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A review of ethical and regulatory issues in the clinical application of stem cell-derived tissue constructs 干细胞衍生组织结构临床应用中的伦理和监管问题综述
Pub Date : 2023-05-16 DOI: 10.12688/molpsychol.17522.1
Alexander R. Harris, Patrick McGivern, F. Gilbert
The potential of organoids and other stem cell-derived tissue constructs (SCTC) to be used for clinical applications is developing rapidly.  Subsequently, there is an increasing need to understand and address the ethical, legal and regulatory issues around their use.  There are a range of health, ethical, regulatory and legal issues associated with SCTCs that will evolve as the technology develops and they become more accepted for clinical use.  SCTCs can be used for drug screening, phenotypic disease screening and regenerative medicine applications.  Each clinical application has different issues and requirements, there is no perfect, one size fits all SCTC that will cover all applications, even where these different applications assess the same treatment, patient or disease.  Currently, there is minimal guidance on the use of SCTCs in clinical applications, but the regulatory requirements will depend on the particular application.  There is a tension between population based and personalised SCTCs for drug screening, phenotypic disease screening and regenerative medicine applications; whether experimental trials and subsequent delivery of safe and effective treatments for small or individual patient groups can be developed and their financial viability.
类器官和其他干细胞衍生组织结构(SCTC)用于临床应用的潜力正在迅速发展。随后,越来越需要了解和解决有关其使用的道德、法律和监管问题。随着技术的发展,sctc在临床应用中越来越被接受,与sctc相关的一系列健康、伦理、监管和法律问题将不断演变。sctc可用于药物筛选、疾病表型筛选和再生医学应用。每个临床应用都有不同的问题和要求,没有完美的,一个尺寸适合所有的SCTC,将涵盖所有的应用,即使这些不同的应用评估相同的治疗,患者或疾病。目前,在临床应用中使用sctc的指导很少,但监管要求将取决于具体的应用。在药物筛选、表型疾病筛选和再生医学应用方面,基于人群的sctc和个性化sctc之间存在紧张关系;是否可以开展实验性试验并随后为小群体或个别患者提供安全有效的治疗,以及它们的经济可行性。
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引用次数: 0
Of looping kinds and unruly objects: the conceptual making of organoids 循环的种类和不规则的物体:类器官的概念制作
Pub Date : 2023-05-10 DOI: 10.12688/molpsychol.17527.1
O. Altınok
Although the traditional approach within ELSA (Ethical, Legal and Social Aspects) initiatives is to have certain kinds of objects “set” or ready to be governed within bioethics, I will claim that the established regime of bioethics and bio law act as governance while influencing the conceptualization of the entities at play, in this example, the organoids. As a small contrast case to making organoids, I will use the regulation and categorization of embryonic research as a more “natural kind” entity research compared to conceptually synthetic research, where the objects to be regulated are shaped by existing practices of language and material alike. While analyzing the conceptual making of the organoids, I will follow the general methodological framework of Ian Hacking in Social Construction of What? (1999) from philosophy of science, particularly his understanding of “looping kinds”. And since Hacking’s understanding of looping kinds is in a relatively vague formulation, I will supply with different structures within co – productionist account of science and technology studies, most notably of works of Jasonoff (2015) of co-productionist accounts and Bensaude – Vincent’s concept of “buzzword coalitions” (2014) in the making of conceptual coalition around organoids. I will use the structure of scientific objects to assign different uses of parts of concepts in the making.
尽管ELSA(伦理、法律和社会方面)倡议中的传统方法是在生物伦理学中“设定”或准备好管理某些类型的对象,但我认为,生物伦理学和生物法的既定制度起到了治理的作用,同时影响了起作用的实体的概念化,在本例中,即类器官。作为制造类器官的一个小对比,我将把胚胎研究的调节和分类作为一种更“自然”的实体研究,而不是概念上的合成研究,在概念上,要调节的对象是由语言和材料的现有实践塑造的。在分析类器官的概念制作时,我将遵循Ian Hacking在《What?(1999)来自科学哲学,特别是他对“循环种类”的理解。由于Hacking对循环类型的理解是相对模糊的,我将在科学和技术研究的共同生产论中提供不同的结构,最值得注意的是,Jasonoff(2015)的合作生产论著作和Bensaude–Vincent关于围绕类器官建立概念联盟的“流行语联盟”概念(2014)。我将使用科学物体的结构来分配概念在制作过程中的不同用途。
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引用次数: 0
Non-canonical odor representation and learning in Dipteran brains 双翅目动物大脑中的非规范气味表征和学习
Pub Date : 2023-05-09 DOI: 10.12688/molpsychol.17525.1
Michael J Rauscher, G. Wolff
For decades, the vinegar fly Drosophila melanogaster has provided a window into the structure and function of the insect olfactory system, revealing a remarkable organizational correspondence between insects and vertebrates. In both clades, olfactory sensory neurons expressing the same class of sensory receptor proteins exclusively target a dedicated neuropil known as a glomerulus. Here, we review recent evidence from Drosophila and other Dipteran taxa that challenges this canonical view, showing widespread co-expression of olfactory sensory proteins within the same neurons. We discuss the consequences of co-expression for early sensory processing in the insect olfactory system. In addition, we situate these findings within the broader framework of olfactory learning, highlighting recent findings that suggest a wider importance of the antennal lobe than has been previously appreciated.
几十年来,醋蝇黑腹果蝇为了解昆虫嗅觉系统的结构和功能提供了一扇窗户,揭示了昆虫和脊椎动物之间显著的组织对应关系。在这两个分支中,表达同一类感觉受体蛋白的嗅觉感觉神经元专门针对一种称为肾小球的专用神经膜。在这里,我们回顾了来自果蝇和其他偶极子分类群的最新证据,这些证据挑战了这一经典观点,显示嗅觉感觉蛋白在同一神经元中广泛共表达。我们讨论了共同表达对昆虫嗅觉系统早期感觉处理的影响。此外,我们将这些发现置于嗅觉学习的更广泛框架内,强调了最近的发现,这些发现表明触角叶的重要性比以前更大。
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引用次数: 0
The welfare of brain organoids 大脑类器官的福利
Pub Date : 2023-05-03 DOI: 10.12688/molpsychol.17523.1
Heather Browning, W. Veit
One of the most urgent challenges arising in bioethics has been the ethical assessment of the use of brain organoids, largely because of the possibility of sentience and the potential that if they can feel, then they might suffer. But while there is a growing literature on the possibility of sentience in brain organoids and why we should take a precautionary approach towards them, there is very little guidance on what it would mean to protect their welfare. In this paper, we address this omission by exploring the question of what the welfare of an organoid might be like, and how we could scientifically assess this question. As we will show, these are difficult questions to answer, given the current lack of empirical data on many of the important features of brain organoids, but we will provide some principled empirically-informed speculation on possible answers, as well as suggestions for future research directions.
生物伦理学中出现的最紧迫的挑战之一是对大脑类器官的使用进行伦理评估,这主要是因为感知的可能性以及如果他们能感觉到,那么他们可能会遭受痛苦的可能性。但是,尽管关于大脑类器官存在感知能力的可能性以及我们为什么应该对它们采取预防措施的文献越来越多,但关于保护它们的福利意味着什么的指导却很少。在这篇论文中,我们通过探索类器官的福利可能是什么样的问题,以及我们如何科学地评估这个问题,来解决这一遗漏。正如我们将要展示的那样,鉴于目前缺乏关于大脑类器官许多重要特征的经验数据,这些问题很难回答,但我们将对可能的答案提供一些原则性的经验推测,以及对未来研究方向的建议。
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引用次数: 1
Political and ethical landscape of brain organoid research 大脑类器官研究的政治和伦理前景
Pub Date : 2023-04-19 DOI: 10.12688/molpsychol.17521.1
Eric Schneider, L. Samsa, Veljko Dubljević
Human cerebral organoids (hCOs), produced in labs through directed cell culture of embryonic or induced pluripotent stem cells, closely replicate the 3-dimensional architecture of the human brain on a micro scale. This technology has been used to model neurological disease and shows promise to complement or supplant animal subjects in preclinical therapeutic investigation. However, attention must be paid by researchers and institutions to the various ethical concerns associated with hCO development. Human-animal chimeras produced through the grafting of hCOs have shown integration of neurological function, calling into question the moral status of both the animal chimeras and the organoid itself. Sensationalist reporting on such acts may also prompt public backlash, potentially jeopardizing hCO research and the promised benefits thereof. Moreover, concerns arise over privacy and consent for past and prospective donors of stem cells used to produce organoids. Genetic information may be considered privileged to the public domain and disrupted trust can reduce the supply of willing donors. Though hCOs are believed thus far to lack the capacity for consciousness and cognitive function, consideration must be given to their potential status as moral agents with further development or enhancement. Boundaries concerning organoids adhered to by researchers have been largely voluntary and informal to this point. By edict or by the power of the purse, governmental regulatory agencies ought to formalize necessary guidelines to ensure compliance with ethical principles and the adequate representation of all affected stakeholders in future decisions.
人类大脑类器官(hCO)是在实验室中通过胚胎或诱导多能干细胞的定向细胞培养产生的,在微观尺度上紧密复制人类大脑的三维结构。这项技术已被用于神经系统疾病的建模,并有望在临床前治疗研究中补充或取代动物受试者。然而,研究人员和机构必须关注与hCO发展相关的各种伦理问题。通过hCO2移植产生的人-动物嵌合体显示出神经功能的整合,这让人对动物嵌合体和类器官本身的道德地位产生了质疑。对此类行为的耸人听闻的报道也可能引发公众的强烈反对,可能危及hCO研究及其承诺的好处。此外,人们还担心用于生产类器官的干细胞的过去和未来捐献者的隐私和同意。基因信息可能被认为是公共领域的特权,而被破坏的信任可能会减少自愿捐赠者的供应。尽管到目前为止,人们认为hCO缺乏意识和认知功能的能力,但随着其进一步发展或增强,必须考虑其作为道德代理人的潜在地位。到目前为止,研究人员对类器官的边界基本上是自愿和非正式的。通过法令或财政权力,政府监管机构应正式制定必要的指导方针,以确保遵守道德原则,并在未来的决策中充分代表所有受影响的利益相关者。
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引用次数: 2
Decreased hippocampal microglial cell activation by methanolic extract from the leaves of Mallotus oppositifolius (Geiseler) Müll. Arg contributes to its antidepressant-like effect 马来莲叶甲醇提取物对海马小胶质细胞活化的影响。精氨酸有助于它的抗抑郁作用
Pub Date : 2023-03-24 DOI: 10.12688/molpsychol.17508.1
K. E. Kukuia, Ferka Yaw Takyi, George J. Dugbartey, Patrick Amoateng, W. Kudzi, S. Amponsah, A. Koomson, Frimpong Appiah, Ofosua Adi-Dako, E. Ameyaw, K. Adutwum-Ofosu
Background: Natural remedies with neuroprotective effect are useful in neuroinflammation-associated depression. Although Mallotus oppositifolius extract (MOE) has previously demonstrated antidepressant and anti-inflammatory properties, its neuroprotective effect remains unknown. Thus, the study evaluated the effect of MOE on lipopolysaccharide (LPS)-induced neuroinflammation-associated depression in mice. Methods: Antidepressant-like effect of MOE (10 - 100 mg/kg), fluoxetine (20 mg/kg) and minocycline (50 mg/kg) was established in naïve Institute of Cancer Research (ICR) mice using the forced swim (FST), tail suspension (TST) and open-space swim (OSST) tests. In a separate experiment, FST and TST were used to assess the effect of an 11-day pre-treatment with MOE (10 - 100 mg/kg) or minocycline (50 mg/kg) on LPS (1 mg/kg) neuroinflammation at 6 and 24 hours post LPS. Following these tests, mice were sacrificed and their hippocampi isolated to evaluate their resting and activated microglial cells using Golgi-Cox staining technique. Open-field test was used to assess locomotor activity. Results: MOE, fluoxetine and minocycline significantly reduced immobility in FST, TST and OSST compared to vehicle (p < 0.05), confirming their antidepressant-like effect. Interestingly, MOE’s antidepressant-like effect was faster than fluoxetine and minocycline. Conversely, LPS treatment increased immobility behavior at 6 and 24 hours, suggestive of neuroinflammation-induced depression. Compared to vehicle group, pre-treatment with MOE and minocycline ameliorated LPS-induced hippocampal microglial activation and reversed increased immobility behavior without affecting locomotor activity (p < 0.05).  Resting microglial cell count was significantly increased by MOE pre-treatment in the OSST-challenged mice compared to vehicle group (p < 0.01). Similarly, MOE pre-treatment reversed LPS-induced reduction in resting microglial count, and restored resting microglial count to normal levels compared to LPS naive vehicle group. Conclusions: Collectively, the results suggest that MOE exerts neuroprotective effect against LPS-induced neuroinflammation by decreasing the activation of microglia and increasing resting microglial count. This contributes to its antidepressant-like effect.
背景:具有神经保护作用的天然药物可用于神经炎症相关的抑郁症。尽管野锦葵提取物(MOE)先前已显示出抗抑郁和抗炎特性,但其神经保护作用尚不清楚。因此,本研究评估了MOE对脂多糖(LPS)诱导的小鼠神经炎症相关抑郁的影响。方法:采用强迫游泳(FST)、尾部悬吊(TST)和开放空间游泳(OSST)试验,在癌症研究所(ICR)小鼠体内建立MOE(10~100mg/kg)、氟西汀(20mg/kg)和米诺环素(50mg/kg)的类抗抑郁作用。在另一项实验中,FST和TST用于评估MOE(10-100 mg/kg)或米诺环素(50 mg/kg)预处理11天对LPS(1 mg/kg)神经炎症在LPS后6小时和24小时的影响。在这些测试之后,处死小鼠并分离其海马,以使用高尔基-考克斯染色技术评估其静息和活化的小胶质细胞。野外试验用于评估运动活动。结果:与赋形剂相比,MOE、氟西汀和米诺环素显著降低了FST、TST和OSST的不动性(p<0.05),证实了它们的抗抑郁作用。有趣的是,MOE的抗抑郁作用比氟西汀和米诺环素更快。相反,LPS治疗在6小时和24小时时增加了不动行为,提示神经炎症诱导的抑郁症。与载体组相比,MOE和米诺环素预处理改善了LPS诱导的海马小胶质细胞活化,并在不影响运动活性的情况下逆转了不动行为的增加(p<0.05)。与载体组比较,OSST攻击小鼠的MOE预处理显著增加了静息小胶质细胞计数(p<0.01)。同样,与LPS初始载体组相比,MOE预处理逆转了LPS诱导的静息小胶质细胞计数的减少,并将静息小胶质胶质细胞计数恢复到正常水平。结论:总之,研究结果表明,MOE通过减少小胶质细胞的活化和增加静息小胶质细胞计数,对LPS诱导的神经炎症具有神经保护作用。这有助于它的抗抑郁作用。
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引用次数: 0
Neural mechanisms for spatial cognition across vertebrates 脊椎动物空间认知的神经机制
Pub Date : 2023-03-10 DOI: 10.12688/molpsychol.17503.1
Ehud Vinepinsky, R. Segev
The ability to navigate the world is a critical cognitive skill that most animals use to find food, shelter, and mates. Understanding the neural basis of navigation requires probing how the brain encodes spatial information through the study of the activity of single neurons and neuronal populations. Classically in vertebrates, studies have centered on the rodent hippocampal formation, which led to the discovery of place, grid, head direction and other cell types. However, since navigation skills are essential to almost all vertebrates, spatial cognition in different species also needs to be explored. In recent years, as a result of advances in technology, new data have emerged on the ways in which space is represented during navigation in the brains of vertebrates other than rodents, including teleost fish, birds, and other mammal species. Here, we review the state of the art on the neural representation of an animal’s position and motion across vertebrates at the level of single neurons. We argue that it is time to pool information across vertebrates to identify the underlying algorithms that lead to successful navigation. Although rodent-based data are important, findings in rodents are unlikely to cover the full spectrum of neural computations supporting navigation strategies in the vertebrate kingdom. Studying other species can shed light on length scales such as in large environments, and different scenarios such as naturalistic environments that are hard to carry out in rodents. In addition, a rodent-centric view may neglect the fact that different species are likely to represent positions in the world in ways that do not exist in mammals. Finally, we provide an outlook for the future which includes prediction about findings in unexplored species, and the opportunities for discoveries and understanding in this field.
导航世界的能力是一项关键的认知技能,大多数动物用它来寻找食物、住所和配偶。理解导航的神经基础需要通过研究单个神经元和神经元群的活动来探索大脑如何编码空间信息。在脊椎动物中,经典的研究集中在啮齿动物的海马形成上,这导致了位置、网格、头部方向和其他细胞类型的发现。然而,由于导航技能对几乎所有脊椎动物都是必不可少的,因此还需要探索不同物种的空间认知。近年来,由于技术的进步,出现了新的数据,揭示了除啮齿动物以外的脊椎动物(包括硬骨鱼、鸟类和其他哺乳动物)在导航过程中空间的表现方式。在这里,我们回顾了在单个神经元水平上脊椎动物的位置和运动的神经表征的最新进展。我们认为,现在是时候汇集脊椎动物之间的信息,以确定导致成功导航的底层算法。尽管基于啮齿动物的数据很重要,但啮齿动物的发现不太可能涵盖脊椎动物王国支持导航策略的神经计算的全部范围。研究其他物种可以阐明在大型环境中的长度尺度,以及在自然环境中难以在啮齿动物中进行的不同场景。此外,以啮齿动物为中心的观点可能忽略了这样一个事实,即不同物种可能以哺乳动物不存在的方式代表世界上的位置。最后,我们对未来进行了展望,包括对未探索物种的发现的预测,以及该领域发现和理解的机会。
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引用次数: 0
What do mammals have to say about the neurobiology of acoustic communication? 哺乳动物对声音交流的神经生物学有什么要说的?
Pub Date : 2023-01-01 Epub Date: 2023-05-04 DOI: 10.12688/molpsychol.17539.1
Angeles Salles, Joshua Neunuebel

Auditory communication is crucial across taxa, including humans, because it enables individuals to convey information about threats, food sources, mating opportunities, and other social cues necessary for survival. Comparative approaches to auditory communication will help bridge gaps across taxa and facilitate our understanding of the neural mechanisms underlying this complex task. In this work, we briefly review the field of auditory communication processing and the classical champion animal, the songbird. In addition, we discuss other mammalian species that are advancing the field. In particular, we emphasize mice and bats, highlighting the characteristics that may inform how we think about communication processing.

听觉交流在包括人类在内的各个分类群中至关重要,因为它使个体能够传达有关威胁、食物来源、交配机会和其他生存所需的社会线索的信息。听觉交流的比较方法将有助于弥合分类群之间的差距,并有助于我们理解这一复杂任务背后的神经机制。在这项工作中,我们简要回顾了听觉交流处理领域和经典的冠军动物鸣禽。此外,我们还讨论了正在推进这一领域的其他哺乳动物物种。特别是,我们强调老鼠和蝙蝠,强调了我们如何思考通信处理的特征。
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引用次数: 0
Early life stress and the role of environmental and molecular moderators in the ontology of pathological and resilient behavioral phenotypes 早期生活压力以及环境和分子调节因子在病理和弹性行为表型本体中的作用
Pub Date : 2022-11-04 DOI: 10.12688/molpsychol.17482.1
Nicholas J. Collins, Taylor S. Campbell, Katelyn M. Donoghue, Urmi Ghosh, Jessica N. Smith, Maeve C. O'Shea, C. Nelson, Olivia K. Bigham, T. Roth
Early life stress (ELS) in the form of trauma or caregiver abuse and neglect is often associated with psychopathology. However, not everyone exposed to ELS develops a pathology; others display resilience, or the ability to adapt and persevere despite ongoing adversity. Several molecular moderator variables between ELS and behavioral phenotypes have been proposed, including single nucleotide polymorphisms (SNPs) and epigenetic markers. Specifically, several SNPs and aberrant methylation or expression of genes associated with neurotransmitter systems and brain-derived neurotrophic factor have been associated with anxiety, depression or schizophrenia. The present review seeks to explore the relationship between SNPs, epigenomics and disease, and offer data to suggest several SNPs may also predict specific treatment efficacy and psychological resilience. Due to this discrepancy in the literature, it is critical that environmental moderators be equally considered in determining the ontology of resilient or pathological phenotypes; this includes the infant-caregiver relationship, and the degree of control, magnitude, and type of the stressor experienced. Finally, we will offer evidence to suggest that several intervention strategies, including drug treatment, environmental enrichment, or exercise can ameliorate many of the psychological, biological, and molecular consequences of ELS exposure, and help shift one toward a resilient phenotype.
以创伤或照顾者虐待和忽视为形式的早期生活压力(ELS)通常与精神病理学有关。然而,并不是每个接触ELS的人都会出现病理;其他人表现出韧性,或者在持续的逆境中适应和坚持的能力。ELS和行为表型之间的几个分子调节变量已经被提出,包括单核苷酸多态性(SNPs)和表观遗传学标记。具体而言,与神经递质系统和脑源性神经营养因子相关的几个SNPs和基因的异常甲基化或表达与焦虑、抑郁或精神分裂症有关。本综述旨在探索SNPs、表观基因组学和疾病之间的关系,并提供数据表明几种SNPs也可以预测特定的治疗效果和心理弹性。由于文献中的这种差异,在确定弹性表型或病理表型的本体论时,同等考虑环境调节因子是至关重要的;这包括婴儿与照顾者的关系,以及所经历的压力源的控制程度、大小和类型。最后,我们将提供证据表明,几种干预策略,包括药物治疗、环境富集或锻炼,可以改善ELS暴露的许多心理、生物学和分子后果,并有助于将其转变为有弹性的表型。
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引用次数: 0
25 Years of Molecular Psychology: The best is yet to come 分子心理学25年:最好的还在后头
Pub Date : 2022-05-17 DOI: 10.12688/molpsychol.17419.1
T. Canli
This editorial defines the scope of the field of Molecular Psychology, which refers to the study of behavior and its underlying neural systems using the toolset of molecular biology, particularly molecular genetics and epigenetics. It is related to other well-established fields that use molecular tools in animal model organisms (Behavioral Neuroscience; Neuroethology) or that focus on molecular mechanisms of human mental health and disease (Molecular Psychiatry; Health Psychology), but extends beyond these fields by its inclusion of broad domains of human behavior; the precise molecular mechanisms by which environmental exposure and experiences modify gene expression; and the ethical, legal, and social implications (ELSI) of these discoveries. Considering the first 25 years of studies that included candidate gene and genome-wide association studies, I suggest a roadmap for the next decade of work. On the launch of F1000 Molecular Psychology: Brain, Behavior & Society, I hope this publication platform will become instrumental in growing this field by promoting a spirit of support and community among its practitioners, embracing transparency and rigor, and publishing novel ideas and studies ranging from pilot and proof-of-concept first steps to gold-standard definitive milestones.
这篇社论定义了分子心理学领域的范围,它指的是使用分子生物学,特别是分子遗传学和表观遗传学的工具集来研究行为及其潜在的神经系统。它与其他在动物模式生物中使用分子工具的成熟领域有关(行为神经科学;神经行为学)或专注于人类心理健康和疾病的分子机制(分子精神病学;健康心理学),但它超越了这些领域,包括人类行为的广泛领域;环境暴露和经历改变基因表达的精确分子机制;以及这些发现的伦理、法律和社会影响(ELSI)。考虑到前25年的研究,包括候选基因和全基因组关联研究,我建议未来十年的工作路线图。在F1000分子心理学:大脑,行为与社会发布之际,我希望这个出版平台能够通过在从业者中促进支持和社区精神,拥抱透明度和严谨性,并发布新颖的想法和研究,从试点和概念验证的第一步到黄金标准的最终里程碑,在这一领域的发展中发挥重要作用。
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引用次数: 0
期刊
Molecular psychology
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