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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 Marc 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 4.5hours.Our 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 4.5hours.Methods and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III(TRACE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical trial.Patients 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 volume6s at 24 hours and NIHSS score change from baseline at 7days.Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days.Discussion 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 4.5hours.Trial registration number NCT05141305.

关键词： Therapy random Rational

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Early anticoagulation in patients with stroke and atrial fibrillation is associated with fewer ischaemic lesions at 1 month: the ATTUNE study

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Stroke & Vascular Neurology 2024年第1期9卷 30-37,I0034页

作者： Angelos Sharobeam Longting Lin Christina Lam Carlos Garcia-Esperon Yash Gawarikar Ronak Patel Matthew Lee-Archer Andrew Wong Michael Roizman Amanda Gilligan Andrew Lee Kee Meng Tan Susan Day Christopher Levi Stephen M Davis Mark Parsons Bernard Yan Melbourne Brain Centre at Royal Melbourne Hospital ParkvilleVictoriaAustralia University of New south Wales south western sydney clinical school LiverpoolNew South WalesAustralia Department of Neurology John Hunter HospitalNewcastleNew South WalesAustralia Department of Neurology Calvary Public HospitalCanberraAustralian Capital TerritoryAustralia Department of Neurology Northern Hospital EppingEppingVictoriaAustralia Department of Neurology Royal Brisbane and Women's HospitalHerstonQueenslandAustralia The University of Queensland school of Medicine HerstonQueenslandAustralia Neurosciences clinical Institute Epworth HealthcareRichmondVirginiaAustralia Department of Neurology Austin HealthUniversity of MelbourneHeidelbergVictoriaAustralia Flinders University College of Medicine and Public Health AdelaideSouth AustraliaAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia The University of sydney Northern clinical school St LeonardsNew South WalesAustralia Department of Neurology and Neurophysiology Liverpool HospitalLiverpoolNew South WalesAustralia

Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic lesions.We aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1month in patients commenced on early(clinical and MRI data were collected at baseline and follow-up,with blinded imaging assessment performed by two authors.Timing of commencement of anticoagulation was at the discretion of the treating stroke physician.Results We recruited 276 patients of whom 208 met the eligibility criteria.The average age was 74.2 years(SD±10.63),and 79(38%)patients were female.Median National Institute of Health Stroke Scale score was 5(IQR 1–12).Median baseline ischaemic lesion volume was 5mL(IQR 2–17).There were a greater number of new ischaemic lesions on follow-up MRI in patients commenced on anticoagulation≥4days after index event(17%vs 8%,p=0.04),but no difference in haemorrhage rates(22%vs 32%,p=0.10).Baseline ischaemic lesion volume of≤5mL was less likely to have a new haemorrhage at 1month(p=0.02).There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of>5mL,regardless of anticoagulation timing.Conclusion Commencing anticoagulation<4days after stroke or TIA is associated with fewer ischaemic lesions at 1month in AF patients.There is no increased rate of haemorrhage with early anticoagulation.These results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated with AF might be safe,but randomised controlled s

关键词： patients lesions ischaemic

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BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

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Neural Regeneration Research 2024年第2期19卷 447-457页

作者： Michael W.Weible II Michael D.Lovelace Hamish D.Mundell Tsz Wai Rosita Pang Tailoi Chan-Ling Bosch Institute Discipline of Anatomy and Histology(F13)University of SydneySydneyNSWAustralia school of Environment and Science Griffith UniversityNathanQLDAustralia Discipline of Medicine Nepean Clinical SchoolFaculty of Medicine and HealthUniversity of SydneyKingswoodNSWAustralia New south Wales Brain Tissue Resource Centre School of Medical SciencesFaculty of Medicine and HealthUniversity of SydneyCharles Perkins Centre(D17)SydneyNSWAustralia

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provid

关键词： BMPRⅡ bone morphogenetic protein histotypic human spinal cord development leukemia inhibitory factor neurosphere organotypic reaggregate sensory columns

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Methyl-salicylate:A surveillance system fortriggering immunity in neighboring plants

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Journal of Integrative Plant Biology 2024年第2期66卷 163-165页

作者： Saumya Jaiswal Durgesh Kumar Tripathi Ravi Gupta JingHe Zhong-Hua Chen Vijay Pratap Singh Plant Physiology Laboratory Department of Botany C.M.P.Degree CollegeA Constituent Post Graduate College ofUniversity of AllahabadPrayagraj 211002India Crop Nanobiology and Molecular Stress Physiology LabAmity Institute of Organic Agriculture Amity University UttarPradeshNoida 201313India College of General Education Kookmin UniversitySeoul 02707South Korea school of Science Western Sydney UniversitySydney 2751New South WalesAustralia Hawkesbury Institute for the Environment Western SydneyUniversitySydney 2751New South WalesAustralia

Plant behavioral actions have been one of the major topicsof research in plant biology and agriculture.These actionsfrom plants are determined by their instant structural andphysical reactions to the circumstances(Bouwmeester et al.,2019).Upon sensing abiotic factors such as salinity,flooding,high temperature,drought,plants make suitable changes intheir physiology and behavior to survive such harsh conditions.

关键词： immunity neighboring salinity

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Molecular biomarkers for vascular cognitive impairment and dementia:the current status and directions for the future

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Neural Regeneration Research 2024年第12期19卷 2579-2580页

作者： Satoshi Hosoki Perminder SSachdev Centre for Healthy Brain Ageing Discipline of Psychiatry and Mental HealthSchool of Clinical MedicineFaculty of Medicine and HealthUniversity of New South WalesSydneyAustralia Department of Neurology National Cerebral and Cardiovascular CenterOsakaJapan

Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive dysfunction.The development of disease-specific treatments and targeted prevention strategies requires precise clinical sub-typing via etiology and pathophysiological processes.Furthermore,recent research advances in biomarkers,especially for Alzheimer's disease(AD)diagnosis,have improved diagnostic precision for dementia.

关键词： prevention diagnosis impairment

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Spatial and temporal patterns of sarcoptic mange in wombats using the citizen science tool,WomSAT

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Integrative Zoology 2024年第3期19卷 387-399页

作者： Sujatha MAYADUNNAGE Hayley Jade STANNARD Peter WEST Julie M.OLD school of Science Western Sydney UniversityHawkesburyNSWAustralia school of Agricultural Environmental and Veterinary SciencesCharles Sturt UniversityWagga WaggaNSWAustralia Department of Primary Industries Orange Agricultural InstituteOrangeNSWAustralia

There is currently limited information regarding the levels of infection and distribution of sarcoptic mange in the wombat population throughout Australia.We analyzed cases of sarcoptic mange in bare-nosed wombats reported into WomSAT,a website and mobile phone application where citizen scientists can upload sightings of wombats,burrows,and sarcoptic mange status.We used Maxent software to predict locations and the environmental factors associated with sarcoptic mange occurrence in bare-nosed wombats.A total of 1379 sarcoptic mange-infected and 3043 non-sarcoptic mange-infected wombats were reported by 674 and 841 citizen scientists,respectively.Of all the wombats reported to WomSAT from 2015 to 2019,31.2%were infected with sarcoptic mange.Sarcoptic mange in bare-nosed wombats was reported in 502 suburbs across four states.New south Wales had the highest number of sarcoptic mange cases reported to WomSAT.There was no statistically significant seasonal variation of sarcoptic mange levels in bare-nosed wombats.The model showed that Euclidean distance to urban areas was the highest contributing factor for sarcoptic mange occurrence.As distance to urban areas decreased,the suitability for sarcoptic mange increased.Annual precipitation was the next contributing factor in the model,with higher rainfall of 400–700 mm correlating to an increase in sarcoptic mange occurrence.As the data collected to date have provided the largest-scale contemporary distribution of sarcoptic mange in wombats,data should continue to be collected by citizen scientists as it is an easy and low-cost method of collecting data over large areas.We suggest targeting the identified hotspot areas and more site-specific studies for studying and mitigating sarcoptic mange in bare-nosed wombats.

关键词： bare-nosed wombats habitat suitability Maxent modeling

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3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

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BIOCELL 2024年第5期48卷 861-872页

作者： XIAOQI WU YECHUAN HE YEQIN YUAN XIAN TAN LIN ZHU DANLING WANG BINYUAN JIANG Hengyang Medical school University of South ChinaHengyang421001China Institute for Future Sciences University of South ChinaChangsha410008China Medical Research Center The Affiliated Changsha Central HospitalHengyang Medical SchoolUniversity of South ChinaChangsha410004China Department of clinical Laboratory The Affiliated Changsha Central HospitalHengyang Medical SchoolUniversity of South ChinaChangsha410004China

Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.

关键词： Nasopharyngeal carcinoma Paclitaxel 3-Methyladenine Cell cycle Apoptosis

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Amorphous electrocatalysts for urea oxidation reaction

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Progress in Natural Science:Materials International 2024年第2期34卷 362-375页

作者： Fenghui Guo Dongle Cheng Qian Chen Hao Liu Zhiliang Wu Ning Han Bing-Jie Ni Zhijie Chen school of Materials Science and Technology China University of Geosciences Shenzhen Academy of Metrology and Quality Inspection Centre for Technology in Water and Wastewater School of Civil and Environmental Engineering University of Technology Sydney College of Safety and Environmental Engineering Shandong University of Science and Technology Institute of Yellow River Delta Earth Surface Processes and Ecological Integrity Shandong University of Science and Technology Discipline of Chemical Engineering Western Australian School of Mines: Minerals Energy and Chemical Engineering Curtin University Department of Materials Engineering school of Civil and Environmental Engineering The University of New South Wales

Electrochemical urea oxidation reaction(UOR) is a promising alternative to oxygen evolution reaction(OER) for realizing energy-saving hydrogen production. Developing efficient electrocatalysts for UOR becomes a central challenge. Recently, amorphous materials have been extensively used as UOR catalysts because of their numerous defective sites and flexible electronic properties. In this review, recent advancements in the development of amorphous UOR electrocatalysts are analyzed. The UOR mechanism is discussed, and the design of amorphous catalysts is then analyzed. The main catalyst design strategies are illustrated, including nanostructure control,heteroatom doping, composition regulation, and heterostructure construction. Also, electrocatalysts' structureperformance correlation is interpreted. Perspectives in this field are proposed for guiding future studies on the development of high-performance amorphous catalysts towards energy sustainability.

关键词： Catalyst design Component regulation Heteroatom doping Heterostructures Hydrogen energy

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Treatment endpoints in ulcerative colitis:Does one size fit all?

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2024年第2期15卷 1-12页

作者： Nikola Mitrev Viraj Kariyawasam Department of Gastroenterology Blacktown HospitalBlacktown 2148NSWAustralia Blacktown/Mt Druitt clinical school University of Western SydneyBlacktown 2148NSWAustralia Department of Gastroenterology Wollongong HospitalLoftus StWollongong 2500NSWAustralia

A treat-to-target strategy in inflammatory bowel disease(IBD)involves treatment intensification in order to achieve a pre-determined endpoint.Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician’s subjective assessment of symptoms.However,choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy.The treatment endpoints for ulcerative colitis(UC),recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)consensus have changed somewhat over time.The latest STRIDE-II consensus advises immediate(clinical response),intermediate(clinical remission and biochemical normalisation)and long-term treatment(endoscopic healing,absence of disability and normalisation of health-related quality of life,as well as normal growth in children)endpoints in UC.However,achieving deeper levels of remission,such as histologic normalisation or healing of the gut barrier function,may further improve outcomes among UC patients.Generally,all medical therapy should seek to improve short-and long-term mortality and morbidity.Hence treatment endpoints should be chosen based on their ability to predict for improvement in short-and long-term mortality and morbidity.Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient.In addition,changing therapy that has achieved partial response may lead to worse outcomes,with failure to recapture response on treatment reversion.Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians,or may have strong opinions re certain therapies.Potential benefits and harms of therapies,incremental benefits of achieving deeper levels of remission,as well as uncertainties of the same,need to be discussed with individual patients,and a treatment endpoint agreed upon with the clinician.Future research should focus on quantifying the incremental b

关键词： Ulcerative colitis Treatment endpoints Endoscopic remission Histologic remission Biomarkers Gut barrier healing

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Mapping the clinical practice of traditional,complementary and integrative medicine in oncology in western countries:A multinational cross-sectional survey

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Journal of Integrative Medicine 2024年第1期22卷 64-71页

作者： Matthias Huemer Sandro Graca Sarah Bitsche Guenter Hofmann Mike Armour Martin Pichler Palliative Care Unit Division of OncologyDepartment of Internal MedicineMedical University of Graz8036 GrazAustria Northern College of Acupuncture York YO16LJUnited Kingdom school of Health and Society Faculty of EducationHealth and WellbeingUniversity of WolverhamptonWolverhampton WV11LYUnited Kingdom National Institute of Complementary Medicine Health Research Institute Western Sydney UniversityPenrith NSW 2751Australia Translational Health Research Institute Western Sydney UniversityPenrith NSW 2751Australia Medical Research Institute of New Zealand Wellington 6021New Zealand Translational Oncology University Hospital of Augsburg86156 AugsburgGermany

Background Many cancer patients seek adjunctive therapies to biomedical cancer treatments at some point of their disease trajectory.While acupuncture is increasingly recommended by leading oncological associations,limited evidence exists concerning the evidence-informed practice and adherence to current guidelines of traditional complementary and integrative medicine(TCIM)practitioners treating cancer patients.Methods An international online-survey assessed the demographical data,clinical practice,and sources of information used by TCIM practitioners in Austria,Germany,United States of America,Australia,and New Zealand.Results In total,404 respondents completed the survey,of which 254(62.9%)treated cancer patients.Most practitioners were acupuncturists and herbalists(57.1%),had(16.8±9.9)years of clinical experience and see a median of 2(1,4)cancer patients per week.Breast cancer(61.8%)is the most common cancer type seen in TCIM clinics.Adjunctive TCIM treatments are frequently concurrent with the patient’s cancer specific treatment(39.9%),which is also reflected by the main goal of a TCIM treatment to alleviate side effects(52.4%).However,only 28.0%of the respondents are in contact with the treating oncologist.According to the respondents,pain is most effectively treated using acupuncture,while herbal medicine is best for cancer-related fatigue.TCIM practitioners mostly use certified courses(33.1%)or online databases(28.3%)but often believe that experts are more reliable to inform their practice(37.0%)than research publications(32.7%).Conclusion Acupuncturists and herbalists commonly treat cancer patients.Most practitioners use TCIM as an adjunct to biomedicine as supportive care and use it largely in accordance with current oncological guidelines.

关键词： Integrative medicine Acupuncture Oncology Evidence-informed practice International survey

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