Medicine and Health Sciences Commons^™

Prevalence, Treatment Patterns, Burden, And Factors Related To Treatment Failure With Sodium-Glucose Cotransporter 2 Inhibitor In Adults With Type 2 Diabetes In The United States, Xi Tan, Yiwen Cao, Yan Wang, Joanna Boland, Mico Guevarra, Lin Xie, Yan Song, Min Ji Kwak

Faculty, Staff and Student Publications

Aims: To evaluate treatment failure of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among adults with type 2 diabetes (T2D) and assess associated risk factors and clinical and economic outcomes in the real-world setting.

Methods: Adults with T2D who initiated SGLT2i were selected from the Komodo's Healthcare Map, an administrative claims database (2016-2024). Treatment failure was defined as discontinuation, add-on/switching, or uncontrolled glycated hemoglobin (HbA1c) without action. Risk factors, treatment patterns, and clinical and economic burden were assessed.

Results: Among 237,295 eligible adults, the overall rate of treatment failure with SGLT2i was 77.3 %, with a median time to failure of 9.14 …

Empirical Tuberculosis Treatment In Human Immunodeficiency Virus (Hiv)-Associated Fever Of Unknown Origin: A Case-Based Rationale, Matthew Antonioli, Samantha H Antonioli, Gabriel M Aisenberg

Faculty, Staff and Student Publications

Fever of unknown origin (FUO) in people living with human immunodeficiency virus (PLHIV) is clinically defined as recurrent fever lasting more than four weeks in the outpatient setting or more than three days during hospitalization, despite a thorough diagnostic evaluation. This evaluation typically includes a comprehensive medical history, physical examination, imaging studies (such as chest radiography), and an extensive range of laboratory tests, including complete blood counts, blood and urine cultures, and metabolic panels. Among the many possible causes, tuberculosis (TB) stands out as a leading concern, given its disproportionate burden in PLHIV. However, whether to initiate empirical anti-tubercular therapy …

Venoarterial Extracorporeal Membrane Oxygenation Is A Feasible Option For Patients With Pregnancy-Associated Diagnoses Who Require Mechanical Circulatory Support, Trishna Parikh, Sabiha Armin, Saad Afzal Khan, Adishwar Rao, Akriti Agrawal, Dev Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used in patients with cardiopulmonary collapse, but data regarding its use in pregnancy is limited. We aimed to identify the clinical characteristics and predictors of in-hospital mortality in female patients requiring VA-ECMO, including evaluating the role of pregnancy.

Methods: In this cross-sectional study, a cohort of female patients aged 19-45 years who required VA-ECMO were identified from the National Inpatient Sample from 2018 to 2021 and further stratified according to presence of pregnancy-associated diagnoses. Baseline characteristics were compared using Pearson chi-square test and Wilcoxon rank-sum test for categorical and continuous variables, respectively. Multivariate …

Ten Practical Tips For A Successful Presentation At An Infectious Disease Clinical Case Conference, Takahiro Matsuo, Pablo C Okhuysen, Ben J Barnett

Faculty, Staff and Student Publications

This mini-review provides 10 practical tips for infectious disease trainees presenting at clinical case conferences. These tips, grounded in principles from education theory, aim to enhance the effectiveness of case presentations.

An Ectopic Pancreatic Mass Inducing Gastric Outlet Obstruction, Rohan Ahuja, Samir Mehta, Nakia Armendariz, Jimmy Q Pham, Madhav Desai

Faculty, Staff and Student Publications

Gastric outlet obstruction (GOO) is a clinical diagnosis characterized by early satiety, abdominal pain, post-prandial vomiting, and weight loss. Here, we present a rare case of an ectopic pancreatic cyst inducing GOO, highlighting the importance of a thorough diagnostic workup. A 40-year-old man with no prior medical or surgical history presented with a six-month history of intermittent epigastric pain, nausea, and vomiting with an inability to tolerate oral intake for a week. CT of the abdomen and pelvis revealed a 4.5 × 3.0 × 2.9 cm, well-circumscribed, peripherally enhancing cystic lesion in the distal pylorus. Initial esophagogastroduodenoscopy (EGD) revealed an …

Exploring Differential Impacts Of A Parent Intervention On Reading And Toy Play Across Ethnic And Linguistic Groups, Sarah Surrain, Susan H. Landry, Tricia A. Zucker, Yoonkyung Ch

Faculty, Staff and Student Publications

The ways that parents respond to their children’s initiations and guide their learning are associated with subsequent language development. Responsive parenting interventions have shown positive impacts on parent behaviors and child outcomes. However, less is known about how intervention effects vary for families from different linguistic and ethnic backgrounds. This secondary analysis of a randomized controlled trial of Play and Learning Strategies examines the effect of the intervention for three subgroups: Spanish-dominant Latine families (n = 142), English-dominant Latine families (n = 112), and non-Latine families (n = 137). Parents of preschool-aged children (M age = …

Breast And Prostate Cancer Survivors’ Understanding Of Risk And Management Of Cardiovascular And Musculoskeletal Side Effects Of Treatment: Findings From Focus Groups, Jack Dalla Via, Chris R. Andrew, Brenton J. Baguley, Nina Stewart, Jonathan M. Hodgson, Joshua R. Lewis, Mandy Stanley, Mary A. Kennedy

Research outputs 2022 to 2026

Purpose: Survival after a cancer diagnosis is improving, increasing the importance of understanding and managing long-term treatment-related adverse effects. This study aimed to understand breast and prostate cancer survivors’ understanding of how cancer treatment may affect cardiovascular and musculoskeletal health. Methods: Australian breast and prostate cancer survivors treated with therapies with known cardiovascular adverse effects were recruited via a private cancer care provider. Participants completed an online background questionnaire, then participated in a focus group. Focus groups were recorded, transcribed, then analysed using reflexive thematic analysis. Results: In total, 26 cancer survivors (15 breast, 11 prostate; mean age 67 years) …

Understanding Perceptions, Attitudes And Experiences Of Nursing Students During Clinical Placement In Primary Health Care Settings – A Scoping Review, Debbie Procter, Kylie Mccullough, Debbie Massey, Karen Strickland

Research outputs 2022 to 2026

Aims: Critically analyse literature on undergraduate nursing students' perceptions, attitudes and experiences during Primary Health Care (PHC) placements and identify factors influencing their satisfaction. These insights may improve educational outcomes, shape career intentions and address workforce shortages. Background: Global nursing shortage, driven by increased demands and high attrition, impacts healthcare worldwide. Australia faces projected shortfalls of 79,473 nurses by 2035, significantly in PHC. Attributing factors include remuneration disparities, inadequate training/mentorship and limited career pathways. Strengthening the PHC nursing workforce is crucial, with undergraduate nursing students providing an important workforce pipeline. Design/Method: Scoping Review protocol was registered using Joanna Briggs Institute's …

A Cross-Sectional Examination Of Missed Infection Control Practices Among Nurses In The Jordanian Hospitals, Muhammad Ahmed Alshyyab, Rania Ali Albsoul, Gerard Fitzgerald, Diana Arabiat

Research outputs 2022 to 2026

Background: Missed infection control practices may negatively impact quality healthcare and patient safety in acute health care settings. Hence, more research is urgently needed especially in Arab countries. To investigate the elements and reasons of missed infection control activities among nurses in Jordan. The sociodemographic correlates with missed infection control activities were also examined. Methods: A cross sectional design was utilized in this study. A convenience sample of 960 nurses from seven hospitals in the North of Jordan was used. The Missed Nursing Care Infection Prevention and Control (MNCIPC) Survey was employed to collect the data. Data were analyzed using …

Foundations And Strategic Vision Of The Canadian Translational Geroscience Network, Guy Hajj-Boutros, Andréa Faust, John Muscedere, Perry Kim, Gilles Gouspillou, Lea Harrington, James L. Kirkland, George A. Kuchel, Jeremy Van Raamsdonk, R. Jane Rylett, Chantal Autexier, Louis R. Lapierre, Michael Kobor, Mohammad Auais, Ann Beliën, Jeroen Aerssens, George Sutphin, Kenneth Rockwood, Alexandra Papaioannou, Marc Sim, Jamie Justice, Nancy Mayo, Gustavo Duque

Research outputs 2022 to 2026

Geroscience is an emerging interdisciplinary field that explores the biological connections between aging and the development of chronic diseases, with the ultimate goal of identifying interventions to extend healthspan and delay age-related conditions. Recognizing the growing importance of this field, the Canadian Translational Geroscience Network (geroscience.ca) was officially launched during a conference held in Montreal on September 5-6, 2024. Building on the momentum of successful Geroscience meetings in Toronto and Montreal in 2023, this milestone event marked a transformative step forward for geroscience in Canada. This event brought together key stakeholders, including the Canadian Frailty Network (CFN), the Canadian Institutes …

Translating Advocacy Into Action: Exploring Oncology Healthcare Professionals’ Awareness And Use Of The Clinical Oncology Society Of Australia Position Statement On Exercise In Cancer Care, Jack Dalla Via, Francesca Cehic, Carolyn J. Peddle-Mcintyre, Christopher R. Andrew, David Mizrahi, Yvonne Zissiadis, Nigel A. Spry, Robert U. Newton, Mary A. Kennedy

Research outputs 2022 to 2026

Purpose: The Clinical Oncology Society of Australia (COSA) position statement on exercise in cancer care encourages all healthcare professionals to discuss, recommend, and refer people with cancer to exercise; however, use of these recommendations in practice is unknown. Methods: Oncology healthcare professionals working in Australia were invited to complete a cross-sectional online survey that assessed contextual factors that influence implementation of COSA exercise guidance in cancer care, based on the Consolidated Framework for Implementation Research. Results: We received 133 survey responses. Most were women (74%), nurses (35%), or oncologists (26%), involved in cancer care for > 10 years (63%), and in …

Models Of Care For Indigenous Children In Rural And Remote Settings: A Global Scoping Review, Joseph Freeman, Thomas Stubbs, Verity Chadwick, Anita Pickard, Tuguy Esgin, Elizabeth J. Elliott, Alexandra Martiniuk

Research outputs 2022 to 2026

Indigenous communities internationally have demonstrated remarkable strength despite significant challenges. Health disparities among Indigenous peoples persist due to historical injustices and ongoing racial discrimination, not inherent vulnerabilities. Disparities are rooted in a legacy of colonisation, systemic exclusion, and socio-economic inequities impacting access to healthcare, education, and employment. Preliminary searches show limited literature on models of care for remote living Indigenous children. This review aimed to identify internationally, effective models of care for Indigenous children in rural and remote areas. A scoping review was conducted, analysing literature on models of care for remote Indigenous children. This study followed the JBI’s Scoping …

The Association Between Sexually Transmitted Infections And Pregnancy Outcomes In The Northern Territory, Australia: A Population-Based Cohort Study, Jennifer Dunne, Gizachew A. Tessema, Matthew Legge, Sylvester Dodzi Nyadanu, Aditi Roy, Amanuel T. Gebremedhin, Jacqueline Hendriks, Tricia Reid-Moore, Gavin Pereira

Research outputs 2022 to 2026

Background: Often asymptomatic in nature, sexually transmitted infections (STIs) are highly prevalent in women of reproductive ages, leading to adverse perinatal outcomes. This study investigated the association between STIs during pregnancy and the risk of adverse perinatal outcomes using comprehensive population-linked data from the Northern Territory (NT), Australia. Methods: This population-based retrospective cohort study examined births (live births and stillbirths) from the NT Perinatal Data Collection and the NT Notifiable Diseases register from 2005 to 2020. All singleton births (N = 59,465) were included, along with infectious disease notifications of four STIs that occurred during pregnancy: chlamydia, gonorrhoea, trichomoniasis, and …

Tissue Engineering: History, Principles, Applications, Challenges, And Future Work, Alexa Cesari, Ms

Student Papers, Posters & Projects

Tissue engineering is a comprehensive and cutting-edge field that leverages principles from multiple scientific disciplines to assist in regenerative medicine. It is defined by the most basic structure of the human body, the cell. When an injury occurs, cells send signals to initiate wound healing processes. In most cases, the body is equipped to heal wounds on its own; however, there are instances where wounds are too severe and cannot undergo proper regeneration. When this occurs, alternative measures are taken to assist in wound repair. With numerous advancements made over the years, tissue engineering has become an increasingly common method …

A Late Presentation Of Benign Cephalic Histiocytosis, Madison A. Hackley, Nicholas D. Brownstone, Shayan Waseh, Simo Huang, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Subclinical Hyperthyroidism Presenting As Urinary Frequency And Polyuria: A Case Report., Hameed H Salah, Elizabeth M Pines

Ambulatory and Primary Care Articles

Hyperthyroidism may present with a variety of symptoms including urinary frequency. This report discusses a case of subclinical hyperthyroidism presenting as generalized weakness, urinary frequency, polyuria, and intermittent diarrhea. However, this elderly patient had a complex past medical history including multinodular nontoxic thyroid goiter with tracheal deviation and multiple recent admissions for aspiration pneumonia, making the diagnosis of subclinical hyperthyroidism less obvious. The patient was managed with intravenous fluids and discharged on propranolol with recommendations to follow-up with endocrinology. This case demonstrates the importance of keeping hyperthyroidism on the differential for urinary frequency and polyuria without other clear etiologies.

Appendicitis, Children's Mercy Kansas City

Clinical Pathways (Formally Known As Care Process Models)

No abstract provided.

Cardiovascular Manifestations Of Pseudoxanthoma Elasticum., Aimee Willett, Vivek V Jasti, Sean M Muir, Jay Anderson

Ambulatory and Primary Care Articles

Pseudoxanthoma elasticum (PXE) is a rare systemic disorder of elastic fibers. The most common manifestations include characteristic papules and ocular angioid streaks. Cardiovascular complications include peripheral arterial disease, hypertension, premature coronary artery disease, and cerebrovascular disease. These associations are secondary to dystrophic elastic fibers, resulting in the calcification of small- to medium-sized arteries. We present the case of a 22-year-old otherwise healthy female patient diagnosed with PXE following a biopsy of a neck lesion. Ophthalmologic evaluation revealed characteristic angioid streaks. The patient also reported early satiety and leg cramping, which prompted referral to gastroenterology and cardiology. Further investigation raised concern …

Oatp1b1/1b3 Deficiency Exacerbates Hyperbilirubinemia In Erythropoietic Protoporphyria, Ruizhi Gu, Fu-Ying Qin, Luxuan Wang, Jiaojiao Zhang, Jacob Emerson, Qing Ma, Jie Lu, Karl E Anderson, Junmei Wang, Xiaochao Ma

Faculty, Staff and Student Publications

Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in ferrochelatase (FECH), leading to the accumulation of its substrate, protoporphyrin IX (PPIX). PPIX is primarily produced in the bone marrow and transported to the liver for excretion. Because PPIX is hydrophobic, its elevated levels can cause bile duct blockage, cholestatic liver injury, and even liver failure. However, the specific transporter responsible for PPIX uptake into hepatocytes remains unclear. The OATP1B1/1B3 transporters, which are expressed in hepatocytes, facilitate the uptake of coproporphyrin III, a structural analog of PPIX. Additionally, OATP1B1/1B3 mediates the uptake of bilirubin, a biomarker of liver injury, from plasma …

Outcomes And Toxicity Following 3 Or More Definitive Courses Of Thoracic Radiation Therapy For Non-Small Cell Lung Cancer, Abigael Odwuor, Percy Lee, Joe Y Chang, Saumil Gandhi, Zhongxing Liao, Steven H Lin, Aileen Chen, Quynh-Nhu Nguyen, Michael S O'Reilly, Stephen G Chun, Julianna Bronk, David Qian, Matthew S Ning

Faculty, Staff and Student Publications

Purpose: Salvage re-irradiation is increasingly utilized to manage non-small cell lung cancer (NSCLC) locoregional recurrence or new lung primaries in previously treated areas. There is sparse information on efficacy and toxicity profile. We report a large experience of patients treated with multiple courses of definitive radiation for new and recurrent NSCLC.

Methods and materials: Medical records of patients who underwent ≥ 3 definitive thoracic radiation therapy (RT) courses for new or recurrent NSCLC at our cancer center from 2012 through 2021 were retrospectively reviewed following institutional review board approval. Toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) …

Heat Shock Induces Alternative Polyadenylation Through Dynamic Dna Methylation And Chromatin Looping, Emily E Fink, Yi Zhang, Briana Santo, Anwita Siddavatam, Rosie Ou, Vishal Nanavaty, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Alternative cleavage and polyadenylation (APA) is a gene regulatory mechanism used by cells under stress to upregulate proteostasis-promoting transcripts, but how cells achieve this remains poorly understood. Previously, we elucidated a DNA methylation-regulated APA mechanism, in which gene body DNA methylation enhances distal poly(A) isoform expression by blocking CCCTC-binding factor (CTCF) binding and chromatin loop formation at APA control regions. We hypothesized that DNA methylation-regulated APA is one mechanism cells employ to induce proteostasis-promoting poly(A) isoforms. At the DNAJB6 cochaperone locus, acute heat shock resulted in binding of stress response transcription factors heat shock factor 1, ATF6, and YY1 at …

Ovarian Cancer Risk And Survival According To Tumor Sex Hormone Receptor Expression: An Ovarian Cancer Association Consortium And Ovarian Tumor Tissue Analysis Consortium Pooled Analysis, Zhuxuan Fu, Lauren Borho, Sarah E Taylor, Linda E Kelemen, Anna Defazio, Penelope M Webb, Martin Köbel, Nicola S Meagher, Renhua Na, Antonis C Antoniou, Alison H Brand, Catherine J Kennedy, Nikilyn Nevins, Paul D P Pharoah, Yurii B Shvetsov, Stacey J Winham, Jennifer Alsop, Matthias W Beckmann, Adelyn Bolithon, Jessica Boros, David D L Bowtell, James D Brenton, Michael E Carney, Anita Chudecka-Głaz, Linda S Cook, Cezary Cybulski, Peter A Fasching, Sian Fereday, Renée T Fortner, María J García, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Arndt Hartmann, Brenda Y Hernandez, Estrid Høgdall, David G Huntsman, Allan Jensen, Mercedes Jimenez-Linan, Janine M Joseph, Beth Y Karlan, Ewa Kaznowska, Susanne K Kjaer, Tomasz Kluz, Jennifer M Koziak, Jenny Lester, Teri A Longacre, Maria Lycke, Valerie Mcguire, Kirsten B Moysich, Rachel A Murphy, Sandra Orsulic, Susan J Ramus, Cristina Rodríguez-Antona, Joseph H Rothstein, Spinder Samra, Weiva Sieh, Helen Steed, Karin Sundfeldt, Aline Talhouk, Jan Uciński, Chen Wang, Nicolas Wentzensen, Alice S Whittemore, Lynne R Wilkens, Thomas Songer, Maria Mori Brooks, Lu Tang, Francesmary Modugno

Faculty, Staff and Student Publications

Objective: Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.

Method: We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) between hormonally-linked factors and tumor AR/ER/PR expression using polytomous logistic regression. We assessed survival by AR/ER/PR tumor expression overall and …

Renal G Protein-Coupled Estrogen Receptor 1 Regulates The Epithelial Sodium Channel Promoting Natriuresis To A Greater Extent In Females, Victoria L Nasci, Jean C Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh M Pochynyuk, James D Stockand, Eman Y Gohar

Faculty, Staff and Student Publications

Hypertension prevalence is lower in women than men. Enhanced renal sodium (Na+) handling in females has been implicated in sex-differences in hypertension. Epithelial Na+ channel (ENaC) is a key contributor to Na+ homeostasis and is regulated by estrogen. Recent evidence suggests G protein-coupled estrogen receptor 1 (GPER1) evokes a female-specific natriuresis that involves endothelin-1 (ET-1). ET-1 has been shown to downregulate ENaC activity, but whether GPER1 regulates ENaC to modulate natriuresis is unknown. We tested the hypothesis that renal GPER1 functionally interacts with ENaC to promote natriuresis in a sex-specific manner. RNAscope confirmed co-expression of GPER1 and ENaC in rat …

Protocol To Detect M22g Modification On Single Trna Iso-Decoders By Immuno-Northern Blotting, Sseu-Pei Hwang, Katherine Barondeau, Catherine Denicourt

Faculty, Staff and Student Publications

tRNA modifications are highly dynamic and play crucial roles in regulating gene expression. Here, we present an assay for analyzing N2, N2-dimethylguanosine (m22G) modifications on tRNAs using an antibody-based detection approach. We describe steps for isolating tRNAs from human cells via ion-exchange chromatography, capturing specific tRNA iso-decoders on streptavidin magnetic beads, and detecting modifications through immuno-northern blotting. This approach enables researchers to investigate other tRNA modifications using specific antibodies or downstream approaches such as mass spectrometry.

Childhood Obesity Body Mass Index And Gut Microbiome: A Cluster Randomized Controlled Pilot Feasibility Study, Marilyn Frenn, Nita Salzman, Vy Lam, Mary Holtz, Andrea Moosreiner, Mauricio Garnier-Villarreal, Maharaj Singh

College of Nursing Faculty Research and Publications

Background:

Prebiotic fiber has been examined as a way to foster gut bacteria less associated with obesity. Tests of prebiotic fiber in reducing obesity have occurred mainly in animals, adults, and Caucasians when the highest obesity rates are in African American and Latinx youth. Response to prebiotic fiber is determined by the pre-existing intestinal microbiota. The type of microbiota varies based on diet and physical activity (PA), so it is important to examine acceptability and response to prebiotic fiber in those most at risk for obesity.

Methods:

This cluster randomized controlled feasibility trial included an online program designed to improve …

Crem Is A Regulatory Checkpoint Of Car And Il-15 Signalling In Nk Cells, Hind Rafei, Rafet Basar, Sunil Acharya, Yu-Sung Hsu, Pinghua Liu, Deqiang Zhang, Toszka Bohn, Qingnan Liang, Vakul Mohanty, Ranjan Upadhyay, Ping Li, Pravin Phadatare, Merve Dede, Donghai Xiong, Huihui Fan, Corry Mathew Jones, Sebastian Kunz, May Daher, Ana Karen Nunez Cortes, Mayra Shanley, Bin Liu, Sadie Mae Moseley, Chenyu Zhang, Dexing Fang, Pinaki Banerjee, Nadima Uprety, Ye Li, Rejeena Shrestha, Xinhai Wan, Hong Shen, Vernikka Woods, April Lamour Gilbert, Seema Rawal, Jinzhuang Dou, Yukun Tan, Jeong-Min Park, Francia Reyes Silva, Alexander Biederstädt, Mecit Kaplan, Xin Ru Jiang, Inci Biederstädt, Bijender Kumar, Silvia Tiberti, Madison Moore, Jingling Jin, Ryan Z Yang, Luis Muniz-Feliciano, Samuel Rosemore, Paul Lin, Gary M Deyter, Natalie Wall Fowlkes, Abhinav K Jain, David Marin, Anirban Maitra, Ken Chen, Tobias Bopp, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer1-3. However, the molecular mechanisms that regulate CAR-NK cell activity remain unclear. Here we identify the transcription factor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function. Transcriptomic analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector function after adoptive transfer in a tumour mouse model, and this peak coincided with signatures of both activation and dysfunction. We demonstrate that both CAR activation and interleukin-15 signalling rapidly induce CREM upregulation in NK cells. Functionally, CREM …

Histone Lysine Methyltransferases Mll3 And Mll4 Direct Gene Expression To Produce Platelets Efficiently, Guozhen Gao, Josimar Dornelas Moreira, Prosun Das, Kevin Lin, Kai Ge, Taiping Chen, Yue Lu, Margarida A Santos

Faculty, Staff and Student Publications

Circulating blood platelets are responsible for maintaining hemostasis. They are released into blood vessels from mature megakaryocytes. Although several transcription factors have been reported to orchestrate the transcriptional programs required for platelet production, how chromatin regulators control these processes is still poorly understood. MLL3 and MLL4 are the main lysine methyltransferases responsible for the deposition of H3K4me1 histone marks at enhancers. MLL3 and MLL4 typically form complexes with other co-factors, such as PTIP. Recently, we showed that loss of PTIP leads to decreased platelet numbers in mice. Here, we find that, although MLL3/4 double deficiency does not alter megakaryopoiesis and …

Using Meta-Analysis: What Exercise Helps Kids With Excess Weight The Most?, Marilyn Frenn

College of Nursing Faculty Research and Publications

No abstract provided.

Polaris: Encorafenib Plus Binimetinib For People With Braf V600-Mutant Melanoma With Brain Metastasis, Alexander M Menzies, Michael A Davies

Faculty, Staff and Student Publications

POLARIS was a study to evaluate different doses of encorafenib plus binimetinib for people with BRAF V600-mutant melanoma with brain metastasis. The first part, known as the safety lead-in, looked at a high dose of encorafenib (300 mg twice daily) combined with standard binimetinib (45 mg twice daily); in the phase 2 part, patients were given the standard dose of encorafenib (450 mg once daily) plus binimetinib. In the safety lead-in, many patients were unable to tolerate the high dose of encorafenib plus binimetinib. Despite recruitment challenges in POLARIS, in the 13 enrolled patients with unresectable metastatic BRAF V600-mutant melanoma …

First-In-Human Phase 1 Study Of Khk2455 Monotherapy And In Combination With Mogamulizumab In Patients With Advanced Solid Tumors, Timothy A Yap, Olivier Rixe, Capucine Baldini, Ursa Brown-Glaberman, Sergey Efuni, David S Hong, Christophe Massard, Jameel Muzaffar, Andreea Varga, Emrullah Yilmaz, Yuta Ikawa, Lisa H Shiue, Yi Liu, Matthew W Hruska, Henry Zhao, Akihiro Tokunaga, Solmaz Sahebjam

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that degrades tryptophan (Trp) to kynurenine (Kyn), which suppresses effector T cells and reduces antitumor activity. KHK2455 is a long-acting selective IDO1 inhibitor that blocks the heme component of the IDO holoenzyme. Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody targeting CCR4. KHK2455 + mogamulizumab demonstrated enhanced antitumor activity in preclinical studies, which led to a first-in-human, two-part, multicenter, open-label, phase 1, dose-escalation, cohort-expansion trial (ClinicalTrials.gov identifier NCT02867007) evaluating the safety/tolerability, pharmacokinetics, and IDO1 activity of KHK2455 alone and in combination with mogamulizumab in patients with treatment-refractory advanced solid tumors. …