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Articles 64561 - 64590 of 818145

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Targeting Undruggable Phosphatase Overcomes Trastuzumab Resistance By Inhibiting Multi-Oncogenic Kinases., Lu Wang, Yusheng Lin, Zhimeng Yao, Nipun Babu, Wan Lin, Chaoying Chen, Liang Du, Songwang Cai, Yunlong Pan, Xiao Xiong, Qiantao Ye, Hongzheng Ren, Dianzheng Zhang, Yexi Chen, Sai-Ching Jim Yeung, Edwin Bremer, Hao Zhang Sep 2024

Targeting Undruggable Phosphatase Overcomes Trastuzumab Resistance By Inhibiting Multi-Oncogenic Kinases., Lu Wang, Yusheng Lin, Zhimeng Yao, Nipun Babu, Wan Lin, Chaoying Chen, Liang Du, Songwang Cai, Yunlong Pan, Xiao Xiong, Qiantao Ye, Hongzheng Ren, Dianzheng Zhang, Yexi Chen, Sai-Ching Jim Yeung, Edwin Bremer, Hao Zhang

PCOM Scholarly Works

AIMS: Resistance to targeted therapy is one of the critical obstacles in cancer management. Resistance to trastuzumab frequently develops in the treatment for HER2

METHODS: Four public datasets were used to screen PTP candidates in relation to trastuzumab responsiveness in HER2

RESULTS: PTPRO was identified as the key PTP which influences trastuzumab responsiveness and patient survival. PTPRO de-phosphorated several TKs, including the previously overlooked substrate ERBB3, thereby inhibiting multiple oncogenic pathways associated with drug resistance. Notably, PTPRO, previously deemed "undruggable," was effectively upregulated by saRNA-loaded nanoparticles. The upregulated PTPRO simultaneously inhibited ERBB3, ERBB2, and downstream SRC signaling pathways, thereby counteracting …


No Really, What Should We Do? An Employer’S Guide To Groff V. Dejoy And Juggling Religious Accommodations In The Workplace, Keegan K. Davis Sep 2024

No Really, What Should We Do? An Employer’S Guide To Groff V. Dejoy And Juggling Religious Accommodations In The Workplace, Keegan K. Davis

Nevada Law Journal

No abstract provided.


Perspectives On The Clinical Use Of Anti-Amyloid Therapy For The Treatment Of Alzheimer's Disease: Insights From The Fields Of Cancer, Rheumatology, And Neurology, Gregory Jicha, Erin Abner, Elif Pinar Coskun, Mark Huffmyer, Thomas Tucker, Peter T. Nelson Sep 2024

Perspectives On The Clinical Use Of Anti-Amyloid Therapy For The Treatment Of Alzheimer's Disease: Insights From The Fields Of Cancer, Rheumatology, And Neurology, Gregory Jicha, Erin Abner, Elif Pinar Coskun, Mark Huffmyer, Thomas Tucker, Peter T. Nelson

Neurology Faculty Publications

Introduction: The advent of disease-modifying therapies for Alzheimer’s disease (AD) has raised many questions and debates in the field as to the clinical benefits, risks, and costs of such therapies. The controversies have resulted in the perception that many clinicians are apprehensive about prescribing these medications to their patient populations. There also remains widespread uncertainty as to the economic impact, cost benefit ratio, and safety oversight for use of these medications in standard clinical care settings.

Methods: To contextualize such issues, the present study compared anti-amyloid biologic therapy (lecanemab) to four commonly used biologic agents in other fields, including trastuzumab …


Analysis Of The Thermal Aging Kinetics Of Tallow, Chicken Oil, Lard, And Sheep Oil, Yun-Chuan Hsieh, Hao Ouyang, Yulin Zhang, Donyau Chiang, Fuqian Yang, Hsin-Lung Chen, Sanboh Lee Sep 2024

Analysis Of The Thermal Aging Kinetics Of Tallow, Chicken Oil, Lard, And Sheep Oil, Yun-Chuan Hsieh, Hao Ouyang, Yulin Zhang, Donyau Chiang, Fuqian Yang, Hsin-Lung Chen, Sanboh Lee

Chemical and Materials Engineering Faculty Publications

Understanding the thermal aging kinetics of animal oils is of vital importance in the storage and applications of animal oils. In this work, we use four different techniques, including UV-Vis spectrometry, viscometry, impedance spectroscopy, and acid–base titration, to study the thermal aging kinetics of tallow, chicken oil, lard, and sheep oil in the temperature range from 120 ◦C to 180 ◦C. The evolutions of the UV-Vis absorbance, dynamic viscosity, electric impedance, and acid titration are discussed with the defect kinetics. The evolutions of the color centers, defects for dynamic viscosity, and electric dipoles follow second-order, first-order, and zero-order kinetics, respectively. …


Development Of Tissue-Engineered Model Of Fibrotic Scarring After Spinal Cord Injury To Study Astrocyte Activation And Neurite Outgrowth In Vitro, Nikolas Ala-Kokko, Inha Baek, Younghye Song Sep 2024

Development Of Tissue-Engineered Model Of Fibrotic Scarring After Spinal Cord Injury To Study Astrocyte Activation And Neurite Outgrowth In Vitro, Nikolas Ala-Kokko, Inha Baek, Younghye Song

Biomedical Engineering Faculty Publications and Presentations

Traumatic spinal cord injuries (SCI) are debilitating injuries affecting twenty-seven million people worldwide and cause functional impairments. Despite decades of research and medical advancements, current treatment options for SCI remain limited, in part due to the complex pathophysiology of spinal cord lesions including cellular transformation and extracellular matrix (ECM) remodeling. Recent studies have increased focus on fibrotic scarring after SCI, and yet much remains unclear about the impact of fibrotic scarring on SCI lesion progression. Here, using collagen and decellularized spinal cord-based composite hydrogels, a three-dimensional (3D) cell culture model mimicking the fibrous core of spinal cord lesions was implemented …


Evaluation Of The Efficiency Of Passive Self-Ligating Versus Conventional Brackets In The Alignment Of Mandibular Crowded Teeth (A Comparative Study), Noha Ibrahim Abdelrahman Professor Sep 2024

Evaluation Of The Efficiency Of Passive Self-Ligating Versus Conventional Brackets In The Alignment Of Mandibular Crowded Teeth (A Comparative Study), Noha Ibrahim Abdelrahman Professor

Dentistry

Aim: Is to compare the efficiency of passive self-ligating versus conventional brackets in the alignment of crowded mandibular teeth. Materials and methods: A randomized clinical trial with Fifty participants visiting the clinic of the Orthodontic Department and fulfilling the eligibility criteria were enrolled in the study. Patients were randomly allocated to group A (Conventional brackets) or group B (Damon Q metal passive self-ligating brackets). The amount of mandibular crowding was assessed by Little’s irregularity index. Subjects in both groups were recalled for follow-up every four weeks till completion of alignment. Results: There was no significant difference in baseline irregularity in …


Antibiotic-Loaded Dendrimer Hydrogels In Periodontal Bone Regeneration: An In Vitro Release Feasibility Study, Nicholas Yesbeck, Da Huang, Caroline Carrico, Parthasarathy Madurantakam, Hu Yang Sep 2024

Antibiotic-Loaded Dendrimer Hydrogels In Periodontal Bone Regeneration: An In Vitro Release Feasibility Study, Nicholas Yesbeck, Da Huang, Caroline Carrico, Parthasarathy Madurantakam, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

The prescription of a course of oral antibiotics following bone grafting procedures is a common practice in clinical periodontics to reduce surgical site infections. The goal of this study is to characterize the release profile of antibiotics via local delivery using dendrimer hydrogels (DH) and to analyze the effect of two different particulate bone allografts on the release of the antibiotics in vitro. DH were synthesized from Poly amidoamine (PAMAM) dendrimer G5 and polyethylene glycol diacrylate, and cefazolin was chosen as the antibiotic. The antibiotic-loaded samples were bathed in PBS and incubated at 37 °C; aliquots were taken (1 h, …


Let’S Not Be Creative: “Rigid Irac” And The Hidden Power Of Formalistic Legal Writing, Andrew J. Turner Sep 2024

Let’S Not Be Creative: “Rigid Irac” And The Hidden Power Of Formalistic Legal Writing, Andrew J. Turner

Journal of Legal Education

No abstract provided.


Dirt/Μ: Automated Extraction Of Root Hair Traits Using Combinatorial Optimization, Peter Pietrzyk, Neen Phan-Udom, Chartinun Chutoe, Lise Pingault, Ankita Roy, Marc Libault, Patompong Johns Saengwilai, Alexander Bucksch Sep 2024

Dirt/Μ: Automated Extraction Of Root Hair Traits Using Combinatorial Optimization, Peter Pietrzyk, Neen Phan-Udom, Chartinun Chutoe, Lise Pingault, Ankita Roy, Marc Libault, Patompong Johns Saengwilai, Alexander Bucksch

Department of Entomology: Faculty Publications

As with phenotyping of any microscopic appendages, such as cilia or antennae, phenotyping of root hairs has been a challenge due to their complex intersecting arrangements in two-dimensional images and the technical limitations of automated measurements. Digital Imaging of Root Traits at Microscale (DIRT/μ) is a newly developed algorithm that addresses this issue by computationally resolving intersections and extracting individual root hairs from two-dimensional microscopy images. This solution enables automatic and precise trait measurements of individual root hairs. DIRT/μ rigorously defines a set of rules to resolve intersecting root hairs and minimizes a newly designed cost function to combinatorically identify …


The War On Higher Education, Athena D. Mutua, Jonathan Feingold, Angela Harris, Emily M. S. Houh, Matthew Patrick Shaw, Francisco Valdes Sep 2024

The War On Higher Education, Athena D. Mutua, Jonathan Feingold, Angela Harris, Emily M. S. Houh, Matthew Patrick Shaw, Francisco Valdes

Journal Articles

Higher education is under assault in the United States. Tracking authoritarian movements across the globe, domestic attacks on individual professors and academic institutions buttress a broader campaign to undermine multiracial democracy and the institutions that sustain and safeguard it. Reflecting on the past academic year, this essay charts the increasingly brazen right-wing efforts in the U.S. Congress and the States to erode academic freedom and university independence— two pillars of our democratic republic. We also identify a bi-partisan source of higher education’s present precarity: the neoliberal policies that precipitated the privatization and corporatization of universities across the country.


Advancements In Apoe And Dementia Research: Highlights From The 2023 Aaic Advancements: Apoe Conference., Courtney M Kloske, Michael E Belloy, Elizabeth E Blue, Gregory R Bowman, Maria C Carrillo, Xiaoying Chen, Ornit Chiba-Falek, Albert A Davis, Gilbert Di Paolo, Francesca Garretti, David Gate, Lesley R. Golden, Jay W Heinecke, Joachim Herz, Yadong Huang, Costantino Iadecola, Lance A Johnson, Takahisa Kanekiyo, Celeste M Karch, Anastasia Khvorova, Sascha J Koppes-Den Hertog, Bruce T Lamb, Paige E Lawler, Yann Le Guen, Alexandra Litvinchuk, Chia-Chen Liu, Simin Mahinrad, Edoardo Marcora, Claudia Marino, Danny M Michaelson, Justin J Miller, Josh M. Morganti, Priyanka S Narayan, Michel S Naslavsky, Marlies Oosthoek, Kapil V Ramachandran, Abhirami Ramakrishnan, Ana-Caroline Raulin, Aiko Robert, Rasha N M Saleh, Claire Sexton, Nilomi Shah, Francis Shue, Isabel J Sible, Andrea Soranno, Michael R Strickland, Julia Tcw, Manon Thierry, Li-Huei Tsai, Ryan A Tuckey, Jason D Ulrich, Rik Van Der Kant, Na Wang, Cheryl L Wellington, Stacie C Weninger, Hussein N Yassine, Na Zhao, Guojun Bu, Alison M Goate, David M Holtzman Sep 2024

Advancements In Apoe And Dementia Research: Highlights From The 2023 Aaic Advancements: Apoe Conference., Courtney M Kloske, Michael E Belloy, Elizabeth E Blue, Gregory R Bowman, Maria C Carrillo, Xiaoying Chen, Ornit Chiba-Falek, Albert A Davis, Gilbert Di Paolo, Francesca Garretti, David Gate, Lesley R. Golden, Jay W Heinecke, Joachim Herz, Yadong Huang, Costantino Iadecola, Lance A Johnson, Takahisa Kanekiyo, Celeste M Karch, Anastasia Khvorova, Sascha J Koppes-Den Hertog, Bruce T Lamb, Paige E Lawler, Yann Le Guen, Alexandra Litvinchuk, Chia-Chen Liu, Simin Mahinrad, Edoardo Marcora, Claudia Marino, Danny M Michaelson, Justin J Miller, Josh M. Morganti, Priyanka S Narayan, Michel S Naslavsky, Marlies Oosthoek, Kapil V Ramachandran, Abhirami Ramakrishnan, Ana-Caroline Raulin, Aiko Robert, Rasha N M Saleh, Claire Sexton, Nilomi Shah, Francis Shue, Isabel J Sible, Andrea Soranno, Michael R Strickland, Julia Tcw, Manon Thierry, Li-Huei Tsai, Ryan A Tuckey, Jason D Ulrich, Rik Van Der Kant, Na Wang, Cheryl L Wellington, Stacie C Weninger, Hussein N Yassine, Na Zhao, Guojun Bu, Alison M Goate, David M Holtzman

Physiology Faculty Publications

INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research.

METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates …


Beyond Machines: Exploring Human Identity In The Times Of Ai, Germán H. Alférez Sep 2024

Beyond Machines: Exploring Human Identity In The Times Of Ai, Germán H. Alférez

Achieve

Secular conflicting worldviews constantly influence our students with assumptions regarding human life, reality, origins, deity, the universe, purpose, truth, values, meaning, and destiny. In this presentation, we will review the concept of worldview and discuss major worldviews with a special emphasis on transhumanism. We will study how, as Adventist educators, we can help our students develop a reliable Biblical worldview from which they can pursue their vocation, make decisions, and prepare for eternity.


A Multifactorial Study Of Factors Influencing Self-Health Behaviors In Dementia, Elizabeth Malkin Sep 2024

A Multifactorial Study Of Factors Influencing Self-Health Behaviors In Dementia, Elizabeth Malkin

Dissertations

The global increase in dementia cases presents a significant public health challenge, particularly given the absence of a cure and the rising healthcare burden on individuals and society. This study aims to examine the influence of knowledge, beliefs, and motivation on self-health behaviors to mitigate the risk of dementia among individuals residing in the United States. With the use of an online survey, the study utilized the U.S. normed MCLHB-DRR scale and supplemental questions about knowledge of risk factors and degree of closeness to family members with dementia to determine whether (1) more closely related relatives (first-degree relatives) and those …


Infertility’S Impact On Couples’ Functioning, Elizabeth Sanders Sep 2024

Infertility’S Impact On Couples’ Functioning, Elizabeth Sanders

Dissertations

Historically, infertility has been a taboo topic of discussion and is often avoided in conversation because of the stigmatization of the diagnosis. According to the World Health Organization (2022), infertility affects 186 million individuals globally. However, there seems to be a gap in the research as it pertains to the psychological well-being and treatment of men and women diagnosed with this condition. While it has become less of a feared topic, it still is not discussed or researched enough, thus further exacerbating the gap in research on mental health and treatment options. The following dissertation completed a critical review of …


Behind Armor Blunt Trauma: Liver Injuries Using A Live Animal Model, Narayan Yoganandan, Alok Shah, Brian D. Stemper, Lewis Somber, Valeta Carol Chancey, Joseph Mcentire Sep 2024

Behind Armor Blunt Trauma: Liver Injuries Using A Live Animal Model, Narayan Yoganandan, Alok Shah, Brian D. Stemper, Lewis Somber, Valeta Carol Chancey, Joseph Mcentire

Biomedical Engineering Faculty Research and Publications

Introduction

While the 44-mm clay penetration criterion was developed in the 1970s for soft body armor applications, and the researchers acknowledged the need to conduct additional tests, the same behind the armor blunt trauma displacement limit is used for both soft and hard body armor evaluations and design considerations. Because the human thoraco-abdominal contents are heterogeneous, have different skeletal coverage, and have different functional requirements, the same level of penetration limit does not imply the same level of protection. It is important to determine the regional responses of different thoraco-abdominal organs to better describe human tolerance and improve the current …


Ataxia Telangiectasia And Rad3-Related (Atr) Inhibitor Camonsertib Dose Optimization In Patients With Biomarker-Selected Advanced Solid Tumors (Tresr Study), Elisa Fontana, Ezra Rosen, Elizabeth K Lee, Martin Højgaard, Niharika B Mettu, Stephanie Lheureux, Benedito A Carneiro, Gregory M Cote, Louise Carter, Ruth Plummer, Devalingam Mahalingam, Adrian J Fretland, Joseph D Schonhoft, Ian M Silverman, Marisa Wainszelbaum, Yi Xu, Danielle Ulanet, Maria Koehler, Timothy A Yap Sep 2024

Ataxia Telangiectasia And Rad3-Related (Atr) Inhibitor Camonsertib Dose Optimization In Patients With Biomarker-Selected Advanced Solid Tumors (Tresr Study), Elisa Fontana, Ezra Rosen, Elizabeth K Lee, Martin Højgaard, Niharika B Mettu, Stephanie Lheureux, Benedito A Carneiro, Gregory M Cote, Louise Carter, Ruth Plummer, Devalingam Mahalingam, Adrian J Fretland, Joseph D Schonhoft, Ian M Silverman, Marisa Wainszelbaum, Yi Xu, Danielle Ulanet, Maria Koehler, Timothy A Yap

Faculty, Staff and Student Publications

BACKGROUND: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus, dose and schedule optimization requires extended follow-up to assess prolonged treatment effects.

METHODS: Long-term safety, tolerability, and antitumor efficacy of 3 camonsertib monotherapy dosing regimens were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on, 4 days off (160 3/4; the preliminary recommended Phase II dose [RP2D]) and two step-down groups of …


Identification Of Hypoxia-Alcamhigh Macrophage- Exhausted T Cell Axis In Tumor Microenvironment Remodeling For Immunotherapy Resistance, Zhenzhen Xun, Huanran Zhou, Mingyi Shen, Yao Liu, Chengcao Sun, Yanhua Du, Zhou Jiang, Liuqing Yang, Qing Zhang, Chunru Lin, Qingsong Hu, Youqiong Ye, Leng Han Sep 2024

Identification Of Hypoxia-Alcamhigh Macrophage- Exhausted T Cell Axis In Tumor Microenvironment Remodeling For Immunotherapy Resistance, Zhenzhen Xun, Huanran Zhou, Mingyi Shen, Yao Liu, Chengcao Sun, Yanhua Du, Zhou Jiang, Liuqing Yang, Qing Zhang, Chunru Lin, Qingsong Hu, Youqiong Ye, Leng Han

Faculty, Staff and Student Publications

Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single-cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia-based intercellular communication hub consisting of malignant cells, ALCAM


Ensemble Pretrained Language Models To Extract Biomedical Knowledge From Literature, Zhao Li, Qiang Wei, Liang-Chin Huang, Jianfu Li, Yan Hu, Yao-Shun Chuang, Jianping He, Avisha Das, Vipina Kuttichi Keloth, Yuntao Yang, Chiamaka S Diala, Kirk E Roberts, Cui Tao, Xiaoqian Jiang, W Jim Zheng, Hua Xu Sep 2024

Ensemble Pretrained Language Models To Extract Biomedical Knowledge From Literature, Zhao Li, Qiang Wei, Liang-Chin Huang, Jianfu Li, Yan Hu, Yao-Shun Chuang, Jianping He, Avisha Das, Vipina Kuttichi Keloth, Yuntao Yang, Chiamaka S Diala, Kirk E Roberts, Cui Tao, Xiaoqian Jiang, W Jim Zheng, Hua Xu

Faculty, Staff and Student Publications

OBJECTIVES: The rapid expansion of biomedical literature necessitates automated techniques to discern relationships between biomedical concepts from extensive free text. Such techniques facilitate the development of detailed knowledge bases and highlight research deficiencies. The LitCoin Natural Language Processing (NLP) challenge, organized by the National Center for Advancing Translational Science, aims to evaluate such potential and provides a manually annotated corpus for methodology development and benchmarking.

MATERIALS AND METHODS: For the named entity recognition (NER) task, we utilized ensemble learning to merge predictions from three domain-specific models, namely BioBERT, PubMedBERT, and BioM-ELECTRA, devised a rule-driven detection method for cell line and …


Improving Large Language Models For Clinical Named Entity Recognition Via Prompt Engineering, Yan Hu, Qingyu Chen, Jingcheng Du, Xueqing Peng, Vipina Kuttichi Keloth, Xu Zuo, Yujia Zhou, Zehan Li, Xiaoqian Jiang, Zhiyong Lu, Kirk Roberts, Hua Xu Sep 2024

Improving Large Language Models For Clinical Named Entity Recognition Via Prompt Engineering, Yan Hu, Qingyu Chen, Jingcheng Du, Xueqing Peng, Vipina Kuttichi Keloth, Xu Zuo, Yujia Zhou, Zehan Li, Xiaoqian Jiang, Zhiyong Lu, Kirk Roberts, Hua Xu

Faculty, Staff and Student Publications

IMPORTANCE: The study highlights the potential of large language models, specifically GPT-3.5 and GPT-4, in processing complex clinical data and extracting meaningful information with minimal training data. By developing and refining prompt-based strategies, we can significantly enhance the models' performance, making them viable tools for clinical NER tasks and possibly reducing the reliance on extensive annotated datasets.

OBJECTIVES: This study quantifies the capabilities of GPT-3.5 and GPT-4 for clinical named entity recognition (NER) tasks and proposes task-specific prompts to improve their performance.

MATERIALS AND METHODS: We evaluated these models on 2 clinical NER tasks: (1) to extract medical problems, treatments, …


Target Engagement And Immunogenicity Of An Active Immunotherapeutic Targeting Pathological Α-Synuclein: A Phase 1 Placebo-Controlled Trial, Pepijn Eijsvogel, Pinaki Misra, Luis Concha-Marambio, Justin D Boyd, Shuang Ding, Lauren Fedor, Yueh-Ting Hsieh, Yu Shuang Sun, Madeline M Vroom, Carly M Farris, Yihua Ma, Marieke L De Kam, Igor Radanovic, Maurits F J M Vissers, Dario Mirski, Ghazal Shareghi, Mohammad Shahnawaz, Wolfgang Singer, Philip Kremer, Geert Jan Groeneveld, Hui Jing Yu, Jean-Cosme Dodart Sep 2024

Target Engagement And Immunogenicity Of An Active Immunotherapeutic Targeting Pathological Α-Synuclein: A Phase 1 Placebo-Controlled Trial, Pepijn Eijsvogel, Pinaki Misra, Luis Concha-Marambio, Justin D Boyd, Shuang Ding, Lauren Fedor, Yueh-Ting Hsieh, Yu Shuang Sun, Madeline M Vroom, Carly M Farris, Yihua Ma, Marieke L De Kam, Igor Radanovic, Maurits F J M Vissers, Dario Mirski, Ghazal Shareghi, Mohammad Shahnawaz, Wolfgang Singer, Philip Kremer, Geert Jan Groeneveld, Hui Jing Yu, Jean-Cosme Dodart

Faculty, Staff and Student Publications

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 μg or 300/300/300 μg (weeks …


Mechanistic Insights Into Metabolic Function Of Dynamin-Related Protein 1, Xin Li, Katherine Pham, Jazmin Ysaguirre, Iqbal Mahmud, Lin Tan, Bo Wei, Long J Shao, Maryam Elizondo, Rabie Habib, Fathima Elizondo, Hiromi Sesaki, Philip L Lorenzi, Kai Sun Sep 2024

Mechanistic Insights Into Metabolic Function Of Dynamin-Related Protein 1, Xin Li, Katherine Pham, Jazmin Ysaguirre, Iqbal Mahmud, Lin Tan, Bo Wei, Long J Shao, Maryam Elizondo, Rabie Habib, Fathima Elizondo, Hiromi Sesaki, Philip L Lorenzi, Kai Sun

Faculty, Staff and Student Publications

Dynamin-related protein 1 (DRP1) plays crucial roles in mitochondrial and peroxisome fission. However, the mechanisms underlying the functional regulation of DRP1 in adipose tissue during obesity remain unclear. To elucidate the metabolic and pathological significance of diminished DRP1 in obese adipose tissue, we utilized adipose tissue-specific DRP1 KO mice challenged with a high-fat diet. We observed significant metabolic dysregulations in the KO mice. Mechanistically, DRP1 exerts multifaceted functions in mitochondrial dynamics and endoplasmic reticulum (ER)-lipid droplet crosstalk in normal mice. Loss of function of DRP1 resulted in abnormally giant mitochondrial shapes, distorted mitochondrial membrane structure, and disrupted cristae architecture. Meanwhile, …


An Analysis Of Suspected Microplastics In The Muscle And Gastrointestinal Tissues Of Fish From Sarasota Bay, Fl: Exposure And Implications For Apex Predators And Seafood Consumers, Eric Conger, Miranda Dziobak, Elizabeth J Berens Mccabe, Tita Curtin, Ayushi Gaur, Randall S Wells, John E Weinstein, Leslie B Hart Sep 2024

An Analysis Of Suspected Microplastics In The Muscle And Gastrointestinal Tissues Of Fish From Sarasota Bay, Fl: Exposure And Implications For Apex Predators And Seafood Consumers, Eric Conger, Miranda Dziobak, Elizabeth J Berens Mccabe, Tita Curtin, Ayushi Gaur, Randall S Wells, John E Weinstein, Leslie B Hart

Faculty, Staff and Student Publications

Microplastics have been found in the gastrointestinal (GI) fluid of bottlenose dolphins (Tursiops truncatus), inhabiting Sarasota Bay, FL, suggesting exposure by ingestion, possibly via contaminated fish. To better understand the potential for trophic transfer, muscle and GI tissues from 11 species of dolphin prey fish collected from Sarasota Bay were screened for microplastics (particles <5 mm diameter). Suspected microplastics were found in 82% of muscle samples (n=89), and 97% of GI samples (n=86). Particle abundance and shapes varied by species (p<0.05) and foraging habit (omnivore vs. carnivore, p<0.05). Pinfish (Lagodon rhomboides) had the highest particle abundance for both tissue types (muscle: 0.38 …


Chemical Screening By Time-Resolved X-Ray Scattering To Discover Allosteric Probes, Chris A Brosey, Todd M Link, Runze Shen, Davide Moiani, Kathryn Burnett, Greg L Hura, Darin E Jones, John A Tainer Sep 2024

Chemical Screening By Time-Resolved X-Ray Scattering To Discover Allosteric Probes, Chris A Brosey, Todd M Link, Runze Shen, Davide Moiani, Kathryn Burnett, Greg L Hura, Darin E Jones, John A Tainer

Faculty, Staff and Student Publications

Drug discovery relies on efficient identification of small-molecule leads and their interactions with macromolecular targets. However, understanding how chemotypes impact mechanistically important conformational states often remains secondary among high-throughput discovery methods. Here, we present a conformational discovery pipeline integrating time-resolved, high-throughput small-angle X-ray scattering (TR-HT-SAXS) and classic fragment screening applied to allosteric states of the mitochondrial import oxidoreductase apoptosis-inducing factor (AIF). By monitoring oxidized and X-ray-reduced AIF states, TR-HT-SAXS leverages structure and kinetics to generate a multidimensional screening dataset that identifies fragment chemotypes allosterically stimulating AIF dimerization. Fragment-induced dimerization rates, quantified with time-resolved SAXS similarity analysis (k


Dopaminergic Neurons In Zona Incerta Drives Appetitive Self-Grooming, Zhiying Jiang, Michelle He, Claire Young, Jing Cai, Yuanzhong Xu, Yanyan Jiang, Hongli Li, Maojie Yang, Qingchun Tong Sep 2024

Dopaminergic Neurons In Zona Incerta Drives Appetitive Self-Grooming, Zhiying Jiang, Michelle He, Claire Young, Jing Cai, Yuanzhong Xu, Yanyan Jiang, Hongli Li, Maojie Yang, Qingchun Tong

Faculty, Staff and Student Publications

Dopaminergic (DA) neurons are known to play a key role in controlling behaviors. While DA neurons in other brain regions are extensively characterized, those in zona incerta (ZITH or A13) receive much less attention and their function remains to be defined. Here it is shown that optogenetic stimulation of these neurons elicited intensive self‐grooming behaviors and promoted place preference, which can be enhanced by training but cannot be converted into contextual memory. Interestingly, the same stimulation increased DA release to periaqueductal grey (PAG) neurons and local PAG antagonism of DA action reduced the elicited self‐grooming. In addition, A13 neurons increased …


Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith Sep 2024

Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith

Faculty, Staff and Student Publications

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the …


A Pilot Study Of The Cd38 Antagonist Daratumumab In Patients With Metastatic Renal Cell Carcinoma Or Muscle-Invasive Bladder Cancer, Matthew T Campbell, Amishi Y Shah, Pavlos Msaouel, Nizar M Tannir, Arlene O Siefker-Radtke, Ashish M Kamat, Neema Navai, Colin P N Dinney, Priya Rao, Charles C Guo, Rahul A Sheth, Aradhana M Venkatesan, Rebecca S Tidwell, Shalini S Yadav, Aidi Gu, Hong Chen, Marc Macaluso, Fei Duan, Sreyashi Basu, Sonali Jindal, Padmanee Sharma Sep 2024

A Pilot Study Of The Cd38 Antagonist Daratumumab In Patients With Metastatic Renal Cell Carcinoma Or Muscle-Invasive Bladder Cancer, Matthew T Campbell, Amishi Y Shah, Pavlos Msaouel, Nizar M Tannir, Arlene O Siefker-Radtke, Ashish M Kamat, Neema Navai, Colin P N Dinney, Priya Rao, Charles C Guo, Rahul A Sheth, Aradhana M Venkatesan, Rebecca S Tidwell, Shalini S Yadav, Aidi Gu, Hong Chen, Marc Macaluso, Fei Duan, Sreyashi Basu, Sonali Jindal, Padmanee Sharma

Faculty, Staff and Student Publications

PURPOSE: We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC).

EXPERIMENTAL DESIGN: Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring …


Mechanisms That Clear Mutations Drive Field Cancerization In Mammary Tissue, Marta Ciwinska, Hendrik A Messal, Hristina R Hristova, Catrin Lutz, Laura Bornes, Theofilos Chalkiadakis, Rolf Harkes, Nathalia S M Langedijk, Stefan J Hutten, Renée X Menezes, Jos Jonkers, Stefan Prekovic, Grand Challenge Precision Consortium, Benjamin D Simons, Colinda L G J Scheele, Jacco Van Rheenen Sep 2024

Mechanisms That Clear Mutations Drive Field Cancerization In Mammary Tissue, Marta Ciwinska, Hendrik A Messal, Hristina R Hristova, Catrin Lutz, Laura Bornes, Theofilos Chalkiadakis, Rolf Harkes, Nathalia S M Langedijk, Stefan J Hutten, Renée X Menezes, Jos Jonkers, Stefan Prekovic, Grand Challenge Precision Consortium, Benjamin D Simons, Colinda L G J Scheele, Jacco Van Rheenen

Faculty, Staff and Student Publications

Oncogenic mutations are abundant in the tissues of healthy individuals, but rarely form tumours1-3. Yet, the underlying protection mechanisms are largely unknown. To resolve these mechanisms in mouse mammary tissue, we use lineage tracing to map the fate of wild-type and Brca1-/-;Trp53-/- cells, and find that both follow a similar pattern of loss and spread within ducts. Clonal analysis reveals that ducts consist of small repetitive units of self-renewing cells that give rise to short-lived descendants. This offers a first layer of protection as any descendants, including oncogenic mutant cells, are constantly lost, thereby limiting the spread of mutations to …


Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden Sep 2024

Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden

School of Medicine Faculty Publications

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for …


Development Amidst Psychological Difficulties: Parents As Developmental Assets, Kimia Shirzad, Sunhye Bai, Jennifer P. Agans Sep 2024

Development Amidst Psychological Difficulties: Parents As Developmental Assets, Kimia Shirzad, Sunhye Bai, Jennifer P. Agans

Journal of Youth Development

No abstract provided.


Thai Parents’ Reasons For Sending Their Children To Premium-Fee International Schools: Strategies For Establishing International Schools, Issara Wongcharoensin Sep 2024

Thai Parents’ Reasons For Sending Their Children To Premium-Fee International Schools: Strategies For Establishing International Schools, Issara Wongcharoensin

Theses and Dissertations from DePaul University

The study investigates the factors influencing Thai parents’ decisions when selecting international schools in the Bangkok Metropolitan Region. It examines how parents’ preferences for educational outcomes shape their choice among UK, US, or IB programs. Key findings reveal that dissatisfaction with Thai public schools drives many families to enroll their children in international schools. These institutions are valued for their supportive community atmosphere, opportunities for foreign college placements, and superior infrastructure. Preferences for different programs reflect distinct priorities: UK programs are preferred for their extracurricular activities, punctuality, and academic reputation; US programs for their emphasis on critical thinking, multiculturalism, and …