间有关。然而,对于原本健康的肥胖青少年在成年早期出现严重疾病的情况,我们的研究还不够深入。我们的目的是调查青少年体重指数与 25 岁前严重发病之间的关联。方法在这项全国性的回顾性队列研究中,我们纳入了 1996 年 1 月 1 日至 2017 年 12 月 31 日期间接受征兵前医学评估、被认为在医学上符合服兵役条件并在 1998 年至 2018 年期间应征加入以色列国防军的 17-21 岁以色列应征者。排除标准为身高或体重缺失,或因非医疗或医学原因不符合服役条件。基线体重指数被转换成特定年龄和特定性别的百分位数,并按照美国疾病控制和预防中心的分类进行分类。主要结果是导致个人丧失完成义务兵役资格的严重发病率。从入伍到服役结束(男性 3 年,女性 2 年)、严重发病或 2021 年 12 月 31 日,对参与者进行了跟踪调查。采用调整了各种社会经济混杂因素的 Cox 模型来计算 BMI 类别严重发病率的危险比 (HR) 和 95% CI。145 702 人被排除在外;144 705 人被认为不符合服兵役条件(133 112 人因非医疗原因,11 593 人因医疗原因),2867 人的身高或体重数据缺失。该研究共纳入了 1 118 653 人(其中男性 622 989 人 [55-7%] ,女性 495 664 人 [44-3%] ),在 2 534 873 人年中记录了 23 347 例严重发病病例。在不同体重指数组别中,男女严重发病率均有所上升。在男性中,与体重指数正常者相比,体重不足的调整后HR值为0-89(95% CI 0-83-0-95),超重为1-21(1-16-1-27),肥胖1级为1-39(1-32-1-47),肥胖2级为2-82(2-60-3-06),肥胖3级为5-14(4-37-6-04)。就女性而言,体重不足的比率为 0-95(95% CI 0-84-1-09),超重的比率为 1-27(1-17-1-37),肥胖等级 1 的比率为 1-63(1-45-1-82),肥胖等级 2 的比率为 4-00(3-46-4-61),肥胖等级 3 的比率为 7-30(5-65-9-43)。在仅限于基线健康状况未受损或在文职等同办公室工作的青少年的敏感性分析中,结果依然存在。减少青少年肥胖将为年轻成年人带来巨大的短期和长期健康益处。
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引用次数: 0
Associations of obesity with co-morbidities in early adult life 肥胖与成年早期并发症的关系
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-15 DOI: 10.1016/s2213-8587(24)00342-5
Thorkild I A Sørensen
No Abstract
无摘要
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引用次数: 0
Putting wellbeing at the core of diabetes care 将健康作为糖尿病护理的核心
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-14 DOI: 10.1016/s2213-8587(24)00345-0
No Abstract
无摘要
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引用次数: 0
Setmelanotide in patients aged 2–5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial 塞美拉诺肽治疗 2-5 岁罕见 MC4R 通路相关肥胖症患者(VENTURE):为期 1 年的开放标签多中心 3 期试验
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-13 DOI: 10.1016/s2213-8587(24)00273-0
Jesús Argente, Charles F Verge, Uzoma Okorie, Ilene Fennoy, Megan M Kelsey, Casey Cokkinias, Cecilia Scimia, Hak-Myung Lee, I Sadaf Farooqi
<h3>Background</h3>Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, has been shown to reduce hunger and weight in patients aged 6 years and older with proopiomelanocortin (POMC) deficiency (including biallelic variants in proprotein convertase subtilisin/kexin type 1 [<em>PCSK1</em>]), leptin receptor (LEPR) deficiency, or Bardet-Biedl syndrome (BBS). No approved therapies for patients younger than 6 years old currently exist. The phase 3, open-label VENTURE trial aimed to evaluate the efficacy and safety of setmelanotide in patients aged 2–5 years with POMC or LEPR deficiency or BBS.<h3>Methods</h3>This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2–5 years who had hyperphagia and obesity due to biallelic <em>POMC</em> (including <em>PCSK1</em>) or <em>LEPR</em> variants or genetically confirmed BBS. Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight. The co-primary endpoints at week 52 were the percentage of patients reaching a 0·2-point decrease or greater in BMI Z score (a statistical measure used to assess BMI in paediatric patients considering a patient's BMI and comparing it to reference values for the same age and sex) and mean percent change in BMI. Additional endpoints measured safety, hunger, weight-related outcomes, and caregiver burden. The study is registered at <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (<span><span>NCT04966741</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>) and is complete.<h3>Findings</h3>Between March 8, 2022, and Sept 18, 2023, 13 patients were screened at the six sites, and 12 patients were enrolled in the study (seven with POMC or LEPR and five with BBS); one patient with BBS was excluded as their BMI was not at the 97th percentile or above. Of the 12 patients enrolled, most were male (seven [58%] <em>vs</em> five [42%] for female) and the mean age was 3·6 years (SD 0·9). 11 patients completed the trial. Ten (83%) of the 12 overall participants reached a 0·2-point reduction or more in BMI Z score per WHO methodology at week 52 (95% CI 58·7–99·8). The mean percent change in BMI from baseline at week 52 was −18% (SD 13) in the overall safety population. Mean percent change in BMI at week 52 was −26% (SD 11) in patients with POMC or LEPR deficiency and −10% (9) in patients with BBS. Mean reductions in secondary endpoints of BMI Z score (3·4 [2·5]) and percent of the BMI 95th percentile (32·5 [22·9]) we
背景塞美拉诺肽是一种黑色素皮质素-4受体(MC4R)激动剂,已被证明可减轻6岁及以上原绒毛膜促皮质素(POMC)缺乏症(包括1型丙蛋白转化酶亚基酶/kexin [PCSK1]的双倍变体)、瘦素受体(LEPR)缺乏症或巴尔德-比德综合征(BBS)患者的饥饿感和体重。目前还没有针对 6 岁以下患者的获批疗法。这项 3 期开放标签 VENTURE 试验旨在评估 Setmelanotide 对 2-5 岁 POMC 或 LEPR 缺乏症或 BBS 患者的疗效和安全性。方法这项 3 期开放标签多中心试验在美国、英国、西班牙和澳大利亚的六个地点进行,招募了符合条件的 2-5 岁患者,这些患者因双唇 POMC(包括 PCSK1)或 LEPR 变异或基因证实的 BBS 而导致吞咽功能亢进和肥胖。开放标签皮下注射塞美拉诺肽,每天一次,持续52周,起始剂量为0-5毫克,每2周剂量增加0-5毫克,直至达到基于体重的最大剂量。第52周的共同主要终点是BMI Z评分(一种用于评估儿科患者BMI的统计方法,考虑患者的BMI并将其与同年龄和性别的参考值进行比较)下降0-2分或更多的患者比例以及BMI平均变化百分比。其他终点指标包括安全性、饥饿感、体重相关结果和护理负担。研究结果2022年3月8日至2023年9月18日期间,6个研究机构共筛查了13名患者,12名患者被纳入研究(7名患有POMC或LEPR,5名患有BBS);1名患有BBS的患者因其BMI未达到或超过97百分位数而被排除在外。在这12名患者中,大多数为男性(7名[58%],5名[42%]为女性),平均年龄为3-6岁(SD 0-9)。11 名患者完成了试验。根据世界卫生组织的方法,在第 52 周时,12 名参与者中有 10 人(83%)的体重指数 Z 值下降了 0-2 点或更多(95% CI 58-7-99-8)。总体安全人群在第 52 周时的 BMI 与基线相比的平均百分比变化为-18%(标度 13)。第52周时,POMC或LEPR缺乏症患者的BMI平均变化百分比为-26%(标准差11),BBS患者的BMI平均变化百分比为-10%(标准差9)。第52周时,次要终点BMI Z评分(3-4 [2-5])和BMI第95百分位数百分比(32-5 [22-9])的平均值均有所下降。91%的护理人员表示患者的饥饿感低于基线值。所有不良反应均为轻度或中度;皮肤色素沉着、呕吐、鼻咽炎、上呼吸道感染和注射部位反应最为常见。据我们所知,这是首次在 6 岁以下患者中进行赛美拉诺肽试验。据我们所知,这是首次在 6 岁以下患者中开展的试验,这些结果表明,该药物可作为早期干预措施用于控制这类人群的肥胖症。
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引用次数: 0
Setmelanotide for the treatment of severe early-childhood genetic obesity 塞美拉诺肽治疗严重的儿童早期遗传性肥胖症
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-13 DOI: 10.1016/s2213-8587(24)00312-7
Christian L Roth
No Abstract
无摘要
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引用次数: 0
Hypothalamic obesity: from basic mechanisms to clinical perspectives 下丘脑肥胖症:从基本机制到临床视角
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-12 DOI: 10.1016/s2213-8587(24)00283-3
Jesús Argente, I Sadaf Farooqi, Julie A Chowen, Peter Kühnen, Miguel López, Eugenia Morselli, Hoong-Wei Gan, Helen A Spoudeas, Martin Wabitsch, Manuel Tena-Sempere
Despite the diverse nature of obesity, there is compelling genetic, clinical, and experimental evidence that endorses the important contribution of brain circuits to this condition. The hypothalamus contains major regulatory circuits for bodyweight homoeostasis, the deregulation of which can lead to obesity. Although functional perturbation of hypothalamic pathways could lie at the basis of common forms of obesity, the term hypothalamic obesity has been created to define those rare forms of severe obesity where a clear hypothalamic substrate can be identified, either of genetic or acquired origin. An in-depth understanding of the pathogenesis, clinical presentation, and therapeutic targets of hypothalamic obesity relies on the comprehension of the physiological basis of hypothalamic pathways governing bodyweight control, the mechanisms (either genetic or acquired) whereby they are perturbed, and the consequences of such perturbation. In this Review, we provide a synoptic overview of hypothalamic obesity, from basic mechanisms to clinical perspectives, with a major focus on current developments and new avenues for the diagnosis and precise treatment of these rare forms of obesity.
尽管肥胖症的性质多种多样,但有令人信服的遗传、临床和实验证据表明,大脑回路对肥胖症有重要影响。下丘脑包含体重平衡的主要调节回路,其失调可导致肥胖。虽然下丘脑通路的功能性扰动可能是常见肥胖症的基础,但下丘脑肥胖症这一术语的出现是为了定义那些罕见的严重肥胖症,在这些肥胖症中,下丘脑的基质可以被明确地识别出来,这些基质可以是遗传的,也可以是后天获得的。要深入了解下丘脑肥胖症的发病机理、临床表现和治疗目标,就必须理解下丘脑控制体重的途径的生理基础、这些途径受到干扰的机制(遗传或后天)以及这种干扰的后果。在本综述中,我们将从基础机制到临床角度对下丘脑肥胖症进行综述,重点关注当前的发展以及诊断和精确治疗这些罕见肥胖症的新途径。
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引用次数: 0
Trends in the incidence of young-adult-onset diabetes by diabetes type: a multi-national population-based study from an international diabetes consortium 按糖尿病类型划分的年轻成人糖尿病发病率趋势:国际糖尿病联盟开展的一项基于人口的多国研究
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-11 DOI: 10.1016/s2213-8587(24)00243-2
Dianna J Magliano, Lei Chen, Jedidiah I Morton, Agus Salim, Bendix Carstensen, Edward W Gregg, Meda E Pavkov, Martti Arffman, Helen M Colhoun, Kyoung Hwa Ha, Tomoaki Imamura, György Jermendy, Dae Jung Kim, Zoltán Kiss, Didac Mauricio, Stuart J McGurnaghan, Yuichi Nishioka, Sarah H Wild, Klas Winell, Jonathan E Shaw

Background

Population-based incidence data on young-adult-onset type 1 diabetes and type 2 diabetes are limited. We aimed to examine secular trends in the incidence of diagnosed type 1 diabetes and type 2 diabetes with an age of onset between 15 and 39 years.

Methods

In this multicountry aggregate data analysis, we assembled eight administrative datasets from high-income jurisdictions and countries (Australia, Denmark, Finland, Hungary, Japan, Scotland, South Korea, and Spain [Catalonia]) that had appropriate data available from an international diabetes consortium (GLOBODIAB) describing incidence by diabetes type among people aged 15–39 years from 2000 to 2020. We modelled type 1 diabetes and type 2 diabetes incidence rates using Poisson regression including age and calendar time by sex.

Findings

During the years 2000–20, there were 349 591 incident diabetes (both types) cases from 346 million person-years of follow-up among people aged 15–39 years. Over time, there was no statistically significant change in the incidence of type 1 diabetes in Hungary and Japan. The incidence of type 1 diabetes significantly increased in Australia, Denmark, Finland, Scotland, South Korea, and Spain, with annual changes ranging from 0·5% to 6·0%. The incidence of type 2 diabetes significantly increased in four of eight jurisdictions (Denmark, Finland, Japan, and South Korea), with annual increases from 2·0% to 8·5%. The magnitude of increase in incidence of type 2 diabetes was greater in Asian than non-Asian jurisdictions. There was no statistically significant change in type 2 diabetes incidence in Australia and Hungary. The incidence of type 2 diabetes significantly decreased in Scotland and Spain, with annual changes of –0·7% and –1·5%, respectively.

Interpretation

There is variability in the trajectory of the incidence of young-adult-onset type 2 diabetes among high-income countries or jurisdictions, with a greater evidence of increase in Asian than non-Asian countries. Evolving trends in the incidence of type 1 and type 2 diabetes in young adults call for the ongoing surveillance of diabetes incidence and a greater research focus on this population.

Funding

US Centers for Disease Control and Prevention, Diabetes Australia Research Programme, and Victoria State Government Operational Infrastructure Support Programme.
背景基于人群的 1 型糖尿病和 2 型糖尿病发病率数据非常有限。在这项多国综合数据分析中,我们收集了来自高收入地区和国家(澳大利亚、丹麦、芬兰、匈牙利、日本、苏格兰、韩国和西班牙[加泰罗尼亚])的八个行政数据集,这些数据集拥有国际糖尿病联盟(GLOBODIAB)提供的适当数据,描述了 2000 年至 2020 年期间 15-39 岁人群中各糖尿病类型的发病率。我们使用泊松回归法(包括按性别划分的年龄和日历时间)对 1 型糖尿病和 2 型糖尿病发病率进行了建模。研究结果2000-20 年间,在对 3.46 亿人年的跟踪调查中,15-39 岁人群中共有 349 591 例糖尿病(两种类型)病例。随着时间的推移,匈牙利和日本的 1 型糖尿病发病率没有明显的统计学变化。澳大利亚、丹麦、芬兰、苏格兰、韩国和西班牙的 1 型糖尿病发病率明显上升,年变化率从 0-5% 到 6-0% 不等。在八个辖区中,有四个辖区(丹麦、芬兰、日本和韩国)的 2 型糖尿病发病率明显增加,年增幅从 2-0% 到 8-5%不等。亚洲辖区 2 型糖尿病发病率的增长幅度大于非亚洲辖区。澳大利亚和匈牙利的 2 型糖尿病发病率在统计上没有明显变化。苏格兰和西班牙的2型糖尿病发病率明显下降,年变化率分别为-0-7%和-1-5%。解释:在高收入国家或辖区中,青年-成人2型糖尿病发病率的变化轨迹各不相同,亚洲国家的发病率上升幅度大于非亚洲国家。青壮年1型和2型糖尿病发病率的变化趋势要求对糖尿病发病率进行持续监测,并加强对这一人群的研究。
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引用次数: 0
Global diabetes incidence trends in young adults 全球青壮年糖尿病发病趋势
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-11 DOI: 10.1016/s2213-8587(24)00286-9
Lars C Stene
No Abstract
无摘要
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引用次数: 0
Disease modifying therapies in diabetes and endocrinology 糖尿病和内分泌学中的疾病调整疗法
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-08 DOI: 10.1016/s2213-8587(24)00336-x
Chantal Mathieu
No Abstract
无摘要
{"title":"Disease modifying therapies in diabetes and endocrinology","authors":"Chantal Mathieu","doi":"10.1016/s2213-8587(24)00336-x","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00336-x","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"6 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Staging schema for early diagnosis of prediabetes 糖尿病前期早期诊断分期图
IF 44.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-07 DOI: 10.1016/s2213-8587(24)00320-6
Michael Bergman, Muhammad Abdul-Ghani, Juliana Chan, Maria Inês Schmidt, Joon Ha, Sang Soo Kim, Arthur S Sherman, Ram Jagannathan, Jaakko Tuomilehto
No Abstract
无摘要
{"title":"Staging schema for early diagnosis of prediabetes","authors":"Michael Bergman, Muhammad Abdul-Ghani, Juliana Chan, Maria Inês Schmidt, Joon Ha, Sang Soo Kim, Arthur S Sherman, Ram Jagannathan, Jaakko Tuomilehto","doi":"10.1016/s2213-8587(24)00320-6","DOIUrl":"https://doi.org/10.1016/s2213-8587(24)00320-6","url":null,"abstract":"No Abstract","PeriodicalId":48790,"journal":{"name":"The Lancet Diabetes & Endocrinology","volume":"12 1","pages":""},"PeriodicalIF":44.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
The Lancet Diabetes & Endocrinology
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