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Targeting hormone-resistant breast cancer cells with docetaxel:a look inside the resistance

Cancer Drug Resistance 2023年第1期6卷 103-115页

作者： Alexander M.Scherbakov Anna A.Basharina Danila V.Sorokin Ekaterina I.Mikhaevich Iman E.Mizaeva alexandra l.mikhaylova Tatiana A.Bogush Mikhail A.Krasil’nikov Department of Experimental Tumor Biology Blokhin N.N.National Medical Research Center of OncologyMoscow 115522Russian Federation Group of Molecular Tumor Markers Blokhin N.N.National Medical Research Center of OncologyMoscow 115522Russian Federation

Aim:The study aims to analyze the effect of long-term incubation of ERα-positive MCF7 breast cancer cells with 4-hydroxytamoxifen(HT)on their sensitivity to tubulin polymerization inhibitor ***:The analysis of cell viability was performed by the MTT *** expression of signaling proteins was analyzed by immunoblotting and flow ***αactivity was evaluated by gene reporter *** establish hormone-resistant subline MCF7,breast cancer cells were treated with 4-hydroxytamoxifen for 12 ***:The developed MCF7/HT subline has lost sensitivity to 4-hydroxytamoxifen,and the resistance index was *** Akt activity(2.2-fold)and decreased ERαexpression(1.5-fold)were revealed in MCF7/HT *** activity of the estrogen receptorαwas reduced(1.5-fold)in MCF7/*** of class Ⅲβ-tubulin expression(TUBB3),a marker associated with metastasis,revealed the following trends:higher expression of TUBB3 was detected in triple-negative breast cancer MDA-MB-231 cells compared to hormone-responsive MCF7 cells(Plowest expression of TUBB3 was found in hormone-resistant MCF7/HT cells(MCF7/HTly 1:2:4).High TUBB3 expression strongly correlated with docetaxel resistance:IC_(50)value of docetaxel for MDA-MB-231 cells was greater than that for MCF7 cells,whereas resistant MCF7/HT cells were the most sensitive to the *** accumulation of cleaved PARP(a 1.6-fold increase)and Bcl-2 downregulation(1.8-fold)were more pronounced in docetaxel-treated resistant cells(Plin D1 decreased(2.8-fold)only in resistant cells after 4 nM docetaxel treatment,while this marker was unchanged in parental MCF7 breast cancer ***:Further development of taxane-based chemotherapy for hormone-resistant cancer looks highly promising,especially for cancers with low TUBB3 expression.

关键词： Cancer docetaxel 4-hydroxytamoxifen classⅢβ-tubulin resistance breast cancer estrogen receptors alpha

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Weight regain after intragastric balloon for pre-surgical weight loss

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2040-2046页

作者： Danielle Abbitt Kevin Choy alexandra Kovar Teresa S Jones Krzysztof J Wikiel Edward l Jones Department of Surgery University of ColoradoAuroraCO 80045United States Department of Surgery Rocky Mountain Regional Veteran Affairs Medical CenterAuroraCO 80045United States

BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related *** can place patients at increased risk of operative and postoperative *** intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well *** To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon *** This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective *** outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were *** criteria included those with balloon in place at time of *** Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective *** patients were required to participate in a 12-month weight management program to be eligible for balloon *** surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip *** average age at placement was 53 years±11 years,majority(91%)were *** average duration of intragastric balloon therapy was 186 days±41 *** average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight ***-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss ***-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon *** pat

关键词： Intragastric balloon Weight loss Obesity Bariatric Body mass index

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*** model of riboflavin transporter deficiency(RTD)disorder reveals deficits in synaptic transmission and movement

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Genes & Diseases 2024年第4期11卷 120-123页

作者： Ramesh K.Narayanan Gonzalo Perez-siles Kamila A.Marzec alexandra Boyling Brent Neumann Manoj P.Menezes Marina l.Kennerson Northcott Neuroscience laboratory ANZAC Research Institute-Sydney Local Health DistrictSydneyNSW 2139Australia Sydney Medical School University of SydneySydneyNSw 2050Australia ANZAC Research Institute-Sydney local Health District SydneyNSW 2139Australia Neuroscience Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVictoria 3800Australia TY Nelson Department of Neurology and Neurosurgery and Kids Neuroscience Children's Hospital at WestmeadWestmeadSydneyNSW2145Australia Paediatrics and Child Health The University of SydneySydneySydneyNSW 2145Australia Molecular Medicine laboratory Concord General Repatriation HospitalSydneyNSW 2139Australia

Riboflavin transporter deficiency(RTD),previously known as Brown-Vialetto-Van laere syndrome,is a childhoodonset neurodegenerative disorder characterized by sensory and motor neuron degeneration causing ataxia,muscle weakness,optic atrophy,and respiratory *** in SlC52A2 and SlC52A3,solute carrier family members that encode riboflavin(RF)transporters RFVT2 and RFVT3,are known to cause RTD types 2 and 3,respectively.

关键词： RTD degeneration TD

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Rare dentin defects:Understanding the pathophysiological mechanisms of COlXVA1 mutations

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Genes & Diseases 2024年第5期11卷 1-5页

作者： Isaac Maximiliano Bugueno Tristan Rey alexandra Jimenez-Armijo Marzena Kawczynski Naji Kharouf Marie-Cecile Maniere Yann Herault Agnes Bloch-Zupan Virginie Haushalterlaugel Institute of Genetics and Molecular and Cellular Biology(IGBMC) CNRS-UMR7104INSERM U1258Universitede StrasbourgIllkirch 67400France Faculty of Dentistry Universitede StrasbourgStrasbourg 67000France Institute of Advanced Studies(USIAS) Universitede StrasbourgStrasbourg 67045France Reference Center for Rare Oral and Dental Diseases(CRMR-O-Rares) Oral Medicine and Surgery DepartmentHopitaux Universitaires de Strasbourg(HUS)Strasbourg 67000France Rare Diseases Health Network“TETE COU”&European Reference Network ERN CRANIO Strasbourg 67000France “Institut de Genetique Medicale d’Alsace” Laboratory of Genetic DiagnosticHopitaux Universitaires de Strasbourg(HUS)Strasbourg 67000France Biomaterials and Bioengineering laboratory Inserm UMR_S 1121Strasbourg 67000France Orofacial Development and Regeneration Faculty of MedicineInstitute of Oral BiologyCentre of Dental MedicineUniversity of ZurichZurich 8032Switzerland

Dentin is a mineralized tissue with a chemical composition similar to bone but with a higher mineralized density and *** constitutes the central structure of the tooth between the internal pulp and external enamel toward the oral cavity or cementum toward the underlying *** dentin defects occur in a variety of rare genetic *** can manifest as“isolated”occurrences such as in dentinogenesis imperfecta(DI)or dentin dysplasia(DD)or can be associated with other symptoms in diseases such as osteogenesis imperfecta,Goldblatt syndrome,microcephalic osteodysplastic primordial dwarfism type II,among others.

关键词： diseases den rigidity

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Microbial community coalescence and nitrogen cycling in simulated mortality decomposition hotspots

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Ecological Processes 2023年第3期12卷 172-188页

作者： Sarah W.Keenan alexandra l.Emmons Jennifer M.DeBruyn Department of Geology and Geological Engineering South Dakota School of Mines and Technology Department of Anthropology University of Tennessee Department of Biosystems Engineering and Soil Science University of Tennessee

Background The pulsed introduction of dead plant and animal material into soils represents one of the primary mechanisms for returning organic carbon(C) and nitrogen(N) compounds to biogeochemical cycles. Decomposition of animal carcasses provides a high C and N resource that stimulates indigenous environmental microbial communities and introduces non-indigenous, carcass-derived microbes to the environment. However, the dynamics of the coalesced microbial communities, and the relative contributions of environment-and carcass-derived microbes to C and N cycling are unknown. To test whether environment-derived, carcass-derived, or the combined microbial communities exhibited a greater influence on C and N cycling, we conducted controlled laboratory experiments that combined carcass decomposition fluids and soils to simulate carcass decomposition hotspots. We selectively sterilized the decomposition fluid and/or soil to remove microbial communities and create different combinations of environment-and carcass-derived communities and incubated the treatments under three temperatures(10, 20, and 30 ℃).Results Carcass-derived bacteria persisted in soils in our simulated decomposition scenarios, albeit at low abundances. Mixed communities had higher respiration rates at 10 and 30 ℃ compared to soil or carcass communities alone. Interestingly, at higher temperatures, mixed communities had reduced diversity, but higher respiration, suggesting functional redundancy. Mixed communities treatments also provided evidence that carcass-associated microbes may be contributing to ammonification and denitrification, but that nitrification is still primarily carried out by native soil *** Our work yields insight into the dynamics of microbial communities that are coalescing during carcass decomposition, and how they contribute to recycling carcasses in terrestrial ecosystems.

关键词： Carcass decomposition Microcosm Nitrogen Carbon Biogeochemical cycling Coalescence

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Cost and value of office-based facial plastic and reconstructive surgery procedures

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第3期9卷 257-261页

作者： alexandra O.Hamberis Mingyang l.Gray Department of Otolaryngology-Head and Neck Surgery Icahn School of Medicineat Mount SinaiNew YorkUSA

Introduction:This chapter will provide an overview of factors affecting the cost of office-based procedures in Facial Plastics and Reconstructive Surgery(FPRS),and will discuss the value of office-based *** and Methods:An in-depth literature review was conducted using multiple primary and secondary *** from multiple disciplines was included in the review,including otolaryngology,anesthesiology,surgery,public health,and ***/Conclusions:A wide variety of procedures can be performed in an FPRS *** upfront costs to the office include laser,electrocautery and surgical *** investments will yield an initial negative cost margin until sufficient case volume is *** is often in the best interest of the patient to perform a procedure in-office and avoid the facility and anesthesia fees associated with a surgical center or *** and reimbursements vary greatly across regions and ***,overall cost depends on payer mix,procedures performed,and productivity of the *** scarcity of literature on this topic as it applies specifically to FPRS indicates that further research is needed to elucidate the value of common facial plastics procedures in an office-based setting.

关键词： facial plastic surgery office-based procedures reconstructive surgery

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The structure of colloidal polyethylenimine-silica nanocomposite microparticles

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Particuology 2023年第5期76卷 86-100页

作者： alexandra Semenova luke W.Giles Mark louis P.Vidallon Bart Follink Paul l.Brown Rico F.Tabor School of Chemistry Monash University19 Rainforest Walk.Clayton3800Australia Rio Tinto Bundoora Technical Development Centre1 Research AvenueBundoora3083Australia

Deposition of silica from an organosilane tetraethoxysilane(TEOS)onto parent polyethylenimine(PEI)microgel particles produces a novel PEI-silica nanocomposite,which possesses greater adsorption ca-pacity for copper ions than either parent *** study explores factors governing interactions of silica with the PEI matrix,along with structural features of resulting PEI-silica composite particles,to explain their properties and determine their application *** influence of initial TEOS/PEI mass ratio and the duration of silica deposition on the final silica content and distribution in the composite are studied.A comparative analysis of the structural architecture of chemically etched silica remnants,original PEI-silica composite particles and the parent PEI-microgel is carried out using X-ray photo-electron spectroscopy,small-angle X-ray scattering,and electron microscopy *** is found that silica sol nanoparticles are evenly distributed throughout the PEI-microgel framework and interlinked with it via electrostatic interactions,enabling a structural model of the PEI-silica nanocomposite to be *** chemical stability of resulting nanocomposite particles in parallel with the parent PEI-microgel is tested and shown to be robust for more than 100 days of storage in aqueous dispersions across a range of pH conditions,highlighting the application potential for these particles in copper capture.

关键词： Polyethylenimine Silica Organic-inorganic composite Nano-scale morphology Small angle X-ray scattering

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Chronotype and self-reported sleep,alertness,and mental health in U.S. sailors

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Military Medical Research 2022年第2期9卷 259-261页

作者： Elizabeth M.Harrison alexandra P.Easterling Emily A.Schmied Suzanne l.Hurtado Gena l.Glickman Center for Circadian Biology University of California San DiegoSan DiegoUSA leidos Inc.San DiegoUSA Health and Behavioral Sciences Department Naval Health Research CenterSan DiegoUSA School of Public Health San Diego State UniversitySan DiegoUSA Departments of Psychiatry and Neuroscience Uniformed Services University of the Health SciencesBethesdaUSA

Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype(“morningness”or “eveningness”) is strongly associated with sleep, health and performance. The objective of this study was to examine associations between validated measures of chronotype and sleep quality, daytime functioning, alertness,and symptoms of depression, anxiety, and post-traumatic stress disorder(PTSD) in US service members(n=298).Although predominantly young males(who skew toward eveningness in civilian populations), these Sailors skewed toward morningness(35.6% morning, 51.3% intermediate). Eveningness was associated with symptoms of depression and PTSD(Pless time in bed(Pleep disruption(Plertness(Pless likely to consider sleep important for performance(Ples should be aligned with endogenous rhythms, whenever possible, and evening chronotypes may benefit from targeted interventions. Chronotype should be examined alongside health and readiness in service members.

关键词： Circadian Chronotype Sleep Military Readiness Depression Anxiety Post-traumatic stress disorder

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The computerized lASSI-BC Test versus the Standard lASSI-l Paper-and-Pencil Version in Community-Based-Samples

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Advances in Alzheimer's Disease 2024年第1期13卷 11-25页

作者： Rosie E. Curiel Cid alexandra Ortega Ubbo Visser Marcela Kitaigorodsky D. Diane Zheng Diana Hincapie Kirsten Horne Crenshaw Ashleigh Beaulieu Brooke Bosworth liz Gallardo Emory Neer Sofia Ramirez Elizabeth A. Crocco Mike Georgiou Efrosyni Sfakianaki David A. loewenstein Center for Cognitive Neuroscience and Aging and Department of Psychiatry and Behavioral Sciences Miller School of Medicine University of Miami Miami FL USA Department of Computer Sciences University of Miami Coral Gables FL USA Nova Southeastern University Fort Lauderdale FL USA Department of Radiology and Nuclear Medicine Miller School of Medicine University of Miami Miami FL USA

Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the lASSI-l. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the lASSI-l (lASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the lASSI-l. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the lASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the lASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil lASSI-l. Overall, the lASSI-BC was comparable, and in some ways, superior to the paper-and-pencil lASSI-l. Advantages of the lASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.

关键词： Mild Cognitive Impairment Proactive Semantic Interference lASSI-l Computerized Cognitive Assessment

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Epidural oscillating field stimulation increases axonal regenerative capacity and myelination after spinal cord trauma

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Neural Regeneration Research 2022年第12期17卷 2730-2736页

作者： Maria Bacova Katarina Bimbova alexandra Kisucka Nadezda lukacova Jan Galik Institute of Neurobiology of Biomedical Research Center Slovak Academy of SciencesSoltesovejKosiceSlovak Republic

Oscillating field stimulation(OFS)with regular alterations in the polarity of electric current is a unique,experimental approach to stimulate,support,and potentially guide the outgrowth of both sensory and motor nerve fibers after spinal cord injury(SCI).In previous experiments,we demonstrated the beneficial effects of OFS in a 4-week survival period after *** this study,we observed the major behavioral,morphological,and protein changes in rats after 15 minutes of T9 spinal compression with a 40 g force,followed by long-lasting OFS(50μA),over a 8-week survival *** groups of rats were analyzed:rats after T9 spinal compression(SCI group);SCI rats subjected to implantation of active oscillating field stimulator(OFS+SCI group);and SCI rats subjected to nonfunctional OFS(nOFS+SCI group).Histopathological analysis of spinal tissue indicated a strong impact of epidural OFS on the reduction of tissue and myelin loss after SCI in the segments adjacent to the lesion *** fluorescent analysis of the most affected areas of spinal cord tissue revealed a higher number of spared axons and oligodendrocytes of rats in the OFS+SCI group,compared with rats in the SCI and nOFS+SCI *** protein levels of neurofilaments(NF-l),growth-associated protein-43(marker for newly sprouted axons),and myelin basic protein in rats were signifiantly increased in the OFS+SCI group than in the nOFS+SCI and SCI *** suggests a supporting role of the OFS in axonal and myelin regeneration after ***,rats in the OFS+SCI group showed great improvements in sensory and motor functions than did rats in the nOFS+SCI and SCI *** these findings suggest that long-lasting OFS applied immediately after SCI can provide a good microenviroment for recovery of damaged spinal tissue by triggering regenreative processes in the acute phase of injury.

关键词： axonal regenerative capacity behavioral assessment epidural stimulation motor recovery myelin regeneration oscillating field stimulation spinal cord injury

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