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Association of Genetic Liability to Psychotic Experiences With Neuropsychotic Disorders and Traits. 精神经历的遗传责任与神经精神障碍和特征的关系。
IF 25.8 Pub Date : 2019-12-01 DOI: 10.1001/jamapsychiatry.2019.2508
Sophie E Legge, Hannah J Jones, Kimberley M Kendall, Antonio F Pardiñas, Georgina Menzies, Matthew Bracher-Smith, Valentina Escott-Price, Elliott Rees, Katrina A S Davis, Matthew Hotopf, Jeanne E Savage, Danielle Posthuma, Peter Holmans, George Kirov, Michael J Owen, Michael C O'Donovan, Stanley Zammit, James T R Walters
<p><strong>Importance: </strong>Psychotic experiences, such as hallucinations and delusions, are reported by approximately 5% to 10% of the general population, although only a small proportion develop psychotic disorders such as schizophrenia. Studying the genetic causes of psychotic experiences in the general population, and its association with the genetic causes of other disorders, may increase the understanding of their pathologic significance.</p><p><strong>Objectives: </strong>To determine whether genetic liability to psychotic experiences is shared with schizophrenia and/or other neuropsychiatric disorders and traits and to identify genetic loci associated with psychotic experiences.</p><p><strong>Design, setting and participants: </strong>Analyses of genetic correlation, polygenic risk scores, and copy number variation were performed using data from participants in the UK Biobank from April 1, 2018, to March 20, 2019, to assess whether genetic liability to psychotic experiences is shared with schizophrenia and/or other neuropsychiatric disorders and traits. Genome-wide association studies of psychotic experience phenotypes were conducted to identify novel genetic loci. Participants in the final analyses after exclusions included 6123 individuals reporting any psychotic experience, 2143 individuals reporting distressing psychotic experiences, and 3337 individuals reporting multiple occurrences of psychotic experiences. A total of 121 843 individuals who did not report a psychotic experience formed the comparator group. Individuals with a psychotic disorder were excluded from all analyses.</p><p><strong>Main outcomes and measures: </strong>Genetic associations with psychotic experience phenotypes.</p><p><strong>Results: </strong>The study included a total of 127 966 participants (56.0% women and 44.0% men; mean [SD] age, 64.0 [7.6] years). Psychotic experiences were genetically correlated with major depressive disorder, schizophrenia, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Analyses of polygenic risk scores identified associations between psychotic experiences and genetic liability for major depressive disorder, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Individuals reporting psychotic experiences had an increased burden of copy number variations previously associated with schizophrenia (odds ratio [OR], 2.04; 95% CI, 1.39-2.98; P = 2.49 × 10-4) and neurodevelopmental disorders more widely (OR, 1.75; 95% CI, 1.24-2.48; P = 1.41 × 10-3). Genome-wide association studies identified 4 significantly associated loci, including a locus in Ankyrin-3 (ANK3 [GenBank NM_020987]) (OR, 1.16; 95% CI, 1.10-1.23; P = 3.06 × 10-8) with any psychotic experience, and a locus in cannabinoid receptor 2 gene (CNR2 [GenBank NM_001841]) (OR, 0.66; 95% CI, 0.56-0.78; P = 3.78 × 10-8) with distressing psychotic experiences. The genome-wide association study of any psychotic
重要性:大约5%至10%的普通人群报告了幻觉和妄想等精神病经历,尽管只有一小部分人会患上精神分裂症等精神病。研究普通人群中精神病经历的遗传原因,及其与其他疾病的遗传原因的关联,可以增加对其病理意义的理解。目的:确定精神病经历的遗传易感性是否与精神分裂症和/或其他神经精神障碍和特征相同,并确定与精神病经历相关的遗传位点。设计、设置和参与者:使用2018年4月1日至2019年3月20日英国生物库参与者的数据,对遗传相关性、多基因风险评分和拷贝数变异进行分析,以评估精神分裂症和/或其他神经精神障碍和特征是否与精神病经历的遗传易感性相同。对精神病体验表型进行全基因组关联研究,以确定新的遗传位点。排除后最终分析的参与者包括6123名报告任何精神病经历的人,2143名报告痛苦精神病经历,3337名报告多次精神病经历。共121 843名没有报告精神病经历的人组成了对照组。患有精神病性障碍的个体被排除在所有分析之外。主要结果和测量:与精神病体验表型的遗传关联。结果:该研究共包括127项 966名参与者(女性56.0%,男性44.0%;平均[SD]年龄64.0[7.6]岁)。精神经历与重度抑郁障碍、精神分裂症、自闭症谱系障碍和注意力缺陷/多动障碍在基因上相关。对多基因风险评分的分析确定了精神病经历与严重抑郁障碍、精神分裂症、双相情感障碍、自闭症谱系障碍和注意力缺陷/多动障碍的遗传易感性之间的关联。报告精神病经历的个体先前与精神分裂症相关的拷贝数变化负担增加(比值比[OR],2.04;95%可信区间,1.39-2.98;P = 2.49 × 10-4)和更广泛的神经发育障碍(OR,1.75;95%CI,1.24-2.48;P = 1.41 × 10-3)。全基因组关联研究确定了4个显著相关的基因座,包括锚蛋白-3基因座(ANK3[GenBank NM_020987])(OR,1.16;95%CI,1.10-1.23;P = 3.06 × 10-8)具有任何精神病经历,并且大麻素受体2基因(CNR2[GenBank NM_001841])位点(OR,0.66;95%CI,0.56-0.78;P = 3.78 × 10-8)有痛苦的精神病经历。任何精神病经历的全基因组关联研究具有基于单核苷酸多态性的低遗传性估计(h2 = 1.71%;95%可信区间,1.02%-2.40%)。结论和相关性:一项基于人群的英国生物库样本的精神病经历的大型遗传关联研究发现,精神病经历与精神分裂症、重性抑郁障碍、双相情感障碍和神经发育障碍之间存在共同的遗传责任。
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引用次数: 0
The Danger of Testing by Selecting Controlled Subsets, with Applications to Spoken-Word Recognition. 选择受控子集测试的危险及其在口语识别中的应用
Pub Date : 2019-01-24 DOI: 10.5334/joc.51
David Liben-Nowell, Julia Strand, Alexa Sharp, Tom Wexler, Kevin Woods

When examining the effects of a continuous variable x on an outcome y, a researcher might choose to dichotomize on x, dividing the population into two sets-low x and high x-and testing whether these two subpopulations differ with respect to y. Dichotomization has long been known to incur a cost in statistical power, but there remain circumstances in which it is appealing: an experimenter might use it to control for confounding covariates through subset selection, by carefully choosing a subpopulation of Low and a corresponding subpopulation of High that are balanced with respect to a list of control variables, and then comparing the subpopulations' y values. This "divide, select, and test" approach is used in many papers throughout the psycholinguistics literature, and elsewhere. Here we show that, despite the apparent innocuousness, these methodological choices can lead to erroneous results, in two ways. First, if the balanced subsets of Low and High are selected in certain ways, it is possible to conclude a relationship between x and y not present in the full population. Specifically, we show that previously published conclusions drawn from this methodology-about the effect of a particular lexical property on spoken-word recognition-do not in fact appear to hold. Second, if the balanced subsets of Low and High are selected randomly, this methodology frequently fails to show a relationship between x and y that is present in the full population. Our work uncovers a new facet of an ongoing research effort: to identify and reveal the implicit freedoms of experimental design that can lead to false conclusions.

在检查连续变量x对结果y的影响时,研究人员可能会选择对x进行二分类,将总体分为两组-低x和高x -并测试这两个亚总体相对于y是否不同。二分类长期以来一直被认为会导致统计能力的成本,但仍然存在吸引人的情况:实验者可以使用它通过子集选择来控制混杂协变量,通过仔细选择相对于控制变量列表平衡的Low亚种群和相应的High亚种群,然后比较亚种群的y值。这种“划分、选择和测试”的方法在心理语言学文献和其他地方的许多论文中都有使用。在这里,我们表明,尽管表面上无害,这些方法的选择可能导致错误的结果,在两个方面。首先,如果以某种方式选择Low和High的平衡子集,则有可能得出在整个总体中不存在的x和y之间的关系。具体来说,我们表明,以前发表的结论,从这个方法得出的,关于一个特定的词汇属性对口语单词识别的影响,实际上似乎并不成立。其次,如果Low和High的平衡子集是随机选择的,那么这种方法通常无法显示整个总体中存在的x和y之间的关系。我们的工作揭示了正在进行的研究工作的一个新方面:识别和揭示可能导致错误结论的实验设计的隐性自由。
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引用次数: 0
Magnetic Circular Dichroism of Substoichiometric Molybdenum Oxide (MoO₃–ₓ) Nanoarchitectures with Polaronic Defects 具有极化合缺陷的亚化学计量氧化钼(MoO₃-ₓ)纳米结构的磁圆二色性
IF 2.781 Pub Date : 2019-01-01 DOI: 10.1021/acs.jpcc.9b03225.s001
Taisei Kimura, H. Yao
Magnetic circular dichroism (MCD) is demonstrated for the first time in substoichiometric molybdenum oxide (MoO₃–ₓ) nanoarchitectures to explore the origin of their near-IR (NIR) transitions. Various nanostructures of MoO₃–ₓ are synthesized by a simple hydrothermal process using an ionic Mo(VI) or metallic Mo(0) precursor. The phase, morphology, and spectroscopic properties of the obtained nanostructures are dependent both on the reaction temperature and the molybdenum precursor. In particular, hexagonal MoO₃–ₓ nanostructures are colored blue with different degrees. To better understand the nature of the electronic states in these nanomaterials, MCD spectroscopy is conducted. A derivative-like MCD response is detected in the vis-NIR region, but it is not attributed to surface magnetoplasmonic modes because of the absence of the peak-energy shift with the increasing refractive index of the dispersion medium. Then, the bisignate MCD signal can be attributed to Faraday B-terms for small-polaronic transitions, arising from two interacting polaronic states close in energy that would give opposite signs under an applied magnetic field. We believe that MCD evaluation for polaronic nanomaterials will expand promising new applications in fields such as semiconductor-based nanophotonics and magneto-optical devices.
首次在亚化学计量的氧化钼(MoO₃-ₓ)纳米结构中证明了磁性圆二色性(MCD),以探索其近红外(NIR)跃迁的起源。采用离子Mo(VI)或金属Mo(0)前驱体,通过简单的水热法合成了多种MoO₃-ₓ纳米结构。所得纳米结构的相、形貌和光谱性质取决于反应温度和钼前驱体。特别是,六边形的MoO₃-ₓ纳米结构被不同程度地涂成蓝色。为了更好地了解这些纳米材料中的电子态的性质,进行了MCD光谱。在可见-近红外区域检测到类似导数的MCD响应,但它不是归因于表面磁等离子体模式,因为没有随色散介质折射率增加而出现的峰值能量位移。然后,双信号MCD信号可以归因于法拉第b项的小极化跃迁,由两个相互作用的极化态产生,能量接近,在外加磁场下会给出相反的符号。我们相信,极化纳米材料的MCD评估将在半导体纳米光子学和磁光器件等领域扩展有前途的新应用。
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引用次数: 0
Influences of Contact Metals on the Performances of MoS₂ Devices under Strains 接触金属对应变下MoS 2器件性能的影响
IF 2.781 Pub Date : 2019-01-01 DOI: 10.1021/acs.jpcc.9b09028.s001
Sian-Hong Tseng, Hung-Yi Chen, W. Hsu, Hsiang-Chen Wang, Yuan-Yao Li, Wen‐Hao Chang, Ming-Pei Lu, M. Lu
The growth of large-area MoS₂ films was achieved through atmospheric pressure chemical vapor deposition via vapor management in this study. The thickness of the MoS₂ film changed upon varying the amount of vapor deposited on the substrate. Gratifyingly, large-area monolayer MoS₂ was obtained under controlled conditions. Studies using transmission electron microscopy and second harmonic generation confirmed that the MoS₂ films were composed of grains having sizes ranging from 40 to 70 μm. Flexible MoS₂ device arrays were fabricated on a polyimide substrate; the device arrays displayed high spatial uniformity in their carrier transport properties. The contact metals affected the electrical characteristics of the MoS₂ devices under strain; the sensitivity of devices featuring Schottky contacts was higher than that of those with ohmic contacts. Importantly, the device arrays exhibit sensitive and endurance performances under strain cycles of up to 10⁵ times. These results suggest a means for the feasible growth of large-area single-layer MoS₂ films, as well as the exploitation of flexible MoS₂ device arrays in strain and human motion sensor applications.
本研究采用气相管理的常压化学气相沉积方法,实现了大面积MoS 2薄膜的生长。随着沉积在衬底上的气相量的变化,MoS 2薄膜的厚度也发生了变化。令人满意的是,在可控条件下获得了大面积的单层MoS 2。通过透射电子显微镜和二次谐波产生的研究证实,MoS 2薄膜由40 ~ 70 μm的晶粒组成。在聚酰亚胺衬底上制备了柔性MoS 2器件阵列;器件阵列的载流子输运特性具有较高的空间均匀性。接触金属对MoS 2器件在应变下的电特性有影响;肖特基触点器件的灵敏度高于欧姆触点器件。重要的是,该器件阵列在高达10次的应变循环下表现出敏感和持久的性能。这些结果为大面积单层MoS 2薄膜的生长以及柔性MoS 2器件阵列在应变和人体运动传感器中的应用提供了一种可行的方法。
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引用次数: 0
Understanding the White-Emitting CaMoO₄ Co-Doped Eu³⁺, Tb³⁺, and Tm³⁺ Phosphor through Experiment and Computation 通过实验和计算了解发光CaMoO₄共掺杂Eu³+、Tb³+、Tm³+荧光粉
IF 2.781 Pub Date : 2019-01-01 DOI: 10.1021/acs.jpcc.9b04123.s001
R. L. Tranquilin, L. Lovisa, C. R. Almeida, C. A. Paskocimas, M. Li, M. C. Oliveira, L. Gracia, J. Andrés, E. Longo, F. Motta, M. Bomio
In this article, the synthesis by means of the spray pyrolysis method, of the CaMoO₄ and rare-earth cation (RE³⁺)-doped CaMoO₄:xRE³⁺ (RE³⁺ = Eu³⁺, Tb³⁺, and Tm³⁺; and x = 1, 2, and 4% mol) compounds, is presented. The as-synthesized samples were characterized using X-ray diffraction, Rietveld refinement, field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and photoluminescence (PL) spectroscopy. To complement and rationalize the experimental results, first-principles calculations, at the density functional theory level, have been performed to analyze the band structure and density of states. In addition, a theoretical method based on the calculations of surface energies and Wulff construction was applied to obtain the morphology transformation of the CaMoO₄ and CaMoO₄:RE³⁺ microstructures. The experimental morphologies can be observed in the FE-SEM images. The PL behavior of the Co-doped samples exhibited well-defined bands in the visible region. The samples with 2 and 4% of RE³⁺ released white emission according to the chromaticity coordinates (0.34, 0.34) and (0.34, 0.33), respectively. The present results provide not only a deep understanding of the structure–property relationships of CaMoO₄-based phosphor but also can be employed as a guideline for the design of the electronic structure of the materials and the fabrication of photofunctional materials with optimal properties, which allows for the modeling of new phosphors for applications in solid-state lighting.
本文通过喷雾热解法,合成了CaMoO₄和稀土阳离子(RE³+)掺杂的CaMoO₄:xRE³+ (RE³+ = Eu³+、Tb³+、Tm³+;x = 1、2和4% mol)的化合物。利用x射线衍射、Rietveld细化、场发射扫描电镜(FE-SEM)、拉曼光谱(Raman spectroscopy)和光致发光(PL)光谱对合成的样品进行了表征。为了补充和合理化实验结果,在密度泛函理论水平上进行了第一性原理计算,分析了能带结构和态密度。此外,采用基于表面能计算和Wulff构式的理论方法,获得了CaMoO₄和CaMoO₄:RE³⁺微观结构的形貌转变。在FE-SEM图像中可以观察到实验形貌。共掺杂样品的PL行为在可见光区表现出明确的条带。含2和4% RE³⁺的样品分别在色度坐标(0.34,0.34)和(0.34,0.33)下释放出白色发光。目前的结果不仅提供了对CaMoO₄基荧光粉的结构-性能关系的深刻理解,而且可以作为材料电子结构设计和具有最佳性能的光功能材料制造的指导方针,从而允许在固态照明中应用的新型荧光粉的建模。
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引用次数: 3
Room-Temperature Quantum Anomalous Hall Effect in Single-Layer CrP₂S₆ 单层CrP₂S₆的室温量子反常霍尔效应
IF 2.781 Pub Date : 2019-01-01 DOI: 10.1021/acs.jpcc.9b04888.s001
Pei Zhao, Yandong Ma, Hao Wang, Baibiao Huang, Ying Dai
The quantum anomalous Hall (QAH) effect is a fascinating quantum phenomenon characterized by a nonzero Chern number defined in the bulk and chiral edge states in the boundary. Up to now, only one magnetically doped topological insulator, suffering from a small bulk band gap, is confirmed to host the QAH effect experimentally. Here, through first-principles calculations, we propose a novel QAH insulator in single-layer (SL) CrP₂S₆. The nontrivial topology in SL CrP₂S₆, identified with the nonzero Chern number (C = −1) and chiral edge states, harbors a nontrivial band gap of 53 meV. Meanwhile, using Monte Carlo simulations, the Curie temperature Tc for its ferromagnetic order is estimated to be 350 K, which is above room temperature and comparable with most of the previously reported two-dimensional ferromagnetic semiconductors. Our findings thus present a feasible platform for achieving the QAH effect at room temperature.
量子反常霍尔效应(QAH)是一种令人着迷的量子现象,其特征是在体态和边界的手性边缘态中定义了一个非零的陈恩数。到目前为止,只有一种具有小块带隙的磁掺杂拓扑绝缘体被实验证实具有QAH效应。在这里,通过第一性原理计算,我们提出了一种单层(SL) CrP₂S₆的新型QAH绝缘子。具有非零陈氏数(C = - 1)和手性边态的SL CrP₂S₆的非平凡拓扑具有53mev的非平凡带隙。同时,利用蒙特卡罗模拟,估计其铁磁序的居里温度Tc为350 K,高于室温,与之前报道的大多数二维铁磁半导体相当。因此,我们的研究结果为在室温下实现QAH效应提供了一个可行的平台。
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引用次数: 0
PET Imaging for Initial Staging and Therapy Assessment in Multiple Myeloma Patients. PET成像对多发性骨髓瘤患者的初始分期和治疗评估
IF 5.6 Pub Date : 2017-02-18 DOI: 10.3390/ijms18020445
Clément Bailly, Rodolphe Leforestier, Bastien Jamet, Thomas Carlier, Mickael Bourgeois, François Guérard, Cyrille Touzeau, Philippe Moreau, Michel Chérel, Françoise Kraeber-Bodéré, Caroline Bodet-Milin

Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells in the bone marrow. MM results in diffuse or focal bone infiltration and extramedullary lesions. Over the past two decades, advances have been made with regard to the diagnosis, staging, treatment, and imaging of MM. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently recommended as the most effective imaging modalities at diagnostic. Yet, recent data from the literature suggest that positron emission tomography combined with computed tomography (PET/CT) using 18F-deoxyglucose (FDG) is a promising technique for initial staging and therapeutic monitoring in this pathology. This paper reviews the recent advances as well as the potential place of a more specific radiopharmaceutical in MM.

多发性骨髓瘤(MM)是一种以骨髓中恶性浆细胞克隆性增生为特征的血液肿瘤。MM导致弥漫性或局灶性骨浸润和髓外病变。在过去的二十年中,在MM的诊断、分期、治疗和成像方面取得了进展。计算机断层扫描(CT)和磁共振成像(MRI)目前被推荐为诊断时最有效的成像方式。然而,最近来自文献的数据表明,正电子发射断层扫描结合使用18f -脱氧葡萄糖(FDG)的计算机断层扫描(PET/CT)是一种很有前途的技术,用于该病理的初始分期和治疗监测。本文综述了近年来的研究进展以及一种更特异的放射性药物在MM中的潜在地位。
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引用次数: 0
Phenotype and multipotency of rabbit (Oryctolagus cuniculus) amniotic stem cells. 兔(Oryctolagus cuniculus)羊膜干细胞的表型和多潜能性。
IF 2.7 Pub Date : 2017-02-07 DOI: 10.1186/s13287-016-0468-z
Jéssica Borghesi, Lara Carolina Mario, Ana Claudia Oliveira Carreira, Maria Angélica Miglino, Phelipe Oliveira Favaron

Background: Stem cells are capable of unlimited self-renewal and are able to remain undifferentiated for extended periods of time prior to their differentiation into specific cell lineages. Because of the issues (ethical and religious) involved in the use of embryonic stem cells and the limited plasticity of adult stem cells, an alternative cell source could be foetal stem cells derived from extra-embryonic tissue, which are highly proliferative, grow in vitro and possess interesting immunogenic characteristics. As a result, the amniotic membrane of several species has been studied as an important new source of stem cells.

Methods: Here, we cultured and characterized mesenchymal progenitor cells derived from the rabbit amniotic membrane, and investigated their differentiation potential. In total, amniotic membranes were collected from eight rabbit foetuses and were isolated by the explant technique. The obtained cells were cultured in DMEM-HIGH glucose and incubated at 37 °C in a humidified atmosphere with 5% CO2.

Results: The cells adhered to the culture plates and showed a high proliferative capacity with fibroblast-like morphologies. The cells showed a positive response for markers for the cytoskeleton, mesenchymal stem cells and proliferation, pluripotency and haematopoietic precursor stem cells. However, the cells were negative for CD45, a marker of haematopoietic cells. Furthermore, the cells had the capacity to be induced to differentiate into osteogenic, adipogenic and chondrogenic lineages. In addition, when the cells were injected into nude mice, we did not observe the formation of tumours.

Conclusions: In summary, our results demonstrate that multipotent mesenchymal stem cells can be obtained from the rabbit amniotic membrane for possible use in future cell therapy applications.

背景:干细胞具有无限自我更新的能力,在分化成特定细胞系之前,能够长时间保持未分化状态。由于使用胚胎干细胞涉及伦理和宗教问题,而且成体干细胞的可塑性有限,因此可从胚外组织中提取胎儿干细胞作为替代细胞来源,这种干细胞增殖能力强,可在体外生长,并具有有趣的免疫原性。方法:在此,我们培养了兔羊膜间充质祖细胞并对其特征进行了描述,还研究了它们的分化潜能。我们总共从 8 个兔胎儿身上采集了羊膜,并通过外植体技术将其分离出来。获得的细胞在 DMEM-高葡萄糖中培养,37 °C、5% CO2 的湿润环境中培养:结果:细胞粘附在培养板上,具有很强的增殖能力,形态类似成纤维细胞。细胞对细胞骨架、间充质干细胞和增殖、多能性和造血前体干细胞的标记呈阳性反应。不过,这些细胞的造血细胞标记 CD45 呈阴性。此外,这些细胞还具有诱导分化为成骨、成脂和软骨细胞系的能力。此外,将细胞注入裸鼠体内时,我们没有观察到肿瘤的形成:总之,我们的研究结果表明,可以从兔羊膜中获得多能间充质干细胞,可用于未来的细胞治疗。
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引用次数: 0
Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains 太赫兹(THz)波动在PDZ域变构特性中的作用
IF 2.781 Pub Date : 2017-01-01 DOI: 10.1021/acs.jpcb.7b06590.s001
Conti Nibali, Valéria, Morra, Giulia, Havenith, Martina, Colombo, Giorgio
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引用次数: 0
Refining the Understanding of the Effects of Prenatal Methamphetamine and Tobacco Exposure on the Developing Brain. 进一步了解产前接触甲基苯丙胺和烟草对大脑发育的影响。
IF 25.8 Pub Date : 2016-12-01 DOI: 10.1001/jamapsychiatry.2016.2845
Annerine Roos, Kirsten Ann Donald
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引用次数: 1
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