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Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on uk Biobank data

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cancer Biology & Medicine 2024年第8期 712-723页

作者： Yu Zhang Chao Sheng Zhangyan Lyu Hongji Dai Fangfang Song Fengju Song Yubei Huang Kexin Chen Department of Epidemiology and Biostatistics Key Laboratory of Molecular Cancer Epidemiology Key Laboratory of Prevention and Control of Human Major Diseases Ministry of Education National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin Medical University

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(Qcancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and ***: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the uk Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk ***: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94; 0.81, 0.73±0.90; mortality: 0.75, 0.64±0.87; 0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk ***: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

关键词： Colorectal cancer incidence mortality polygenic risk score screening

Targeting muscle to treat Charcot-Marie-Tooth disease

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Neural Regeneration research 2024年第8期19卷 1653-1654页

作者： David Villarroel-Campos James N.Sleigh Department of Neuromuscular Diseases and UCL Queen Square Motor Neuron Disease Centre UCL Queen Square Institute of NeurologyUniversity College LondonLondonUK uk Dementia research Institute University College LondonLondonUK

Charcot-Marie-Tooth disease(CMT)is a hereditary peripheral neuropathy causing muscle weakness/wasting and sensory dysfunction predominantly in limb *** patients display gait abnormalities,foot deformities,loss of sens... 详细信息

关键词： Marie sensation neuropathy

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Simplified prediction models for acoustic installation effects of train-mounted equipment

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Railway Engineering Science 2024年第2期32卷 125-143页

作者： David Thompson Dong Zhao Giacomo Squicciarini Institute of Sound and Vibration research University of SouthamptonSouthampton SO171BJUK

Acoustic models of railway vehicles in standstill and pass-by conditions can be used as part of a virtual certification process for new *** each piece of auxiliary equipment,the sound power measured on a test bench is combined with meas-ured or predicted transfer *** is important,however,to allow for installation effects due to shielding by fairings or the train *** the current work,fast-running analytical models are developed to determine these installation *** model for roof-mounted sources takes account of diffraction at the corner of the train body or fairing,using a barrier *** equipment mounted under the train,the acoustic propagation from the sides of the source is based on free-field Green’s *** bottom surfaces are assumed to radiate initially into a cavity under the train,which is modelled with a simple diffuse field *** sound emitted from the gaps at the side of the cavity is then assumed to propagate to the receivers according to free-field Green’s *** show good agreement with a 2.5D boundary element model and with *** uncertainty and parametric uncertainty are *** largest variability occurs due to the height and impedance of the ground,especially for a low *** leads to standard deviations of up to 4 dB at low *** the roof-mounted sources,uncertainty over the location of the corner used in the equivalent barrier model can also lead to large standard deviations.

关键词： Train noise Auxiliary equipment Acoustic installation effects Virtual certification Uncertainty

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied Healthresearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical research Centre University of LeicesterLeicesterUK Stroke research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA research and Graduate Services University of NottinghamNottinghamUK Community and Health research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

3D printing of poly(ethyleneimine)-functionalized Mg-Al mixed metal oxide monoliths for direct air capture of CO_(2)

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Journal of Energy Chemistry 2024年第9期96卷 491-500页

作者： Qingyang Shao Zhuozhen Gan Bingyao Ge Xuyi Liu Chunping Chen Dermot O’Hare Xuancan Zhu research Center of Solar Power&Refrigeration School of Mechanical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Chemistry research Laboratory Department of ChemistryUniversity of OxfordOxford OX13TAUK

Direct air capture(DAC)of CO_(2)plays an indispensable role in achieving carbon-neutral goals as one of the key negative emission *** large air flows are required to capture the ultradilute CO_(2)from the air,lab-synthesized adsorbents in powder form may cause unacceptable gas pressure drops and poor heat and mass transfer efficiencies.A structured adsorbent is essential for the implementation of gas-solid contactors for cost-and energy-efficient DAC *** this study,efficient adsorbent poly(ethyleneimine)(PEI)-functionalized Mg-Al-CO_(3)layered double hydroxide(LDH)-derived mixed metal oxides(MMOs)are three-dimensional(3D)printed into monoliths for the first time with more than 90%adsorbent *** printing process has been optimized by initially printing the LDH powder into monoliths followed by calcination into MMO *** structure exhibits a 32.7%higher specific surface area and a 46.1%higher pore volume,as compared to the direct printing of the MMO powder into a *** impregnation of PEI,the monolith demonstrates a large adsorption capacity(1.82 mmol/g)and fast kinetics(0.7 mmol/g/h)using a CO_(2)feed gas at 400 ppm at 25℃,one of the highest values among the shaped DAC *** of the amino-polymers during the post-printing process affects the diffusion of CO_(2),resulting in slower adsorption kinetics of pre-impregnation monoliths compared to post-impregnation *** optimal PEI/MeOH ratio for the post-impregnation solution prevents pores clogging that would affect both adsorption capacity and kinetics.

关键词： 3D printing Mixed metal oxides Amine functionalization Structured adsorbent Direct air capture

The Triple Combination of Meropenem,Avibactam,and a Metallo-b-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different b-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling Alistair James Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna Jordan Mathias Jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher Joseph Schofield Timothy Walsh Department of Biology&Ineos Oxford Institute for Antimicrobial research University of OxfordOxford OX13REUK Chemistry research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

Fluidization and Transport of Vibrated Granular Matter:A Review of Landmark and Recent Contributions

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Fluid Dynamics & Materials Processing 2024年第1期20卷 1-29页

作者： Peter Watson Sebastien Vincent Bonnieu Marcello Lappa Department of Mechanical and Aerospace Engineering University of StrathclydeGlasgowUK European Space Agency European Space Research and Technology CentreNoordwijkNetherland

We present a short retrospective review of the existing literature about the dynamics of(dry)granular matter under the effect of *** main objective is the development of an integrated resource where vital information about past findings and recent discoveries is provided in a single *** attention is paid to those works where successful synthetic routes to as-yet unknown phenomena were *** landmark results are analyzed,while smoothly blending them with a history of the field and introducing possible categorizations of the prevalent *** no classification is perfect,and it is hard to distillate general properties out of specific observations or realizations,two possible ways to interpret the existing results are defined according to the type of forcing or the emerging(ensuing)regime of *** particular,first results concerning the case where vibrations and gravity are concurrent(vertical shaking)are examined,then the companion situation with vibrations perpendicular to gravity(horizontal shaking)is *** classes are introduced as follows:(1)Regimes where sand self-organizes leading to highly regular geometrical“pulsating”patterns(thin layer case);(2)Regimes where the material undergoes“fluidization”and develops an internal multicellular convective state(tick layers case);(3)Regimes where the free interface separating the sand from the overlying gas changes inclination or develops a kind a patterned configuration consisting of stable valleys and mountains or travelling waves;(4)Regimes where segregation is produced,i.e.,particles of a given size tend to be separated from the other grains(deep containers).Where possible,an analogy or parallelism is drawn with respect to the companion field of fluid-dynamics for which the assumption of“continuum”can be applied.

关键词： Granular materials vibrations fluidization flowability symmetry breaking

Framework and Key Technologies of Human-machine Hybrid-augmented Intelligence System for Large-scale Power Grid Dispatching and Control

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CSEE Journal of Power and Energy Systems 2024年第1期10卷 1-12页

作者： Shixiong Fan Jianbo Guo Shicong Ma Lixin Li Guozheng Wang Haotian Xu Jin Yang Zening Zhao China Electric Power research Institute Beijing 100192China the Beijing Huairou Laboratory Beijing 101400China School of Engineering the University of GlasgowGlasgow G128QQUK

With integration of large-scale renewable energy,new controllable devices,and required reinforcement of power grids,modern power systems have typical characteristics such as uncertainty,vulnerability and openness,which makes operation and control of power grids face severe security *** of artificial intelligence(AI)technologies represented by machine learning in power grid regulation is limited by reliability,interpretability and generalization ability of complex *** of hybrid-augmented intelligence(HAI)based on human-machine collaboration(HMC)is a pivotal direction for future development of AI technology in this *** on characteristics of applications in power grid regulation,this paper discusses system architecture and key technologies of human-machine hybrid-augmented intelligence(HHI)system for large-scale power grid dispatching and control(PGDC).First,theory and application scenarios of HHI are introduced and analyzed;then physical and functional architectures of HHI system and human-machine collaborative regulation process are *** technologies are discussed to achieve a thorough integration of human/machine ***,state-of-theart and future development of HHI in power grid regulation are summarized,aiming to efficiently improve the intelligent level of power grid regulation in a human-machine interactive and collaborative way.

关键词： Artificial intelligence human-machine collaborative control human-machine hy brid intelligence optimization and evolution power grid dispatching and control