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Simultaneously targeting extracellular vesicle trafficking and TGF-β receptor kinase activity blocks signaling hyperactivation and metastasis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 308-325页

作者： Adilson Fonseca Teixeira Yanhong Wang Josephine Iaria Peter ten Dijke Hong-Jian Zhu Department of Surgery(The royal melbourne hospital) The University of MelbourneParkvilleVICAustralia Huagene Institute Kecheng Science and Technology ParkPukou DistrictNanjingJiangsuChina Department of Cell and Chemical Biology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands

Metastasis is the leading cause of cancer-related *** growth factor beta(TGF-β)signaling drives metastasis and is strongly enhanced during cancer ***,the use of on-target TGF-βsignaling inhibitors in the treatment of cancer patients remains unsuccessful,highlighting a gap in the understanding of TGF-βbiology that limits the establishment of efficient anti-metastatic ***,we show that TGF-βsignaling hyperactivation in breast cancer cells is required for metastasis and relies on increased small extracellular vesicle(sEV)*** sEV’s unique role,TGF-βsignaling levels induced by sEVs exceed the activity of matching concentrations of soluble ligand TGF-β.Further,genetic disruption of sEV secretion in highlymetastatic breast cancer cells impairs cancer cell aggressiveness by reducing TGF-βsignaling to nearly-normal ***,TGF-βsignaling activity in non-invasive breast cancer cells is inherently low,but can be amplified by sEVs,enabling invasion and metastasis of poorly-metastatic breast cancer *** the translational potential of inhibiting sEV trafficking in advanced breast cancers,treatment with dimethyl amiloride(DMA)decreases sEV secretion,TGF-βsignaling activity,and breast cancer progression in *** both the sEV trafficking and TGF-βsignaling by combining DMA and SB431542 at suboptimal doses potentiated this effect,normalizing the TGF-βsignaling in primary tumors to potently reduce circulating tumor cells,metastasis,and tumor ***,this study establishes sEVs as critical elements in TGF-βbiology,demonstrating the feasibility of inhibiting sEV trafficking as a new therapeutic approach to impair metastasis by normalizing TGF-βsignaling levels in breast cancer cells.

关键词： metastasis doses invasion

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Spreadsheet quality assurance:a literature review

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Frontiers of Computer Science 2024年第2期18卷 61-82页

作者： Pak-Lok POON Man Fai LAU Yuen Tak YU Sau-Fun TANG School of Engineering and Technology Central Queensland UniversityMelbourne 3000Australia Department of Computing Technologies Swinburne University of TechnologyHawthorn 3122Australia Department of Computer Science City University of Hong KongHong Kong SAR 999077China The royal Victorian Eye and Ear hospital East Melbourne 3002Australia

Spreadsheets are very common for information processing to support decision making by both professional developers and non-technical end ***,business intelligence and artificial intelligence are increasingly popular in the industry nowadays,where spreadsheets have been used as,or integrated into,intelligent or expert systems in various application ***,it has been repeatedly reported that faults often exist in operational spreadsheets,which could severely compromise the quality of conclusions and decisions based on the *** a view to systematically examining this problem via survey of existing work,we have conducted a comprehensive literature review on the quality issues and related techniques of spreadsheets over a 35.5-year period(from January 1987 to June 2022)for target journals and a 10.5-year period(from January 2012 to June 2022)for target *** other findings,two major ones are:(a)Spreadsheet quality is best addressed throughout the whole spreadsheet life cycle,rather than just focusing on a few specific stages of the life cycle.(b)Relatively more studies focus on spreadsheet testing and debugging(related to fault detection and removal)when compared with spreadsheet specification,modeling,and design(related to development).As prevention is better than cure,more research should be performed on the early stages of the spreadsheet life *** by our comprehensive review,we have identified the major research gaps as well as highlighted key research directions for future work in the area.

关键词： decision support system end-user computing end-user programming Excel spreadsheet

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Path signature-based XAI-enabled network time series classification

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Science China(Information Sciences) 2024年第7期67卷 91-106页

作者： Le SUN Yueyuan WANG Yongjun REN Feng XIA Department of Jiangsu Collaborative Innovation Center of Atmospheric Environment and Equipment Technology(CICAEET) Nanjing University of Information Science and Technology School of Computing Technologies Royal Melbourne Institute of Technology

Classifying network time series(NTS) is crucial for automating network administration and ensuring cyberspace security. It enables the detection of anomalies, the identification of network attacks,and the monitoring of performance issues, thereby providing valuable support for network protection and optimization. However, modern communication networks pose challenges for NTS classification *** include handling large-scale and complex NTS data, extracting features from intricate datasets, and addressing explainability requirements. These challenges are particularly pronounced for complex 5G networks. Notably, explainability has become crucial for the widespread deployment of network automation for 5G networks and beyond. To tackle these challenges, we propose a path-signature-based NTS classification model called recurrent signature(Recur Sig). This innovative model is designed to overcome the time-consuming feature selection problem by utilizing deep-learning(DL) techniques. Additionally, it provides a solution for addressing the black-box issue associated with DL models in network automation systems(NAS) by incorporating an explainable classification approach. Extensive experimentation on various public datasets demonstrates that Recur Sig outperforms existing models in accuracy and explainability. The results indicate its potential for application in cyberspace security and automated network management, offering an explainable solution for network protection and optimization.

关键词： network time series classification explainable artificial intelligence path signature automated network management recurrent neural network

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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 *** aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1month in patients commenced on early(5mL,regardless of anticoagulation *** Commencing anticoagulation<4days after stroke or TIA is associated with fewer ischaemic lesions at 1month in AF *** is no increased rate of haemorrhage with early *** results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated w

关键词： patients lesions ischaemic

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Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca^(2+)-dependent AMPK/mTOR pathway

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 420-434页

作者： Liu-Hui Huang Jiao Lyu Sheng Chen Ting-Yi Liang Yu-Qing Rao Ping Fei Jing Li Hai-Ying Jin Pei-Quan Zhao Department of Ophthalmology Shanghai Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Ophthalmology Shanghai Tenth People’s Hospital Affiliated with Shanghai Tongji University School of MedicineShanghai 200072China Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVictoria 3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVictoria 3002Australia Shenzhen Eye hospital Shenzhen Key Laboratory of OphthalmologyAffiliated Shenzhen Eye Hospital of Jinan UniversityShenzhen 518040Guangdong ProvinceChina Department of Ophthalmology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China

●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in *** chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein *** transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy *** electron microscopy was used to detect the existence of *** interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related *** cytometry was employed to test the apoptosis and intracellular Ca^(2+)*** membrane potential was measured by JC-1 *** cell counting kit-8 assay was used to calculate the cellular *** wound healing assay was used to evaluate the wound closure *** 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in *** 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression *** Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early *** on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic *** stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration *** of autophagy by ATG7 knockdown had sim

关键词： cataract posterior capsular opacification lens epithelial cell hyperosmotic stress autophagy apoptosis transient receptor potential vanilloid 1

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Impact of scandium and terbium on the mechanical properties,corrosion behavior,and biocompatibility of biodegradable Mg-Zn-Zr-Mn alloys

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Journal of Magnesium and Alloys 2024年第2期12卷 546-572页

作者： Khurram Munir Jixing Lin Xian Tong Arne Biesiekierski Yuncang Li Cuie Wen School of Engineering RMIT UniversityMelbourneVictoria 3001Australia School and hospital of Stomatology Wenzhou Medical UniversityWenzhou 325027China

Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone *** earth elements(REEs)have demonstrated their effectiveness in tailoring the corrosion and mechanical behavior of Mg *** study methodically investigated the impacts of scandium(Sc)and terbium(Tb)in tailoring the corrosion resistance,mechanical properties,and biocompatibility of Mg–0.5Zn–0.35Zr–0.15Mn(MZZM)alloys fabricated via casting and hot *** indicate that addition of Sc and Tb improved the strength of MZZM alloys via grain size reduction and solid solution strengthening *** extruded MZZM–(1–2)Sc–(1–2)Tb(wt.%)alloys exhibit compressive strengths within the range of 336–405 MPa,surpassing the minimum required strength of 200 MPa for bone implants by a significant *** polarization tests revealed low corrosion rates of as–cast MZZM(0.25 mm/y),MZZM–2Tb(0.45 mm/y),MZZM–1Sc–1Tb(0.18 mm/y),and MZZM–1Sc–2Tb(0.64 mm/y),and extruded MZZM(0.17 mm/y),MZZM–1Sc(0.15 mm/y),MZZM-2Sc(0.45 mm/y),MZZM-1Tb(0.17 mm/y),MZZM-2Tb(0.10 mm/y),MZZM–1Sc-1Tb(0.14 mm/y),MZZM-1Sc-2Tb(0.40 mm/y),and MZZM–2Sc–2Tb(0.51 mm/y)alloys,which were found lower compared to corrosion rate of high-purity Mg(~1.0 mm/y)reported in the ***,addition of Sc,or Tb,or Sc and Tb to MZZM alloys did not adversely affect the viability of SaOS2 cells,but enhanced their initial cell attachment,proliferation,and spreading shown via polygonal shapes and *** study emphasizes the benefits of incorporating Sc and Tb elements in MZZM alloys,as they effectively enhance corrosion resistance,mechanical properties,and biocompatibility simultaneously.

关键词： Corrosion property In vitro cytotoxicity Magnesium alloys Mechanical property Rare earth elements

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Cost burden following esophagectomy:A single centre observational study

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2255-2269页

作者： Vered Buchholz Dong Kyu Lee David S Liu Ahmad Aly Stephen A Barnett Riley Hazard Peter Le Benjamin Kioussis Vijayaragavan Muralidharan Laurence Weinberg Department of Surgery Austin HealthMelbourne 3084VictoriaAustralia Department of Anesthesiology and Pain Medicine Dongguk University Ilsan HospitalSeoul 14566GoyangSouth Korea Department of Surgery Austin HealthThe University of MelbourneMelbourne 3084VictoriaAustralia Department of Anesthesia Austin HealthMelbourne 3084VictoriaAustralia Department of Anesthesia Austin HospitalHeidelberg 3084VictoriaAustralia Department of Critical Care The University of MelbourneMelbourne 3084VictoriaAustralia

BACKGROUND Cost analyses of patients undergoing esophagectomy is valuable for identifying modifiable expenditure drivers to target and curtail costs while improving the quality of *** aimed to define the cost-complication relationship after esophagectomy and delineate the incremental contributions to *** To assess the relationship between the hospital costs and potential cost drivers post esophagectomy and investigate the relationship between the cost-driving variables(predicting variables)and hospital costs(dependent variable).METHODS In this retrospective single center study,the severity of complications was graded using the Clavien-Dindo(CD)classification *** esophagectomy complications were categorized and defined according to consensus *** costing data included the in-hospital costs of the index admission and any unplanned admission within 30 postoperative *** used correlation analysis to assess the relationship between key clinical variables and hospital costs(in United States dollars)to identify cost drivers.A mediation model was used to investigate the relationship between these variables and hospital *** A total of 110 patients underwent primary esophageal *** median admission cost was $47822.7(interquartile range:35670.2-68214.0).The total effects on costs were $13593.9(95%CI:10187.1-17000.8,Phospital *** institutional initiatives and strategies are needed to enhance patient outcomes and minimize costs.

关键词： Anesthesia Esophagectomy Complications Cancer Surgery

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Thirteen years to get from b to a:one of the neglected isoforms of IL-37 enters the stage

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Cellular & Molecular Immunology 2024年第2期21卷 201-202页

作者： Steven X.Cho Ina Rudloff Andrew M.Ellisdon Claudia A.Nold-Petry Marcel F.Nold Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Pediatrics Monash UniversityMelbourneVICAustralia Cancer Program Biomedicine Discovery InstituteMonash UniversityMelbourneVICAustralia Monash Newborn Monash Children’s HospitalMelbourneVICAustralia

Interleukin(IL)-37 is one of the few anti-inflammatory members of the predominantly pro-inflammatory IL-1 cytokine ***-37 possesses alarmin-like properties[1]and exerts its activities via intracellular[2]as well as cell surface receptor-dependent mechanisms,and the latter involves IL-1R8 and IL-18Rα[3].Because of its powerful and broad-spectrum“peacemaking”[4]functions,considerable efforts have been invested in developing IL-37-based anti-inflammatory therapeutics[5,6].

关键词： Interleukin neglected cytokine

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Global trend of nondrug and nonsedativehypnotic treatment forinsomnia: a bibliometric study

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Journal of Traditional Chinese Medicine 2024年第3期44卷 595-608页

作者： LEI Hanzhou XU Guixing WEI Zepeng ZHAO Ling LIANG Fanrong Acupuncture and Tuina School Chengdu University of Traditional Chinese Medicine Department of Haematology Royal North Shore Hospital

OBJECTIVE: To present a bibliometric analysis of global scientific publications on the nondrug and nonsedative hypnotic treatment of insomnia with regard to influential institutions, publications, countries, research hotspots,trends, and frontiers. METHODS: A literature review was conducted by searching the Web of Science Core Collection(Wo SCC) and China National Knowledge Infrastructure(CNKI) databases to identify all publications related to the nondrug and nonsedative hypnotic treatment of insomnia from 2000 to 2021. Eligible publications were reviewed, including annual publication increments, citation analyses, international collaborations, and keyword analyses. The data were analysed using Cite Space(vers5.8.R3, 6.1.R2 and 6.1.6, College of Computing and Informatics, Philadelphia, PA, USA) and virtualized by knowledge maps. RESULTS:In total, 9832 publications were included in this analysis. The results from the WoSCC showed that the United States of America(Count = 2268, 40.33%), Stanford University(Count = 141, 2.51%), and the United States Department of Health and Human Services were the leading country, institute, and funding agency regarding the number of publications, respectively. “Cognitive-behavioural therapy” was the most popular research topic generated from the cocited reference. The most frequently co-occurring keywords were insomnia, cognitive behavioural therapy, disorder, depression, quality of life, Meta-analysis, older adult, sleep, prevalence and efficacy, while keywords including clinical practice guideline, guideline, and Tai Chi remained popular after 2021. Circadian rhythm was the strongest research frontier for 2000-2021. In China, Chengdu University of Traditional Chinese Medicine(Count = 69, 4.79%) was the most productive institute in this field. The most frequently co-occurring keywords from Chinese literature were sleep disorder, sleep quality, acupuncture and moxibustion, Parkinson's disease, transcranial magnetic stimulation, health

关键词： CiteSpace bibliometrics cognitive behavioral therapy complementary therapies hypnotics and sedatives scientometrics visualization analysis

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Loculated pericardial hematoma diagnosed with point-of-care ultrasound

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World Journal of Emergency Medicine 2024年第3期15卷 241-242页

作者： Joaquín Valle Alonso Esther Montoro Leandro Noblia Emergency Department Royal Bournemouth HospitalBournemouth 14450UK Emergency Department Hospital Santa LuciaCartagena 30202Spain

Pericardial hematoma is a rare but potentially lifethreatening consequence following cardiac surgery that requires prompt recognition and *** can present with symptoms such as chest pain,dyspnea,tachycardia,and hypotension,which may mimic other post-operative *** pericardial hematoma compressing the atria might be difficult to *** and hematoma are more common in patients receiving early anticoagulant therapy.A focused cardiac ultrasound (Fo CUS) plays a pivotal role in the diagnosis,revealing the presence of pericardial effusion and signs of cardiac *** aim of this report was to provide a prompt diagnosis of loculated pericardial hematoma via Fo CUS in the emergency department (ED).

关键词： hematoma diagnosis cardiac

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