• 【关于致突变性和致癌性的综合决策树测试策略,符合欧盟REACH法规的要求。】 复制标题 收藏 收藏
    DOI:10.1177/026119290803601s05 复制DOI
    作者列表:Combes R,Grindon C,Cronin MT,Roberts DW,Garrod JF
    BACKGROUND & AIMS: :Liverpool John Moores University and FRAME recently conducted a research project sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for using alternative methods (both in vitro and in silico) for mutagenicity (genotoxicity) and carcinogenicity testing--two toxicity endpoints, which, together with reproductive toxicity, are of pivotal importance for the REACH system. The manuscript critically discusses well-established testing approaches, and in particular, the requirement for short-term in vivo tests for confirming positive mutagenicity, and the need for the rodent bioassay for detecting non-genotoxic carcinogens. Recently-proposed testing strategies focusing on non-animal approaches are also considered, and our own testing scheme is presented and supported with background information. This scheme makes maximum use of pre-existing data, computer (in silico) and in vitro methods, with weight-of-evidence assessments at each major stage. The need for the improvement of in vitro methods, to reduce the generation of false-positive results, is also discussed. Lastly, ways in which reduction and refinement measures can be used are also considered, and some recommendations are made for future research to facilitate the implementation of the proposed testing scheme.
    背景与目标: :利物浦约翰摩尔大学和FRAME最近进行了由Defra赞助的研究项目,该研究项目涉及欧盟REACH(化学品注册,评估和授权)系统中动物测试替代品的现状,以进行化学品安全性测试和风险评估。该项目涵盖了与REACH系统相关的所有主要毒性终点。本文重点介绍了使用替代方法(体外和计算机模拟)进行致突变性(遗传毒性)和致癌性测试的前景-两个毒性终点以及生殖毒性对于REACH系统至关重要。该手稿严格地讨论了已建立的测试方法,尤其是对短期的体内测试以确认阳性诱变性的要求,以及对啮齿动物生物测定法以检测非遗传毒性致癌物的需求。还考虑了最近提出的针对非动物方法的测试策略,并提出了我们自己的测试方案并提供了背景信息的支持。该方案最大程度地利用了现有数据,计算机(计算机模拟)和体外方法,并在每个主要阶段进行了证据权重评估。还讨论了改进体外方法以减少假阳性结果的产生的需求。最后,还考虑了减少和改进措施的使用方法,并为将来的研究提出了一些建议,以促进拟议的测试方案的实施。
  • 【关于queussine,癌症中转移RNA的过修饰。】 复制标题 收藏 收藏
    DOI:10.4161/rna.2.4.2417 复制DOI
    作者列表:Pathak C,Jaiswal YK,Vinayak M
    BACKGROUND & AIMS: :Queuosine is a highly modified nucleoside analogue of guanosine. It is present only in the first position of anticodon loop of specific tRNA i.e., tRNA(his), tRNA(asp), tRNA(asn) and tRNA(tyr) and post transcriptionally modified with base-for-base exchange of guanine to queuine. The transfer RNA modifying enzyme transfer RNA guanine transglycosylase (TGTase) catalyzes the modification of tRNAs. Transfer RNA is completely modified with respect to queuosine in mature tissue, however modification is often incomplete in mitotically active cells. Hypomodification of transfer RNA is correlated with cell proliferation and malignancy. In the present study queuosine modification of transfer RNA and TGTase activity is compared in normal, Dalton's lymphoma ascites transplanted (DLAT) cancerous and queuine treated DLAT cancerous mouse liver. Transfer RNA of cancerous mouse is hypomodified in terms of queuosine modification. TGTase activity of cancerous mouse is found to decrease to less then half of enzyme activity of normal mouse; suggesting that the enzyme may be responsible for transfer RNA hypomodification. Exogenous treatment of queuine during development of cancer improves the queuosine modification of transfer RNA. The activators NaPP and ATP enhance TGTase activity of normal and DLAT cancerous mouse, where as 7mG inhibits the TGTase activity.
    背景与目标: :Queuosine是鸟苷的高度修饰的核苷类似物。它仅存在于特定tRNA的反密码子环的第一个位置,即tRNA(his),tRNA(asp),tRNA(asn)和tRNA(tyr),并经鸟嘌呤至奎宁的碱基对碱基交换而被转录后修饰。转移RNA修饰酶转移RNA鸟嘌呤转糖基酶(TGTase)催化tRNA的修饰。相对于成熟组织中的奎宁,转移RNA已被完全修饰,但是在有丝分裂活性细胞中修饰通常是不完全的。转移RNA的过低修饰与细胞增殖和恶性肿瘤相关。在本研究中,比较了正常,道尔顿氏淋巴瘤腹水移植(DLAT)癌性和队列治疗的DLAT癌性小鼠肝中转移RNA和TGTase活性的队列蛋白修饰。就槲皮素修饰而言,癌小鼠的转移RNA被修饰不足。发现癌性小鼠的TGTase活性降低至正常小鼠的一半以下;提示该酶可能是导致转移RNA修饰不足的原因。在癌症发生过程中对奎因进行外源治疗可改善转移RNA的奎因修饰。 NaPP和ATP激活剂可增强正常小鼠和DLAT癌小鼠的TGTase活性,而7mG则可抑制TGTase活性。
  • 【在法医精神病学护理中尊重患者的自主权。】 复制标题 收藏 收藏
    DOI:10.1111/j.1939-3938.2005.tb00007.x 复制DOI
    作者列表:Rose DN
    BACKGROUND & AIMS: :A fundamental issue that forensic psychiatric nurses struggle with is respect for patient autonomy, as the two liberal prerequisites for autonomy, liberty and rationality, are either absent or compromised in forensic psychiatric settings. In this paper, a contemporary feminist perspective of autonomy, relational autonomy, will be advanced as an alternative approach to the traditional liberalist, Kantian, perspective of autonomy. The concepts of autonomy, paternalism, and justice will be discussed in relation to forensic psychiatric nursing.
    背景与目标: :法医精神科护士努力解决的一个基本问题是对患者自治的尊重,因为在法医精神病学环境中,自治,自由和合理性这两个自由先决条件不存在或受到损害。在本文中,将提出当代女性主义的自治观点关系自治,作为对传统的自由主义康德式自治观点的替代方法。自治,家长式和正义的概念将与法医精神病学护理相关地进行讨论。
  • 【大肠肿瘤中微血管的形态分析与肝转移的形成有关。】 复制标题 收藏 收藏
    DOI:10.1002/jso.1164 复制DOI
    作者列表:Yamamura T,Tsukikawa S,Yamada K,Yamaguchi S
    BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Overexpression of VEGF and proliferation of microvessels are strongly related to liver metastases, however, morphologic analyses of microvessels in liver metastases have not been reported. The purpose of the present study was to examine the correlation between liver metastases and the diameters of microvessel lumens in the tumor tissue.

    METHODS:Fifty-nine patients with liver metastases from colorectal cancers and 112 patients who underwent curative colorectal resection and survived without any recurrence were reviewed. Microvessel density (MVD) and the diameters of the lumens of individual microvessels were assessed.

    RESULTS:There was a significant difference in terms of the mean MVD of primary tumors between patients with liver metastases and those without liver metastases. The numbers of patients with liver metastases who had microvessels 100-200 microm in diameter and microvessels more than 200 microm in diameter were significantly greater than patients without liver metastases. Microvessels with lumens more than 100 microm in diameter were not detected in the liver metastatic lesion.

    CONCLUSION:Large microvessels in the primary tumor favor intravasation of cancer cells.

    背景与目标: 背景和目的:VEGF的过表达和微血管的增殖与肝转移密切相关,但是,尚未见有关肝转移中微血管的形态学分析的报道。本研究的目的是研究肝转移与肿瘤组织中微血管腔直径之间的相关性。

    方法:59例大肠癌肝转移患者回顾了112例行结直肠癌根治性切除术且未复发的患者。评估了微血管密度(MVD)和单个微血管的内腔直径。

    结果:肝病患者之间原发性肿瘤的平均MVD有显着差异转移和无肝转移者。直径为100-200微米的微血管和直径大于200微米的微血管的肝转移患者人数明显高于无肝转移的患者。在肝转移病灶中未检测到管腔直径大于100微米的微血管。

    结论:原发性肿瘤中的大微血管有利于癌细胞的浸润。

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  • 【牙医和牙科学生对处方抗生素预防感染性心内膜炎的相关指南的知识和依从性:系统评价。】 复制标题 收藏 收藏
    DOI:10.1016/j.jebdp.2019.01.007 复制DOI
    作者列表:Cummins J,McCarthy M,Esterman A,Karve A,Lee A
    BACKGROUND & AIMS: BACKGROUND:It is essential that dental clinicians, including dental students, have sufficient knowledge of and adhere to relevant prophylactic guidelines for the prevention of infective endocarditis. Because the overprescription of antibiotics contributes to the development of drug resistance, antibiotic stewardship should be at the forefront of patient care. The aim of this review is to determine the level of knowledge and compliance of dentists and dental students to relevant guidelines regarding antibiotic prophylaxis for the prevention of infective endocarditis. In addition, we aim to identify the factors that influence the level of knowledge and compliance. MATERIALS AND METHODS:The following electronic databases were searched: MEDLINE (OvidSP), Scopus, Web of Science, CINAHL (EBSCOhost), and Informit Health Database. Inclusion criteria were (1) published quantitative studies that assessed dentists' and dental students' knowledge of and compliance with relevant guidelines for prescribing antibiotic prophylaxis for the prevention of infective endocarditis; (2) studies in English; and (3) studies published on any date. The National Institutes of Health, National Heart, Lung and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to appraise each of the included studies. The required data were collected and formatted to provide a narrative synthesis. RESULTS:A total of 3427 articles were identified, 167 full-text articles were reviewed, and 43 articles from 37 studies were included. Overall knowledge of guidelines ranged from as low as 1.9% to as high as 100% depending on the detail being examined. No statistically significant difference was found between dental students' and qualified dentists' knowledge. Overall compliance with guidelines ranged from 40% to 81%. Respondents' age and postgraduate training were the variables most associated with dentists' knowledge of guidelines for infective endocarditis. A limitation of this review is that only quantitative studies in English were assessed. CONCLUSION:Knowledge levels of guidelines for antibiotic prophylaxis varied greatly depending on the study design, respondent characteristics, and time period factors. There is a lack of research published on compliance rates for dentists and dental students with respect to guidelines for the prevention of infective endocarditis.
    背景与目标: 背景:至关重要的是,包括牙科学生在内的牙科临床医生必须具有足够的知识并遵守相关的预防性指南,以预防感染性心内膜炎。由于抗生素的过量处方会导致耐药性的发展,因此抗生素管理应成为患者护理的重中之重。这篇综述的目的是确定牙医和牙科学生对预防感染性心内膜炎的抗生素预防相关指南的了解程度和依从性。此外,我们旨在确定影响知识水平和合规性的因素。
    材料和方法:搜索以下电子数据库:MEDLINE(OvidSP),Scopus,Web of Science,CINAHL(EBSCOhost)和Informit Health数据库。纳入标准是:(1)已发表的定量研究评估了牙医和牙科学生对预防感染性心内膜炎的抗生素预防处方的了解和遵守情况; (2)英语学习; (3)在任何日期发表的研究。美国国立卫生研究院,国家心脏,肺和血液研究所用于观察性队列研究和跨学科研究的质量评估工具用于评估每个纳入的研究。收集所需数据并格式化以提供叙述性综合。
    结果:共鉴定了3427篇文章,审查了167篇全文文章,并纳入了来自37个研究的43篇文章。根据所检查的细节,指南的总体知识范围从低至1.9%到高至100%。牙科学生的知识和合格的牙医的知识之间没有发现统计学上的显着差异。总体上符合准则的范围从40%到81%。受访者的年龄和研究生培训是与牙医了解感染性心内膜炎指南最相关的变量。该评论的局限性在于仅评估了英语的定量研究。
    结论:根据研究设计,应答者特征和时间因素,抗生素预防指南的知识水平差异很大。关于预防感染性心内膜炎的指南,目前还缺乏关于牙医和牙科学生的依从率的研究。
  • 【经假肢排列改变的经胫截肢者的稳定性极限。】 复制标题 收藏 收藏
    DOI:10.1016/j.apmr.2013.05.019 复制DOI
    作者列表:Kolarova B,Janura M,Svoboda Z,Elfmark M
    BACKGROUND & AIMS: OBJECTIVES:To evaluate the limits of stability (LOS) in persons with transtibial amputation (TTA), and to determine the effects of prosthetic alignment alterations on motor control strategies. DESIGN:Before-and-after trial. SETTING:A kinesiology laboratory at a university hospital. PARTICIPANTS:Male patients with TTA (n=10) and controls (n=17). INTERVENTIONS:Prosthetic alignment. MAIN OUTCOME MEASURES:For the LOS test, the maximum excursion, endpoint excursion, direction control, movement velocity, and reaction time with inclination in the forward direction, toward the amputated leg/right leg, and in the backward direction, and toward the nonamputated leg/left leg. Measurements were performed using the following 5 prosthetic alignments: the optimal alignment, with the prosthesis shorter by 1cm, with the prosthesis longer by 1cm, and with the prosthetic foot in 5° of extra plantar flexion and 5° of extra dorsiflexion. RESULTS:Compared with the control group, maximum excursion and direction control were lower (P<.05) in patients with TTA with backward body inclination for all tested prosthetic alignments. Direction control in backward inclination was reduced (P<.05) compared with other tested directions for all assessed prosthetic alignments. Differences between the tested alignments were not significant in any of the tested directions. CONCLUSIONS:Patients with TTA have decreased voluntary body inclination backward within the LOS for all tested prosthetic alignments. Compared with controls, changes in prosthetic foot settings by means of rotation in the sagittal plane had a larger impact on movement strategy in patients with TTA than did changes to the length of the prosthesis.
    背景与目标: 目的:评估胫骨截肢(TTA)患者的稳定性(LOS)极限,并确定假体排列改变对运动控制策略的影响。
    设计:试用前后。
    地点:大学医院的运动机能实验室。
    参与者:男性TTA患者(n = 10)和对照组(n = 17)。
    干预:假体对齐。
    主要观察指标:对于LOS测试,最大偏移,端点偏移,方向控制,运动速度和反应时间,向前,向截肢/右腿,向后截肢,向后,向非截肢倾斜腿/左腿。使用以下5种假体对齐方式进行测量:最佳对齐方式,假体短1cm,假体长1cm,假脚足底弯曲5°,背背弯曲5°。
    结果:与对照组相比,对于所有测试的假体排列,TTA身体向后倾斜的患者的最大偏移和方向控制均较低(P <.05)。对于所有评估的假体排列,与其他测试方向相比,向后倾斜的方向控制减少了(P <.05)。在任何测试方向上,测试对齐之间的差异均不显着。
    结论:对于所有测试的假体排列,患有TTA的患者在LOS内向后减少了自愿的身体倾斜。与对照组相比,在TTA患者中,通过矢状面旋转引起的假脚设置改变对假肢长度的影响更大。
  • 【TIITS对人类四级神经胶质瘤中细胞毒性淋巴细胞的免疫调节作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.cellimm.2012.05.006 复制DOI
    作者列表:Kumar P,Acharya S,Chatterjee S,Kumari A,Chaudhuri S,Singh MK,Ghosh SN,Chaudhuri S
    BACKGROUND & AIMS: :T11 target structure (T11TS), a membrane glycoprotein has been documented with antineoplastic activity in animal model in our lab. Previously, in animal study we have documented T11TS induced cytotoxic abrogation of tumor cells. Encouraged by these established findings by our group and as prerequisite for clinical trial, this study has been designed to assess the cytotoxic potential of the patient's lymphocytes in in vitro study of autologous human glioma as modulated by T11TS. Meningioma samples were chosen as disease control group. The data produced indicates T11TS induced up regulation of cytotoxicity of T lymphocytes in grade I and II glioma. Significant enhancement of cytotoxic protein, perforin and granzyme suggest cytotoxic death of T11TS induced target tumor. Also, T11TS downregulates the TGF-β secretion in grade I and II tumor cells. These preliminary findings may help in pushing this molecule into pharmaceutical domain.
    背景与目标: :T11靶结构(T11TS),一种膜糖蛋白已在我们实验室的动物模型中被证明具有抗肿瘤活性。以前,在动物研究中,我们已经记录了T11TS诱导的肿瘤细胞细胞毒素消除。受我们小组这些既定发现的鼓舞,并作为临床试验的前提,本研究旨在评估在体外研究受T11TS调节的自体人类神经胶质瘤患者淋巴细胞的细胞毒性潜力。选择脑膜瘤样品作为疾病对照组。产生的数据表明,T11TS诱导了I级和II级神经胶质瘤中T淋巴细胞的细胞毒性上调。细胞毒性蛋白,穿孔素和颗粒酶的显着增强表明T11TS诱导的靶肿瘤的细胞毒性死亡。同样,T11TS下调I级和II级肿瘤细胞中TGF-β的分泌。这些初步发现可能有助于将该分子推入药物领域。
  • 【设施接生员对孕产妇和新生儿健康技能的了解与自我评价的信心:尼日利亚初级卫生保健机构的经验。】 复制标题 收藏 收藏
    DOI:10.4314/mmj.v31i3.8 复制DOI
    作者列表:Esan O,Fatusi A,Ojo T
    BACKGROUND & AIMS: Background:Competent and skilled birth attendants are critical in the reduction of maternal and infant morbidity and mortality at delivery. This study aimed to determine the association between knowledge and self-rated confidence in facility birth attendants affiliated with maternal and neonatal health (MNH) interventions. Methods:A descriptive cross-sectional study was conducted in 24 primary healthcare facilities in Osun state, Nigeria among 128 consenting facility birth attendants who were selected via a multi-stage sampling technique. Each attendant received a semi-structured interviewer-administered questionnaire. The dependent variables included the respondent's level of knowledge in MNH interventions and their self-rated confidence in MNH skills such as the provision of antenatal care service, normal labour, use of a partograph and the management of obstetric complications and post-partum haemorrhage. Bivariate analysis of factors associated with knowledge and self-rated confidence in MNH skills was performed with statistical significance set at p<0.05. Results:Only 48 (37.5%) of the respondents had good knowledge of all of the assessed interventions; worse performances were reported with regards to the respondent's knowledge of normal labour and partograph use. However, 96 (75%) of respondents were confident in performing 75% of the skills assessed. Our analysis identified two factors that were significantly associated with a good knowledge of MNH skills: the cadre of the birth attendants (p<0.001) and training in life-saving skills (p=0.001). The knowledge of our respondents relating to most of the MNH interventions assessed was not significantly associated with their self-rated confidence in the required skills. Conclusion:The confidence of facility birth attendants in MNH skills was not knowledge-based and could frustrate national efforts to reduce maternal and perinatal deaths. We recommend effective and evidence-based training of all cadres of facility birth attendants to ensure that the skills being practiced clinically are based on adequate knowledge.
    背景与目标: 背景:合格和熟练的接生员对于降低产妇和婴儿的发病率和死亡率至关重要。这项研究旨在确定与产妇和新生儿健康(MNH)干预相关的设施接生员的知识与自评信心之间的关联。
    方法:描述性横断面研究在尼日利亚奥森州的24家主要医疗机构中进行,该研究采用多阶段抽样技术从128名同意的机构接生员中选出。每位服务员都收到了由访谈员管理的半结构化问卷。因变量包括受访者对MNH干预的知识水平,以及他们对MNH技能的自评信心,例如提供产前护理服务,正常分娩,使用分形仪以及管理产科并发症和产后出血。对与MNH技能的知识和自我评估的自信心相关的因素进行双变量分析,统计学显着性设为p <0.05。
    结果:只有48(37.5%)位被调查者对所有评估的干预措施都有很好的了解;据报告,关于受访者的正常劳动和零件使用情况,表现较差。但是,有96名(75%)的受访者对完成所评估技能的75%有信心。我们的分析确定了与MNH技能的良好知识显着相关的两个因素:接生人员的干部(p <0.001)和救生技能的培训(p = 0.001)。我们的受访者对大多数MNH干预措施的了解与他们对所需技能的自我评价信心没有显着相关。
    结论:设施接生员对MNH技能的信心不是基于知识的,可能会挫伤国家减少孕产妇和围产儿死亡的努力。我们建议对设施接生的所有干部进行有效且循证的培训,以确保临床实践的技能是基于足够的知识。
  • 【三维共形放射治疗后新诊断的胶质母细胞瘤相对于放射治疗前磁共振波谱发现的复发分析模式。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijrobp.2007.03.019 复制DOI
    作者列表:Park I,Tamai G,Lee MC,Chuang CF,Chang SM,Berger MS,Nelson SJ,Pirzkall A
    BACKGROUND & AIMS: PURPOSE:To determine whether the combined magnetic resonance imaging (MRI) and magnetic resonance spectroscopy imaging (MRSI) before radiation therapy (RT) is valuable for RT target definition, and to evaluate the feasibility of replacing the current definition of uniform margins by custom-shaped margins based on the information from MRI and MRSI. METHODS AND MATERIALS:A total of 23 glioblastoma multiforme (GBM) patients underwent MRI and MRSI within 4 weeks after surgery but before the initiation of RT and at 2-month follow-up intervals thereafter. The MRSI data were quantified on the basis of a Choline-to-NAA Index (CNI) as a measure of spectroscopic abnormality. A combined anatomic and metabolic region of interest (MRI/S) consisting of T2-weighted hyperintensity, contrast enhancement (CE), resection cavity, and CNI2 (CNI >or= 2) based on the pre-RT imaging was compared to the extent of CNI2 and the RT dose distribution. The spatial relationship of the pre-RT MRI/S and the RT dose volume was compared with the extent of CE at each follow-up. RESULTS:Nine patients showed new or increased CE during follow-up, and 14 patients were either stable or had decreased CE. New or increased areas of CE occurred within CNI2 that was covered by 60 Gy in 6 patients and within the CNI2 that was not entirely covered by 60 Gy in 3 patients. New or increased CE resided within the pre-RT MRI/S lesion in 89% (8/9) of the patients with new or increased CE. CONCLUSION:These data indicate that the definition of RT target volumes according to the combined morphologic and metabolic abnormality may be sufficient for RT targeting.
    背景与目标: 目的:确定放射治疗(RT)之前的磁共振成像(MRI)和磁共振波谱成像(MRSI)的组合对于RT目标定义是否有价值,并评估用定制的方法代替当前定义的均匀余量的可行性-根据MRI和MRSI的信息对边缘进行整形。
    方法和材料:总共23例多形性胶质母细胞瘤(GBM)患者在手术后4周内,开始RT之前以及随后的2个月随访期间接受了MRI和MRSI。 MRSI数据基于胆碱到NAA指数(CNI)进行量化,以衡量光谱异常。比较基于T2加权的高强度,造影剂增强(CE),切除腔和CNI2(CNI>或= 2)组成的感兴趣的解剖和代谢组合区域(MRI / S),在一定程度上CNI2和RT剂量分布的关系。在每次随访时,将RT前MRI / S与RT剂量的空间关系与CE的程度进行比较。
    结果:9例患者在随访期间显示出新的或增加的CE,14例病情稳定或CE降低。 6例患者的CNG2内出现新的或增加的CE区域,被60 Gy覆盖; 3例患者的CNI2内未完全被60 Gy覆盖。在新的或增加的CE患者中,有89%(8/9)的患者在RT之前的MRI / S病变中存在新的或增加的CE。
    结论:这些数据表明,根据形态和代谢异常的结合来确定RT靶标的量可能足以作为RT靶标。
  • 【使用基于簇的欠采样方法从不平衡方面预测乳腺癌。】 复制标题 收藏 收藏
    DOI:10.1155/2019/7294582 复制DOI
    作者列表:Zhang J,Chen L,Abid F
    BACKGROUND & AIMS: :To overcome the two-class imbalanced problem existing in the diagnosis of breast cancer, a hybrid of K-means and Boosted C5.0 (K-Boosted C5.0) is proposed which is based on undersampling. K-means is utilized to select the informative samples near the boundary. During the training phase, the K-means algorithm clusters the majority and minority instances and selects a similar number of instances from each cluster. Boosted C5.0 is then used as the classifier. As there is one different instance selection factor via clustering that encourages the diversity of the training subspace in K-Boosted C5.0, it would be a great advantage to get better performance. To test the performance of the new hybrid classifier, it is implemented on 12 small-scale and 2 large-scale datasets, which are the often used datasets in class imbalanced learning. The extensive experimental results show that our proposed hybrid method outperforms most of the competitive algorithms in terms of Matthews' correlation coefficient (MCC) and accuracy indices. It can be a good alternative to the well-known machine learning methods.
    背景与目标: :为克服乳腺癌诊断中存在的两类不平衡问题,基于欠采样,提出了K-均值和Boosted C5.0(K-Boosted C5.0)的混合体。利用K均值选择边界附近的信息量样本。在训练阶段,K-means算法将多数和少数实例聚类,并从每个聚类中选择相似数量的实例。然后将Boosted C5.0用作分类器。由于通过聚类存在一个不同的实例选择因子,可以鼓励K-Boosted C5.0中训练子空间的多样性,因此获得更好的性能将是一个巨大的优势。为了测试新混合分类器的性能,它在12个小型和2个大型数据集上实现,这是班级不平衡学习中经常使用的数据集。大量的实验结果表明,在Matthews的相关系数(MCC)和准确性指标方面,我们提出的混合方法优于大多数竞争算法。它可以替代众所周知的机器学习方法。
  • 【二甲双胍对2型糖尿病患者动脉粥样硬化病变中乙二醛酶1活性的影响。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2019-03-01
    来源期刊:Vasa
    DOI:10.1024/0301-1526/a000762 复制DOI
    作者列表:Peters AS,Wortmann M,Fleming TH,Nawroth PP,Bruckner T,Böckler D,Hakimi M
    BACKGROUND & AIMS: BACKGROUND:The enzyme glyoxalase1 (GLO1) is the main opponent in the degradation of the reactive metabolite methylglyoxal (MG), which by glycation of macromolecules is involved in atherogenesis. Reduced GLO1-activity in atherosclerotic tissue is known to be associated with diabetes. It has been shown that treatment of patients with type 2 diabetes with metformin leads to increased GLO1-activity in peripheral-blood-cells. The aim of this study was to evaluate whether metformin treatment increases GLO1-activity in atherosclerotic lesions of patients with type 2 diabetes. PATIENTS AND METHODS:Patients with type 2 diabetes and carotid artery disease were included into the study prospectively. Type of diabetes-medication was documented upon admission along with demographic and clinical history. Using shock frozen endarterectomy-derived carotid artery plaques, GLO1-activity as well as protein expression was measured by a spectophotometric assay and western-blotting respectively. RESULTS:33 patients (76 % male, mean age 71 years) were included into the study and were divided according to treatment with metformin or not (15 vs. 18 patients). GLO1-activity was increased by the factor 1.36 when treated with metformin - however, not significantly (0.86 vs. 0.63 U/mg, p = 0.056). Normalisation of GLO1-activity onto GLO1-expression level lead to a significant increase by more than twofold (8.48 vs. 3.85, p = 0.044) while GLO1-protein levels did not differ significantly. GLO1-activity correlated positively with increasing HbA1c, especially under metformin treatment. CONCLUSIONS:Treatment with metformin in patients with type 2 diabetes is associated with enhanced GLO1-activity in atherosclerotic lesions. Regarding the macro- and microvascular complications in these patients further studies are needed to gain more insight into the effect of metformin on the GLO/MG system.
    背景与目标: 背景:乙二醛酶1(GLO1)是反应性代谢产物甲基乙二醛(MG)降解的主要对手,后者通过大分子糖基化参与动脉粥样硬化的形成。已知动脉粥样硬化组织中GLO1活性降低与糖尿病有关。已经显示,用二甲双胍治疗2型糖尿病患者会导致外周血细胞中GLO1活性增加。这项研究的目的是评估二甲双胍治疗是否增加2型糖尿病患者的动脉粥样硬化病变中的GLO1活性。
    患者与方法:前瞻性纳入了2型糖尿病和颈动脉疾病的患者。入院时记录了糖尿病用药的类型以及人口统计学和临床​​病史。使用激冷冷冻内膜切除术衍生的颈动脉斑块,分别通过分光光度法和蛋白质印迹法测量GLO1活性和蛋白质表达。
    结果:33名患者(76%的男性,平均年龄71岁)被纳入研究,并根据是否接受二甲双胍治疗进行了划分(15例对18例)。用二甲双胍治疗时,GLO1活性增加了1.36倍-但没有显着提高(0.86比0.63 U / mg,p = 0.056)。 GLO1活性在GLO1表达水平上的标准化导致显着增加两倍以上(8.48对3.85,p = 0.044),而GLO1蛋白水平没有显着差异。 GLO1活性与HbA1c增加呈正相关,尤其是在二甲双胍治疗下。
    结论:2型糖尿病患者用二甲双胍治疗与动脉粥样硬化病变中GLO1活性增强有关。关于这些患者的大血管和微血管并发症,需要进一步研究以进一步了解二甲双胍对GLO / MG系统的作用。
  • 【关于压力应对策略的精神病患者的童年创伤和同种异体负荷的历史。】 复制标题 收藏 收藏
    DOI:10.1016/j.psyneuen.2020.104645 复制DOI
    作者列表:Piotrowski P,Frydecka D,Kotowicz K,Stańczykiewicz B,Samochowiec J,Szczygieł K,Misiak B
    BACKGROUND & AIMS: :Elevated allostatic load (AL) index, which is a cumulative measure of biological dysregulations associated with stress exposure, has been demonstrated in patients with psychosis. However, it remains unknown whether a history of childhood trauma (CT) might contribute to elevated AL index in psychosis. Therefore, we aimed to investigate the association between AL index, a history of CT and coping styles in patients with psychotic disorders. Participants were 65 patients with schizophrenia-spectrum disorders and 56 healthy controls (HCs). The AL index was computed based on percentile distributions of 15 biomarkers in HCs. The AL index was significantly higher in patients with psychosis. A history of parental antipathy was associated with elevated AL index in both groups of participants. A history of any categories of CT and sexual abuse were associated with higher AL index only in patients with psychosis. Social diversion (seeking social interactions in case of stressful experiences) mediated the association between sexual abuse and the AL index in the group of patients. There was a significant direct effect of sexual abuse on the AL index (this specific CT was associated with higher AL index). However, indirect effect of sexual trauma on AL through social diversion was opposite to direct effect. Childhood adversities, especially sexual abuse and parental antipathy, might contribute to elevated AL index in patients with psychosis. The effect of sexual abuse on the AL index might be specific to psychosis. Engagement in social interactions in case of stressful situations might alleviate biological dysregulations associated with CT.
    背景与目标: :精神病患者已证明,高水平的同种异体负荷(AL)指数是与压力暴露有关的生物学失调的累积量度。但是,尚不清楚儿童创伤史(CT)是否可能导致精神病患者的AL指数升高。因此,我们旨在研究精神病患者的AL指数,CT病史和应对方式之间的关系。参加者有65例精神分裂症-频谱障碍患者和56例健康对照(HCs)。 AL指数是根据HC中15种生物标志物的百分比分布计算得出的。精神病患者的AL指数显着较高。两组参与者的父母反感病史都与AL指数升高有关。任何类型的CT和性虐待史都仅在精神病患者中与较高的AL指数相关。社会转移(在有压力经历的情况下寻求社会互动)介导了患者群体中性虐待与AL指数之间的关联。性虐待对AL指数有显着的直接影响(该特定的CT与较高的AL指数有关)。然而,通过社会转移对AL造成的性创伤的间接影响与直接影响相反。童年时期的逆境,尤其是性虐待和父母的反感,可能会导致精神病患者的AL指数升高。性虐待对AL指数的影响可能是精神病特有的。在有压力的情况下参与社交互动可能会减轻与CT相关的生物学失调。
  • 【关于第四个障碍的跨大西洋融合?】 复制标题 收藏 收藏
    DOI:10.2165/00019053-200624002-00009 复制DOI
    作者列表:Cohen J
    BACKGROUND & AIMS: :There appears to be movement towards convergence between the US and Europe in terms of the objectives of prescription drug cost containment, improvement in and more equitable access to pharmaceuticals, and minimisation of variation in clinical practice. In addition, policymakers in the US and Europe are resorting to the use of similar evidence-based approaches to achieve these policy objectives. However, using the examples of clinical practice guidelines, new drug appraisals for reimbursement, reference pricing and prescription to over-the-counter switching, I illustrate how the development and implementation of such approaches are a function not only of evidence but also of politics. Because all politics is local and differs across countries, and settings within countries, this logically has resulted in instances of divergence in the development and implementation of evidence-based approaches. Evidence improves policy decisions by offering quantitative insight into how well new technologies work, and for whom, but such data do not eliminate vexing trade-offs between the benefits provided and the acceptability of risks and costs incurred to achieve those benefits. Judgments on trade-offs depend in part on the interests and values of stakeholders. And these interests and values help shape how policy makers responsible for drug reimbursement in the US and Europe develop and apply the same types of evidence-based approaches differently.
    背景与目标: :就处方药成本控制,改善和更公平地获得药品以及最小化临床实践差异的目标而言,美国和欧洲之间似乎正在趋于融合。此外,美国和欧洲的决策者正在采取类似的基于证据的方法来实现这些政策目标。但是,以临床实践指南,报销新药评估,参考价和处方转换为处方的例子为例,我说明了这种方法的开发和实施不仅是证据的功能,也是政治功能的功能。由于所有政治都是地方性的,并且在不同国家之间以及在国家内部设置不同,因此从逻辑上讲,这导致在开发和实施基于证据的方法方面存在分歧。证据可以通过定量地了解新技术的运行状况以及对谁的作用来改善政策决策,但是此类数据并不能消除在提供的收益与为实现这些收益而承受的风险和成本的可接受性之间的艰难权衡。权衡的判断部分取决于利益相关者的利益和价值。这些利益和价值观有助于塑造负责美国和欧洲药品报销的政策制定者如何以不同的方式开发和应用相同类型的循证方法。
  • 【关于继发性KIT突变引起的伊马替尼耐药性的胃肠道间质瘤(GIST)新辅助伊马替尼治疗后的手术管理。】 复制标题 收藏 收藏
    DOI:10.1245/s10434-006-9228-0 复制DOI
    作者列表:Haller F,Detken S,Schulten HJ,Happel N,Gunawan B,Kuhlgatz J,Füzesi L
    BACKGROUND & AIMS: BACKGROUND:In metastasized GISTs, resistance to imatinib after initial tumour response has been associated with observation of secondary mutations in the activation loop of KIT. The aim of the current study was to evaluate the tumour response and observance of secondary KIT mutations in a case of GIST undergoing neoadjuvant imatinib therapy. METHODS:We report on a case of an initially unresectable gastric GIST with curative resection after 10 months of neoadjuvant imatinib therapy. Mutation analysis of KIT was performed on a pretherapeutic biopsy specimen, as well as on the resected tumour specimen. RESULTS:The pretherapeutic biopsy revealed cKit positive tumour cells with mutation of KIT exon 11 Del 560-576. The remaining tumour mass after neoadjuvant imatinib therapy almost exclusively consisted of hypocellular myxohyalinale stroma with rare microfoci of cKit positive tumour cells. Laser microdissection of several tumour microfoci revealed two additional point mutations located in the activation loop of KIT exon 17, C809G and N822Y, each observed separately in a distinct microfocus. Neither of these two point mutations has been reported in a GIST so far. CONCLUSIONS:Neoadjuvant imatinib therapy successfully reduces tumour size in GISTs. Since resistance relevant secondary mutations of the activation loop of KIT may be observed after neoadjuvant imatinib therapy, the time elapse with preoperative imatinib therapy should be chosen as short as curative tumour resection or function sparing surgery can be carried out. The determination of the optimal time point for surgery is therefore a critical event and will be discussed.
    背景与目标: 背景:在转移的GIST中,初始肿瘤反应后对伊马替尼的耐药性与观察到的KIT激活环中的继发突变有关。本研究的目的是评估在接受新辅助伊马替尼治疗的GIST病例中的肿瘤反应和对继发性KIT突变的观察。
    方法:我们报告了在新辅助伊马替尼治疗10个月后最初无法切除的胃GIST并进行根治性切除的病例。在治疗前的活检标本以及切除的肿瘤标本上进行了KIT的突变分析。
    结果:治疗前的活检显示cKit阳性肿瘤细胞具有KIT外显子11 Del 560-576突变。新辅助伊马替尼治疗后剩余的肿瘤块几乎完全由具有cKit阳性肿瘤细胞稀有微灶的低细胞粘液性角质层基质组成。几个肿瘤微灶的激光显微切割揭示了位于KIT外显子17,C809G和N822Y激活环中的另外两个点突变,分别在不同的微焦点处分别观察到。到目前为止,这两个点突变均未在GIST中报告。
    结论:新辅助伊马替尼治疗可成功减少GISTs的肿瘤大小。由于在新辅助伊马替尼治疗后可能会观察到与耐药相关的KIT激活环的继发突变,因此应选择术前伊马替尼治疗的时间,因为可以进行根治性肿瘤切除或可以保留功能的手术。因此,确定手术的最佳时间点是关键事件,将进行讨论。
  • 【与唾液相对于磷酸钙饱和有关的人龈上体内牙结石的形成。】 复制标题 收藏 收藏
    DOI:10.1016/s0003-9969(96)00120-3 复制DOI
    作者列表:Poff AM,Pearce EL,Larsen MJ,Cutress TW
    BACKGROUND & AIMS: The aim was to establish if there is a correlation between the rate of formation of supragingival calculus and the degree of supersaturation of saliva with respect to apatite, brushite and other calcium phosphates. The rate of calculus formation was estimated by measuring the calculus formed on lingual surfaces of the lower incisors in 15 individuals during 30 days. Submandibular saliva stimulated with citric acid and resting whole saliva, alter pH determination and ultrafiltration to remove protein was analysed for calcium, phosphate, sodium, potassium and carbonate. The degree of saturation with respect to calcium phosphates was calculated using a computer program. The rate of calculus formation among the 15 participants ranged widely, from a score of 0.5 to a high of 15. A close correlation (r = 0.91) between salivary pH and degree of supersaturation was found A weak correlation between calcium and calculus formation was also found. But neither for unstimulated nor stimulated saliva was a significant relation between supersaturation with respect to any of the calcium phosphates and the rate of calculus formation observed. Therefore, taking into consideration the background of the wide range of rates of calculus formation and of degrees of supersaturation, it was concluded that relation between them is unlikely, and the use of degree of saturation as a diagnostic tool seems unreliable.

    背景与目标: 目的是确定龈上结石的形成速率与唾液相对于磷灰石,透钙磷石和其他磷酸钙的过饱和度之间是否存在相关性。通过测量30天中15个人的下门牙舌表面形成的牙结石,估计牙结石形成的速率。用柠檬酸刺激下颌下唾液并静息整个唾液,改变pH测定并进行超滤以去除蛋白质,分析钙,磷酸盐,钠,钾和碳酸盐的含量。使用计算机程序计算相对于磷酸钙的饱和度。 15名参与者的牙结石形成率差异很大,从0.5分到最高15分。唾液pH值与过饱和度之间存在密切相关性(r = 0.91)。钙与牙结石形成之间的相关性也很弱。成立。但是,无论是未经刺激的唾液还是刺激的唾液,在任何磷酸钙的过饱和度与观察到的牙石形成速率之间都没有显着的关系。因此,考虑到微积分形成速率和过饱和度的范围很广的背景,可以得出结论,它们之间的关系不太可能,并且将饱和度用作诊断工具似乎是不可靠的。
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