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Mechanical Design of Long-Term Body-Adhered Medical Devices to Maximize On-Body Survival 长期人体粘附医疗器械的机械设计,最大限度地提高人体生存能力
Pub Date : 2021-01-01 DOI: 10.4236/jbise.2021.149028
B. Ferry, J. Abraham
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引用次数: 0
Identification of Novel CDK9 Inhibitors with Better Inhibitory Activity and Higher Selectivity for Cancer Treatment by an Effective Two-Stage Virtual Screening Strategy 通过有效的两阶段虚拟筛选策略鉴定具有更好抑制活性和更高选择性的新型CDK9抑制剂用于癌症治疗
Pub Date : 2021-01-01 DOI: 10.4236/jbise.2021.1412032
Szu-Hung Chen, Yu-Ru Wang, Yih Ho, Shuhua Lin, Hsuan-Liang Liu
The aberrant overexpression of cyclin-dependent kinase 9 (CDK9) in cancer cells results in the loss of proliferative control, making it an attractive therapeutic target for various cancers. However, the highly structural similarity between CDK9 and CDK2 makes the development of novel selective CDK9 inhibitors a challenging task and thus limits their clinical applications. Here, an effective two-stage virtual screening strategy was developed to identify novel CDK9 inhibitors with better inhibitory activity and higher selectivity. The first screening stage aims to select potential compounds with better inhibitory activity than Roniciclib, one of the most effective CDK9 inhibitors, through reliable structure-based phar-macophoric virtual screening and accurate molecular docking analyses. The second stage employs a very detailed visual inspection process, in solvation energy and/or reducing polar solvation energy can significantly improve the binding affinity of these CDK9 inhibitors. Their clinical potentials to serve as anticancer drug candidates can be further evaluated through a series of in vitro/in vivo bioassays in the future. To the best of our knowledge, this is the first attempt to identify novel CDK9 inhibitors with both better inhibitory activity and higher selectivity through an effective two-stage virtual screening strategy.
细胞周期蛋白依赖性激酶9 (CDK9)在癌细胞中的异常过表达导致增殖控制的丧失,使其成为各种癌症的有吸引力的治疗靶点。然而,CDK9和CDK2之间的高度结构相似性使得开发新的选择性CDK9抑制剂成为一项具有挑战性的任务,从而限制了它们的临床应用。本研究开发了一种有效的两阶段虚拟筛选策略,以鉴定具有更好抑制活性和更高选择性的新型CDK9抑制剂。第一阶段筛选旨在通过可靠的基于结构的药理虚筛选和精确的分子对接分析,筛选出比目前最有效的CDK9抑制剂之一Roniciclib具有更好抑制活性的潜在化合物。第二阶段采用非常详细的目视检查过程,在溶剂化能和/或减少极性溶剂化能可以显著提高这些CDK9抑制剂的结合亲和力。它们作为抗癌候选药物的临床潜力可以在未来通过一系列体外/体内生物测定进一步评估。据我们所知,这是首次尝试通过有效的两阶段虚拟筛选策略确定具有更好抑制活性和更高选择性的新型CDK9抑制剂。
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引用次数: 1
In Vitro Susceptibility of Dermatophytes to Anti-Fungal Drugs and Aqueous Acacia nilotica Leaf Extract in Lagos, Nigeria 尼日利亚拉各斯地区皮肤真菌对抗真菌药物和尼罗卡金合欢叶提取物的体外敏感性研究
Pub Date : 2021-01-01 DOI: 10.4236/JBISE.2021.142008
M. Fowora, F. U. Onyeaghasiri, Abdullateef O. Olanlege, I. O. Edu-Muyideen, Olumide Adebesin
Dermatophytes were earlier reported to respond well to anti-fungal agents; however, an upsurge in resistance with the high cost of these agents increased the use of medicinal plants for treatment. This study investigated the sensitivity pattern of dermatophytes to oral anti-fungal drugs and aqueous leaf extract of the plant, Acacia nilotica. The extract was tested against seven strains of dermatophytes Arthroderma otae, Trichophyton interdigitale, Trichophyton mentagrophyte, Microsporum ferrugineum, Arthroderma vespertilii, Arthroderma quadrifidum, and Arthroderma multifidum, previously isolated from diabetic patients. The minimum inhibitory and fungicidal concentrations of the plant extracts and the standard antifungal agents were evaluated using modifications of the broth macro dilution method of the National Committee for Clinical Laboratory Standards M38-A2 protocol. There was a significant difference in the Minimum Inhibitory concentrations (MIC) of the dermatophytes to the three antifungal drugs tested (p Acacia nilotica had an inhibitory effect on all the dermatophytes tested, and showed anti-fungal activity in a dose-dependent relationship between 0.625 - 1.25 mg/ml. Though the inhibitions of the dermatophytes were significantly higher with the standard anti-fungal drugs as compared to the plant extract (p Arthroderma quadrifidum, which was resistant to all the anti-fungal drugs, had the highest inhibition with A. nilotica. Some circulating dermatophyte strains in Nigeria are griseofulvin and/or itraconazole resistant which may influence the spread of infection and A. nilotica aqueous leaf extract showed a strong anti-dermatophytic activity.
早前报道皮肤真菌对抗真菌药物反应良好;然而,由于这些药物价格高昂,耐药性激增,增加了使用药用植物进行治疗。本研究考察了皮肤真菌对口服抗真菌药物和金合欢叶片水提物的敏感性。对从糖尿病患者中分离到的7株皮癣菌进行了抑菌试验,分别为:阔叶节皮菌、趾间毛癣菌、长植毛癣菌、铁小孢子菌、大枯叶节皮菌、四棱节皮菌和多裂节皮菌。采用国家临床实验室标准委员会M38-A2方案的肉汤宏观稀释法进行修改,评估植物提取物和标准抗真菌剂的最低抑菌和杀真菌浓度。三种抗真菌药物对三种皮肤真菌的最低抑菌浓度(MIC)均有抑制作用,且在0.625 ~ 1.25 mg/ml之间呈剂量依赖关系。虽然标准抗真菌药物对皮肤真菌的抑制作用明显高于植物提取物,但对所有抗真菌药物均具有抗性的四节皮草(p Arthroderma quadriidum)对nilotica的抑制作用最高。尼日利亚一些流行的皮肤真菌菌株对灰黄霉素和/或伊曲康唑具有抗性,这可能会影响感染的传播,而尼罗卡草叶水提取物显示出较强的抗皮肤真菌活性。
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引用次数: 4
Expert System for the Diagnosis and Prognosis of Common Dental Diseases Using Bayes Network 基于贝叶斯网络的常见口腔疾病诊断与预后专家系统
Pub Date : 2021-01-01 DOI: 10.4236/jbise.2021.1411031
Grace Tam-Nurseman, Philip Achimugu, Oluwatolani Achimugu, H. Anabi, Sseggujja Husssein
Expert systems are being utilized increasingly in medical fields for the purposes of assisting diagnosis and treatment planning. Existing systems used few symptoms for dental diagnosis. In Dentistry, few symptoms are not enough for diagnosis. In this research, a conditional probability model (Bayes rule) was developed with increased number of symptoms associated with a disease for diagnosis. A test set of recurrent cases was then used to test the diagnostic capacity of the system. The generated diagnosis matched that of the human experts. The system was also tested for its capacity to handle uncommon dental diseases and the system portrayed useful potential.
专家系统越来越多地用于医学领域,以协助诊断和治疗计划。现有的系统很少使用症状进行牙科诊断。在牙科中,很少有症状不足以进行诊断。在本研究中,建立了一个条件概率模型(贝叶斯规则),增加了与疾病相关的症状数量用于诊断。然后使用一组复发病例测试来测试该系统的诊断能力。生成的诊断与人类专家的诊断相匹配。该系统还测试了其处理罕见牙病的能力,并描绘了该系统的有用潜力。
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引用次数: 1
Web Control System for Transcorneal Electric Stimulation Devices 经角膜电刺激装置的网络控制系统
Pub Date : 2021-01-01 DOI: 10.4236/jbise.2021.1412039
Jorge Santiago Amaya, Cristhian Alejandro Romero González, Kevin Alexis Aguilar Bailon
The electrical stimulation systems dedicated to generating unconventional waveforms have been shown to have a positive effect in the treatment of channelopathies, for example, in open-angle glaucoma. However, these signals can be distorted due to different external circumstances, which could lead to counterproductive effects in treatments such as increased intraocular pressure IOP or other effects that are unknown due to poor electrical signaling. In the present work, a web control system capable of communicating with transcorneal electrical stimulation equipment is proposed for the remote control of treatments applied to patients suffering from various ocular channelopathies. As the first phase of this system, it will only focus on treating patients with open-angle glaucoma since this disease is characterized by an increase in IOP and can be immediately measured by an ophthalmologist.
专门用于产生非常规波形的电刺激系统已被证明在治疗通道病变(例如开角型青光眼)方面具有积极作用。然而,这些信号可能由于不同的外部环境而扭曲,这可能导致治疗中的反效果,如眼压升高或其他由于电信号不良而未知的影响。在目前的工作中,提出了一种能够与经角膜电刺激设备通信的网络控制系统,用于远程控制各种眼通道病变患者的治疗。作为该系统的第一阶段,它将只专注于治疗开角型青光眼患者,因为这种疾病的特点是IOP升高,可以立即由眼科医生测量。
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引用次数: 1
Investigation of Hammering Sound Frequency to Prevent Intraoperative Fracture during Total Hip Arthroplasty 锤击声频率预防全髋关节置换术中骨折的研究
Pub Date : 2021-01-01 DOI: 10.4236/jbise.2021.1410029
R. Sakai, Tatsuki Kitazato, K. Uchiyama, Kazuhiro Yoshida, Takeaki Yamamoto, N. Takahira, M. Ujihira
Background: The 1st peak frequency of the hammering sound in total hip arthroplasty may serve as an evaluation index to prevent intraoperative fracture. Fixation of the stem and femur cannot be acquired unless the 1st peak frequency of hammering the stem into the femur stabilizes, and fixation can be judged as acquired when the 1st peak frequency becomes constant. To investigate whether the environmental sound in the operating room can be differentiated from the hammering sound of total hip arthroplasty, the 1st peak frequency of the hammering sound when impacting the stem into the femur with a hammer was identified. Method: The hammering sound of impacting the stem into a biomechanical test material through an impactor was analyzed using a fast Fourier transform analyzer. Environmental sound in the operating room was simulated and the 1st peak frequency of the sound on collision between the operator’s voice and the surgical instrument was measured. The 1st peak frequency of hammering sound was compared between patients indicated for total hip arthroplasty and healthy individuals to investigate whether there is a difference due to bone quality. Results: The natural frequency of the impactor was 3.41 ± 0.05 kHz, and the 1st peak frequency of the femur, stem, and impactor was 2.43 ± 1.45 kHz. The 1st peak frequency of hammering sound on simulated femur in patients indicated for total hip arthroplasty was 2.98 ± 0.73 kHz and that in healthy individuals was 2.15 ± 0.32 kHz. This sug-gested that the hammering sound in total hip arthroplasty-indicated patients overlaps with the frequency of the collision sound of surgical instruments. Conclusion: To develop a sys-Open
背景:全髋关节置换术中锤击声第1峰频率可作为预防术中骨折的评价指标。柄与股骨的固定只有在打入股骨的第一个峰值频率稳定后才能获得,当第一个峰值频率保持不变时即可判断为获得固定。为探讨手术室内环境声能否与全髋关节置换术的锤击声区分,我们确定了用锤击杆撞击股骨时的锤击声的第1个峰值频率。方法:采用快速傅立叶变换分析仪对冲击器冲击杆撞击生物力学试验材料时产生的锤击声进行分析。模拟手术室环境声,测量手术者声音与手术器械碰撞时的第一峰频率。比较全髋关节置换术患者与健康人群的锤击声第一峰频率,探讨是否因骨质量不同而存在差异。结果:冲击器的固有频率为3.41±0.05 kHz,股骨、椎体和冲击器的第一峰值频率为2.43±1.45 kHz。全髋关节置换术患者模拟股骨锤击声第1峰频率为2.98±0.73 kHz,健康人为2.15±0.32 kHz。这提示全髋关节置换术患者的锤击声与手术器械碰撞声的频率有重叠。结论:开发一种系统开放
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引用次数: 1
Hyperbaric Oxygen Treatment for Diabetic Retinopathy and Neuropathy in a Streptozotocin Induced Diabetic Rat Model 高压氧治疗链脲佐菌素诱导的糖尿病大鼠视网膜病变和神经病变
Pub Date : 2021-01-01 DOI: 10.4236/jbise.2021.1412033
J. Madsen, M. Skov, Kasper Hansen, C. Laustsen, Niels Ejskjær, Henning Andersen, M. Pedersen
Aim: Diabetes Mellitus is a global public health challenge with major and potentially de-vastating complications, and concomitant complications include retinopathy and neuropathy due to hypoxia and microvascular dysfunction. In this study, we investigated the effect of hyperbaric oxygen therapy as a method to transiently improve tissue oxygenation on diabetic retinopathy and neuropathy in a streptozotocin induced type-1 diabetic rat model (Wistar). Methods: Streptozotocin induced type-1 diabetic rats received 10 sessions of 2-h hyperbaric oxygen exposures (pO 2 = 309 kPa) over 2 weeks. Animals were exposed to light stimuli to produce light evoked potentials to estimate the effect of oxygen treatment on diabetic retinopathy. Sciatic nerves were exposed and stimulated to produce muscle evoked potential, which were recorded in the muscles of the foot and subsequently used to evaluate the effect of oxygen treatment on diabetic neuropathy. Results: We found significantly shorter light evoked potential latency and increased amplitude in hyperbaric oxygen treated animals. No change was found in nerve conduction. Conclusions: This study showed that hyperbaric oxygen therapy is a potentially effective treatment for diabetic retinopathy, im-proving both latency and amplitude of light evoked potentials.
目的:糖尿病是一个全球性的公共卫生挑战,具有严重和潜在的破坏性并发症,伴随并发症包括视网膜病变和由缺氧和微血管功能障碍引起的神经病变。在本研究中,我们在链脲佐菌素诱导的1型糖尿病大鼠模型(Wistar)中研究了高压氧治疗作为一种短暂改善组织氧合的方法对糖尿病视网膜病变和神经病变的影响。方法:链脲佐菌素诱导的1型糖尿病大鼠在2周内接受10次2小时高压氧暴露(pO 2 = 309 kPa)。动物暴露于光刺激下产生光诱发电位,以评估氧治疗对糖尿病视网膜病变的影响。暴露并刺激坐骨神经产生肌肉诱发电位,在足部肌肉中记录肌肉诱发电位,随后用于评估氧治疗对糖尿病神经病变的影响。结果:我们发现高压氧处理动物的光诱发电位潜伏期明显缩短,振幅明显增加。神经传导未见改变。结论:本研究表明高压氧治疗是糖尿病视网膜病变的潜在有效治疗方法,可改善光诱发电位的潜伏期和振幅。
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引用次数: 0
The Use of Artificial Intelligence on Segmental Volumes, Constructed from MRI and CT Images, in the Diagnosis and Staging of Cervical Cancers and Thyroid Cancers: A Study Protocol for a Randomized Controlled Trial 人工智能在分段体积上的应用,从MRI和CT图像构建,在宫颈癌和甲状腺癌的诊断和分期:一项随机对照试验的研究方案
Pub Date : 2021-01-01 DOI: 10.4236/jbise.2021.146025
Tudor Florin Ursuleanu, Andreea Roxana Luca, L. Gheorghe, Roxana Grigorovici, Stefan Iancu, Maria Hlusneac, C. Preda, A. Grigorovici
Rationale and Objectives: Accurately establishing the diagnosis and staging of cervical and thyroid cancers is essential in medical practice in determining tumor extension and dissemination and involves the most accurate and effective therapeutic approach. For accurate diagnosis and staging of cervical and thyroid cancers, we aim to create a diagnostic method, optimized by the algorithms of artificial intelligence and validated by achieving accurate and favorable results by conducting a clinical trial, during which we will use the diagnostic method optimized by artificial intelligence (AI) algorithms, to avoid errors, to increase the understanding on interpretation computer tomography (CT) scan, magnetic resonance imaging (MRI) of the doctor and improve therapeutic planning. Materials and Methods: The optimization of the computer assisted diagnosis (CAD) method will consist in the development and formation of artificial intelligence models, using algorithms and tools used in segmental volumetric constructions to generate 3D images from MRI/CT. We propose a comparative study of current developments in “DICOM” image processing by volume rendering technique, the use of the transfer function for opacity and color, shades of gray from “DICOM” images projected in a three-dimensional space. We also use artificial intelligence (AI), through the technique of Generative Adversarial Networks (GAN), which has proven to be effective in representing complex data distributions, as we do in this study. Validation of the diagnostic method, optimized by algorithm of artificial intelligence will consist of achieving accurate results on diagnosis and staging of cervical and thyroid cancers by conducting a randomized, controlled clinical trial, for a period of 17 months. Results: We will validate the CAD method through a clinical study and, secondly, we use various network topologies specified above, which have produced promising results in the tasks of image model recognition and by using this mixture. By using this method in medical practice, we aim to avoid errors, provide precision in diagnosing, staging and establishing the therapeutic plan in cancers of the cervix and thyroid using AI. Conclusion: The use of the CAD method can increase the quality of life by avoiding intra and postoperative complications in surgery, intraoperative orientation and the precise determination of radiation doses and irradiation zone in radiotherapy.
理由和目的:准确确定宫颈癌和甲状腺癌的诊断和分期在确定肿瘤扩散和扩散的医疗实践中至关重要,并涉及最准确和有效的治疗方法。为了准确诊断和分期宫颈癌和甲状腺癌,我们的目标是创建一种诊断方法,通过人工智能算法优化,并通过进行临床试验获得准确和有利的结果进行验证,在此过程中我们将使用人工智能(AI)算法优化的诊断方法,避免错误,增加对计算机断层扫描(CT)解释的理解。磁共振成像(MRI),提高医生的治疗计划。材料和方法:计算机辅助诊断(CAD)方法的优化将包括人工智能模型的开发和形成,使用分段体结构中使用的算法和工具从MRI/CT生成3D图像。我们建议通过体绘制技术、使用传递函数来处理不透明度和颜色、投影在三维空间中的“DICOM”图像的灰度,对“DICOM”图像处理的当前发展进行比较研究。我们还通过生成对抗网络(GAN)技术使用人工智能(AI),正如我们在本研究中所做的那样,该技术已被证明在表示复杂数据分布方面是有效的。通过人工智能算法优化的诊断方法的验证将包括通过进行为期17个月的随机对照临床试验,获得宫颈癌和甲状腺癌的准确诊断和分期结果。结果:我们将通过临床研究验证CAD方法,其次,我们使用上述指定的各种网络拓扑,这些拓扑在图像模型识别任务和使用这种混合物中产生了有希望的结果。通过在医疗实践中使用这种方法,我们的目的是避免错误,提供准确的诊断,分期和制定治疗方案的人工智能在宫颈癌和甲状腺癌。结论:采用CAD方法可避免术中及术后并发症,术中定位准确,放疗剂量及照射区确定准确,提高患者的生活质量。
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引用次数: 4
Finite Element Simulation of In-Stent Restenosis with Tissue Growth Model 基于组织生长模型的支架内再狭窄有限元模拟
Pub Date : 2021-01-01 DOI: 10.4236/JBISE.2021.142005
Jie Cheng, Lucy T. Zhang
In this study, a finite element simulation of in-stent restenosis (ISR) is conducted to simulate the deployment and expansion of a stent in an occluded artery with a contact model and a mechanics-based growth model. A tissue growth model based on the multiplicative decomposition of deformation is applied to investigate the growth of the plaque and artery wall upon the stent’s implantation. Due to the high stresses at the contact points between the stent struts and the tissue, further tissue injury or restenosis is observed. The simulation results show that after the stent deployment, the von Mises stress is significantly larger in the plaque compared to the artery wall, especially in the region that is in contact with the stent. However, the growth of the plaque and artery tends to even out the stress concentration over time. The tissue growth is found to be more significant near the inner wall than the outer layer. A 0.77 mm restenosis is predicted, which agrees with published clinical observations. The features of the artery growth are carefully analyzed, and the underlying mechanism is discussed. This study is the first attempt to apply finite element analysis to artery restenosis, which establishes a framework for predicting ISR’s occurrence and severity. The results also provide insights into understanding the underlying mechanism of in-stent restenosis.
本研究对支架内再狭窄(ISR)进行有限元模拟,采用接触模型和基于力学的生长模型模拟支架在闭塞动脉内的展开和扩张。采用基于变形乘法分解的组织生长模型研究支架植入过程中斑块和动脉壁的生长情况。由于支架支柱和组织之间接触点的高应力,进一步的组织损伤或再狭窄被观察到。模拟结果表明,支架铺开后,斑块内的von Mises应力明显大于动脉壁,尤其是与支架接触的区域。然而,随着时间的推移,斑块和动脉的生长会使压力浓度趋于平衡。发现靠近内壁的组织生长比靠近外层的组织生长更明显。预测再狭窄0.77 mm,这与已发表的临床观察结果一致。仔细分析了动脉生长的特点,并讨论了潜在的机制。本研究首次尝试将有限元分析应用于动脉再狭窄,建立了预测动脉再狭窄发生和严重程度的框架。该结果也为理解支架内再狭窄的潜在机制提供了见解。
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引用次数: 0
Human Heterogeneity and Survival of the Species: How Did It Arise and Being Sustained?—The Conundrum Facing Researchers 人类的异质性和物种的生存:它是如何产生和维持的?——研究人员面临的难题
Pub Date : 2021-01-01 DOI: 10.4236/JBISE.2021.145018
D. Hart
Current humans, Homo sapiens, are genetically and epigenetically very heterogeneous, and subsequently also biologically and physiologically heterogeneous. Much of this heterogeneity likely arose during evolutionary processes, via various iterations of humanoid lineages, and interbreeding. While advantageous from a species perspective, the heterogeneity of humans poses serious challenges to researchers attempting to understand complex disease processes. While the use of inbred preclinical models makes the research effort more effective at some levels, the findings are often not translatable to the more heterogeneous human populations. This conundrum leads to considerable research activity with inbred preclinical models, but modest progress in understanding many complex human conditions and diseases. This article discusses several of the issues around human heterogeneity and the need to change some directions in preclinical model research. Using newer Artificial Intelligence and Machine Learning approaches can begin to deduce important elements from the complexity of human heterogeneity.
现在的人类,智人,在遗传和表观遗传上都是异质的,因此在生物学和生理学上也是异质的。这种异质性很可能是在进化过程中产生的,通过各种类人猿血统的迭代和杂交。虽然从物种的角度来看是有利的,但人类的异质性给试图理解复杂疾病过程的研究人员带来了严峻的挑战。虽然使用近交临床前模型使研究工作在某些层面上更有效,但研究结果往往不能转化为更异质的人群。这一难题导致了大量的近交临床前模型研究活动,但在理解许多复杂的人类状况和疾病方面进展甚微。本文讨论了关于人类异质性的几个问题,以及在临床前模型研究中需要改变一些方向。使用更新的人工智能和机器学习方法可以开始从人类异质性的复杂性中推断出重要的元素。
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引用次数: 2
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生物医学工程(英文)
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