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A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan Cuccia Rachael Coates Blake Nassar Ethan Littlefield elizabeth C.Martin Adam T.Melvin Cain Department of Chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of Chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural Engineering Louisiana State UniversityBaton RougeLA 70803USA Department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to *** is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause *** this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and *** device provides a platform to evaluate the effects of FSS on MCF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the *** of the effects of FSS on MCF-7 cells was carried out utilizing two approaches:single cell analysis and bulk *** single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an FSS magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell *** understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKT,and JAK/*** demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-STAT3 were ***,there was no change in p-ERK1/*** is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were *** together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer *** findin

关键词： fluid breast estrogen

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Assessment of Online Transgender Healthcare Teaching Modules for Internal Medicine Residents and Fellows

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Open Journal of Internal Medicine 2024年第2期14卷 259-268页

作者： elizabeth M. Lamos Rana Malek Department of Medicine University of Maryland School of Medicine Baltimore MD USA

Background: Transgender healthcare is not a formal learning requirement in Internal Medicine residency or fellowship. The National LGBTQ Task Force appealed to urgently train clinicians on the effective care of transgender patients. Few studies address the successful implementation of transgender healthcare teaching and education in graduate medical education. purpose: The purpose was to design an online asynchronous curriculum to address the need for improved transgender healthcare education in graduate medical education and assess change in knowledge and comfort in transgender healthcare for residents and fellow learners. Methods: A 6-module curriculum was developed using established guidelines and ACGME competencies as a framework for content. To assess curriculum effectiveness, participants received anonymous pre- and post-curriculum surveys which included a multiple-choice knowledge assessment, Likert scale comfort questions focusing on healthcare skills, and open-ended feedback questions. Results: Twenty-six internal medicine residents and fellows participated in the curriculum (2022-2023). There was a 69% post-survey response rate. participants improved their gender-affirming knowledge after completing the curriculum (p Conclusion: This online curriculum was successful in increasing knowledge and comfort in transgender care for IM residents and fellows. It provides a promising framework to address this gap in curricular content.

关键词： Education Fellow Resident Transgender

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The Interventional Capacity of Community Health Volunteers for Screening and Linkages of Non-Communicable Diseases in Nyeri County, Kenya

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Open Journal of preventive Medicine 2024年第4期14卷 61-78页

作者： Kenneth Mugambi Jackline Nyaberi elizabeth Echoka Kemri Graduate School Nairobi Kenya Jomo Kenyatta University of Science & Technology Nairobi Kenya

Non-communicable diseases (NCDs) account for 63% of mortalities. Approximately 80% of these NCD-related deaths occur in LMICs. A quasi-experimental study utilizing a non-equivalent pre-and post-test was conducted from May 2022 to March 2023 with 370 study participants. Multistage cluster and random sampling were used to select ten community units, and therefore, 150 CHVs were chosen for the control unit, and 150 were used to form the interventional group. Data was collected from the KOBO app. Six (6) homogenous FGDs comprised ten members, and 10 KII were conducted across study sites. Quantitative data was analyzed using SpSS version 28.0, and qualitative data was audio-recorded, transcribed, and analyzed via N-Vivo 12. The study shows that 59.3% of respondents have minimal information, and 92.7% (n = 139) have no clear understanding of NCDs, with a pre-intervention capacity of 48.8%. Independent sample t-test showed a significant difference in capacity from a pre-intervention average of 48.75 (SD ± 5.7)%, which increased to 68.28 (SD ± 7.6)%, p plays a pivotal role in grassroots healthcare delivery but requires optimization for NCD management.

关键词： Intervention Community Health Volunteers Non-Communicable Disease Screening Linkages

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How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

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Journal of Sport and Health Science 2024年第4期13卷 537-547页

作者： Jacqueline Josee van Ierssel Olivia Galea Kirsten Holte Caroline Luszawski elizabeth Jenkins Jennifer O’Neil Carolyn A Emery Rebekah Mannix Kathryn Schneider Keith Owen Yeates Roger Zemek Children’s Hospital of Eastern Ontario Research Institute OttawaON K1H 8L1Canada The Centre for Health Activity and Rehabilitation ResearchUniversity of OtagoDunedin 9016New Zealand Sport Injury prevention Research Centre Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada Alberta Children’s Hospital Research Institute University of Calgary CalgaryAB T2N 1N4Canada Hotchkiss Brain Institute University of CalgaryCalgaryAB T2N 4N1Canada Department of psychology University of CalgaryCalgaryAB T2N 1N4Canada g Faculty of MedicineUniversity of OttawaOttawaON K1H 8M5Canada School of Rehabilitation Sciences University of OttawaOttawaON K1H 8M5Canada Bruyere Research Institute OttawaON K1N 5C8Canada Departments of pediatrics and Emergency Medicine Harvard Medical SchoolBostonMA 02115USA Departments of pediatrics and Emergency Medicine University of OttawaOttawaON K1H 8M5Canada

purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following ***:We searched MEDLINE,Embase,psycInfo,CINAHL,and Web of Science up to May *** reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)*** information was sought my study authors where reporting was *** of bias(ROB)was assessed with the Cochrane ROB-2 *** examining non-pharmacological interventions following ***:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck *** scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified *** completeness improved after TIDieR and CERT publication,but p

关键词： Concussion Intervention Randomized controlled trial Systematic review

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Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice

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World Journal of Gastroenterology 2020年第23期26卷 3225-3235页

作者： Lakshini Y Herat Natalie C Ward Aaron L Magno elizabeth p.rakoczy Marcio G Kiuchi Markus p Schlaich Vance B Matthews School of Biomedical Sciences Dobney Hypertension CentreRoyal Perth Hospital UnitUniversity of Western AustraliaPerth 6000Australia Faculty of Health and Medical Sciences University of Western AustraliaCrawley 6009Australia Faculty of Health Sciences School of Public HealthCurtin UniversityBentley 6102Australia Research Centre Royal Perth HospitalPerth 6000Australia Department of Molecular Ophthalmology University of Western AustraliaCrawley 6009Australia Dobney Hypertension Centre School of MedicineRoyal Perth Hospital UnitUniversity of Western AustraliaPerth 6000Australia Department of Cardiology and Department of Nephrology Royal Perth HospitalPerth 6000Australia

BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated *** protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic *** To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse *** The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield *** Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba ***, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced

关键词： Sodium glucose co-transporter inhibitors Sodium glucose co-transporter 2 Diabetes Diabetic retinopathy Mouse Gut microbiota Empagliflozin Dapagliflozin Succinate Akimba

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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of pKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand p.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal elizabeth A.Repasky Kelvin p.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and pathogenesis program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA present address:University of Colorado Boulder BoulderCO 80309USA present address:Dana Farber Cancer Institute BostonMA 02215USA present address:Massachusetts Institute of Technology BostonMA 02139USA present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of pKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,pKM alternative splicing occurred independently of CD28-driven pI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 pKM2

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淮北煤田中高阶煤储层物性表征及深部有利区预测研究

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非常规油气 2024年

作者：侯海海 elizabeth Cruz pérez 陈泓圳胡博何倩黄乡琴辽宁工程技术大学矿业学院

为定量表征淮北煤田中高阶煤储层物性特征，采用工业分析、显微煤岩组分定量、低温氮吸附、高压压汞、核磁共振等实验手段，对淮北煤田7个煤样的物性特征进行了研究。结果表明，淮北煤田煤显微组分以镜质组为主，最大镜质组反射率变化... 详细信息

为定量表征淮北煤田中高阶煤储层物性特征，采用工业分析、显微煤岩组分定量、低温氮吸附、高压压汞、核磁共振等实验手段，对淮北煤田7个煤样的物性特征进行了研究。结果表明，淮北煤田煤显微组分以镜质组为主，最大镜质组反射率变化较大，在0.7%-2.5%之间，可能受燕山期郯庐和太行山岩浆活动的共同影响。该煤质具有中-高灰分、低-极低硫含量、低磷、中高热值的特点。从低阶煤到中阶煤，由于脱水作用较强，煤基质收缩，吸附孔隙和渗流孔隙体积减小，裂隙体积增大；从中阶煤到高阶煤，吸附孔具有明显的优势，表明其对甲烷的吸附能力增强。预测淮北煤田宿县矿区的南坪深部、桃园祁南深部、彭桥深部、朱仙庄北部，临涣矿区的任楼赵集深部、许疃深部，濉萧矿区的萧西深部为该区煤层气勘探的较有利区，

关键词：淮北煤田煤储层物性孔裂隙结构煤层气有利区优选

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A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia

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Animal Models and Experimental Medicine 2024年第3期7卷 367-376页

作者： Lauren S.Kelly Jennifer A.Munley Erick E.pons Kolenkode B.Kannan elizabeth M.Whitley Letitia E.Bible philip A.Efron Alicia M.Mohr Department of Surgery and Sepsis and Critical Illness Research Center University of Florida College of MedicineGainesvilleFloridaUSA pathogenesis LLCGainesvilleFloridaUSA

Background:Severe trauma is associated with systemic inflammation and organ *** rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human *** aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic ***:Male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock(LCHS),multicompartmental polytrauma(pT)(unilateral lung contusion,hemorrhagic shock,cecectomy,bifemoral pseudofracture),or na?ve ***,plasma toll-l ike receptor 4(TLR4),hemoglobin,spleen to body weight ratio,bone marrow(BM)erythroid progenitor(CFU-GEMM,BFU-E,and CFU-E)growth,plasma granulocyte colony-stimulating factor(G-CSF)and right lung histologic injury were assessed on day 7,with significance defined as p valuespolytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS(p=0.0002)along with elevated plasma TLR4(pppleen to body weight ratios(p=0.004).Both LCHS and pT demonstrated suppression of CFU-E and BFU-E growth compared to naive(ppplasma G-CSF was elevated in pT compared to both na?ve and LCHS(pp=0.02).LCHS and pT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial ***:Multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia,splenic tissue enlargement,weight loss,and increased inflammatory activity compared to a less severe *** may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.

关键词： anemia i nflammation polytrauma pseudofracture shock

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A novel diagnostic gene region for distinguishing between two pest fruit flies:Bactrocera tryoni(Froggatt)and Bactrocera neohumeralis(Hardy)(Diptera:Tephritidae)

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Insect Science 2024年第4期31卷 1285-1295页

作者： Melissa L.Starkie elizabeth V.Fowler Alexander M.piper Xiaocheng Zhu pauline Wyatt David Gopurenko Matt N.Krosch Francesca Strutt Karen F.Armstrong Hamish patrick Mark K.Schutze Mark J.Blacket Department of Agriculture and Fisheries BiosecurityBrisbaneQueenslandAustralia Agriculture Victoria AgriBioBundooraVictoriaAustralia Department of primary Industries Wagga Wagga Agricultural InstituteWagga WaggaNew South WalesAustralia Forensic Services Group Queensland Police ServiceBrisbaneQueenslandAustralia Department of pest-management and Conservation Lincoln UniversityLincolnNew Zealand Better Border Biosecurity(B3 B3nz.org.nz)LincolnNew Zealand

Bactrocera tryoni and Bactrocera neohumeralis are morphologically similar sibling pest fruit fly species that possess different biological attributes,geographic distributions,and host *** need to differentiate between the two species is critical for accurate pest status assessment,management,biosecurity,and maintenance of reference *** morphologically similar,adults may be separated based on subtle characters;however,some characters exhibit intraspecific variability,creating overlap between the two ***,there is currently no single molecular marker or rapid diagnostic assay that can reliably distinguish between *** and ***;therefore,ambiguous samples remain *** we report the first molecular marker that can consistently distinguish between *** and *** diagnostic region consists of two adjacent single nucleotide polymorphisms(SNps)within the pangolin(pan)gene *** confirmed the genotypes of each species are consistent across their distributional range,then developed a tetra-primer amplification refractory mutation system(ARMS)pCR assay for rapid diagnosis of the *** assay utilizes four primers in multiplex,with two outer universal primers,and two internal primers:one designed to target two adjacent SNps(AA)present in *** and the other targeting adjacent SNps present in ***(GG).The assay accurately discriminates between the two species,but their SNp genotypes are shared with other nontarget tephritid fruit fly ***,this assay is most suited to adult diagnostics where species confirmation is necessary in determining ambiguous surveillance trap catches;maintaining pure colony lines;and in Sterile Insect Technique management responses.

关键词： ARMS-pCR colony molecular diagnostics pangolin tetra-primer

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Quantifying Kinematic Tremor in an NGLY1-Deficient Individual: A Case Study

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Case Reports in Clinical Medicine 2024年第1期13卷 25-36页

作者： Brock Futrell Christopher Alexander Malaya Dacia Martinez Diaz Christian Alfaro Hannah elizabeth Gustafson Subhalakshmi Chandrasekaran Rhea Mohan phatak Bernhard Suter Charles Shannon Layne Department of Health and Human performance University of Houston Houston USA Center for Neuromotor and Biomechanics Research University of Houston Houston USA Department of Computer Science and Engineering Texas A&M University College Station USA Blue Bird Circle Rett Center Texas Children’s Hospital Houston USA Baylor College of Medicine Houston USA Center for NeuroEngineering and Cognitive Science University of Houston Houston USA

NGLY1 Deficiency is an autosomal recessive congenital disorder that has been identified in less than 100 individuals. Most individuals with NGLY1 Deficiency display hyperkinetic movement disorders, including choreiform, athetoid, dystonic myoclonic, dyskinetic, and dysmetric movements. Developing a consistent and concise consensus on the classification and evaluation of tremors is essential to forward the research and treatment of tremors. It has also been reported that some individuals with NGLY1 Deficiency demonstrate tremor, but such tremor has never been formally investigated. The primary objective of this study is to determine if an individual with NGLY1 Deficiency demonstrates an identifiable tremor during a series of arm movements and, if so, describe the frequency and power characteristics of that tremor. Arm movement kinematics were obtained using a 16-camera Vicon system, and time series trajectory waveforms for three planes of a marker placed on the hand were developed. Custom MATLAB scripts were utilized to compute Fast Fourier Transformations of the data within the identified waveform segments. A mean frequency of 2.30 Hz (SD = 1.05) with a mean power of 5.02 |p1(f)| (SD = 4.63) suggests that our participant’s kinematic data did display a persistent tremor in both hands across all tasks and movement planes. Analyses of the reaching hand and the non-reaching hand suggest the participant displayed an action tremor in both postural and intention (kinetic) tremors. Future directions should include assessing additional individuals with NGLY1 Deficiency to determine if the tremor is a distinguishable disorder behavior. Additionally, evaluating other anatomical sites, such as the elbow, head, and lower limbs, would provide further insights into the characteristics of this tremor.

关键词： Tremor NGLY Fast Fourier Transformation Reaching Hyperkinetic Movement

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