Digital Commons Network^™

Care Levels For Fetal Therapy Centers, Ahmet A Baschat, Sean B Blackwell, Debnath Chatterjee, James J Cummings, Stephen P Emery, Shinjiro Hirose, Lisa M Hollier, Anthony Johnson, Sarah J Kilpatrick, Francois I Luks, M Kathryn Menard, Lawrence B Mccullough, Julie S Moldenhauer, Anita J Moon-Grady, George B Mychaliska, Michael Narvey, Mary E Norton, Mark D Rollins, Eric D Skarsgard, Kuojen Tsao, Barbara B Warner, Abigail Wilpers, Greg Ryan

Faculty, Staff and Student Publications

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels …

Aims: Increasing Diversity In Graduate Medical Education Leadership, Lahia Yemane, Emma Omoruyi, Patricia Poitevien, Rebecca Blankenburg

Faculty, Staff and Student Publications

No abstract provided.

The Pendulum Of Fontan Fenestration, Nadia Hernandez, Sudipta Sen, Johanna Blair De Haan, Stephen Haskins, Amit Pawa

Faculty, Staff and Student Publications

No abstract provided.

Are Thyrotropin-Releasing Hormone (Trh) And Analog Taltirelin Viable Reversal Agents Of Opioid-Induced Respiratory Depression?, Marieke Hyke Algera, Joseph F Cotten, Monique Van Velzen, Marieke Niesters, Martijn Boon, Daniel S Shoham, Kaye E Dandrea, Rutger Van Der Schrier, Albert Dahan

Faculty, Staff and Student Publications

Opioid-induced respiratory depression (OIRD) is a potentially life-threatening complication of opioid consumption. Apart from naloxone, an opioid antagonist that has various disadvantages, a possible reversal strategy is treatment of OIRD with the hypothalamic hormone and neuromodulator thyrotropin-releasing hormone (TRH). In this review, we performed a search in electronic databases and retrieved 52 papers on the effect of TRH and TRH-analogs on respiration and their efficacy in the reversal of OIRD in awake and anesthetized mammals, including humans. Animal studies show that TRH and its analog taltirelin stimulate breathing via an effect at the preBötzinger complex, an important respiratory rhythm generator …

Impact Of Covid19 On Maxillofacial Fractures In The Province Of L’Aquila, Abruzzo, Italy Review Of 296 Patients Treated With Statistical Comparison Of The Two-Year Pre-Covid19 And Covid19, Filippo Giovannetti, Ettore Lupi, Danilo Di Giorgio, Secondo Scarsella, Antonio Oliva, Desiderio Di Fabio, Paolo Prata, Giada Petricca, Valentino Valentini

Faculty, Staff and Student Publications

The aim of this study was to understand the impact of the COVID-19 pandemic on the epidemiology of maxillofacial trauma in a regional trauma center in L'Aquila, Abruzzo, Italy, during the first wave of the pandemic and comparted it to an equivalent period from 2015 to 2018. The authorshave retrospectively analyzed personal data, site of trauma, etiology, and mechanism of injury. Statistical analysis has been carried out utilizing IBM SPSS Statistics software (IBM Corp., Armonk, NY) and significance was accepted for P values of 0.05) as opposed to the etiology in which the road traffic accidents decreased in favor of …

A Multi-Task Gaussian Process Self-Attention Neural Network For Real-Time Prediction Of The Need For Mechanical Ventilators In Covid-19 Patients, Kai Zhang, Siddharth Karanth, Bela Patel, Robert Murphy, Xiaoqian Jiang

Faculty, Staff and Student Publications

OBJECTIVE: The Coronavirus Disease 2019 (COVID-19) pandemic has overwhelmed the capacity of healthcare resources and posed a challenge for worldwide hospitals. The ability to distinguish potentially deteriorating patients from the rest helps facilitate reasonable allocation of medical resources, such as ventilators, hospital beds, and human resources. The real-time accurate prediction of a patient's risk scores could also help physicians to provide earlier respiratory support for the patient and reduce the risk of mortality.

METHODS: We propose a robust real-time prediction model for the in-hospital COVID-19 patients' probability of requiring mechanical ventilation (MV). The end-to-end neural network model incorporates the Multi-task …

External Validation Of A Laboratory Prediction Algorithm For The Reduction Of Unnecessary Labs In The Critical Care Setting, Linda T Li, Tongtong Huang, Elmer V Bernstam, Xiaoqian Jiang

Faculty, Staff and Student Publications

BACKGROUND: Unnecessary laboratory tests contribute to iatrogenic harm and are a major source of waste in the health care system. We previously developed a machine learning algorithm to help clinicians identify unnecessary laboratory tests, but it has not been externally validated. In this study, we externally validate our machine learning algorithm.

METHODS: To externally validate the machine learning algorithm that was originally trained on the Medical Information Mart for Intensive Care (MIMIC) III database, we tested the algorithm in a separate institution. We identified and abstracted data for all patients older than 18 years admitted to the intensive care unit …

Peripheral Blood Gene Expression Profiling Shows Predictive Significance For Response To Mycophenolate In Systemic Sclerosis-Related Interstitial Lung Disease, Shervin Assassi, Elizabeth R Volkmann, W Jim Zheng, Xuan Wang, Holly Wilhalme, Marka A Lyons, Michael D Roth, Donald P Tashkin

Faculty, Staff and Student Publications

OBJECTIVES: To characterise the peripheral blood cell (PBC) gene expression changes ensuing from mycophenolate mofetil (MMF) or cyclophosphamide (CYC) treatment and to determine the predictive significance of baseline PBC transcript scores for response to immunosuppression in systemic sclerosis (SSc)-related interstitial lung disease (ILD).

METHODS: PBC RNA samples from baseline and 12-month visits, corresponding to the active treatment period of both arms in Scleroderma Lung Study II, were investigated by global RNA sequencing. Joint models were created to examine the predictive significance of

RESULTS: 134 patients with SSc-ILD (CYC=69 and MMF=65) were investigated. CYC led to an upregulation of erythropoiesis, inflammation …

Differential Effects Of Dietary Macronutrients On The Development Of Oncogenic Kras-Mediated Pancreatic Ductal Adenocarcinoma, Liang Zhu, Juntao Ji, Jianjia Ma, Dan Wang, Muyun Liu, James Xianxing Du, Rong Chen, Wei Hou, James L Abbruzzese, Craig D Logsdon, Vincent W Yang, Yongde Luo, Weiqin Lu

Faculty, Staff and Student Publications

KRAS mutations are prevalent in patients with pancreatic ductal adenocarcinoma (PDAC) and are critical to fostering tumor growth in part by aberrantly rewiring glucose, amino acid, and lipid metabolism. Obesity is a modifiable risk factor for pancreatic cancer. Corroborating this epidemiological observation, mice harboring mutant KRAS are highly vulnerable to obesogenic high-fat diet (HFD) challenges leading to the development of PDAC with high penetrance. However, the contributions of other macronutrient diets, such as diets rich in carbohydrates that are regarded as a more direct source to fuel glycolysis for cancer cell survival and proliferation than HFD, to pancreatic tumorigenesis remain …

Cardiovascular Outcomes In Aortopathy: Gentac Registry Of Genetically Triggered Aortic Aneurysms And Related Conditions, Kathryn W Holmes, Sheila Markwardt, Kim A Eagle, Richard B Devereux, Jonathan W Weinsaft, Federico M Asch, Scott A Lemaire, Cheryl L Maslen, Howard K Song, Dianna M Milewicz, Siddharth K Prakash, Dongchuan Guo, Shaine A Morris, Reed E Pyeritz, Rita C Milewski, William J Ravekes, H C Dietz, Ralph V Shohet, Michael Silberbach, Mary J Roman

Faculty, Staff and Student Publications

BACKGROUND: The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.

OBJECTIVES: The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.

METHODS: The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome …

Detoxification Role Of Metabolic Glutathione S-Transferase (Gst) Genes In Blood Lead Concentrations Of Jamaican Children With And Without Autism Spectrum Disorder, Mohammad H Rahbar, Maureen Samms-Vaughan, Sori Kim, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakspeare-Pellington, Katherine A Loveland

Faculty, Staff and Student Publications

Glutathione S-transferases (GST) are involved in the detoxification of exogenous chemicals including lead (Pb). Using data from 344 pairs of autism spectrum disorder (ASD) cases and age- and sex-matched typically developing (TD) controls (2−8 years old) from Jamaica, we investigated the interaction between three GST genes and ASD status as determinants of blood Pb concentrations (BPbCs). We found that ASD cases had lower geometric mean BPbCs than TD children (1.74 vs. 2.27 µg/dL, p < 0.01). Using a co-dominant genetic model, ASD cases with the Ile/Val genotype for the GSTP1 Ile105Val polymorphism had lower GM BPbCs than TD controls, after adjusting for a known interaction between GSTP1 and GSTT1, child’s parish, socioeconomic status, consumption of lettuce, fried plantains, and canned fish (Ile/Val: 1.78 vs. 2.13 µg/dL, p = 0.03). Similarly, among carriers of the I/I or I/D (I*) genotype for GSTT1 and GSTM1, ASD cases had lower adjusted GM BPbCs than TD controls (GSTT1 I*: 1.61 vs. 1.91 µg/dL, p = 0.01; GSTM1 I*: 1.71 vs. 2.04 µg/dL, p = 0.01). Our findings suggest that genetic polymorphisms in GST genes may influence detoxification of Pb by the enzymes they encode in Jamaican children with and without ASD.

Food Insecurity And Health-Related Concerns Among Elementary Schoolteachers During The Covid-19 Pandemic, Fangyu Li, Nivedhitha Parthasarathy, Feng Zhang, Ru-Jye Chuang, Mallika Mathur, Mike Pomeroy, Jacqueline Noyola, Christine M Markham, Shreela V Sharma

Faculty, Staff and Student Publications

INTRODUCTION: US school systems underwent major upheaval, including closures, implementation of virtual and/or hybrid learning, and stringent infection mitigation protocols, during the initial phase of the COVID-19 pandemic. We aimed to examine the association between food insecurity and perceived health, perceived stress, and social determinants of health concerns among elementary schoolteachers serving predominantly low-income children during the COVID-19 pandemic.

METHODS: Brighter Bites, a nonprofit organization that weekly distributes fresh fruits and vegetables and nutrition education materials to more than 300 schools serving racial and ethnic minority populations with low income, conducts annual surveys of participating teachers to help determine subsequent …

Resistant Maltodextrin Consumption In A Double-Blind, Randomized, Crossover Clinical Trial Induces Specific Changes In Potentially Beneficial Gut Bacteria, Volker Mai, Alyssa M Burns, Rebecca J Solch, Jennifer C Dennis-Wall, Maria Ukhanova, Bobbi Langkamp-Henken

Faculty, Staff and Student Publications

Background: We have previously reported that the addition of resistant maltodextrin (RMD), a fermentable functional fiber, to the diet increases fecal weight as well as the amount of fecal bifidobacteria. Here, we report on the targeted analysis of changes in potentially beneficial gut bacteria associated with the intervention. Objective: The primary objective of this study was to determine the effect of adding 0, 15 and 25 g RMD to the diets of healthy free-living adults on potentially beneficial gut bacteria. Methods: We expanded on our previously reported microbiota analysis in a double-blind, placebo-controlled feeding study (NCT02733263) by performing additional qPCR …

Association Study Between Mucin 4 (Muc4) Polymorphisms And Idiopathic Recurrent Pregnancy Loss In A Korean Population, Ji-Hyang Kim, Han-Sung Park, Jeong-Yong Lee, Eun-Ju Ko, Young-Ran Kim, Hee-Young Cho, Woo-Sik Lee, Eun-Hee Ahn, Nam-Keun Kim

Faculty, Staff and Student Publications

Recurrent pregnancy loss (RPL) is the loss of two or more consecutive pregnancies before 20 weeks of gestational age. Our study investigated whether mucin 4 (MUC4) polymorphisms are associated with RPL. MUC polymorphisms (rs882605 C>A, rs1104760 A>G, rs2688513 A>G, rs2258447 C>T, and rs2291652 A>G) were genotyped in 374 women with RPL and 239 controls of Korean ethnicity using polymerase chain reaction-restriction fragment length polymorphism analysis and the TaqMan probe SNP genotyping assay. Differences in genotype frequencies between cases of RPL and the controls were compared. MUC4 rs882605 C>A and rs1104760 A>G polymorphisms were …

Impact Of Estrogen Receptor Expression On Prognosis Of Ovarian Cancer According To Antibody Clone Used For Immunohistochemistry: A Meta-Analysis, Chun Wai Ng, Kwong-Kwok Wong

Faculty, Staff and Student Publications

Background: The prognostic value of the expression of estrogen receptor (ER) subtypes ER⍺ and ERβ in ovarian cancer has previously been evaluated by meta-analyses. However, the results are contradictory and controversial.

Methods: We conducted an updated meta-analysis with stringent inclusion criteria to ensure homogeneous studies to determine the effect of ER subtypes on ovarian cancer prognosis. Articles were retrieved by systematic search of PubMed and Web of Science for articles dated up to June 2021. Only studies with known hazard ratio (HR) and antibody clone for immunochemistry (IHC) were included. Pooled HRs with the corresponding 95% confidence intervals (CIs) were …

Electrographic Seizures In Neonates With A High Risk Of Encephalopathy, Wan-Hsuan Chen, Oi-Wa Chan, Jainn-Jim Lin, Ming-Chou Chiang, Shao-Hsuan Hsia, Huei-Shyong Wang, En-Pei Lee, Yi-Shan Wang, Cheng-Yen Kuo, Kuang-Lin Lin, On The Behalf Of The Icns Group

Faculty, Staff and Student Publications

Background: Neonatal encephalopathy is caused by a wide variety of acute brain insults in newborns and presents with a spectrum of neurologic dysfunction, such as consciousness disturbance, seizures, and coma. The increased excitability in the neonatal brain appears to be highly susceptible to seizures after a variety of insults, and seizures may be the first clinical sign of a serious neurologic disorder. Subtle seizures are common in the neonatal period, and abnormal clinical paroxysmal events may raise the suspicion of neonatal seizures. Continuous video electroencephalographic (EEG) monitoring is the gold standard for the diagnosis of neonatal seizures. The aim of …

A Crosstalk Between Gut And Brain In Sepsis-Induced Cognitive Decline\, Vijayasree V Giridharan, Jaqueline S Generoso, Leonardo Lence, Gabriela Candiotto, Emílio Streck, Fabricia Petronilho, Anilkumar Pillai, Tarek Sharshar, Felipe Dal-Pizzol, Tatiana Barichello

Faculty, Staff and Student Publications

BACKGROUND: Sepsis is a potentially fatal disease characterized by acute organ failure that affects more than 30 million people worldwide. Inflammation is strongly associated with sepsis, and patients can experience impairments in memory, concentration, verbal fluency, and executive functioning after being discharged from the hospital. We hypothesize that sepsis disrupts the microbiota-gut-brain axis homeostasis triggering cognitive impairment. This immune activation persists during treatment, causing neurological dysfunction in sepsis survivors.

METHODS: To test our hypothesis, adult Wistar rats were subjected to cecal-ligation and perforation (CLP) or sham (non-CLP) surgeries. The animals were subjected to the [

RESULTS: Compared to the control …

Tissue-Specific Variations In Transcription Factors Elucidate Complex Immune System Regulation, Hengwei Lu, Yi-Ching Tang, Assaf Gottlieb

Faculty, Staff and Student Publications

Gene expression plays a key role in health and disease. Estimating the genetic components underlying gene expression can thus help understand disease etiology. Polygenic models termed "transcriptome imputation" are used to estimate the genetic component of gene expression, but these models typically consider only the cis regions of the gene. However, these cis-based models miss large variability in expression for multiple genes. Transcription factors (TFs) that regulate gene expression are natural candidates for looking for additional sources of the missing variability. We developed a hypothesis-driven approach to identify second-tier regulation by variability in TFs. Our approach tested two models …

Mutational Activation Of The Nrf2 Pathway Upregulates Kynureninase Resulting In Tumor Immunosuppression And Poor Outcome In Lung Adenocarcinoma, Johannes F Fahrmann, Ichidai Tanaka, Ehsan Irajizad, Xiangying Mao, Jennifer B Dennison, Eunice Murage, Julian Casabar, Jeffrey Mayo, Qian Peng, Muge Celiktas, Jody V Vykoukal, Soyoung Park, Ayumu Taguchi, Oliver Delgado, Satyendra C Tripathi, Hiroyuki Katayama, Luisa Maren Solis Soto, Jaime Rodriguez-Canales, Carmen Behrens, Ignacio Wistuba, Samir Hanash, Edwin J Ostrin

Faculty, Staff and Student Publications

Activation of the NRF2 pathway through gain-of-function mutations or loss-of-function of its suppressor KEAP1 is a frequent finding in lung cancer. NRF2 activation has been reported to alter the tumor microenvironment. Here, we demonstrated that NRF2 alters tryptophan metabolism through the kynurenine pathway that is associated with a tumor-promoting, immune suppressed microenvironment. Specifically, proteomic profiles of 47 lung adenocarcinoma (LUAD) cell lines (11 KEAP1 mutant and 36 KEAP1 wild-type) revealed the tryptophan-kynurenine enzyme kynureninase (KYNU) as a top overexpressed protein associated with activated NRF2. The siRNA-mediated knockdown of NFE2L2, the gene encoding for NRF2, or activation of the NRF2 …

Dedifferentiation-Mediated Stem Cell Niche Maintenance In Early-Stage Ductal Carcinoma In Situ Progression: Insights From A Multiscale Modeling Study, Joseph D Butner, Prashant Dogra, Caroline Chung, Javier Ruiz-Ramírez, Sara Nizzero, Marija Plodinec, Xiaoxian Li, Ping-Ying Pan, Shu-Hsia Chen, Vittorio Cristini, Bulent Ozpolat, George A Calin, Zhihui Wang

Faculty, Staff and Student Publications

We present a multiscale agent-based model of ductal carcinoma in situ (DCIS) to study how key phenotypic and signaling pathways are involved in the early stages of disease progression. The model includes a phenotypic hierarchy, and key endocrine and paracrine signaling pathways, and simulates cancer ductal growth in a 3D lattice-free domain. In particular, by considering stochastic cell dedifferentiation plasticity, the model allows for study of how dedifferentiation to a more stem-like phenotype plays key roles in the maintenance of cancer stem cell populations and disease progression. Through extensive parameter perturbation studies, we have quantified and ranked how DCIS is …

Pirtobrutinib Inhibits Wild-Type And Mutant Bruton’S Tyrosine Kinase-Mediated Signaling In Chronic Lymphocytic Leukemia, Burcu Aslan, Gorkem Kismali, Lakesla R Iles, Ganiraju C Manyam, Mary L Ayres, Lisa S Chen, Mihai Gagea, Maria Teresa Sabrina Bertilaccio, William G Wierda, Varsha Gandhi

Faculty, Staff and Student Publications

Pirtobrutinib (LOXO-305), a reversible inhibitor of Bruton's tyrosine kinase (BTK), was designed as an alternative strategy to treat ibrutinib-resistant disease that develops due to C481 kinase domain mutations. The clinical activity of pirtobrutinib has been demonstrated in CLL, but the mechanism of action has not been investigated. We evaluated pirtobrutinib in 4 model systems: first, MEC-1, a CLL cell line overexpressing BTKWT, BTKC481S, or BTKC481R; second, murine models driven by MEC-1 overexpressing BTKWT or BTKC481S; third, in vitro incubations of primary CLL cells; and finally, CLL patients during pirtobrutinib therapy (NCT03740529, ClinicalTrials.gov). Pirtobrutinib inhibited BTK activation as well …

Three-Dimensional Evaluation Of Isodose Radiation Volumes In Cases Of Severe Mandibular Osteoradionecrosis For The Prediction Of Recurrence After Segmental Resection, Haye H Glas, Joep Kraeima, Silke Tribius, Frank K J Leusink, Carsten Rendenbach, Max Heiland, Carmen Stromberger, Ashkan Rashad, Clifton D Fuller, Abdallah S R Mohamed, Stephen Y Lai, Max J H Witjes

Faculty, Staff and Student Publications

Background: Pre-operative margin planning for the segmental resection of affected bone in mandibular osteoradionecrosis (ORN) is difficult. The aim of this study was to identify a possible relation between the received RT dose, exposed bone volume and the progression of ORN after segmental mandibular resection.

Method: Patients diagnosed with grade 3-4 ORN for which a segmental resection was performed were included in the study. Three-dimensional reconstructions of RT isodose volumes were fused with postoperative imaging. The primary outcome was the recurrence of ORN after segmental resection. Subsequently, RT exposed mandibular bone volumes were calculated and the location of the bone …

Tite-Boin12: A Bayesian Phase I/Ii Trial Design To Find The Optimal Biological Dose With Late-Onset Toxicity And Efficacy, Yanhong Zhou, Ruitao Lin, J Jack Lee, Daniel Li, Li Wang, Ruobing Li, Ying Yuan

Faculty, Staff and Student Publications

In the era of immunotherapies and targeted therapies, the focus of early phase clinical trials has shifted from finding the maximum tolerated dose to identifying the optimal biological dose (OBD), which maximizes the toxicity-efficacy trade-off. One major impediment to using adaptive designs to find OBD is that efficacy or/and toxicity are often late-onset, hampering the designs’ real-time decision rules for treating new patients. To address this issue, we propose the model-assisted TITE-BOIN12 design to find OBD with late-onset toxicity and efficacy. As an extension of the BOIN12 design, the TITE-BOIN12 design also uses utility to quantify the toxicity-efficacy trade-off. We …

Gli1 Activates Pro-Fibrotic Pathways In Myelofibrosis Fibrocytes, Taghi Manshouri, Ivo Veletic, Ping Li, C Cameron Yin, Sean M Post, Srdan Verstovsek, Zeev Estrov

Faculty, Staff and Student Publications

Bone marrow (BM) fibrosis was thought to be induced exclusively by mesenchymal stromal cells (MSCs). However, we and others found that neoplastic fibrocytes induce BM fibrosis in myelofibrosis (MF). Because glioma-associated oncogene-1 (GLI1), an effector of the Hedgehog pathway, plays a role in the induction of BM fibrosis, we wondered whether GLI1 affects fibrocyte-induced BM fibrosis in MF. Multiplexed fluorescence immunohistochemistry analysis of MF patients' BM detected high levels of GLI1 in MF fibrocytes compared to MSCs or normal fibrocytes. Immunostaining, RNA in situ hybridization, gene expression analysis, and western immunoblotting detected high levels of GLI1 and GLI1-induced matrix metalloproteases …

Making National Cancer Institute-Designated Comprehensive Cancer Center Knowledge Accessible To Community Oncologists Via An Online Tumor Board: Longitudinal Observational Study, Maitri Kalra, Elizabeth Henry, Kelly Mccann, Meghan S Karuturi, Jean G Bustamante Alvarez, Amanda Parkes, Robert Wesolowski, Mei Wei, Sarah S Mougalian, Gregory Durm, Angel Qin, Caitlin Schonewolf, Meghna Trivedi, Avan J Armaghani, Frederick H Wilson, Wade T Iams, Anita A Turk, Praveen Vikas, Michael Cecchini, Sam Lubner, Priyadarshini Pathak, Kristen Spencer, Vadim S Koshkin, Matthew K Labriola, Catherine H Marshall, Katy E Beckermann, Marina N Sharifi, Anthony C Bejjani, Varsha Hotchandani, Samir Housri, Nadine Housri

Faculty, Staff and Student Publications

Background: Expert knowledge is often shared among multidisciplinary academic teams at tumor boards (TBs) across the country, but these conversations exist in silos and do not reach the wider oncology community.

Objective: Using an oncologist-only question and answer (Q&A) website, we sought to document expert insights from TBs at National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs) to provide educational benefits to the oncology community.

Methods: We designed a process with the NCI-CCCs to document and share discussions from the TBs focused on areas of practice variation on theMednet, an interactive Q&A website of over 13,000 US oncologists. The faculty translated …

Platelets Increase The Expression Of Pd-L1 In Ovarian Cancer, Min Soon Cho, Hani Lee, Ricardo Gonzalez-Delgado, Dan Li, Tomoyuki Sasano, Wendolyn Carlos-Alcalde, Qing Ma, Jinsong Liu, Anil K Sood, Vahid Afshar-Kharghan

Faculty, Staff and Student Publications

The interactions between platelets and cancer cells activate platelets and enhance tumor growth. Platelets increase proliferation and epithelial-mesenchymal transition in cancer cells, inhibit anoikis, enhance the extravasation of cancer cells, and protect circulating tumor cells against natural killer cells. Here, we have identified another mechanism by which platelets dampen the immune attack on cancer cells. We found that platelets can blunt the antitumor immune response by increasing the expression of inhibitory immune checkpoint (PD-L1) on ovarian cancer cells in vitro and in vivo. Platelets increased PD-L1 in cancer cells via contact-dependent (through NF-κB signaling) and contact-independent (through TFGβR1/Smad signaling) pathways. …

Cardiovascular Disease Prevention Education Using A Virtual Environment In Sexual-Minority Men Of Color With Hiv: Protocol For A Sequential, Mixed Method, Waitlist Randomized Controlled Trial, S Raquel Ramos, Constance Johnson, Gail Melkus, Trace Kershaw, Marya Gwadz, Harmony Reynolds, Allison Vorderstrasse

Faculty, Staff and Student Publications

Background: It is estimated that 70% of all deaths each year in the United States are due to chronic conditions. Cardiovascular disease (CVD), a chronic condition, is the leading cause of death in ethnic and racial minority males. It has been identified as the second most common cause of death in persons with HIV. By the year 2030, it is estimated that 78% of persons with HIV will be diagnosed with CVD.

Objective: We propose the first technology-based virtual environment intervention to address behavioral, modifiable risk factors associated with cardiovascular and metabolic comorbidities in sexual-minority men of color with HIV. …

An Observational Retrospective Study Of Adverse Events And Behavioral Outcomes During Pediatric Dental Sedation, Kawtar Zouaidi, Gregory Olson, Helen H Lee, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Purpose: The purpose of this study was to examine a university-based dental electronic health records (EHR) database to identify sedation-related adverse events (AEs) and assess patients' behavioral outcomes during routine pediatric dental sedations (PDSs) in a dental school clinic.

Methods: A database was screened for patients younger than 18 years old who had received dental sedation in 2019. The qualifying EHRs were then accessed and sedations were reviewed for AEs, which were categorized using a 12-point classification system and the Tracking and Reporting Outcomes of Procedural Sedation Tool. Patient behaviors were assessed using provider progress notes and categorized as presence/ …

Chronic Lymphocytic Leukemia Progression Diagnosis With Intrinsic Cellular Patterns Via Unsupervised Clustering, Pingjun Chen, Siba El Hussein, Fuyong Xing, Muhammad Aminu, Aparajith Kannapiran, John D Hazle, L Jeffrey Medeiros, Ignacio I Wistuba, David Jaffray, Joseph D Khoury, Jia Wu

Faculty, Staff and Student Publications

Identifying the progression of chronic lymphocytic leukemia (CLL) to accelerated CLL (aCLL) or transformation to diffuse large B-cell lymphoma (Richter transformation; RT) has significant clinical implications as it prompts a major change in patient management. However, the differentiation between these disease phases may be challenging in routine practice. Unsupervised learning has gained increased attention because of its substantial potential in data intrinsic pattern discovery. Here, we demonstrate that cellular feature engineering, identifying cellular phenotypes via unsupervised clustering, provides the most robust analytic performance in analyzing digitized pathology slides (accuracy = 0.925, AUC = 0.978) when compared to alternative approaches, such …

Targeting A Chemo-Induced Adaptive Signaling Circuit Confers Therapeutic Vulnerabilities In Pancreatic Cancer, Xu Feng, Mengfan Tang, Merve Dede, Dan Su, Guangsheng Pei, Dadi Jiang, Chao Wang, Zhen Chen, Mi Li, Litong Nie, Yun Xiong, Siting Li, Jeong-Min Park, Huimin Zhang, Min Huang, Klaudia Szymonowicz, Zhongming Zhao, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

Exploiting cancer vulnerabilities is critical for the discovery of anticancer drugs. However, tumor suppressors cannot be directly targeted because of their loss of function. To uncover specific vulnerabilities for cells with deficiency in any given tumor suppressor(s), we performed genome-scale CRISPR loss-of-function screens using a panel of isogenic knockout cells we generated for 12 common tumor suppressors. Here, we provide a comprehensive and comparative dataset for genetic interactions between the whole-genome protein-coding genes and a panel of tumor suppressor genes, which allows us to uncover known and new high-confidence synthetic lethal interactions. Mining this dataset, we uncover essential paralog gene …