Medicine and Health Sciences Commons^™

How Does Facilitation In Healthcare Work? Using Mechanism Mapping To Illuminate The Black Box Of A Meta-Implementation Strategy, Amy M Kilbourne, Elvin Geng, Ingrid Eshun-Wilson, Shannon Sweeney, Donna Shelley, Deborah J Cohen, Joann E Kirchner, Maria E Fernandez, Michael L Parchman

Faculty, Staff and Student Publications

BACKGROUND: Healthcare facilitation, an implementation strategy designed to improve the uptake of effective clinical innovations in routine practice, has produced promising yet mixed results in randomized implementation trials and has not been fully researched across different contexts.

OBJECTIVE: Using mechanism mapping, which applies directed acyclic graphs that decompose an effect of interest into hypothesized causal steps and mechanisms, we propose a more concrete description of how healthcare facilitation works to inform its further study as a meta-implementation strategy.

METHODS: Using a modified Delphi consensus process, co-authors developed the mechanistic map based on a three-step process. First, they developed an initial …

How Does Facilitation In Healthcare Work? Using Mechanism Mapping To Illuminate The Black Box Of A Meta-Implementation Strategy, Amy M Kilbourne, Elvin Geng, Ingrid Eshun-Wilson, Shannon Sweeney, Donna Shelley, Deborah J Cohen, Joann E Kirchner, Maria E Fernandez, Michael L Parchman

Faculty, Staff and Student Publications

BACKGROUND: Healthcare facilitation, an implementation strategy designed to improve the uptake of effective clinical innovations in routine practice, has produced promising yet mixed results in randomized implementation trials and has not been fully researched across different contexts.

OBJECTIVE: Using mechanism mapping, which applies directed acyclic graphs that decompose an effect of interest into hypothesized causal steps and mechanisms, we propose a more concrete description of how healthcare facilitation works to inform its further study as a meta-implementation strategy.

METHODS: Using a modified Delphi consensus process, co-authors developed the mechanistic map based on a three-step process. First, they developed an initial …

Next-Generation Boron Drugs And Rational Translational Studies Driving The Revival Of Bnct, Danushka S Seneviratne, Omran Saifi, Yuri Mackeyev, Timothy Malouff, Sunil Krishnan

Faculty, Staff and Student Publications

BNCT is a high-linear-energy transfer therapy that facilitates tumor-directed radiation delivery while largely sparing adjacent normal tissues through the biological targeting of boron compounds to tumor cells. Tumor-specific accumulation of boron with limited accretion in normal cells is the crux of successful BNCT delivery. Given this, developing novel boronated compounds with high selectivity, ease of delivery, and large boron payloads remains an area of active investigation. Furthermore, there is growing interest in exploring the immunogenic potential of BNCT. In this review, we discuss the basic radiobiological and physical aspects of BNCT, traditional and next-generation boron compounds, as well as translational …

Candida Albicans Hyphal Morphogenesis Within Macrophages Does Not Require Carbon Dioxide Or Ph-Sensing Pathways, Hannah B Wilson, Michael C Lorenz

Faculty, Staff and Student Publications

The opportunistic fungal pathogen Candida albicans has evolved a variety of mechanisms for surviving inside and escaping macrophages, including the initiation of filamentous growth. Although several distinct models have been proposed to explain this process at the molecular level, the signals driving hyphal morphogenesis in this context have yet to be clarified. Here, we evaluate the following three molecular signals as potential hyphal inducers within macrophage phagosomes: CO2, intracellular pH, and extracellular pH. Additionally, we revisit previous work suggesting that the intracellular pH of C. albicans fluctuates in tandem with morphological changes in vitro. Using time-lapse microscopy, we observed …

Surfactant Protein A Attenuates Generalized And Localized Neuroinflammation In Neonatal Mice, Caroline E Crocker, Romana Sharmeen, Thu T Tran, Amir M Khan, Wen Li, Joseph L Alcorn

Faculty, Staff and Student Publications

Surfactant protein A (SP-A) has important roles in innate immunity and modulation of pulmonary and extrapulmonary inflammation. Given SP-A has been detected in rat and human brain, we sought to determine if SP-A has a role in modulating inflammation in the neonatal mouse brain. Neonatal wildtype (WT) and SP-A-deficient (SP-A−/−) mice were subjected to three models of brain inflammation: systemic sepsis, intraventricular hemorrhage (IVH) and hypoxic-ischemic encephalopathy (HIE). Following treatment, RNA was isolated from brain tissue and expression of cytokine and SP-A mRNA was determined by real-time quantitative RT-PCR analysis. In the sepsis model, expression of most cytokine mRNAs was …

Correction Of T-Cell Repertoire And Autoimmune Diabetes In Nod Mice By Non-Myeloablative T-Cell Depleted Allogeneic Hsct, Rakefet Sidlik Muskatel, Bar Nathansohn-Levi, Shlomit Reich-Zeliger, Michal Mark, Liat Stoler-Barak, Chava Rosen, Irit Milman-Krentsis, Esther Bachar Lustig, Robert Pete Gale, Nir Friedman, Yair Reisner

Faculty, Staff and Student Publications

The induction of partial tolerance toward pancreatic autoantigens in the treatment of type 1 diabetes mellitus (T1DM) can be attained by autologous hematopoietic stem cell transplantation (HSCT). However, most patients treated by autologous HSCT eventually relapse. Furthermore, allogeneic HSCT which could potentially provide a durable non-autoimmune T-cell receptor (TCR) repertoire is associated with a substantial risk for transplant-related mortality. We have previously demonstrated an effective approach for attaining engraftment without graft versus host disease (GVHD) of allogeneic T-cell depleted HSCT, following non-myeloablative conditioning, using donor-derived anti-3rd party central memory CD8 veto T cells (Tcm). In the present study, we investigated …

An Exploratory Study On Strategies Adopted By Parents Who Use E-Cigarettes To Negotiate Risk Perceptions Of Their Children's Secondhand Exposure And Parental Role Modeling, Joon Kyung Nam, Jesse P Zatloff, Su-Wei Wong, Hsien-Chang Lin, Wei-Chung Su, Anne Buu

Faculty, Staff and Student Publications

Existing health messages mainly targeted youth susceptible to vaping or parents who do not have much knowledge about e-cigarettes. This study makes a unique contribution by conducting the first in-depth investigation of e-cigarette-using parents' risk perceptions and parental role modeling and how these two factors affect their vaping behaviors at home or implementation of any strategies to reduce their children's risk. Fifteen parents who used e-cigarettes participated in a semi-structured interview. Interview transcripts were coded and analyzed through a deductive approach of thematic analysis. This study demonstrates the need to develop and disseminate future health messages for e-cigarette-using parents who …

Immunologic Predictors For Clinical Responses During Immune Checkpoint Blockade In Patients With Myelodysplastic Syndromes, Sung-Eun Lee, Feng Wang, Maison Grefe, Abel Trujillo-Ocampo, Wilfredo Ruiz-Vasquez, Koichi Takahashi, Hussein A Abbas, Pamella Borges, Dinler Amaral Antunes, Gheath Al-Atrash, Naval Daver, Jeffrey J Molldrem, Andrew Futreal, Guillermo Garcia-Manero, Jin S Im

Faculty, Staff and Student Publications

PURPOSE: The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA).

EXPERIMENTAL DESIGN: Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment.

RESULTS: Clinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and …

An Opportunity To Increase Collaborative Science In Fetal, Infant, And Toddler Neuroimaging, Marta Korom, M Catalina Camacho, Aiden Ford, Hana Taha, Dustin Scheinost, Marisa Spann, Kelly A Vaughn

Faculty, Staff and Student Publications

The field of fetal, infant, and toddler (FIT) neuroimaging research—including magnetic resonance imaging (MRI), electroencephalography (EEG), magnetoencephalography, and functional near-infrared spectroscopy, among others—offers pioneering insights into early brain development and has grown in popularity over the past 2 decades. In broader neuroimaging research, multisite collaborative projects, data sharing, and open-source code have increasingly become the norm, fostering big data, consensus standards, and rapid knowledge transfer and development. Given the aforementioned benefits, along with recent initiatives from funding agencies to support multisite and multimodal FIT neuroimaging studies, the FIT field now has the opportunity to establish sustainable, collaborative, and open science …

Structural Insights Into Ligand Recognition And Selectivity Of Somatostatin Receptors, Corey F Hryc, Venkata K P S Mallampalli, Evgeniy I Bovshik, Stavros Azinas, Guizhen Fan, Irina I Serysheva, Genevieve C Sparagna, Matthew L Baker, Eugenia Mileykovskaya, William Dowhan

Faculty, Staff and Student Publications

Cardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of this lipid-protein interaction is still lacking. To address the essential role of cardiolipin in supercomplex organization, we report cryo-EM structures of a wild type supercomplex (IV

Effects Of Prenatal Pesticide Exposure On The Fetal Brain And Placenta Transcriptomes In A Rodent Model, Corina Lesseur, Kirtan Kaur, Sean D Kelly, Karen Hermetz, Randy Williams, Ke Hao, Carmen J Marsit, W Michael Caudle, Jia Chen

Faculty, Staff and Student Publications

Organophosphate and pyrethroid pesticides are among the most extensively used insecticides worldwide. Prenatal exposures to both classes of pesticides have been linked to a wide range of neurobehavioral deficits in the offspring. The placenta is a neuroendocrine organ and the crucial regulator of the intrauterine environment; early-life toxicant exposures could impact neurobehavior by disrupting placental processes. Female C57BL/6 J mice were exposed via oral gavage to an organophosphate, chlorpyrifos (CPF) at 5 mg/kg, a pyrethroid, deltamethrin (DM), at 3 mg/kg, or vehicle only control (CTL). Exposure began two weeks before breeding and continued every three days until euthanasia at gestational …

Surgeons’ Knowledge Regarding Perioperative Pain Management In Patients With Opioid Use Disorder: A Survey Among 260 Members Of The American College Of Surgeons, Caroline E Crocker, Romana Sharmeen, Thu T Tran, Amir M Khan, Wen Li, Joseph L Alcorn

Faculty, Staff and Student Publications

Surfactant protein A (SP-A) has important roles in innate immunity and modulation of pulmonary and extrapulmonary inflammation. Given SP-A has been detected in rat and human brain, we sought to determine if SP-A has a role in modulating inflammation in the neonatal mouse brain. Neonatal wildtype (WT) and SP-A-deficient (SP-A

Clinically Stable Covid-19 Patients Presenting To Acute Unscheduled Episodic Care Venues Have Increased Risk Of Hospitalization: Secondary Analysis Of A Randomized Control Trial, Joseph Bledsoe, Scott C Woller, Maria Brooks, Frank C Sciurba, Jerry A Krishnan, Deborah Martin, Peter Hou, Janet Y Lin, Andrei Kindzelski, Eileen Handberg, Bridget-Anne Kirwan, Elaine Zaharris, Lauren Castro, Nancy L Shapiro, Carl J Pepine, Sarah Majercik, Zhuxuan Fu, Yongqi Zhong, Vidya Venugopal, Yu-Hsuan Lai, Paul M Ridker, Jean M Connors

Faculty, Staff and Student Publications

BACKGROUND: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial.

METHODS: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive …

Dynamic Conformational Switching Underlies Tfiih Function In Transcription And Dna Repair And Impacts Genetic Diseases, Jina Yu, Chunli Yan, Thomas Dodd, Chi-Lin Tsai, John A Tainer, Susan E Tsutakawa, Ivaylo Ivanov

Faculty, Staff and Student Publications

Transcription factor IIH (TFIIH) is a protein assembly essential for transcription initiation and nucleotide excision repair (NER). Yet, understanding of the conformational switching underpinning these diverse TFIIH functions remains fragmentary. TFIIH mechanisms critically depend on two translocase subunits, XPB and XPD. To unravel their functions and regulation, we build cryo-EM based TFIIH models in transcription- and NER-competent states. Using simulations and graph-theoretical analysis methods, we reveal TFIIH's global motions, define TFIIH partitioning into dynamic communities and show how TFIIH reshapes itself and self-regulates depending on functional context. Our study uncovers an internal regulatory mechanism that switches XPB and XPD activities …

Predict Validity For Prognosis Of Breast Cancer Patients With Pathogenic Brca1/2 Variants, Taru A Muranen, Anna Morra, Sofia Khan, Daniel R Barnes, Manjeet K Bolla, Joe Dennis, Renske Keeman, Goska Leslie, Michael T Parsons, Qin Wang, Thomas U Ahearn, Kristiina Aittomäki, Irene L Andrulis, Banu K Arun, Sabine Behrens, Katarzyna Bialkowska, Stig E Bojesen, Nicola J Camp, Jenny Chang-Claude, Kamila Czene, Peter Devilee, Susan M Domchek, Alison M Dunning, Christoph Engel, D Gareth Evans, Manuela Gago-Dominguez, Montserrat García-Closas, Anne-Marie Gerdes, Gord Glendon, Pascal Guénel, Eric Hahnen, Ute Hamann, Helen Hanson, Maartje J Hooning, Reiner Hoppe, Louise Izatt, Anna Jakubowska, Paul A James, Vessela N Kristensen, Fiona Lalloo, Geoffrey J Lindeman, Arto Mannermaa, Sara Margolin, Susan L Neuhausen, William G Newman, Paolo Peterlongo, Kelly-Anne Phillips, Miquel Angel Pujana, Johanna Rantala, Karina Rønlund, Emmanouil Saloustros, Rita K Schmutzler, Andreas Schneeweiss, Christian F Singer, Maija Suvanto, Yen Yen Tan, Manuel R Teixeira, Mads Thomassen, Marc Tischkowitz, Vishakha Tripathi, Barbara Wappenschmidt, Emily Zhao, Douglas F Easton, Antonis C Antoniou, Georgia Chenevix-Trench, Paul D P Pharoah, Marjanka K Schmidt, Carl Blomqvist, Heli Nevanlinna

Faculty, Staff and Student Publications

We assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by PREDICT score percentiles, the observed mortality was consistently lower than …

Clinical Characteristics And Survival Of Pulmonary Arterial Hypertension With Or Without Interstitial Lung Disease In Systemic Sclerosis, Jessica L Fairley, Dylan Hansen, Laura Ross, Susanna Proudman, Joanne Sahhar, Gene-Siew Ngian, Jennifer Walker, Lauren V Host, Kathleen Morrisroe, Diane Apostolopoulous, Nava Ferdowsi, Michelle Wilson, Maryam Tabesh, Wendy Stevens, Mandana Nikpour

Faculty, Staff and Student Publications

Objectives

To describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD).

Methods

Participants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan–Meier estimates and Cox-regression modelling.

Results

Of 1561 participants, 7% fulfilled criteria for …

Common Signaling Pathways Involved In Alzheimer's Disease And Stroke: Two Faces Of The Same Coin, Tushar Kanti Das, Bhanu Priya Ganesh, Kaneez Fatima-Shad

Faculty, Staff and Student Publications

Alzheimer's disease (AD) and stroke are two interrelated neurodegenerative disorders which are the leading cause of death and affect the neurons in the brain and central nervous system. Although amyloid-β aggregation, tau hyperphosphorylation, and inflammation are the hallmarks of AD, the exact cause and origin of AD are still undefined. Recent enormous fundamental discoveries suggest that the amyloid hypothesis of AD has not been proven and anti-amyloid therapies that remove amyloid deposition have not yet slowed cognitive decline. However, stroke, mainly ischemic stroke (IS), is caused by an interruption in the cerebral blood flow. Significant features of both disorders are …

Efficient Cancer Modeling Through Crispr-Cas9/Hdr-Based Somatic Precision Gene Editing In Mice, Wen Bu, Chad J Creighton, Kelsey S Heavener, Carolina Gutierrez, Yongchao Dou, Amy T Ku, Yiqun Zhang, Weiyu Jiang, Jazmin Urrutia, Wen Jiang, Fei Yue, Luyu Jia, Ahmed Atef Ibrahim, Bing Zhang, Shixia Huang, Yi Li

Faculty, Staff and Student Publications

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either

Meqtl Mapping In The Genoa Study Reveals Genetic Determinants Of Dna Methylation In African Americans, Lulu Shang, Wei Zhao, Yi Zhe Wang, Zheng Li, Jerome J Choi, Minjung Kho, Thomas H Mosley, Sharon L R Kardia, Jennifer A Smith, Xiang Zhou

Faculty, Staff and Student Publications

Identifying genetic variants that are associated with variation in DNA methylation, an analysis commonly referred to as methylation quantitative trait locus (meQTL) mapping, is an important first step towards understanding the genetic architecture underlying epigenetic variation. Most existing meQTL mapping studies have focused on individuals of European ancestry and are underrepresented in other populations, with a particular absence of large studies in populations with African ancestry. We fill this critical knowledge gap by performing a large-scale cis-meQTL mapping study in 961 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We identify a total of 4,565,687 cis-acting meQTLs …

Social Cognition Across Bipolar Disorder And Behavioral Variant Frontotemporal Dementia: An Exploratory Study, Izabela Guimarães Barbosa, Flávia Da Mata Chiácchio Leite, Maxime Bertoux, Henrique Cerqueira Guimarães, Luciano Inácio Mariano, Leandro Boson Gambogi, Antônio Lúcio Teixeira, Paulo Caramelli, Leonardo Cruz De Souza

Faculty, Staff and Student Publications

OBJECTIVES: Bipolar disorder type 1 (BD1) and behavioral-variant frontotemporal dementia (bvFTD) share similar behavioral and cognitive symptoms, rendering the differential diagnosis between them a clinical challenge. We investigated the accuracy of social cognition (SC) measures to differentiate bvFTD from BD.

METHODS: We included three groups of participants: early-onset BD1 (in remission, n=20), bvFTD (n=18), and cognitively healthy controls (HC) (n=40), matched for age, schooling, and sex. All participants underwent cognitive assessment, including the Facial Emotion Recognition (FER) and Modified Faux-Pas (mFP) tests, which assess mentalizing.

RESULTS: Compared to HC, BD1 and bvFTD patients underperformed on both SC measures. BD1 and …

Five-Year Follow-Up Of Zuma-1 Supports The Curative Potential Of Axicabtagene Ciloleucel In Refractory Large B-Cell Lymphoma, Sattva S Neelapu, Caron A Jacobson, Armin Ghobadi, David B Miklos, Lazaros J Lekakis, Olalekan O Oluwole, Yi Lin, Ira Braunschweig, Brian T Hill, John M Timmerman, Abhinav Deol, Patrick M Reagan, Patrick Stiff, Ian W Flinn, Umar Farooq, Andre H Goy, Peter A Mcsweeney, Javier Munoz, Tanya Siddiqi, Julio C Chavez, Alex F Herrera, Nancy L Bartlett, Adrian A Bot, Rhine R Shen, Jinghui Dong, Kanwarjit Singh, Harry Miao, Jenny J Kim, Yan Zheng, Frederick L Locke

Faculty, Staff and Student Publications

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% …

Confidence-Based Laboratory Test Reduction Recommendation Algorithm, Tongtong Huang, Linda T Li, Elmer V Bernstam, Xiaoqian Jiang

Faculty, Staff and Student Publications

BACKGROUND: We propose a new deep learning model to identify unnecessary hemoglobin (Hgb) tests for patients admitted to the hospital, which can help reduce health risks and healthcare costs.

METHODS: We collected internal patient data from a teaching hospital in Houston and external patient data from the MIMIC III database. The study used a conservative definition of unnecessary laboratory tests, which was defined as stable (i.e., stability) and below the lower normal bound (i.e., normality). Considering that machine learning models may yield less reliable results when trained on noisy inputs containing low-quality information, we estimated prediction confidence to assess the …

Phase Ii Trial Of Neoadjuvant Sitravatinib Plus Nivolumab In Patients Undergoing Nephrectomy For Locally Advanced Clear Cell Renal Cell Carcinoma, Jose A Karam, Pavlos Msaouel, Cara L Haymaker, Surena F Matin, Matthew T Campbell, Amado J Zurita, Amishi Y Shah, Ignacio I Wistuba, Enrica Marmonti, Dzifa Y Duose, Edwin R Parra, Luisa Maren Solis Soto, Caddie Laberiano-Fernandez, Marisa Lozano, Alice Abraham, Max Hallin, Curtis D Chin, Peter Olson, Hirak Der-Torossian, Xiaohong Yan, Nizar M Tannir, Christopher G Wood

Faculty, Staff and Student Publications

Sitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 inhibitors such as nivolumab. We report a single-arm, interventional, phase 2 study of neoadjuvant sitravatinib in combination with nivolumab in patients with locally advanced clear cell renal cell carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) prior to surgery with a null hypothesis ORR = 5% and the alternative hypothesis set at ORR = 30%. Secondary endpoints were safety; pharmacokinetics (PK) of sitravatinib; immune effects, including changes in programmed cell death-ligand 1 expression; time-to-surgery; and disease-free survival …

Physician Views On The Provision Of Information On Immune Checkpoint Inhibitor Therapy To Patients With Cancer And Pre-Existing Autoimmune Disease: A Qualitative Study, Maria A Lopez-Olivo, Gabrielle F Duhon, Juan I Ruiz, Mehmet Altan, Hussein Tawbi, Adi Diab, Clifton O Bingham, Cassandra Calabrese, Natalia I Heredia, Robert J Volk, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but can cause severe immune-related adverse events (irAEs) and flares of autoimmune conditions in cancer patients with pre-existing autoimmune disease. The objective of this study was to identify the information physicians perceived as most useful for these patients when discussing treatment initiation with ICIs. Twenty physicians at a cancer institution with experience in the treatment of irAEs were interviewed. Qualitative thematic analysis was performed to organize and interpret data. The physicians were 11 medical oncologists and 9 non-oncology specialists. The following themes were identified: (1) current methods used by physicians to provide …

Newly Diagnosed Papillary Craniopharyngioma With Braf V600e Mutation Treated With Single-Agent Selective Braf Inhibitor Dabrafenib: A Case Report, Mayank Rao, Meenakshi Bhattacharjee, Scott Shepard, Sigmund Hsu

Faculty, Staff and Student Publications

We report a case of a patient with newly diagnosed, locally extensive and cystic, suprasellar papillary craniopharyngioma successfully treated with single-agent Dabrafenib. The patient was symptomatic with gait imbalance with falls, lethargic episodes, fatigue and incontinence. Diagnostic imaging demonstrated a cystic suprasellar tumor extending into the third ventricle causing obstructive hydrocephalus. The tumor was partially debulked, and bilateral shunts were placed. NGS sequencing demonstrated BRAF V600E mutation, and the patient was prescribed dual agent Dabrafenib and Trametinib. However, due to insurance denial for Trametinib, he only received single-agent Dabrafenib (150mg BID). The treatment resulted in a major response (over two …

Functional Neuronal Circuits Promote Disease Progression In Cancer, Anthony C Restaino, Austin Walz, Samuel J Vermeer, Jeffrey Barr, Attila Kovács, Robin R Fettig, Daniel W Vermeer, Hunter Reavis, Caitlin S Williamson, Christopher T Lucido, Tuany Eichwald, Dalia K Omran, Euihye Jung, Lauren E Schwartz, Maria Bell, Desirae M Muirhead, Jody E Hooper, William C Spanos, Ronny Drapkin, Sebastien Talbot, Paola D Vermeer

Faculty, Staff and Student Publications

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the …

Late Health Outcomes Among Survivors Of Wilms Tumor Diagnosed Over Three Decades: A Report From The Childhood Cancer Survivor Study, Brent R Weil, Andrew J Murphy, Qi Liu, Rebecca M Howell, Susan A Smith, Christopher B Weldon, Elizabeth A Mullen, Arin L Madenci, Wendy M Leisenring, Joseph P Neglia, Lucie M Turcotte, Kevin C Oeffinger, Amanda M Termuhlen, Sogol Mostoufi-Moab, Jennifer M Levine, Kevin R Krull, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Saro H Armenian

Faculty, Staff and Student Publications

Purpose: To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens.

Methods: Cumulative incidence of late mortality (≥ 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of ≥ 4 chemotherapy agents.

Results: Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to …

Sirolimus Versus Cyclosporine A In Patients With Primary Acquired Pure Red Cell Aplasia: A Prospective Cohort Study, Yuan Yang, Zengwei Tang, Yuzhou Huang, Qinglin Hu, Shuqing Wang, Jiang Ji, Yali Du, Chen Yang, Miao Chen, Shimin Hu, Bing Han

Faculty, Staff and Student Publications

No abstract provided.

A Stability Indicating Lc-Ms/Ms Method For Quantification Of A Nox Inhibitor R14 In Its Bisulfite Adduct Form For Pharmacokinetic Studies, Yang Wang, Jing Ma, Shiaw-Yih Lin, Huan Xie, Dong Liang

Faculty, Staff and Student Publications

R14, also known as NOX Inhibitor VII, is a potent inhibitor of NADPH oxidases (NOX) which has recently been identified as a novel agent targeting to triple-negative breast cancer. It is also rapidly degraded in collected pharmacokinetic plasma and blood samples even stored under - 70 °C. The purpose of this study was to develop a stability indicating LC-MS/MS assay that would be suitable for quantification of R14 in plasma and blood. In the presence of sodium sulfite under acidic pH, R14, an aryl lactam compound which is not a typically reactive compound for bisulfite addition, readily and completely converted …

Ppigcf: A Protein-Protein Interaction-Based Gene Correlation Filter For Optimal Gene Selection, Soumen Kumar Pati, Manan Kumar Gupta, Ayan Banerjee, Saurav Mallik, Zhongming Zhao

Faculty, Staff and Student Publications

Biological data at the omics level are highly complex, requiring powerful computational approaches to identifying significant intrinsic characteristics to further search for informative markers involved in the studied phenotype. In this paper, we propose a novel dimension reduction technique, protein-protein interaction-based gene correlation filtration (PPIGCF), which builds on gene ontology (GO) and protein-protein interaction (PPI) structures to analyze microarray gene expression data. PPIGCF first extracts the gene symbols with their expression from the experimental dataset, and then, classifies them based on GO biological process (BP) and cellular component (CC) annotations. Every classification group inherits all the information on its CCs, …