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Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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World Journal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： jeffrey A Lowell michael J Farber Keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States Preclinical Studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined *** et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this *** importance of controlled trials should be stressed in establishing new treatment *** prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy

Comparisons of oxbow lake fish assemblages in relation to bigheaded carp establishment in the lower White River, Arkansas

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Ecological Processes 2024年第1期13卷 188-205页

作者： michael A.Eggleton Cody J.Salzmann Joseph E.Kaiser Shannon C.F.smith Department of Aquaculture and Fisheries University of Arkansas at Pine Bluff Arkansas Game and Fish Commission Virginia Institute of Marine Science

Background Since the late 1990s, bigheaded carps(largely silver carp [Hypophthalmichthys molitrix] but also bighead carp [H. nobilis]) have established throughout the lower Mississippi River basin. Using previously studied oxbow lakes in the lower White River basin, Arkansas, we compared current(2017, “post-carp” establishment) fish assemblages to historical(2002, “pre-carp” establishment) fish assemblages. Fish assemblages were comprehensively assessed using multiple gears, including boat electrofishing, mini-fyke nets, and experimental small-mesh gill *** T-tests suggested that fish assemblage indices of richness, diversity, evenness, and dominance were often greater(P 0.05) between the pre-carp and post-carp period with fish assemblages depicted using mini-fyke nets. Nonmetric multidimensional scaling analyses indicated that fish assemblages differed structurally between pre-carp and post-carp periods. Assemblage differences were linked to both small and large abundance changes for more than 20 species. Abundances of gizzard shad(Dorosoma cepedianum), emerald shiner(Notropis atherinoides), pugnose minnow(Opsopoeodus emiliae), crappies(Pomoxis spp.), bluegill(Lepomis macrochirus), orangespotted sunfish(L. humilis), and yellow bass(Morone mississippiensis) declined between the pre-carp and postcarp periods. Conversely, abundances of weed shiner(N. texanus), pallid shiner(Hybopsis amnis), longear sunfish(L. megalotis), buffalofishes(Ictiobus spp.), and gars(Lepisosteus spp.) generally increased during the same *** Although not possible to conclude assemblage shifts were entirely related to bigheaded carps due to the absence of an appropriate reference system where carps did not establish, the wide establishment of these carps is one of the most pervasive changes to have occurred in the lower White

关键词： Bigheaded carp Silver carp Aquatic nuisance species Fish assemblage Oxbow lake Large river

Predictors of survival in autoimmune liver disease overlap syndromes

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World Journal of Hepatology 2024年第9期16卷 1269-1277页

作者： Dujinthan Jayabalan Yi Huang Luis Calzadilla-Bertot Malik Janjua Bastiaan de Boer John Joseph Wendy Cheng Simon Hazeldine Briohny W smith Gerry C MacQuillan michael C Wallace George Garas Leon A Adams Gary P jeffrey Medical School University of Western AustraliaNed-lands 6009Western AustraliaAustralia Department of Hepatology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia Department of Anatomical Pathology PathWest Laboratory MedicineNedlands 6009Western AustraliaAustralia Department of Gastroenterology and Hepatology Royal Perth HospitalPerth 6000Western AustraliaAustralia Department of Gastroenterology and Hepatology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Medical School University of Western AustraliaNedl-ands 6009Western AustraliaAustralia

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is *** To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related *** Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort ***-related death or transplantation(liver-related mortality)was determined using a population-based data linkage *** scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and *** was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any *** Survival in the rare,AILDOS is *** current study supports the LOS as a predictor of liver-related mortality in AIH-PBC *** trials investigating predictors of survival in AILDOS are required.

关键词： Autoimmune liver disease overlap syndromes Liver outcome score Liver-related death Hepascore Autoimmune hepatitis Primary biliary cholangitis Primary sclerosing cholangitis

Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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Journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold Jenifer Murphy-smith Chee H.Ng David Mischoulon Gerard J.Byrne Chad A.Bousman Con Stough michael Berk Jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression Clinical and Research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia Departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Psychiatry the University of MelbourneMelbourne 3052Australia Centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and Clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical Psychiatry

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Smoking cessation prior to elective total joint arthroplasty results in sustained abstinence postoperatively

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World Journal of Orthopedics 2024年第7期15卷 627-634页

作者： Billy Insup Kim jeffrey O'Donnell Colleen M Wixted Thorsten Markus Seyler William A Jiranek michael Paul Bolognesi Sean Patrick Ryan Department of Orthopedic Surgery Hospital for Special SurgeryNew YorkNY 10021United States Department of Orthopedic Surgery New York UniversityNew YorkNY 10003United States Department of Orthopedic Surgery Duke University HospitalDurhamNC 27560United States

BACKGROUND Tobacco use is a well-documented modifiable risk factor for perioperative *** To determine the tobacco abstinence rates of patients who made cessation efforts prior to a total joint arthroplasty(TJA)*** A retrospective evaluation was performed on 88 self-reported tobacco users who underwent TJA between 2014-2022 and had tobacco cessation dates within 3 mo of *** patients were contacted via phone survey to understand their tobacco use pattern,and patient reported outcomes.A total of 37 TJA patients *** Our cohort was on average 61-years-old,60%(n=22)women,with an average body mass index of 30 kg/m^(2).The average follow-up time was 2.9±1.9 years.A total of 73.0%(n=27)of patients endorsed complete abstinence from tobacco use prior to *** cessation methods were used perioperatively including prescription therapy(13.5%),over the counter nicotine replacement(18.9%),cessation programs(5.4%).At final follow up,43.2%(n=16)of prior tobacco smokers reported complete *** who were able to maintain cessation postoperatively had improved Patient-Reported Outcomes Measurement Information System(PROMIS)-10 mental health scores(49 vs 58;P=0.01),and hip dysfunction and osteoarthritis outcome score for joint replacement(***)scores(63 vs 82;P=0.02).No patients in this cohort had a prosthetic joint infection or required revision *** We report a tobacco cessation rate of 43.2%in patients undergoing elective TJA nearly 3 years *** undergoing TJA who were able to remain abstinent had improved PROMIS-10 mental health scores and *** *** perioperative period provides clinicians a unique opportunity to assist active tobacco smokers with cessation efforts and improve postoperative outcomes.

关键词： Smoking cessation Total joint arthroplasty Outcomes Tobacco use Postoperative abstinence

Storylines of family medicine Ⅰ:framing family medicine–history,values and perspectives

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Family Medicine and Community Health 2024年第S3期12卷 2-11页

作者： William B Ventres Leslie A Stone Kathleen T Rowland Richard H Streiffer michael D Macechko Julia A Roulier jeffrey M Borkan Larry A Green Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family and Preventive Medicine Rush Medical College of Rush UniversityChicagoIllinoisUSA College of Community Health Sciences University of AlabamaTuscaloosaAlabamaUSA UAMS Northwest Regional Campus Family Medicine Residency Program FayettevilleArkansasUSA UAMS North Central Regional Campus Family Medicine Residency Program BatesvilleArkansasUSA Family Medicine Brown University Warren Alpert Medical SchoolProvidenceRhode IslandUSA University of Colorado School of Medicine AuroraColoradoUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅰ:framing family medicine—history,values,and perspectives’,the authors address the following themes:‘Notes on Storylines of Family Medicine’,‘Family medicine—the generalist specialty’,‘Family medicine’s achievements—a glass half full assessment’,‘Family medicine’s next 50 years—toward filling our glasses’,‘Four enduring truths of family medicine’,‘Names matter’,‘Family medicine at its core’and‘The ecology of medical care.’May readers find much food for thought in these essays.

关键词： glasses illustration Notes

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.smith Tiffany M.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA Laboratory Medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of Medicine The University of ArizonaTucsonAZ 85724USA Department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

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A randomized controlled trial of Promoting Physical Activity in Regional and Remote Cancer Survivors(PPARCS)

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Journal of Sport and Health Science 2024年第1期13卷 81-89页

作者： Sarah J.Hardcastle Chloe Maxwell-smith Vinicius Cavalheri Terry Boyle Marta Leyton Román Cameron Platell michael Levitt Christobel Saunders Frank Sardelic Sophie Nightingale Jacob McCormick Craig Lynch Paul A.Cohen Max Bulsara Dana Hince Sport and Physical Activity Research Centre Sheffield Hallam UniversitySheffieldS102BPUK Institute for Health Research The University of Notre DameFremantleWA 6959Australia Curtin School of Population Health Curtin UniversityPerthWA 6845Australia Curtin School of Allied Health Curtin UniversityPerthWA 6845Australia Allied Health South Metropolitan Health ServiceMurdochWA 6150Australia Australian Centre for Precision Health University of South AustraliaAdelaideSA 5001Australia Department of Didactics of Musical Plastic and Body ExpressionUniversity of ExtremaduraCaceres 10071Spain St.John of God Subiaco Hospital PerthWA 6008Australia Department of Surgery University of MelbourneMelbourneVIC 3010Australia Tamara Private Hospital TamworthNSW 2340Australia Peter MacCallum Cancer Centre MelbourneVIC 3000Australia College of Health and Medicine Australian National UniversityCanberraACT 2600Australia Division of Obstetrics and Gynaecology Medical SchoolUniversity of Western AustraliaPerthWA 6009Australia

Background:Physical activity(PA)is important for cancer *** of remotely delivered interventions are needed to assist in reaching under-served non-metropolitan cancer *** objective of this study was to ascertain whether wearable technology,coupled with health coaching was effective in increasing PA in breast and colorectal cancer survivors living in regional and remote areas in ***:Cancer survivors from 5 states were randomized to intervention and control *** participants were given a Fitbit Charge 2TMand received up to 6 telephone health coaching *** participants received PA print *** assessments at baseline and 12 weeks measured moderate-to-vigorous PA(MVPA),light PA,and sedentary ***:Eighty-seven participants were recruited(age=63±11 years;74(85%)female).There was a significant net improvement in MVPA of 49.8 min/week,favoring the intervention group(95%confidence interval(95%CI):13.6-86.1,p=0.007).There was also a net increase in MVPA bouts of 39.5 min/week(95%CI:11.9-67.1,p=0.005),favoring the intervention *** groups improved light PA and sedentary behavior,but there were no between-group ***:This’s the first study to demonstrate that,when compared to standard practice(i.e.,PA education),a wearable technology intervention coupled with distance-based health coaching,improves MVPA in non-metropolitan cancer *** results display promise for the use of scalable interventions using smart wearable technology in conjunction with phone-based health coaching to foster increased PA in geographically disadvantaged cancer survivors.

关键词： Behavior change Exercise Health disparities Oncology Wearable technology

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Statistical evaluation of 571 GaAs quantum point contact transistors showing the 0.7 anomaly in quantized conductance using cryogenic on-chip multiplexing

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Chip 2024年第3期3卷 21-28页

作者： Pengcheng Ma Kaveh Delfanazari Reuben K.Puddy Jiahui Li Moda Cao Teng Yi Jonathan P.Griffiths Harvey E.Beere David A.Ritchie michael J.Kelly Charles G.smith Cavendish Laboratory Department of PhysicsUniversity of CambridgeCambridge CB30HEUK James Watt School of Engineering University of GlasgowGlasgow G128QQUK Electrical Engineering Division University of CambridgeCambridge CB30FAUK

Themass production and the practical number of cryogenic quantum devices producible in a single chip are limited to the number of electrical contact pads and wiring of the cryostat or dilution *** is,therefore,beneficial to contrast themeasurements of hundreds of devices fabricated in a single chip in one cooldown process to promote the scalability,integrability,reliability,and reproducibility of quantum devices and to save evaluation time,cost and ***,we used a cryogenic on-chip multiplexer architecture and investigated the statistics of the 0.7 anomaly observed on the first three plateaus of the quantized conductance of semiconductor quantum point contact(QPC)*** single chips contain 256 split gate field-effect QPC transistors(QFET)each,with two 16-branch multiplexed source-drain and gate pads,allowing individual transistors to be selected,addressed and controlled through an electrostatic gate voltage process.A total of 1280 quantum transistors with nano-scale dimensions are patterned in 5 different chips of GaAs *** the measurements of 571 functioning QFETs taken at temperatures T[1.4 K and T[40 mK,it is found that the spontaneous polarisation model and Kondo effect do not fit our ***,some of the features in our data largely agreed with van Hove model with short-range *** approach provides further insight into the quantum mechanical properties and microscopic origin of the 0.7 anomaly in QFETs,paving the way for the development of semiconducting quantum circuits and integrated cryogenic electronics,for scalable quantum logic control,readout,synthesis,and processing applications.

关键词： Cryogenic chip Cryogenic quantum multiplexer Semi-conductor quantum integrated circuit Quantumﬁeld effect transistors Quantum point contacts Chip-scale cryogenic electronics