Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network

Open Access. Powered by Scholars. Published by Universities.®

Discipline
Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 64801 - 64830 of 818017

Full-Text Articles in Entire DC Network

Medicinally Privileged Natural Chalcones: Abundance, Mechanisms Of Action, And Clinical Trials, Sophia M. Villa, Justin Z. Heckman, Debasish Bandyopadhyay Sep 2024

Medicinally Privileged Natural Chalcones: Abundance, Mechanisms Of Action, And Clinical Trials, Sophia M. Villa, Justin Z. Heckman, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences Faculty Publications

Chalcones have been utilized for centuries as foods and medicines across various cultures and traditions worldwide. This paper concisely overviews their biosynthesis as specialized metabolites in plants and their significance, potential, efficacy, and possibility as future medicines. This is followed by a more in-depth exploration of naturally occurring chalcones and their corresponding mechanisms of action in human bodies. Based on their mechanisms of action, chalcones exhibit many pharmacological properties, including antioxidant, anti-inflammatory, anticancer, antimalarial, antiviral, and antibacterial properties. Novel naturally occurring chalcones are also recognized as potential antidiabetic drugs, and their effect on the GLUT-4 transporter is investigated. In addition, …


In Vivo Anti-Acetylcholinesterase, Antioxidant Activities And Acute Toxicity Of The Alkaloid Fraction From Hippeastrum Reticulatum, Trang Huyen Xuan Hoang, Quan Van Le, Hoai Thi Nguyen, Huong Thanh Phung Sep 2024

In Vivo Anti-Acetylcholinesterase, Antioxidant Activities And Acute Toxicity Of The Alkaloid Fraction From Hippeastrum Reticulatum, Trang Huyen Xuan Hoang, Quan Van Le, Hoai Thi Nguyen, Huong Thanh Phung

The Thai Journal of Pharmaceutical Sciences

Background: Hippeastrum reticulatum (HR) belongs to the Amaryllidaceae, a well-known ornamental family.Objectives: This study was designed to reveal in vivo anti-acetylcholinesterase (AChE) and antioxidant activities and evaluate the acute toxicity of the alkaloid fraction (AF). Methods: The D-galactose-induced aging model and the scopolamine-induced cognitive-deficit model were used for the in vivo tests. The median lethal dose (LD50) of the AF was determined using the Litchfield and Wilcoxon method. Results: On the aging model, the AF at 10 and 15 mg/kg significantly improved the antioxidant markers including superoxide dismutase, glutathione peroxidase, and malonyl dialdehyde. Upon the scopolamine-injected …


Highly Toxic Aβ Begets More Aβ, Merc M. Kemeh, Noel Lazo Sep 2024

Highly Toxic Aβ Begets More Aβ, Merc M. Kemeh, Noel Lazo

Chemistry

No abstract provided.


Effects Of Increased Nitrate Intake From Beetroot Juice On Blood Markers Of Oxidative Stress And Inflammation In Older Adults With Hypertension, Rebeka Fejes, Nina Pilat, Martin Lutnik, Stefan Weisshaar, Anna M. Weijler, Karsten Krüger, Agnes Draxler, Laura Bragagna, Jonathan M. Peake, Richard J. Woodman, Kevin D. Croft, Catherine P. Bondonno, Jonathan M. Hodgson, Karl Heinz Wagner, Michael Wolzt, Oliver Neubauer Sep 2024

Effects Of Increased Nitrate Intake From Beetroot Juice On Blood Markers Of Oxidative Stress And Inflammation In Older Adults With Hypertension, Rebeka Fejes, Nina Pilat, Martin Lutnik, Stefan Weisshaar, Anna M. Weijler, Karsten Krüger, Agnes Draxler, Laura Bragagna, Jonathan M. Peake, Richard J. Woodman, Kevin D. Croft, Catherine P. Bondonno, Jonathan M. Hodgson, Karl Heinz Wagner, Michael Wolzt, Oliver Neubauer

Research outputs 2022 to 2026

Background: Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans. Aim: In this randomised, placebo-controlled crossover study, by measuring a combination of multiple blood biomarkers, we evaluated whether previously reported benefits of dietary nitrate translate to a reduced oxidative stress and an improved inflammation status in 15 men and women (age range: 56–71 years) with treated hypertension. Methods: We investigated the …


Individual-Based Modelling Of Adaptive Physiological Traits Of Cyanobacteria: Responses To Light History, Mohammad Hassan Ranjbar, David P. Hamilton, Michael L. Pace, Amir Etemad-Shahidi, Cayelan C. Carey, Fernanda Helfer Sep 2024

Individual-Based Modelling Of Adaptive Physiological Traits Of Cyanobacteria: Responses To Light History, Mohammad Hassan Ranjbar, David P. Hamilton, Michael L. Pace, Amir Etemad-Shahidi, Cayelan C. Carey, Fernanda Helfer

Research outputs 2022 to 2026

Adaptive physiological traits of cyanobacteria allow plasticity of responses to environmental change at multiple time scales. Most conventional phytoplankton models only simulate responses to current conditions without incorporating antecedent environmental history and adaptive physiological traits, thereby potentially missing mechanisms that influence dynamics. We developed an individual-based model (IBM) that incorporates information on light exposure history and cell physiology coupled with a hydrodynamic model that simulates mixing and transport. The combined model successfully simulated cyanobacterial growth and respiration in a whole-lake nutrient enrichment experiment in a temperate lake (Peter Lake, Michigan, USA). The model also incorporates non-photochemical quenching (NPQ) to improve …


Detection And Prevalence Of A Novel Bandavirus Related To Guertu Virus In Amblyomma Gemma Ticks And Human Populations In Isiolo County, Kenya, Hellen Koka, Solomon Langat, Samuel Oyola, Faith Cherop, Gilbert Rotich, James Mutisya, Victor Ofula, Konongoi Limbaso, Juliette R. Ongus, Joel Lutomiah, Rosemary Sang Sep 2024

Detection And Prevalence Of A Novel Bandavirus Related To Guertu Virus In Amblyomma Gemma Ticks And Human Populations In Isiolo County, Kenya, Hellen Koka, Solomon Langat, Samuel Oyola, Faith Cherop, Gilbert Rotich, James Mutisya, Victor Ofula, Konongoi Limbaso, Juliette R. Ongus, Joel Lutomiah, Rosemary Sang

All Peer-Reviewed Publications

Introduction Emerging tick-borne viruses of medical and veterinary importance are increasingly being reported globally. This resurgence emphasizes the need for sustained surveillance to provide insights into tick-borne viral diversity and associated potential public health risks. We report on a virus tentatively designated Kinna virus (KIV) in the family Phenuiviridae and genus Bandavirus. The virus was isolated from a pool of Amblyomma gemma ticks from Kinna in Isiolo County, Kenya. High throughput sequencing of the virus isolate revealed close relatedness to the Guertu virus. The virus genome is consistent with the described genomes of other members of the genus Bandavirus, with …


Regretting Nothing, Or Regretting Everything? Postfeminism, Femininity, And Regret In Miss Austen Regrets, Jessica Taylor Sep 2024

Regretting Nothing, Or Regretting Everything? Postfeminism, Femininity, And Regret In Miss Austen Regrets, Jessica Taylor

Research outputs 2022 to 2026

This article considers how regret is mobilized within a postfeminist cultural context, taking the 2007 BBC film Miss Austen Regrets (dir. Jeremy Lovering, UK) as its case study. The article proposes that what is regretted in postfeminist culture speaks to the values and tensions that underpin this cultural context and explores how the expression or experience of regret is treated as proof of women's failures of subjectivity and decision-making. Through examining three of the main characters — Jane Austen, Cassandra Austen, and Fanny Austen Knight — and their interactions with regret, this article argues that both normative femininity and feminist …


Health Behaviors And Physical Health Among Young Adults With Varying Psychometric Schizotypy, Christopher Liong Sep 2024

Health Behaviors And Physical Health Among Young Adults With Varying Psychometric Schizotypy, Christopher Liong

Dissertations, Theses, and Capstone Projects

Schizophrenia has consistently been associated with increased rates of physical illness and early mortality. One explanation for this association might be poor health behaviors, as people with schizophrenia are more sedentary, less physically active, and more likely to engage in substance use compared to the general population. Schizotypy may be conceptualized as the phenotypic expression of increased risk for schizophrenia spectrum disorders, and dimensional models of schizotypy suggest that it varies on a continuum ranging from non-clinical (i.e. low schizotypy) to clinical (i.e. high schizotypy and dysfunction, as in schizophrenia). Though schizotypy and schizophrenia appear to share similar deficits and …


Synthesis Of C-Di- And C-Tri- Saccharides From Glycosyl Crotylating Agents, Steven Truong Sep 2024

Synthesis Of C-Di- And C-Tri- Saccharides From Glycosyl Crotylating Agents, Steven Truong

Dissertations, Theses, and Capstone Projects

The involvement of carbohydrates in a plethora of fundamental biological pathways, including disease related processes, has created a demand for molecular probes for elucidating these mechanisms. Accordingly, synthesis of tailored and diverse carbohydrate-like molecules, commonly referred to as glycomimetics, is a very active area of research. Among the more popular classes of glycomimetics are C-glycosides, analogues in which the anomeric carbon of a parent sugar is attached to a carbon substituent. C-glycosides have attracted attention in the medicinal chemistry community as there are several naturally occurring examples with interesting pharmacologically activity. C-glycosides are also of interest because in …


Investigating The Usability Of Xai In Ai-Based Image Classification, Jan Stodt, Christoph Reich, Nathan Clarke Sep 2024

Investigating The Usability Of Xai In Ai-Based Image Classification, Jan Stodt, Christoph Reich, Nathan Clarke

School of Engineering, Computing and Mathematics

This paper investigates the usability of XAI (Explainable Artificial Intelligence) in AI-based image classification, particularly for non-experts like medical professionals. XAI provides the user of AI systems with an explanation for a particular decision. But the usability of such explanations remains an open point of discussion. The investigation highlights that there is a need for integrating explainability in the design of the classification approach. This paper will present an approach to classify the parts of an object separately and then utilize a white box model (decision tree) for the final classification. This is enriched by additional information, achieving understandability of …


Survey Of Soilborne Pathogens Infecting Strawberry In Oxnard, California & Effect Of Planting Date And Chill Treatment On Yield Of Strawberry, Samantha Z. Simard Sep 2024

Survey Of Soilborne Pathogens Infecting Strawberry In Oxnard, California & Effect Of Planting Date And Chill Treatment On Yield Of Strawberry, Samantha Z. Simard

Master's Theses

Survey to quantify the frequency of the five main pathogens (Macrophomina phaseolina, Fusarium oxysporum f. sp. fragariae races 1 and 2, Verticillium dahliae, and Phytophthora spp.) infecting strawberry in the Oxnard growing district of California. M. phaseolina was the most prevalent pathogen detected in diseased plants in the Oxnard growing district, present in 67.6% of samples positive for at least one pathogen. F. oxysporum f. sp. fragariae race 1 (35.3%), V. dahlia (8.8%), F. oxysporum f. sp. fragariae race 2 (5.9%) and Phytophthora spp. (2.9%) followed at lower prevalence. Associations were found between fewer drip irrigation lines …


Spatial Planning Offshore Wind Energy Farms In California For Mediating Fisheries And Wildlife Conservation Impacts, Crow White, Yi-Hui Wang, Ryan K. Walter, Benjamin Ruttenberg, Danny Han, Eli Newman, Ethan R. Deyle, Sucharita Gopal, Les Kaufman Sep 2024

Spatial Planning Offshore Wind Energy Farms In California For Mediating Fisheries And Wildlife Conservation Impacts, Crow White, Yi-Hui Wang, Ryan K. Walter, Benjamin Ruttenberg, Danny Han, Eli Newman, Ethan R. Deyle, Sucharita Gopal, Les Kaufman

Physics

Achieving a blue economy will require reconciling the value of emerging ocean uses with their impacts on the seascape and sectors with historical access to marine resources and areas. To meet this challenge, we developed an analytical framework for conducting marine spatial planning through tradeoff analysis, and applied it to prospective offshore wind energy development in the ∼974 km2 Morro Bay, California, USA Wind Energy Area (WEA). We generated spatial data layers estimating MW power production and impacts on fisheries value and marine wildlife conservation (seabird and cetacean populations) from wind farm development. We then quantified each sector's response to …


Draft Genome Sequences Of Four Corynebacterium Amycolatum Strains Isolated From Female Urine Samples, Alex Kula, Grace Chilton, James Damaso, Yusef Golzar, Fatima Rushnaiwala, Helen Appleberry, Alan J. Wolfe, Catherine Putonti Sep 2024

Draft Genome Sequences Of Four Corynebacterium Amycolatum Strains Isolated From Female Urine Samples, Alex Kula, Grace Chilton, James Damaso, Yusef Golzar, Fatima Rushnaiwala, Helen Appleberry, Alan J. Wolfe, Catherine Putonti

Biology: Faculty Publications and Other Works

Corynebacterium amycolatum is an emerging pathogen of the urinary tract. Here, we present the draft genomes for four strains isolated from urine collected from symptomatic and asymptomatic female participants.


Putting Gpt-4o To The Sword: A Comprehensive Evaluation Of Language, Vision, Speech, And Multimodal Proficiency, Sakib Shahriar, Brady D. Lund, Nishith Reddy Mannuru, Muhammad Arbab Arshad, Kadhim Hayawi, Ravi Varma Kumar Bevara, Aashrith Mannuru, Laiba Batool Sep 2024

Putting Gpt-4o To The Sword: A Comprehensive Evaluation Of Language, Vision, Speech, And Multimodal Proficiency, Sakib Shahriar, Brady D. Lund, Nishith Reddy Mannuru, Muhammad Arbab Arshad, Kadhim Hayawi, Ravi Varma Kumar Bevara, Aashrith Mannuru, Laiba Batool

All Works

As large language models (LLMs) continue to advance, evaluating their comprehensive capabilities becomes significant for their application in various fields. This research study comprehensively evaluates the language, vision, speech, and multimodal capabilities of GPT-4o. The study employs standardized exam questions, reasoning tasks, and translation assessments to assess the model’s language capability. Additionally, GPT-4o’s vision and speech capabilities are tested through image classification and object-recognition tasks, as well as accent classification. The multimodal evaluation assesses the model’s performance in integrating visual and linguistic data. Our findings reveal that GPT-4o demonstrates high accuracy and efficiency across multiple domains in language and reasoning …


Mondoa And Aki And Aki-To-Ckd Transition, Shihomi Maeda, Shinsuke Sakai, Yoshitsugu Takabatake, Takeshi Yamamoto, Satoshi Minami, Jun Nakamura, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Hiroaki Yonishi, Sho Matsui, Atsuhiro Imai, Ryuya Edahiro, Hitomi Yamamoto-Imoto, Isao Matsui, Seiji Takashima, Ryoichi Imamura, Norio Nonomura, Motoko Yanagita, Yukinori Okada, Andrea Ballabio, Shuhei Nakamura, Tamotsu Yoshimori, Yoshitaka Isaka Sep 2024

Mondoa And Aki And Aki-To-Ckd Transition, Shihomi Maeda, Shinsuke Sakai, Yoshitsugu Takabatake, Takeshi Yamamoto, Satoshi Minami, Jun Nakamura, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Hiroaki Yonishi, Sho Matsui, Atsuhiro Imai, Ryuya Edahiro, Hitomi Yamamoto-Imoto, Isao Matsui, Seiji Takashima, Ryoichi Imamura, Norio Nonomura, Motoko Yanagita, Yukinori Okada, Andrea Ballabio, Shuhei Nakamura, Tamotsu Yoshimori, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

Key Points:

  1. The expression of MondoA was decreased in the renal tubules of patients with CKD.

  2. Genetic ablation of MondoA in proximal tubules inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon.

  3. MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the transcription factor EB-peroxisome proliferator-activated receptor-γ coactivator-1α axis.

Background: Elderly individuals and patients with CKD are at a higher risk of AKI. The transcription factor MondoA is downregulated in the kidneys of aged individuals or patients with AKI; however, its roles in AKI development and the AKI-to-CKD transition remain …


The Cerebellum Modulates Thirst, Ila Mishra, Bing Feng, Bijoya Basu, Amanda M Brown, Linda H Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V Sillitoe, Yanlin He, Atul R Chopra Sep 2024

The Cerebellum Modulates Thirst, Ila Mishra, Bing Feng, Bijoya Basu, Amanda M Brown, Linda H Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V Sillitoe, Yanlin He, Atul R Chopra

Duncan NRI Faculty and Staff Publications

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by …


Understanding The Mystery Of R-Loops And Their Relationship To Nucleolar Stress, Kevin Shane Sep 2024

Understanding The Mystery Of R-Loops And Their Relationship To Nucleolar Stress, Kevin Shane

Master's Theses

Genomic instability is an increase in the likelihood of DNA mutations and genetic changes during cell division, a common feature in cancer cells. One cause of genomic instability comes from the aberrant formation of three-stranded nucleic acid structures called R-loops. R-loop form when an RNA strand hybridizes to its complementary strand of DNA, forming a stable RNA:DNA hybrid and displacing one free strand of DNA 1. Accumulation of unscheduled R-loops can lead to replication stress, fork collision, gene expression changes, and double-strand breaks that are underlying causes of genome instability and the development of many diseases, including cancer 2. Many …


Metabolic Cell Death In Cancer: Ferroptosis, Cuproptosis, Disulfidptosis, And Beyond, Chao Mao, Min Wang, Li Zhuang, Boyi Gan Sep 2024

Metabolic Cell Death In Cancer: Ferroptosis, Cuproptosis, Disulfidptosis, And Beyond, Chao Mao, Min Wang, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

Cell death resistance represents a hallmark of cancer. Recent studies have identified metabolic cell death as unique forms of regulated cell death resulting from an imbalance in the cellular metabolism. This review discusses the mechanisms of metabolic cell death-ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, and alkaliptosis-and explores their potential in cancer therapy. Our review underscores the complexity of the metabolic cell death pathways and offers insights into innovative therapeutic avenues for cancer treatment.


Sex Disparities In Mortality After Endovascular Therapy In Large Core Infarcts, Ngoc Mai Le, Camille Neal-Harris, Emmanuel C Ebirim, Ananya S Iyyangar, Hussain Azeem, Anjan N Ballekere, Saagar Dhanjani, Eunyoung Lee, Sunil A Sheth Sep 2024

Sex Disparities In Mortality After Endovascular Therapy In Large Core Infarcts, Ngoc Mai Le, Camille Neal-Harris, Emmanuel C Ebirim, Ananya S Iyyangar, Hussain Azeem, Anjan N Ballekere, Saagar Dhanjani, Eunyoung Lee, Sunil A Sheth

Faculty, Staff and Student Publications

Background: In recent large core endovascular therapy (EVT) trials of large vessel occlusion acute ischemic stroke (AIS), treatment was associated with reduced rates of mortality. Because post-AIS mortality can be influenced by societal and biological factors that differ between women and men, we investigate sex-based differences in mortality outcomes following EVT in large core AIS.

Methods: From our prospectively collected multicenter registry across 4 comprehensive stroke centers in the Greater Houston area, we identified patients from 2017 to 2022 with large vessel occlusion AIS and large infarct core. Large infarct core was defined by computed tomography perfusion exceeding 70 mL …


Emerging Treatment Landscape For Guillain-Barré Syndrome (Gbs): What’S New?, Alina Sprenger-Svačina, Martin K R Svačina, Tong Gao, Gang Zhang, Kazim A Sheikh Sep 2024

Emerging Treatment Landscape For Guillain-Barré Syndrome (Gbs): What’S New?, Alina Sprenger-Svačina, Martin K R Svačina, Tong Gao, Gang Zhang, Kazim A Sheikh

Faculty, Staff and Student Publications

Introduction: Guillain-Barré syndrome (GBS) is a monophasic immune neuropathic disorder characterized by acute paralysis. A significant portion of patients are left with residual deficits, which presents a considerable global healthcare challenge. The precise mechanisms underlying GBS pathogenesis are not fully elucidated. Recent studies have focused on postinfectious molecular mimicry and identified involvement of IgG autoantibodies and innate immune effectors in GBS. Intravenous immunoglobulins (IVIg) and plasma exchange (PE) are two established evidence-based immunomodulatory treatments for GBS, but a significant proportion of GBS patients fails to respond adequately to either therapy. This emphasizes an urgent need for novel and more potent …


A Call To Action: The Shea Research Agenda To Combat Healthcare-Associated Infections., Jennie H. Kwon, Sonali D. Advani, Westyn Branch-Elliman, Barbara I. Braun, Vincent Chi-Chung Cheng, Kathleen Chiotos, Peggy Douglas, Shruti K. Gohil, Sara C. Keller, Eili Y. Klein, Sarah L. Krein, Eric T. Lofgren, Katreena Merrill, Rebekah W. Moehring, Elizabeth Monsees, Luci Perri, Felicia Scaggs Huang, Mark A. Shelly, Felicia Skelton, Emily S. Spivak, Pranavi V. Sreeramoju, Katie J. Suda, Joseph Y. Ting, Gregory David Weston, Mohamed H. Yassin, Matthew J. Ziegler, Lona Mody Sep 2024

A Call To Action: The Shea Research Agenda To Combat Healthcare-Associated Infections., Jennie H. Kwon, Sonali D. Advani, Westyn Branch-Elliman, Barbara I. Braun, Vincent Chi-Chung Cheng, Kathleen Chiotos, Peggy Douglas, Shruti K. Gohil, Sara C. Keller, Eili Y. Klein, Sarah L. Krein, Eric T. Lofgren, Katreena Merrill, Rebekah W. Moehring, Elizabeth Monsees, Luci Perri, Felicia Scaggs Huang, Mark A. Shelly, Felicia Skelton, Emily S. Spivak, Pranavi V. Sreeramoju, Katie J. Suda, Joseph Y. Ting, Gregory David Weston, Mohamed H. Yassin, Matthew J. Ziegler, Lona Mody

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


Radiation Therapy Quality Assurance Analysis Of Alliance A021501: Preoperative Mfolfirinox Or Mfolfirinox Plus Hypofractionated Radiation Therapy For Borderline Resectable Adenocarcinoma Of The Pancreas, Leila T Tchelebi, Diana Segovia, Koren Smith, Qian Shi, T J Fitzgerald, Michael D Chuong, Tyler J Zemla, Eileen M O'Reilly, Jeffrey A Meyerhardt, Eugene J Koay, Jessica Lowenstein, Ardaman Shergill, Matthew H G Katz, Joseph M Herman Sep 2024

Radiation Therapy Quality Assurance Analysis Of Alliance A021501: Preoperative Mfolfirinox Or Mfolfirinox Plus Hypofractionated Radiation Therapy For Borderline Resectable Adenocarcinoma Of The Pancreas, Leila T Tchelebi, Diana Segovia, Koren Smith, Qian Shi, T J Fitzgerald, Michael D Chuong, Tyler J Zemla, Eileen M O'Reilly, Jeffrey A Meyerhardt, Eugene J Koay, Jessica Lowenstein, Ardaman Shergill, Matthew H G Katz, Joseph M Herman

Faculty, Staff and Student Publications

Purpose: Alliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered.

Methods and materials: SBRT (6.6 Gy × 5) was intended but hypofractionated RT (5 Gy × 5) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable …


Strategies For The Development Of Metalloimmunotherapies, Xiaoqi Sun, Xingwu Zhou, Xiaoyue Shi, Omar A Abed, Xinran An, Yu Leo Lei, James J Moon Sep 2024

Strategies For The Development Of Metalloimmunotherapies, Xiaoqi Sun, Xingwu Zhou, Xiaoyue Shi, Omar A Abed, Xinran An, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Metal ions play crucial roles in the regulation of immune pathways. In fact, metallodrugs have a long record of accomplishment as effective treatments for a wide range of diseases. Here we argue that the modulation of interactions of metal ions with molecules and cells involved in the immune system forms the basis of a new class of immunotherapies. By examining how metal ions modulate the innate and adaptive immune systems, as well as host-microbiota interactions, we discuss strategies for the development of such metalloimmunotherapies for the treatment of cancer and other immune-related diseases.


Co-Targeting Sos1 Enhances The Antitumor Effects Of Krasg12c Inhibitors By Addressing Intrinsic And Acquired Resistance, Venu Thatikonda, Hengyu Lyu, Sabine Jurado, Kaja Kostyrko, Christopher A Bristow, Christoph Albrecht, Donat Alpar, Heribert Arnhof, Oliver Bergner, Karin Bosch, Ningping Feng, Sisi Gao, Daniel Gerlach, Michael Gmachl, Melanie Hinkel, Simone Lieb, Astrid Jeschko, Annette A Machado, Thomas Madensky, Ethan D Marszalek, Mikhila Mahendra, Gabriella Melo-Zainzinger, Jessica M Molkentine, Philipp A Jaeger, David H Peng, Robyn L Schenk, Alexey Sorokin, Sandra Strauss, Francesca Trapani, Scott Kopetz, Christopher P Vellano, Mark Petronczki, Norbert Kraut, Timothy P Heffernan, Joseph R Marszalek, Mark Pearson, Irene C Waizenegger, Marco H Hofmann Sep 2024

Co-Targeting Sos1 Enhances The Antitumor Effects Of Krasg12c Inhibitors By Addressing Intrinsic And Acquired Resistance, Venu Thatikonda, Hengyu Lyu, Sabine Jurado, Kaja Kostyrko, Christopher A Bristow, Christoph Albrecht, Donat Alpar, Heribert Arnhof, Oliver Bergner, Karin Bosch, Ningping Feng, Sisi Gao, Daniel Gerlach, Michael Gmachl, Melanie Hinkel, Simone Lieb, Astrid Jeschko, Annette A Machado, Thomas Madensky, Ethan D Marszalek, Mikhila Mahendra, Gabriella Melo-Zainzinger, Jessica M Molkentine, Philipp A Jaeger, David H Peng, Robyn L Schenk, Alexey Sorokin, Sandra Strauss, Francesca Trapani, Scott Kopetz, Christopher P Vellano, Mark Petronczki, Norbert Kraut, Timothy P Heffernan, Joseph R Marszalek, Mark Pearson, Irene C Waizenegger, Marco H Hofmann

Faculty, Staff and Student Publications

Combination approaches are needed to strengthen and extend the clinical response to KRASG12C inhibitors (KRASG12Ci). Here, we assessed the antitumor responses of KRASG12C mutant lung and colorectal cancer models to combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus the KRASG12C inhibitor, adagrasib. We found that responses to BI-3406 plus adagrasib were stronger than to adagrasib alone, comparable to adagrasib with SHP2 (SHP2i) or EGFR inhibitors and correlated with stronger suppression of RAS-MAPK signaling. BI-3406 plus adagrasib treatment also delayed the emergence of acquired resistance and elicited antitumor responses from adagrasib-resistant models. Resistance to KRASG12Ci seemed to be driven by …


Surgical Necrotizing Enterocolitis And Spontaneous Intestinal Perforation Lead To Severe Growth Failure In Infants, Allison L Speer, Kevin P Lally, Claudia Pedroza, Yuxin Zhang, Brenda B Poindexter, Walter J Chwals, Susan R Hintz, Gail E Besner, David K Stevenson, Robin K Ohls, William E Truog, Barbara J Stoll, Matthew A Rysavy, Abhik Das, Jon E Tyson, Martin L Blakely Sep 2024

Surgical Necrotizing Enterocolitis And Spontaneous Intestinal Perforation Lead To Severe Growth Failure In Infants, Allison L Speer, Kevin P Lally, Claudia Pedroza, Yuxin Zhang, Brenda B Poindexter, Walter J Chwals, Susan R Hintz, Gail E Besner, David K Stevenson, Robin K Ohls, William E Truog, Barbara J Stoll, Matthew A Rysavy, Abhik Das, Jon E Tyson, Martin L Blakely

Faculty, Staff and Student Publications

Objective: We aimed to determine the incidence of growth failure in infants with necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) and whether initial laparotomy versus peritoneal drainage (PD) impacted the likelihood of growth failure.

Summary background data: Infants with surgical NEC and SIP have high mortality, and most have neurodevelopmental impairment and poor growth. Existing literature on growth outcomes for these infants is limited.

Methods: This is a preplanned secondary study of the Necrotizing Enterocolitis Surgery Trial dataset. The primary outcome was growth failure (Z-score for weight < -2.0) at 18 to 22 months. We used logistic regression, including diagnosis and treatment, as covariates. Secondary outcomes were analyzed using the Fisher exact or Pearson χ2 test for categorical variables and the Wilcoxon rank sum test or one-way ANOVA for continuous variables.

Results: Among 217 survivors, 207 infants (95%) had primary outcome data. Growth …


Bioengineering Of Intestinal Grafts, Madushani Herath, Allison L Speer Sep 2024

Bioengineering Of Intestinal Grafts, Madushani Herath, Allison L Speer

Faculty, Staff and Student Publications

Intestinal failure manifests as an impaired capacity of the intestine to sufficiently absorb vital nutrients and electrolytes essential for growth and well-being in pediatric and adult populations. Although parenteral nutrition remains the mainstay therapeutic approach, the pursuit of a definitive and curative strategy, such as regenerative medicine, is imperative. Substantial advancements in the field of engineered intestinal tissues present a promising avenue for addressing intestinal failure; nevertheless, extensive research is still necessary for effective translation from experimental benchwork to clinical bedside applications.


Lessons Learnt From Broad-Spectrum Coronavirus Antiviral Drug Discovery, Andrew A Bolinger, Jun Li, Xuping Xie, Hongmin Li, Jia Zhou Sep 2024

Lessons Learnt From Broad-Spectrum Coronavirus Antiviral Drug Discovery, Andrew A Bolinger, Jun Li, Xuping Xie, Hongmin Li, Jia Zhou

Faculty, Staff and Student Publications

Introduction: Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the most recent SARS-CoV-2 responsible for the COVID-19 pandemic, pose significant threats to human populations over the past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic to severe distress syndromes (ARDS), resulting in high morbidity and mortality.

Areas covered: The accelerated advancements in antiviral drug discovery, spurred by the COVID-19 pandemic, have shed new light on the imperative to develop treatments effective against a broad spectrum of CoVs. This perspective discusses strategies and …


Ketamine’S Mechanism Of Action With An Emphasis On Neuroimmune Regulation: Can The Complement System Complement Ketamine’S Antidepressant Effects?, Brandi Quintanilla, Carlos A Zarate, Anilkumar Pillai Sep 2024

Ketamine’S Mechanism Of Action With An Emphasis On Neuroimmune Regulation: Can The Complement System Complement Ketamine’S Antidepressant Effects?, Brandi Quintanilla, Carlos A Zarate, Anilkumar Pillai

Faculty, Staff and Student Publications

Over 300 million people worldwide suffer from major depressive disorder (MDD). Unfortunately, only 30-40% of patients with MDD achieve complete remission after conventional monoamine antidepressant therapy. In recent years, ketamine has revolutionized the treatment of MDD, with its rapid antidepressant effects manifesting within a few hours as opposed to weeks with conventional antidepressants. Many research endeavors have sought to identify ketamine's mechanism of action in mood disorders; while many studies have focused on ketamine's role in glutamatergic modulation, several studies have implicated its role in regulating neuroinflammation. The complement system is an important component of the innate immune response vital …


A Case Of Persistent Intra-Abdominal Stenotrophomonas Maltophilia Infection Despite Bacteriophage Therapy, Grace D Cullen, Keiko Christine Salazar, Austen Lee Terwilliger, Saima Aslam, Justin R Clark, Anthony W Maresso, Paul L Bollyky, Jenny R Aronson Sep 2024

A Case Of Persistent Intra-Abdominal Stenotrophomonas Maltophilia Infection Despite Bacteriophage Therapy, Grace D Cullen, Keiko Christine Salazar, Austen Lee Terwilliger, Saima Aslam, Justin R Clark, Anthony W Maresso, Paul L Bollyky, Jenny R Aronson

Faculty, Staff and Students Publications

Multidrug resistant infections are a challenge in the health care setting and a cause of patient morbidity and mortality. Bacteriophages (phages) are viruses that target and kill bacteria and have been used in patients to treat bacterial infections. We present a case of disseminated Stenotrophomonas maltophilia infection, with pulmonary, intra-abdominal and bloodstream involvement. The patient was treated with a combination of antibiotics and personalized phage therapy, administered daily for 12 days both intravenously as well as via intra-abdominal drains. Phage therapy was well-tolerated, the patient cleared S. maltophilia from their bloodstream and their intra-abdominal abscesses were stable or decreased in …


Pnpla3, Obesity, And Heavy Alcohol Use In Cirrhosis Patients May Exert A Synergistic Increase Hepatocellular Carcinoma Risk, Aaron P Thrift, Fasiha Kanwal, Hyeyeun Lim, Hao Duong, Yanhong Liu, Amit G Singal, Saira Khaderi, Sumeet K Asrani, Christopher I Amos, Hashem B El-Serag Sep 2024

Pnpla3, Obesity, And Heavy Alcohol Use In Cirrhosis Patients May Exert A Synergistic Increase Hepatocellular Carcinoma Risk, Aaron P Thrift, Fasiha Kanwal, Hyeyeun Lim, Hao Duong, Yanhong Liu, Amit G Singal, Saira Khaderi, Sumeet K Asrani, Christopher I Amos, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors.

METHODS: We analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint …