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Combination treatment of inflammatory bowel disease:Present status and future perspectives

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World Journal of gastroenterology 2024年第15期30卷 2068-2080页

作者： John K Triantafillidis Constantinos g Zografos Manousos M Konstadoulakis Apostolos e Papalois Inflammatory Bowel Disease Unit "Metropolitan General"HospitalHolargos 15562AtticaGreece Hellenic Society for gastrointestinal Oncology 354 Iera OdosChaidari 12461AtticaGreece The 2^(nd)Department of Surgery University of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece Unit of Surgical Research and Training The 2^(nd)Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing d

关键词： Biologics for immune-mediated conditions Dual-targeted treatment Combination treatment Inflammatory bowel disease Crohn’s

Pressurized environments directly influence friction and wear of dry steel contacts—Investigations in a novel high fluid pressure tribometer

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Friction 2024年第7期12卷 1599-1617页

作者： Paul ReICHLe Jakob BARZ georg UMLAUF günter e.M.TOVAR Institute of Interfacial Process engineering and Plasma Technology(IgVP) University of StuttgartStuttgart 70569Germany Fraunhofer Institute for Interfacial engineering and Biotechnology(IgB) Stuttgart 70569Germany

To reduce the usage of classical lubricants in deep drawing,a new tribological system based on volatile lubricants was developed.Therefore,a volatile medium is injected under high pressure into the interstice between drawing tool and sheet metal.Depending on temperature and pressure,the temporary lubricant may exist in its gaseous or liquid phase.In this study,a novel high fluid pressure tribometer was designed to investigate the friction and wear of dry steel contacts under comparable conditions like in dry deep drawing.Therefore,a new ball-on-disc tribometer was designed and integrated into a high-pressure vessel.To specifically investigate the effects of different environments(technical air,liquid and gaseous carbon dioxide,nitrogen,argon)at atmospheric and high pressure(0.1 MPa,6 MPa)on tribology,the specimens and all components were operating unlubricated.During the experiments,the friction was measured continuously.Results show that the highest friction occurs in air and the lowest in carbon dioxide environment.Subsequent to the experiments,the wear of the specimens was assessed along with changes in surface chemistry related to tribochemical reactions.Therefore,the tribology of the dry sliding contacts is correlated to changes of the surface chemistry.Also differences as well as similarities regarding the different fluid environments are shown.As the results show,the differences between the media used are most pronounced at elevated pressure.Concluding,this work gives clear indications on the suitability of volatile lubricants in dry friction or rather gas lubrication,especially for dry deep drawing.

关键词： dry friction and dry wear gas lubrication carbon dioxide tribo-layer dry metal forming

Collective coherent emission of electrons in strong laser fields and perspective for hard x-ray lasers

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Matter and Radiation at extremes 2024年第2期9卷 1-3页

作者： e.g.gelfer A.M.Fedotov O.Klimo S.Weber extreme Light Infrastructure eRIC ELI Beamlines Facility25241 Dolní BřežanyCzech Republic HiLASe Centre Institute of Physics of the Czech Academy of Sciences25241 Dolní BřežanyCzech Republic National Research Nuclear University MePhI Moscow 115409Russia FNSPe Czech Technical University in Prague11519 PragueCzech Republic

Coherent motion of particles in a plasma can imprint itself on radiation.The recent advent of high-power lasers—allowing the nonlinear inverse Compton-scattering regime to be reached—has opened the possibility of looking at collective effects in laser–plasma interactions.Under certain conditions,the collective interaction of many electrons with a laser pulse can generate coherent radiation in the hard x-ray regime.This perspective paper explains the limitations under which such a regime might be attained.

关键词： laser scattering coherent

Barosinusitis due to routine weather changes:A cross-sectional analysis of public websites

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 18-23页

作者： James C.Campbell Julia e.Canick Philip g.Chen Ralph Abi Hachem David W.Jang Department of Head and Neck Surgery&Communication Sciences Duke University School of MedicineDurhamNorth CarolinaUSA Duke University School of Medicine DurhamNorth CarolinaUSA Department of Otolaryngology-Head and Neck Surgery University of Texas Health Science Center San AntonioSan AntonioTexasUSA

Background:Sinusitis is a common diagnosis that can be erroneously associated with routine weather‐related barometric pressure changes.In actuality,these pressure changes likely exacerbate migraine headaches,which can cause facial pain and pressure rather than true sinus inflammation.Objective:The present study sought to characterize the representation of both sinusitis and migraine in association with barometric pressure changes across websites on the Internet.Methods:An Internet search for relevant terms was conducted,and content of the resulting pages was assessed for associations between weather‐related pressure changes and either sinusitis or migraine.Variations in reported results across different subtypes of Internet sources were analyzed.The primary outcomes measured were(1)whether a given media source associated barometric weather changes with sinusitis,(2)whether that source associated barometric weather changes with migraine,and(3)treatment options offered by that source.Results:Of the 116 included webpages,36(31.03%)associated sinusitis and routine barometric pressure changes.Of these,10(27.77%)were otolaryngology practice sites.Sixty‐seven webpages(57.76%)associated migraine and routine barometric pressure changes.Of these,nonotolaryngology webpages were more likely to report this link.Conclusions:Otolaryngology practice sites were observed to be the most frequent professional medical resource reporting the unsubstantiated claim that routine barometric pressure changes are associated with sinusitis.Nonotolaryngology sources were more likely to link weather‐related pressure changes to migraine.These results suggest that opportunities exist for otolaryngology practice sites to educate patients about nonrhinogenic headache etiologies.

关键词： acute rhinosinusitis balloon sinus dilation headache migraine sinusitis

Dysregulated bidirectional epithelial-mesenchymal crosstalk:A core determinant of lung fibrosis progression

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 27-33页

作者： Liudi Yao Zijian Xu 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

Progressive lung fibrosis is characterized by dysregulated extracellular matrix(eCM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully explained.Within human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(eMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties.This review will focus on the role of eMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

关键词： Lung fibrosis epithelial-mesenchymal transition(eMT) Crosstalk

Identific tion of quantitative trait loci and associated candidate genes for pregnancy success in Angus–Brahman crossbred heifers

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Journal of Animal Science and Biotechnology 2024年第1期15卷 162-170页

作者： Quinn A.Hoorn gabriel A.Zayas eduardo e.Rodriguez Laura M.Jensen Raluca g.Mateescu Peter J.Hansen Department of Animal Sciences Donald Henry Barron Reproductive and Perinatal Biology Research Programand the Genetics InstituteUniversity of FloridaGainesvilleFLUSA School of Applied Systems Biology La Trobe UniversityBundooraVIC 3083Australia

Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef production.Results genome-wide association studies(gWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation gWAS was performed using data from another farm. Heifers were genotyped with the Bovine ggP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination(AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI(PAI;n = 1,481) and pregnancy status at the end of the breeding season(PeBS;n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PeBS, respectively. In the PAI model, one quantitative trait locus(QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PeBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were identified.Conclusions In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations with larger populations could lead to the develo

关键词： Beef cattle Fertility gWAS QTL

Unimolecular Reactions of e-glycolaldehyde Oxide and Its Reactions with One and Two Water Molecules

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Research 2024年第1期2023卷 809-824页

作者： Yan Sun Bo Long Donald g.Truhlar Department of Physics Guizhou UniversityGuiyang 550025China College of Materials Science and engineering Guizhou Minzu UniversityGuiyang 550025China Department of Chemistry Chemical Theory Centerand Supercomputing InstituteUniversity of MinnesotaMinneapolisMN 55455-0431USA

The kinetics of Criegee intermediates are important for atmospheric modeling.However,the quantitative kinetics of Criegee intermediates are still very limited,especially for those with hydroxy groups.Here,we calculate rate constants for the unimolecular reaction of e-glycolaldehyde oxide[e-hydroxyethanal oxide,e-(CH_(2)OH)CHOO],for its reactions with H_(2)O and(H_(2)O)_(2),and for the reaction of the e-(CH_(2)OH)CHOO…H_(2)O complex with H_(2)O.For the highest level of electronic structure,we use W3X-L//CCSD(T)-F12a/cc-pVDZ-F12 for the unimolecular reaction and the reaction with water and W3X-L//DF-CCSD(T)-F12b/jun-cc-pVDZ for the reaction with 2 water molecules.For the dynamics,we use a dual-level strategy that combines conventional transition state theory with the highest level of electronic structure and multistructural canonical variational transition state theory with small-curvature tunneling with a validated density functional for the electronic structure.

关键词： structure kinetics molecular

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 unknown.We 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 signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces eMT as a conse-quence.In 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 differentiation.Together,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

Commentary on "Association of daily sitting time and leisure-time physical activity with body fat among U.S.adults"

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Journal of Sport and Health Science 2024年第2期13卷 127-129页

作者： Barbara e.Ainsworth School of exercise and Health Shanghai University of SportShanghai 200438China

In their study,association of daily sitting time and leisure-time physical activity (LTPA) with body fat among U.S.Adults,Liao et al.^(1) analyzed data from the 2011-2018 National Health and examination Survey to examine associations between h/day sitting,meeting (or not meeting) the U.S.Physical Activity guidelines of≥150 min/week of moderate-and vigorous-intensity LTPA,and combinations of sitting time and LTPA on totaland trunk percent body fat (BF%).

关键词： U.S. adult among