Medicine and Health Sciences Commons^™

Personalized Trial Ethics And Institutional Review Board Submissions, Joyce P Samuel, Susan H Wootton

Faculty, Staff and Student Publications

The ethical and regulatory oversight of any clinical activity related to human subjects is commonly determined based on its categorization as either clinical practice or research. Prominent bioethicists have criticized the traditional distinctions used to delineate these categories, calling them counterproductive and outmoded, and arguing that learning and clinical practice should be deliberately and appropriately integrated. Personalized trials represent a clinical activity with characteristics that overlap both categories, making ethical and regulatory oversight requirements less straightforward. When the primary intent of the personalized trial is to assist in the conduct of individualized patient care with an emphasis on protecting the …

Boosting The Electron Beam Transmittance Of Field Emission Cathode Using A Self-Charging Gate, Dongyang Xiao, Huanhuan Du, Leimeng Sun, Xiaochen Suo, Yurong Wang, Yili Zhang, Shaolin Zhang, Shuangyang Kuang, Fangjing Hu, Liangcheng Tu, Daren Yu, Peiyi Song

Faculty, Staff and Student Publications

The gate-type carbon nanotubes cathodes exhibit advantages in long-term stable emission owing to the uniformity of electrical field on the carbon nanotubes, but the gate inevitably reduces the transmittance of electron beam, posing challenges for system stabilities. In this work, we introduce electron beam focusing technique using the self-charging SiN_x/Au/Si gate. The potential of SiN_x is measured to be approximately −60 V quickly after the cathode turning on, the negative potential can be maintained as the emission goes on. The charged surface generates rebounding electrostatic forces on the following electrons, significantly focusing the electron beam on the …

Evaluating Noninvasive Brain Stimulation To Treat Overactive Bladder In Individuals With Multiple Sclerosis: A Randomized Controlled Trial Protocol, Betsy H Salazar, Kristopher A Hoffman, John A Lincoln, Christof Karmonik, Hamida Rajab, Santosh A Helekar, Rose Khavari

Faculty, Staff and Student Publications

Background

Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD.

Methods

By employing an advanced neuro-navigation …

Prevention And Potential Treatment Strategies For Respiratory Syncytial Virus, Bo-Wen Sun, Peng-Peng Zhang, Zong-Hao Wang, Xia Yao, Meng-Lan He, Rui-Ting Bai, Hao Che, Jing Lin, Tian Xie, Zi Hui, Xiang-Yang Ye, Li-Wei Wang

Faculty, Staff and Student Publications

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and …

Dementia Prediction In Older Adults Using Sex-Specific Health Trajectory Clustering, Omar A Ibrahim, Muskan Garg, Sunyang Fu, Maria Vassilaki, Ronald C Petersen, Jennifer St Sauver, Sunghwan Sohn

Faculty, Staff and Student Publications

With increasing number of people living with dementia, the problem of late diagnosis significantly impacts a person's quality of life while early signs of dementia may provide useful insights to facilitate better treatment plans. With time, this progressive neurodegenerative syndrome could progress from mild cognitive impairment to dementia. A pattern of health conditions can be characterized in unsupervised manner to help predict this progress. As a significant extension to our previous work with streaming clustering model, we consider additional information for predicting dementia onset. With empirical observations, we discover the importance of examining sex and age to predict dementia onset. …

Interplay Between Atrx And Idh1 Mutations Governs Innate Immune Responses In Diffuse Gliomas, Seethalakshmi Hariharan, Benjamin T Whitfield, Christopher J Pirozzi, Matthew S Waitkus, Michael C Brown, Michelle L Bowie, David M Irvin, Kristen Roso, Rebecca Fuller, Janell Hostettler, Sharvari Dharmaiah, Emiley A Gibson, Aaron Briley, Avani Mangoli, Casey Fraley, Mariah Shobande, Kevin Stevenson, Gao Zhang, Prit Benny Malgulwar, Hannah Roberts, Martin Roskoski, Ivan Spasojevic, Stephen T Keir, Yiping He, Maria G Castro, Jason T Huse, David M Ashley

Faculty, Staff and Student Publications

Stimulating the innate immune system has been explored as a therapeutic option for the treatment of gliomas. Inactivating mutations in ATRX, defining molecular alterations in IDH-mutant astrocytomas, have been implicated in dysfunctional immune signaling. However, little is known about the interplay between ATRX loss and IDH mutation on innate immunity. To explore this, we generated ATRX-deficient glioma models in the presence and absence of the IDH1R132H mutation. ATRX-deficient glioma cells are sensitive to dsRNA-based innate immune agonism and exhibit impaired lethality and increased T-cell infiltration in vivo. However, the presence of IDH1R132H dampens baseline expression of key innate immune genes …

Building A More Diverse Public Health Informatics Workforce: Preliminary Results, Susan H Fenton, Gabriela Mustata Wilson

Faculty, Staff and Student Publications

The US public health infrastructure has been historically underfunded, a condition that was exacerbated by the COVID-19 pandemic. This was especially noted in the area of public health informatics. It was also acknowledged that the lack of a diverse public health workforce made it more difficult to address biases and disparities effectively. In 2021 the Office of the National Coordinator awarded $73 million to 10 awardees to develop public health informatics and technology (PHIT) workforce training. The Gaining Equity in Training for Public Health Informatics and Technology (GET PHIT) award utilizes various methods to train and engage minority and underserved …

Insights On The Future Of Digital Health: An Analysis Of Twitter Posts Of Imia Fellows, David T Marc, Karima Lalani, Susan H Fenton, Kerryn Butler-Henderson

Faculty, Staff and Student Publications

The COVID-19 pandemic has reshaped technology-enhanced services in health and care organizations globally. As the world pivots towards a post-COVID-19 environment, it is essential to examine emerging trends amongst thought leaders in the health information technology sector. This study queried Twitter feeds of IMIA Fellows from 2013 through 2022, utilizing combinations of sentiment analysis, latent dirichlet allocation, and document analysis methods. The results provided a glimpse of positive sentiment year upon year, with the most negative sentiment prevalent in 2020, due to the onset of the pandemic. The findings from this study can be strategically used to analyze emerging trends …

Exploring A Mechanism Toward Automated Feedback For Cancer Patient Self-Reporting, Kevin Phong, Mengchen Ding, Youmin Cho, Yun Jiang, Yang Gong

Faculty, Staff and Student Publications

"Infobuttons" spearheaded electronic health records (EHR) based decision support by offering automated knowledge resources to physicians. However, how such a mechanism could be leveraged to provide optimal resources to patients remains unanswered. Informatics approaches are expected to utilize more relevant information beyond EHR, such as patient-reported outcomes, to support clinical decisions. This pilot study is intended to explore how patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in EHR can be incorporated and how to recommend tailored content to cancer patients via automated feedback.

Extracting Drug-Protein Relation From Literature Using Ensembles Of Biomedical Transformers, Avisha Das, Zhao Li, Qiang Wei, Jianfu Li, Liang-Chin Huang, Yan Hu, Rongbin Li, Wenjin Jim Zheng, Hua Xu

Faculty, Staff and Student Publications

Automatic extraction of relations between drugs/chemicals and proteins from ever-growing biomedical literature is required to build up-to-date knowledge bases in biomedicine. To promote the development of automated methods, BioCreative-VII organized a shared task - the DrugProt track, to recognize drug-protein entity relations from PubMed abstracts. We participated in the shared task and leveraged deep learning-based transformer models pre-trained on biomedical data to build ensemble approaches to automatically extract drug-protein relation from biomedical literature. On the main corpora of 10,750 abstracts, our best system obtained an F1-score of 77.60% (ranked 4th among 30 participating teams), and on the large-scale corpus of …

An Icd For The Digital World: What Does The Icd-11 Research Show?, Susan H Fenton, Mary H Stanfill, Kathy Giannangelo

Faculty, Staff and Student Publications

The 11th revision of the International Classification of Diseases (ICD) is now available for use. A literature search was conducted to review and summarize the research conducted to date. In addition to the ease of integration into electronic health records using standard digital tools such as uniform resource identifiers and application programming interfaces, ICD-11 and the World Health Organization provided linearization for mortality and morbidity, ICD-11-MMS, promise improved backward compatibility to ICD-10; increased availability in multiple languages; greater detail for clinical use, including traditional Chinese medicine; and enhanced maintenance for continued relevance. The studies reviewed here support the superior content …

Challenges In Selecting Patient-Reported Outcome Measures For Use In A Patient-Facing Technology, Priyank Raj, Youmin Cho, Yun Jiang, Yang Gong

Faculty, Staff and Student Publications

Patient-reported outcome measures (PROMs) have been increasingly integrated into patient-facing technologies to engage and empower patients in cancer self-management at home. However, researchers and developers face several challenges in selecting the best-suited PROMs for patient-facing technologies, due to the complex nature of the disease, the multitude of PROMs with high psychometric quality, and the lack of clear standards for PROM utilization. In this paper, we have discussed these challenges, illustrated by breast cancer instruments.

A Patient-Centered Approach To Collecting And Displaying Patient Identifiers, Christina Van Hal, Jennifer L Mills, Mary Gatmaitan, Yang Gong

Faculty, Staff and Student Publications

Patient identifiers such as name, date of birth, or gender are the first line of defense to ensure the accuracy of the health data displayed in health information exchange. Health data display is the impetus for clinical decisions and patient outcomes and directly correlates with promoting interoperability and health information exchange. Therefore, constant monitoring of quality metrics is imperative for clinical leaders to keep a pulse on what is happening within their organizations. However, the electronic health records (EHRs) designer should also take precautions to ensure the visualizations are not misleading, given that EHRs have been shown in some studies …

A Quantitative Analysis Of Patient-Facing Technologies For Patient Self-Reporting, Mengchen Ding, Youmin Cho, Yun Jiang, Yang Gong

Faculty, Staff and Student Publications

Dramatic improvements in patient-facing technologies have demonstrated the potential to transform healthcare delivery for a 360-degree holistic view of care. A key question regarding how such technologies affect patient self-reporting still needs to be answered. This study presents the technologies and their associated key variables via quantitative analysis. Associations were found between single-platform and web-based applications (apps), Android apps and physician view, mental health disease, and user feedback. The results are intended to inform future design, development, and evaluation of patient-facing technologies. More systematic, theory-driven, framework-based design and evaluation are necessary to fully characterize the effectiveness and maintenance of patient-facing …

User-Centered Data Display For Clinicians To Diagnose And Manage Hypertension, Carly Ho, Oluwatumininu Layinka, Valerie Chukelu, Kevin Phong, Yang Gong

Faculty, Staff and Student Publications

The accurate diagnosis and effective treatment of hypertension are hindered by challenges stemming from limited access to comprehensive blood pressure (BP) data and the need for clinical context surrounding BP readings. Using handwritten tables for home-monitored BP exacerbates issues related to integration of electronic health records (EHRs) and trend analysis. This study employs user-centered design principles to develop prototypes for BP data visualization, with the primary goal of harmonizing disparate BP data sources to empower clinicians in precise hypertension diagnosis and management.

Learning From Non-Routine Events And Teamwork In Intensive Care Units: Challenges And Opportunities, Yang Gong, You Chen

Faculty, Staff and Student Publications

Patients admitted to intensive care units (ICUs) have profound and complex illnesses, often fraught with uncertainties in diagnoses, treatments, and care decisions. Clinicians often deviate from best practices to handle ICUs' myriad complexities and uncertainties. Non-routine events (NREs), defined as any aspect of care perceived by clinicians as deviations from optimal care, are latent and frequent safety threats that, if left unchecked, can be precursors to adverse events. Proper identification and analysis of NREs that represent latent safety threats have been proposed as a feasible and more effective approach for performance improvement than traditional root cause analysis for patient safety …

Literature Analysis On Ontologies Applied In Clinical Decision Support Systems, Xia Jing, Hua Min, Yang Gong, Paul Biondich, David Robinson, Timothy D Law, Christian G Nohr, Arild Faxvaag, Lior Rennert, Nina C Hubig, Ronald W Gimbel

Faculty, Staff and Student Publications

No abstract provided.

Severe Dysphagia With Eosinophilic Esophagitis Pattern Of Injury Related To Pembrolizumab Therapy, James S Barnett, Kevin K Yu, Xavier Rivera Rivera, Asmeen Bhatt

Faculty, Staff and Student Publications

While immune checkpoint inhibitor (ICI) therapies are effective treatments for many cancers, ICI therapies are associated with immune-related adverse events. We present a 67-year-old man with non-small cell lung carcinoma, who developed severe dysphagia with biopsies from an esophagogastroduodenoscopy showing histopathology consistent with eosinophilic esophagitis while on ICI maintenance therapy with pembrolizumab. The patient's symptoms worsened despite standard therapy. However, he had complete resolution of dysphagia symptoms once pembrolizumab was discontinued. While immune-related adverse events affecting the gastrointestinal system are increasingly recognized, ICI-associated eosinophilic esophagitis is a rare entity.

Effect Of Russian Current Expert Modes On Quadriceps Muscle Torque In Healthy Adults: A Single-Blinded Randomized Controlled Trial, Ansam Hasan, Ibrahim Moustafa, Tamer Shousha

Faculty, Staff and Student Publications

BACKGROUND: Russian current (RC), a well-known neuromuscular electrical stimulation operating at 2500 Hz, has demonstrated significant strength improvement over traditional exercises due to its high tolerance and low pain provocation. Despite extensive NMES parameter research, the specific effects of expert modes, particularly ON2 and Rest, remain unexplored. This study investigates the direct effect of these expert modes on quadriceps muscle strength in healthy adults.

METHODS: This is a single-blind, randomization-controlled trial. Forty-eight healthy university students (31 females, 17 males) were assigned in two randomized experimental groups either the ON2 or Rest mode for a 15-minute electrical stimulation session. Quadriceps maximum …

Short-Term Impact Of Low-Intensity Exercise With Blood Flow Restriction On Mild Knee Osteoarthritis In Older Adults: A Pilot Study, Kang-Ho Kim, Seung-Ho Kang, Nackhwan Kim, Jaehyeong Choi, Seok Kang

Faculty, Staff and Student Publications

This pilot study aimed to investigate the immediate impact of low-intensity exercises with blood flow restriction (BFR) on older adults with knee osteoarthritis (KOA). Fifteen patients with KOA who were over 50 years old, participated and underwent low-intensity resistance knee exercises at 30% of their one-repetition maximum with BFR three times/week for two weeks. Pre- and post-exercise assessments included pain levels, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, isokinetic knee strength, lower extremity muscle volume (via leg circumference and muscle thickness), functional performance tests (timed up-and-go [TUG] and sit-to-stand [STS]), skeletal muscle index (SMI) using bioelectrical impedance analysis, …

Novel Strategies To Improve The Cardioprotective Effects Of Cardioplegia, Estefanie Osorio-Llanes, Jairo Castellar-López, Wendy Rosales-Rada, Yulieth Montoya, John Bustamante, Ricardo Zalaquett, Roberto Bravo-Sagua, Jaime A Riquelme, Gina Sánchez, Mario Chiong, Sergio Lavandero, Evelyn Mendoza-Torres

Faculty, Staff and Student Publications

The use of cardioprotective strategies as adjuvants of cardioplegic solutions has become an ideal alternative for the improvement of post-surgery heart recovery. The choice of the optimal cardioplegia, as well as its distribution mechanism, remains controversial in the field of cardiovascular surgery. There is still a need to search for new and better cardioprotective methods during cardioplegic procedures. New techniques for the management of cardiovascular complications during cardioplegia have evolved with new alternatives and additives, and each new strategy provides a tool to neutralize the damage after ischemia/reperfusion events. Researchers and clinicians have committed themselves to studying the effect of …

Exploring Novel Frontiers: Leveraging Stat3 Signaling For Advanced Cancer Therapeutics, Taiwo Adesoye, Debasish Tripathy, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Signal Transducer and Activator of Transcription 3 (STAT3) plays a significant role in diverse physiologic processes, including cell proliferation, differentiation, angiogenesis, and survival. STAT3 activation via phosphorylation of tyrosine and serine residues is a complex and tightly regulated process initiated by upstream signaling pathways with ligand binding to receptor and non-receptor-linked kinases. Through downstream deregulation of target genes, aberrations in STAT3 activation are implicated in tumorigenesis, metastasis, and recurrence in multiple cancers. While there have been extensive efforts to develop direct and indirect STAT3 inhibitors using novel drugs as a therapeutic strategy, direct clinical application remains in evolution. In this …

Crispr Screening Identifies Bet And Mtor Inhibitor Synergy In Cholangiocarcinoma Through Serine Glycine One Carbon, Yan Zhu, Dengyong Zhang, Pooja Shukla, Young-Ho Jung, Prit Benny Malgulwar, Sharmeen Chagani, Medina Colic, Sarah Benjamin, John A Copland, Lin Tan, Philip L Lorenzi, Milind Javle, Jason T Huse, Jason Roszik, Traver Hart, Lawrence N Kwong

Faculty, Staff and Student Publications

Patients with cholangiocarcinoma have poor clinical outcomes due to late diagnoses, poor prognoses, and limited treatment strategies. To identify drug combinations for this disease, we have conducted a genome-wide CRISPR screen anchored on the bromodomain and extraterminal domain (BET) PROTAC degrader ARV825, from which we identified anticancer synergy when combined with genetic ablation of members of the mTOR pathway. This combination effect was validated using multiple pharmacological BET and mTOR inhibitors, accompanied by increased levels of apoptosis and cell cycle arrest. In a xenograft model, combined BET degradation and mTOR inhibition induced tumor regression. Mechanistically, the 2 inhibitor classes converged …

Hedgehog Activation Promotes Osteogenic Fates Of Growth Plate Resting Zone Chondrocytes Through Transient Clonal Competency, Shion Orikasa, Yuki Matsushita, Hiroaki Manabe, Michael Fogge, Zachary Lee, Koji Mizuhashi, Naoko Sakagami, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP-Indian hedgehog feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP+ resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we specifically activated Hedgehog signaling in PTHrP+ resting chondrocytes and traced the fate of their descendants using a tamoxifen-inducible Pthrp-creER line with patched-1-floxed and tdTomato reporter alleles. Hedgehog-activated PTHrP+ chondrocytes …

Intratumoral Biosynthesis Of Gold Nanoclusters By Pancreatic Cancer To Overcome Delivery Barriers To Radiosensitization, Aaron S Schwartz-Duval, Yuri Mackeyev, Iqbal Mahmud, Philip L Lorenzi, Mihai Gagea, Sunil Krishnan, Konstantin V Sokolov

Faculty, Staff and Student Publications

Nanoparticle delivery to solid tumors is a prime challenge in nanomedicine. Here, we approach this challenge through the lens of biogeochemistry, the field that studies the flow of chemical elements within ecosystems as manipulated by living cellular organisms and their environments. We leverage biogeochemistry concepts related to gold cycling against pancreatic cancer, considering mammalian organisms as drivers for gold nanoparticle biosynthesis. Sequestration of gold nanoparticles within tumors has been demonstrated as an effective strategy to enhance radiotherapy; however, the desmoplasia of pancreatic cancer impedes nanoparticle delivery. Our strategy overcomes this barrier by applying an atomic-scale agent, ionic gold, for intratumoral …

Relationship Between Religiosity And Hpv Vaccine Initiation And Intention In Urban Black And Hispanic Parents, Deidra Carroll Coleman, Christine Markham, Vincent Guilamo-Ramos, Diane Santa Maria

Faculty, Staff and Student Publications

OBJECTIVE: Religion is believed to be an important sociocultural influence in the U.S., but little is known about how religiosity shapes the human papillomavirus (HPV) vaccine decision in racial/ethnic minorities. The purpose of this study was to examine the relationship between religiosity and HPV vaccine initiation and intention among urban, racial/ethnic minority parents of adolescents 11-14 years old.

DESIGN: This study employed a descriptive, cross-sectional design using baseline data from Black and Hispanic parents (N = 175 and 285, respectively) recruited from medically underserved communities. Chi-square tests for independence and independent-samples t-tests were run to assess sociodemographic differences in vaccine …

Human Whole-Exome Genotype Data For Alzheimer's Disease, Yuk Yee Leung, Adam C Naj, Yi-Fan Chou, Otto Valladares, Michael Schmidt, Kara Hamilton-Nelson, Nicholas Wheeler, Honghuang Lin, Prabhakaran Gangadharan, Liming Qu, Kaylyn Clark, Amanda B Kuzma, Wan-Ping Lee, Laura Cantwell, Heather Nicaretta, Jonathan Haines, Lindsay Farrer, Sudha Seshadri, Zoran Brkanac, Carlos Cruchaga, Margaret Pericak-Vance, Richard P Mayeux, William S Bush, Anita Destefano, Eden Martin, Gerard D Schellenberg, Li-San Wang

Faculty, Staff and Student Publications

The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to a joint analysis. Here we present a bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen sequencing centers in the Alzheimer's Disease Sequencing Project. The joint-genotype called variant-called format (VCF) file contains only positions within the union of capture kits. The VCF was then processed specifically to account for the batch effects arising from the use of different capture kits from different studies. We identified 8.2 million autosomal variants. 96.82% of the variants are high-quality, and …

Trex2 Deficiency Suppresses Spontaneous And Genotoxin-Associated Mutagenesis, Teresa Marple, Mi Young Son, Xiaodong Cheng, Jun Ho Ko, Patrick Sung, Paul Hasty

Faculty, Staff and Student Publications

TREX2, a 3'-5' exonuclease, is a part of the DNA damage tolerance (DDT) pathway that stabilizes replication forks (RFs) by ubiquitinating PCNA along with the ubiquitin E3 ligase RAD18 and other DDT factors. Mismatch repair (MMR) corrects DNA polymerase errors, including base mismatches and slippage. Here we demonstrate that TREX2 deletion reduces mutations in cells upon exposure to genotoxins, including those that cause base lesions and DNA polymerase slippage. Importantly, we show that TREX2 generates most of the spontaneous mutations in MMR-mutant cells derived from mice and people. TREX2-induced mutagenesis is dependent on the nuclease and DNA-binding attributes of TREX2. …

Non-Canonical Hedgehog Signaling Mediates Profibrotic Hematopoiesis-Stroma Crosstalk In Myeloproliferative Neoplasms, Jessica E Pritchard, Juliette E Pearce, Inge A M Snoeren, Stijn N R Fuchs, Katrin Götz, Fabian Peisker, Silke Wagner, Adam Benabid, Niklas Lutterbach, Vanessa Klöker, James S Nagai, Monica T Hannani, Anna K Galyga, Ellen Sistemich, Bella Banjanin, Niclas Flosdorf, Eric Bindels, Kathrin Olschok, Katharina Biaesch, Nicolas Chatain, Neha Bhagwat, Andrew Dunbar, Rita Sarkis, Olaia Naveiras, Marie-Luise Berres, Steffen Koschmieder, Ross L Levine, Ivan G Costa, Hélène F E Gleitz, Rafael Kramann, Rebekka K Schneider

Faculty, Staff and Student Publications

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a …

A Study To Assess The Efficacy Of Enasidenib And Risk-Adapted Addition Of Azacitidine In Newly Diagnosed Idh2-Mutant Aml, Sheng F Cai, Ying Huang, Jennie R Lance, Hsiaoyin Charlene Mao, Andrew J Dunbar, Samantha N Mcnulty, Todd Druley, Yan Li, Maria R Baer, Wendy Stock, Tibor Kovacsovics, William G Blum, Gary J Schiller, Rebecca L Olin, James M Foran, Mark Litzow, Tara Lin, Prapti Patel, Matthew C Foster, Michael Boyiadzis, Robert H Collins, Jordan Chervin, Abigail Shoben, Jo-Anne Vergilio, Nyla A Heerema, Leonard Rosenberg, Timothy L Chen, Ashley O Yocum, Franchesca Druggan, Sonja Marcus, Mona Stefanos, Brian J Druker, Alice S Mims, Uma Borate, Amy Burd, John C Byrd, Ross L Levine, Eytan M Stein

Faculty, Staff and Student Publications

Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of …