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Mechanisms of acquired resistance of BRCA1/2-driven tumors to platinum compounds and pARp inhibitors

World Journal of Clinical Oncology 2021年第7期12卷 544-556页

作者： Evgeny Imyanitov anna sokolenko Department of Tumor Growth Biology N.N.Petrov Institute of OncologySaint-Petersburg 197758Russia Department of Medical Genetics St.-Petersburg Pediatric Medical UniversitySaint-Petersburg 194100Russia Department of Oncology I.I.Mechnikov North-Western Medical UniversitySaint-Petersburg 191015Russia

Molecular pathogenesis of tumors arising in BRCA1/2 germ-line mutation carriers usually includes somatic inactivation of the remaining allele of the involved ***,BRCA1/2-driven cancers are sensitive to platinum-based therapy and poly(ADp-ribose)polymerase inhibitors(pARpi).Long-term exposure to these drugs may result in the emergence of secondary BRCA1/2 mutations,which restore the open-reading frame of the affected *** platinum/pARpi crossresistance mechanism applies both for BRCA1 and BRCA2 genes and has been repeatedly validated in various laboratory models and multiple clinical *** are some other routes associated with the partial rescue of BRCA1/2 function or the development of BRCA1/2-independent pathways for genomic maintenance;however,their actual clinical relevance remains to be *** addition,studies on the short-term neoadjuvant therapy for ovarian cancer revealed that even chemonaive BRCA1-driven tumors contain a small proportion of BRCA1-proficient *** pre-existing cells with retained BRCA1 heterozygosity rapidly repopulate the tumor mass during platinum exposure,but become outcompeted by BRCA1-deficient cells during therapy *** of the platinum/pARpi resistance pathways has led to the development of novel therapeutic approaches,which aim to improve the management of BRCA1/2-related cancers and are currently undergoing preclinical and clinical evaluation.

关键词： BRCA1/2 mutations platinum-based therapy poly(ADp-ribose)polymerase inhibitors Drug resistance Secondary mutations Intratumoral heterogeneity Neoadjuvant therapy

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Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： Siva S.V.p.Sakamuri Anil Sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi pradeepkiran priyanka Rawat Arubala p.Reddy Erika Orlov pHemachandra Reddy Department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Department of pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Department of public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAp-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

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Subject Area Risk Assessment of Four Hungarian Universities with a View to the QS University Rankings by Subject

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Journal of Data and Information Science 2022年第4期7卷 61-80页

作者： péter Sasvári anna Urbanovics public Governance and International Studies University of Public ServiceHungary University of Miskolc Hungary

purpose:The aim of our paper is to investigate the role of a mentor leading a research team in the overall scientific performance of an academic institution and the possible risks of their departure with a special attention to their publication ***/methodology/approach:By using SciVal subject area data,we composed a formula describing the level of vulnerability of any given university in the case of losing any of its leading mentors,identifying other risk factors by dividing their careers into separate ***:It turns out that the higher field-weighed citation impact is,the better position universities reach in the rankings by subject and the vulnerability of institutions highly depends on the mentors,especially in view of their contribution to the topic *** limitations:The analysis covers the publication output of leading researchers working at four Hungarian universities,the scope of the analysis is worth being *** implications:Our analysis has the potential to give an applicable systemic approach as well as a data collection scheme to university managements so as to formulate an inclusive and comprehensive research strategy involving the introduction of a reward system aimed at publications and further encouraging national and international research ***/value:The methodology and the principles of risk assessment laid down in our paper are not restricted to measuring the vulnerability level of a limited group of academic institutions,they can be appropriately used for investigating the role of mentors or leading researchers at every university across the globe.

关键词： QS Rankings by Subject Scientific Competitiveness Risk Analysis Subject Area Exposure

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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SpAST spastin

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Microbial-inspired self-healing of concrete cracks by sodium silicate-coated recycled concrete aggregates served as bacterial carrier

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Frontiers of Structural and Civil Engineering 2024年第1期18卷 14-29页

作者： Jing XU Xianzhi WANG Wu YAO anna A.KULMINSKAYA Surendra p.SHAH Key Laboratory of Advanced Civil Engineering Materials(Ministry of Education) School of Materials Science and EngineeringTongji UniversityShanghai 201804China petersburg Nuclear physics Institute Named by B.p.Konstantinov of National Research Centre Kurchatov InstituteGatchina 188300Russia Center for Advanced Construction Materials University of Texas at ArlingtonArlingtonTX 76019USA

Microbially induced carbonate precipitation(MICp)is a promising technique for the autonomous healing of concrete *** this study,the effect of pH on MICp was *** results indicate that the MICp process was inhibited when the pH was higher than *** vaterite and calcite were produced when the pH wasproduced when the pH was>*** concrete aggregates(RCA)coated with sodium silicate have been proposed as protective carriers for microbial healing *** the presence of the coated RCA resulted in a loss of the splitting tension strength of the concrete,the loaded healing agents were highly efficient in self-healing *** incorporated with 20%RCA loaded with healing agents exhibited the best self-healing *** the initial crack widths were between 0.3 and 0.4 mm,the 7-d mean healing rate was approximately 90%.At 28 d,the crack area filling ratio was 86.4%,while its water tightness recovery ratio was 74.4%and 29.8%,respectively,for rapid and slow *** study suggests that RCA coated with sodium silicate is an effective method for packaging microbial healing agents and has great potential for developing cost-effective self-healing concrete.

关键词： self-healing microbial-induced carbonate precipitation water uptake recycled concrete aggregate protective carrier

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pregnancy and inflammatory bowel disease: Do we provide enough patient education? A British study of 1324 women

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World Journal of Gastroenterology 2016年第36期22卷 8219-8225页

作者： Isabel Carbery Jihane Ghorayeb anna Madill Christian p Selinger Leeds Gastroenterology Institute Leeds Teaching Hospitals NHS Trust School of psychology University of Leeds

AIM To examine patient knowledge and factors influencing knowledge about pregnancy in British women with inflammatory bowel disease(IBD).METHODS This is a post hoc analysis of a study of female members of Crohn's and Colitis United Kingdom, aged 18-45 years who were sent an online questionnaire recording patient demographics, education, employment, marital status, and disease characteristics. Disease related pregnancy knowledge was recorded using Crohn's and colitis pregnancy knowledge score(CCpKnow).RESULTS Of 1324 responders, 776(59%) suffered from Crohn's disease, 496(38%) from ulcerative colitis and 52(4%) from IBD-uncategorised. CCpKnow scores were poor(0-7) in 50.8%, adequate(8-10) in 23.6%, good(11-13) in 17.7% and very good(≥ 14) in 7.8%. Multiple linear regression analysis revealed that higher CCpKnow scores were independently associated with higher educational achievement(p p = 0.003) and having consulted a health care professional about pregnancy and IBD(p = 0.001). CONCLUSION Knowledge was poor in 50%. Speaking with healthcare professionals was a modifiable factor associated with better knowledge. This illustrates the importance of disease related pregnancy

关键词： Inflammatory bowel disease Ulcerative colitis Crohn’s disease patient knowledge pregnancy Reproduction

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Effects of habitat configuration on biodiversity along gradients of forest cover on the Swiss plateau

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Forest Ecosystems 2024年第5期11卷 659-669页

作者： Yiwen pan anna M.Hersperger Gang Ge Michael p.Nobis Key Laboratory of poyang Lake Environment and Resource Utilization Ministry of EducationSchool of Resources&EnvironmentNanchang UniversityNanchang330031China Swiss Federal Institute for Forest Snow and Landscape Research WSLZürcherstrasse 1118903BirmensdorfSwitzerland School of Life Sciences Nanchang UniversityNanchang330031China

The negative effects of habitat loss on biodiversity are undisputed,while the effect of habitat configuration,i.e.,the spatial arrangement of habitat area,has been debated for *** develop a more comprehensive understanding,it is important to know when and how configuration *** this study,we tested whether forest configuration influences the richness of species in groups characterized by varying shade tolerance in different ways and how such effects are related to habitat amount(i.e.,the percentage of forest cover)at the landscape *** on 104 survey plots(each measuring 1km^(2))of vascular plants on the Swiss plateau,and using two statistical approaches(i.e.,multiple regression and path analysis),we modeled the effects of habitat amount and configuration(measured as number of forest patches,total edge length,and proximity index)across all the plots and separately for three habitat amount classes:30%forest *** we modeled all plots together,we found that,after controlling for habitat amount,the forest configuration significantly affected species *** we considered the different habitat amount classes separately,most of the significant effects of habitat configuration on species richness occurred only for habitat amounts ofponse to forest configuration differed among species with different shade *** forest area waspatches and the total edge length on the species richness of light-demanding forest species were greater than the effect of habitat amount,whereas neither configuration metric affected the richness of shade-tolerant *** conclusion,our findings highlight the importance of configuration in landscapes with a small amount of *** the same time,they demonstrate that considering the confounding factors(*** traits)is important for understanding the effects of forest configuration on biodiversity and that genera

关键词： Forest plants Habitat amount Landscape fragmentation Species richness Swiss plateau

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Machine learning applications in healthcare clinical practice and research

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World Journal of Clinical Cases 2025年第1期13卷 16-21页

作者： Nikolaos-Achilleas Arkoudis Stavros p papadakos Research Unit of Radiology and Medical Imaging School of MedicineNational and Kapodistrian University of AthensAthens 11528Greece 2^(nd)Department of Radiology “Attikon”General University HospitalMedical SchoolNational and Kapodistrian University of AthensChaidari 12462Greece Department of Gastroenterology Laiko General HospitalNational and Kapodistrian University of AthensAthens 11527Greece

Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human *** its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and *** this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical *** authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and *** addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+***,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.

关键词： Machine Learning Artificial Intelligence Clinical practice Research Glomerular filtration rate Non-alcoholic fatty liver disease Medicine

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