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Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic cerebrovascular Events III (TRAcE III): a randomised, phase III, open- label, controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong Bruce c V campbell Ma.c.fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang Neurology Beijing Tiantan HospitalBeijingChina china National clinical Research center for Neurological Diseases BeijingChina Department of Medicine and Neurology The University of MelbourneMelbourneVictoriaAustralia Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of Neurology and comprehensive Stroke center Massachusetts General HospitalBostonMassachusettsUSA Department of Neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within *** study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LVO)of anterior circulation beyond *** and design Tenecteplase Reperfusion Therapy in Acute Ischaemic cerebrovascular Events-III(TRAcE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical *** who had an ischaemic stroke due to anterior circulation LVO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volumech ratio≥1.8 and mismatch volume≥15mL)based on cT perfusion or MRI perfusion-weighted imaging(PWI)were included and randomised to rhTNK-tPA 0.25mg/kg(single bolus)to a maximum of 25mg or standard medical ***,we will exclude patients who are intended for direct *** will be followed up for 90 *** outcomes Primary efficacy outcome is modified Rankin Scale(mRS)score≤1 at 90 *** efficacy outcomes include ordinal distribution of mRS at 90 days,major neurological improvement defined by a decrease≥8 points compared with the initial deficit or a score≤1 on the National Institutes of Health Stroke Scale(NIHSS)at 72 hours,mRS score≤2 at 90 days,the rate of improvement on Tmax>6s at 24 hours and NIHSS score change from baseline at *** outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 *** TRAcE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond *** registration number NcT05141305.

关键词： Therapy random Rational

Polycystic Ovarian Syndrome (PcOS): Exploring Its Impact on Obstetrical Outcomes

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Open Journal of Obstetrics and Gynecology 2024年第8期14卷 1111-1123页

作者： Ranjitha Vasa Gayatri Venkataraman Kelly Gorman Rythika Francis Elise Zwicklbauer Julia fisher Polina Safovich Mudar Dalloul Ozgul Muneyyirci-Delale Department of Obstetrics and Gynecology SUNY Downstate Health Science University Brooklyn United States of America Department of Obstetrics and Gynecology Kings County Hospital Center NYC Health and Hospitals Brooklyn United States of America

Polycystic ovarian syndrome (PcOS) disrupts ovulation leading to both infertility and miscarriage;yet, its impact on obstetrical outcomes remains largely uncertain due to conflicting findings. We analyzed data from the cDc Pregnancy Risk Assessment of Monitoring System, specifically Standard core and Phase 8 responses, with 9549 respondents across the United States through SPSS 28 software in this cross-sectional study. Two variables assessed PcOS status in respondents: history of PcOS and PcOS during pregnancy. With a history of PcOS, there were significantly increased odds of diabetic (OR 1.665, p cy, neonatal mortality (OR 1.550, p cesarean section (c/S) (OR 1.489, p cOS diagnosed during pregnancy, there were significantly greater odds of diabetes (OR 3.278, p cy, and significantly decreased risk for small for gestational age (2 standard deviations) (OR 0.337, p = 0.024). PcOS is a significant risk factor that contributes to maternal morbidity. Our results support the hypothesis that PcOS’ impact extends well into a woman’s obstetrical journey, with varying degrees of associated adverse maternal and fetal risks. Preliminary pathophysiologic explanations associated with PcOS gestational diabetes include pre-existing insulin resistance. Meanwhile, altered placentation and endovascular changes associated with PcOS secondary to a baseline deranged metabolic environment predispose patients to developing hypertensive disorders, PPROM, and preterm delivery. Associations between neonatal mortality and c/S can be attributed to elevated maternal body mass index. The pathophysiologic link between PcOS and the above obstetrical outcomes still remains unknown, necessitating further investigation;however, this study identifies the outcomes that

关键词： PcOS Polycystic Ovarian Syndrome Obstetrics Reproduction Pregnancy

Microenvironmental influences on T cell immunity in cancer and inflammation

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cellular & Molecular Immunology 2022年第3期19卷 316-326页

作者： Darren R.Heintzman Emilie L.fisher Jeffrey c.Rathmell Department of Pathology Microbiologyand ImmunologyVanderbilt University Medical CenterNashvilleTN37205USA Vanderbilt center for Immunobiology Vanderbilt University Medical CenterNashvilleTN37205USA

T cell metabolism is dynamic and highly *** the intrinsic metabolic programs of T cell subsets are integral to their distinct differentiation and functional patterns,the ability of cells to acquire nutrients and cope with hostile microenvironments can limit these pathways.T cells must function in a wide variety of tissue settings,and how T cells interpret these signals to maintain an appropriate metabolic program for their demands or if metabolic mechanisms of immune suppression restrain immunity is an area of growing *** in inflamed and cancer tissues,a wide range of changes in physical conditions and nutrient availability are now acknowledged to shape *** include fever and increased temperatures,depletion of critical micro and macro-nutrients,and accumulation of inhibitory waste *** we review several of these factors and how the tissue microenvironment both shapes and constrains immunity.

关键词： immunometabolism T cell microenvironment cancer inflammation

Beta-HcG Levels and Ovarian Ultrasonography Results among Non-Pregnant Women of Reproductive Age in Port Harcourt, Nigeria: A cross-Sectional Study

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Journal of Biosciences and Medicines 2024年第5期12卷 233-241页

作者： celine c. Agonsi Francis Anacletus Joel Aluko chinemerem Eleke Joy c. Samuel African centre of Public Health and Toxicological Research (AcE-PUTOR) University of Port Harcourt Choba Nigeria Department of Nursing Science University of Port Harcourt Choba Nigeria

Background: certain ovarian cancers that were previously common in postmenopausal women are now increasingly observed in women of reproductive age. The research on using β-HcG as a diagnostic biomarker for ovarian cancer in women of reproductive age is ongoing. Aim: This study assessed the level of serum β-HcG in non-pregnant women of reproductive age and determined its potential association with suspicious ovarian ultrasonography results. Methods: The study was conducted in Port Harcourt, Nigeria. This study adopted a cross-sectional design on a quota sample of 224 case notes of women aged 18 - 40 years obtained from eight diagnostic centres. A data extraction form was used for data collection. Data analysis employed descriptive statistics, chi-square, fisher’s exact test, and Odds Ratio at 95% confidence and 5% significance levels. Results: About 5.8% of the participants exhibited detectable levels of serum β-HcG above 5 IU/L (World Health Organization reference) at a mean concentration of 5.87 (±1.75) IU/L. About 4.0% of the participants had suspicious ovarian lesions identified through ultrasonography. Participants with elevated serum β-HcG levels above the WHO reference were 59 times more likely to have suspicious ovarian lesions (Odds ratio: 59.4, 95%cI: 12.3 - 287.8, p β-HcG level and age (p = 0.041) as well as parity (p conclusion: Serum β-HcG levels above the WHO reference in non-pregnant women were associated with suspicious ovarian lesions. More rigorous primary research, systematic reviews, and meta-analyses are needed to confirm the findings of this study.

关键词： Biomarkers Ovarian cancer Pregnancy Ultrasonography

Tenecteplase Reperfusion therapy in Acute ischaemic cerebrovascular Events-Ⅱ (TRAcE Ⅱ): rationale and design

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Stroke & Vascular Neurology 2022年第1期7卷 71-76页

作者： Shuya Li Bruce c V campbell Lee H Schwamm Ma.c.fisher Mark Parsons Hao Li Yuesong Pan Yongjun Wang china National clinical Research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Medicine and Neurology University of MelbourneMelbourneVictoriaAustralia Department of Neurology and comprehensive Stroke center Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of Neurology Liverpool HospitalSouth Western Sydney Clinical SchoolSydneyNew South WalesAustralia

Background and purpose Tenecteplase(TNK)is a promising agent for treatment of acute ischaemic stroke(AIS).We hypothesised that recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)is non-inferior to rt-PA in achieving excellent functional outcome at 90 days,when administered within 4.5 hours of ischaemic stroke *** and design Tenecteplase Reperfusion therapy in Acute ischemic cerebrovascular Events(TRAcE)is a phase Ⅲ,multicentre,prospective,randomised,open-label,blinded-end point non-inferiority *** eligible for intravenous thrombolysis therapy are randomised to rhTNK-tPA 0.25 mg/kg(single bolus)to a maximum of 25 mg or rt-PA 0.9 mg/kg(10%bolus+90%infusion/1 hour)to a maximum of 90 *** considered necessary for the patient’s health may be given at the discretion of the investigator during 90-day *** outcomes The primary study outcome is excellent functional outcome defined as modified Rankin Scale(mRS)0–1 at 90 *** efficacy outcomes include favourable functional outcome defined as mRS≤2 at 90 days,ordinal distribution of mRS and major neurological improvement on the National Institutes of Health Stroke *** outcomes are symptomatic intracranial haemorrhage within 36 hours and death from any *** There is no completed registration study of TNK in AIS *** Ⅱ strives to provide evidence for a new drug application for rhTNK-tPA in AIS within 4.5 hours through a well-designed and rigorously executed randomised trial in china.

关键词： infusion acute rational

Elastic constants of Nickel Oxide

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chinese Physics Letters 1991年第3期8卷 153-156页

作者： WANG Jifang fisher,E.S. M.H.Manghnzmi Institute of Physics Academia SinicaBeijing 100080 Argonne National Laboratory ArgonneIllinoisUSA Hawaii Institute of Geophysics University of HawaiiHonoluluHawaiiUSA

Previous measurements of the single crystal elastic constants of NiO by ultrasonic techniques have been in wide *** paper gives the results of recent data obtained from several well characterized NiO single *** present results for the antiferromagnetic phase at 298K are different from the previous data and rectify certain questions about the elastic anisotropy ratio c_(44)/c'and bulk modulus K_(s).

关键词： crystals Elastic modulus

Associations of self-reported and device-assessed physical activity with fatigue,quality of life,and sleep quality in adults living with and beyond cancer

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Journal of Sport and Health Science 2023年第6期12卷 664-673,F0003页

作者： Phillippa Lally Natalie Ella Miller claire Lawrence Rebecca J Beeken Abigail fisher Department of Behavioural Science and Health University College LondonLondon WC1E 6BTUK Department of Psychology University of SurreyGuildford GU27XHUK Leeds Institute of Health Sciences Leeds LS29NLUK

Background Greater physical activity is associated with improved outcomes in people living with and beyond ***,most studies in exercise oncology use self-reported measures of physical *** have explored agreement between self-reported and device-based measures of physical activity in people living with and beyond *** study aimed to describe physical activity in adults affected by cancer across self-reported and device-assessed activity,to explore levels of agreement between these measures in terms of their utility for categorizing participants as meeting/not meeting physical activity guidelines,and to explore whether meeting guidelines is associated with fatigue,quality of life,and sleep *** A total of 1348 adults living with and beyond cancer from the Advancing Survivorship cancer Outcomes Trial completed a survey assessing fatigue,quality of life,sleep quality,and physical *** Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to calculate a Leisure Score Index(LSI)and an estimate of moderate-to-vigorous physical activity(MVPA).Average daily steps and weekly aerobic steps were derived from pedometers worn by *** The percentage of individuals meeting physical activity guidelines was 44.3%using LSI,49.5%using MVPA,10.8%using average daily steps,and 28.5%using weekly aerobic ***(cohen'sκ)between self-reported and pedometer measures ranged from 0.13(LSI *** daily steps)to 0.60(LSI ***).After adjusting for sociodemographic and health-related covariates,meeting activity guidelines using all measures was associated with not experiencing severe fatigue(odds ratios(ORs):1.43–1.97).Meeting guidelines using MVPA was associated with no quality-of-life issues(OR=1.53).Meeting guidelines using both self-reported measures were associated with good sleep quality(ORs:1.33–1.40).conclusion Less than half of all adults affected by cancer are meeting physical activity guidelines,

关键词： cancer survivorship Fatigue Physical activity Quality of life SleepTagedAPTARAEnd

Gut microbiota in preterm infants receiving breast milk or mixed feeding

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World Journal of clinical Pediatrics 2024年第2期13卷 135-145页

作者： Sandra Gabriela Sánchez-González Bárbara Gabriela cárdenas-del-castillo Elvira Garza-González Gerardo R Padilla-Rivas Isaías Rodríguez-Balderrama consuelo Treviño-Garza Fernando Félix Montes-Tapia Gerardo c Palacios-Saucedo Anthony Gutiérrez-Rodríguez Manuel Enrique de-la-O-cavazos Department of Pediatrics Hospital Universitario“Dr.JoséEleuterio González”Universidad Autónoma de Nuevo LeónMonterrey 64460Nuevo LeónMéxico Departamento de Bioquímica y Medicina Molecular Universidad Autónoma de Nuevo LeónMonterrey 64460Nuevo LeónMéxico Department of Biochemistry and Molecular Medicine Universidad Autónoma de Nuevo LeónMonterrey 64460Nuevo LeónMéxico Department of Pediatric Surgery Hospital Universitario"Dr.JoséEleuterio González"Monterrey 64460Nuevo LeónMéxico

BAcKGROUND Preterm birth is the leading cause of mortality in newborns,with very-low-birthweight infants usually experiencing several *** milk is considered the gold standard of nutrition,especially for preterm infants with delayed gut colonization,because it contains beneficial microorganisms,such as Lactobacilli and *** To analyze the gut microbiota of breastfed preterm infants with a birth weight of 1500 g or *** An observational study was performed on preterm infants with up to 36.6 wk of gestation and a birth weight of 1500 g or less,born at the University Hospital ***éEleuterio González at Monterrey,Mexico.A total of 40 preterm neonates were classified into breast milk feeding(BM)and mixed feeding(MF)groups(21 in the BM group and 19 in the MF group),from October 2017 to June *** samples were collected before they were introduced to any feeding *** full enteral feeding was achieved,the composition of the gut microbiota was analyzed using 16S rRNA gene *** variables were compared using Student’s t-test or using the Mann–Whitney U test for nonparametric ***,evenness,equitability,Margalef’s index,fisher’s alpha,chao-1 index,and Shannon’s diversity index were also *** No significant differences were observed at the genus level between the *** comparison indicated higher counts of Alphaproteobacteria and Betaproteobacteria in the initial compared to the final sample of the BM group(Pcounts of Gammaproteobacteria were detected in the final than in the initial sample(P=0.040).According to the Margalef index,fisher’s alpha,and chao-1 index,a decrease in species richness from the initial to the final sample,regardless of the feeding type,was observed(Pcteroidetes,Actinobacteria,Firmicutes,and Proteobacteria,with Proteobacteria being the most ***,no significant differences were

关键词： Gut microbiota Human milk Preterm infant Proteobacteria Very low birth weight 16S rRNA

Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21

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The Journal of Biomedical Research 2010年第2期24卷 87-99页

作者： Aarti Ruparelia Frances Wiseman Olivia Sheppard Victor L.J.Tybulewicz Elizabeth M.c.fisher Department of Neurodegenerative Disease UCL Institute of Neurology MRc National Institute for Medical Research

Elizabeth fisher and Victor collaboratively for many years on Tybulewicz have worked the Down syndrome mouse model project. Elizabeth fisher＇s background is in molecular genetics and mouse models, with an interest in anueploidy. Victor Tybulewicz is an immunologist whose primary interest is in signal transduction from the antigen receptors of B and T cells.

关键词： Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21