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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

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

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： nanocrystal quantum dots semiconductor substrate interface atomic structure high resolutiontransmission electronmicroscopy energy and charge transfer solar cells

Update in the treatment of intracranial atherosclerotic disease

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Stroke & Vascular Neurology 2020年第1期5卷 59-64页

作者： zachary R Barnard Michael j Alexander Neurosurgery Cedars-Sinai Medical CenterLos AngelesCaliforniaUSA

This review highlights the recent evolution of the imaging,medical management,surgical options and endovascular therapies for symptomatic intracranial atherosclerotic disease(ICAD).Recent imaging developments including optical coherence tomography and other modalities to assess the intracranial arteries for symptomatic ICAD are reviewed,not only to diagnose ICAD but to determine if ICAD plaques have any high-risk features for *** future developments in the treatment of ICAD are discussed,including the development of trackable drug-coated balloons for the cerebral circulation to treat primary or restenotic arteries,new iterations of self-expanding intracranial stents with easier delivery systems,and the re-examination of indirect surgical bypass techniques for *** addition to these important technological developments,however,is the evolving evidence regarding the best treatment window for these techniques and additional factors in medical management which can improve patient outcomes in this devastating pathology.

关键词： intracranial balloon arteries

Evolutionary diversity as a catalyst for biological discovery

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Integrative Zoology 2018年第6期13卷 616-633页

作者： zachary V.jOHNSON Larry j.YOUNG School of Biological Sciences Georgia Institute of TechnologyAtlantaGeorgiaUSA Center for Translational Social Neuroscience Silvio O.Conte Center for Oxytocin and Social CognitionDepartment of Psychiatry and Behavioral SciencesYerkes National Primate Research CenterEmory UniversityAtlantaGeorgiaUSA

The tremendous diversity of animal behaviors has inspired generations of scientists from an array of biological *** complement investigations of ecological and evolutionary factors contributing to behavioral evolution,modern sequencing,gene editing,computational and neuroscience tools now provide a means to discover the proximate mechanisms upon which natural selection acts to generate behavioral *** behaviors are motivated behaviors that can differ tremendously between closely related species,suggesting phylogenetic plasticity in their underlying biological *** addition,convergent evolution has repeatedly given rise to similar forms of social behavior and mating systems in distantly related *** behavioral divergence and convergence provides an entry point for understanding the neurogenetic mechanisms contributing to behavioral *** argue that the greatest strides in discovering mechanisms contributing to social behavioral diversity will be achieved through integration of interdisciplinary comparative approaches with modern tools in diverse species *** review recent advances and future potential for discovering mechanisms underlying social behavioral variation;highlighting patterns of social behavioral evolution,oxytocin and vasopressin neuropeptide systems,genetic/transcriptional“toolkits,”modern experimental tools,and alternative species systems,with particular emphasis on Microtine rodents and Lake Malawi cichlid fishes.

关键词： cichlids oxytocin and vasopressin social behavior toolkits voles

The extended renin-angiotensin system: a promising target for traumatic brain injury therapeutics

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Neural Regeneration Research 2020年第6期15卷 1025-1026页

作者： zachary C.janatpour Aviva j.Symes Department of Pharmacology Uniformed Services University

Traumatic brain injury(TBI)is a leading cause of death and disability *** assessments estimate that over 27 million cases of TBI occur annually,resulting in over 8 million years lived with disability(GBD 2016 Dementia Collaborators,2019).Over 30 clinical trials have failed to show efficacy in TBI,and patients are currently left without any promising therapeutic options(Villapol et al.,2015).The pathophysiology of TBI is commonly divided into primary and secondary *** injury refers to the parenchymal damage that occurs as an immediate consequence of acute kinetic energy transfer to the brain(i.e.,membrane rupture,hemorrhage,axotomy,etc.).Secondary injury encompasses the deleterious molecular and cellular responses that occur in response to the primary injury in the minutes,hours or days *** search for therapeutics that mitigate the effects of the secondary injury and/or assist endogenous repair processes remains a large focus of TBI research(Umschweif et al.,2014;Villapol et al.,2015;janatpour et al.,2019).

关键词： injuries endogenous injury

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

A decision framework for identifying models to estimate forest ecosystem services gains from restoration

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Forest Ecosystems 2016年第2期3卷 126-137页

作者： zachary L. Christin Kenneth j. Bagstad Michael A. Verdone Earth Economics 107 N Tacoma Ave Tacoma WA 98403 USA. U.S. Geological Survey Geosciences & Environmental Change Science Center Box 25046 MS 980 Denver CO 80225 USA. International Union for the Conservation of Nature 1630 Connecticut Ave. NW #300 Washington DC 20009 USA.

Restoring degraded forests and agricultural lands has become a global conservation priority. A growing number of tools can quantify ecosystem service tradeoffs associated with forest restoration. This evolving ＂tools landscape＂ presents a dilemma： more tools are available, but selecting appropriate tools has become more challenging. We present a Restoration Ecosystem Service Tool Selector （RESTS） framework that describes key characteristics of 13 ecosystem service assessment tools. Analysts enter information about their decision context, services to be analyzed, and desired outputs. Tools are filtered and presented based on five evaluative criteria： scalability, cost, time requirements, handling of uncertainty, and applicability to benefit-cost analysis. RESTS uses a spreadsheet interface but a web-based interface is planned. Given the rapid evolution of ecosystem services science, RESTS provides an adaptable framework to guide forest restoration decision makers toward tools that can help quantify ecosystem services in support of restoration.

关键词： Decision support Ecosystem services Forest restoration Modeling Valuation Comparative toolsassessment