CRF

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  • 文章类型: Journal Article
    不适应可塑性与疼痛等疾病的慢性化有关,但是从急性疼痛到慢性疼痛的转变在机制上还没有得到很好的理解。杏仁核中央核(CeA)的神经可塑性已成为损伤引起的疼痛的感觉和情感方面的机制,尽管证据来自几乎仅在急性疼痛条件下进行的研究,并且对细胞类型特异性不了解。这里,我们报道了神经性疼痛中基因不同和投射特异性CeA神经元的时间依赖性变化.急性期CRF投射神经元的过度兴奋和臂旁(PB)输入的突触可塑性转变为慢性期非CRF神经元无突触可塑性的过度兴奋。因此,PB→CeA途径的化学遗传抑制减轻了急性疼痛相关行为,但不是慢性的,神经性疼痛。神经可塑性的细胞类型特异性时间变化为临床观察提供了神经生物学证据,即慢性疼痛不仅仅是急性疼痛的长期持续存在。
    Maladaptive plasticity is linked to the chronification of diseases such as pain, but the transition from acute to chronic pain is not well understood mechanistically. Neuroplasticity in the central nucleus of the amygdala (CeA) has emerged as a mechanism for sensory and emotional-affective aspects of injury-induced pain, although evidence comes from studies conducted almost exclusively in acute pain conditions and agnostic to cell type specificity. Here, we report time-dependent changes in genetically distinct and projection-specific CeA neurons in neuropathic pain. Hyperexcitability of CRF projection neurons and synaptic plasticity of parabrachial (PB) input at the acute stage shifted to hyperexcitability without synaptic plasticity in non-CRF neurons at the chronic phase. Accordingly, chemogenetic inhibition of the PB→CeA pathway mitigated pain-related behaviors in acute, but not chronic, neuropathic pain. Cell-type-specific temporal changes in neuroplasticity provide neurobiological evidence for the clinical observation that chronic pain is not simply the prolonged persistence of acute pain.
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  • 文章类型: Journal Article
    中胚层奖励制度与社会关系的晋升和奖励利益有关。在社会一夫一妻制的草原田鼠(Microtusochogaster)中,配对键的建立可以通过对育种伴侣的强烈偏好和对不熟悉的物种的积极排斥来显示。中脑边缘多巴胺信号通过伏隔核中的多巴胺传递和受体活性影响田鼠内键相关行为。然而,只有一个实验研究了腹侧被盖区(VTA),一个产生大量前脑和中脑多巴胺的区域,调节这些社会行为。具体来说,在短暂的求偶过程中,VTA中谷氨酸或GABA神经元的抑制促进了雄性草原田鼠的伴侣偏好形成。VTA是一种含有多巴胺的异质结构,GABA,和谷氨酸神经元以及接受各种投射,包括促肾上腺皮质激素释放因子(CRF),建议调节多巴胺释放。
    我们使用药理学操作来检查VTA中的GABA和CRF信号如何调节雄性和雌性草原田鼠的伴侣偏好形成。具体来说,我们使用了3小时的伴侣偏好测试,社会选择测试,为了评估在1小时同居期间输注双瓜碱和CRF后伴侣偏好的形成,以及CRFR1拮抗剂muscimol和CP154526,在与异性同居的24小时内。
    我们的研究表明,GABAA受体拮抗剂,VTA中的CRF提倡合作伙伴偏好,而低剂量的麝香酚,GABAA受体激动剂,和CP154526,一种CRFR1拮抗剂,抑制了雄性和雌性草原田鼠的伴侣偏好。
    这项研究表明,GABA和CRF输入到VTA中对于在雄性和雌性草原田鼠中形成伴侣偏好是必要的。
    UNASSIGNED: The mesolimbic reward system is associated with the promotion and rewarding benefits of social relationships. In the socially monogamous prairie vole (Microtus ochrogaster), the establishment of a pair bond can be displayed by a robust preference for a breeding partner and aggressive rejection of unfamiliar conspecifics. Mesolimbic dopamine signaling influences bond-related behaviors within the vole through dopamine transmission and receptor activity in the nucleus accumbens. However, only one experiment has examined how the ventral tegmental area (VTA), a region that produces much of the fore- and mid-brain dopamine, regulates these social behaviors. Specifically, inhibition of either glutamate or GABA neurons in the VTA during a brief courtship promoted a partner preference formation in male prairie voles. The VTA is a heterogeneous structure that contains dopamine, GABA, and glutamate neurons as well as receives a variety of projections including corticotropin-releasing factor (CRF) suggested to modulate dopamine release.
    UNASSIGNED: We used pharmacological manipulation to examine how GABA and CRF signaling in the VTA modulate partner preference formation in male and female prairie voles. Specifically, we used a 3 h partner preference test, a social choice test, to assess the formation of a partner preference following an infused bicuculline and CRF during a 1 h cohabitation and muscimol and CP154526, a CRFR1 antagonist, during a 24 h cohabitation with an opposite-sex conspecific.
    UNASSIGNED: Our study demonstrated that bicuculline, a GABA A receptor antagonist, and CRF in the VTA promoted a partner preference, whereas low-dose muscimol, a GABA A receptor agonist, and CP154526, a CRFR1 antagonist, inhibited a partner preference in both male and female prairie voles.
    UNASSIGNED: This study demonstrated that GABA and CRF inputs into the VTA is necessary for the formation of a partner preference in male and female prairie voles.
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  • 文章类型: Journal Article
    食用菌种类的多样性和真菌学知识的程度对研究提出了重大挑战,耕种,和食用菌的普及。为了应对这一挑战,迫切需要一种快速准确的获取相关信息的方法。问答(Q&A)系统的出现有可能解决此问题。命名实体识别(NER)为构建食用菌智能问答系统提供了基础。在食用菌领域,缺乏适用于NER的公开中文语料库,和传统方法难以在NER过程中捕获长距离依赖。
    本文描述了食用菌领域中文语料库的建立,并介绍了一种基于XLNet和条件随机场(CRF)的食用菌信息NER方法。我们的方法将迭代扩张卷积神经网络(IDCNN)与CRF相结合。首先,利用XLNet模型作为基础,引入了IDCNN层。该层通过扩展卷积内核的接收场来解决跨话语捕获特征的有限容量。IDCNN层的输出被输入到CRF层,这减轻了任何标签逻辑错误,从而为与食用菌有关的NER任务提供了全球最佳标签。
    实验结果表明,所提出的模型达到的精度达到0.971,召回率为0.986,F1-得分为0.979。
    所提出的模型在这些评估指标方面优于现有方法,有效识别与食用菌信息相关的实体,为知识图谱的构建提供方法论支持。
    UNASSIGNED: The diversity of edible fungus species and the extent of mycological knowledge pose significant challenges to the research, cultivation, and popularization of edible fungus. To tackle this challenge, there is an urgent need for a rapid and accurate method of acquiring relevant information. The emergence of question and answer (Q&A) systems has the potential to solve this problem. Named entity recognition (NER) provides the basis for building an intelligent Q&A system for edible fungus. In the field of edible fungus, there is a lack of a publicly available Chinese corpus suitable for use in NER, and conventional methods struggle to capture long-distance dependencies in the NER process.
    UNASSIGNED: This paper describes the establishment of a Chinese corpus in the field of edible fungus and introduces an NER method for edible fungus information based on XLNet and conditional random fields (CRFs). Our approach combines an iterated dilated convolutional neural network (IDCNN) with a CRF. First, leveraging the XLNet model as the foundation, an IDCNN layer is introduced. This layer addresses the limited capacity to capture features across utterances by extending the receptive field of the convolutional kernel. The output of the IDCNN layer is input to the CRF layer, which mitigates any labeling logic errors, resulting in the globally optimal labels for the NER task relating to edible fungus.
    UNASSIGNED: Experimental results show that the precision achieved by the proposed model reaches 0.971, with a recall of 0.986 and an F1-score of 0.979.
    UNASSIGNED: The proposed model outperforms existing approaches in terms of these evaluation metrics, effectively recognizing entities related to edible fungus information and offering methodological support for the construction of knowledge graphs.
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  • 文章类型: Journal Article
    HIV-1的特点是由于其高复制率导致了显著的遗传多样性,易错的逆转录酶和重组事件。在乌干达,HIV-1亚型的多样性主要以A亚型为主,D,和A1/D独特重组形式(URFs)。在这项研究中,我们对已知抗逆转录病毒治疗(ART)状态的患者的HIV深层序列进行了分析,以确定亚型,并确定研究人群中流行的耐药突变.在为下一代测序(NGS)处理的187个参与者样本中,137(73%)被成功分类。大多数HIV-1病毒株被归类为A型亚型(75,55%),D(43,31%),与其他亚型,包括C(3,2%),A1/D(9,7%)和CRF10_CD(1,<1%)。9个完整A1/DHIV基因组的重组分析鉴定了本文所述的新重组模式。此外,我们第一次在乌干达报道,来自维多利亚湖岛捕鱼社区的渔民的HIV-1CRF10_CD菌株。
    HIV-1 is characterized by remarkable genetic diversity resulting from its high replication rate, error-prone reverse transcriptase enzyme and recombination events. In Uganda, HIV-1 subtype diversity is mostly dominated by subtypes A, D, and A1/D Unique Recombinant Forms (URFs). In this study, deep sequences of HIV from patients with known antiretroviral therapy (ART) status were analyzed to determine the subtypes and to identify drug-resistance mutations circulating in the study population. Of the 187 participant samples processed for next-generation sequencing (NGS), 137 (73%) were successfully classified. The majority of HIV-1 strains were classified as subtype A (75, 55%), D (43, 31%), with other subtypes including C (3, 2%), A1/D (9, 7%) and CRF10_CD (1, <1%). Recombinant analysis of nine complete A1/D HIV genomes identified novel recombination patterns described herein. Furthermore, we report for the first time in Uganda, an HIV-1 CRF10_CD strain from a fisherfolk in a Lake Victoria Island fishing community.
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  • 文章类型: Journal Article
    背景:有必要协调和标准化临床研究病例报告表(CRF)中使用的数据变量,以促进在多个临床研究中收集的患者数据的合并和共享。对于专注于传染病的临床研究尤其如此。公共卫生可能高度依赖于这些研究的结果。因此,有一种更高的紧迫性来产生有意义的,可靠的见解,理想情况下基于高样本数量和质量数据。核心数据元素的实施和互操作性标准的合并可以促进统一的临床数据集的创建。
    目的:本研究的目的是比较,协调,并标准化变量,这些变量集中在6项国际传染病临床研究中用作CRF一部分的诊断测试中,最终,然后为正在进行的和未来的研究提供全研究通用数据元素(CDE),以促进跨试验收集数据的互操作性和可比性.
    方法:为了确定CDE,我们回顾并比较了包含在所有6项传染病研究中和所有研究中用于数据收集的CRF的元数据。我们检查了医学系统化命名法-临床术语中国际语义标准代码的可用性,国家癌症研究所词库,和逻辑观察标识符名称和代码系统,用于明确表示构成CDE的诊断测试信息。然后,我们提出了2个数据模型,这些模型结合了已识别的CDE的语义和句法标准。
    结果:在分析范围内考虑的216个变量中,我们确定了11个CDE来描述诊断测试(特别是,血清学和测序)用于传染病:病毒谱系/进化枝;测试日期,type,表演者,和制造商;目标基因;定量和定性结果;和样本标识符,type,和收集日期。
    结论:确定用于感染性疾病的CDE是促进整个临床研究中数据子集的交换和可能合并的第一步(并且,大型研究项目),以进行可能的共享分析,以增加发现的力量。为了互操作性,临床研究数据的协调和标准化路径可以以两种方式铺就。首先,映射到标准术语确保每个数据元素的(变量)定义是明确的,并且它有一个,跨研究的独特解释。第二,这些数据的交换是通过以标准交换格式“包装”来辅助的,如快速医疗保健互操作性资源或临床数据交换标准联盟的临床数据采集标准协调模型。
    It is necessary to harmonize and standardize data variables used in case report forms (CRFs) of clinical studies to facilitate the merging and sharing of the collected patient data across several clinical studies. This is particularly true for clinical studies that focus on infectious diseases. Public health may be highly dependent on the findings of such studies. Hence, there is an elevated urgency to generate meaningful, reliable insights, ideally based on a high sample number and quality data. The implementation of core data elements and the incorporation of interoperability standards can facilitate the creation of harmonized clinical data sets.
    This study\'s objective was to compare, harmonize, and standardize variables focused on diagnostic tests used as part of CRFs in 6 international clinical studies of infectious diseases in order to, ultimately, then make available the panstudy common data elements (CDEs) for ongoing and future studies to foster interoperability and comparability of collected data across trials.
    We reviewed and compared the metadata that comprised the CRFs used for data collection in and across all 6 infectious disease studies under consideration in order to identify CDEs. We examined the availability of international semantic standard codes within the Systemized Nomenclature of Medicine - Clinical Terms, the National Cancer Institute Thesaurus, and the Logical Observation Identifiers Names and Codes system for the unambiguous representation of diagnostic testing information that makes up the CDEs. We then proposed 2 data models that incorporate semantic and syntactic standards for the identified CDEs.
    Of 216 variables that were considered in the scope of the analysis, we identified 11 CDEs to describe diagnostic tests (in particular, serology and sequencing) for infectious diseases: viral lineage/clade; test date, type, performer, and manufacturer; target gene; quantitative and qualitative results; and specimen identifier, type, and collection date.
    The identification of CDEs for infectious diseases is the first step in facilitating the exchange and possible merging of a subset of data across clinical studies (and with that, large research projects) for possible shared analysis to increase the power of findings. The path to harmonization and standardization of clinical study data in the interest of interoperability can be paved in 2 ways. First, a map to standard terminologies ensures that each data element\'s (variable\'s) definition is unambiguous and that it has a single, unique interpretation across studies. Second, the exchange of these data is assisted by \"wrapping\" them in a standard exchange format, such as Fast Health care Interoperability Resources or the Clinical Data Interchange Standards Consortium\'s Clinical Data Acquisition Standards Harmonization Model.
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  • 文章类型: Preprint
    轻度创伤性脑损伤(mTBI)是由于mTBI相关的慢性衰弱性认知和精神病发病率引起的重大健康负担。来自我们实验室的最新证据表明,在皮质下结构的水平上,奖励/动机回路功能可能失调,外侧囊(LHb),我们证明了在青春期后期(〜8周龄)暴露于mTBI损伤的年轻成年雄性小鼠中,mTBI诱导的自我护理修饰行为动机缺陷中过度活跃的LHb的因果作用。在这里,我们通过进一步表征mTBI的这种重复性闭合性颅脑损伤模型对LHb兴奋性的神经行为影响来扩展这一观察。促肾上腺皮质激素释放因子(CRF)对LHb活性的调节,以及动机对自我照顾行为的行为反应,在存在社会或威胁相关刺激的情况下,方法与回避行为。我们表明,mTBI增加了雌性小鼠的LHb自发补品活动,类似于我们先前在雄性小鼠中观察到的活动,并促进了雄性和雌性小鼠的LHb神经元过度兴奋和超极化诱导的LHb爆发。有趣的是,mTBI仅增加雄性小鼠的LHb内在兴奋性,同时具有较高水平的超极化激活的阳离子电流(HCN/Ih),并降低M型钾电流的水平,同时增强M电流而不改变LHb神经元的内在兴奋性。雌性小鼠。由于大脑CRF系统的持续失调被认为有助于慢性精神病发病率,并且LHb神经元对CRF高度反应,然后,我们测试了LHbCRF子系统是否在mTBI之后开始使用。我们发现,在LHb中对CRF受体1型(CRFR1)的体外抑制可使mTBI诱导的LHb补品活性增强和两性的过度兴奋性正常化,表明增强的LHb内CRF-CRFR1介导的信号传导有助于mTBI后的整体LHb过度活跃。行为上,mTBI降低了雌性小鼠和雄性小鼠自我保健修饰的动机。mTBI还通过将先天防御行为转变为更被动的动作锁定而不是逃避行为来改变迫在眉睫的阴影任务中的防御行为,以应对雄性和雌性小鼠的空中威胁,并延长雌性小鼠逃避反应的潜伏期。同时,这种mTBI模型降低了雄性小鼠的社会偏好,在雄性和雌性小鼠的新颖社交遭遇中,它引起了更高的社会新颖性寻求。总的来说,我们的研究为mTBI临床前模型用于调查男女性别中mTBI相关的奖赏回路功能障碍和情绪/动机相关的行为缺陷提供了进一步的翻译效度,同时揭示了该模型的一些性二态神经行为效应,这些效应在青春期后期暴露于这种类型的mTBI损伤时可能对年轻男性和女性产生不同的影响.
    Mild traumatic brain injury (mTBI) is a significant health burden due to mTBI-related chronic debilitating cognitive and psychiatric morbidities. Recent evidence from our laboratory suggests a possible dysregulation within reward/motivational circuit function at the level of a subcortical structure, the lateral habenula (LHb), where we demonstrated a causal role for hyperactive LHb in mTBI-induced motivational deficits in self-care grooming behavior in young adult male mice when exposed to mTBI injury during late adolescence (at ~8 weeks old). Here we extended this observation by further characterizing neurobehavioral effects of this repetitive closed head injury model of mTBI in both young adult male and female mice on LHb excitability, corticotropin releasing factor (CRF) modulation of LHb activity, and behavioral responses of motivation to self-care behavior, and approach versus avoidance behavior in the presence of a social- or threat-related stimulus. We show that mTBI increases LHb spontaneous tonic activity in female mice similar to what we previously observed in male mice as well as promoting LHb neuronal hyperexcitability and hyperpolarization-induced LHb bursting in both male and female mice. Interestingly, mTBI only increases LHb intrinsic excitability in male mice coincident with higher levels of the hyperpolarization-activated cation currents (HCN/Ih) and reduces levels of the M-type potassium currents while potentiating M-currents without altering intrinsic excitability in LHb neurons of female mice. Since persistent dysregulation of brain CRF systems is suggested to contribute to chronic psychiatric morbidities and that LHb neurons are highly responsive to CRF, we then tested whether LHb CRF subsystem becomes engaged following mTBI. We found that in vitro inhibition of CRF receptor type 1 (CRFR1) within the LHb normalizes mTBI-induced enhancement of LHb tonic activity and hyperexcitability in both sexes, suggesting that an augmented intra-LHb CRF-CRFR1-mediated signaling contributes to the overall LHb hyperactivity following mTBI. Behaviorally, mTBI diminishes motivation for self-care grooming in female mice as in male mice. mTBI also alters defensive behaviors in the looming shadow task by shifting the innate defensive behaviors towards more passive action-locking rather than escape behaviors in response to an aerial threat in both male and female mice as well as prolonging the latency to escape responses in female mice. While, this model of mTBI reduces social preference in male mice, it induces higher social novelty seeking during the novel social encounters in both male and female mice. Overall, our study provides further translational validity for the use of this preclinical model of mTBI for investigation of mTBI-related reward circuit dysfunction and mood/motivation-related behavioral deficits in both sexes while uncovering a few sexually dimorphic neurobehavioral effects of this model that may differentially affect young males and females when exposed to this type of mTBI injury during late adolescence.
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  • 文章类型: Journal Article
    针对临床电子病历中因缺少中文注释而导致实体识别性能差的问题,本文提出了一种结合BART融合技术的多医学实体识别方法F-MNER,Bi-LSTM,和CRF。首先,清洗后,编码,分割电子病历,使用双向自回归变换器(BART)模型动态融合所获得的语义表示。然后,使用双向长短期记忆(Bi-LSTM)网络捕获顺序信息。最后,条件随机场(CRF)用于解码和输出多任务实体识别。在CCKS2019数据集上进行了实验,具有microavgPrecision,宏平均召回,加权平均精度达到0.880、0.887和0.883,微平均F1分数,宏平均F1分数,加权平均F1评分分别达到0.875、0.876和0.876。与现有模型相比,我们的方法在三个评估指标(微观平均值,宏观平均值,加权平均)在相同的数据集条件下。在加权平均的情况下,精度,回想一下,F1得分为19.64%,15.67%,分别比现有BERT-BiLSTM-CRF模型高17.58%。使用我们的MF-MNER对实际的临床数据集进行实验,精度,回想一下,在micro-avg评估机制下,F1得分分别为0.638、0.825和0.719。精度,回想一下,在宏观平均评估机制下,F1得分分别为0.685、0.800和0.733。精度,回想一下,在加权平均评估机制下,F1得分分别为0.647、0.825和0.722。以上结果表明,我们的方法MF-MNER可以集成BART的优点,Bi-LSTM,和CRF层,显著提高下游命名实体识别任务的性能,只需少量注释,在召回得分方面取得了出色的表现,具有一定的现实意义。复制本文结果的源代码和数据集可在https://github.com/xfwang1969/MF-MNER获得。
    To address the problem of poor entity recognition performance caused by the lack of Chinese annotation in clinical electronic medical records, this paper proposes a multi-medical entity recognition method F-MNER using a fusion technique combining BART, Bi-LSTM, and CRF. First, after cleaning, encoding, and segmenting the electronic medical records, the obtained semantic representations are dynamically fused using a bidirectional autoregressive transformer (BART) model. Then, sequential information is captured using a bidirectional long short-term memory (Bi-LSTM) network. Finally, the conditional random field (CRF) is used to decode and output multi-task entity recognition. Experiments are performed on the CCKS2019 dataset, with micro avg Precision, macro avg Recall, weighted avg Precision reaching 0.880, 0.887, and 0.883, and micro avg F1-score, macro avg F1-score, weighted avg F1-score reaching 0.875, 0.876, and 0.876 respectively. Compared with existing models, our method outperforms the existing literature in three evaluation metrics (micro average, macro average, weighted average) under the same dataset conditions. In the case of weighted average, the Precision, Recall, and F1-score are 19.64%, 15.67%, and 17.58% higher than the existing BERT-BiLSTM-CRF model respectively. Experiments are performed on the actual clinical dataset with our MF-MNER, the Precision, Recall, and F1-score are 0.638, 0.825, and 0.719 under the micro-avg evaluation mechanism. The Precision, Recall, and F1-score are 0.685, 0.800, and 0.733 under the macro-avg evaluation mechanism. The Precision, Recall, and F1-score are 0.647, 0.825, and 0.722 under the weighted avg evaluation mechanism. The above results show that our method MF-MNER can integrate the advantages of BART, Bi-LSTM, and CRF layers, significantly improving the performance of downstream named entity recognition tasks with a small amount of annotation, and achieving excellent performance in terms of recall score, which has certain practical significance. Source code and datasets to reproduce the results in this paper are available at https://github.com/xfwang1969/MF-MNER .
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  • 文章类型: Journal Article
    卵巢高级别浆液性癌(OHGSC)是世界上最常见的卵巢癌类型。基因组测序已经确定了妇科癌症中染色质重塑因子(CRF)的突变,比如透明细胞癌,子宫内膜样癌和子宫内膜浆液性癌。然而,据我们所知,CRFs和OHGSC之间的关联仍未被探索.本研究旨在探讨OHGSC中CRF功能障碍的临床病理和分子特征。通过多种方法分析了CRF改变,包括对来自癌症基因组图谱(TCGA)的585例卵巢浆液性癌病例的公开下一代测序(NGS)数据的分析,免疫组织化学(IHC),和DNA拷贝数测定,对203例手术切除的OHGSC样本进行了分析。在公共NGS数据集中,最常见的遗传改变是肌动蛋白样蛋白6A(ACTL6A)扩增,达19.5%.Switch/蔗糖不可发酵相关,矩阵关联,染色质亚家族c成员2(SMARCC2)扩增(3.1%)的肌动蛋白依赖性调节因子与总生存期(OS)显着降低有关。此外,染色体结构域-解旋酶-DNA结合蛋白4(CHD4)扩增(5.7%)显示出不利的结果趋势,虽然没有统计学意义。IHC显示ARID1A蛋白表达缺失(2.5%),SMARCA2(2.5%)和SMARCA4(3.9%)。ACTL6A的蛋白表达水平,SMARCC2和CHD4使用H评分进行评估。ACTL6A蛋白表达水平较低的患者OS显著降低。在ACTL6A(66.2%)和SMARCC2(33.5%)中证明了拷贝数增加或基因扩增,CHD4显示浅缺失或深缺失(70.7%)。然而,这些CRF的蛋白质水平没有统计学上的显着差异,在不同的拷贝数改变(CNA)之间。总的来说,OHGSC表现出CNAs和蛋白质丢失,表明CRF中可能的基因改变。此外,ACTL6A蛋白表达水平与不良预后之间存在显著关联.基于这些发现,建议CRFs可以作为OHGSC的预后标志物。
    Ovarian high-grade serous carcinoma (OHGSC) is the most common type of ovarian cancer worldwide. Genome sequencing has identified mutations in chromatin remodeling factors (CRFs) in gynecological cancer, such as clear cell carcinoma, endometrioid carcinoma and endometrial serous carcinoma. However, to the best of our knowledge, the association between CRFs and OHGSC remains unexplored. The present study aimed to investigate the clinicopathological and molecular characteristics of CRF dysfunction in OHGSC. CRF alterations were analyzed through numerous methods, including the analysis of public next-generation sequencing (NGS) data from 585 ovarian serous carcinoma cases from The Cancer Genome Atlas (TCGA), immunohistochemistry (IHC), and DNA copy number assays, which were performed on 203 surgically resected OHGSC samples. In the public NGS dataset, the most frequent genetic alteration was actin-like protein 6A (ACTL6A) amplification at 19.5%. Switch/sucrose non-fermentable related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) amplification (3.1%) was associated with significantly decreased overall survival (OS). In addition, chromodomain-helicase-DNA-binding protein 4 (CHD4) amplification (5.7%) exhibited unfavorable outcome trends, although not statistically significant. IHC revealed the protein expression loss of ARID1A (2.5%), SMARCA2 (2.5%) and SMARCA4 (3.9%). The protein expression levels of ACTL6A, SMARCC2 and CHD4 were evaluated using H-score. Patients with low protein expression levels of ACTL6A showed a significantly decreased OS. Copy number gain or gene amplification was demonstrated in ACTL6A (66.2%) and SMARCC2 (33.5%), while shallow deletion or deep deletion was demonstrated in CHD4 (70.7%). However, there was no statistically significant difference in protein levels of these CRFs, between the different copy number alterations (CNAs). Overall, OHGSC exhibited CNAs and protein loss, indicating possible gene alterations in CRFs. Moreover, there was a significant association between the protein expression levels of ACTL6A and poor prognosis. Based on these findings, it is suggested that CRFs could serve as prognostic markers for OHGSC.
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  • 文章类型: Journal Article
    电力盗窃对分布式电网构成了重大威胁,导致非技术损失(NTL),这可能会严重扰乱电网功能。随着电网向联网用户集中供电,任何未经授权的消耗都会损害电网并危及整体供电质量。在处理大量数据量时,检测这种欺诈行为变得具有挑战性。智能电网通过实现双向电力流动提供解决方案,从而促进检测,分析,并实施新措施解决数据流问题。主要目标是提供基于深度学习的合并模型,以检测电力盗窃并保护智能电网。这项研究引入了一种创新的方法来克服当前窃电检测系统的局限性,主要依赖于分析一维(1-D)电数据。这些方法在识别盗窃实例时通常表现出不足的准确性。为了应对这一挑战,本文提出了一种称为RNN-BiLSTM-CRF模型的集成模型。该模型融合了递归神经网络(RNN)和双向长短期记忆(BiLSTM)架构的优势。值得注意的是,所提出的模型利用了一维(1-D)和二维(2-D)电力消耗数据,从而提高了盗窃检测过程的有效性。实验结果表明,在检测电力盗窃方面,准确率达到93.05%,令人印象深刻。超越该域中现有模型的性能。
    Electricity theft presents a substantial threat to distributed power networks, leading to non-technical losses (NTLs) that can significantly disrupt grid functionality. As power grids supply centralized electricity to connected consumers, any unauthorized consumption can harm the grids and jeopardize overall power supply quality. Detecting such fraudulent behavior becomes challenging when dealing with extensive data volumes. Smart grids provide a solution by enabling two-way electricity flow, thereby facilitating the detection, analysis, and implementation of new measures to address data flow issues. The key objective is to provide a deep learning-based amalgamated model to detect electricity theft and secure the smart grid. This research introduces an innovative approach to overcome the limitations of current electricity theft detection systems, which predominantly rely on analyzing one-dimensional (1-D) electric data. These approaches often exhibit insufficient accuracy when identifying instances of theft. To address this challenge, the article proposes an ensemble model known as the RNN-BiLSTM-CRF model. This model amalgamates the strengths of recurrent neural network (RNN) and bidirectional long short-term memory (BiLSTM) architectures. Notably, the proposed model harnesses both one-dimensional (1-D) and two-dimensional (2-D) electricity consumption data, thereby enhancing the effectiveness of the theft detection process. The experimental results showcase an impressive accuracy rate of 93.05% in detecting electricity theft, surpassing the performance of existing models in this domain.
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  • 文章类型: Journal Article
    心血管疾病和癌症是西方世界死亡的主要原因,并且具有共同的危险因素。降低心肺功能(CRF)是心血管疾病发病率和癌症生存率的主要决定因素。在这篇综述中,我们讨论了癌症引起的实质障碍,细胞,和线粒体功能,这限制了CRF,并可能通过运动训练拮抗和减弱。我们显示了CRF对癌症生存的影响及其对癌症相关治疗的心脏毒性的减弱作用。尚未针对每个肿瘤实体提供量身定制的运动计划,因为在运动处方之前没有进行足够的心肺运动测试(CPET)并且运动方式变化很大的异质人群中进行了几项试验。有新的证据表明,运动可能是癌症治疗的重要支柱,也是减轻心脏毒性治疗效果的工具。我们讨论了有氧运动和阻力训练的方式及其改善癌症患者CRF的潜力,并提供了癌症运动训练周期模型的示例。
    Cardiovascular diseases and cancer are the leading causes of death in the Western world and share common risk factors. Reduced cardiorespiratory fitness (CRF) is a major determinant of cardiovascular morbidity and cancer survival. In this review we discuss cancer- induced disturbances of parenchymal, cellular, and mitochondrial function, which limit CRF and may be antagonized and attenuated through exercise training. We show the impact of CRF on cancer survival and its attenuating effects on cardiotoxicity of cancer-related treatment. Tailored exercise programs are not yet available for each tumor entity as several trials were performed in heterogeneous populations without adequate cardiopulmonary exercise testing (CPET) prior to exercise prescription and with a wide variation of exercise modalities. There is emerging evidence that exercise may be a crucial pillar in cancer treatment and a tool to mitigate cardiotoxic treatment effects. We discuss modalities of aerobic exercise and resistance training and their potential to improve CRF in cancer patients and provide an example of a periodization model for exercise training in cancer.
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