Digital Commons Network^™

Hsp90: Bringing It All Together, Georgios Ioannis Karras, Giorgio Colombo, Andrea N Kravats

Faculty, Staff and Student Publications

Heat-shock protein 90 (Hsp90) is an ancient and multifaceted protein-folding machine essential for most organisms. The past 40 years have uncovered remarkable complexity in the regulation and function of Hsp90, which dwarfs most other machines in the cell in sophistication. Here, we propose four analogies to illustrate Hsp90's sophistication: a multifunctional Swiss Army knife, an automobile engine and its controls, a switchboard acting as a hub and directing signals, and an orchestra conductor setting the tempo of a symphony. Although each of these analogies represents some key Hsp90 activities, none of them captures the entirety of Hsp90's complexity. Together, these …

From Stable Teamwork To Dynamic Teaming In The Ambulatory Care Diagnostic Process, Scott I Tannenbaum, Eric J Thomas, Sigall K Bell, Eduardo Salas

Faculty, Staff and Student Publications

Dynamic teaming is required whenever people must coordinate with one another in a fluid context, particularly when the fundamental structures of a team, such as membership, priorities, tasks, modes of communication, and location are in near-constant flux. This is certainly the case in the contemporary ambulatory care diagnostic process, where circumstances and conditions require a shifting cast of individuals to coordinate dynamically to ensure patient safety. This article offers an updated perspective on dynamic teaming commonly required during the ambulatory diagnostic process. Drawing upon team science, it clarifies the characteristics of dynamic diagnostic teams, identifies common risk points in the …

Incorporating Pediatrics In Clinical Education: A Call To Action In Inpatient Pharmacy Practice., Caroline M Sierra, Amanda C Capino, Cober M Petrea, Lea S Eiland, Norm Fenn Bcps, Bcpps, Nicholas M Fusco, Lucas E Orth

Parkview Pharmacy Department

Background

The recently revised 2025 Accreditation Council for Pharmacy Education (ACPE) Standards state the expectations of Advanced Pharmacy Practice Experiences (APPEs) are to “emphasize continuity of care and incorporate acute, chronic, and wellness-promoting patient-care services…[and] expose students to diverse patient populations as related to age, sex race/ethnicity, socioeconomic factors…and disease states.”1 These expectations describe the conditions under which student pharmacists are expected to develop and demonstrate competence in the entrustable professional activities (EPAs), which were revised in 2022 to more accurately reflect current pharmacy practice.2 However, the definition of required APPE (Standard 3.2.d.) states that the inpatient patient …

Mutational And Co-Mutational Landscape Of Early Onset Colorectal Cancer, Jumanah Yousef Alshenaifi, Guglielmo Vetere, Giulia Maddalena, Mahmoud Yousef, Michael G White, John Paul Shen, Eduardo Vilar, Christine Parseghian, Arvind Dasari, Van Karlyle Morris, Ryan Huey, Michael J Overman, Robert Wolff, Kanwal P Raghav, Jason Willis, Kristin Alfaro, Andy Futreal, Y Nancy You, Scott Kopetz

Faculty, Staff and Student Publications

Introduction: Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Methods: Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

Results: EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs. 59%), and advanced-stage disease. Molecular analyses revealed differences in mutation patterns, with EOCRC having higher frequencies of TP53 (74% vs. 68%, p < 0.01) and SMAD4 (17% vs. 14%, p = 0.015), while BRAF (5% vs. 11%, p < 0.001) and NOTCH1 (2.7% vs. 4.1%, p = 0.01) mutations …

Establishment Of The Nichols Strain As The Type Strain Of Treponema Pallidum, Steven J Norris

Faculty, Staff and Student Publications

In this article, it is proposed that the Nichols strain of Treponema pallidum be established as the type strain. T. pallidum was first identified as the causative agent of syphilis in 1905, and the Nichols strain was isolated in 1912 by inoculation of a rabbit with cerebrospinal fluid from a patient with neurosyphilis. The Nichols strain has been maintained by serial passage in rabbits for over a century, and historically most studies of T. pallidum have been conducted using this strain. In recent years, a procedure for continuous in vitro culture of T. pallidum in a tissue culture system has …

Angiotensin-(1-9) Improves The Cardioprotective Effects Of Del Nido Cardioplegia Against Ischemia/Reperfusion Injury, Evelyn Mendoza-Torres, Gina Sanchez, Wendy Rosales, María Clara Ospino, Luis Antonio Díaz-Ariza, Yuliet Montoya, John Bustamante, Jaime A Riquelme, Mario Chiong, Sergio Lavandero

Faculty, Staff and Student Publications

Del Nido cardioplegia (DNC), a blood-and-crystalloid solution containing high and low concentrations of potassium and calcium, respectively, is used as a single-dose antegrade infusion to induce immediate cardiac arrest in the surgery of patients with cardiovascular diseases requiring extracorporeal circulation. Adding cardioprotective molecules may further reduce the damage-triggered ischemia/reperfusion (I/R) injury. Angiotensin-(1-9) (Ang-(1-9)) and angiotensin-(1-7) (Ang-(1-7)), members of the counter-regulatory renin-angiotensin system, have shown cardioprotective effects in cardiac hypertrophy and I/R models. This study aimed to evaluate the effects of Ang-(1-9) and Ang-(1-7), as adjuvants of the DNC, on cardioprotection and ventricular function in isolated rat hearts subjected to I/R …

Five-Year Outcomes Of Lenadogene Nolparvovec Gene Therapy In Leber Hereditary Optic Neuropathy, Patrick Yu-Wai-Man, Nancy Newman, Valérie Biousse, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo Sadun, Robert C Sergott, Rabih Hage, Simona Degli Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Magali Taiel, José-Alain Sahel

Department of Neurology Faculty Papers

IMPORTANCE: Limited studies have assessed the long-term benefit/risk of gene therapy for Leber hereditary optic neuropathy (LHON).

OBJECTIVE: To determine the safety and efficacy of lenadogene nolparvovec in patients with LHON due to the MT-ND4 gene variant for up to 5 years after administration.

DESIGN, SETTING, AND PARTICIPANTS: The RESCUE and REVERSE Long-Term Follow-up Study (RESTORE), conducted from 2018 to 2022, is the 5-year follow-up study of the 2 phase 3 clinical studies RESCUE (Efficacy Study of Lenadogene Nolparvovec for the Treatment of Vision Loss Up to 6 Months From Onset in LHON Due to the MT-ND4 Mutation) and REVERSE …

Best Practices For Delivering Neoadjuvant Therapy In Pancreatic Ductal Adenocarcinoma, Jordan M Cloyd, Angela Sarna, Matthew J Arango, Susan E Bates, Manoop S Bhutani, Mark Bloomston, Vincent Chung, Efrat Dotan, Cristina R Ferrone, Patricia F Gambino, Ajit H Goenka, Karyn A Goodman, William A Hall, Jin He, Melissa E Hogg, Shiva Jayaraman, Avinash Kambadakone, Matthew H G Katz, Alok A Khorana, Andrew H Ko, Eugene J Koay, David A Kooby, Somashekar G Krishna, Liliana K Larsson, Richard T Lee, Anirban Maitra, Nader N Massarweh, Sameh Mikhail, Mahvish Muzaffar, Eileen M O'Reilly, Manisha Palta, Maria Q B Petzel, Philip A Philip, Marsha Reyngold, Daniel Santa Mina, Davendra P S Sohal, Tilak K Sundaresan, Susan Tsai, Kea L Turner, Timothy J Vreeland, Steve Walston, M Kay Washington, Terence M Williams, Jennifer Y Wo, Rebecca A Snyder

Faculty, Staff and Student Publications

Importance: Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.

Objective: To develop consensus best practices for delivering NT to patients with localized PDAC.

Design, setting, and participants: This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature …

Undervaluing Nondrug Rewards Or Overvaluing Cocaine? Cocaine Demand Relates To Cocaine Use Severity More Strongly Than Anhedonia In Individuals With Cocaine Use Disorder, Cecilia Nunez, Jin H Yoon, Constanza De Dios, Vincent Dang, Scott D Lane, Jessica N Vincent, Joy M Schmitz, Margaret C Wardle

Faculty, Staff and Student Publications

Cocaine use disorder (CUD) is a major public health issue, and greater cocaine use severity has been associated with worse treatment retention and outcomes. Therefore, greater understanding of processes that influence cocaine use is needed. Both anhedonia (i.e., undervaluation of non-drug rewards) and cocaine demand (i.e., cocaine valuation) are related to cocaine use severity and thematically related to each other at face value, but no studies have directly compared these outcomes to our knowledge. The current study represents a secondary analysis from a two-phase sequential, multiple assignment, randomized trial (SMART) aimed at developing adaptive interventions for CUD. We examined the …

Analyzing The Creation And Use Of Abbreviations In Cardiology And Cardiac Imaging Society Guidelines., Christopher R. Green, Rui Zhang, Raymond F. Stainback, Sofia W. Ye, Daniel Forsha, Enrique Garcia-Sayan, Jeffrey C. Hill, Carol Mitchell, Vera H. Rigolin, Vandana Sachdev, Partho P. Sengupta, Vincent L. Sorrell, Jordan B. Strom, Alexander M. Ye, Cynthia C. Taub

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Abbreviation use in clinical and academic cardiology is widespread, yet there are few guidelines regulating the creation and utilization of abbreviations. Inconsistent abbreviations can introduce ambiguity and pose challenges to practice and research.

OBJECTIVES: The authors aimed to analyze how abbreviations are created and utilized in general cardiology and cardiac imaging society guidelines in order to assess whether ambiguities and discrepancies exist between societies.

METHODS: Abbreviation data were collected from 7 national and international societies of general cardiology and cardiac imaging over a 6-year span (2018-2023). Data were linguistically coded for abbreviation type, unique occurrence, meaning or sense count, …

Diagnostic Accuracy Prior To Congenital Heart Defect Surgery: A Multicenter Collaboration., Shobha S. Natarajan, Kasey Chaszczewski, Chris Penney, Steve Ampah, Douglas Ryba, Andrea T. Kennedy, Robert Olsen, Shubhika Srivastava, Matthew J. Campbell, Mya Carney, Carol Prospero, Lisa Elliott, Carlie Brewer, Michael Dimaria, Nitin Madan, Seda Tierney, Meaghan Beattie, Ritu Sachdeva, Joan Lipinski, Kenan W D Stern, Grace Kong, Preeta Dhanantwari, Elena N. Kwon, Hari Rajagopal, Carolyn Taylor, Tammy Churchill, Aura A. Sanchez Mejia, Deidra Abenlah Ansah, Anitha Parthiban, Hasti Sanandajifar, Sowmya Balasubramanian, David A. Parra, Kimberly Crum, Corey Stiver, Aarti H. Bhat, Pei-Ni Jone, Stefani Samples, Kathleen Van't Hof, Curt Degroff, Dalia Lopez-Colon, Meryl S. Cohen

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Echocardiography is the mainstay for diagnosing congenital heart disease (CHD). Diagnostic errors can lead to suboptimal surgical outcomes.

OBJECTIVES: This multicenter pediatric echocardiography collaborative learning initiative explores reasons for diagnostic errors, investigates associations between patient- and center-specific factors and errors, and relays the benefits of a multicenter approach to decrease these errors as a first step to improve CHD surgical outcomes.

METHODS: Participating centers submitted diagnostic evaluations on patients prior to 2-ventricle repair into a central database. We held virtual meetings to revise variables and discuss cases to learn from each other.

RESULTS: Fourteen pediatric echocardiography laboratories entered data …

Immunogenomic Determinants Of Exceptional Response To Immune Checkpoint Inhibition In Renal Cell Carcinoma, Tejas Jammihal, Renee Maria Saliby, Chris Labaki, Hanna Soulati, Juan Gallegos, Arnau Peris, Dustin Mccurry, Chunlei Yu, Valisha Shah, Deepak Poduval, Talal El Zarif, Nourhan El Ahmar, Yasmin Nabil Laimon, Marc Eid, Aseman Bagheri Sheshdeh, Katherine M Krajewski, Florian A Büttner, Matthias Schwab, Daniel Heng, Rafael C Casellas, Kunal Rai, Niki M Zacharias Millward, Pavlos Msaouel, Jose Karam, Sabina Signoretti, Eliezer Van Allen, Toni K Choueiri, David A Braun, Sachet A Shukla

Faculty, Staff and Student Publications

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF). In the IO/IO cohort, clonal neoantigen load was significantly higher in persons with …

The Metabolic Basis Of Cancer-Related Fatigue, Robert Dantzer, Brandon Chelette, Elisabeth G Vichaya, A Phillip West, Aaron Grossberg

Faculty, Staff and Student Publications

Although we are all familiar with the sensation of fatigue, there are still profound divergences on what it represents and its mechanisms. Fatigue can take various forms depending on the condition in which it develops. Cancer-related fatigue is considered a symptom of exhaustion that is often present at the time of diagnosis, increases in intensity during cancer therapy, and does not always recede after completion of treatment. It is usually attributed to the inflammation induced by damage-associated molecular patterns released by tumor cells during cancer progression and in response to its treatment. In this review, we argue that it is …

Phase Ii Study Of Copanlisib In Patients With Pten Loss: Results From Nci-Match Ecog-Acrin Trial (Eay131) Subprotocols Z1g And Z1h, Mohamed A Gouda, Zihan Wei, Jordi Rodon, Michael A Davies, Filip Janku, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David R Patton, P Mickey Williams, Stanley R Hamilton, Raymond Liu, Daniela A Bota, Paul L Swiecicki, Gary L Buchschacher, James V Tricoli, Barbara A Conley, Carlos L Arteaga, Lyndsay N Harris, Peter J O'Dwyer, Alice P Chen, Keith T Flaherty

Faculty, Staff and Student Publications

Purpose: Copanlisib, a pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with activity predominantly against the PI3K-delta and PI3K-alpha isoforms, has shown promising results in preclinical cancer models with PTEN loss. Herein, we report the activity and safety data from the Z1G and Z1H subprotocols, which included patients with PTEN loss, of the National Cancer Institute Molecular Analysis for Therapy Choice trial.

Methods: Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of PTEN mutation or deletion status were included in subprotocol Z1G, and patients with a deleterious mutation in the PTEN gene and retained expression of PTEN …

Safety And Efficacy Of Toripalimab In Patients With Cholangiocarcinoma: An Open-Label, Phase 1 Study, Aung Naing, Amit Mahipal, Milind Javle, Judy Wang, Todd M Bauer, David L Bajor, Anthony D Elias, Anthony Shields, Elizabeth Davis, Sant Chawla, Howard Safran, John D Powderly, Gina D'Amato, Christian F Meyer, Xiongwen Tang, Sheng Yao, Patricia Keegan

Faculty, Staff and Student Publications

Introduction: This was the first phase 1 study conducted in the United States. It consisted of dose-escalation (part A) and multiple indication-specific cohort expansion (part B), investigating the safety and preliminary efficacy of toripalimab (anti-programmed cell death-1 inhibitor) in patients with advanced malignancies.

Methods: Patients with advanced malignancies that progressed after treatment with at least one prior line of standard systemic therapy, including the patients with advanced/recurrent cholangiocarcinoma (CCA), received toripalimab 240 mg every 3 weeks in part B. The primary endpoint was safety assessment. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), …

Wearable Penile Devices: The Techring, Gal Saffati, Daniela Orozco Rendon, Riley Daily, Mohit Khera, John P Mulhall

Faculty, Staff and Students Publications

The integration of wearable technology into healthcare has transformed patient monitoring, particularly in urology. Wearable penile devices (WPDs), such as the FirmTech TechRing, offer real-time data on erectile function, providing critical insights into nocturnal penile tumescence (NPT) patterns that can indicate underlying health issues. This piece highlights the potential of the FirmTech TechRing, a WPD, to advance erectile function monitoring by providing real-time data on NPT and intra-coital activity. It explores its promise in detecting early dysfunction, assessing cardiovascular risk, and enhancing proactive health management. By measuring parameters like firmness, girth expansion, and the frequency of erections, the TechRing enables …

Accelerated Symptom Improvement In Parkinson’S Disease Via Remote Internet-Based Optimization Of Deep Brain Stimulation Therapy: A Randomized Controlled Multicenter Trial, Alireza Gharabaghi, Sergiu Groppa, Marta Navas-Garcia, Alfons Schnitzler, Laura Muñoz-Delgado, Vicky L. Marshall, Jessica Karl, Lin Zhang, Ramiro Alvarez, Mary S. Feldman, Michael J. Soileau, Lan Luo, S. Elizabeth Zauber, Benjamin L. Walter, Chengyuan Wu, Hong Lei, Damian M. Herz, Ming-Hua Chung, Yagna Pathak, Bram Blomme, Binith Cheeran, Corneliu Luca, Daniel Weiss

Department of Neurosurgery Faculty Papers

BACKGROUND: Deep brain stimulation (DBS) has emerged as an important therapeutic intervention for neurological and neuropsychiatric disorders. After initial programming, clinicians are tasked with fine-tuning DBS parameters through repeated in-person clinic visits. We aimed to evaluate whether DBS patients achieve clinical benefit more rapidly by incorporating remote internet-based adjustment (RIBA) of stimulation parameters into the continuum of care.

METHODS: We conducted a randomized controlled multicenter study (ClinicalTrails.gov NCT05269862) involving patients scheduled for de novo implantation with a DBS System to treat Parkinson's Disease. Eligibility criteria included the ability to incorporate RIBA as part of routine follow-up care. Ninety-six patients were …

Recent Advances In Cardiac Resynchronization Therapy: Current Treatment And Future Direction, Arasalan Siddiqui, Vasiliki Tasouli-Drakou, Marc Ringor, Micael V. Dicaro, Brianna Yee, Kachon Lei, Tahir Tak

Department of Internal Medicine Faculty Research

Cardiac Resynchronization Therapy (CRT) has been established as a major component of heart failure management, resulting in a significant reduction in patient morbidity and death for patients with increased QRS duration, low left ventricular ejection fraction (LVEF), and high risk of arrhythmias. The ability to synchronize both ventricles, lower heart failure hospitalizations, and optimize clinical outcomes are some of the attractive characteristics of biventricular pacing, or CRT. However, the high rate of CRT non-responders has led to the development of new modalities including leadless CRT pacemakers (CRT-P) and devices focused on conduction system pacing (CSP). This comprehensive review aims to …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

Deep Learning-Based Auto-Segmentation For Liver Yttrium-90 Selective Internal Radiation Therapy, Jun Li, Wookjin Choi, Rani Anne

Department of Radiation Oncology Faculty Papers

The aim was to evaluate a deep learning-based auto-segmentation method for liver delineation in Y-90 selective internal radiation therapy (SIRT). A deep learning (DL)-based liver segmentation model using the U-Net3D architecture was built. Auto-segmentation of the liver was tested in CT images of SIRT patients. DL auto-segmented liver contours were evaluated against physician manually-delineated contours. Dice similarity coefficient (DSC) and mean distance to agreement (MDA) were calculated. The DL-model-generated contours were compared with the contours generated using an Atlas-based method. Ratio of volume (RV, the ratio of DL-model auto-segmented liver volume to manually-delineated liver volume), and ratio of activity (RA, …

Cross-Platform Analysis Of Mammography Narratives: A Comparative Study On Social Media Engagement, Thomas Stirrat, Jonathan Garner, Parth Tailor, Daniel Weitz, Muhammad Umair, Yusuf T. Akpolat

Journal of Patient-Centered Research and Reviews

Purpose: This study examines the representation of mammography on social media platforms, specifically, X (Twitter), Facebook, TikTok, and Instagram, from 2006 to 2023. X (Twitter) went public in 2006, Facebook in 2004, Instagram in 2012, and TikTok in 2018 (after merging with Musical.ly). The analysis starts from after the public launch years to analyze personal experiences shared online.

Methods: A retrospective content analysis was conducted on 1,771 posts using specific hashtags related to mammography. Posts were categorized into themes including emotional and psychological impacts, clinical and procedural details, and social and supportive interactions. The analysis involved summarizing the distribution of …

Performance And Safety Of The Extravascular Implantable Cardioverter Defibrillator Through Long-Term Follow-Up: Final Results From The Pivotal Study., Paul Friedman, Francis Murgatroyd, Lucas V A Boersma, Jaimie Manlucu, Bradley P Knight, Nicolas Clémenty, Christophe Leclercq, Anish Amin, Béla Merkely, Ulrika Maria Birgersdotter-Green, Joseph Yat Sun Chan, Mauro Biffi, Reinoud Elwin Knops, Gregory Engel, Ignacio Muñoz Carvajal, Laurence M Epstein, Venkata Sagi, Jens Brock Johansen, Maciej Sterliński, Clemens Steinwender, Troy Hounshell, Richard Abben, Amy E Thompson, Yan Zhang, Christopher Wiggenhorn, Sarah Willey, Ian Crozier

Heart and Vascular Articles

BACKGROUND: Substernal lead placement of the extravascular implantable cardioverter defibrillator (EV ICD) permits both defibrillation at thresholds similar to those seen with transvenous implantable cardioverter defibrillators and effective anti-tachycardia pacing (ATP) while avoiding the vasculature and associated complications. The global Pivotal study has shown the EV ICD system to be safe and effective through 6 months, but long-term experience has yet to be published. Our aim was to report the performance and safety of the EV ICD system throughout the study.

METHODS: The EV ICD Pivotal study was a prospective, global, single-arm, premarket clinical study. Individuals with a Class I …

Overcoming Cd226-Related Immune Evasion In Acute Myeloid Leukemia With Cd38 Car-Engineered Nk Cells, Luciana Melo Garcia, Achintyan Gangadharan, Pinaki Banerjee, Ye Li, Andy G X Zeng, Hind Rafei, Paul Lin, Bijender Kumar, Sunil Acharya, May Daher, Luis Muniz-Feliciano, Gary M Deyter, Gabriel Dominguez, Jeong Min Park, Francia Reyes Silva, Ana Karen Nunez Cortes, Rafet Basar, Nadima Uprety, Mayra Shanley, Mecit Kaplan, Enli Liu, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226. CRISPR-Cas9 deletion of CD226 led to reduced LFA-1 recruitment, poor synapse formation, and decreased NK cell anti-leukemic activity. Engineering NK cells to express a chimeric antigen receptor targeting the AML antigen CD38 (CAR38) could overcome the need for CD226 to establish strong immune synapses. LFA-1 …

Tfap2e Is Implicated In Central Nervous System, Orofacial And Maxillofacial Anomalies, Jeshurun C Kalanithy, Enrico Mingardo, Jil D Stegmann, Ramgopal Dhakar, Tikam Chand Dakal, Jill A Rosenfeld, Wen-Hann Tan, Stephanie A Coury, Audrey C Woerner, Jessica Sebastian, Paul A Levy, Leah R Fleming, Lea Waffenschmidt, Tobias T Lindenberg, Öznur Yilmaz, Khadija Channab, Bimaljeet K Babra, Andrea Christ, Britta Eiberger, Selina Hölzel, Clara Vidic, Felix Häberlein, Nina Ishorst, Juan E Rodriguez-Gatica, Behnaz Pezeshkpoor, Patrick A Kupczyk, Olivier M Vanakker, Sara Loddo, Antonio Novelli, Maria L Dentici, Albert Becker, Holger Thiele, Jennifer E Posey, James R Lupski, Alina C Hilger, Heiko M Reutter, Waltraut M Merz, Gabriel C Dworschak, Benjamin Odermatt

Faculty, Staff and Students Publications

Background: Previous studies in mouse, Xenopus and zebrafish embryos show strong tfap2e expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 (TFAP2E) in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.

Methods: Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies. Exome variant prioritisation prompted TFAP2E gene for functional analysis in zebrafish embryos. Embryonic morphology and development were assessed after antisense morpholino (MO) knockdown (KD), CRISPR/Cas9 knockout and overexpression …

Statistical Identification Of Cell Type-Specific Spatially Variable Genes In Spatial Transcriptomics, Lulu Shang, Peijun Wu, Xiang Zhou

Faculty, Staff and Student Publications

An essential task in spatial transcriptomics is identifying spatially variable genes (SVGs). Here, we present Celina, a statistical method for systematically detecting cell type-specific SVGs (ct-SVGs)-a subset of SVGs exhibiting distinct spatial expression patterns within specific cell types. Celina utilizes a spatially varying coefficient model to accurately capture each gene's spatial expression pattern in relation to the distribution of cell types across tissue locations, ensuring effective type I error control and high power. Celina proves powerful compared to existing methods in single-cell resolution spatial transcriptomics and stands as the only effective solution for spot-resolution spatial transcriptomics. Applied to five real …

A Comprehensive Quality Improvement Program To Improve Intubation Performance In Critical Care Transport, Andrew P. Reimer

Faculty Scholarship

Objective: Advanced airway management is a primary skill critical care transport teams provide. There are several measures of performance for airway management that can be tracked and improved through quality improvement initiatives. The purpose of this project was to improve first-pass intubation success rates and the associated Definitive Airway Sans Hypoxia/Hypotension on First Attempt (DASH-1A) metric—definitive airway without hypoxia or hypotension. Methods: A multiyear quality improvement initiative was undertaken. Best practices from the literature were identified and implemented through the Institute for Healthcare Improvement Model for Improvement using a plan-do-study-act cycle approach. Improvement cycles included airway training in a cadaver …

Atm Expression And Activation In Ataxia Telangiectasia Patients With And Without Class Switch Recombination Defects, Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani

Department of Neurology Faculty Papers

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

METHODS: A-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression …

High Cellular Plasticity State Of Medulloblastoma Local Recurrence And Distant Dissemination, Hailong Liu, Jing Zhang, Ziwei Wang, Wei Wang, Dongming Han, Xuan Chen, Yu Su, Jiao Zhang, Craig Daniels, Olivier Saulnier, Zeyuan John Wang, Chunyu Gu, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yahui Zhao, Yifei Jiang, Yu Gao, Zijia Liu, Mingxu Ma, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yanfeng Shi, Tao Yang, Wenxing Li, Xueling Qi, Zejun Duan, Junping Zhang, Mingshan Zhang, Chunjiang Yu, Wei Jin, Xinguang Yu, Yu Tian, Shuaicheng Li, Chunde Li, Michael D Taylor, Jiankang Li, Yong-Qiang Liu, Xiaoguang Qiu, Tao Jiang

Faculty, Staff and Students Publications

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets. Chromosomal alteration evaluation revealed distinct genetic subclones during MB progression, such as chr7q gain and chr11 loss in Group_3 …

Racial And Ethnic Disparities In Human Papillomavirus Vaccination Among Us-Born And Foreign-Born Adults Aged 18 To 26 Years In The United States, Itunu Sokale, Jane Montealegre, Ann O Amuta, Abiodun Oluyomi, Aaron P Thrift

Faculty, Staff and Students Publications

Background/objectives: Human papillomavirus (HPV) is linked to multiple cancers that can be prevented through vaccination. While the optimal age for vaccination is in childhood and adolescence, vaccination recommendations include adults through age 26 who missed childhood/adolescent vaccination. There are limited data about disparities among adults eligible for catch-up HPV vaccination. We conducted a comprehensive examination of HPV vaccination among US young adults, disaggregating the group by race/ethnicity and nativity status to identify subgroups that may require additional interventions.

Methods: We analyzed 2019 and 2022 data of individuals aged 18-26 years from the National Health Interview Survey. Generalized linear models using …

Moud 2.0: A Clinical Algorithm And Implementation Evaluation Protocol For Sublingual And Injectable Buprenorphine Treatment Of Opioid Use Disorder, Brandon Joa, Eric Fung, Michael Weinstein, Lara Weinstein

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Primary care is the initial contact point for most patients with opioid use disorder (OUD) but lacks tools for guiding treatment. Only a small fraction of patients access evidence-based care. Long-acting injectable buprenorphine has potential to improve medication adherence and program retention in low-barrier primary care treatment settings. We present the first clinical decision support algorithm incorporating long-acting buprenorphine (LAIB) in primary care. We include a protocol for a future evaluation of the algorithm's implementation process, "Medication for Opioid Use Disorder (MOUD) 2.0," at a housing and integrated care clinic at a Federally Qualified Health Center.

METHODS: Literature review …