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Cherry on Top or Real Need? A Review of Explainable Machine Learning in Kidney Transplantation. 是 "顶上的樱桃 "还是 "真正的需要"?肾移植中的可解释机器学习回顾。
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-05-21 DOI: 10.1097/TP.0000000000005063
Alvaro Assis de Souza, Andrew P Stubbs, Dennis A Hesselink, Carla C Baan, Karin Boer

Research on solid organ transplantation has taken advantage of the substantial acquisition of medical data and the use of artificial intelligence (AI) and machine learning (ML) to answer diagnostic, prognostic, and therapeutic questions for many years. Nevertheless, despite the question of whether AI models add value to traditional modeling approaches, such as regression models, their "black box" nature is one of the factors that have hindered the translation from research to clinical practice. Several techniques that make such models understandable to humans were developed with the promise of increasing transparency in the support of medical decision-making. These techniques should help AI to close the gap between theory and practice by yielding trust in the model by doctors and patients, allowing model auditing, and facilitating compliance with emergent AI regulations. But is this also happening in the field of kidney transplantation? This review reports the use and explanation of "black box" models to diagnose and predict kidney allograft rejection, delayed graft function, graft failure, and other related outcomes after kidney transplantation. In particular, we emphasize the discussion on the need (or not) to explain ML models for biological discovery and clinical implementation in kidney transplantation. We also discuss promising future research paths for these computational tools.

多年来,有关实体器官移植的研究一直在利用大量医疗数据的获取以及人工智能(AI)和机器学习(ML)的使用来回答诊断、预后和治疗问题。然而,尽管存在人工智能模型是否能为回归模型等传统建模方法带来价值的问题,但其 "黑箱 "性质是阻碍其从研究转化为临床实践的因素之一。为了提高医疗决策支持的透明度,我们开发了几种能让人类理解这些模型的技术。这些技术应有助于人工智能缩小理论与实践之间的差距,让医生和患者对模型产生信任,允许对模型进行审计,并促进遵守新兴的人工智能法规。但肾移植领域是否也存在这种情况呢?本综述报告了 "黑盒 "模型在诊断和预测肾移植后异体移植排斥反应、移植功能延迟、移植失败和其他相关结果方面的使用和解释。我们特别强调了在肾移植的生物学发现和临床实施中解释 ML 模型的必要性(或不必要性)的讨论。我们还讨论了这些计算工具未来大有可为的研究路径。
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引用次数: 0
Tacrolimus-loaded Drug Delivery Systems in Vascularized Composite Allotransplantation: Lessons and Opportunities for Local Immunosuppression. 血管化复合异体移植中的他克莫司给药系统:局部免疫抑制的教训与机遇。
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-05-21 DOI: 10.1097/TP.0000000000005049
Bilal Ben Brahim, Isabel Arenas Hoyos, Lei Zhang, Esther Vögelin, Radu Olariu, Robert Rieben

Long-term systemic immunosuppression is needed for vascularized composite allotransplantation (VCA). The high rate of acute rejection episodes in the first posttransplant year, the development of chronic rejection, and the adverse effects that come along with this treatment, currently prevent a wider clinical application of VCA. Opportunistic infections and metabolic disturbances are among the most observed side effects in VCA recipients. To overcome these challenges, local immunosuppression using biomaterial-based drug delivery systems (DDS) have been developed. The aim of these systems is to provide high local concentrations of immunosuppressive drugs while reducing their systemic load. This review provides a summary of recently investigated local DDS with different mechanisms of action such as on-demand, ultrasound-sensitive, or continuous drug delivery. In preclinical models, ranging from rodent to porcine and nonhuman primate models, this approach has been shown to reduce systemic tacrolimus (TAC) load and adverse effects, while prolonging graft survival. Localized immunosuppression using biomaterial-based DDS represents an encouraging approach to enhance graft survival and reduce toxic side effects of immunosuppressive drugs in VCA patients. Preclinical models using TAC-releasing DDS have demonstrated high local immunosuppressive effects with a low systemic burden. However, to reduce acute rejection events in translational animal models or in the clinical reality, the use of additional low-dose systemic TAC treatment may be envisaged. Patients may benefit through efficient graft immunosuppression and survival with negligible systemic adverse effects, resulting in better compliance and quality of life.

血管化复合体同种异体移植(VCA)需要长期的全身免疫抑制。移植后第一年内急性排斥反应的高发率、慢性排斥反应的发展以及伴随这种治疗而来的不良反应,目前阻碍了 VCA 在临床上的广泛应用。机会性感染和代谢紊乱是在 VCA 受体中观察到最多的副作用。为了克服这些挑战,人们开发出了使用生物材料给药系统(DDS)进行局部免疫抑制的方法。这些系统的目的是提供高浓度的局部免疫抑制药物,同时减少其全身负荷。本综述概述了最近研究的具有不同作用机制的局部 DDS,如按需给药、超声敏感给药或连续给药。在从啮齿动物到猪和非人灵长类动物的临床前模型中,这种方法已被证明可以减少全身他克莫司(TAC)的负荷和不良反应,同时延长移植物的存活时间。使用基于生物材料的 DDS 进行局部免疫抑制是提高 VCA 患者移植物存活率和减少免疫抑制药物毒副作用的一种令人鼓舞的方法。使用 TAC 释放型 DDS 的临床前模型已经证明,局部免疫抑制效果高,而全身负担低。然而,为了减少转化动物模型或临床实践中的急性排斥反应,可以考虑使用额外的低剂量全身 TAC 治疗。患者可通过有效的移植物免疫抑制和存活而获益,同时全身不良反应可忽略不计,从而提高依从性和生活质量。
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引用次数: 0
Liver Retransplantation Using Living Donor Grafts: A Feasible Approach for Chronic Allograft Failure. 使用活体供体移植物进行肝脏再移植:治疗慢性异体移植失败的可行方法
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-08-06 DOI: 10.1097/TP.0000000000005164
Kosuke Tanaka, Takashi Ito, Yoichiro Uchida, Yuki Masano, Shinya Okumura, Masaaki Hirata, Shoichi Kageyama, Takayuki Anazawa, Yukinori Koyama, Satoshi Ogiso, Takamichi Ishii, Kazuyuki Nagai, Etsuro Hatano

Background: The indication of living donor liver retransplantation (re-LDLT) for retransplant candidates with chronic allograft failure (CAF) is increasing because of the high mortality rate of patients on the waiting list. However, evidence supporting re-LDLT for CAF remains scarce because of technical difficulties. We aimed to examine the feasibility based on our significant case experience.

Methods: A total of 95 retransplant cases (adult: 53, pediatric: 42) between 2000 and 2020 were retrospectively reviewed. Graft survival after re-LDLT and deceased donor liver retransplantation (re-DDLT) was compared among recipients with CAF and acute allograft failure (AAF).

Results: Re-LDLTs for CAF were performed in 58 (61.1%) cases, re-DDLTs for CAF in 16 (16.8%) cases, re-LDLTs for AAF in 13 (13.7%) cases, and re-DDLTs for AAF in 8 (8.4%) cases. Re-DDLTs have become increasingly prevalent over time. Retransplantation for AAF results in lower graft survival than that for CAF in both adult and pediatric cases. All adult recipients who underwent re-LDLT for AAF died within 1 y after retransplantation. The 5-y graft survival between re-LDLT and re-DDLT for CAF was not significantly different (73.8% versus 75.0%, P  = 0.84). Operation time and blood loss were not significantly different.

Conclusions: The survival rate of re-LDLT for recipients with CAF is permissible. Re-LDLT may be another treatment option for recipients with CAF.

背景:由于等待名单上患者的死亡率较高,对慢性异体移植失败(CAF)的再移植候选者进行活体肝脏再移植(re-LDLT)的适应症正在增加。然而,由于技术上的困难,支持再LDLT治疗CAF的证据仍然很少。我们的目的是根据我们的重要病例经验研究其可行性:我们对 2000 年至 2020 年间的 95 例再移植病例(成人 53 例,儿童 42 例)进行了回顾性研究。比较了CAF和急性同种异体移植失败(AAF)受者再LDLT和死亡供体肝脏再移植(re-DDLT)后的移植物存活率:结果:58例(61.1%)因CAF进行了再LDLT,16例(16.8%)因CAF进行了再DDLT,13例(13.7%)因AAF进行了再LDLT,8例(8.4%)因AAF进行了再DDLT。随着时间的推移,DDLT 再移植越来越普遍。在成人和儿童病例中,AAF再移植的移植物存活率均低于CAF。所有因 AAF 而接受再 LDLT 的成人受者均在再移植后 1 年内死亡。CAF的再LDLT和再DDLT的5年移植物存活率没有显著差异(73.8%对75.0%,P = 0.84)。手术时间和失血量无明显差异:结论:CAF受者再LDLT的存活率是允许的。结论:CAF受者的再LDLT存活率是允许的,再LDLT可能是CAF受者的另一种治疗选择。
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引用次数: 0
Research Highlights. 研究亮点。
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-12-07 DOI: 10.1097/TP.0000000000005285
Atharva Kale, Natasha M Rogers
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引用次数: 0
Transplantation: A Priority in the Healthcare Agenda. 移植:医疗议程中的优先事项。
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-22 DOI: 10.1097/TP.0000000000005182
Elmi Muller, Beatriz Dominguez-Gil, Curie Ahn, Marina Berenguer, Massimo Cardillo, Efstratios Chatzixiros, Paolo Cortesi, Marisa Herson, Andre Ilbawi, Vivekanand Jha, Beatriz Mahillo, Derek M Manas, Alejandro Nino-Murcia, Faissal A M Shaheen, Peter Stock, Luciano Potena

Background: In November 2023, in the context of the Spanish Presidency of the Council of the European Union, the Organization National de Transplante organized a global summit discussing global action in transplantation for the next decade. This article reports the recommendations supporting the need to prioritize transplantation in healthcare systems.

Methods: The working group investigated how transplantation addresses noncommunicable disease mortality, particularly related to kidney and liver disease. They also investigated how transplantation can contribute to the achievement of several of the United Nations Sustainable Development Goals, especially Goal 3 (good health and well-being), Goal 8 (sustained, inclusive, and sustainable economic growth and employment for all), and Goal 13 (combat climate change and its impact).

Results: By prioritizing transplantation, the increased availability and accessibility of life-saving organs and tissues to the public will not only lead to saving more lives and improving health outcomes for individual patients but also contribute to the development of a resilient health system in general in that country as a consequence of developing the infrastructure required for transplantation.

Conclusions: The ethical principles associated with transplantation promote the principles of solidarity in society by fostering the donation process and equity in access to therapy. This article aims to advocate for the widespread availability of solid organ, tissue, and cell transplantation for all patients.

背景:2023 年 11 月,在西班牙担任欧盟理事会主席国期间,西班牙国家移植组织(Organization National de Transplante)组织了一次全球峰会,讨论未来十年全球移植行动。本文报告了支持医疗系统优先考虑移植的建议:工作组调查了移植如何降低非传染性疾病死亡率,尤其是与肾脏和肝脏疾病相关的死亡率。他们还调查了移植如何促进联合国可持续发展目标的实现,特别是目标 3(良好的健康和福祉)、目标 8(人人享有持续、包容和可持续的经济增长和就业)和目标 13(应对气候变化及其影响):通过将移植作为优先事项,向公众提供更多挽救生命的器官和组织,不仅可以挽救更多的生命,改善患者的健康状况,而且由于发展了移植所需的基础设施,还有助于在该国建立一个具有复原力的总体卫生系统:与移植相关的伦理原则通过促进捐献过程和公平获得治疗来促进社会团结的原则。本文旨在倡导为所有患者广泛开展实体器官、组织和细胞移植。
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引用次数: 0
Developing and Expanding Deceased Organ Donation to Its Maximum Therapeutic Potential: An Actionable Global Challenge From the 2023 Santander Summit. 发展和扩大死者器官捐献,使其发挥最大治疗潜力:2023 年桑坦德峰会提出的一个可行的全球挑战。
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-22 DOI: 10.1097/TP.0000000000005234
Dale Gardiner, Andrew McGee, Ali Abdul Kareem Al Obaidli, Matthew Cooper, Krista L Lentine, Eduardo Miñambres, Sanjay Nagral, Helen Opdam, Francesco Procaccio, Sam D Shemie, Michael Spiro, Martín Torres, David Thomson, Amy D Waterman, Beatriz Domínguez-Gil, Francis L Delmonico

On November 9 and 10, 2023, the Organización Nacional de Trasplantes (ONT), under the Spanish Presidency of the Council of the European Union, convened in Santander a Global Summit entitled "Towards Global Convergence in Transplantation: Sufficiency, Transparency and Oversight." This article summarizes two distinct but related challenges elaborated at the Santander Summit by Working Group 2 that must be overcome if we are to develop and expand deceased donation worldwide and achieve the goal of self-sufficiency in organ donation and transplantation. Challenge 1: the need for a unified concept of death based on the permanent cessation of brain function. Working group 2 proposed that challenge 1 requires the global community to work toward a uniform, worldwide definition of human death, conceptually unifying circulatory and neurological criteria of death around the cessation of brain function and accepting that permanent cessation of brain function is a valid criterion to determine death. Challenge 2: reducing disparities in deceased donation and increasing organ utilization through donation after the circulatory determination of death (DCDD). Working group 2 proposed that challenge 2 requires the global community to work toward increasing organ utilization through DCDD, expanding DCDD through in situ normothermic regional perfusion, and expanding DCDD through ex situ machine organ perfusion technology. Recommendations for implementation are described.

2023 年 11 月 9 日和 10 日,西班牙担任欧盟理事会主席国期间,国家移植组织(ONT)在桑坦德召开了题为 "实现全球移植趋同 "的全球峰会:充分性、透明度和监督 "的全球峰会。本文总结了第二工作组在桑坦德峰会上阐述的两个不同但相关的挑战,如果我们要在全球范围内发展和扩大死者捐献,实现器官捐献和移植自给自足的目标,就必须克服这两个挑战。挑战 1:需要一个基于大脑功能永久停止的统一死亡概念。第 2 工作组提出,挑战 1 要求全球社会努力对人类死亡进行全球统一定义,在概念上围绕脑功能停止统一循环和神经死亡标准,并接受脑功能永久停止是确定死亡的有效标准。挑战 2:通过循环系统确定死亡后的捐献,减少死者捐献方面的差异,提高器官利用率。第 2 工作组提出,挑战 2 要求全球社会努力通过 DCDD 提高器官利用率,通过原位常温区域灌注扩大 DCDD,以及通过体外机器器官灌注技术扩大 DCDD。本文介绍了实施建议。
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引用次数: 0
Toward Equity in Global Access to SoHO-based Therapies: Recommendations for Action. 促进全球公平获得基于 SoHO 的疗法:行动建议》。
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-22 DOI: 10.1097/TP.0000000000005106
Dominique E Martin, Kristof Van Assche, Lilia Cervantes, John L R Forsythe, Thomas Muller, Alicia Perez-Blanco, Esteve Trias, Milka Bengochea, Alexander M Capron, Riadh A S Fadhil, Anna Forsberg, Noble Gracious, Marisa R Herson, Rumeyza Kazancioğlu, Luc Noel, Benita Padilla, Marta Lopez-Fraga

Therapies derived from substances of human origin (SoHOs) such as organs, cells, and tissues provide life-saving or life-changing treatment for millions of people worldwide each year. However, many people lack timely access to SoHO-based therapies because of insufficient supplies of these exceptional health resources and/or broader barriers in access to healthcare. Despite well-established governmental commitments to promote health equity in general and equity of access to SoHOs in particular, information about inequities in access to most SoHO-based therapies is scarce. Furthermore, the issue of equitable allocation of SoHO-based therapies has received little attention from policymakers and ethicists, except in the context of organ allocation for transplantation. Consequently, the extent and nature of potential inequities within and between countries are largely unknown, and few sources of guidance are available to support progress toward equity in global access to SoHO-based therapies. We present here the findings of an international ethics working group convened in preparation for the 2023 Global Summit on Convergence in Transplantation, organized in Santander, Spain. The group sought to assess potential gaps in knowledge about inequities involving SoHO-based therapies, to elucidate systemic factors that may influence access to these therapies, and to consider how policies and frameworks governing access to and allocation of SoHO-based therapies may promote equity when it is necessary to define boundaries in access because of insufficiency of supply. In discussing these challenges, we also outline several recommendations for action by governments and health authorities.

源自人体器官、细胞和组织等人体来源物质(SOHOs)的疗法每年为全球数百万人提供挽救生命或改变生命的治疗。然而,由于这些特殊健康资源供应不足和/或在获得医疗保健方面存在更广泛的障碍,许多人无法及时获得基于 SoHO 的疗法。尽管政府已承诺促进健康公平,特别是促进 SoHOs 的公平使用,但有关大多数 SoHO 治疗不公平的信息却很少。此外,除了在器官移植分配的背景下,SOHO疗法的公平分配问题很少受到政策制定者和伦理学家的关注。因此,国家内部和国家之间可能存在的不公平现象的程度和性质在很大程度上是未知的,而且几乎没有任何指导来源可用于支持全球公平获得基于 SoHO 的疗法。为筹备在西班牙桑坦德举行的 2023 年全球移植融合峰会,我们在此介绍一个国际伦理工作组的研究成果。该工作组旨在评估有关SOHO疗法不公平现象的潜在知识差距,阐明可能影响获得这些疗法的系统性因素,并考虑在因供应不足而有必要确定获得SOHO疗法的界限时,有关获得和分配SOHO疗法的政策和框架如何才能促进公平。在讨论这些挑战时,我们还概述了供政府和卫生当局采取行动的若干建议。
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引用次数: 0
Research Highlights. 研究突出了。
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-12-07 DOI: 10.1097/TP.0000000000005285
Atharva Kale, Natasha M Rogers
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引用次数: 0
Waitlist Time, Age, and Social Vulnerability: Impact on the Survival Benefit of Deceased Donor Kidney Transplantation Versus Long-term Dialysis Among Patients With End-stage Renal Disease. 候诊时间、年龄和社会脆弱性:对终末期肾病患者死体肾移植与长期透析的生存获益的影响。
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-12-07 DOI: 10.1097/TP.0000000000005149
Keith McCullough
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引用次数: 0
Age Is Just a Number for Older Kidney Transplant Patients. 年龄只是老年肾移植患者的一个数字
IF 5.3 2区 医学 Q1 IMMUNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-05-21 DOI: 10.1097/TP.0000000000005073
Evelien E Quint, Robert A Pol, Dorry L Segev, Mara A McAdams-DeMarco

The rise in the mean age of the global population has led to an increase in older kidney transplant (KT) patients. This demographic shift, coupled with the ongoing organ shortage, requires a nuanced understanding of which older adults are most suitable for KT. Recognizing the increased heterogeneity among older adults and the limitations of solely relying on chronological age, there is a need to explore alternative aging metrics beyond chronological age. In this review, we discuss the impact of older age on access to KT and postoperative outcomes. Emphasizing the need for a comprehensive evaluation that extends beyond chronological age, we explore alternative aging metrics such as frailty, sarcopenia, and cognitive function, underscoring their potential role in enhancing the KT evaluation process. Most importantly, we aim to contribute to the ongoing discourse, fostering an optimized approach to KT for the rapidly growing population of older adults.

全球人口平均年龄的上升导致老年肾移植(KT)患者的增加。这种人口结构的变化,再加上持续的器官短缺,要求我们对哪些老年人最适合接受肾移植有一个细致入微的了解。由于认识到老年人之间的异质性增加以及仅依赖于纪年年龄的局限性,有必要探索纪年年龄之外的其他衰老指标。在这篇综述中,我们讨论了老年人对接受 KT 和术后结果的影响。我们强调需要进行超越生理年龄的全面评估,并探讨了衰弱、肌肉疏松症和认知功能等替代性衰老指标,强调了它们在加强 KT 评估过程中的潜在作用。最重要的是,我们的目标是为正在进行的讨论做出贡献,为快速增长的老年人群提供优化的 KT 方法。
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引用次数: 0
期刊
Transplantation
全部 Geobiology Appl. Clay Sci. Geochim. Cosmochim. Acta J. Hydrol. Org. Geochem. Carbon Balance Manage. Contrib. Mineral. Petrol. Int. J. Biometeorol. IZV-PHYS SOLID EART+ J. Atmos. Chem. Acta Oceanolog. Sin. Acta Geophys. ACTA GEOL POL ACTA PETROL SIN ACTA GEOL SIN-ENGL AAPG Bull. Acta Geochimica Adv. Atmos. Sci. Adv. Meteorol. Am. J. Phys. Anthropol. Am. J. Sci. Am. Mineral. Annu. Rev. Earth Planet. Sci. Appl. Geochem. Aquat. Geochem. Ann. Glaciol. Archaeol. Anthropol. Sci. ARCHAEOMETRY ARCT ANTARCT ALP RES Asia-Pac. J. Atmos. Sci. ATMOSPHERE-BASEL Atmos. Res. Aust. J. Earth Sci. Atmos. Chem. Phys. Atmos. Meas. Tech. Basin Res. Big Earth Data BIOGEOSCIENCES Geostand. Geoanal. Res. GEOLOGY Geosci. J. Geochem. J. Geochem. Trans. Geosci. Front. Geol. Ore Deposits Global Biogeochem. Cycles Gondwana Res. Geochem. Int. Geol. J. Geophys. Prospect. Geosci. Model Dev. GEOL BELG GROUNDWATER Hydrogeol. J. Hydrol. Earth Syst. Sci. Hydrol. Processes Int. J. Climatol. Int. J. Earth Sci. Int. Geol. Rev. Int. J. Disaster Risk Reduct. Int. J. Geomech. Int. J. Geog. Inf. Sci. Isl. Arc J. Afr. Earth. Sci. J. Adv. Model. Earth Syst. J APPL METEOROL CLIM J. Atmos. Oceanic Technol. J. Atmos. Sol. Terr. Phys. J. Clim. J. Earth Sci. J. Earth Syst. Sci. J. Environ. Eng. Geophys. J. Geog. Sci. Mineral. Mag. Miner. Deposita Mon. Weather Rev. Nat. Hazards Earth Syst. Sci. Nat. Clim. Change Nat. Geosci. Ocean Dyn. Ocean and Coastal Research npj Clim. Atmos. Sci. Ocean Modell. Ocean Sci. Ore Geol. Rev. OCEAN SCI J Paleontol. J. PALAEOGEOGR PALAEOCL PERIOD MINERAL PETROLOGY+ Phys. Chem. Miner. Polar Sci. Prog. Oceanogr. Quat. Sci. Rev. Q. J. Eng. Geol. Hydrogeol. RADIOCARBON Pure Appl. Geophys. Resour. Geol. Rev. Geophys. Sediment. Geol.
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