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Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?

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Neural Regeneration Research 2024年第1期19卷 29-34页

作者： Marta Zagrebelsky martin Korte Division of Cellular Neurobiology Zoological InstituteTU BraunschweigBraunschweigGermany Helmholtz Centre for Infection Research AG NINDBraunschweigGermany

Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin rec

关键词： Alzheimer's disease brain-derived neurotrophic factor depression Parkinson's disease tropomyosin receptor kinase B receptor

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Comprehensive Euler/Lagrange modelling including particle erosion for confined gas-solid flows

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Particuology 2024年第1期84卷 209-235页

作者： Guiherme A.Novelletto Ricardo martin Sommerfeld Multiphase Flow Systems Institute of Process EngineeringOtto-von-Guericke-University MagdeburgHoher Weg 7b06120Halle(Saale)Germany

The present research aims to assess the capability of a comprehensive Euler/Lagrange approach for predicting gas-solid flows and the associated solid particle erosion.The open-source code OpenFOAM®4.1 was used to carry out the numerical simulations,where the standard Lagrangian libraries were substantially extended to account for all necessary models.Particles are tracked considering both translational and rotational motion as well as all relevant forces,such as gravity/buoyancy,drag and transverse lift due to shear and particle rotation.The tracking time step was dynamically adapted ac-cording to the locally relevant time scales,which drastically reduces computational times.Stochastic approaches are adopted to model particle turbulent dispersion,particle collisions with rough walls and particle-particle interactions.Five solid particle erosion models,available in the literature,were considered to estimate pipe bend erosion.Three study cases are provided to validate the adopted nu-merical approach and erosion models extensively.The first case intends to evaluate the ability of the extended CFD code to predict the behaviour of gas-solid flows in pneumatic conveying systems.This goal is achieved by comparing the numerical results with the experimental data obtained by Huber(1997)and Huber and Sommerfeld(1994,1998)in a pneumatic conveying system.Here,the importance of considering inter-particle collisions and surface roughness for predicting particle velocity,mass flux and mean diameter distributions in gas-solid flows is highlighted.The second and third case intend to evaluate the ability of the erosion models in estimating bend erosion in diluted gas-solid flows.The erosion data obtained experimentally by Mazumder et al.(2008)and Solnordal et al.(2015)in very dilut pneumatic conveying systems is used for validating the numerical results,neglecting now inter-particle collisions and two-way coupling.Besides a comprehensive analysis of the different influential properties on erosion,the innovation of the present stud

关键词： Pneumatic conveying Pipe bend Numerical calculation(CFD) Euler/Lagrange approach Erosion models Wall roughness

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Differential roles of seed and sprout regeneration in forest diversity and productivity after disturbance

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Forest Ecosystems 2024年第3期11卷 371-380页

作者： Marek Mejstrík martin Svatek martina Pollastrini martin Sramek Radim Matula Department of Forest Ecology Faculty of Forestry and Wood SciencesCzech University of Life Sciences PragueKamýcka 12916500PragueCzech Republic Department of Forest Botany Dendrology and GeobiocoenologyFaculty of Forestry and Wood TechnologyMendel University in BrnoZemedelska 361300BrnoCzech Republic Department of Agriculture FoodEnvironment and ForestryUniversity of FirenzePiazzale Delle Cascine 2850144FirenzeItaly

Natural regeneration after disturbances is a key phase of forest development,which determines the trajectory of successional changes in tree species composition and diversity.Regenerating trees can originate from either seeds or sprouts produced by disturbed trees with sprouting ability.Although both regeneration strategies often develop and co-occur after a disturbance,they tend to affect forest development differently due to significant functional differences.However,the origin of tree regeneration is rarely distinguished in post-disturbance forest surveys and ecological studies,and the differential roles of seed and sprout regeneration in forest productivity and diversity remain poorly understood.To address these research gaps,we explored the role of sprout and seed regeneration in the formation of woody species diversity and above-ground biomass(AGB)productivity in early-stage forest development.Data were collected in two experimental forest stands in the Czech Republic,where trees were cut with varying intensities with the density of residual(uncut)trees ranging from 0 to 275 trees per hectare.All trees were mapped and their sizes were measured before cutting and then,either as a stump with sprouts or a residual tree,remeasured 11 years later.In addition,all tree saplings were mapped and measured 11 years after logging,and their origin(sprout or seed)was identified.To assess abundances and productivity,we estimated AGB of all2,685 sprouting stumps of 19 woody species and 504 generative(i.e.,seed origin)individuals of 16 woody species,using allometric equations.Mixed-effects models were used to analyze the effects of each regeneration strategy on woody species diversity and the total AGB under varying densities of residual trees.Nonmetric multidimensional scaling was used to evaluate the effect of regeneration strategies on species composition.AGB and diversity of sprouts were significantly higher than those of seed regeneration.Sprouts formed on average97.1%of the total regeneration AGB in H ady and 98.6%in

关键词： Resprouting Seeding Residual trees Tree diversity Above-ground biomass

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Increased number of symptoms during the acute phase of SARS-CoV-2 infection in athletes is associated with prolonged time to return to full sports performance—AWAREⅧ

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Journal of Sport and Health Science 2024年第3期13卷 280-287,I0001页

作者： Carolette Snyders Marlise Dyer Nicola Sewry Esme Jordaan martin Schwellnus Sport Exercise Medicine and Lifestyle Institute(SEMLI)Faculty of Health SciencesUniversity of PretoriaPretoria 0083South Africa Section Sports Medicine Faculty of Health SciencesUniversity of PretoriaPretoria 0083South Africa IOC Research Centre of South Africa Pretoria 0083South Africa Biostatistics Unit South African Medical Research CouncilTygerberg 7505South Africa Statistics and Population Studies Department University of the Western CapeCape Town 7535South Africa

Purpose The aim of the study was to identify factors associated with prolonged time to return to full performance(RTFP)in athletes with recent severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Methods Prospective cohort study with cross sectional analysis.A total of 84 athletes with confirmed SARS-CoV-2 infection assessed at a coronavirus disease 2019 recovery clinic gave a history of age,sex,type/level of sport,co-morbidities,pre-infection training hours,and 26 acute SARS-CoV-2 symptoms from 3 categories(“nose and throat”,“chest and neck”,and“whole body”/systemic).Data on days to RTFP were obtained by structured interviews.Factors associated with RTFP were demographics,sport participation,history of co-morbidities,pre-infection training history,and acute symptoms(type,number).Outcomes were:(a)days to RTFP(median,interquartile range(IQR))in asymptomatic(n=7)and symptomatic athletes(n=77),and(b)hazard ratios(HRs;95%confidence interval)for symptomatic athletes with vs.without a factor(univariate,multiple models).HR0.05).Factors associated with prolonged RTFP(univariate models)were:females(HR=0.57;p=0.014),endurance athletes(HR=0.41;p<0.0001),co-morbidity number(HR=0.75;p=0.001),and respiratory disease history(HR=0.54;p=0.026).In symptomatic athletes,prolonged RTFP(multiple models)was significantly associated with increased“chest and neck”(HR=0.85;p=0.017)and“nose and throat”(HR=0.84;p=0.013)symptoms,but the association was more profound between prolonged RFTP and increased total number of“all symptoms”(HR=0.91;p=0.001)and“whole body”/systemic(HR=0.82;p=0.007)symptoms.Conclusion A larger number of total symptoms and specifically“whole body”/systemic symptoms during the acute phase of SARS-CoV-2 infection in athletes is associated with prolonged RTFP.

关键词： Athletes COVID-19 Performance Recovery Return to play

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Time trends and outcomes of gastrostomy placement in a Swedish national cohort over two decades

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World Journal of Gastroenterology 2024年第10期30卷 1358-1367页

作者： martin Löfling Skogar Magnus Sundbom Department of Surgical Sciences Uppsala UniversityUppsala 75185Sweden

BACKGROUND Percutaneous endoscopic gastrostomy(PEG)and laparoscopically inserted gastrostomy have become the gold standard for adult patients and children,respectively,requiring long-term enteral nutrition support.Procedure-related mortality is a rare event,often reported to be zero in smaller studies.National data on 30-d mortality and long-term survival rates after gastrostomy placement are scarce in the literature.AIM To study the use of gastrostomies in Sweden from 1998-2019 and to analyze procedure-related mortality and short-term(<30 d)and long-term survival.METHODS In this retrospective,population-based cohort study,individuals that had received a gastrostomy between 1998-2019 in Sweden were included.Individuals were identified in the Swedish National Patient Register,and survival analysis was possible by cross-referencing the Swedish Death Register.The cohort was divided into three age groups:Children(0-18 years);adults(19-64 years);and elderly(≥65 years).Kaplan-Meier with log-rank test and Cox regression were used for survival analysis.RESULTS In total 48682 individuals(52%males,average age 60.9±25.3 years)were identified.The cohort consisted of 12.0%children,29.5%adults,and 58.5%elderly.An increased use of gastrostomies was observed during the study period,from 13.7/100000 to 22.3/100000 individuals(P<0.001).The use of PEG more than doubled(about 800 to 1800/year),with a corresponding decrease in open gastrostomy(about 700 to 340/year).Laparoscopic gastrostomy increased more than ten-fold(about 20 to 240/year).Overall,PEG,open gastrostomy,and laparoscopic gastrostomy constituted 70.0%(n=34060),23.3%(n=11336),and 4.9%(n=2404),respectively.Procedure-related mortality was 0.1%(n=44)overall(PEG:0.05%,open:0.24%,laparoscopic:0.04%).The overall 30-d mortality rate was 10.0%(PEG:9.8%,open:12.4%,laparoscopic:1.7%)and decreased from 11.6%in 1998-2009 vs 8.5%in 2010-2019(P<0.001).One-year and ten-year survival rates for children,adults,and elderly were 93.7%,67.5%,and 42.1%and 79.9%,39.2%,and 6.8%,respectively.Th

关键词： Gastrostomy Percutaneous endoscopic gastrostomy Dysphagia Enteral nutrition Long-term Survival Complication

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Optimization of product characteristics of porous carbon agglomerates using a design of experiments in fluidized bed agglomeration

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Particuology 2024年第6期89卷 258-269页

作者： martin Oelofse Robert Rack Marcelle Hilden Peter Langguth Department of Pharmaceutical Technology and Biopharmaceutics Johannes Gutenberg UniversityMainzGermany Carbon Advanced Solutions GmbH HeuchelheimGermany

Spraying parameters during particle agglomeration processes can affect the agglomeration kinetics and particle growth.This study was conducted to better understand the influence of the spraying parameters in a fluidized bed wet agglomeration process,and the influence on the stability characteristics of carbon tablets.A formulation based on fine carbon and peroxide powder,as well as carboxymethyl cellulose as a binder,was used to produce agglomerates in a first production step.Thereafter in a second production step carbon tablets with a high porosity were molded for the customer goods industry.The optimization of the compressive strength of these carbon tablets was the goal of the trials.Carbon agglomerates were produced with a laboratory scale granulator called“ProCell”and were compressed with a five-cavity mechanical press.The screening of the agglomeration process parameters and their influence on the agglomerates quality,as well as the performance characteristics of the carbon tablets,were investigated using a multilevel factorial design.The experimental runs were done by varying atomized air pressure and feed rate of the fluid.This was determined by the design model.The findings of the statistical trials showed that low atomized air pressure and a low feed rate lead to a higher tablet compressive strength.

关键词： Wet agglomeration Fluidized bed Design of experiments Carbon agglomerates and tablets

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Diagnostic tools for fecal incontinence: Scoring systems are the crucial first step

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World Journal of Gastroenterology 2024年第6期30卷 516-522页

作者： Peter Liptak martin Duricek Peter Banovcin Clinic of Internal Medicine-Gastroenterology University Hospital in MartinJessenius Faculty of Medicine in MartinComenius UniversityMartin 03601Slovakia

The main aim of this editorial is to comment on the recent article published by Garg et al in the World Journal of Gastroenterology 2023;29:4593-4603.This original research presents a new scoring system for fecal incontinence.Fecal incontinence is a chronic disease with a severe impact on the quality of life of the patients.Substantial social stigmatization often leads to significant underreporting of the condition even during visits to a specialist and could lead to further misman-agement or non-existent management of the disease.An important fact is that patients are often unable to describe their condition when not asked precisely defined questions.This problem is partially resolved by scoring questionnaires.Several scoring systems are commonly used;however,each of them has their shortcomings.For example,the absence of different kinds of leakage besides flatus and stool could further lead to underscoring the incontinence severity.Therefore,there has long been a call for a more precise scoring system.The correct identification of the presence and severity of fecal incontinence is paramount for further diagnostic approach and for choosing the appropriate therapy option.This editorial describes fecal incontinence,its effect on quality of life in general and further evaluates the diagnostic approach with a particular focus on symptom scoring systems and their implications for clinical practice.

关键词： Incontinence Fecal Scoring system Questionary Quality of life

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Second-order error analysis of the averaged L1 scheme L1 for time-fractional initial-value and subdiffusion problems

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Science China Mathematics 2024年第7期67卷 1641-1664页

作者： Jinye Shen Fanhai Zeng martin Stynes School of Mathematics Southwestern University of Finance and EconomicsChengdu611130China School of Mathematics Shandong UniversityJinan250100China Applied and Computational Mathematics Division Beijing Computational Science Research CenterBeijing100193China

Fractional initial-value problems(IVPs) and time-fractional initial-boundary value problems(IBVPs), each with a Caputo temporal derivative of order α ∈(0, 1), are considered. An averaged variant of the well-known L1 scheme is proved to be O(N^(-2)) convergent for IVPs on suitably graded meshes with N points, thereby improving the O(N^(-(2-α))) convergence rate of the standard L1 scheme. The analysis relies on a delicate decomposition of the temporal truncation error that yields a sharp dependence of the order of convergence on the degree of mesh grading used. This averaged L1 scheme can be combined with a finite difference or piecewise linear finite element discretization in space for IBVPs, and under a restriction on the temporal mesh width, one gets again O(N^(-2)) convergence in time, together with O(h^(2)) convergence in space,where h is the spatial mesh width. Numerical experiments support our results.

关键词： time-fractional subdiffusion averaged L1 scheme

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Experimental investigation of radiative heat propagation in a simplified generic packed bed

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Particuology 2024年第5期88卷 149-160页

作者： Matthias Tyslik Lukas Pörtner Siegmar Wirtz martin Schiemann Institute of Energy Plant Technology Ruhr-University Bochum44780 BochumGermany

A novel test rig for the investigation of radiative heat transfer in packed beds has been developed and is introduced with representative experimental results.The individual components and the calibration are discussed.The generic packed bed is realized in a simplified way by an arrangement of parallel rods,which represent particles in pseudo-2D.In this arrangement,electrically heated rods provide the radiation propagating through the rod array to heat the passive counterparts.A sophisticated temperature-control scheme with a large number of thermocouples and infrared-imaging provides in-depth information about heat transfer in the system.Spectral radiation intensities are determined with a Fourier-transform infrared spectroscopy,which has been modified and validated for this specific application.In order to compare the influence of different surface properties of particles on the heat propagation and surface reflections,rod samples made of stainless steel and magnesium oxide are used.The influence of material properties becomes clearly visible by comparing the high radiation intensities resulting from a stainless steel rod array to the same geometry built from magnesium oxide rods.In addition,the influence of the surface properties is particularly evident in the infrared images since the reflections are significantly higher for the stainless steel samples than for the magnesium oxide samples.The experimental results in the current work demonstrate the ability of the test rig to provide data with a well-defined accuracy as a validation base for numerical radiation simulations in packed beds.

关键词： Thermal radiation Spectral reflections Fourier-transform infrared spectroscopy

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Optimizing artificial intelligence in sepsis management: Opportunities in the present and looking closely to the future

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Journal of Intensive Medicine 2024年第1期4卷 34-45页

作者： Darragh O’Reilly Jennifer McGrath Ignacio martin-Loeches Department of Intensive Care Medicine Multidisciplinary Intensive Care Research Organization(MICRO)St James’HospitalDublinIreland Department of Respiratory Intensive care Hospital ClinicUniversitat de BarcelonaIDIBAPSCIBERESBarcelonaSpain

Sepsis remains a major challenge internationally for healthcare systems.Its incidence is rising due to poor public awareness and delays in its recognition and subsequent management.In sepsis,mortality increases with every hour left untreated.Artificial intelligence(AI)is transforming worldwide healthcare delivery at present.This review has outlined how AI can augment strategies to address this global disease burden.AI and machine learning(ML)algorithms can analyze vast quantities of increasingly complex clinical datasets from electronic medical records to assist clinicians in diagnosing and treating sepsis earlier than traditional methods.Our review highlights how these models can predict the risk of sepsis and organ failure even before it occurs.This gives providers additional time to plan and execute treatment plans,thereby avoiding increasing complications associated with delayed diagnosis of sepsis.The potential for cost savings with AI implementation is also discussed,including improving workflow efficiencies,reducing administrative costs,and improving healthcare outcomes.Despite these advantages,clinicians have been slow to adopt AI into clinical practice.Some of the limitations posed by AI solutions include the lack of diverse data sets for model building so that they are widely applicable for routine clinical use.Furthermore,the subsequent algorithms are often based on complex mathematics leading to clinician hesitancy to embrace such technologies.Finally,we highlight the need for robust political and regulatory frameworks in this area to achieve the trust and approval of clinicians and patients to implement this transformational technology。

关键词： Artificial intelligence Data science Machine learning Intensive care unit(ICU) Critical care Sepsis

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