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Infectious Disease Modelling 2022年第1期7卷 184-198页

作者： Nicholas Steyn Audrey Lustig Shaun C.Hendy Rachelle N.Binny michael j.plank Department of Physics University of AucklandNew Zealand School of Mathematics and Statistics University of CanterburyNew Zealand Te Punaha Matatini Centre of Research Excellence in Complex SystemsNew Zealand Manaaki Whenua LincolnNew Zealand

We couple a simple model of quarantine and testing strategies for international travellers with a model for transmission of SARS-CoV-2 in a partly vaccinated population.We use this model to estimate the risk of an infectious traveller causing a community outbreak under various border control strategies and different levels of vaccine coverage in the population.Results are calculated from N¼100,000 independent realisations of the stochastic model.We find that strategies that rely on home isolation are significantly higher risk than the current mandatory 14-day stay in government-managed isolation.Nevertheless,combinations of testing and home isolation can still reduce the risk of a community outbreak to around one outbreak per 100 infected travellers.We also find that,under some circumstances,using daily lateral flow tests or a combination of lateral flow tests and polymerase chain reaction(PCR)tests can reduce risk to a comparable or lower level than using PCR tests alone.Combined with controls on the number of travellers from countries with high prevalence of COVID-19,our results allow different options for managing the risk of COVID-19 at the border to be compared.This can be used to inform strategies for relaxing border controls in a phased way,while limiting the risk of community outbreaks as vaccine coverage increases.

关键词： vaccine testing border

An assessment of the potential impact of the Omicron variant of SARS-CoV-2 in Aotearoa New Zealand

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Infectious Disease Modelling 2022年第2期7卷 94-105页

作者： Giorgia Vattiato Oliver Maclaren Audrey Lustig Rachelle N.Binny Shaun C.Hendy michael j.plank School of Mathematics and Statistics University of CanterburyChristchurchNew Zealand Department of Physics University of AucklandAucklandNew Zealand Manaaki Whenua LincolnNew Zealand Department of Engineering Science University of AucklandAucklandNew Zealand

New Zealand delayed the introduction of the Omicron variant of SARS-CoV-2 into the community by the continued use of strict border controls through to january 2022.This allowed time for vaccination rates to increase and the roll out of third doses of the vaccine(boosters)to begin.It also meant more data on the characteristics of Omicron became available prior to the first cases of community transmission.Here we present a mathematical model of an Omicron epidemic,incorporating the effects of the booster roll out and waning of vaccine-induced immunity,and based on estimates of vaccine effectiveness and disease severity from international data.The model considers differing levels of immunity against infection,severe illness and death,and ignores waning of infection-induced immunity.This model was used to provide an assessment of the potential impact of an Omicron wave in the New Zealand population,which helped inform government preparedness and response.At the time the modelling was carried out,the date of introduction of Omicron into the New Zealand community was unknown.We therefore simulated outbreaks with different start dates,as well as investigating different levels of booster uptake.We found that an outbreak starting on 1 February or 1 March led to a lower health burden than an outbreak starting on 1 january because of increased booster coverage,particularly in older age groups.We also found that outbreaks starting later in the year led to worse health outcomes than an outbreak starting on 1 March.This is because waning immunity in older groups started to outweigh the increased protection from higher booster coverage in younger groups.For an outbreak starting on 1 February and with high booster uptake,the number of occupied hospital beds in the model peaked between 800 and 3,300 depending on assumed transmission rates.We conclude that combining an accelerated booster programme with public health measures to flatten the curve are key to avoid overwhelming the healthcare system.

关键词： COVID-19 Epidemiological modelling Immunity Infectious diseases Public health Vaccination

Harnessing naturally occurring mutations for T-cell therapy:a potential new avenue to enhance treatment efficacy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1799-1801页

作者： michael Hiltensperger jürgen Ruland Kilian Schober Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und HygieneFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany Institute of Clinical Chemistry and Pathobiochemistry School of MedicineTechnical University of MunichMunichGermany TranslaTUM Center for Translational Cancer ResearchTechnical University of MunichMunichGermany German Cancer Consortium(DKTK) HeidelbergGermany German Center for Infection Research(DZIF) partner site MunichMunichGermany FAU Profile Center Immunomedicine Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Garcia et al.use a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rejection and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.

关键词： al. cancer potential

Universal Hyperthermal Model for Mass Extinctions

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journal of Earth Science 2024年第2期35卷 704-707页

作者： michael j.Benton Paleobiology Research Group School of Earth SciencesUniversity of BristolLife Sciences BuildingTyndall AvenueBristolBS81TQUK

INTRODUCTION Earth scientists have long sought universal features of past extinction crises.It can be argued that each past extinction event was a singularity,caused by combinations of circumstances that are unique in each case,and therefore that the search for common causes is futile.However,a key feature of the uniformitarian approach to geology is that past processes are the same as modern-day processes and,with that in mind,earth scientists are keen to use their knowledge to contribute some understanding to the study of the present and future climate crisis.

关键词： extinction singularity Extinction

Dietary fibre effects and the interplay with exogenous carbohydrases in poultry nutrition

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Animal Nutrition 2024年第1期16卷 231-240页

作者： michael R.Bedford Birger Svihus Aaron j.Cowieson AB Vista Feed Ingredients Ltd Norwegian University of Life Sciences DSM Nutritional Products

A comprehensive understanding of the role of dietary fibre in non-ruminant animal production is elusive. Equivocal and conflated definitions of fibre coupled with significant analytical complexity,interact with poorly defined host and microbiome relationships. Dietary fibre is known to influence gut development, feed intake and passage rate, nutrient absorption, microbiome taxonomy and function, gut p H, endogenous nutrient loss, environmental sustainability, animal welfare and more. Whilst significant gaps persist in our understanding of fibre in non-ruminant animal production, there is substantial interest in optimizing the fibre fraction of feed to induce high value phenotypes such as improved welfare,live performance and to reduce the environmental footprint of animal production systems. In order to achieve these aspirational goals, it is important to tackle dietary fibre with the same level of scrutiny as is currently done for other critical nutrient classes such as protein, minerals and vitamins. The chemical,mechanical and nutritional role of fibre must be explored at the level of monomeric sugars, oligosaccharides and polysaccharides of varying molecular weight and decoration, and this must be in parallel to standardisation of analytical tools and definitions for speciation. To further complicate subject, exogenous carbohydrases recognise dietary fibre as a focal substrate and have varying capacity to generate lower molecular weight carbohydrates that interact differentially with the host and the enteric microbiome. This short review article will explore the interactive space between dietary fibre and exogenous carbohydrases and will include their nutritional and health effects with emphasis on functional development of the gut, microbiome modulation and host metabolism.

关键词： Fibre Carbohydrase Nutrition Microbiome Gastro-intestinal development Feed

Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson j.michael Taylor University of Cincinnati College of Medicine CincinnatiOHUSA Department of Pediatrics University of CincinnatiCincinnatiOHUSA Department of Neurology and Rehabilitation Medicine University of CincinnatiCincinnatiOHUSA Division of Pediatric Rehabilitation Medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA Division of Neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh june 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain injury

The Global Energy and Water Exchanges(GEWEX)Project in Central Asia:The Case for a Regional Hydroclimate Project

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Advances in Atmospheric Sciences 2024年第5期41卷 777-783页

作者： michael BRODY Maksim KULIKOV Sagynbek ORUNBAEV Peter j.VAN OEVELEN International Agricultural University Tashkent 111200Uzbekistan George Mason University FairfaxVirginia 22030USA University of Central Asia Bishkek 720001Kyrgyz Republic American University of Central Asia Bishkek 720060Kyrgyz Republic International GEWEX project George Mason UniversityFairfaxVirginia 22030USA

Central Asia consists of the former Soviet Republics,Kazakhstan,Kyrgyz Republic,Tajikistan,Turkmenistan,and Uzbekistan.The region’s climate is continental,mostly semi-arid to arid.Agriculture is a significant part of the region’s economy.By its nature of intensive water use,agriculture is extremely vulnerable to climate change.Population growth and irrigation development have significantly increased the demand for water in the region.Major climate change issues include melting glaciers and a shrinking snowpack,which are the foundation of the region’s water resources,and a changing precipitation regime.Most glaciers are located in Kyrgyzstan and Tajikistan,leading to transboundary water resource issues.Summer already has extremely high temperatures.Analyses indicate that Central Asia has been warming and precipitation might be increasing.The warming is expected to increase,but its spatial and temporal distribution depends upon specific global scenarios.Projections of future precipitation show significant uncertainties in type,amount,and distribution.Regional Hydroclimate Projects(RHPs)are an approach to studying these issues.Initial steps to develop an RHP began in 2021 with a widely distributed online survey about these climate issues.It was followed up with an online workshop and then,in 2023,an in-person workshop,held in Tashkent,Uzbekistan.Priorities for the Global Energy and Water Exchanges(GEWEX)project for the region include both observations and modeling,as well as development of better and additional precipitation observations,all of which are topics for the next workshop.A well-designed RHP should lead to reductions in critical climate uncertainties in policy-relevant timeframes that can influence decisions on necessary investments in climate adaptation.

关键词： GEWEX Central Asia climate change agriculture

NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Schafer Sudena Wang michael j.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathoph

关键词： calcium EF hand mitochondria nervous system signal transduction

Measurement,associations,patterns,and promotion:Unveiling vital areas in physical activity epidemiology

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journal of Sport and Health Science 2024年第5期13卷 605-607页

作者： Kara M.Whitaker Guest editor michael j.LaMonte Department of Health&Human Physiology University of IowaIowa CityIA 52242USA Department of Epidemiology and Environmental Health University of BuffaloBuffaloNY 14214 USA

Physical activity(PA)epidemiology first emerged as a new field of study around the 1950s with publication of seminal investigations on London civil servants1 and has continued to evolve as a scientific discipline to present time.This subdiscipline of epidemiology studies the frequencies,distributions,and dynamics of PA and its impact on human health,morbidity,and mortality.Research over the past 75 years has demonstrated numerous health benefits of PA.Based on these research findings,the World Health Organization recommends adults aged 18-64 years engage in at least 150-300 min of moderate-intensity aerobic PA per week,or at least 75-150 min of vigorous-intensity aerobic PA per week,or a combination of both intensities.

关键词： epidemiology promotion continued

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 treatment.Many well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to why.The present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo responders.Methods 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 response.Monoaminergic genetic polymorphisms were also assessed.Placebo response was measured based on change in Montgomery-Asberg Depression Rating Scale score.The association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects models.Results 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 response.An increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant therapy.Single 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 comparisons.Conclusion 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 response.Several variables appeared to predict the placebo response.Such findings may encourage future trial designs which could dampen placebo response,improve as

关键词： Randomized controlled trial Placebo Depression Nutraceutical Psychiatry