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Engineering human spinal microphysiological systems to model opioid-induced tolerance

Bioactive Materials 2023年第4期22卷 482-490页

作者： Hongwei Cai Zheng Ao Chunhui Tian Zhuhao Wu connor kaurich Zi Chen Mingxia Gu Andrea G.Hohmann Ken Mackie Feng Guo Department of Intelligent Systems Engineering Indiana UniversityBloomingtonIN47405United States Department of Surgery Brigham and Women’s Hospital/Harvard Medical SchoolBostonMA02115United States Division of Pulmonary Biology Center for Stem Cell and Organoid Medicine(CuSTOM)Cincinnati Children’s Hospital Medical CenterCincinnatiOH45229United States University of Cincinnati School of Medicine CincinnatiOH45229United States Gill Center for Biomolecular Science and Department of Psychological and Brain SciencesIndiana UniversityBloomingtonIN47405United States

pioids are commonly used for treating chronic ***,with continued use,they may induce tolerance and/or hyperalgesia,which limits therapeutic *** human mechanisms of opioid-induced tolerance and hyperalgesia are significantly understudied,in part,because current models cannot fully recapitulate human ***,we engineered novel human spinal microphysiological systems(MPSs)integrated with plug-and-play neural activity sensing for modeling human nociception and opioid-induced *** spinal MPS consists of a flattened human spinal cord organoid derived from human stem cells and a 3D printed organoid holder device for plug-and-play neural activity *** found that the flattened organoid design of MPSs not only reduces hypoxia and necrosis in the organoids,but also promotes their neuron maturation,neural activity,and functional *** further demonstrated that prolonged opioid exposure resulted in neurochemical correlates of opioid tolerance and hyperalgesia,as measured by altered neural activity,and downregulation ofμ-opioid receptor expression of human spinal *** MPSs are scalable,cost-effective,easy-to-use,and compatible with commonly-used well-plates,thus allowing plug-and-play measurements of neural *** believe the MPSs hold a promising translational potential for studying human pain etiology,screening new treatments,and validating novel therapeutics for human pain medicine.

关键词： Microphysiological systems Organ-on-chip In-situ electrical sensing Spinal cord organoids Opioid-induced tolerance and hyperalgesia Neural activity

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Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

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Neural Regeneration Research 2025年第1期20卷 205-206页

作者： Sarah Fullam Sean O’Dowd Antoinette O’connor Department of Neurology Tallaght University HospitalDublinIreland Academic Unit of Neurology Trinity College DublinIreland

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of *** evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic *** the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for ***,the expensive and invasive nature of these tests limits their scalability.

关键词： Blood Alzheimer diagnosis

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PyCFTBoot:A Flexible Interface for the Conformal Bootstrap

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Communications in Computational Physics 2017年第6期22卷 1-38页

作者： connor Behan Department of Physics and Astronomy Stony Brook UniversityStony BrookNY 11790USA

We introduce PyCFTBoot,a wrapper designed to reduce the barrier to entry in conformal bootstrap calculations that require semidefinite *** and SDPB are used for the most intensive symbolic and numerical steps *** reviewing the built-in algorithms for conformal blocks,we explain how to use the code through a number of examples that verify past *** an application,we show that the multi-correlator bootstrap still appears to single out the Wilson-Fisher fixed points as special theories in dimensions between 3 and 4 despite the recent proof that they violate unitarity.

关键词： CFT conformal bootstrap python semidefinite programming

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Experimental Evidence for Coverage Preferences in Flood Insurance

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International Journal of Disaster Risk Science 2022年第2期13卷 178-189页

作者： J.connor Darlington Niko Yiannakoulias School of Earth.Environment and Society McMaster UniversityHamilton.ON L8S 4K1Canada

We used a hypothetical choice experiment to estimate the effect of dwelling value and coverage limits on the probability of purchasing flood insurance while holding the probability of flooding and insurance price constant. The results indicate that demand for flood insurance is negatively associated with the amount of insurance coverage. For people assigned higher-valued dwellings, however, the opposite effect is observed. Since more coverage is generally preferred to less, all else being equal, differences in purchase probability dependent on dwelling value indicate an inconsistent approach to home protection. The higher probability of purchasing flood insurance from people in higher-valued dwellings may indicate an investment into the home as a financial asset, a strategy that is not observed to the same extent among people in lower-valued dwellings. This suggests that use of coverage limits may be differentially preferred based on dwelling value, such that low coverage insurance may have lower uptake for those in high-valued dwellings. As Canada evaluates a national flood insurance program, this research suggests that variable coverage maximums could be a way to increase accessibility and uptake of *** research shows an inconsistent demand for flood insurance, dependent on dwelling value and independent of income.

关键词： Canada Flood insurance Insurance choice experiment Willingness-to-buy

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The electrochemical detection of bioterrorism agents: a review of the detection, diagnostics, and implementation of sensors in biosafety programs for Class A bioweapons

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Microsystems & Nanoengineering 2021年第1期7卷 21-39页

作者： connor O’Brien Kathleen Varty Anna Ignaszak Department of Chemistry University of New Brunswick30 Dineen DriveFrederictonNB E3B 5A3Canada

During the past year,disease has shown us the iron grip it can hold over a population of *** systems can be overwhelmed,economies can be brought into recession,and many people can be harmed or *** weaponized,diseases can be manipulated to create a detriment to health while becoming an economic burden on any *** is consequently prudent that easy detection of bioweapons is available to governments for protecting their *** sensing displays many distinct advantages,such as its low limit of detection,low cost to run,rapid generation of results,and in many instances *** therefore present a wide array of electrochemical sensing platforms currently being fabricated,a brief summary of Class A bioweapons,and the potential future of bioweapon detection and biosafety.

关键词： electrochemical instance programs

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Telemetry research on elusive wildlife: A synthesis of studies on giant pandas

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Integrative Zoology 2016年第4期11卷 295-307页

作者： Thomas connor Vanessa HULL Jianguo LIU Center for Systems Integration and Sustainability Michigan State UniversityEast LansingUSA

Telemetry studies that track animals through space and time can lead to advances in scientific understanding that are vital in conservation *** example,telemetry studies of the giant panda(Ailuropoda melanoleuca)have shed light on many aspects of panda biology,but small sample sizes in each separate study make it difficult to draw broad *** overcome this problem we conducted the first synthesis of all 5 panda telemetry studies conducted to *** these data we investigated patterns in 6 main topics:home range,space-use interactions,core areas,movement patterns,seasonal migration and natal *** found that panda home range sizes do not vary between 2 main mountain ranges(Qionglai and Qinling),as was previously *** results also suggest that female pandas increase their movement in the mating season:a behavior typically attributed only to *** found and summarized telemetry and genetic evidence for female natal dispersal in the giant *** synthesis highlights the need for additional research relating panda behavior to human disturbance factors,and can aid future studies on giant pandas as well as other species.

关键词： giant panda home range natal dispersal synthesis wildlife telemetry

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Surgery for pancreatic necrosis:“Whom, when and what”

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World Journal of Gastroenterology 2004年第12期10卷 1697-1698页

作者： S connor JP Neoptolemos Department of Surgery Royal Liverpool University HospitalDaulby StreetLiverpoolL69 3GAUK

Acute pancreatitis is a common condition in which 70% of patients will recover with simple medical management. For patients who develop extensive or infected pancreatic necrosis the outcome is significantly different with a high morbidity and mortality. Surgery is the mainstay of treatment for these patients but several unresolved issues remain including who requires surgery, when is the optimal time to intervene and what technique should be used.

关键词：外科手术胰腺坏疽死亡率介入技术

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Stem cell-based in utero therapies for spina bifida: implications for neural regeneration

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Neural Regeneration Research 2019年第2期14卷 260-261页

作者： connor Long Lee Lankford Aijun Wang Surgical Bioengineering Laboratory Department of Surgery University of California Davis School of Medicine Institute for Paediatric Regenerative Medicine Shriners Hospital for Children Department of Biomedical Engineering University of California Davis School of Engineering

The history: Myelomeningocele - also known as spina bifida- is a devastating congenital anomaly of the central nervoussystem that is caused by the malformation of the spinal cordand vertebral column during embryogenesis. Depending onthe location of the spina bifida lesion on the spine, patientssuffer from neurological dysfunction ranging from paresisand incontinence to complete paralysis. The current standardof care for spina bifida is in utero surgical repair of the defect,which has been shown to minimize the secondary deficits associatedwith this disorder (Adzick et al., 2011). Despite thesesuccesses, this approach does not reliably improve neurologicfunction of affected children. Several groups, including ourown, have performed studies aimed at augmenting the inutero surgical repair of spina bifida by applying principlesof stem cell and tissue engineering to provide an enhancedprotection of the exposed neural elements (Saadai et al., 2011,2013; Wang et al., 2015; Brown et al., 2016). The ultimategoal of these studies is to improve the neurologic function inpatients while maintaining the benefits of the existing fetalsurgical treatment.

关键词： spina bifida The et al

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Integrative multi-omics and systems bioinformatics in translational neuroscience:A data mining perspective

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Journal of Pharmaceutical Analysis 2023年第8期13卷 836-850页

作者： Lance M.O'connor Blake A.O'connor Su Bin Lim Jialiu Zeng Chih Hung Lo College of Biological Sciences University of MinnesotaMinneapolisMN55455USA School of Pharmacy University of WisconsinMadisonWI53705USA Department of Biochemistry and Molecular Biology Ajou University School of MedicineSuwon16499South Korea Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore308232Singapore

Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed *** mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms,which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative ***,integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain *** this review,we first summarize data mining studies utilizing datasets from the individual type of omics analysis,including epigenetics/epigenomics,transcriptomics,proteomics,metabolomics,lipidomics,and spatial omics,pertaining to Alzheimer's disease,Parkinson's disease,and multiple *** then discuss multi-omics integration approaches,including independent biological integration and unsupervised integration methods,for more intuitive and informative interpretation of the biological data obtained across different omics *** further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain ***,we recommend a combination of high dimensional bioinformatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery,therapeutic development,and elucidation of disease *** conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personaliz

关键词： Multi-omics integration Systems bioinformatics Data mining Human brain profile reconstruction Translational neuroscience

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Role of radiation therapy in gastric adenocarcinoma

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World Journal of Gastroenterology 2006年第10期12卷 1511-1520页

作者： Lisa Hazard John O'connor Courtney Scaife Departments of Radiation Oncology University of Utah School of Medicine Salt Lake CityUTUnited States Department of Radiation Oncology Tulane University New OrleansLAUnited States Departments of Surgery University of Utah School of Medicine Salt Lake CityUTUnited States

Outcomes in patients with gastric cancer in the United States remain disappointing, with a five-year overall survival rate of approximately 23%. Given high rates of local-regional control following surgery, a strong rationale exists for the use of adjuvant radiation therapy. Randomized trials have shown superior local control with adjuvant radiotherapy and improved overall survival with adjuvant chemoradiation. The benefit of adjuvant chemoradiation in patients who have undergone D2 lymph node dissection by an experienced surgeon is not known, and the benefit of adjuvant radiation therapy in addition to adjuvant chemotherapy continues to be defined. In unresectable disease, chemoradiation allows long-term survival in a small number of patients and provides effective palliation. Most trials show a benefit to combined modality therapy compared to chemotherapy or radiation therapy alone. The use of pre-operative, intra-operative, 3D conformal, and intensity modulated radiation therapy in gastric cancer is promising but requires further study. The current article reviews the role of radiation therapy in the treatment of resectable and unresectable gastric carcinoma, focusing on current recommendations in the United States.

关键词： Radiation therapy Gastric cancer Stomach cancer Chemoradiation Adjuvant therapy Neoadjuvant therapy Intra-operative radiation therapy 3D conformal radiation therapy Intensity modulated radiation therapy

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