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Comparing the transmission potential from sequence and surveillance data of 2009 North American influenza pandemic waves

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Infectious Disease Modelling 2023年第1期8卷 240-252页

作者： Venkata R.Duvvuri Joseph T.Hicks Lambodhar Damodaran Martin Grunnill Thomas Braukmann Jianhong Wu Jonathan B.Gubbay Samir N.Patel Justin Bahl Public health Ontario TorontoOntarioCanada Department of Laboratory Medicine and Pathobiology Faculty of MedicineUniversity of TorontoTorontoOntarioCanada Laboratory for Industrial and Applied Mathematics Department of Mathematics and StatisticsYork UniversityTorontoOntarioCanada Center for the Ecology of Infectious Disease Department of Infectious DiseasesInstitute of BioinformaticsUniversity of GeorgiaAthensGeorgia Department of Epidemiology and Biostatistics Institute of BioinformaticsUniversity of GeorgiaAthensGeorgia Duke-NUS Graduate Medical School Singapore

Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics.In this study,we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data.The impact of the choice of tree-priors,informative epidemiological priors,and evolutionary parameters on the transmission potential estimation is evaluated.North American Influenza A(H1N1)pdm09 hemagglutinin(HA)gene sequences are analyzed using the coalescent and birth-death tree prior models to estimate the basic reproduction number(R_(0)).Epidemiological priors gathered from published literature are used to simulate the birth-death skyline models.Path-sampling marginal likelihood estimation is conducted to assess model fit.A bibliographic search to gather surveillancebased R_(0)values were consistently lower(mean≤1.2)when estimated by coalescent models than by the birth-death models with informative priors on the duration of infectiousness(mean≥1.3 to≤2.88 days).The user-defined informative priors for use in the birth-death model shift the directionality of epidemiological and evolutionary parameters compared to non-informative estimates.While there was no certain impact of clock rate and tree height on the R_(0)estimation,an opposite relationship was observed between coalescent and birth-death tree priors.There was no significant difference(p=0.46)between the birth-death model and surveillance R0 estimates.This study concludes that treeprior methodological differences may have a substantial impact on the transmission potential estimation as well as the evolutionary parameters.The study also reports a consensus between the sequence-based R_(0)estimation and surveillanceased R_(0)stimates.Altogether,these outcomes shed light on the potential role of phylodynamic modeling to augment existing surveillance and epidemiological activities to better assess

关键词： Phylodynamics Pandemic 2009 H1N1 Reproduction number Coalescent growth models Birth-death models Pathogen sequence data Public health

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Neuronal guidance genes in health and diseases

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Protein & Cell 2023年第4期14卷 238-261页

作者： Junichi Yuasa-Kawada Mariko Kinoshita-Kawada Yoshio Tsuboi Jane Y.Wu Department of Neurology Fukuoka University7.451 NanakumaJohnan.kuFukuoka 814-0180Japan Department of Neurology Center for Genetic MedicineLurie Cancer CenterNorthwestern University Feinberg School of MedicineWard Building Box 6117303E.Chicago AvenueChicagoIlinois 60611.USA

Neurons migrate from their birthplaces to the destinations,and extending axons navigate to their synaptic targets by sensing various extracellular cues in spatiotemporally controlled manners.These evolutionally conserved guidance cues and their receptors regulate multiple aspects of neural development to establish the highly complex nervous system by mediating both short-and long-range cell-cell communications.Neuronal guidance genes(encoding cues,receptors,or downstream signal transducers)are critical not only for development of the nervous system but also for synaptic maintenance,remodeling,and function in the adult brain.One emerging theme is the combinatorial and complementary functions of relatively limited classes of neuronal guidance genes in multiple processes,including neuronal migration,axonal guidance,synaptogenesis,and circuit formation.Importantly,neuronal guidance genes also regulate cell migration and cell-cell communications outside the nervous system.We are just beginning to understand how cells integrate multiple guidance and adhesion signaling inputs to determine overall cellular/subcellular behavior and how aberrant guidance signaling in various cell types contributes to diverse human diseases,ranging from developmental,neuropsychiatric,and neurodegenerative disorders to cancer metastasis.We review classic studies and recent advances in understanding signaling mechanisms of the guidance genes as well as their roles in human diseases.Furthermore,we discuss the remaining chalienges and therapeutic potentials of modulating neuronal guidance pathways in neural repair.

关键词： axon guidance neuronal migration synaptogenesis neural circuit formation neural mapping cell-cell communications angiogenesis organogenesis cancermetastasis

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Accelerated neutral atom beam(ANAB)and gas clustered ion beam(GCIB)treatment of implantable device polymers leads to decreased bacterial attachment in vitro and decreased inflammation in vivo

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再生工程(英文) 2023年第3期4卷 257-264页

作者： Joseph Khoury Ti Zhang David B.Earle M.Laird Forrest Exogenesis Corporation BillericaMA 01821USA Department of Pharmaceutical Chemistry School of PharmacyThe University of KansasLawrenceKS 66047USA Surgical Services Tufts UniversityLowell General HospitalLowellMA 01854USA

Infections at the placement site of biomaterial-based devices and subsequent scar formation results in morbidity,which may require revision surgery.Biomaterials intended for permanent implantation in the body need to be biologically inert to avoid excessive foreign body response and to reduce bacterial attachment.In this study,we show that polymeric materials commonly used in medical devices,including polyetheretherketone(PEEK)and polypropylene,treated by gas cluster ion beam(GCIB)or by accelerated neutral atom beam(ANAB)result in a nanoscale-modified surface topography that changes the ability of extracellular proteins to bind.This leads to decreased bacterial attachment and an attenuated inflammatory response using both in vitro and in vivo assays.Differential adsorption of extracellular proteins to the polymeric surface improved the competitive attachment of osteoblasts over bacteria,without resorting to growth factor of antibiotic use.

关键词： Biofilm formation Surgical mesh Biomaterial surface Biomedical device Inflammation

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From hardware store to hospital:a COVID-19-inspired,cost-effective,open-source,in vivo-validated ventilator for use in resource-scarce regions

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Bio-Design and Manufacturing 2022年第1期5卷 133-140页

作者： Matthew H.Park Yuanjia Zhu Hanjay Wang Nicholas ATran Jinsuh Jung Michael JPaulsen Annabel M.Imbrie‑Moore Samuel Baker Robert Wilkerson Mateo Marin‑Cuartas Danielle M.Mullis Y.Joseph Woo Department of Cardiothoracic Surgery Stanford UniversityFalk Cardiovascular Research Building CV-235300 Pasteur DriveStanfordCA 94305-5407USA Department of Mechanical Engineering Stanford UniversityStanfordCAUSA Department of Bioengineering Stanford UniversityStanfordCAUSA Department of Comparative Medicine Stanford UniversityStanfordCAUSA University Department of Cardiac Surgery Leipzig Heart CenterLeipzigGermany

Resource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients,and these shortages are especially devastating in developing countries.To help alleviate this strain,we have designed and tested the accessible low-barrier in vivo-validated economical ventilator(ALIVE Vent),a COVID-19-inspired,cost-effective,open-source,in vivo-validated solution made from commercially available components.The ALIVE Vent operates using compressed oxygen and air to drive inspiration,while two solenoid valves ensure one-way flow and precise cycle timing.The device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large animals.Our functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator stockpiling.The large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation status.The FiO2,respiratory rate,inspiratory to expiratory time ratio,positive-end expiratory pressure,and peak inspiratory pressure were successfully maintained within normal,clinically validated ranges,and the animals were recovered without any complications.In regions with limited access to ventilators,the ALIVE Vent can help alleviate shortages,and we have ensured that all used materials are publicly available.While this pandemic has elucidated enormous global inequalities in healthcare,innovative,cost-effective solutions aimed at reducing socio-economic barriers,such as the ALIVE Vent,can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19.

关键词： COVID-19 Ventilator Open-source

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Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins,and drugs

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2624-2639页

作者： Yamin Li Zhongfeng Ye Hanyi Yang Qiaobing Xu Department of Biomedical Engineering Tufts UniversityMedfordMA 02155USA Department of Pharmacology State University of New YorkUpstate Medical UniversitySyracuseNY 13210USA

Lipid nanoparticle(LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology.LNPs can encapsulate and deliver a wide variety of bioactive agents,including the small molecule drugs,proteins and peptides,and nucleic acids.However,as the physicochemical properties of small-and macromolecular cargos can vary drastically,every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner.Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery.In this Review,we highlight our recent progress in the design,synthesis,characterization,evaluation,and optimization of combinatorial LNPs with novel structures and properties for the delivery of small-and macromolecular therapeutics both in vitro and in vivo.These delivery systems have enormous potentials for cancer therapy,antimicrobial applications,gene silencing,genome editing,and more.We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.

关键词： Lipid nanoparticle Combinatorial library Drug delivery Cancer therapy Protein delivery Gene therapy

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Deep learning in cortical surface-based neuroimage analysis:a systematic review

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Intelligent Medicine 2023年第1期3卷 46-58页

作者： Fenqiang Zhao Zhengwang Wu Gang Li Department of Radiology and Biomedical Research Imaging Center University of North Carolina at Chapel HillNC 27599United States

Deep learning approaches,especially convolutional neural networks(CNNs),have become the method of choice in the field of medical image analysis over the last few years.This prevalence is attributed to their excellent abilities to learn features in a more effective and efficient manner,not only for 2D/3D images in the Euclidean space,but also for meshes and graphs in non-Euclidean space such as cortical surfaces in neuroimaging analysis field.The brain cerebral cortex is a highly convoluted and thin sheet of gray matter(GM)that is thus typically represented by triangular surface meshes with an intrinsic spherical topology for each hemisphere.Accordingly,novel tailored deep learning methods have been developed for cortical surface-based analysis of neuroimaging data.This paper reviewsed the representative deep learning techniques relevant to cortical surface-based analysis and summarizes recent major contributions to the field.Specifically,we surveyed the use of deep learning techniques for cortical surface reconstruction,registration,parcellation,prediction,and other applications.We concluded by discussing the open challenges,limitations,and potentials of these techniques,and suggested directions for future research.

关键词： Deep learning Cortical surface-based analysis Neuroimage analysis Reconstruction Registration Parcellation

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Characterizing motor impulsivity of individuals classified as overweight to obese

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Sports Medicine and health Science 2023年第4期5卷 314-318页

作者： Kyle D.Flack Robert E.Anderson III Kylie F.McFee Bridgette T.Day Department of Dietetics and Human Nutrition College of AgricultureUniversity of KentuckyLexingtonKYUSA

Deficits in the impulse control system are an important predictor of energy intake and body weight.Adults classified as overweight to obese may possess these deficits as a general behavioral trait or they may be foodspecific.The present study assessed motor impulsivity(ability to suppress a pre-potent response)when presented with food and neutral(non-food)cues,testing if deficits in motor impulsivity is specific to food cues or a general trait among participants classified as overweight to obese.The proportion of inhibitory failures to no-go targets following food cues(10.8%)was significantly greater than the proportion of inhibitory failures to no-go targets following neutral cues(1.9%,p<0.001).These differences remained when covering for sex and hunger.This indicates deficits in food-specific impulse control(as opposed to general impulse control)are present in those classified as overweight to obese.Understanding the specific aspect of impulse control that is present in this population is needed for the development of future impulse control training interventions that seek to change eating behaviors as a means for weight control.

关键词： Impulsivity Inhibitory control Impulse control Response inhibition Food cues Obesity Go/NoGo task

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Challenges and Opportunities Modeling the Dynamic Tumor Matrisome

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Biomedical Engineering Frontiers 2023年第1期4卷 239-246页

作者： Shelly R.Peyton Manu O.Platt Edna Cukierman Department of Chemical Engineering University of Massachusetts AmherstAmherstMAUSA Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory UniversityAtlantaGAUSA Cancer Signaling&Microenvironment Program Marvin and Concetta Greenberg Pancreatic Cancer Institute.Fox Chase Cancer CenterTemple HealthPhiladelphiaPAUSA

We need novel strategies to target the complexity of cancer and,particularly,of metastatic disease.As an example of this complexity,certain tissues are particularly hospitable environments for metastases,whereas others do not contain fertile microenvironments to support cancer cell growth.Continuing evidence that the extracellular matrix(ECM)of tissues is one of a host of factors necessary to support cancer cell growth at both primary and secondary tissue sites is emerging.Research on cancer metastasis has largely been focused on the molecular adaptations of tumor cells in various cytokine and growth factor environments on 2-dimensional tissue culture polystyrene plates.Intravital imaging,conversely,has transformed our ability to watch,in real time,tumor cell invasion,intravasation,extravasation,and growth.Because the interstitial ECM that supports all cells in the tumor microenvironment changes over time scales outside the possible window of typical intravital imaging,bioengineers are continuously developing both simple and sophisticated in vitro controlled environments to study tumor(and other)cell interactions with this matrix.In this perspective,we focus on the cellular unit responsible for upholding the pathologic homeostasis of tumor-bearing organs,cancer-associated fibroblasts(CAFs),and their selfgenerated ECM.The latter,together with tumoral and other cell secreted factors,constitute the“tumor matrisome”.We share the challenges and opportunities for modeling this dynamic CAF/ECM unit,the tools and techniques available,and how the tumor matrisome is remodeled(e.g.,via ECM proteases).We posit that increasing information on tumor matrisome dynamics may lead the field to alternative strategies for personalized medicine outside genomics.

关键词： invasion organs environments

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Future of the current anticoronaviral agents: A viewpoint on thevalidation for the next COVIDs and pandemics

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BIOCELL 2023年第10期47卷 2133-2139页

作者： AMGAD M.RABIE Drug Discovery&Clinical Research Department Dikernis General Hospital(DGH)Dikernis35744Egypt

Despite the global decline in the severity of the coronavirus disease 2019 (COVID-19) cases, the disease stillrepresents a major concern to the relevant scientific and medical communities. The primary concern of drug scientists,virologists, and other concerned specialists in this respect is to find ready-to-use suitable and potent anticoronaviraltherapies that are broadly effective against the different species/strains of the coronaviruses in general, not only againstthe current and previous coronaviruses (e.g., the recently-appeared severe acute respiratory syndrome coronavirus 2“SARS-CoV-2”), i.e., effective antiviral agents for treatment and/or prophylaxis of any coronaviral infections, includingthose of the coming ones from the next species and strains (if any). As an expert in this field, I tried, in this up-to-dateperspective “viewpoint” article, to evaluate the suitability and applicability of using the currently-availableanticoronaviral agents for the next coronavirus diseases (COVIDs) and coronaviral pandemics, highlighting the mostimportant general guidelines that should be considered in the next pandemics from the therapeutic points of view.

关键词： SARS-CoV-2/COVID-19 Spike(S)protein/Main protease(Mpro)/RNA-dependent RNA polymerase(RdRp) General anticoronaviral drug Specific anti-COVID-19 medication Molnupiravir/Nirmatrelvir/Riboprine/Ensitrelvir Drug design and development

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Redesigning green revolution trait with increased grain yield and nitrogen utilization efficiency by reducing brassinosteroid signaling in semidwarf wheat

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中国科学:生命科学英文版 2023年第10期66卷 2448-2450页

作者： Hongqing Guo Yanhai Yin Department of Genetics Development and Cell BiologyPlant Sciences InstituteIowa State UniversityAmes Iowa 50011USA

Securing food and feed for the increasing world population and decreasing arable land is one of the major challenges of our time.Green revolution or agriculture revolution was propelled by the use of semidwarf rice and wheat varieties around the world since the 1960s(Peng et al.,1999;Sasaki et al.,2002).The semi-dwarfness leads to lodging resistance and thus allows planting of crops in high densities。

关键词： dwarf crops planting

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