当前共找到 1276 篇文献分享,本页显示第 701 - 720 篇。
701.
庞庞
(2023-02-28 21:02):
#paper doi:https://doi.org/10.1038/nn.4164 Parcellating cortical functional networks in individuals
大脑网络的位置、大小等属性具有个体差异。之前的研究忽略了这些差异,运用组水平的分区模板计算功能连接矩阵,导致功能连接个体间差异的混淆。本研究是第一个提出个体化功能网络的研究,基于组水平网络分区模板迭代的思路,获得了具有可重复性、可以捕捉个体间差异、可通过电刺激验证的功能网络个体化分区,为我们进行个体化功能网络的研究提供了新思路。
Abstract:
The capacity to identify the unique functional architecture of an individual's brain is a crucial step toward personalized medicine and understanding the neural basis of variation in human cognition and …
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The capacity to identify the unique functional architecture of an individual's brain is a crucial step toward personalized medicine and understanding the neural basis of variation in human cognition and behavior. Here we developed a cortical parcellation approach to accurately map functional organization at the individual level using resting-state functional magnetic resonance imaging (fMRI). A population-based functional atlas and a map of inter-individual variability were employed to guide the iterative search for functional networks in individual subjects. Functional networks mapped by this approach were highly reproducible within subjects and effectively captured the variability across subjects, including individual differences in brain lateralization. The algorithm performed well across different subject populations and data types, including task fMRI data. The approach was then validated by invasive cortical stimulation mapping in surgical patients, suggesting potential for use in clinical applications.
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702.
小W
(2023-02-28 20:31):
#paper doi:https://doi.org/10.1016/j.cell.2022.12.027
Loss of epigenetic information as a cause of mammalian aging 本文主要论述细胞对DNA断裂(DSB)修复过程中染色质修饰剂的重新定位(RCM)的变化,侵蚀了表观遗传图谱,这种表观遗传信息的丢失加速了细胞衰老和老化。本文使用I-PpoI内切酶建立 DSB 的细胞和小鼠(ICE)老化模型,通过比较十个月后肝脏、皮肤、脑、肌肉、活力等方面在代谢、基因组、表观遗传和组蛋白水平的衰老标志物,ICE 小鼠较对照小鼠 表现更高的老化速度。提出以下观点:1.哺乳动物的衰老与DSB修复效率相关,但与其他类型的修复无关,可能是因为只有对细胞生存的严重威胁才足以破坏表观基因组,从而导致衰老。2.RCM反应会发育破坏基因、DNA甲基转移酶(DNMTs)的表达模式,并释放被沉默的逆转录转座子。3.通过OSK(Yamanaka因子Oct4、Sox2、Klf4)处理,衰老细胞的衰老标记物的水平恢复到与阴性对照相似的水平,(哺乳动物衰老细胞可能保留了恢复年轻的表观遗传信息)。4.表观遗传信息的丢失是衰老的原因。
Abstract:
All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of …
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All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.
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703.
哪有情可长
(2023-02-28 20:25):
#paper Atlas of exercise metabolism reveals timedependent signatures of metabolic homeostasis,Cell Metabolism,15 January 2022, doi.org/10.1016/j.cmet.2021.12.016. 组织对运动的敏感性和反应会因为运动时间和生物钟的调整而不同,目前什么时间运动能够引发理想代谢结果还没有完全确定。作者为了解决组织如何独立和协调的对定时运动做出反应,利用7种小鼠组织和血清在一天不同的时间点进行急性运动后鉴定起代谢物的反应。通过对不同组织之间代谢物的动力学比较分析,揭示了一天中特定时间运动的局部和全身代谢物的无差异。通过构建运动代谢图谱,发现了跟跟时间依赖性运动代谢产物2-HB的产生和分布的清晰和生理背景,说明了运动对代谢的健康有促进作用。另外该作者在2018年,cell上也发表了一篇生物钟相关的文章:Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks。作者同时对8个小鼠组织进行了24小时代谢组学分析。在系统能量平衡和慢性营养应激(高脂饮食[HFD])的背景下,展示了昼夜节律代谢的时空图谱。
Abstract:
Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is …
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Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared global metabolite responses of seven different mouse tissues and serum after an acute exercise bout performed at different times of the day. Comparative analyses of intra- and inter-tissue metabolite dynamics, including temporal profiling and blood sampling across liver and hindlimb muscles, uncovered an unbiased view of local and systemic metabolic responses to exercise unique to time of day. This comprehensive atlas of exercise metabolism provides clarity and physiological context regarding the production and distribution of canonical and novel time-dependent exerkine metabolites, such as 2-hydroxybutyrate (2-HB), and reveals insight into the health-promoting benefits of exercise on metabolism.
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704.
Vincent
(2023-02-28 19:08):
#paper DOI: https://doi.org/10.1038/s41592-021-01205-4 DOME: recommendations for supervised machine learning validation in biology. Nat Methods 2021. 机器学习方法在生物学领域变得越发重要,理想情况下机器学习预测结果最好能够被生物实验所验证,但是目前绝大多数的文章并没有配套的实验验证步骤,而只是通过计算指标来反映模型的性能,但这类计算指标往往受很多步骤的影响(例如数据集选择,训练集测试集的拆分,正负样本平衡性等等),导致最后的结论不一定稳定可靠。这篇评论文章旨在号召相关领域应该建立一套机器学习研究的写作和汇报标准,从而提高该领域内机器学习应用的交流效率。这篇文章从数据,算法,模型,评价四个方面列举了诸多影响模型性能的因素,并建议研究者在发表机器学习的文章时应该参照这四个方面的问题,详细阐述方法的细节,以此推动文章评审的效率,提高研究的透明度和可重复性
Abstract:
No abstract available.
705.
周周复始
(2023-02-28 17:22):
#paper DOI: 10.1007/978-3-030-87735-4_21 CAS-Net: Conditional Atlas Generation and Brain Segmentation for Fetal MRI. 为了解决图像伪影和噪声以及训练标签不精确的问题,提出了一种新的架构,在一个端到端的pipeline中同时学习分割和生成条件图谱,同时基于微分同胚配准来保证图谱生成的平滑性和连续性 。该图谱使模型能够在不依赖于输入图像的强度值的情况下学习解剖先验,并提高分割性能,特别是在图像质量差没有金标准训练标签的情况下。用该方法在dHCP的253个被试上进行了训练和评估,结果表明,可以生成具有明显边界的特定年龄条件图谱。
Abstract:
Fetal Magnetic Resonance Imaging (MRI) is used in prenatal diagnosis and to assess early brain development. Accurate segmentation of the different brain tissues is a vital step in several brain …
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Fetal Magnetic Resonance Imaging (MRI) is used in prenatal diagnosis and to assess early brain development. Accurate segmentation of the different brain tissues is a vital step in several brain analysis tasks, such as cortical surface reconstruction and tissue thickness measurements. Fetal MRI scans, however, are prone to motion artifacts that can affect the correctness of both manual and automatic segmentation techniques. In this paper, we propose a novel network structure that can simultaneously generate conditional atlases and predict brain tissue segmentation, called CAS-Net. The conditional atlases provide anatomical priors that can constrain the segmentation connectivity, despite the heterogeneity of intensity values caused by motion or partial volume effects. The proposed method is trained and evaluated on 253 subjects from the developing Human Connectome Project (dHCP). The results demonstrate that the proposed method can generate conditional age-specific atlas with sharp boundary and shape variance. It also segment multi-category brain tissues for fetal MRI with a high overall Dice similarity coefficient (DSC) of 85.2% for the selected 9 tissue labels.
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706.
小年
(2023-02-28 16:39):
#paper doi: 10.1172/JCI46043. Circadian rhythms, sleep, and metabolism. J Clin Invest. 2011 Jun;121(6):2133-41. 昼夜节律遗传基础的发现扩展了我们对行为和生理学的时间组织的认识。大脑和身体之间的新陈代谢是以每日“昼夜节律”的方式调节的,然而,系统地扰乱活动的昼夜节律模式,会导致正常代谢模式的破坏,包括肥胖、糖尿病和心血管疾病,与代谢功能障碍,文中评估了molecular timing如何为理解和开发肥胖和糖尿病的治疗方法创造新的机会。未来的研究将继续侧重于扩大我们对大脑和外周时钟如何在细胞自主和非自主水平上协调调节代谢过程的理解,营养通量如何将有关环境的信息转化为时钟,以及昼夜节律对人类健康和疾病的影响。
Abstract:
The discovery of the genetic basis for circadian rhythms has expanded our knowledge of the temporal organization of behavior and physiology. The observations that the circadian gene network is present …
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The discovery of the genetic basis for circadian rhythms has expanded our knowledge of the temporal organization of behavior and physiology. The observations that the circadian gene network is present in most living organisms from eubacteria to humans, that most cells and tissues express autonomous clocks, and that disruption of clock genes results in metabolic dysregulation have revealed interactions between metabolism and circadian rhythms at neural, molecular, and cellular levels. A major challenge remains in understanding the interplay between brain and peripheral clocks and in determining how these interactions promote energy homeostasis across the sleep-wake cycle. In this Review, we evaluate how investigation of molecular timing may create new opportunities to understand and develop therapies for obesity and diabetes.
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707.
张浩彬
(2023-02-28 15:49):
#paper 10.5555/2503308.2188396 Noise-Contrastive Estimation of Unnormalized Statistical Models, with Applications to Natural Image Statistics啃一下nce。nce主要是解决一个问题,当分类类别太多的失衡,softmax的归一化因子计算量太大,于是作者提出nce作为一个替代。作者很巧妙地设计了一个代理任务,把原有的分类问题,转化为一个吧目标从噪声样本中识别出来的二分类问题,从而规避了计算规范化因子的计算量问题。并且作者证明了,当样本趋向于无穷的时候,nce等价于mle。
Abstract:
We consider the task of estimating, from observed data, a probabilistic model that is parameterized by a finite number of parameters. In particular, we are considering the situation where the …
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We consider the task of estimating, from observed data, a probabilistic model that is parameterized by a finite number of parameters. In particular, we are considering the situation where the model probability density function is unnormalized. That is, the model is only specified up to the partition function. The partition function normalizes a model so that it integrates to one for any choice of the parameters. However, it is often impossible to obtain it in closed form. Gibbs distributions, Markov and multi-layer networks are examples of models where analytical normalization is often impossible. Maximum likelihood estimation can then not be used without resorting to numerical approximations which are often computationally expensive. We propose here a new objective function for the estimation of both normalized and unnormalized models. The basic idea is to perform nonlinear logistic regression to discriminate between the observed data and some artificially generated noise. With this approach, the normalizing partition function can be estimated like any other parameter. We prove that the new estimation method leads to a consistent (convergent) estimator of the parameters. For large noise sample sizes, the new estimator is furthermore shown to behave like the maximum likelihood estimator. In the estimation of unnormalized models, there is a trade-off between statistical and computational performance. We show that the new method strikes a competitive trade-off in comparison to other estimation methods for unnormalized models. As an application to real data, we estimate novel two-layer models of natural image statistics with spline nonlinearities.
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708.
半面阳光
(2023-02-28 14:45):
#paper https://doi.org/10.1016/j.gim.2022.11.004 Genetics in Medicine, 2023, Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). ACMG在2022年12月发表了最新版的NIPT应用指南。这个版本的指南是对2016版指南的更新。这次更新过程中,ACMG的NIPS专项小组采用系统性综述和GRADE“证据到决策”框架等分析评估方法,对NIPS用于一般风险人群的各项参数进行了评估,形成了6条主要应用性建议。相较于传统的筛查方法,NIPS在21、18和13三体的筛查性检测中,无论单胎妊娠还是双胎妊娠,都展现了其优越性。ACMG给出明确意见,建议一般风险人群采用NIPS进行21、18和13三体的筛查,以替代传统筛查手段。同时明确指出,建议使用NIPS来筛查胎儿性染色体非整倍体异常。除了这几条给出“强烈建议”的意见之外,指南还对NIPS用于小片段缺失以及其他类型CNVs的检测给出了指导性建议。
IF:6.600Q1
Genetics in medicine : official journal of the American College of Medical Genetics,
2023-02.
DOI: 10.1016/j.gim.2022.11.004
PMID: 36524989
Abstract:
PURPOSE: This workgroup aimed to develop an evidence-based clinical practice guideline for the use of noninvasive prenatal screening (NIPS) for pregnant individuals at general risk for fetal trisomy 21, trisomy …
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PURPOSE: This workgroup aimed to develop an evidence-based clinical practice guideline for the use of noninvasive prenatal screening (NIPS) for pregnant individuals at general risk for fetal trisomy 21, trisomy 18, or trisomy 13 and to evaluate the utility of NIPS for other chromosomal disorders.METHODS: The NIPS Evidence-Based Guideline Work Group (n = 7) relied on the results from the recent American College of Medical Genetics and Genomics (ACMG) systematic review to form the evidentiary basis of this guideline. Workgroup members used the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework to draft recommendations. The guideline underwent extensive internal and external peer review with a public comment period before approval by the ACMG Board of Directors.RESULTS: Evidence consistently demonstrated improved accuracy of NIPS compared with traditional screening methods for trisomies 21, 18, and 13 in singleton and twin gestations. Identification of rare autosomal trisomies and other microdeletion syndromes with NIPS is an emerging area of interest.CONCLUSION: ACMG strongly recommends NIPS over traditional screening methods for all pregnant patients with singleton and twin gestations for fetal trisomies 21, 18, and 13 and strongly recommends NIPS be offered to patients to screen for fetal sex chromosome aneuploidy.
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709.
姗姗来迟
(2023-02-27 21:25):
#paper
https://openaccess.thecvf.com/content_CVPR_2019/html/Tang_Learning_to_Compose_Dynamic_Tree_Structures_for_Visual_Contexts_CVPR_2019_paper.html
title:为视觉上下文组成动态树结构的学习
提出,将图像中的objects放置到视觉上下文中,组成动态树结构,帮助场景图生成和视觉问答等视觉推理任务。该可视化上下文树模型,称为VCTREE,有两个关键优势:
1)高效且富有表现力的二叉树编码了对象之间固有的并行/层次关系;
2)动态结构从图像到图像,从任务到任务,允许更多内容/任务特定的消息传递。
CVPR 2019,
2018.
DOI: 10.48550/arXiv.1812.01880
Abstract:
We propose to compose dynamic tree structures that place the objects in an image into a visual context, helping visual reasoning tasks such as scene graph generation and visual Q&A. …
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We propose to compose dynamic tree structures that place the objects in an image into a visual context, helping visual reasoning tasks such as scene graph generation and visual Q&A. Our visual context tree model, dubbed VCTree, has two key advantages over existing structured object representations including chains and fully-connected graphs: 1) The efficient and expressive binary tree encodes the inherent parallel/hierarchical relationships among objects, e.g., "clothes" and "pants" are usually co-occur and belong to "person"; 2) the dynamic structure varies from image to image and task to task, allowing more content-/task-specific message passing among objects. To construct a VCTree, we design a score function that calculates the task-dependent validity between each object pair, and the tree is the binary version of the maximum spanning tree from the score matrix. Then, visual contexts are encoded by bidirectional TreeLSTM and decoded by task-specific models. We develop a hybrid learning procedure which integrates end-task supervised learning and the tree structure reinforcement learning, where the former's evaluation result serves as a self-critic for the latter's structure exploration. Experimental results on two benchmarks, which require reasoning over contexts: Visual Genome for scene graph generation and VQA2.0 for visual Q&A, show that VCTree outperforms state-of-the-art results while discovering interpretable visual context structures.
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710.
Spring
(2023-02-27 21:24):
#paper
Metabolically (un)healthy obesity and risk of obesity-related cancers: a pooled study
合并研究:新陈代谢(非)健康的肥胖和与肥胖有关的癌症风险
10.1093/jnci/djad008
基于超79万名欧洲人BMI和代谢评分(通过血压、血糖和甘油三酯定义),评估代谢处于异常或正常的人群与癌症风险间的关联;
相比代谢健康体重正常者,代谢异常的肥胖人群患肥胖相关癌症、结直肠癌、胆囊癌等风险增加,子宫内膜癌、肝癌和肾细胞癌的风险最高;
代谢健康的肥胖人群患肥胖相关癌症、男性结肠癌、子宫内膜癌和胆囊癌等风险增加,尽管风险关系较弱;
BMI和代谢健康状况叠加会增加肥胖相关癌症、直肠癌及子宫内膜癌等风险。
Abstract:
BACKGROUND: Studies of obesity with or without metabolic aberrations, commonly termed metabolically unhealthy or healthy obesity, in relation to cancer risk are scarce.METHODS: We investigated body mass index (normal weight, …
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BACKGROUND: Studies of obesity with or without metabolic aberrations, commonly termed metabolically unhealthy or healthy obesity, in relation to cancer risk are scarce.METHODS: We investigated body mass index (normal weight, overweight, obesity) jointly and in interaction with metabolic health status in relation to obesity-related cancer risk (n = 23 630) among 797 193 European individuals. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to define metabolically healthy and unhealthy status. Hazard ratios (HRs) and multiplicative interactions were assessed using Cox regression, and additive interactions were assessed using the relative excess risk for interaction. All statistical tests were 2-sided.RESULTS: Metabolically unhealthy obesity, with a baseline prevalence of 7%, was, compared with metabolically healthy normal weight, associated with an increased relative risk of any obesity-related cancer and of colon, rectal, pancreas, endometrial, liver, gallbladder, and renal cell cancer (P < .05), with the highest risk estimates for endometrial, liver, and renal cell cancer (HR = 2.55-3.00). Metabolically healthy obesity showed a higher relative risk for any obesity-related cancer and colon (in men), endometrial, renal cell, liver, and gallbladder cancer, though the risk relationships were weaker. There were no multiplicative interactions, but there were additive, positive interactions between body mass index and metabolic health status on obesity-related and rectal cancer among men and on endometrial cancer (P < .05).CONCLUSIONS: This study highlights that the type of metabolic obesity phenotype is important when assessing obesity-related cancer risk. In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention.
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711.
颜林林
(2023-02-27 21:12):
#paper doi:10.3390/ijms24043588 International Journal of Molecular Sciences, 2023, A DNA Finite-State Machine Based on the Programmable Allosteric Strategy of DNAzyme. 本研究利用核酶(一种具有特定序列和构象的DNA分子,本身具有切割特定核酸片段的催化能力)的特性,构建了一个具有不同状态的纳米机器体系,通过加入不同的核酸分子(作为输入),使体系中发生链置换反应,从而使人工设计的核酶分子,可逆地改变为不同状态,并通过切割报告核酸分子输出荧光信号进行确认,从实验上验证了用DNA分子实现有限状态机的可行性。除了实时监测反应体系的荧光信号外,本研究也通过电泳对体系中存在的各个核酸分子进行了确认。本研究分别实现了两状态和五状态的有限状态机,从概念上验证了,可以通过增加不同序列的核酸分子,实现状态机的状态数量扩展,可据此进一步研发更复杂的DNA纳米分子机器。
IF:4.900Q2
International journal of molecular sciences,
2023-Feb-10.
DOI: 10.3390/ijms24043588
PMID: 36834996
Abstract:
Living organisms can produce corresponding functions by responding to external and internal stimuli, and this irritability plays a pivotal role in nature. Inspired by such natural temporal responses, the development …
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Living organisms can produce corresponding functions by responding to external and internal stimuli, and this irritability plays a pivotal role in nature. Inspired by such natural temporal responses, the development and design of nanodevices with the ability to process time-related information could facilitate the development of molecular information processing systems. Here, we proposed a DNA finite-state machine that can dynamically respond to sequential stimuli signals. To build this state machine, a programmable allosteric strategy of DNAzyme was developed. This strategy performs the programmable control of DNAzyme conformation using a reconfigurable DNA hairpin. Based on this strategy, we first implemented a finite-state machine with two states. Through the modular design of the strategy, we further realized the finite-state machine with five states. The DNA finite-state machine endows molecular information systems with the ability of reversible logic control and order detection, which can be extended to more complex DNA computing and nanomachines to promote the development of dynamic nanotechnology.
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712.
钟鸣
(2023-02-27 19:18):
#paper doi:10.3389/fvets.2020.00388 Assisting Decision-Making on Age of Neutering for 35 Breeds of Dogs: Associated Joint Disorders, Cancers, and Urinary Incontinence
这是一篇有关犬的最佳绝育年龄的循证研究。此前已经发现,绝育会增加犬罹患关节疾病和癌症的风险,无论性别是雌性或雄性。绝育时的年龄也同样会影响到这些疾病的发生,但由于不同品种间犬的体格和遗传背景相差很大,因此作者团队对包括柯基、贵宾、比格、金毛、德牧在内的共35个品种的犬的绝育年龄与健康状况做了调查,样本主要来源于作者所在的动物医院。作者详细报告了每个品种犬的关节疾病与肿瘤疾病患病风险增加与绝育年龄或性别的相关性,总的来说不同品种有相应的最佳绝育年龄,甚至同一品种的不同性别个体也有不同的最佳绝育年龄。但这篇研究中没有涉及到不同品种杂交犬的最佳绝育年龄。
Abstract:
Neutering (including spaying) of male and female dogs in the first year after birth has become routine in the U.S. and much of Europe, but recent research reveals that for …
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Neutering (including spaying) of male and female dogs in the first year after birth has become routine in the U.S. and much of Europe, but recent research reveals that for some dog breeds, neutering may be associated with increased risks of debilitating joint disorders and some cancers, complicating pet owners' decisions on neutering. The joint disorders include hip dysplasia, cranial cruciate ligament tear or rupture, and elbow dysplasia. The cancers include lymphoma, mast cell tumor, hemangiosarcoma, and osteosarcoma. In previous studies on the Golden Retriever, Labrador Retriever and German Shepherd Dog, neutering before a year of age was associated with increased risks of one or more joint disorders, 2-4 times that of intact dogs. The increase was particularly seen with dogs neutered by 6 months of age. In female Golden Retrievers, there was an increase in one or more of the cancers followed to about 2-4 times that of intact females with neutering at any age. The goal of the present study was to expand and use the same data collection and analyses to cover an additional 29 breeds, plus three varieties of Poodles. There were major breed differences in vulnerability to neutering, both with regard to joint disorders and cancers. In most cases, the caregiver can choose the age of neutering without increasing the risks of these joint disorders or cancers. Small-dog breeds seemed to have no increased risks of joint disorders associated with neutering, and in only two small breeds (Boston Terrier and Shih Tzu) was there a significant increase in cancers. To assist pet owners and veterinarians in deciding on the age of neutering a specific dog, guidelines that avoid increasing the risks of a dog acquiring these joint disorders or cancers are laid out for neutering ages on a breed-by-breed and sex basis.
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713.
徐炳祥
(2023-02-27 14:05):
#paper doi: 10.1186/gb-2012-13-10-r98, 2012, CHANCE: comprehensive software for quality control and validation of ChIP-seq data。ChIP-seq是目前解析特定蛋白质在基因组上结合位点的最流行高通量方法,也是表观遗传学中的常用技术。这篇旧文回顾了ChIP-seq中常见的实验误差,包括抗体的活性,免疫共沉淀反应的效率,PCR反应引起的偏倚,文库制备和测序过程引入的误差等。并针对每一项给出了可行的评估策略,其附带工具对ChIP-seq文库的质量检查和失败文库的归因等工作都是有益的。
Abstract:
ChIP-seq is a powerful method for obtaining genome-wide maps of protein-DNA interactions and epigenetic modifications. CHANCE (CHip-seq ANalytics and Confidence Estimation) is a standalone package for ChIP-seq quality control and …
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ChIP-seq is a powerful method for obtaining genome-wide maps of protein-DNA interactions and epigenetic modifications. CHANCE (CHip-seq ANalytics and Confidence Estimation) is a standalone package for ChIP-seq quality control and protocol optimization. Our user-friendly graphical software quickly estimates the strength and quality of immunoprecipitations, identifies biases, compares the user's data with ENCODE's large collection of published datasets, performs multi-sample normalization, checks against quantitative PCR-validated control regions, and produces informative graphical reports. CHANCE is available at https://github.com/songlab/chance.
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714.
笑对人生
(2023-02-26 23:52):
#paper doi: 10.1016/j.cell.2017.10.001. Epub 2017 Oct 26. McGranahan N, et al. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution. Cell. 2017 Nov 30;171(6):1259-1271.e11.
背景:CD8+ T细胞在机体内的杀伤肿瘤的免疫应答起到至关重要的作用。肿瘤细胞表面的肿瘤抗原并不能直接激活CD8+ T细胞,而必须经抗原提呈细胞(APC)摄入后加工成短肽,并通过表面的MHC-I类分子呈递至CD8+ T细胞。因此,MHC-抗原肽-TCR复合物的形成是CD8+ T细胞激活肿瘤免疫杀伤的关键一步(后续还需要有共刺激分子提供的第二信号,例如CD28)。人类组织相容性复合体(major histocompatibility complex,MHC)是一组编码动物主要组织相容性抗原基因群的统称。人类白细胞抗原(human leucocyte antigen,HLA)是MHC的表达产物。HLA I类分子存在于所有有核细胞(含血小板和网织红细胞)表面。过去的研究表明,HLA的杂合性缺失(loss of heterozygosity in human leukocyte antigen ,LOHHLA)会影响T细胞的肿瘤抗原识别,导致肿瘤免疫逃逸。人体大部分细胞都含有两套HLA分子编码基因,它们分别来自父本和母本,如果HLA发生LOH,则意味着其中一套的编码基因可能发生完全或部分丢失。每个人的基因组包含多达6种不同HLA I类分子的等位基因,它们由三个基因(HLA-A,HLA-B和HLA-C)编码,位于6号染色体上。
研究内容:本研究开发一个基于高通量测序数据,专门计算HLA等位基因拷贝数变化,用于发现HLA的LOH的计算工具,名为LOHHLA。LOHHLA的主要分析流程包括:(1)从来自肿瘤和正常对照的样本的bam文件中提取HLA区域的reads,并转换成fastq文件。(2)将提取的reads重新比对到多个HLA等位基因区域,利用OptiType或Polysolver进行HLA分型。利用samtools计算mpileup,每一个比对位点的覆盖深度。(3)根据每个位点的测序深度的不同,确定同源HLA等位基因的多态性位点(call SNP)。(4)获取HLA等位基因区域的logR(tumor/normal coverage ratio,肿瘤组织和正常组织深度的比值)和BAF(类似VAF,对于每个多态性位点,HLA allele 1深度/(HLA allel1深度+HLA allel2))。(5)在考虑肿瘤纯度和倍性的情况下,对每个HLA基因计算HLA等位基因拷贝数变化。
本文应用该工具,在来自TRACERx队列的90位早期非小细胞肺癌(NSCLCs)患者中,发现40%(36/90)的患者存在HLA的LOH。进一步地,这些HLA的LOH与亚克隆新抗原负荷升高、APOBEC介导的体细胞突变产生、毒性T细胞活性增加以及肿瘤PD-L1表达阳性相关。
Abstract:
Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus …
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Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. VIDEO ABSTRACT.
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715.
李翛然
(2023-02-26 22:56):
#paper Klippel-Feil Syndrome: Pathogenesis, Diagnosis, and Management doi: 10.1093/eurheartj/ehab424 这篇文章主要讲了先天性脊柱畸形 klippel-feil综合症一些活跃突变和关键性信号通路的研究。 与一般的假设不同,传统普遍认为先天性脊柱畸形一般都是与脊柱神经系统相关的调控基因有关。但实际上,从Kippel-feil综合症,患者同样具有其他疾病的显著特征。 带来一些新的思路
Abstract:
AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing …
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AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies.METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation.CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.
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716.
姗姗来迟
(2023-02-16 20:44):
#paper https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4247187 Hierarchical Reasoning Based on Perception Action Cycle for Visual Question Answering
- 受PAC机制的启发,设计了HIPA。HIPA遵循一种分层模式,通过对两种模态使用注意力模块来独立地解释视觉和语言特征,然后将聚合的特征传递到推理循环中。
- 受人类感知心理过程的启发,HIPA提出将视觉理解分为注意、组织和理解三个阶段。视觉理解的划分促进了对视觉特征的框架理解。
- 使用余弦相似度和曼哈顿距离的标准差作为视觉和语言特征的评价指标。
SSRN Electronic Journal,
2022.
DOI: 10.2139/ssrn.4247187
Abstract:
Recent visual question answering (VQA) frameworks employ different combinations of attention techniques to derive a correct answer. Attention techniques in vision-language tasks have mostly achieved success through the improvement of …
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Recent visual question answering (VQA) frameworks employ different combinations of attention techniques to derive a correct answer. Attention techniques in vision-language tasks have mostly achieved success through the improvement of local features for both modalities. Attention as a concept is heavily established by human cognition mechanism. Different combinations of attention techniques are not well proven as a means of human cognition. Neural networks were originally inspired by the structure of the human brain. Many researchers have recently resorted to frameworks that resemble the human brain, and their models have achieved high performance. To this end, we aim to consider a framework that utilizes human biological and psychological concepts to achieve a good understanding of vision and language modalities. In this view, we introduce a hierarchical reasoning based on a perception action cycle (HIPA) framework to tackle VQA tasks. It integrates the reasoning process of multi-modalities with the perception action cycle (PAC), which explains the learning mechanism of humans about the surrounding world. It comprehends the visual modality through three phases of reasoning: object-level attention, organization, and interpretation. It comprehends the language modality through word-level attention, interpretation, and conditioning. Subsequently, vision and language modalities are interpreted dependently in a cyclic and hierarchical way throughout the entire framework. For further assessment of the visual and language features, we argue that image-question pairs of the same answer ought to have similar visual and language features eventually. As a result, we conduct visual and language feature evaluation experiments using metrics such as standard deviation of cosine similarity and Manhattan distance. We show that employing PAC in our framework improves the standard deviation compared with other VQA frameworks. For further assessment, we also test the novel proposed HIPA on the visual relationship detection (VRD) tasks. The proposed method achieves the state-of-the-art results on the TDIUC and VRD datasets and obtains competitive results on the VQA 2.0 dataset.
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717.
张德祥
(2023-02-10 20:03):
#paper https://doi.org/10.48550/arXiv.2210.15889 Towards Data-and Knowledge-Driven Artificial Intelligence: A Survey on Neuro-Symbolic Computing 神经符号计算 (NeSy) 追求认知的符号和统计范式的整合,多年来一直是人工智能 (AI) 的活跃研究领域。由于 NeSy 有望调和符号表示的推理和可解释性优势以及神经网络中的稳健学习,它可能会成为下一代 AI 的催化剂。在本文中,我们系统地概述了 NeSy AI 研究的重要和最新进展。首先,我们介绍了这一领域的研究历史,涵盖了早期的工作和基础。我们进一步讨论背景概念并确定 NeSy 发展背后的关键驱动因素。之后,我们根据强调该研究范式的几个主要特征对最近具有里程碑意义的方法进行了分类,包括神经符号整合、知识表示、知识嵌入和功能。然后,我们简要讨论现代 NeSy 方法在几个领域的成功应用。最后,我们确定了未解决的问题以及潜在的未来研究方向。这项调查有望帮助新的研究人员进入这个快速发展的领域,并加速向数据和知识驱动的 AI 迈进。
arXiv,
2022.
DOI: 10.48550/arXiv.2210.15889
Abstract:
Neural-symbolic computing (NeSy), which pursues the integration of the symbolic and statistical paradigms of cognition, has been an active research area of Artificial Intelligence (AI) for many years. As NeSy …
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Neural-symbolic computing (NeSy), which pursues the integration of the symbolic and statistical paradigms of cognition, has been an active research area of Artificial Intelligence (AI) for many years. As NeSy shows promise of reconciling the advantages of reasoning and interpretability of symbolic representation and robust learning in neural networks, it may serve as a catalyst for the next generation of AI. In the present paper, we provide a systematic overview of the important and recent developments of research on NeSy AI. Firstly, we introduce study history of this area, covering early work and foundations. We further discuss background concepts and identify key driving factors behind the development of NeSy. Afterward, we categorize recent landmark approaches along several main characteristics that underline this research paradigm, including neural-symbolic integration, knowledge representation, knowledge embedding, and functionality. Then, we briefly discuss the successful application of modern NeSy approaches in several domains. Finally, we identify the open problems together with potential future research directions. This survey is expected to help new researchers enter this rapidly-developing field and accelerate progress towards data-and knowledge-driven AI.
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718.
龙海晨
(2023-02-05 17:58):
#paper Feng H, Cao B, Peng X, Wei Q. Cancer-associated fibroblasts strengthen cell proliferation and EGFR TKIs resistance through aryl hydrocarbon receptor dependent signals in non-small cell lung cancer. BMC Cancer. 2022 Jul 13;22(1):764. doi: 10.1186/s12885-022-09877-7. PMID: 35831824; PMCID: PMC9281029.文章属于研究肿瘤的领域。进一步描述了CAF在癌症EGFR-TKIs耐药性发展中的作用。阐述了CAF与EGFR TKIs耐药相关的潜在机制,其依赖于Kyn/AhR/AKT/ERK信号通路。阻断AhR可有效改善EGFR TKIs的结果,为临床治疗癌症提供了一种新的策略。
Abstract:
The tumor microenvironment is a dynamic cellular milieu that interacts with cancer cells and promotes tumor progression and metastasis. However, the specific mechanisms by which the tumor microenvironment impacts cancer …
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The tumor microenvironment is a dynamic cellular milieu that interacts with cancer cells and promotes tumor progression and metastasis. However, the specific mechanisms by which the tumor microenvironment impacts cancer cells' behaviors remain poorly understood. In this study, enriched cancer-associated fibroblasts (CAFs) were observed in tumor tissues isolated from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) resistant non-small cell lung cancer (NSCLC) patients. CAFs isolated from tumor tissues were capable of producing tryptophan metabolite kynurenine (Kyn), which significantly increased the proliferation and EGFR TKIs resistance of NSCLC cells. In this study, it was further observed that the activation of tryptophan 2,3-dioxygenase (TDO) in CAFs, resulted in the enhanced capability of tryptophan metabolism in them compared to normal fibroblasts. As a result, Kyn produced by CAFs facilitated the up-regulation of Aryl Hydrocarbon Receptor (AhR) signals in NSCLC, thereby resulting in the downstream ATK and ERK signaling pathways activation. Finally, inhibition of AhR signals efficiently prevented tumor growth and development of EGFR TKIs resistance, eventually improved the outcome of EGFR TKIs, and described a promising therapeutic strategy for NSCLC.
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719.
DeDe宝
(2023-02-01 00:18):
#paper https://doi.org/10.1016/j.neuroimage.2021.118723. NeuroImage 2018. Structural connectivity-based segmentation of the human entorhinal cortex
在啮齿动物中,将内嗅皮层分割为内侧(MEC)与外侧(LEC)具有明确的定义和特征。然而,在人类中,MEC和LEC的对应确切位置却仍然不确定。之前功能性磁共振成像 (fMRI) 研究已将人类内嗅皮层细分为后内侧 (pmEC) 和前外侧 (alEC)部分,但是成像方式和种子区域(seed)对划分结果的影响仍不明确。本研究使用扩散张量成像(DTI) 和概率纤维束成像,根据与已知选择性投射到的其他大脑区域的差异连接来分割人类内嗅皮层的MEC和LEC。我们将 MEC定义为与前下托和压后皮层(RSC) 的联系更紧密的内嗅皮层,LEC定义为与远端 CA1、近端dCA1pSub)以及外侧眶额叶皮层(OFC) 的联系更紧密的内嗅皮层。尽管我们的DTI分割比之前的 fMRI 研究具有更大的内侧-外侧成分,但我们的结果表明人类 MEC 和 LEC 同系物具有朝向后-前和内侧-外侧轴的边界,支持 pmEC 后内侧 (pmEC) 和前外侧 (alEC)的划分方式。
Abstract:
The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional …
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The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posteromedial (pmEC) and anterolateral (alEC) parts, but uncertainty remains about the choice of imaging modality and seed regions, in particular in light of a substantial revision of the classical model of EC connectivity based on novel insights from rodent anatomy. Here, we used structural, not functional imaging, namely diffusion tensor imaging (DTI) and probabilistic tractography to segment the human EC based on differential connectivity to other brain regions known to project selectively to MEC or LEC. We defined MEC as more strongly connected with presubiculum and retrosplenial cortex (RSC), and LEC as more strongly connected with distal CA1 and proximal subiculum (dCA1pSub) and lateral orbitofrontal cortex (OFC). Although our DTI segmentation had a larger medial-lateral component than in the previous fMRI studies, our results show that the human MEC and LEC homologues have a border oriented both towards the posterior-anterior and medial-lateral axes, supporting the differentiation between pmEC and alEC.
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720.
王昊
(2023-01-31 23:53):
#paper Learned Image Compression with Discretized Gaussian Mixture Likelihoods and Attention Modules http://arxiv.org/abs/2001.01568 Zhengxue Cheng, Heming Sun, Masaru Takeuchi, and Jiro Katto. 2020. Learned Image Compression with Discretized Gaussian Mixture Likelihoods and Attention Modules. Retrieved January 31, 2023. VCM图像编码基线方法(cheng2020网络),用于机器视觉编码的特征提取阶段,是图像压缩方法类算法。作者提出使用离散的高斯混合似然来参数化潜在表示的分布,可以获得更准确和灵活的概率模型。此外,作者还使用attention module来提高网络对图像中复杂区域的关注能力。具体地,作者提出使用离散高斯混合模型来对latent representation进行熵估计,这样可以对y提供多个最可能的均值,而每一个mixture的方差可以更小,达到的效果是实现更准确的概率模型,节约编码y所需要的比特数。第二,作者还加入了简化版的attention modules,可以提高网络对于non-zero responses,即复杂区域的关注,同时不引入过多的训练复杂度。
arXiv,
2020.
Abstract:
Image compression is a fundamental research field and many well-known compression standards have been developed for many decades. Recently, learned compression methods exhibit a fast development trend with promising results. …
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Image compression is a fundamental research field and many well-known compression standards have been developed for many decades. Recently, learned compression methods exhibit a fast development trend with promising results. However, there is still a performance gap between learned compression algorithms and reigning compression standards, especially in terms of widely used PSNR metric. In this paper, we explore the remaining redundancy of recent learned compression algorithms. We have found accurate entropy models for rate estimation largely affect the optimization of network parameters and thus affect the rate-distortion performance. Therefore, in this paper, we propose to use discretized Gaussian Mixture Likelihoods to parameterize the distributions of latent codes, which can achieve a more accurate and flexible entropy model. Besides, we take advantage of recent attention modules and incorporate them into network architecture to enhance the performance. Experimental results demonstrate our proposed method achieves a state-of-the-art performance compared to existing learned compression methods on both Kodak and high-resolution datasets. To our knowledge our approach is the first work to achieve comparable performance with latest compression standard Versatile Video Coding (VVC) regarding PSNR. More importantly, our approach generates more visually pleasant results when optimized by MS-SSIM. This project page is at this https URL this https URL
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