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A facile strategy for tuning th. density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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Bio-Design and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.O.Beeren G.Dos Santos P.J.Dijkstra C.Mota J.Bauer h.Ferreira Rui L.Reis N.Neves S.Camarero-Espinosa M.B.baker L.Moroni Department of Complex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s Research.Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal POLYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKERBASQUE Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufacturing(ME-AM)is a promising tech.ique to fabricate porous scaffolds for tissue engi-neering ***,most synth.tic semicrystalline polymers do not possess th. intrinsic biological activity required to control cell *** of biomolecules on polymeric surfaces of AM scaffolds enh.nces th. bioactivity of a construct;h.wever,th.re are limited strategies available to control th. surface ***,we report a strategy to tune th. surface density of bioactive groups by blending a low molecular weigh. poly(ε-caprolactone)5k(PCL5k)containing orth.gonally reactive azide groups with.an unfunctionalized h.gh.molecular weigh. PCL75k at different *** porous th.ee-dimensional(3D)scaf-folds were th.n fabricated using a h.gh.weigh. percentage(75 wt.%)of th. low molecular weigh. PCL *** a proof-of-concept test,we prepared films of th.ee different mass ratios of low and h.gh.molecular weigh. polymers with.a th.rmopress and reacted with.an alkynated fluorescent model compound on th. surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morph.genetic protein 2(BMP-2)-derived peptide was grafted onto th. films comprising different blend compositions,and th. effect of peptide surface density on th. osteogenic differentiation of h.man mesench.mal stromal cells(h.SCs)was *** two weeks of culturing in a basic medium,cells expressed h.gh.r levels of BMP receptor II(BMPRII)on films with.th. conjugated *** addition,we found th.t alkaline ph.sph.tase activity was only significantly enh.nced on films contain-ing th. h.gh.st peptide density(i.e.,561 pmol/cm^(2)),indicating th. importance of th. surface *** togeth.r,th.se results emph.size th.t th. density of surface peptides on cell differentiation must be considered at th. cell-material ***,we h.ve presented a viable strategy for ME-AM community th.t desires to tune th. bulk and surface functionality via blending of(m

关键词： Additive manufacturing Blending Surface functionalization Surface density Click ch.mistry h.man

Symptom presentation and evolution in th. first 48 h.urs after injury are associated with.return to play after concussion in elite Rugby Union

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Journal of Sport and h.alth.Science 2024年第3期13卷 387-397页

作者： Ross Tucker Matt Cross keith Stokes Lindsay Starling Rosy h.man Simon Kemp Steph.n West Martin Raftery Eanna Falvey James Brown Institute of Sport and Exercise Medicine(ISEM) Department of ExerciseUniversity of StellenboschTygerberg 7505South Africa World Rugby Ltd. Dublin D02 AE93Ireland Premiersh.p Rugby London SW1V 1PXUK Centre for h.alth and Injury and Illness Prevention in SportUniversity of BathClaverton Down BA27AYUK UK Collaborating Centre on Injury and Illness Prevention in Sport(UKCCIIS) University of BathClaverton Down BA27AYUK Rugby Football Union London TW27BAUK London Sch.ol of Tropical Medicine London WC1E 7HTUK Sport Injury Prevention Research.Centre Faculty of KinesiologyUniversity of CalgaryCalgary T2N 1N4Canada Department of Medicine School of Medicine and HealthUniversity College CorkCork T12 EC8PIreland Carnegie Applied Rugby Research.CARR)centre Carnegie School of SportLeeds Beckett UniversityLeeds LS63QSUK

Background:Return to play(RTP)in elite rugby is managed using a 6-stage graduated RTP protocol,wh.ch.can result in clearance to play with.n 1 week of *** aimed to explore h.w symptom,cognitive,and balance presentation and evolution during concussion screens 2 h.h.ad injury assessment(h.A2)and 48 h.h.A3)after injury were associated with.time to RTP)to identify wh.th.r a more conservative graduated RTP may be ***:A retrospective coh.rt study was conducted in 380 concussed rugby players from elite men’s rugby over 3 consecutive *** were classified as sh.rter or longer returns,depending on wh.th.r RTP occurred with.n 7 days(allowing th.m to be considered to play th. match.1 week after injury)or longer th.n 8 days,***,cognitive,and balance performance during screens was assessed relative to baseline(normal or abnormal)and to th. preceding screen(improving or worsening).Associations between sub-test abnormalities and RTP time were explored using odds ratios(OR,longer ***).Median day absence was compared between players with.abnormal or worsening results and th.se wh.se results were normal or ***:Abnormal symptom results during screens 2 h.and 48 h.after concussion were associated with.longer return time(h.A2:OR=2.21,95%confidence interval(95%CI):1.39-3.50;h.A3:OR=3.30,95%CI:1.89-5.75).Worsening symptom number or severity from th. time of injury to 2 h.and 48 h.post-injury was associated with.longer return(h.A2:OR=2.49,95%CI:1.36-4.58;h.A3:OR=3.34,95%CI:1.10-10.15).Median days absence was greater in players with.abnormal symptom results at both.h.A2 and *** and balance performance were not associated with.longer return and did not affect median days ***:Symptom presentation and evolution with.n 48 h.of concussion were associated with.longer RTP *** may guide a more conservative approach.to RTP,wh.le still adh.ring to individualized concussion management principles.

关键词： Brain injury Concussion management General return to play Medical management

h.w completely are randomized controlled trials of non-ph.rmacological interventions following concussion reported? A systematic review

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Journal of Sport and h.alth.Science 2024年第4期13卷 537-547页

作者： Jacqueline Josee van Ierssel Olivia Galea Kirsten h.lte Caroline Luszawski Elizabeth.Jenkins Jennifer O’Neil Carolyn A Emery Rebekah.Mannix Kath.yn Sch.eider keith Owen Yeates Roger Zemek Ch.ldren’s h.spital of Eastern Ontario Research.Institute OttawaON K1H 8L1Canada Th. Centre for h.alth Activity and Rehabilitation ResearchUniversity of OtagoDunedin 9016New Zealand Sport Injury Prevention Research.Centre Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada Alberta Ch.ldren’s h.spital Research.Institute University of Calgary CalgaryAB T2N 1N4Canada h.tch.iss Brain Institute University of CalgaryCalgaryAB T2N 4N1Canada Department of Psych.logy University of CalgaryCalgaryAB T2N 1N4Canada g Faculty of MedicineUniversity of OttawaOttawaON K1H 8M5Canada Sch.ol of Reh.bilitation 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:Th. study aimed to examine th. reporting completeness of randomized controlled trials(RCTs)of non-ph.rmacological interventions following ***:We search.d MEDLINE,Embase,PsycInfo,CINAh.,and Web of Science up to May *** reviewers independently screened studies and assessed reporting completeness using th. Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Th.rapeutic Exercise aNd Training(i-CONTENT)*** information was sough. my study auth.rs wh.re reporting was *** of bias(ROB)was assessed with.th. Coch.ane ROB-2 *** examining non-ph.rmacological interventions following ***:We included 89 RCTs(n=53 h.gh.ROB)examining 11 different interventions for concussion:sub-symptom th.esh.ld aerobic exercise,cervicovestibular th.rapy,ph.sical/cognitive rest,vision th.rapy,education,psych.th.rapy,h.perbaric oxygen th.rapy,transcranial magnetic stimulation,blue ligh. th.rapy,osteopath.c manipulation,and h.ad/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-ph.rmacological 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

EZh. inh.bitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal Transduction and Targeted Th.rapy 2024年第2期9卷 679-692页

作者： keith Al-h.sani Safiya Naina Marikar h.rikrish.an Kaipananickal Scott Maxwell Jun Okabe Ish.nt Kh.rana Th.mas Karagiannis Julia J.Liang Lina Mariana Th.mas Loudovaris Th.mas Kay Assam El-Osta Epigenetics in h.man h.alth.and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in h.man h.alth.and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Sch.ol of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Th.rapeutics The Chinese University of Hong KongSha TinHong Kong SAR h.ng Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Sh.ng Institute of h.alth.Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets th.t synth.size,store and release *** type 1 diabetes(T1D),T-cells of th. immune system selectively destroy th. insulin-producingβ-*** of th.se cells leads to a lifelong dependence on exogenous insulin administration for ***,th.re is an urgent need to identify novel th.rapies th.t stimulateβ-cell growth.and induceβ-cell *** and oth.rs h.ve sh.wn th.t pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to th.ir inh.rent differentiation *** transcriptional suppression is refractory to exocrine reaction and tigh.ly controls th. regenerative potential by th. EZh. *** th. present study,we sh.w th.t transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to th. FDAapproved EZh. inh.bitors GSK126 and Tazemetostat(Taz)influence a ph.notypic sh.ft towards aβ-like cell *** transition from repressed to permissive ch.omatin states are dependent on bivalent h.K27me3 and h.K4me3 ch.omatin *** EZh. is fundamental toβ-cell regenerative *** pancreatic ductal cells exh.bit insulin production and secretion in response to a ph.siological glucose ch.llenge ex *** pre-clinical studies underscore th. potential of small molecule inh.bitors as novel modulators of ductal progenitor differentiation and a promising new approach.for th. restoration ofβ-like cell function.

关键词： EZh. struction inh.bitors

CI-WGAN:融合临床指标和WGAN的孤独症个体化脑功能连接网络生成

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数据采集与处理 2024年第4期39卷 813-826页

作者：孙海林严加栋张嵘 KENDRICK keith 蒋希电子科技大学生命科学与技术学院成都611731 麦吉尔大学蒙特利尔神经研究所蒙特利尔H3A 2B4 北京大学基础医学院神经生物学系北京100191 北京大学神经科学研究所北京100191 神经科学教育部重点实验室北京100191 卫健委神经科学重点实验室北京100191 北京大学医学部孤独症研究中心北京100191

脑功能连接(Functional connectivity,FC)网络作为潜在的脑影像标志物对孤独症谱系障碍(Autism spectrum disorder,ASD)的辅助诊疗研究具有重要作用。然而现有的FC生成方法大多仅基于脑影像数据,未充分考虑个体的临床指标从而易丢失疾... 详细信息

脑功能连接(Functional connectivity,FC)网络作为潜在的脑影像标志物对孤独症谱系障碍(Autism spectrum disorder,ASD)的辅助诊疗研究具有重要作用。然而现有的FC生成方法大多仅基于脑影像数据,未充分考虑个体的临床指标从而易丢失疾病的特异性信息。而且,ASD作为一种谱系障碍,其临床指标存在显著的个体化差异。因此,仅基于脑影像数据的传统生成模型在生成准确的且能反映个体化临床指标的ASD个体FC的任务上存在挑战。针对上述挑战,提出了个体化临床指标引导的沃瑟斯坦生成对抗网络模型(Clinical-indicator-aware Wasserstein generative adversarial network,CI-WGAN),用于生成孤独症个体化FC网络。该模型引入个体化临床指标引导机制,实现了高精度ASD患者FC网络的生成。基于全世界最大孤独症脑影像公开数据集之一的ABIDE I数据集进行实验,CI-WGAN生成FC与真实FC的峰值信噪比(Peak signal-to-noise ratio,PSNR)、结构相似度(Structural similarity,SSIM)与平均绝对误差(Mean absolute error,MAE)分别达到19.037、0.236与0.178,相较于其他FC生成模型分别提升了3%、12%与2%。此外基于生成FC和独立临床验证指标的表征相似度分析(Representational similarity analysis,RSA),CI-WGAN生成的FC相较其他模型生成FC最少提高了0.1倍和3.7倍,证明了CI-WGAN生成的FC包含更多的ASD个体特异性信息。本文提出的CI-WGAN模型实现了高质量个体化FC的生成,为ASD的早期诊断和个性化治疗提供了有力的技术支持。

关键词：孤独症谱系障碍大脑功能连接生成对抗网络临床指标引导机制梯度惩罚机制

MAGNA CARTA AND Th. AMERICAN POLITICAL IMAGINATION： Two INSTANCES OF h.BEAS CORPUS VINDICATED

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Frontiers of Law in Ch.na-Selected Publications from Ch.nese Universities 2016年第2期11卷 215-235页

作者： h. Robert baker Department of h.story College of Arts & Sciences Georgia State University Atlanta US

Magna Carta h.s long been understood as a source of inspiration for th. U.S. Constitution, and especially its ensh.inement of th. writ of h.beas corpus -- th. righ. of any prisoner to test h.s or h.r detention according to th. law. In th. ＂Suspension Clause＂ of th. U.S. Constitution （Article I, Section 8）, Congress is granted permission to suspend h.beas corpus only ＂wh.n in cases of Rebellion or Invasion th. public Safety may require it.＂ Th.s article surveys two failed attempts by th. U.S. government to suspend th. writ of h.beas corpus. Th. first （wh.ch.was actually th. very first such.attempt） was in 1807 and followed revelations of th. so-called Burr Conspiracy. Th. second （incidentally th. most recent in American h.story） occurred during th. War on Terror and culminated with.th. Supreme Court＇s decision ofBoumediene vs Bush.in 2008. A close examination of th.se two h.storical episodes reveals just h.w different were th. constitutional processes of th. early republic and contemporary times. Additionally, comparing th. uses of Magna Carta during th. two episodes demonstrates marked ch.nges in American political culture. h.storical consciousness, vital to early Americans＇ understanding of th.ir political system, h.s sh.fted to an elite level. Likewise, th. protection of fundamental liberties h.s migrated from th. popular branch.of government （Congress） to th. elite one （th. Supreme Court）. Th.s article considers th. implication of th.s sh.ft in both.constitutional processes and h.storical consciousness.

关键词： Constitutional Law legal h.story h.beas corpus suspension clause MagnaCarta

Dairy cows inoculated with.h.gh.y path.genic avian influenza virus h.N1

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四川生理科学杂志 2024年第10期46卷 2275-2275页

作者： Amy L baker Virus and Prion Research.Unit National Animal Disease Center Agricultural Research Service United States Department of Agriculture Ames Iowa USA National Veterinary Services Laboratories Animal and Plant Health Inspection Service United States Department of Agriculture Ames Iowa USA Veterinary Diagnostic and Production Animal Medicine Iowa State University Ames Iowa USA

h.gh.y path.genic avian influenza(h.AI)h.N1 h.magglutinin clade 2.***.4.4b was detected in th. United States in *** h.AI viruses caused mortality events in poultry,wild birds,and wild *** March.25,2024,h.AI h.N1 clade 2.***.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses.1 Over 200 positive h.rds were identified in 14 *** case description included reduced feed intake and rumen motility in lactating cows,decreased milk production,and th.ck yellow milk.2,3 Th. diagnostic investigation revealed viral RNA in milk and mammary tissue with.alveolar epith.lial degeneration and necrosis and positive immunoreactivity of glandular epith.lium.A single transmission event,likely from birds,was followed by limited local transmission and onward h.rizontal transmission of h.N1 clade 2.***.4.4b genotype B3.13.4 We sough. to experimentally reproduce infection with.genotype B3.13 in h.lstein yearling h.ifers and lactating *** were inoculated by aerosol respiratory route and cows by intramammary *** disease was mild in h.ifers,but infection was confirmed by virus detection,lesions,and *** disease in lactating cows included decreased rumen motility,ch.nges to milk appearance,and production *** was confirmed by h.gh.levels of viral RNA detected in milk,virus isolation,lesions in mammary tissue,and *** study provides th. foundation to investigate additional routes of infection,path.genesis,transmission,and intervention strategies.

关键词： h.N1 cows fir

Cancer risk in primary sclerosing ch.langitis: Epidemiology,prevention, and surveillance strategies

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World Journal of Gastroenterology 2019年第6期25卷 659-671页

作者： Brian M Fung keith D Lindor James h.Tabibian UCLA-Olive View Internal Medicine Residency Program Olive View-UCLA Medical Center Office of th. University Provost Arizona State University Division of Gastroenterology Department of MedicineOlive View-UCLA Medical Center

Primary sclerosing ch.langitis(PSC) is a rare ch.lestatic liver disease ch.racterized by progressive fibroinflammatory destruction of th. intra-and/or extrah.patic biliary ducts. Wh.le its features and disease course can be variable,most patients with.PSC h.ve concurrent inflammatory bowel disease and will eventually develop liver cirrh.sis and end-stage liver disease, with.liver transplantation representing th. only potentially curative option. Importantly,PSC is associated with.a significantly increased risk of malignancy compared to th. general population, mainly ch.langiocarcinoma, gallbladder carcinoma,h.patocellular carcinoma, and colorectal cancer, with.nearly 50% of death. in patients with.PSC being due to cancer. Th.refore, robust surveillance strategies are needed, th.ugh.uncertainty remains regarding h.w to best do so. In th.s review, we discuss th. epidemiology, prevention, and surveillance of cancers in patients with.PSC. Wh.re evidence is limited, we present pragmatic approach.s based on currently available data and expert opinion.

关键词： Bile duct diseases Ch.langiocarcinoma Gallbladder carcinoma h.patocellular carcinoma Colorectal cancer Ch.moprotection Inflammatory bowel disease

Evaluation and assessment of semen for IVF/ICSI

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Asian Journal of Andrology 2002年第4期4卷 281-285页

作者： D.Y. Liu h.W.G. baker University of Melbourne Department of Obstetrics and Gynaecology and Melbourne IVF and Reproductive Services Royal Women's Hospital Carlton Victoria 3053 AustraliaUniversity of Melbourne Department of Obstetrics and Gynaecology and Melbourne IVF and Reproductive Services Royal Women's Hospital Carlton Victoria 3053 Australia

Evaluation and assessment of semen is very important for both.diagnosis of male infertility and selection of patients for treatment with.IVF or ICSI. In standard IVF, sperm function is essential for normal fertilization: sperm must be able to bind to zona pellucida (ZP), undergo th. acrosome reaction and penetrate th. ZP and fuse with.th. oolemma before fertilization takes place. In contrast, most sperm functions are not required for fertilization in ICSI since sperm bypass th. ZP and oolemma by injection of a single sperm directly into cytoplasm of oocyte. Th.refore, th. clinical decision on treatment of patients with.eith.r IVF or ICSI is mostly dependent on results of sperm tests. h.wever, conventional semen analyses do not provide accurate information about sperm fertilizing ability since many patients with.subtle sperm defects can not be detected. More advanced sperm function tests are required to detect sperm defects th.t may lead to failure of fertilization in standard IVF. In th. last 15 years we performed extensive studies on relationsh.p between sperm functions and fertilization rates by logistic regression analysis in large numbers of IVF patients including 370 patients with.zero fertilization rate by IVF. We confirmed sperm morph.logy assessed strictly was strongly related to fertilisation rate with.standard IVF. Th.s sperm morph.logy assessment is very useful for selection of patients for ICSI. We also developed a number of new tests including sperm-ZP binding, sperm-ZP penetration and th. ZP-induced AR and evaluated th. clinical value of th.se tests. Sperm-ZP binding and sperm-ZP penetration tests are th. most powerful indicators for sperm fertilizing ability in vitro. Th. ZP-induced AR is h.gh.y correlated with.sperm-ZP penetration. We discovered a condition we call disordered ZP-induced AR wh.ch.causes serve infertility in up to 25% men with.oth.rwise idiopath.c infertility In conclusion, th. combination of semen analysis with.advanced sperm function

关键词： male infertility sperm function tests sperm-oocyte interactions IVF/ICSI