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Alteration in immune function in patients with fatty liver disease

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Hepatoma Research 2022年第1期8卷 363-375页

作者： Stephanie N.Gregory Shruthi R.Perati zachary j.brown Department of Surgery Rutgers Robert Wood Johnson Medical SchoolNew BrunswickNJ 08901USA Division of Surgical Oncology Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusOH 43210USA

Nonalcoholic fatty liver disease(NAFLD)is a disease spectrum that spans simple steatosis,fibrosis,and ultimately cirrhosis,and is a leading cause of chronic liver disease *** severe variant of NAFLD,non-alcoholic steatohepatitis(NASH),is characterized by triglyceride accumulation within hepatocytes and the subsequent inflammatory pathway activation,ultimately progressing to cirrhosis in 10%-20%of *** is a known major risk factor for the development of hepatocellular carcinoma(HCC),and there is emerging data demonstrating the impact of NASH on immune subsets and the tumor microenvironment that may influence therapeutic *** review describes the various ways in which the immune system is altered in patients with *** innate immune system in NASH shows alterations in dendritic and Kupffer cells,impaired cytotoxicity of Natural Killer cells,and an accumulation of ***,there is emerging evidence emphasizing the role of the adaptive immune system in the development and progression of NASH,seen in the alteration of B-cells,T-cells,and NKT *** to the complex interplay of the immune system in NAFLD/NASH and its progression to HCC,many current treatments focus on targeting immune cells for HCC ***,immune checkpoint inhibitors such as atezolizumab and bevacizumab have been approved as first-line therapy for unresectable *** an emerging field of research,further studies and clinical trials are needed to understand the complex interface of NASH,HCC and the immune response.

关键词： Non-alcoholic steatohepatitis nonalcoholic fatty liver disease steatohepatitis immunology hepatocellular carcinoma

Stability Analysis and Performance Evaluation of Additive Mixed-Precision Runge-Kutta Methods

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Communications on Applied Mathematics and Computation 2024年第1期6卷 705-738页

作者： Ben Burnett Sigal Gottlieb zachary j.Grant Center for Scientific Computing and Data Science Research UMass DartmouthNorth DartmouthMassachusettsUSA CSME Michigan State UniversityEast LansingMichiganUSA

Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and *** specially designed methods use reduced precision for the implicit computations and full precision for the explicit *** this work,we analyze the stability properties of these methods and their sensitivity to the low-precision rounding errors,and demonstrate their performance in terms of accuracy and *** develop codes in FORTRAN and julia to solve nonlinear systems of ODEs and PDEs using the mixed-precision additive Runge-Kutta(MP-ARK)*** convergence,accuracy,and runtime of these methods are *** show that for a given level of accuracy,suitably chosen MP-ARK methods may provide significant reductions in runtime.

关键词： Mixed precision Runge-Kutta methods Additive methods Accuracy

Sparse-Grid Implementation of Fixed-Point Fast Sweeping WENO Schemes for Eikonal Equations

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Communications on Applied Mathematics and Computation 2024年第1期6卷 3-29页

作者： zachary M.Miksis Yong-Tao Zhang Department of Applied and Computational Mathematics and Statistics University of Notre DameNotre DameIN46556USA

Fixed-point fast sweeping methods are a class of explicit iterative methods developed in the literature to efficiently solve steady-state solutions of hyperbolic partial differential equations(PDEs).As other types of fast sweeping schemes,fixed-point fast sweeping methods use the Gauss-Seidel iterations and alternating sweeping strategy to cover characteristics of hyperbolic PDEs in a certain direction simultaneously in each sweeping *** resulting iterative schemes have a fast convergence rate to steady-state ***,an advantage of fixed-point fast sweeping methods over other types of fast sweeping methods is that they are explicit and do not involve the inverse operation of any nonlinear local ***,they are robust and flexible,and have been combined with high-order accurate weighted essentially non-oscillatory(WENO)schemes to solve various hyperbolic PDEs in the *** multidimensional nonlinear problems,high-order fixed-point fast sweeping WENO methods still require quite a large amount of computational *** this technical note,we apply sparse-grid techniques,an effective approximation tool for multidimensional problems,to fixed-point fast sweeping WENO methods for reducing their computational ***,we focus on fixed-point fast sweeping WENO schemes with third-order accuracy(Zhang et al.2006[41]),for solving Eikonal equations,an important class of static Hamilton-jacobi(H-j)*** experiments on solving multidimensional Eikonal equations and a more general static H-j equation are performed to show that the sparse-grid computations of the fixed-point fast sweeping WENO schemes achieve large savings of CPU times on refined meshes,and at the same time maintain comparable accuracy and resolution with those on corresponding regular single grids.

关键词： Fixed-point fast sweeping methods Weighted essentially non-oscillatory(WENO)schemes Sparse grids Static Hamilton-jacobi(H-j)equations Eikonal equations

Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps:A pilot study

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World journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 29-36页

作者： jorge A.Gutierrez III jeremy L.Barth Rodney j.Schlosser Thomas S.Edwards Timothy L.Smith zachary M.Soler Department of Otolaryngology-Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Regenerative Medicine&Cell Biology Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Otolaryngology-Head and Neck Surgery Oregon Health&Science UniversityPortlandOregonUSA

Objectives:Prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory *** purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens,comparing normosmic and dysosmic CRS patients without polyps(CRSsNP).Methods:Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus *** subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic(n=7)and normosmic(n=4)***:Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 *** stringent criteria for multiple comparisons,one upregulated gene(Immediate Early Response 3[IER3])had an false discovery rate(FDR)correction adjustedP value considered statistically significant(P<0.001,fold change 2.69).Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients(P<0.05,FDR correction)including IL-4 and IL-13 signaling,IL-10 signaling,and rhodopsin-like ***:RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory *** study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with *** study also prompts questions regarding the role of IL-10,rhodopsin-like receptors,andIER3 in the pathogenesis of olfactory dysfunction.

关键词： chronic rhinosinusitis without nasal polyps olfactory dysfunction RNA sequencing

Comparison of trigeminal lateralization with differing stimulants

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World journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 66-69页

作者： Tiffany Chen Nicolas S.Poupore Michael C.Shih Thomas S.Edwards Shaun A.Nguyen zachary M.Soler Rodney j.Schlosser Department of Otolaryngology‐Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA

Trigeminal-specific stimulants have been shown to activate different receptors preferentially and this likely accounts for variation in sensory *** is unclear whether trigeminal sensitivity is similar across different transient receptor potential(TRP)receptors or if dysfunction of different receptors results in differing patient ***,a prospective cohort study was conducted,consisting of trigeminal lateralization testing with three different stimulants(eucalyptol,isothiocyanate,acetic acid),olfaction testing with Sniffin'Sticks,and measurement of various patient‐reported outcome measures(PROMs).A total of 50 participants were enrolled across the olfactory *** TDI score was 27.1±8.3(range 7.0–39.5)with 38%normosmic and 62%*** trigeminal lateralization scores out of 20 in the overall cohort were 16.18(2.78)for eucalyptol,14.94(3.49)for mustard oil,and 15.28(3.68)for *** showed a significant correlation with threshold scores of Sniffin'Sticks.A significant correlation was found between acetic acid and various *** of the lateralization scores of the trigeminal stimulants correlated to each other significantly and there was no correlation to *** lack of correlation suggests that the measured sensitivity of one type of TRP receptor may not translate to similar sensitivity of the other *** investigations with TRPV1 and TRPA1 agonists are needed to corroborate our findings.

关键词： chemosensory olfaction trigeminal TRP receptor

Characterizing the patient experience during neoadjuvant therapy for pancreatic ductal adenocarcinoma:A qualitative study

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World journal of Gastrointestinal Oncology 2022年第6期14卷 1175-1186页

作者： Lena Stevens zachary j.brown Ryan Zeh Christina Monsour Sharla Wells-Di Gregorio Heena Santry Aslam M Ejaz Timothy Michael Pawlik jordan M Cloyd Department of Surgery The Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of General Surgery University of Pittsburgh Medical CenterPittsburghPA 15213United States Department of Psychiatry Center for Palliative CareThe Ohio State University Wexner Medical CenterColumbusOH 43210United States

BACKGROUND Neoadjuvant therapy(NT)has increasingly been utilized for patients with localized pancreatic ductal adenocarcinoma(PDAC).It is the recommended approach for borderline resectable(BR)and locally advanced(LA)cancers and an increasingly utilized option for potentially resectable(PR)*** its increased use,little research has focused on patient-centered metrics among patients undergoing NT,including patient experiences,preferences,and recommendations.A better understanding of all aspects of the patient experience during NT may identify opportunities to design interventions aimed at improving quality of life;it may also facilitate the completion of NT and receipt of surgery,ultimately optimizing long-term *** To understand the experience of patients initiating and receiving NT to identify opportunities to improve neoadjuvant cancer care *** Semi-structured interviews of patients with localized PDAC during NT were conducted to explore their experience initiating and receiving *** took place between August 2020 and October *** to the descriptive nature of the research,questions were open *** were conducted over the phone,audio recorded and then *** interviews were coded by two independent researchers using NVivo 12,iteratively identifying themes until thematic saturation was *** integrative approach to qualitative analysis was used,utilizing both inductive and deductive *** A total of 12 patients with localized PDAC were *** with BR(n=7),PR(n=2),and LA(n=3)cancers participated in the *** patients indicated that choosing NT was the doctor’s recommendation,while most reported not being familiar with the concept of NT(n=11)and that NT was presented as the only option(n=8).Five themes describing the patient experience emerged:physical symptoms,emotional symptoms,coping mechanisms,access to care,and life *** most commonly cited recommendation for

关键词： Pancreatic ductal adenocarcinoma Neoadjuvant therapy Patient experience Patient-centered care Quality of life Qualitative research

Nanocrystal-semiconductor interface： Atomic-resolution cross-sectional transmission electron microscope study of lead sulfide nanocrystal quantum dots on crystalline silicon

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Nano Research 2014年第2期7卷 219-227页

作者： zachary Lingley Krishnamurthy Mahalingam Siyuan Lus Gail j. brown Anupam Madhukar Mork Family Department of Chemical Engineering and Materials Science University of Southern California Los Angeles California 90089 USA Air Force Research Laboratory Materials and Manufacturing Directorate Wright-Patterson Air Force Base Ohio 45433-7707 USA Department of Physics and Astronomy University of Southern California Los Angeles California 90089 USA

We report on a cross-sectional high resolution transmission electron microscope study of lead sulfide nanocrystal quantum dots (NCQDs) dispersed on electron-transparent silicon nanopillars that enables nearly atomically-resolved simultaneous imaging of the entire composite: the quantum dot, the interfacial region, and the silicon substrate. Considerable richness in the nanocrystal shape and orientation with respect to the substrate lattice is observed. The average NCQD-substrate separation is found to be significantly smaller than the length of the ligands on the NCQDs. Complementary photoluminescence measurements show that light emission from PbS NCQDs on silicon is effectively quenched which we attribute to intrinsic mechanisms of energy and charge transfer from PbS NCQDs to Si.

关键词：透射电子显微镜原子分辨率纳米晶体硫化铅结晶硅量子点半导体界面横截面

A GPU-Accelerated Mixed-Precision WENO Method for Extremal Black Hole and Gravitational Wave Physics Computations

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Communications on Applied Mathematics and Computation 2023年第1期5卷 97-115页

作者： Scott E.Field Sigal Gottlieb zachary j.Grant Leah F.Isherwood Gaurav Khanna University of Massachusetts Dartmouth North DartmouthMA 02747USA Department of Computational and Applied Mathematics Oak Ridge National LaboratoryOak RidgeTN 37830USA University of Rhode Island KingstonRI 02881USA

We develop and use a novel mixed-precision weighted essentially non-oscillatory(WENO)method for solving the Teukolsky equation,which arises when modeling perturbations of Kerr black *** show that WENO methods outperform higher-order finite-difference methods,standard in the discretization of the Teukolsky equation,due to the need to add dissipation for stability purposes in the *** particular,as the WENO scheme uses no additional dissipation,it is well suited for scenarios requiring long-time evolution such as the study of price tails and gravitational wave emission from extreme mass ratio *** the mixed-precision approach,the expensive computation of the WENO weights is performed in reduced floating-point precision that results in a significant speedup factor of≈*** addition,we use state-of-the-art Nvidia general-purpose graphics processing units and cluster parallelism to further accelerate the WENO *** optimized WENO solver can be used to quickly generate accurate results of significance in the field of black hole and gravitational wave *** apply our solver to study the behavior of the Aretakis charge—a conserved quantity,that if detected by a gravitational wave observatory like LIGO/Virgo would prove the existence of extremal black holes.

关键词： Numerical methods-Finite differencing Hyperbolic Partial differential equations Black holesblack holes WENO

Neoadjuvant therapy for pancreatic ductal adenocarcinoma:Opportunities for personalized cancer care

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World journal of Gastroenterology 2021年第27期27卷 4383-4394页

作者： Ahmad Hamad zachary j.brown Aslam M Ejaz Mary Dillhoff jordan M Cloyd Department of Surgery The Ohio State University Wexner Medical CenterColumbusOH 43215United States

Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignancy that is best treated in a multidisciplinary fashion using surgery,chemotherapy,and *** chemotherapy has shown to have a significant survival benefit in patients with resected ***,up to 50%of patients fail to receive adjuvant chemotherapy due to postoperative complications,poor patient performance status or early disease *** order to ensure the delivery of chemotherapy,an alternative strategy is to administer systemic treatment prior to *** oncology refers to the application of diverse strategies to target therapies specific to characteristics of a patient’s *** traditionally emphasized in selecting targeted therapies based on molecular,genetic,and radiographic biomarkers for patients with metastatic disease,the neoadjuvant setting is a prime opportunity to utilize personalized *** this article,we describe the current evidence for the use of neoadjuvant therapy(NT)and highlight unique opportunities for personalized care in patients with PDAC undergoing NT.

关键词： Pancreatic cancer Preoperative therapy FOLFIRINOX Precision oncology Patient-reported outcomes Personalized medicine Targeted therapy Whipple Pancreatectomy