Medical Specialties Commons^™

Characterization Of The Cholesterol Biosynthetic Pathway In Dioscorea Transversa, Lauren J Salisbury, Stephen J Fletcher, Jeanette E Stok, Luke R Churchman, Joanne T Blanchfield, James J De Voss

Faculty, Staff and Student Publications

Cholesterol is the precursor of bioactive plant metabolites such as steroidal saponins. An Australian plant, Dioscorea transversa, produces only two steroidal saponins: 1β-hydroxyprotoneogracillin and protoneogracillin. Here, we used D. transversa as a model in which to elucidate the biosynthetic pathway to cholesterol, a precursor to these compounds. Preliminary transcriptomes of D. transversa rhizome and leaves were constructed, annotated, and analyzed. We identified a novel sterol side-chain reductase as a key initiator of cholesterol biosynthesis in this plant. By complementation in yeast, we determine that this sterol side-chain reductase reduces Δ^24,28 double bonds required for phytosterol biogenesis as well …

Oncolytic Dnx-2401 Virotherapy Plus Pembrolizumab In Recurrent Glioblastoma: A Phase 1/2 Trial, Farshad Nassiri, Vikas Patil, Leeor S Yefet, Olivia Singh, Jeff Liu, Rachel M A Dang, Takafumi N Yamaguchi, Mariza Daras, Timothy F Cloughesy, Howard Colman, Priya U Kumthekar, Clark C Chen, Robert Aiken, Morris D Groves, Shirley S Ong, Rohan Ramakrishna, Michael A Vogelbaum, Simon Khagi, Thomas Kaley, Jason M Melear, David M Peereboom, Analiz Rodriguez, Maxim Yankelevich, Suresh G Nair, Vinay K Puduvalli, Kenneth Aldape, Andrew Gao, Álvaro López-Janeiro, Carlos E De Andrea, Marta M Alonso, Paul Boutros, Joan Robbins, Warren P Mason, Adam M Sonabend, Roger Stupp, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang, Gelareh Zadeh

Faculty, Staff and Student Publications

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response …

Sex- And Ethnic-Specific Patterns In The Incidence Of Hip Fracture Among Older Us Asian And Non-Hispanic White Adults, Joan C Lo, Malini Chandra, David R Lee, Jeanne A Darbinian, Nancy P Gordon, David W Zeltser, Christopher D Grimsrud, Catherine Lee

Faculty, Staff and Student Publications

BACKGROUND: Asian and Pacific Islander (Asian/PI) adults have lower hip fracture incidence than non-Hispanic White (NHW) adults, but data regarding Asian/PI subgroups are limited. We compared hip fracture incidence among older US Asian/PI and NHW populations, including ethnic subgroup differences.

METHODS: Using observational data from a California healthcare system, we identified Asian/PI and NHW adults aged ≥50 years (2000-2019) and followed subjects to 2021 for hip fracture determined by principal/primary hospital diagnosis or by secondary hospital diagnosis with hip/femur procedure codes. Age-adjusted hip fracture incidence was calculated with 95% confidence intervals (CIs). Log-Poisson regression was used to determine fracture incidence …

Metabolic Adaptation To Consume Butyrate Under Prolonged Resource Exhaustion, Sophia Katz, Claudia Grajeda-Iglesias, Bella Agranovich, Alia Ghrayeb, Ifat Abramovich, Sabrin Hilau, Eyal Gottlieb, Ruth Hershberg

Faculty, Staff and Student Publications

Bacteria must often survive following the exhaustion of their external growth resources. Fitting with this need, many bacterial species that cannot sporulate, can enter a state known as long term stationary phase (LTSP) in which they can persist for years within spent media. Several recent studies have revealed the dynamics of genetic adaptation of Escherichia coli under LTSP. Yet, the metabolic consequences of such genetic adaptation were not addressed. Here, we characterized the metabolic changes LTSP populations experience, over the first 32 days under LTSP. This allowed us to link genetic adaptations observed in a convergent manner across LTSP populations …

Differential Effects Of An Ed-To-Home Care Transitions Intervention In An Older Adult Population: A Latent Class Analysis, Rebecca K Green, Kenneth J Nieser, Gwen C Jacobsohn, Amy L Cochran, Thomas V Caprio, Jeremy T Cushman, Amy J H Kind, Michael Lohmeier, Manish N Shah

Faculty, Staff and Student Publications

BACKGROUND: Older adults frequently return to the emergency department (ED) within 30 days of a visit. High-risk patients can differentially benefit from transitional care interventions. Latent class analysis (LCA) is a model-based method used to segment the population and test intervention effects by subgroup.

OBJECTIVES: We aimed to identify latent classes within an older adult population from a randomized controlled trial evaluating the effectiveness of an ED-to-home transitional care program and test whether class membership modified the intervention effect.

RESEARCH DESIGN: Participants were randomized to receive the Care Transitions Intervention or usual care. Study staff collected outcomes data through medical …

An End-To-End In-Silico And In-Vitro Drug Repurposing Pipeline For Glioblastoma, Ko-Hong Lin, Jay-Jiguang Zhu, Judith A Smith, Yejin Kim, Xiaoqian Jiang

Faculty, Staff and Student Publications

Our study aims to address the challenges in drug development for glioblastoma, a highly aggressive brain cancer with poor prognosis. We propose a computational framework that utilizes machine learning-based propensity score matching to estimate counterfactual treatment effects and predict synergistic effects of drug combinations. Through our in-silico analysis, we identified promising drug candidates and drug combinations that warrant further investigation. To validate these computational findings, we conducted in-vitro experiments on two GBM cell lines, U87 and T98G. The experimental results demonstrated that some of the identified drugs and drug combinations indeed exhibit strong suppressive effects on GBM cell growth. Our …

The Tgf-Β Superfamily As Potential Therapeutic Targets In Pancreatic Cancer, William A Grobman, Grecio J Sandoval, Torri D Metz, Tracy A Manuck, Rebecca G Clifton, Brenna L Hughes, George R Saade, Monica Longo, Amber Sowles, Kelly Clark, Hyagriv N Simhan, Dwight J Rouse, Hector Mendez-Figueroa, Cynthia Gyamfi-Bannerman, Jennifer L Bailit, Maged M Costantine, Harish M Sehdev, Alan T N Tita, George A Macones

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate whether preterm birth rates changed in relation to the onset of the coronavirus disease 2019 (COVID-19) pandemic and whether any change depended on socioeconomic status.

METHODS: This is an observational cohort study of pregnant individuals with a singleton gestation who delivered in the years 2019 and 2020 at 1 of 16 U.S. hospitals of the Maternal-Fetal Medicine Units Network. The frequency of preterm birth for those who delivered before the onset of the COVID-19 pandemic (ie, in 2019) was compared with that of those who delivered after its onset (ie, in 2020). Interaction analyses were performed for …

It Is Better To Light A Candle Than To Curse The Darkness: Single-Cell Transcriptomics Sheds New Light On Pancreas Biology And Disease, Amelia T Cephas, William L Hwang, Anirban Maitra, Oren Parnas, Kathleen E Delgiorno

Faculty, Staff and Student Publications

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult to study organs, such as the pancreas. With the advent of these technologies and approaches, the field has grown, in just a few years, from profiling pancreas disease states to identifying molecular mechanisms of therapy resistance in pancreatic ductal adenocarcinoma, a particularly deadly cancer. Single-cell transcriptomics and related spatial approaches have identified previously undescribed epithelial and stromal cell types and states, how these populations change with disease progression, and potential mechanisms of action which will serve as the basis …

Causal Linkage Of Presence Of Mutant Npm1 To Efficacy Of Novel Therapeutic Agents Against Aml Cells With Mutant Npm1, Christopher P Mill, Warren Fiskus, Kaberi Das, John A Davis, Christine E Birdwell, Tapan M Kadia, Courtney D Dinardo, Naval Daver, Koichi Takahashi, Koji Sasaki, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Sanam Loghavi, Hagop Kantarjian, Kapil N Bhalla

Faculty, Staff and Student Publications

In AML with NPM1 mutation causing cytoplasmic dislocation of NPM1, treatments with Menin inhibitor (MI) and standard AML chemotherapy yield complete remissions. However, the causal and mechanistic linkage of mtNPM1 to the efficacy of these agents has not been definitively established. Utilizing CRISPR-Cas9 editing to knockout (KO) or knock-in a copy of mtNPM1 in AML cells, present studies demonstrate that KO of mtNPM1 from AML cells abrogates sensitivity to MI, selinexor (exportin-1 inhibitor), and cytarabine. Conversely, the knock-in of a copy of mtNPM1 markedly sensitized AML cells to treatment with MI or cytarabine. Following AML therapy, most elderly patients with …

Dural Sinus Narrowing In Patients With Spontaneous Anterior Skull Base Cerebrospinal Fluid Leak, Karim W Asi, Brian H Cameron, Elliot R Friedman, Jeffrey P Radabaugh, Martin J Citardi, Amber U Luong, William C Yao

Faculty, Staff and Student Publications

OBJECTIVES: Current evidence suggests a link between idiopathic intracranial hypertension (IIH) and spontaneous cerebrospinal fluid (sCSF) leak, as well as between IIH and dural venous sinus (DVS) narrowing. However, there are limited data linking DVS narrowing and sCSF leak. This study aims to determine the prevalence of DVS narrowing in patients with sCSF leak.

METHODS: A retrospective review of all patients with sCSF leak that presented to a tertiary academic center from 2008 to 2019. Preoperative imaging was independently reviewed by two neuroradiologists to evaluate for DVS narrowing. Available literature was used to estimate the prevalence of DVS narrowing in …

National Institutes Of Health Diversity Supplement Awards: Experience Of Radiation Oncology Principal Investigators And Trainees, Afua A Yorke, Michael K Rooney, Jillian Rigert, Amy C Moreno, Clifton D Fuller, Eric C Ford

Faculty, Staff and Student Publications

No abstract provided.

Adaptive Immunity In Genitourinary Cancers, Madhuri Koti, Trinity Bivalacqua, Peter C Black, Toni Cathomen, Matthew D Galsky, James L Gulley, Molly A Ingersoll, Ashish M Kamat, Wassim Kassouf, D Robert Siemens, Jianjun Gao

Faculty, Staff and Student Publications

Context: While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor, response rates in patients with prostate cancer have remained poor. The factors underlying suboptimal outcomes observed in patients treated with novel immunotherapies are still to be resolved.

Objective: To review the literature and describe the key adaptive immune physiological events associated with cancer progression and therapeutic response in genitourinary (GU) cancers.

Evidence acquisition: We performed a nonsystematic, collaborative narrative review to highlight recent advancements leading to the current state of knowledge on the critical mediators …

The Correlation Between Neonatal Intensive Care Unit Safety Culture And Quality Of Care, Karan Sud, Navneet Narula, Elena Aikawa, Eloisa Arbustini, Philippe Pibarot, Giampaolo Merlini, Robert S Rosenson, Surya V Seshan, Edgar Argulian, Amir Ahmadi, Fang Zhou, Andre L Moreira, Nancy Côté, Sotirios Tsimikas, Valentin Fuster, Sam Gandy, Robert O Bonow, Olga Gursky, Jagat Narula

Faculty, Staff and Student Publications

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits …

Impact Of Transfused Citrate On Pathophysiology In Massive Transfusion, Jacob B Schriner, J Michael Van Gent, M Adam Meledeo, Scott D Olson, Bryan A Cotton, Charles S Cox, Brijesh S Gill

Faculty, Staff and Student Publications

This narrative review article seeks to highlight the effects of citrate on physiology during massive transfusion of the bleeding patient.

DATA SOURCES: A limited library of curated articles was created using search terms including "citrate intoxication," "citrate massive transfusion," "citrate pharmacokinetics," "hypocalcemia of trauma," "citrate phosphate dextrose," and "hypocalcemia in massive transfusion." Review articles, as well as prospective and retrospective studies were selected based on their relevance for inclusion in this review.

STUDY SELECTION: Given the limited number of relevant studies, studies were reviewed and included if they were written in English. This is not a systematic review nor a …

Association Between Early Prostacyclin Therapy And Extracorporeal Life Support Use In Patients With Congenital Diaphragmatic Hernia, Akila B Ramaraj, Samuel E Rice-Townsend, Carrie L Foster, Delphine Yung, Emma O Jackson, Ashley H Ebanks, Matthew T Harting, Rebecca A Stark, Congenital Diaphragmatic Hernia Study Group

Faculty, Staff and Student Publications

IMPORTANCE: Prostacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension in neonates. Its use may decrease the need for extracorporeal life support (ECLS).

OBJECTIVE: To evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH.

DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study from the CDH Study Group (CDHSG) registry of patients born from January 2007 to December 2019. Patients were from 88 different tertiary pediatric referral centers worldwide that contributed data to the CDHSG. Patients were included in the study if they were admitted within the first …

Perception Of Treatment Success And Impact On Function With Antibiotics Or Appendectomy For Appendicitis: A Randomized Clinical Trial With An Observational Cohort, Callie M Thompson, Emily C Voldal, Giana H Davidson, Sabrina E Sanchez, Patricia Ayoung-Chee, Jesse Victory, Mary Guiden, Bonnie Bizzell, Jacob Glaser, Christopher Hults, Thea P Price, Nicole Siparsky, Kristin Ohe, Katherine A Mandell, Daniel A Deugarte, Amy H Kaji, Lisandra Uribe, Lillian S Kao, Krislynn M Mueck, Farhood Farjah, Wesley H Self, Sunday Clark, F Thurston Drake, Katherine Fischkoff, Elizaveta Minko, Joseph Cuschieri, Brett Faine, Dionne A Skeete, Naila Dhanani, Mike K Liang, Anusha Krishnadasan, David A Talan, Erin Fannon, Larry G Kessler, Bryan A Comstock, Patrick J Heagerty, Sarah E Monsell, Sarah O Lawrence, David R Flum, Danielle C Lavallee, Writing Group For The Coda Collaborative

Faculty, Staff and Student Publications

OBJECTIVE: To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days.

SUMMARY BACKGROUND DATA: The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes.

METHODS: We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized …

Use Of Telemedicine For Postdischarge Assessment Of The Surgical Wound: International Cohort Study, And Systematic Review With Meta-Analysis, Nihr Global Health Research Unit On Global Surgery, Globalsurg Collaborative

Faculty, Staff and Student Publications

OBJECTIVE: This study aimed to determine whether remote wound reviews using telemedicine can be safely upscaled, and if standardized assessment tools are needed.

BACKGROUND: Surgical site infection (SSI) is the most common complication of surgery worldwide, and frequently occurs after hospital discharge. Evidence to support implementation of telemedicine during postoperative recovery will be an essential component of pandemic recovery.

METHODS: The primary outcome of this study was SSI reported up to 30 days after surgery (SSI), comparing rates reported using telemedicine (telephone and/or video assessment) to those with in-person review. The first part of this study analyzed primary data from …

Stress Reactivity After Pediatric Traumatic Brain Injury: Relation With Behavioral Adjustment, Taiane De Azevedo Cardoso, Ritele H Silva, Jessica L Fernandes, Camila O Arent, Graziela Amboni, Laura A Borba, Alex Paulo Z Padilha, Maria Eduarda M Botelho, Amanda L Maciel, Tatiana Barichello, Rodrigo Morales, Silvio José B Soares, Margarete D Bagatini, Claudia Dallagnol, Marta Elisa Brighenti, Zuleide Maria Ignácio, João Quevedo, Luciane B Ceretta, Gislaine Z Réus

Faculty, Staff and Student Publications

BACKGROUND: Although many studies have pointed out a possible relationship between COVID-19 and the presence of psychiatric disorders, the majority of the studies have significant limitations. This study investigates the influence of COVID-19 infection on mental health.

METHODS: This cross-sectional study included an age- and sex-matched sample of adult individuals positive (cases) or negative (controls) for COVID-19. We evaluated the presence of psychiatric conditions and C-reactive protein (CRP).

RESULTS: Findings showed greater severity of depressive symptoms, higher levels of stress, and greater CRP in cases. The severity of depressive and insomnia symptoms, as well as the CRP were more remarkable …

Effects Of Different Spectrum Of Leds On Retinal Degeneration Through Regulating Endoplasmic Reticulum Stress, Wenyi Chen, Rong Lin, Kunhong Xiao, Kun Yuan, Zhongjiang Chen, Yan Huang

Faculty, Staff and Student Publications

PURPOSE: To evaluate the impact of full-spectrum light-emitting diodes (LEDs) on albino guinea pigs' retina and investigate the roles of short-wavelength opsin (S-opsin) and endoplasmic reticulum (ER) stress in light-induced retinal degeneration (LIRD).

METHODS: Three-week-old albino guinea pigs (n = 30) were distributed into five groups under 12/12 light/dark cycles with indoor natural light (NC; 300-500 lux, n = 6), full-spectrum LEDs (FL; 300 lux, n = 6; 3000 lux, n = 6), and commercial cold-white LEDs (CL; 300 lux, n = 6; 3000 lux, n = 6) and raised for 28 days. Hematoxylin and eosin staining and transmission electron …

Ccr7 Mediated Mimetic Dendritic Cell Vaccine Homing In Lymph Node For Head And Neck Squamous Cell Carcinoma Therapy, Jiabin Xu, Hong Liu, Tao Wang, Zhenfu Wen, Haolin Chen, Zeyu Yang, Liyan Li, Shan Yu, Siyong Gao, Le Yang, Kan Li, Jingyuan Li, Xiang Li, Lixin Liu, Guiqing Liao, Yongming Chen, Yujie Liang

Faculty, Staff and Student Publications

Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy-M-Exo) is developed via fusing tumor-derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the …

Cest-Mri For Body Oncologic Imaging: Are We There Yet?, Elena Vinogradov, Jochen Keupp, Ivan E Dimitrov, Stephen Seiler, Ivan Pedrosa

Faculty, Staff and Student Publications

Chemical exchange saturation transfer (CEST) MRI has gained recognition as a valuable addition to the molecular imaging and quantitative biomarker arsenal, especially for characterization of brain tumors. There is also increasing interest in the use of CEST-MRI for applications beyond the brain. However, its translation to body oncology applications lags behind those in neuro-oncology. The slower migration of CEST-MRI to non-neurologic applications reflects the technical challenges inherent to imaging of the torso. In this review, we discuss the application of CEST-MRI to oncologic conditions of the breast and torso (i.e., body imaging), emphasizing the challenges and potential solutions to address …

Effects Of Short-Term Nicotine Deprivation On Delay Discounting Among Young, Experienced, Exclusive Ends Users: An Initial Study, Irene Pericot-Valverde, Jin H Yoon, Kaileigh A Byrne, Moonseong Heo, Jiajing Niu, Alain H Litwin, Diann E Gaalema

Faculty, Staff and Student Publications

Delay discounting describes how rapidly delayed rewards lose value as a function of delay and serves as one measure of impulsive decision-making. Nicotine deprivation among combustible cigarette smokers can increase delay discounting. We aimed to explore changes in discounting following nicotine deprivation among electronic nicotine delivery systems (ENDS) users. Thirty young adults (aged 18-24 years) that exclusively used ENDS participated in two laboratory sessions: one with vaping as usual and another after 16 hr of nicotine deprivation (biochemically assessed). At each session, participants completed a craving measure and three hypothetical delay discounting tasks presenting choices between small, immediate rewards and …

2021 Aapm Equity, Diversity, And Inclusion Climate Survey Executive Summary, Kristi R G Hendrickson, Stephen M Avery, Richard Castillo, Laura Cervino, Ashley Cetnar, Nolan L Gagne, Wendy Harris, Amirh Johnson, Megan E Lipford, Nadia Octave, Kelly C Paradis, Angélica Pérez-Andújar, Surendra Prajapati, Julianne Pollard-Larkin

Faculty, Staff and Student Publications

Purpose: The American Association of Physicists in Medicine (AAPM) shares the results, conclusions, and recommendations from the initial Equity, Diversity, and Inclusion Climate Survey conducted in 2021.

Methods and materials: The climate survey targeted medical physicists who are full members of the AAPM and included demographic inquiries and questions intended to assess the working environmental climate in terms of a sense of belonging and inclusion, experiences of discrimination and harassment, and obstacles to participation within the AAPM. The survey invitation was sent to 5,500 members. Responses were collected from 1385 members (response rate of 25%) between January and February 2021. …

Survival Outcomes Of Patients With Mycosis Fungoides Involving The External Ear And Ear Canal, Alex J Wilkinson, Marc-Elie Nader, Dianna Roberts, Madeleine Duvic, Jillian R Gunther, Bouthaina S Dabaja, Paul W Gidley

Faculty, Staff and Student Publications

OBJECTIVES/HYPOTHESIS: Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Disease involvement of specific locations may be more significant than simply the symptoms associated with that site; it is possible that involvement of certain sites could be associated with poor prognosis. We aimed to evaluate the outcomes of patients with MF with documented involvement of the EAC and external ear.

STUDY DESIGN: Retrospective analysis.

METHODS: We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021.

RESULTS: We report the largest series of patients with MF involving the external ear and EAC. …

Redox-Dependent Activation Of Lung Epithelial Stat3 Is Required For Inducible Protection Against Bacterial Pneumonia, Vikram V Kulkarni, Yongxing Wang, Jezreel Pantaleon Garcia, Scott E Evans

Faculty, Staff and Student Publications

The lung epithelium is dynamic, capable of considerable structural and functional plasticity in response to pathogen challenges. Our laboratory has demonstrated that an inhaled combination of a Toll-like receptor (TLR) 2/6 agonist and a TLR9 agonist (Pam2ODN) results in robust protection against otherwise lethal pneumonias. We have previously shown that intact epithelial TLR signaling and generation of multisource epithelial reactive oxygen species (ROS) are required for inducible protection. Further investigating the mechanisms underlying this phenomenon of inducible resistance, reverse-phase protein array analysis demonstrated robust STAT3 (signal transducer and activator of transcription 3) phosphorylation following treatment of lung epithelial cells. We …

A 3d Perfusable Platform For In Vitro Culture Of Patient Derived Xenografts, Lindsey K Sablatura, Kristin M Bircsak, Peter Shepherd, Madhavi Bathina, Karla Queiroz, Mary C Farach-Carson, Rick A Kittles, Pamela E Constantinou, Anthony Saleh, Nora M Navone, Daniel A Harrington

Faculty, Staff and Student Publications

Many advanced cancer models, such as patient-derived xenografts (PDXs), offer significant benefits in their preservation of the native tumor's heterogeneity and susceptibility to treatments, but face significant barriers to use in their reliance on a rodent host for propagation and screening. PDXs remain difficult to implement in vitro, particularly in configurations that enable both detailed cellular analysis and high-throughput screening (HTS). Complex multilineage co-cultures with stromal fibroblasts, endothelium, and other cellular and structural components of the tumor microenvironment (TME) further complicate ex vivo implementation. Herein, the culture of multiple prostate cancer (PCa)-derived PDX models as 3D clusters within engineered biomimetic …

Author Correction: Comprehensive Molecular Characterization Of Mitochondrial Genomes In Human Cancers, Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J Yoon, Yang Yang, Inigo Martincorena, Chad J Creighton, John N Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J Campbell, Han Liang

Faculty, Staff and Student Publications

No abstract provided.

Fighting The Obesity Pandemic During The Covid-19 Pandemic, Jordan E Grubbs, Haley J Daigle, Megan Shepherd, Robert E Heidel, Kyle L Kleppe, Matthew L Mancini, Gregory J Mancini

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic created delays in surgical care. The population with obesity has a high risk of death from COVID-19. Prior literature shows the most effective way to combat obesity is by weight loss surgery. At different times throughout the COVID-19 pandemic, elective inpatient surgeries have been halted due to bed availability. Recognizing that major complications following bariatric surgery are extremely low (bleeding 0-4%, anastomotic leaks 0.8%), we felt outpatient bariatric surgery would be safe for low-risk patients. Complications such as DVT, PE, infection, and anastomotic leaks typically present after 7 days postoperatively, well outside the usual length of …

Obesity Medicine As A Subspecialty And United States Certification - A Review, Angela Fitch, Deborah B Horn, Christopher D Still, Lydia C Alexander, Sandra Christensen, Nicholas Pennings, Harold Edward Bays

Faculty, Staff and Student Publications

BACKGROUND: Certification of obesity medicine for physicians in the United States occurs mainly via the American Board of Obesity Medicine (ABOM). Obesity medicine is not recognized as a subspecialty by the American Board of Medical Specialties (ABMS) or the American Osteopathic Association (AOA). This review examines the value of specialization, status of current ABOM Diplomates, governing bodies involved in ABMS/AOA Board Certification, and the advantages and disadvantages of an ABMS/AOA recognized obesity medicine subspecialty.

METHODS: Data for this review were derived from PubMed and appliable websites. Content was driven by the expertise, insights, and perspectives of the authors.

RESULTS: The …

Utility And Usability Of Laser Speckle Contrast Imaging (Lsci) For Displaying Real-Time Tissue Perfusion/Blood Flow In Robot-Assisted Surgery (Ras): Comparison To Indocyanine Green (Icg) And Use In Laparoscopic Surgery, Yao Z Liu, Shinil K Shah, Christina M Sanders, Chibueze A Nwaiwu, Alyson F Dechert, Saloni Mehrotra, Steven D Schwaitzberg, Peter C W Kim, Erik B Wilson

Faculty, Staff and Student Publications

BACKGROUND: Utility and usability of laser speckle contrast imaging (LSCI) in detecting real-time tissue perfusion in robot-assisted surgery (RAS) and laparoscopic surgery are not known. LSCI displays a color heatmap of real-time tissue blood flow by capturing the interference of coherent laser light on red blood cells. LSCI has advantages in perfusion visualization over indocyanine green imaging (ICG) including repeat use on demand, no need for dye, and no latency between injection and display. Herein, we report the first-in-human clinical comparison of a novel device combining proprietary LSCI processing and ICG for real-time perfusion assessment during RAS and laparoscopic surgeries. …