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

Diseases Commons™

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

Life Sciences

Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 1231 - 1260 of 4378

Full-Text Articles in Diseases

Evaluation Of The Effect Of Enterococcus Cecorum Exposure During Late Embryogenesis On Systemic Disease And Early Performance In Broiler Chickens, Marcela Arango May 2023

Evaluation Of The Effect Of Enterococcus Cecorum Exposure During Late Embryogenesis On Systemic Disease And Early Performance In Broiler Chickens, Marcela Arango

Graduate Theses and Dissertations

The objective of this thesis was to investigate the effects of Enterococcus cecorum (EC) administration into the amnion at day 18 of embryogenesis on performance and septicemia development in broiler chickens. Chapter I consists of a brief overview of the thesis. Chapter II provides a literature review on EC-related disease in broiler chickens and methods to isolate, detect, and differentiate between commensal and pathogenic strains of EC. Chapter III consists of a study conducted to determine if different EC strains isolated from field cases that exhibited septicemia and high mortality impacted hatchability, livability, organ colonization, and early performance in broiler …


Barriers To Colonoscopy In Uk Colorectal Cancer Screening Programmes: Qualitative Interviews With Ethnic Minority Groups, Robert S Kerrison, Natalie Gil, Elizabeth Travis, Robyn Jones, Katriina L Whitaker, Colin Rees, Stephen Duffy, Christian Von Wagner May 2023

Barriers To Colonoscopy In Uk Colorectal Cancer Screening Programmes: Qualitative Interviews With Ethnic Minority Groups, Robert S Kerrison, Natalie Gil, Elizabeth Travis, Robyn Jones, Katriina L Whitaker, Colin Rees, Stephen Duffy, Christian Von Wagner

Faculty, Staff and Student Publications

OBJECTIVE: People from ethnic minority backgrounds are less likely to attend colonoscopy, following faecal immunochemical test screening, and are more likely to be diagnosed with colorectal cancer at an advanced stage as a result. The aim of this research was to explore the barriers and facilitators to attending colonoscopy, perceived by ethnic minority groups living in the United Kingdom.

METHODS: Semi-structured online and telephone interviews were conducted with thirty men and women of Black-African (n = 5), Black-Caribbean (n = 5), South Asian (n = 10) and White British (n = 10) descent. Participants were eligible for screening, but had …


Pathway-Driven Rare Germline Variants Associated With Transplant-Associated Thrombotic Microangiopathy (Ta-Tma), Zhihui Zhang, Wei Hong, Qian Wu, Spiridon Tsavachidis, Jian-Rong Li, Christopher I Amos, Chao Cheng, Sarah E Sartain, Vahid Afshar-Kharghan, Jing-Fei Dong, Pavan Bhatraju, Paul J Martin, Robert S Makar, Pavan K Bendapudi, Ang Li May 2023

Pathway-Driven Rare Germline Variants Associated With Transplant-Associated Thrombotic Microangiopathy (Ta-Tma), Zhihui Zhang, Wei Hong, Qian Wu, Spiridon Tsavachidis, Jian-Rong Li, Christopher I Amos, Chao Cheng, Sarah E Sartain, Vahid Afshar-Kharghan, Jing-Fei Dong, Pavan Bhatraju, Paul J Martin, Robert S Makar, Pavan K Bendapudi, Ang Li

Faculty, Staff and Student Publications

The significance of rare germline mutations in transplant-associated thrombotic microangiopathy (TA-TMA) is not well studied. We performed a genetic association study in 100 adult TA-TMA patients vs. 98 post-transplant controls after matching by race, sex, and year. We focused on 5 pathways in complement, von Willebrand factor (VWF) function and related proteins, VWF clearance, ADAMTS13 function and related proteins, and endothelial activation (3641variants in 52 genes). In the primary analysis focused on 189 functional rare variants, no differential variant enrichment was observed in any of the pathways; specifically, 29 % TA-TMA and 33 % controls had at least 1 rare …


Associations Between Avocado Intake And Lower Rates Of Incident Type 2 Diabetes In Us Adults With Hispanic/Latino Ancestry, Alexis C Wood, Mackenzie K Senn, Jerome I Rotter May 2023

Associations Between Avocado Intake And Lower Rates Of Incident Type 2 Diabetes In Us Adults With Hispanic/Latino Ancestry, Alexis C Wood, Mackenzie K Senn, Jerome I Rotter

Faculty, Staff and Students Publications

BACKGROUND/PURPOSE: Hispanic/Latinos in the US are at increased risk for type 2 diabetes (T2D). Data suggest that avocado intake is associated with better glycemic control, but whether this translates to protection from T2D has not been studied. The goal of the current analyses was to examine whether consuming avocados at baseline is associated with lower incident T2D over a six-year period, compared to not consuming avocados at baseline.

SUBJECTS/METHODS: Using data from a large population of US adults with Hispanic ancestry, without known or unknown T2D at baseline (N=6,159), participants were classified as avocado consumers (N=983) or non-consumers (N=5,176) based …


Exploring The Plausibility Of Human Ecosystem Disruption Being The Cause For Increased Viral Prevalence, Andrew Ventura May 2023

Exploring The Plausibility Of Human Ecosystem Disruption Being The Cause For Increased Viral Prevalence, Andrew Ventura

University Honors Theses

Viral diseases and their prevalence--including both the number of cases and the appearance of new viruses--has increased in the last century, and these diseases have become an increasing threat to human health and well-being. The influenza and COVID-19 pandemics served both as introductions and reminders respectively to the power these viruses have to destroy and disrupt human life. As such, it intimates a necessity to investigate possible causes for the increase in these deadly diseases. Among these plausible causes is the dilution effect hypothesis, which states that decreasing the biodiversity of an ecosystem increases a pathogen's ability to infect, both …


Health And Nutritional Status Among Internally Displaced Children Under Five Years, During The Civil War: Sri Lankan Experience, Madhuka Ambagahage Apr 2023

Health And Nutritional Status Among Internally Displaced Children Under Five Years, During The Civil War: Sri Lankan Experience, Madhuka Ambagahage

Indonesian Journal of Public Health Nutrition (IJPHN)

Around the globe, 1 in 6 children become vulnerable to grave physical and mental violence, hunger, sexual assaults, and exploitation of human rights due to war. These adversities are multi-dimensional, synergistic, and often subtle. This study attempted to evaluate the health and nutritional status of children aged under five years and living in the war zone of Sri Lanka, in view of improving the health services delivered to them. The study used a descriptive cross-sectional design. The study sample, 400, was based on probability proportionate and then systematic sampling drawn from IDP camps located in the Vavuniya district. Validated instruments …


The Effectiveness Of Nem (Nutrizone Educational Media) Compared With Knowledge And Attitudes In Early Adults In The West Jakarta Region, Daniel Hartanto, Laras Sitoayu, Lintang Purwara Dewanti, Harna Harna, Mertien Sa’Pang Apr 2023

The Effectiveness Of Nem (Nutrizone Educational Media) Compared With Knowledge And Attitudes In Early Adults In The West Jakarta Region, Daniel Hartanto, Laras Sitoayu, Lintang Purwara Dewanti, Harna Harna, Mertien Sa’Pang

Indonesian Journal of Public Health Nutrition (IJPHN)

Metabolic syndrome is a disease that often occurs in early adulthood. Maintaining a good lifestyle to prevent non-communicable diseases is very important to maintain a good quality of life. In early adulthood, most of them are still not exposed to information related to metabolic syndrome, so it is necessary to provide interventions associated with it. This study uses the Nutrizone gameboard intervention media. Good early adults’ knowledge and attitude about Metabolic Syndrome may lead to a good lifestyle that prevents them from suffering from NCDs. An intervention media may improve their knowledge and attitude. The research design used was pre-experimental …


Dietary Determinants Of Stunting And Underweight In Under- Five Years Children In Pengasinan Health Center's (Puskesmas) Working Area, Depok, West Java, Muthia Syifa Rahmadina, Ratih Qamara Dewi, Arif Hidayat, Satria Yudistira, Fadila Wirawan Apr 2023

Dietary Determinants Of Stunting And Underweight In Under- Five Years Children In Pengasinan Health Center's (Puskesmas) Working Area, Depok, West Java, Muthia Syifa Rahmadina, Ratih Qamara Dewi, Arif Hidayat, Satria Yudistira, Fadila Wirawan

Indonesian Journal of Public Health Nutrition (IJPHN)

Stunting and underweight are public health problems, especially in under-five children. This study aims to explore the dietary determinants of stunting and underweight. Participants were 52 under-five children who visited Posyandu in Pengasinan and Bedahan, Depok. Body weight for age z-score (WAZ) and height for age z-score (HAZ) were measured with standardized measurement tools by trained operators. Questionnaires were administered to determine sociodemographic, maternal, and child health history, sanitation, disease history, and exclusive breastfeeding history. Data on food intake was obtained through the semi-quantitative Food Frequency Questionnaire and 24-hour recall. There was a significant correlation between the mother’s income with …


Factors Related To The Incidence Of Diarrhea Of Children Aged 24-59 Months In Karangkamulyan Village, Cihara District, Lebak Regency In 2020, Hafshah Farah Fadhilah, Kusharisupeni Djokosujono, Ratu Ayu Dewi Sartika Apr 2023

Factors Related To The Incidence Of Diarrhea Of Children Aged 24-59 Months In Karangkamulyan Village, Cihara District, Lebak Regency In 2020, Hafshah Farah Fadhilah, Kusharisupeni Djokosujono, Ratu Ayu Dewi Sartika

Indonesian Journal of Public Health Nutrition (IJPHN)

Diarrhea remains a major issue in developing countries, including Indonesia, and is a leading cause of malnutrition and death. Banten is one of the provinces with a high incidence of diarrhea. In 2019, the district with the highest number of diarrhea cases for all ages in Banten was Lebak with a total of 50,270 cases. The age group with the greatest number of diarrhea cases was toddlers with over 14,000 cases. This study aimed to investigate the relationship between the incidence of diarrhea and the characteristics of toddlers and their parents, personal hygiene, and environmental sanitation. The study used secondary …


Analysis Of Energy Balance In Obese Healthcare Workers, Nani Cahyani Sudarsono, Ria Lestari, Tiffany Georgine T’Sidkenu Widjaja Apr 2023

Analysis Of Energy Balance In Obese Healthcare Workers, Nani Cahyani Sudarsono, Ria Lestari, Tiffany Georgine T’Sidkenu Widjaja

Indonesian Journal of Public Health Nutrition (IJPHN)

Obesity is a global health challenge that seriously affects developing countries, including Indonesia. It is important to discover the energy balance calculated from energy intake and energy expenditure in obese individuals, especially in obese healthcare workers. This study aimed to analyze the balance of energy intake and expenditure, body composition, and physical activity level in obese healthcare workers at the Exercise Center of Indonesia Medical Education and Research Institute (IMERI FKUI). A cross-sectional study was held at Exercise Center IMERI FKUI. Total sampling was the sampling method utilized in the study. Study participants (aged above 18 years) were screened by …


Associated Food Parenting Practices And Other Factors With Fruit And Vegetable Consumption In Students In Jakarta, Indonesia, Gina Amalia Chaerunnisa, Triyanti Triyanti Apr 2023

Associated Food Parenting Practices And Other Factors With Fruit And Vegetable Consumption In Students In Jakarta, Indonesia, Gina Amalia Chaerunnisa, Triyanti Triyanti

Indonesian Journal of Public Health Nutrition (IJPHN)

The increased risk of non-communicable diseases is still a problem in Indonesia, one of which is the lack of consumption of fruits and vegetables. The available data shows that although fruits and vegetables have a protective/protective effect on the incidence of non-communicable diseases but in real life, the average consumption of fruits and vegetables is still below the recommended intake. Thus, the protective effect cannot be seen clearly. This study aims to describe the consumption of fruits and vegetables and determine the factors of food parenting practices and other factors related to the consumption of fruits and vegetables in students …


Prevalence Of Dog Heartworm (Dirofilaria Immitis) Infection In Invasive Aedes Aegypti And Aedes Albopictus Mosquitoes In Southern California, Irene Hui Ying Lee, Donghwi Kim, Romina Lee Apr 2023

Prevalence Of Dog Heartworm (Dirofilaria Immitis) Infection In Invasive Aedes Aegypti And Aedes Albopictus Mosquitoes In Southern California, Irene Hui Ying Lee, Donghwi Kim, Romina Lee

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.


Increased Risk Of Dementia In Patients With Atopic Dermatitis: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Minah Cho, Kyung Do Han, Sang Hyun Cho, Ji Hyun Lee Apr 2023

Increased Risk Of Dementia In Patients With Atopic Dermatitis: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Minah Cho, Kyung Do Han, Sang Hyun Cho, Ji Hyun Lee

Faculty, Staff and Student Publications

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with bimodal incidence peaks in early childhood and middle-aged and older adults. Few studies have focused on the risk of dementia in AD. The aims of this study were to analyse the incidence, and risk factors for dementia in patients with AD. This nationwide population-based retrospective cohort study enrolled 38,391 adults ≥ 40 years of age with AD and 2,643,602 controls without AD from the Korean National Health Insurance System (NHIS) database from 2009 to 2016. The cumulative incidence probability of all-cause dementia, Alzheimer's disease, or vascular dementia at 8 years …


Wellness Review 2022, Part 2, Martin Huecker, Brian A. Ferguson, Jacob Shreffler Apr 2023

Wellness Review 2022, Part 2, Martin Huecker, Brian A. Ferguson, Jacob Shreffler

Journal of Wellness

Introduction: Similar to prior reviews, the Journal of Wellness editors searched the literature from the second half of 2022 for an interesting and impactful selection of publications on wellness in healthcare professionals.

Methods: Editors conducted a standard keyword search in Pubmed, focusing chiefly on large journals, interventional trials, and other prospective research. We included papers published between July 1, 2022 and December 31, 2022.

Literature in Review: Finding several hundred publications, we excluded editorials, reviews, and some smaller, less generalizable papers. A final 25 significant studies focusing on wellness in medical professionals were sorted into the following categories: logistics, creativity …


Localization Of Ctg-Repeat-Containing Transgenes In Drosophila Melanogaster Myotonic Dystrophy Models, Andrea Waltrip Apr 2023

Localization Of Ctg-Repeat-Containing Transgenes In Drosophila Melanogaster Myotonic Dystrophy Models, Andrea Waltrip

Departmental Honors & Graduate Capstone Projects

Myotonic Dystrophy Type 1, DM1, is a multi-systemic muscle wasting disorder that results from expression of expanded CTG repeats in the DMPK gene in humans. Three transgenic Drosophila melanogaster lines have been created containing 60, 250, or 480 CTG repeats to model DM1. The transgenic repeats are expressed using the GAL4/UAS system. Expression of long-repeat transgenes ((CTG)250 and i(CTG)480) produces phenotypes consistent with DM1, relative to control lines ((CTG)60). The precise chromosomal location of insertion of the transgenes has not been reported. We used classical genetic approaches to localize CTG-repeat transgene insertion to a specific …


Characterization Of Toxoplasma Gondii Calcium Regulator Proteins Tggt1_253640 And Tggt1_222060 For Toxoplasma Gondii Growth And Invasion, Abigail Delapenha Apr 2023

Characterization Of Toxoplasma Gondii Calcium Regulator Proteins Tggt1_253640 And Tggt1_222060 For Toxoplasma Gondii Growth And Invasion, Abigail Delapenha

Departmental Honors & Graduate Capstone Projects

Toxoplasma gondii is an opportunistic apicomplexan parasite infecting humans and livestock. Infection in immunocompromised individuals can cause neurological damage and infection during pregnancy can lead to fetal death. These parasites engage in a complex life cycle, involving repeated invasion of the host cell and egress from the host cell. Calcium signaling is an important regulatory mechanism for many essential processes in the parasite, including gliding motility (actomyosin-dependent mode of motion), invasion, and egress. Our work here focuses on two previously uncharacterized calcium regulator proteins (TGGT1_253640 and TGGT1_222060). To characterize the role of these proteins in parasite viability and calcium regulation, …


Increased Breast And Colorectal Cancer Risk In Type 2 Diabetes: Awareness Among Adults With And Without Diabetes And Information Provision On Diabetes Websites, Laura Ashley, Kathryn A Robb, Daryl B O'Connor, Rebecca Platt, Mollie Price, Olivia Robinson, Elizabeth Travis, Lorraine Lipscombe, Ramzi Ajjan, Rebecca Birch Apr 2023

Increased Breast And Colorectal Cancer Risk In Type 2 Diabetes: Awareness Among Adults With And Without Diabetes And Information Provision On Diabetes Websites, Laura Ashley, Kathryn A Robb, Daryl B O'Connor, Rebecca Platt, Mollie Price, Olivia Robinson, Elizabeth Travis, Lorraine Lipscombe, Ramzi Ajjan, Rebecca Birch

Faculty, Staff and Student Publications

BACKGROUND: People with type 2 diabetes mellitus (T2DM) have a higher risk of developing breast and bowel cancers but are less likely to participate in cancer screening.

PURPOSE: Two interlinked studies examined public awareness of the fact that T2DM increases breast and bowel cancer risk, and provision of this information on diabetes websites.

METHODS: Study-1: phase-1 surveyed awareness of T2DM-increased cancer risk in a nationally-representative British sample aged 50-74 (N = 1,458) and compared respondents with and without T2DM (n = 125 vs. n = 1,305); phase-2 surveyed an additional exclusively T2DM sample (N = 319). Study-2: High-ranking diabetes websites …


A Potential Role Of Gsk-3beta In The Development Of Pain Post-Spinal Cord Injury, Emily Ernst Apr 2023

A Potential Role Of Gsk-3beta In The Development Of Pain Post-Spinal Cord Injury, Emily Ernst

Undergraduate Theses

Chronic neuropathic pain is a very common consequence following spinal cord injury (SCI) and poses significant clinical challenge. Current treatments are largely ineffective and as a result, patients are often left with debilitating pain at and below the level of the spinal cord injury. After spinal injury, a cascade of events occurs within the nervous system. One important aspect of this cascade for investigation is the anatomical changes that occur post-SCI. There is evidence of maladaptive sprouting/growth in sensory nerve fibers that is thought to play a role in the development and amplification of pain signals. Sprouting of primary afferents …


Characterizing Movement Patterns Of Nomadic Pastoralists And Their Exposure To Rift Valley Fever In Kenya, G. Mosomtai, J. L. Kasiiti, R. M. Murithi, P. Sandström, T. Landmann, O. W. Lwande, O. A. Hassan, C. Ahlm, R. Sang, M. Evander, Z. Szantoi, G. Ottavianelli Apr 2023

Characterizing Movement Patterns Of Nomadic Pastoralists And Their Exposure To Rift Valley Fever In Kenya, G. Mosomtai, J. L. Kasiiti, R. M. Murithi, P. Sandström, T. Landmann, O. W. Lwande, O. A. Hassan, C. Ahlm, R. Sang, M. Evander, Z. Szantoi, G. Ottavianelli

All Peer-Reviewed Publications

The role of animal movement in spreading infectious diseases is highly recognized by various legislations and institutions such as the World Organisation for Animal Health and the International Animal Health Code. The increased interactions at the nexus of human-animal-ecosystem interface have seen an unprecedented introduction and reintroduction of new zoonotic diseases with high socio-economic impacts such as the COVID-19 pandemic. Rift Valley fever (RVF) is a zoonotic disease that affects both humans and animals and is transmitted by Aedes mosquitoes or through contact with the body fluids of infected animals. This study seeks to characterize movement patterns of pastoralist and …


A Meta-Narrative Review: Efficacy Of Non-Invasive Prenatal Testing (Nipt) In The Detection Of Sex Chromosomal Aneuploidy In Singleton Pregnancy, Tien T. Dao, Arianna Fields, Annie Huynh, Nikkita Mcghee, Christian Pellegrini Apr 2023

A Meta-Narrative Review: Efficacy Of Non-Invasive Prenatal Testing (Nipt) In The Detection Of Sex Chromosomal Aneuploidy In Singleton Pregnancy, Tien T. Dao, Arianna Fields, Annie Huynh, Nikkita Mcghee, Christian Pellegrini

Research Methods Poster Session 2023

Abstract:

Objective: To assess the efficacy of Noninvasive Prenatal Testing (NIPT) as a screening method for Sex Chromosomal Aneuploidy (SCA) and its application in clinical practice.

Methods: Searches on Pubmed and M.D. Anderson Cancer Center Research Medical Library was performed to identify primary research articles published between January 2018 to April 2023.

Results: The average combined SCA's PPV was 46.08%. The average PPV for 45, X, 47, XXX, 47, XXY, and 47, XYY was 26.05%, 44.82%, 50.21%, and 62.99%, respectively. The average PPV for 46, XY was 1.18%; however, there is a lack of statistical data for 46, XY. NIPT …


Learning In A Virtual Environment To Improve Type 2 Diabetes Outcomes: Randomized Controlled Trial, Constance M Johnson, Gail D'Eramo Melkus, Louise Reagan, Wei Pan, Sathya Amarasekara, Katherine Pereira, Nancy Hassell, Sarah Nowlin, Allison Vorderstrasse Apr 2023

Learning In A Virtual Environment To Improve Type 2 Diabetes Outcomes: Randomized Controlled Trial, Constance M Johnson, Gail D'Eramo Melkus, Louise Reagan, Wei Pan, Sathya Amarasekara, Katherine Pereira, Nancy Hassell, Sarah Nowlin, Allison Vorderstrasse

Faculty, Staff and Student Publications

Background: Given the importance of self-management in type 2 diabetes mellitus (T2DM), a major aspect of health is providing diabetes self-management education and support. Known barriers include access, availability, and the lack of follow through on referral to education programs. Virtual education and support have increased in use over the last few years.

Objective: The purpose of the Diabetes Learning in a Virtual Environment (LIVE) study was to compare the effects of the LIVE intervention (educational 3D world) to a diabetes self-management education and support control website on diet and physical activity behaviors and behavioral and metabolic outcomes in adults …


The "Great Debate" At Melanoma Bridge 2022, Naples, December 1st-3rd, 2022, Paolo A Ascierto, Christian Blank, Alexander M Eggermont, Claus Garbe, Jeffrey E Gershenwald, Omid Hamid, Axel Hauschild, Jason J Luke, Janice M Mehnert, Jeffrey A Sosman, Hussein A Tawbi, Mario Mandalà, Alessandro Testori, Corrado Caracò, Iman Osman, Igor Puzanov Apr 2023

The "Great Debate" At Melanoma Bridge 2022, Naples, December 1st-3rd, 2022, Paolo A Ascierto, Christian Blank, Alexander M Eggermont, Claus Garbe, Jeffrey E Gershenwald, Omid Hamid, Axel Hauschild, Jason J Luke, Janice M Mehnert, Jeffrey A Sosman, Hussein A Tawbi, Mario Mandalà, Alessandro Testori, Corrado Caracò, Iman Osman, Igor Puzanov

Faculty, Staff and Student Publications

The Great Debate session at the 2022 Melanoma Bridge congress (December 1-3) featured counterpoint views from leading experts on five contemporary topics of debate in the management of melanoma. The debates considered the choice of anti-lymphocyte-activation gene (LAG)-3 therapy or ipilimumab in combination with anti-programmed death (PD)-1 therapy, whether anti-PD-1 monotherapy is still acceptable as a comparator arm in clinical trials, whether adjuvant treatment of melanoma is still a useful treatment option, the role of adjuvant therapy in stage II melanoma, what role surgery will continue to have in the treatment of melanoma. As is customary in the Melanoma Bridge …


Interrogating Bromodomain Inhibitor Resistance In Kmt2a-Rearranged Leukemia Through Combinatorial Crispr Screens, Shaela Wright, Jianzhong Hu, Hong Wang, Judith Hyle, Yang Zhang, Guoqing Du, Marina Y Konopleva, Steven M Kornblau, Mohamed Nadhir Djekidel, Wojciech Rosikiewicz, Beisi Xu, Rui Lu, Jun J Yang, Chunliang Li Apr 2023

Interrogating Bromodomain Inhibitor Resistance In Kmt2a-Rearranged Leukemia Through Combinatorial Crispr Screens, Shaela Wright, Jianzhong Hu, Hong Wang, Judith Hyle, Yang Zhang, Guoqing Du, Marina Y Konopleva, Steven M Kornblau, Mohamed Nadhir Djekidel, Wojciech Rosikiewicz, Beisi Xu, Rui Lu, Jun J Yang, Chunliang Li

Faculty, Staff and Student Publications

Bromo- and extra-terminal domain inhibitors (BETi) have exhibited therapeutic activities in many cancers. However, the mechanisms controlling BETi response and resistance are not well understood. We conducted genome-wide loss-of-function CRISPR screens using BETi-treated KMT2A-rearranged (KMT2A-r) cell lines. We revealed that Speckle-type POZ protein (SPOP) gene (Speckle Type BTB/POZ Protein) deficiency caused significant BETi resistance, which was further validated in cell lines and xenograft models. Proteomics analysis and a kinase-vulnerability CRISPR screen indicated that cells treated with BETi are sensitive to GSK3 perturbation. Pharmaceutical inhibition of GSK3 reversed the BETi-resistance phenotype. Based on this observation, a combination therapy regimen inhibiting both …


Association Of Suppressive Myeloid Cell Enrichment With Aggressive Oropharynx Squamous Cell Carcinoma, Changlin Yang, Rekha Garg, Kristanna Fredenburg, Frances Weidert, Hector Mendez-Gomez, Robert Amdur, Ji-Hyun Lee, Jamie Ku, Jesse Kresak, Stephanie Staras, Andrew G Sikora, Lily Wang, Daniel Mcgrail, Duane Mitchell, Elias Sayour, Natalie Silver Apr 2023

Association Of Suppressive Myeloid Cell Enrichment With Aggressive Oropharynx Squamous Cell Carcinoma, Changlin Yang, Rekha Garg, Kristanna Fredenburg, Frances Weidert, Hector Mendez-Gomez, Robert Amdur, Ji-Hyun Lee, Jamie Ku, Jesse Kresak, Stephanie Staras, Andrew G Sikora, Lily Wang, Daniel Mcgrail, Duane Mitchell, Elias Sayour, Natalie Silver

Faculty, Staff and Student Publications

BACKGROUND: While immune-cell infiltrated tumors, such as human papillomavirus positive (HPV+) ororpharyngeal squamous cell carcinomas (OPSCC) have been associated with an improved clinical prognosis, there is evidence to suggest that OPSCCs are also subjected to increased immunoregulatory influence. The objective of this study was to assess whether patients with clinically aggressive OPSCC have a distinct immunosuppressive immune signature in the primary tumor.

METHODS: This retrospective case-control study analyzed 37 pre-treatment tissue samples from HPV+ and HPV-negative OPSCC patients treated at a single institution. The cases were patients with known disease recurrence and the controls were patients without disease recurrence. An …


Cancer Cell-Extrinsic Roles For The Androgen Receptor In Prostate Cancer, Andrew W Hahn, Bilal A Siddiqui, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Cindy K Miranti, Daniel E Frigo Apr 2023

Cancer Cell-Extrinsic Roles For The Androgen Receptor In Prostate Cancer, Andrew W Hahn, Bilal A Siddiqui, Javier Leo, Eleonora Dondossola, Kaitlin J Basham, Cindy K Miranti, Daniel E Frigo

Faculty, Staff and Student Publications

Given the central role of the androgen receptor (AR) in prostate cancer cell biology, AR-targeted therapies have been the backbone of prostate cancer treatment for over 50 years. New data indicate that AR is expressed in additional cell types within the tumor microenvironment. Moreover, targeting AR for the treatment of prostate cancer has established side effects such as bone complications and an increased risk of developing cardiometabolic disease, indicating broader roles for AR. With the advent of novel technologies, such as single-cell approaches and advances in preclinical modeling, AR has been identified to have clinically significant functions in other cell …


Serinc5 Restricts Hiv Membrane Fusion By Altering Lipid Order And Heterogeneity In The Viral Membrane, Amanda E Ward, Daria Sokovikova, Melvin Neal Waxham, Frederick A Heberle, Ilya Levental, Kandice R Levental, Volker Kiessling, Judith M White, Lukas K Tamm Apr 2023

Serinc5 Restricts Hiv Membrane Fusion By Altering Lipid Order And Heterogeneity In The Viral Membrane, Amanda E Ward, Daria Sokovikova, Melvin Neal Waxham, Frederick A Heberle, Ilya Levental, Kandice R Levental, Volker Kiessling, Judith M White, Lukas K Tamm

Faculty, Staff and Student Publications

The host restriction factor, Serinc5, incorporates into budding HIV particles and inhibits their infection by an incompletely understood mechanism. We have previously reported that Serinc5 but not its paralogue, Serinc2, blocks HIV cell entry by membrane fusion, specifically by inhibiting fusion pore formation and dilation. A body of work suggests that Serinc5 may alter the conformation and clustering of the HIV fusion protein, Env. To contribute an additional perspective to the developing model of Serinc5 restriction, we assessed Serinc2 and Serinc5's effects on HIV pseudoviral membranes. By measuring pseudoviral membrane thickness via cryo-electron microscopy and order via the fluorescent dye, …


Mechanisms Of Response And Resistance To Combined Decitabine And Ipilimumab For Advanced Myeloid Disease, Livius Penter, Yang Liu, Jacquelyn O Wolff, Lin Yang, Len Taing, Aashna Jhaveri, Jackson Southard, Manishkumar Patel, Nicole M Cullen, Kathleen L Pfaff, Nicoletta Cieri, Giacomo Oliveira, Seunghee Kim-Schulze, Srinika Ranasinghe, Rebecca Leonard, Taylor Robertson, Elizabeth A Morgan, Helen X Chen, Minkyung H Song, Magdalena Thurin, Shuqiang Li, Scott J Rodig, Carrie Cibulskis, Stacey Gabriel, Pavan Bachireddy, Jerome Ritz, Howard Streicher, Donna S Neuberg, F Stephen Hodi, Matthew S Davids, Sacha Gnjatic, Kenneth J Livak, Jennifer Altreuter, Franziska Michor, Robert J Soiffer, Jacqueline S Garcia, Catherine J Wu Apr 2023

Mechanisms Of Response And Resistance To Combined Decitabine And Ipilimumab For Advanced Myeloid Disease, Livius Penter, Yang Liu, Jacquelyn O Wolff, Lin Yang, Len Taing, Aashna Jhaveri, Jackson Southard, Manishkumar Patel, Nicole M Cullen, Kathleen L Pfaff, Nicoletta Cieri, Giacomo Oliveira, Seunghee Kim-Schulze, Srinika Ranasinghe, Rebecca Leonard, Taylor Robertson, Elizabeth A Morgan, Helen X Chen, Minkyung H Song, Magdalena Thurin, Shuqiang Li, Scott J Rodig, Carrie Cibulskis, Stacey Gabriel, Pavan Bachireddy, Jerome Ritz, Howard Streicher, Donna S Neuberg, F Stephen Hodi, Matthew S Davids, Sacha Gnjatic, Kenneth J Livak, Jennifer Altreuter, Franziska Michor, Robert J Soiffer, Jacqueline S Garcia, Catherine J Wu

Faculty, Staff and Student Publications

The challenge of eradicating leukemia in patients with acute myelogenous leukemia (AML) after initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either after allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naïve setting. Integrative transcriptome-based analysis of 304 961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were …


Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla Apr 2023

Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla

Faculty, Staff and Student Publications

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A …


Molecular Mechanisms Of Ferroptosis And Updates Of Ferroptosis Studies In Cancers And Leukemia, Hiroki Akiyama, Bing Z Carter, Michael Andreeff, Jo Ishizawa Apr 2023

Molecular Mechanisms Of Ferroptosis And Updates Of Ferroptosis Studies In Cancers And Leukemia, Hiroki Akiyama, Bing Z Carter, Michael Andreeff, Jo Ishizawa

Faculty, Staff and Student Publications

Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is …


The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria Apr 2023

The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer’s disease (AD) but has limited blood–brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known. Given that amyloid and tau pathology are characteristics of AD, the effects of cTfRMAb-EPO were studied in a tauopathy mouse model (PS19). Six-month-old PS19 mice were injected intraperitoneally with either saline (PS19-Saline; n = 9) or cTfRMAb-EPO (PS19-cTfRMAb-EPO, 10 mg/kg; …