Medical Specialties Commons^™

Rational Design Of Highly Potent And Selective Covalent Map2k7 Inhibitors, Dalton R Kim, Meghan J Orr, Ada J Kwong, Kristine K Deibler, Hasan H Munshi, Cory Seth Bridges, Taylor Jie Chen, Xiaoyu Zhang, H Daniel Lacorazza, Karl A Scheidt

Faculty, Staff and Students Publications

The mitogen-activated protein kinase signaling cascade is conserved across eukaryotes, where it plays a critical role in the regulation of activities including proliferation, differentiation, and stress responses. This pathway propagates external stimuli through a series of phosphorylation events, which allows external signals to influence metabolic and transcriptional activities. Within the cascade, MEK, or MAP2K, enzymes occupy a molecular crossroads immediately upstream to significant signal divergence and cross-talk. One such kinase, MAP2K7, also known as MEK7 and MKK7, is a protein of great interest in the molecular pathophysiology underlying pediatric T cell acute lymphoblastic leukemia (T-ALL). Herein, we describe the rational …

3-Phosphoinositide-Dependent Kinase 1 Drives Acquired Resistance To Osimertinib, Ismail M Meraz, Mourad Majidi, Bingliang Fang, Feng Meng, Lihui Gao, Ruping Shao, Renduo Song, Feng Li, Yonathan Lissanu, Huiqin Chen, Min Jin Ha, Qi Wang, Jing Wang, Elizabeth Shpall, Sung Yun Jung, Franziska Haderk, Philippe Gui, Jonathan Wesley Riess, Victor Olivas, Trever G Bivona, Jack A Roth

Faculty, Staff and Students Publications

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of …

Co-Clinical Imaging Metadata Information (Cimi) For Cancer Research To Promote Open Science, Standardization, And Reproducibility In Preclinical Imaging, Stephen M Moore, James D Quirk, Andrew W Lassiter, Richard Laforest, Gregory D Ayers, Cristian T Badea, Andriy Y Fedorov, Paul E Kinahan, Matthew Holbrook, Peder E Z Larson, Renuka Sriram, Thomas L Chenevert, Dariya Malyarenko, John Kurhanewicz, A Mcgarry Houghton, Brian D Ross, Stephen Pickup, James C Gee, Rong Zhou, Seth T Gammon, Henry Charles Manning, Raheleh Roudi, Heike E Daldrup-Link, Michael T Lewis, Daniel L Rubin, Thomas E Yankeelov, Kooresh I Shoghi

Faculty, Staff and Students Publications

Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute's (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an …

Management Of Primary Spontaneous Pneumothorax In Children: A Single Institution Protocol Analysis, Shai Stewart Md, James Fraser, Nelimar Cruz-Centeno, Derek Marlor, Rebecca M. Rentea, Pablo Aguayo, David Juang, Jason D. Fraser, Charles L. Snyder, Richard J. Hendrickson, Tolulope A. Oyetunji, Shawn D. St.Peter

Research Days

Background: Primary spontaneous pneumothorax (PSP) affects 3.4 per 100,000 children in the United States. Regardless of the initial management, additional procedures, and prolonged hospital length of stay (LOS) may occur. There is currently no consensus in the pediatric surgical community on the optimal management of these patients, which has resulted in marked variability in management. The Midwest Pediatric Surgery Consortium (MWPSC), of which our site is a participant, suggested a management algorithm to include simple aspiration upon presentation, and if this fails, VATS should be considered.

Objectives/Goal: The purpose of this study was to evaluate the outcomes of instituting a …

Sepsis-Induced Acute Lung Injury (Ali) And The Development Of Bronchopulmonary Dysplasia (Bpd) In Premature Infants., Jacob S. Ward, Hung-Wen Yeh, Megan Tucker, Venkatesh Sampath

Research Days

Background: Bronchopulmonary dysplasia (BPD) is a significant cause of morbidity and mortality in premature infants with several known risk factors. Recent literature described the harmful effect of inflammation on the developing lung. Recently, we showed that late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) causes acute lung injury (ALI) in preterm infants as measured by increases in pulmonary severity scores (PSS). The aim of this study was to investigate the association between LOS-induced ALI and BPD outcomes. We hypothesized that LOS would increase the likelihood of developing BPD, and the associated LOS-induced ALI will add to the ability to predict development …

Institutional Outcomes Of Blunt Liver & Splenic Injury In The Atomac Era, Shai Stewart Md, James Fraser, Rebecca M. Rentea, Pablo Aguayo, David Juang, Jason D. Fraser, Charles L. Snyder, Richard J. Hendrickson, Shawn D. St.Peter, Tolulope A. Oyetunji

Research Days

Background: The Arizona-Texas-Oklahoma-Memphis-Arkansas Consortium (ATOMAC) practice management guideline (PMG) was created to standardize management of blunt liver or spleen injury (BLSI) across pediatric trauma centers. Evaluations of institutional outcomes after its adoption remain scarce. We describe our outcomes since PMG adoption at our institution.

Objectives/Goal: The purpose of this study was to assess patient outcomes and resource utilization after implementation of this protocol. We hypothesized there is no difference in length of stay (LOS) or complications regardless of grade of isolated injuries to the liver or spleen. In addition, there is limited guidance on the management of concurrent injuries to …

Predicting Avascular Necrosis After Unstable Slipped Capital Femoral Epiphysis, Jonathan Warren, Alexander Metoxen, Michael Held, Brant Ansley, Berglund Lisa

Research Days

Background: There is no consensus in the literature on the risk of developing avascular necrosis (AVN) after unstable slipped capital femoral epiphysis (SCFE). In recent years, a number of studies have sought to better characterize risk factors for AVN in this population. However, to the best of our knowledge, there is no study that uses predictive modeling to assess the chance of developing AVN based on different patient-centric factors.

Objectives/Goal: Our goal is to assess whether or not previously-published risk factors for AVN in unstable SCFE such as duration of symptoms, reduction type, type of surgery, timing of surgery, and …

Laparoscopic Versus Open Inguinal Hernia Repair: A Single Institution Comparison Of 1200 Patients, Shai Stewart Md, Wendy Jo Svetanoff, James Fraser, Rebecca M. Rentea, Pablo Aguayo, David Juang, Jason D. Fraser, Charles L. Snyder, Richard J. Hendrickson, Shawn D. St.Peter, Tolulope A. Oyetunji

Research Days

Background: : Laparoscopy has become the standard of care for many pediatric surgical procedures; however, there is no consensus regarding the optimal approach for inguinal hernia repair (IHR). We report our experience over an 8-year period with open and laparoscopic inguinal hernia repair (LIHR).

Objectives/Goal: We aim to describe our experience within a free-standing tertiary care pediatric institution and compare outcomes between open and laparoscopic repair of pediatric inguinal hernias.

Methods/Design: A retrospective review of patients under 18 years who underwent IHR between June 2010 and June 2017 was performed. The open technique utilizes high ligation of the internal ring, …

“There’S A Difference In Practice When You Have To Make The Decision”: Autonomy In Pediatric Emergency Medicine Fellowship, Katherine Dunne, Vivek Dubey, Sarkan Toy, Camryn Martinez, Kelsey Gavin, Christopher S. Kennedy

Research Days

Background: The Accreditation Council for Graduate Medical Education allows individual training programs to define appropriate supervision and autonomy commensurate with the trainees’ knowledge, clinical competence, and patient complexity and acuity. In pediatric emergency medicine (PEM), supervision is not standardized and subject to supervisor discretion, creating variability in trainee autonomy.

Objectives/Goal: To explore the concept of autonomy from the perspectives of PEM fellows and faculty.

Methods/Design: We conducted a qualitative study consisting of semi-structured interviews of PEM fellows and faculty from a large, single-center pediatric emergency medicine fellowship program. A trained interviewer conducted the interviews over an electronic interview platform. Audio …

A Novel Approach For Laparoscopic Direct Inguinal Hernia Repair In Children, Shai Stewart Md, Charlene Dekonenko, Nelimar Cruz-Centeno, Derek Marlor, Jason D. Fraser

Research Days

Background: Inguinal hernia repair is one of the most common operations performed by pediatric surgeons, and the frequency of laparoscopy for repair is increasing. The vast majority of these are indirect hernias and therefore how to best repair a direct defect when seen during laparoscopy is still unknown. Simple high ligation of the hernia sac (as is done in an indirect hernia) does not repair the inguinal floor weakness/defect seen in a direct hernia.

Objectives/Goal: We therefore present a case of laparoscopic bilateral indirect and direct inguinal hernia repair, commonly known as pantaloon hernia, repaired without mesh and utilizing the …

Institutional Use Of Ultrasound In The Evaluation Of Cryptorchidism, Shai Stewart Md, Dae H. Kim, Nelimar Cruz-Centeno, Derek Marlor, James Fraser, Tolulope A. Oyetunji Md Mph, Shawn D. St.Peter

Research Days

Background, Objectives/Goal, Methods/Design, Results, Conclusions limited to 500 words Background: In 2014, the American Urological Association guidelines recommended against the performance of ultrasound and other imaging modalities in the evaluation of patients with cryptorchidism prior to expert consultation. We hypothesized that ultrasound remains overused by referring physicians.

Objectives/Goal: We aimed to examine our institutional experience and measure adherence to currently available guidelines.

Methods/Design: An institutional review board (IRB) approved retrospective review of ultrasound utilization in the evaluation of patients with cryptorchidism was performed from June 1, 2016, to June 30, 2018, at a single tertiary level pediatric hospital.

Results: We …

Antibiotic Monotherapy Vs Dual-Drug Therapy In Perforated Appendicitis: Single Center Retrospective Review, Shai Stewart Md, Nelimar Cruz-Centeno, Derek Marlor, Dae H. Kim, Shawn D. St Peter, Tolulope A. Oyetunji Md Mph

Research Days

Background: The optimal antibiotic regimen in perforated appendicitis to reduce intraabdominal abscess (IAA) formation has not yet been agreed upon in the pediatric surgery community. We aimed to evaluate the outcomes of patients with perforated appendicitis when intravenous antibiotic monotherapy with Piperacillin-Tazobactam (PT) versus dual-drug therapy with Ceftriaxone and Metronidazole (CM) are administered. We hypothesized there is no difference in the rate of IAA formation with antibiotic monotherapy, as opposed to our once-daily dosed, institutional standard dual-drug therapy.

Objectives/Goal: The goal was to determine if our current management protocols for acute appendicitis were delivering the best possible results for our …

Two Adolescent Idiopathic Scoliosis (Ais) Cases, Two Surgeons, One Operating Room, One Day. Faster And Safer Than One Case In A Day., Jonathan Warren, Robert C. Link, Sean Bonanni, John T. Anderson, Richard M. Schwend

Research Days

Background: To lessen surgical times for AIS patients undergoing posterior spinal instrumentation and fusion (PSIF), our department developed a quality improvement initiative where two AIS cases were completed in one day by a specialized team with two surgeons operating together in the same operating room (OR).

Objectives/Goal: Our purpose is to describe the results of this initiative and compare operative times and outcomes to single cases completed by a single surgeon during the same period.

Methods/Design: From 2017-2023, patients aged 10-18 years with AIS were scheduled to undergo primary PSIF on the dedicated “Two Spine Tuesday” at our institution (Group …

Gastrointestinal Bleeding As Initial Manifestation Of Injection Drug Use-Associated Amyloidosis, Mohammed Rifat Shaik, Nishat Anjum Shaikh, Elvina Yunasan, Erika Wheeler, Robert T Chow

Journal of Community Hospital Internal Medicine Perspectives

Systemic amyloidosis has been reported in the context of injection drug use, usually related to ongoing chronic inflammation and persistent cutaneous infections. The kidneys are almost always the first organs affected in that setting. Involvement of the gastrointestinal tract is less common and rarely the initial site of presentation. We present a case of systemic amyloidosis that primarily manifested in the gastrointestinal tract, occurring in the setting of chronic injection drug use. The patient's hemoglobin level dropped progressively over time due to ongoing, slow gastrointestinal bleeding, prompting an endoscopic examination that ultimately confirmed the presence of gastrointestinal amyloidosis. As the …

Recurrent Psychosis In Non-Celiac Gluten Sensitivity, Scarlet Louis-Jean, Shire Chaudhry

Journal of Community Hospital Internal Medicine Perspectives

Neuropsychological manifestations following food exposures in patients with food sensitivities are increasingly being identified in the literature, as understanding of the gut-brain axis is further improved. Non-celiac gluten sensitivity (NCGS) has been shown to occur in individuals without serological or biopsied evidence of celiac disease (CD), who manifest psychotic or mood disorders that resolve following elimination of gluten. In this case history, we discuss a similar manifestation in a 31-year-old woman without serological evidence of CD, whose psychiatric symptoms improve with gluten elimination.

Prevalence And Impact Of Gastrointestinal Manifestations In Covid-19 Patients: A Systematic Review, Bassam Hossain, Shoreh Qazi, Sumair Ahmad, Atif Saleem, Amanke Oranu, Fahad Malik

Journal of Community Hospital Internal Medicine Perspectives

Background and Objective: The aim of this study is to systematically analyze and summarize the implications of COVID-19 on the digestive system by quantitatively evaluating the prevalence of gastrointestinal symptoms such as nausea, vomiting, abdominal pain, constipation, diarrhea, anorexia. reported in COVID-19 cases. We simultaneously investigated other variables to determine the association of such symptoms in COVID-19 patients which can potentially influence the disease prognosis and outcome. This systematic review presents an updated literature on the issue as it requires more scientific discussion in order to better inform the medical community and authorities so that appropriate measures can be taken …

Home Oxygen And Monitoring For Covid-19 Patients: A Multidisciplinary Team Approach, Mahta Salehi, Shehrose Chaudry, Rebecca B. Newman, Josette Hartnett, Suzanne J. Rose, Forugh Homayounrooz

Journal of Community Hospital Internal Medicine Perspectives

Introduction: During the initial COVID-19 pandemic peak, Stamford Hospital implemented a home oxygen program (HOP) to create a comprehensive, multi-disciplinary outpatient initiative without sacrificing a safe discharge. Primary care physicians monitored program participants, whose only indication for remaining admitted was an oxygen requirement. We retrospectively examined participant co-morbidities and outcomes, including death and readmission rates to evaluate HOP safety.

Methods: A retrospective analysis of program participants discharged between April 2020-Janurary 2021 was performed. Variables included demographics, oxygen requirement, days enrolled in the HOP, and major comorbidities such as cardiovascular disease (CVD), diabetes (DM), hypertension (HTN), obesity, chronic kidney disease, malignancies …

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 …

Maintenance Of Chronicity Signatures In Fibroblasts Isolated From Recessive Dystrophic Epidermolysis Bullosa Chronic Wound Dressings Under Culture Conditions, Cristian De Gregorio, Evelyng Catalán, Gabriel Garrido, Pilar Morandé, Jimena Castillo Bennett, Catalina Muñoz, Glenda Cofré, Ya-Lin Huang, Bárbara Cuadra, Paola Murgas, Margarita Calvo, Fernando Altermatt, María Joao Yubero, Francis Palisson, Andrew P. South, Marcelo Ezquer, Ignacia Fuentes

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients.

RESULTS: In order to explore a more efficient, non-invasive in vitro model for RDEB studies, …

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 …

Immune Checkpoint B7-H3 Is A Therapeutic Vulnerability In Prostate Cancer Harboring Pten And Tp53 Deficiencies, Wei Shi, Yin Wang, Yuehui Zhao, Justin Jimin Kim, Haoyan Li, Chenling Meng, Feiyu Chen, Jie Zhang, Duncan H Mak, Vivien Van, Javier Leo, Brad St Croix, Ana Aparicio, Di Zhao

Faculty, Staff and Student Publications

Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3/CD276) is an immune checkpoint molecule and has emerged as a promising therapeutic target. However, much remains to be understood regarding B7-H3's role in cancer progression, predictive biomarkers for B7-H3-targeted therapy, and combinatorial strategies. Our multi-omics analyses identified B7-H3 as one of the most abundant immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Here, we sought in vivo genetic evidence for, and mechanistic understanding of, the role of B7-H3 in PTEN/TP53-deficient prostate …

Brexucabtagene Autoleucel For Relapsed Or Refractory Mantle Cell Lymphoma In Standard-Of-Care Practice: Results From The Us Lymphoma Car T Consortium, Yucai Wang, Preetesh Jain, Frederick L Locke, Matthew J Maurer, Matthew J Frank, Javier L Munoz, Saurabh Dahiya, Amer M Beitinjaneh, Miriam T Jacobs, Joseph P Mcguirk, Julie M Vose, Andre Goy, Charalambos Andreadis, Brian T Hill, Kathleen A Dorritie, Olalekan O Oluwole, Abhinav Deol, Jonas Paludo, Bijal Shah, Trent Wang, Rahul Banerjee, David B Miklos, Aaron P Rapoport, Lazaros Lekakis, Armin Ghobadi, Sattva S Neelapu, Yi Lin, Michael L Wang, Michael D Jain

Faculty, Staff and Student Publications

Purpose: Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication.

Patients and methods: Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of …

Sensor-Controlled Digital Game For Heart Failure Self-Management: Protocol For A Randomized Controlled Trial, Kavita Radhakrishnan, Christine Julien, Matthew O'Hair, Rachel Tunis, Grace Lee, Angelica Rangel, James Custer, Tom Baranowski, Paul J Rathouz, Miyong T Kim

Faculty, Staff and Students Publications

BACKGROUND: Heart failure (HF) is the leading cause of hospitalization among older adults in the United States. There are substantial racial and geographic disparities in HF outcomes, with patients living in southern US states having a mortality rate 69% higher than the national average. Self-management behaviors, particularly daily weight monitoring and physical activity, are extremely important in improving HF outcomes; however, patients typically have particularly low adherence to these behaviors. With the rise of digital technologies to improve health outcomes and motivate health behaviors, sensor-controlled digital games (SCDGs) have become a promising approach. SCDGs, which leverage sensor-connected technologies, offer the …

Exrna-Eclip Intersection Analysis Reveals A Map Of Extracellular Rna Binding Proteins And Associated Rnas Across Major Human Biofluids And Carriers, Emily L Laplante, Alessandra Stürchler, Robert Fullem, David Chen, Anne C Starner, Emmanuel Esquivel, Eric Alsop, Andrew R Jackson, Ionita Ghiran, Getulio Pereira, Joel Rozowsky, Justin Chang, Mark B Gerstein, Roger P Alexander, Matthew E Roth, Jeffrey L Franklin, Robert J Coffey, Robert L Raffai, Isabelle M Mansuy, Stavros Stavrakis, Andrew J Demello, Louise C Laurent, Yi-Ting Wang, Chia-Feng Tsai, Tao Liu, Jennifer Jones, Kendall Van Keuren-Jensen, Eric Van Nostrand, Bogdan Mateescu, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small …