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The change of paradigm in the treatment of HER2-positive breast cancer with the development of newgeneration antibody-drug conjugates

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Cancer Drug Resistance 2023年第1期6卷 45-58页

作者： santiago Escriva-de-Romani Cristina Saura Medical Oncology Service Breast Cancer UnitVall d’Hebron Institute of Oncology(VHIO)Passeig de la Vall d’Hebron119Barcelona 08035Spain

HER2-positive breast cancer is an aggressive *** a result of the development of specific HER2-targeted therapies,such as trastuzumab,more than 20 years ago,the prognosis of these patients has *** HER2-positive breast cancer patients are achieving better survival rates upon treatment with anti-HER2 therapies than patients with HER2-negative *** HER2 blockade with trastuzumab and pertuzumab combined with a taxane achieved an unprecedented survival of over 57 months in first-line *** emtansine,the first antibody-drug conjugate approved for patients in second-line treatment was a potent cytotoxic agent bound to trastuzumab and is currently a standard therapeutic *** the progress in treatment development,most patients develop resistance and eventually *** in the design of antibody-drug conjugates have led to the development of new generation drugs with enhanced properties,such as trastuzumab deruxtecan and trastuzumab duocarmazine,which are significantly changing the paradigm in the treatment of HER2-positive metastatic breast cancer.

关键词： Breast cancer HER2-positive ADCs New drugs Mechanisms of resistance

All-nanofiber self-powered PTFE/PA66 device for real-time breathing monitor by scalable solution blow spinning technology

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Nano Research 2022年第9期15卷 8458-8464页

作者： Pan Li Yibo Liu Han Zhang Zhiping Hu luna Jia Dongkui Liu Lu Yu Bo Li Youwei Yao School of Materials Science and Engineering Tsinghua UniversityBeijing 100084China Institute of Materials Research Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China

All-nanofiber self-powered device was fabricated using simple,low-cost,safe,and scalable solution blow spinning(SBS)technology for real-time respiratory monitor and timely identification of respiratory obstruction ***(PTFE)and polyamide-66(PA66)nanofibers were selected as triboelectric pairs,owing to strong ability to gain electrons of PTFE and supply electrons of ***(ethylene oxide)(PEO)was added to regulate spinning solution viscosity and prepare PTFE/PEO nanofibers,and the morphology and diameter distribution of nanofibers were *** nanofiber film was obtained after the decomposition of PEO in PTFE/PEO nanofiber and melt flow of PTFE pellets in a limited region,and possessed a tensile strength of 1.05 MPa and elongation at a break of 288.58%.Later,PTFE/PA66 all-nanofiber self-powered device was constructed containing PA66 nanofibers,and Au deposition film was used as electrodes by magnetron *** as-obtained device showed robust electrical performance with an open circuit voltage of~110 V at a loading force of 10 N,a short-circuit current of~5 uA at a loading force of 10 N and a frequency of 4 Hz,a maximum power density of 562 mW·m^(–2),and a current of 3.1 uA at a loading resistance of 30 MΩ.Based on the triboelectric mechanism,the device possessed stable response and effective sensibility for stimuli,was used to monitor human breathing conditions,prevent suffocation,and distinguish slow,normal,and fast breathing,with an output voltage of~0.08 V perceived in one normal respiratory circle.

关键词： polytetrafluoroethylene(PTFE) nanofibers triboelectric flexible electronics

WHICH IS THE USE OF SYSTEMS THEORY IN LITERATURE ANALYSIS？： THE DISCOVERY OF THE PLACE IN LA MANCHA IN DON QUIXOTE

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Journal of Systems Science and Systems Engineering 2017年第4期26卷 517-530页

作者： Francisco Parra-luna Complutense University of Madrid Yucatan 26 28231 Las Rozas Spain

The use of systems theory to attempt to determine which ＂place in La Mancha＂ was the one whose name Cervantes could not quite recall in his universal novel, appears to be ordained to change certain attitudes towards science held in Cervanfine literature. The reason： after four centuries of literary analysis, systemic methodology has proven able to identify the famous ＂place＂ with acceptable accuracy. Nonetheless, certain reasonable doubts persist around the suitability of a strictly scientific analysis of literature. In light of those doubts, the present article aims primarily to facilitate critique both of the systemic approach adopted and its outcome.

关键词： Don Quixote place in La Mancha systems theory epistemological totality determinantvariables

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孟河医派马培之治疗青风内障思想浅析

中国中医眼科杂志 2024年第4期34卷 360-363页

作者：李雪菲冯俊牛露娜李宝赢荆鲁中国中医科学院博士后流动站北京100700 中国中医科学院眼科医院北京100040

青风内障作为慢性内障性眼病,包含现代不同类型青光眼的不同病变阶段,是导致不可逆性失明的主要原因之一,中医学认为青风内障多属痰火搏结、精血不足、气机郁滞等。孟河医派代表人物马培之精通诸科,其临证医案中灵活辨证、化裁合宜,用... 详细信息

青风内障作为慢性内障性眼病,包含现代不同类型青光眼的不同病变阶段,是导致不可逆性失明的主要原因之一,中医学认为青风内障多属痰火搏结、精血不足、气机郁滞等。孟河医派代表人物马培之精通诸科,其临证医案中灵活辨证、化裁合宜,用药纯正质朴,以培补肝肾之法治疗青风内障多例,本文就其诊治青风内障的学术思想进行深入分析,探讨其辨治思路、用药规律,总结经验,为临床上诊治青光眼提供思路。

关键词：青风内障孟河医派马培之方证对应

基于机器学习的刀具磨损状态智能预测方法研究

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机电工程技术 2024年第2期53卷 29-34,123页

作者：梁璐娜魏建安袁雅阁吴国阳徐军贵州大学机械工程学院贵阳550025

以刀具为研究载体,运用人工智能和智能优化等先进技术,成功实现了刀具磨损状态的智能预测。研究重点在于建立有效的刀具磨损状态预测方法,全面解析刀具磨损机理、形式及磨钝标准等关键信息。同时,构建了自采刀具磨损状态监测平台,以便... 详细信息

以刀具为研究载体,运用人工智能和智能优化等先进技术,成功实现了刀具磨损状态的智能预测。研究重点在于建立有效的刀具磨损状态预测方法,全面解析刀具磨损机理、形式及磨钝标准等关键信息。同时,构建了自采刀具磨损状态监测平台,以便收集并处理相关数据。在数据处理过程中,采用小波滤噪和EMD-Shannon能量熵进行特征筛选,构建出特征空间数据集,为后续构建预测模型提供坚实的数据基础。结合支持向量机分类算法和智能优化算法,构建出刀具磨损状态的智能预测框架。此框架不仅提高了预测精度,也为维护人员提供了强有力的工具,利于更好地进行刀具磨损状态的预测和维护工作。为增强实际应用价值,将所取得的成果整合至基于MATLAB GUI的刀具磨损状态智能监测原型系统,以图形界面方式呈现预测结果,使用户直观地了解和掌握刀具的磨损状态。结果表明,该方法具有高精度,刀具磨损状态的识别精度可达84%,为相关领域提供了可靠的技术支持。

关键词：刀具磨损智能监测系统特征选择智能优化算法支持向量机

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Rock mass structural recognition from drill monitoring technology in underground mining using discontinuity index and machine learning techniques

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International Journal of Mining Science and Technology 2023年第5期33卷 555-571页

作者： Alberto Fernández JoséA.Sanchidrián Pablo Segarra santiago Gómez Enming Li Rafael Navarro Universidad Politécnica de Madrid–ETSI Minas y Energía Spain Universidad de Salamanca–GIR Charrock Spain

A procedure to recognize individual discontinuities in rock mass from measurement while drilling(MWD)technology is developed,using the binary pattern of structural rock characteristics obtained from in-hole images for *** from two underground operations with different drilling technology and different rock mass characteristics are considered,which generalizes the application of the methodology to different sites and ensures the full operational integration of MWD data *** approaches are followed for site-specific structural model building:a discontinuity index(DI)built from variations in MWD parameters,and a machine learning(ML)classifier as function of the drilling parameters and their *** prediction ability of the models is quantitatively assessed as the rate of recognition of discontinuities observed in borehole *** between the parameters involved in the models for each site,and differences in their weights,highlight the site-dependence of the resulting *** ML approach offers better performance than the classical DI,with recognition rates in the range 89%to 96%.However,the simpler DI still yields fairly accurate results,with recognition rates 70%to 90%.These results validate the adaptive MWD-based methodology as an engineering solution to predict rock structural condition in underground mining operations.

关键词： Drill monitoring technology Rock mass characterization Underground mining Similarity metrics of binary vectors Structural rock factor Machine learning

Cell extrusion in development and cancer,what MARCKS the difference for epithelial integrity?

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BIOCELL 2022年第3期46卷 639-644页

作者： LUCÍA VELOZ santiago A.BOSCH GONZALO APARICIO FLAVIO R.ZOLESSI Sección Biología Celular Facultad de CienciasUniversidad de la RepúblicaMontevideoCP 11400Uruguay Institut Pasteur de Montevideo MontevideoCP 11400Uruguay Sección Biofísica y Biología de Sistemas Facultad de CienciasUniversidad de la RepúblicaMontevideoCP 11400Uruguay

Cell extrusion is an active mechanism to eliminate non-viable or supernumerary cells in healthy *** also plays a role in carcinogenesis,both in tumor growth(apical extrusion)and metastasis(basal extrusion).Embryonic tissues like the neuroepithelium,on the other hand,present rates of proliferation comparable to that of carcinomas,without the occurrence of cell ***,the downregulation or phosphorylation of actinmodulating proteins like MARCKS,causes extensive neuroepithelial apical cell *** changes in MARCKS proteins phosphorylation and expression have also been correlated to carcinogenesis,we propose here an integrated model for their functions in epithelial integrity.

关键词： Epithelial-mesenchymal plasticity Carcinoma Neurulation Neuroepithelium Phosphorylation

Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia

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Neural Regeneration Research 2022年第7期17卷 1423-1430页

作者： santiago E.Charif M.Florencia Vassallu Lara Salvañal Lionel M.Igaz IFIBIO Houssay Grupo de Neurociencia de SistemasFacultad de MedicinaUniversidad de Buenos Aires-CONICETBuenos AiresArgentina

Protein synthesis is essential for cells to perform life metabolic *** alterations of protein content can lead to particular *** have an intrinsic array of mechanisms and pathways that are activated when protein misfolding,accumulation,aggregation or mislocalization *** of them(like the unfolded protein response)represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis(also known as proteostasis).This is even more important in neurons,as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with *** neurodegenerative pathologies such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct,unbalanced protein *** amyotrophic lateral sclerosis and frontotemporal dementia,the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa(TDP-43).TDP-43 is an RNA binding protein that participates in RNA metabolism,among other *** of TDP-43(*** and mislocalization)can dramatically affect neurons,and this has been linked to disease *** of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease *** variants can be causative of degeneration onset and *** neurodegenerative diseases(including amyotrophic lateral sclerosis and frontotemporal dementia)have no cure at the moment;however,modulating translation has recently emerged as an attractive approach that can be performed at several steps(***

关键词： amyotrophic lateral sclerosis frontotemporal dementia neurodegeneration neurodegenerative diseases protein imbalance protein synthesis modulation proteostasis therapeutical compounds transactive response DNA-binding protein of 43 kDa translation unfolded protein response

Smart dental materials for antimicrobial applications

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Bioactive Materials 2023年第6期24卷 1-19页

作者： Carolina Montoya Lina Roldan Michelle Yu Sara Valliani Christina Ta Maobin Yang santiago Orrego Department of Oral Health Sciences Kornberg School of DentistryTemple UniversityPhiladelphiaPAUSA Bioengineering Research Group(GIB) Universidad EAFITMedellínColombia Department of Endodontology Kornberg School of DentistryTemple UniversityPhiladelphiaPAUSA Bioengineering Department College of EngineeringTemple UniversityPhiladelphiaPAUSA

Smart biomaterials can sense and react to physiological or external environmental stimuli(e.g.,mechanical,chemical,electrical,or magnetic signals).The last decades have seen exponential growth in the use and development of smart dental biomaterials for antimicrobial applications in *** biomaterial systems offer improved efficacy and controllable bio-functionalities to prevent infections and extend the longevity of dental *** review article presents the current state-of-the-art of design,evaluation,advantages,and limitations of bioactive and stimuli-responsive and autonomous dental materials for antimicrobial ***,the importance and classification of smart biomaterials are ***,the categories of bioresponsive antibacterial dental materials are systematically itemized based on different stimuli,including pH,enzymes,light,magnetic field,and *** each category,their antimicrobial mechanism,applications,and examples are ***,we examined the limitations and obstacles required to develop clinically relevant applications of these appealing technologies.

关键词： Antimicrobial Antibacterial Antifungal Smart dental materials Bioresponsive biomaterials Stimuli-responsive Restorative dentistry Biofilm Antibiofilm Bioactive