Medical Specialties Commons^™

Rare Epigenetic Alterations Are Conserved Across Hematopoietic Differentiation Stages After Mycobacterial Infection, Brandon T Tran, Pamela N Luna, Ruoqiong Cao, Duy T Le, Apoorva Thatavarty, Laure Maneix, Bailee N Kain, Scott Koh, Andre Catic, Katherine Y King

Faculty, Staff and Students Publications

Infection leads to durable cell-autonomous changes in hematopoietic stem and progenitor cells (HSPCs), resulting in production of innate immune cells with heightened immunity. The mechanisms underlying this phenomenon, termed central trained immunity, remain poorly understood. We hypothesized that infection induces histone modifications leading to changes in chromatin accessibility that are conserved during differentiation from HSPCs to myeloid progenitors and monocytes. We conducted genome-wide surveillance of histone marks H3K27ac and H3K4me3 and chromatin accessibility in hematopoietic stem cells, multipotent progenitor 3, granulocyte-monocyte progenitors, monocytes and macrophages of naïve and Mycobacterium avium infected mice. Interferon signaling pathways and related transcription factor binding …

To Jump Or Not To Jump: Comparing Effects Of Phenotypic Plasticity On The Visual Responses And Escape Behavior Of Locusts And Grasshoppers, Soumi Mitra, Saina Namazifard, David Mario Bellini, Alexis Leigh Sarne, Bidisha Halder, Margaret Ruth Eisenbrandt, Aliya Macknojia, Jiayi Luo, Samme Xie, Hojun Song, Chenghang Zong, Fabrizio Gabbiani, Richard Burkett Dewell

Faculty, Staff and Students Publications

Locusts exhibit remarkable phenotypic plasticity changing their appearance and behavior from solitary to gregarious when population density increases. These changes include morphological differences in the size and shape of brain regions, but little is known about plasticity within individual neurons and alterations in behavior not directly related to aggregation or swarming. We investigated looming escape behavior and the properties of a well-studied collision-detection neuron in gregarious and solitarious animals of three closely related species, the desert locust (Schistocerca gregaria), the Central American locust (S. piceifrons) and the American bird grasshopper (S. americana). For this neuron, the lobula giant movement detector …

Implementing The Nyu Electronic Patient Visit Assessment (Epva), Janet H Van Cleave, Abraham A Brody, Dena Schulman-Green, Kenneth S Hu, Zujun Li, Stephen B Johnson, Vincent J Major, Christopher E Lominska, Jessica R Bauman, Alexander N Hanania, Ghia V Tatlonghari, Marcely Tsikis, Brian L Egleston

Faculty, Staff and Students Publications

Background: Aggressive treatment with multimodal therapies such as surgery, chemotherapy, and radiation therapy has improved survival in head and neck cancer (HNC) but at a human cost of a substantial symptom burden and impact on quality of life. We developed the NYU Electronic Patient Visit Assessment (ePVA)© for HNC as a digital patient-reported symptom monitoring system that enables early symptom detection and real-time interventions at the point of care. With this study protocol, we aim to test the effectiveness of the ePVA in improving HNC outcomes in real-world settings and to identify implementation strategies optimizing its effectiveness.

Methods: We will …

Circulating Tumor Dna Refines Risk Stratification Of Neoadjuvant Therapy-Resistant Breast Tumors, Mark Jesus M Magbanua, Nayelis A Manon, Denise M Wolf, Samuel Rivero-Hinojosa, Ziad Ahmed, Rosalyn W Sayaman, Antony Tin, Derrick Renner, Ekaterina Kalashnikova, Lamorna Brown-Swigart, Gillian L Hirst, Christina Yau, Wen Li, Claudine Isaacs, Rebecca A Shatsky, Amy S Clark, Alexandra Zimmer, Amy L Delson, Angel Rodriguez, Minetta C Liu, Paula R Pohlmann, Laura J Esserman, Hope S Rugo, Angela Demichele, Laura Van 'T Veer

Faculty, Staff and Student Publications

Early-stage breast cancers resistant to neoadjuvant therapy (NAT), characterized by high residual cancer burden (RCB) after treatment, have an increased risk of metastatic recurrence. Here, we show that circulating tumor DNA (ctDNA) detected using a tumor-informed test (1) can improve risk stratification of patients with NAT-resistant tumors (RCB-II/RCB-III) and (2) predict response to NAT. Stratification using ctDNA status at pretreatment or post-NAT and ctDNA dynamics identified NAT-resistant tumors with a significantly decreased risk of metastatic recurrence. ctDNA clearance as early as week 3 across receptor subtypes predicted favorable responses to NAT, including immunotherapies. Interestingly, less than a fifth of patients …

Single Cell Spatial Profiling Of The Matrisome Identifies Region-Specific Adhesion And Signaling Networks In Glioblastoma, Arpan De, Santiago A Forero, Ali Pirani, John E Morales, Marisol De La Fuente-Granada, Sumod Sebastian, Jason T Huse, Leomar Y Ballester, Jeffrey S Weinberg, Frederick F Lang, Kadir C Akdemir, Joseph H Mccarty

Faculty, Staff and Student Publications

The human brain contains a milieu of extracellular matrix (ECM) components that promote normal development and physiology. ECM signaling pathways are often dysregulated in brain pathologies including the malignant cancer glioblastoma (GBM). Here, we used single-cell spatial transcriptomic platforms to map the expression of nearly 400 ECM genes in matching non-cancerous brain and GBM samples. At least four different GBM cell populations have been identified that show unique ECM expression profiles and spatial enrichment in distinct intratumor regions. Spatial mapping demonstrates largely non-overlapping expression signatures of ECM components in GBM stromal cell types, particularly in vascular endothelial cells and microglia/macrophages. …

Standardizing Sepsis Care Across A Lifespan: A Multidisciplinary Approach To Reduce Variation, Vijayakrishnan Poondi Srinivasan, Jillian Gregory, Sarah Chang

MaineHealth Maine Medical Center

Sepsis is a life-threatening condition affecting patients of all ages and remains a leading cause of mortality, hospitalizations, and healthcare costs worldwide. In pediatrics, severe sepsis accounts for millions of deaths annually, with approximately 176,000 hospitalizations and an 8% mortality rate each year in the U.S. In adults, it contributes to 35% of in-hospital deaths and is the leading cause of readmissions. These data underscore the urgent need for timely recognition, standardized interventions, and consistent, evidence-based care across populations.

Imaging Reactive Oxygen Species With L-012 Reveals Neutrophil Extracellular Trap Formation In Pancreatic Ductal Adenocarcinoma, Angisha Basnet, Kaitlyn M Landreth, Michael Sestito, Kristen Ranson, Seth T Gammon, David Piwnica-Worms, Brian A Boone, Tracy W Liu

Faculty, Staff and Student Publications

Neutrophils, key effector cells of the innate immune system, combat pathogens through mechanisms including the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). While these responses are critical for host defense, prolonged elevation of ROS and dysregulated NETosis mediated by neutrophils have been implicated in autoimmune diseases, chronic inflammation, and cancer. In pancreatic ductal adenocarcinoma (PDAC), a highly aggressive and inflammatory malignancy, an increase in neutrophils infiltrating the tumor microenvironment promotes cancer progression and metastasis through increased ROS production and NET release. Using bioluminescence imaging with the reporter L-012 and NET assays, we assessed …

Precise Diagnosis Of Small Invasive Pulmonary Nodules Driven By Single-Cell Immune Signatures In Peripheral Blood, Yang Xia, Yin Zhu, Sai Zhang, Mo Zhou, Jiaqi Zhou, Guanxin Xu, Baiqin Zhao, Guofei Zhang, Qiyuan Wang, Bin Wang, Zexin Chen, Hongyu Shi, Xiuning Le, Tony Mok, Wei Chen, Junqiang Fan, Weiwei Yin, Wen Li

Faculty, Staff and Student Publications

Early detection of lung cancer is crucial for improving patient outcomes. However, accurately diagnosing invasive pulmonary nodules and predicting tumor invasiveness remain major clinical challenges. Given the established role of immune dysfunction in cancer development, we hypothesize that peripheral immune profiling could provide a strategy for managing pulmonary nodules. In this multi-center, prospective study, we combine peripheral immune profiling via mass cytometry with machine learning algorithms to develop an integrated pulmonary nodule management platform. This platform accurately distinguishes invasive from non-invasive pulmonary nodules (AUC = 0.952), outperforming established clinical and radiomics-based models. Furthermore, it effectively predicts tumor invasiveness, differentiating minimally …

Epidemiology, Presentation, And Diagnosis Of Type 2 Diabetes Mellitus In Children And Adolescents, Bisher Alsabbagh, Whard Alsabbagh

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents has increased substantially over recent decades, paralleling rising rates of pediatric obesity and metabolic risk. Youth-onset T2DM is characterized by significant insulin resistance accompanied by an inadequate compensatory insulin response, resulting in progressive hyperglycemia and early beta-cell dysfunction. Incidence varies widely among racial and ethnic groups, with the highest rates observed in non-Hispanic Black, Hispanic, Native American, Asian American, and Pacific Islander youth. Risk factors include obesity, family history, high-risk ethnicity, pubertal insulin resistance, prenatal metabolic exposures, and comorbid conditions such as polycystic ovary syndrome. Clinical presentation ranges …

Endothelial-Derived Extracellular Vesicles During Exercise In Copd Patients, Samuel C Okpechi, Dorota Wyczechowska, Bennett Deboisblanc, Jessica L Johnson, Mohamed A Ghonim, Natalie Bauer, Hamid A Boulares, Matthew R Lammi

School of Medicine Faculty Publications

Introduction: There are no treatments directly targeting the pulmonary vasculature in chronic obstructive pulmonary disease (COPD), and further characterization of the underlying endothelial cell (EC) abnormalities could be helpful in drug development. Methods: We investigated the influence of exercise and the prostacyclin analog iloprost on extracellular vesicles derived from ECs (eEVs) in 15 moderate–severe COPD patients who were enrolled in a randomized, placebo-controlled crossover trial of iloprost. Results: Active smokers had a profile consistent with inflammatory-derived EVs, while exacerbation-prone COPD subjects had a profile consistent with apoptosis-derived eEVs. There were no significant effects of iloprost on eEV levels. However, there …

A Review Of Recent And Developing Studies Regarding Percutaneous Coronary Intervention (Pci): A Narrative Review, Bisher Alsabbagh, Azeez Shala, Joshua Rupert, Abdallah Elsayed

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

This comprehensive literature review synthesizes the most recent evidence and evolving clinical guidelines concerning percutaneous coronary intervention (PCI) from 2015 to 2025. The study integrates findings from 42 peer-reviewed trials, meta-analyses, registries, and international guideline statements issued by the American College of Cardiology/American Heart Association (ACC/AHA), European Society of Cardiology (ESC), and related societies. Results reveal a decade-long evolution in PCI practice marked by a shift from anatomy-driven to physiology and imaging-guided decision-making, supported by tools such as fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). Modern guidelines emphasize individualized, team-based revascularization …

Bayesian Learning To Reduce Cardiac Risk Of Patients With Locally Advanced Non-Small Cell Lung Cancer Based On Personalized Radiation Therapy Prescription, Ruitao Lin, Mei Chen, Xiaodong Zhang, Tianlin Xu, Ting Xu, Rachel C Maguire, Kelsey L Corrigan, Efstratios Koutroumpakis, Joe Y Chang, Steven H Lin, Aileen B Chen, Quynh-Nhu Nguyen, Saumil J Gandhi, Matthew S Ning, Julianna Bronk, Stephen Chun, Ali Ajdari, Joshua S Niedzielski, Jinzhong Yang, Xinru Chen, Tinsu Pan, Qing H Meng, Anne S Tsao, Anita Deswal, Radhe Mohan, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Radiation-induced heart damage is a significant concern in the treatment of non-small cell lung cancer (NSCLC) that can have debilitating or life-threatening consequences. Current strategies focus on minimizing heart exposure, but individual susceptibility varies. Existing evidence also suggests that a uniform "one-size-fits-all" dosimetric constraint for the heart may not be optimal for all patients.

Methods and materials: We developed a prospective study using Bayesian continuous learning and adaptation to develop a framework for personalized adaptive radiation treatment (PART) to reduce cardiovascular adverse events among patients with locally advanced NSCLC. The trial includes a Bayesian personalized risk prediction model to …

Health-Related Quality Of Life In The Era Of Immune Checkpoint Blockade: What Do Patient-Reported Outcomes Reveal?, Alexandra M Dunker, Neha Malik, Kathryn J Krause, Emily Z Keung, Jason B Liu, Elise F Nassif Haddad, Neeta Somaiah, Heather G Lyu, Christina L Roland

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by providing durable survival gains, but understanding their effects on patient health-related quality of life (HRQL) is critical.

Methods: We performed a narrative review of cross-sectional surveys, early-phase trials, and large-scale phase II and III randomized controlled clinical trials assessing FDA-approved ICIs, including programmed cell death protein 1 (PD-1) inhibitors, programmed death ligand 1 (PD-L1) inhibitors, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors, with emphasis on patient-reported HRQL. Validated HRQL instruments were summarized, and for pivotal trials, the positioning of HRQL outcomes as primary, secondary, or exploratory endpoints was taken …

Using Mean Airway Pressure (Map) As An Indicator To Help Predict Successful Extubationof Preterm And Term Infants In A Neonatal Intensive Care Unit, William F. Bucher, Rrt-Nps, Eliza C. Desantis, Md

Division of Pulmonary, Allergy, and Critical Care Medicine Posters

Background
Extubation of preterm and term infants in a neonatal intensive care setting has always proven to be a challenge often resulting in failure. One of the challenges to a successful extubation in this vulnerable patient population is maintaining proper lung inflation at the time of extubation. We often rely on the use of the mean airway pressure (MAP) as an indicator to help predict patient readiness to extubate these patients.

Methods
23 patients ranging from 24 weeks to 41 weeks corrected gestational age were extubated from either conventional mechanical ventilation (CMV) or high frequency ventilation (HFV) using their mean …

Proteome-Wide Association Study Of Prostate Cancer Risk Across Populations, Hua Zhong, Jingjing Zhu, Shuai Liu, Chong Wu, Liang Wang, Seamus P. Whelton, Catherine H. Marshall, Michael J. Blaha, Peter Durda, Xiuqing Guo, Craig W. Johnson, Henry J. Lin, Kent D. Taylor, Russell P. Tracy, Ronit I. Yarden, Ani W. Manichaikul, Stephen S. Rich, Jerome I. Rotter, Rajat Deo, Ruth F. Dubin, Peter Ganz, Lang Wu

School of Graduate Studies Faculty Publications

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls …

Sex Hormones Influence Ormdl3 Expression: Implications For Sex-Associated Asthma Phenotype, Elisabetta Granato, Ida Cerqua, Antonietta Rossi, Maria Antonietta Riemma, Maria Chiara Monti, Giusy Ferraro, Barbara Romano, Maria Francesca Nanì, Danilo D'Avino, Martina Simonelli, Joshua Malo, Francesca Polverino, Bruno D'Agostino, Giuseppe Cirino, Fiorentina Roviezzo

Faculty, Staff and Students Publications

Background: Genetic polymorphisms in sphingolipid metabolism, particularly involving the orosomucoid-like 3 (ORMDL3) gene, have been associated with asthma risk. Notably, asthma prevalence and severity exhibit pronounced sex differences, emerging in childhood and persisting into adulthood. However, the molecular mechanisms underlying this sexual dimorphism remain incompletely elucidated.

Objective: We investigated whether ORMDL3 contributes to sex differences in airway function and asthma-like features.

Methods: ORMDL3 expression was measured in lung tissues from healthy male and female human donors and in human bronchial epithelial cells (BEAS-2B) after exposure to 17β-estradiol (E2), Dermatophagoides pteronyssinus 1 (Der p 1), or both. A murine preparation of …

Characterization Of Peg-Modified Composite Membranes For Microfluidic Oxygenator Applications, Nicholas C. Higgins, David G. Blauvelt, Shuvo Roy

Department of Pediatrics Faculty Papers

Microfluidic oxygenators promise to advance extracorporeal membrane oxygenation (ECMO) devices with enhanced hemodynamics and low prime volume. We are developing a silicon-based membrane oxygenator that will offer improved gas transfer and fluid flow control. Polyethylene glycol (PEG) has been used to improve hemocompatibility by providing excellent resistance to protein adsorption. Here, we characterized a polyethylene glycol surface modification of composite silicon–PDMS membranes to evaluate their effects on microfluidic oxygenator properties. X-ray photoelectron spectroscopy (XPS) and water contact angle goniometry confirmed successful PEG attachment, evidenced by the presence of characteristic C-O bonds and increased hydrophilicity, which was stable for 2 weeks. …

Actin Dysregulation Induces Neuroendocrine Plasticity And Immune Evasion: A Vulnerability Of Small Cell Lung Cancer, Yoojeong Seo, Shengzhe Zhang, Jinho Jang, Kyung-Pil Ko, Kee-Beom Kim, Yuanjian Huang, Dong-Wook Kim, Bongjun Kim, Gengyi Zou, Jie Zhang, Sohee Jun, Wonhong Chu, Nicole A Kirk, Ye Eun Hwang, Young Ho Ban, Shilpa S Dhar, Joseph M Chan, Min Gyu Lee, Charles M Rudin, Kwon-Sik Park, Jae-Il Park

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. Capping protein inhibiting regulator of actin dynamics (CRACD) that promotes actin polymerization, is frequently inactivated in SCLC. However, the role of CRACD loss in SCLC is unknown. Here we show that CRACD depletion drives neuroendocrine (NE) cell plasticity and immune evasion in SCLC. Mechanistically, CRACD inactivation disrupts actin organization, leading to suppression of Yap1-NOTCH signaling and subsequent NE gene upregulation. Simultaneously, CRACD loss drives EZH2-mediated histone methylation via nuclear actin disruption, leading to repression of MHC-I genes and depletion of CD8⁺ T cells. Consequently, CRACD-downregulated tumors exhibit …

Proteome-Wide Association Study Of Prostate Cancer Risk Across Populations, Hua Zhong, Jingjing Zhu, Shuai Liu, Chong Wu, Liang Wang, Seamus P Whelton, Catherine H Marshall, Michael J Blaha, Peter Durda, Xiuqing Guo, Craig W Johnson, Henry J Lin, Kent D Taylor, Russell P Tracy, Ronit I Yarden, Ani W Manichaikul, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Peter Ganz, Lang Wu

Faculty, Staff and Student Publications

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls …

Minimally Invasive Approach To Cervical Intraspinal Air Gun Pellet In A Pediatric Patient, Olivia F. Patch, John H. Wilkinson, Joaquin A. Hidalgo

Neurosurgery

Background The authors report a case of a 12-year-old girl who presented for neurosurgical evaluation one month after sustaining a ballistic injury to the anterior left side of her neck from a pellet gun accidental firing. Immediately following the misfire, the patient experienced pain in the left side of her neck that radiated to her shoulder, down her posterior arm, and to her middle fingers on the left hand. Subsequently, the patient experienced lingering numbness and developed progressive weakness in her left arm. The patient denied trouble swallowing or any other deficits. Radiographic studies of the cervical spine revealed a …

Reimagining Pediatric Care: The Future Of Telehealth, Mike Smith, Morgan Waller

Pediatrics in Practice: A CME Podcast

Telehealth has transformed the way families access pediatric care, offering convenience without compromising quality. In this episode, we sit down with Morgan Waller, Director of Telemedicine at Children’s Mercy, to explore the latest advancements in pediatric telehealth. From innovative technologies to strategies for improving access in rural communities, we discuss how virtual care is shaping the future of pediatrics and what it means for families and providers alike.

Click here to stream the podcast episode.

Outcomes After Ulnar Collateral Ligament Reconstruction And Repair In Nonthrowing Athletes, William L. Johns, Neel K. Patel, Benjamin Miltenberg, Ryan W. Paul, Adeeb J. Hanna, Michael C. Ciccotti, Steven B. Cohen, Michael G. Ciccotti, Christopher C. Dodson

Rothman Institute Papers

BACKGROUND: Surgical management of ulnar collateral ligament (UCL) tears in nonthrowing athletes is less commonly performed, and the outcomes of that management have not been thoroughly described.

PURPOSE: To describe the clinical outcomes of surgical management of UCL injury in nonthrowing athletes.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: A retrospective review was conducted on all patients who underwent UCL reconstruction or repair across a 10-year period (2010-2020), with nonthrowing athletes who had >2-year follow-up being specifically identified. Demographic variables such as age, sport participation, concomitant procedures, and graft type, as well as postoperative outcomes such as complications, …

A Case Of The Blue Blues: The Safety Issue Of Recognizing And Avoiding The Retinal Toxicity Of Methylene Blue Compared To Brilliant Blue And Trypan Blue, Sidra Zafar, Jose S. Pulido, Samir N. Patel, Yoshihiro Yonekawa, Jordan D. Deaner

Wills Eye Hospital Papers

While blue vital dyes remain indispensable in ophthalmic surgery, medication errors, particularly the inadvertent use of methylene blue instead of trypan blue and brilliant blue, pose a significant risk to patient safety. Methylene blue has been reported to cause damage to anterior segment structures, We reported a case of inner retinal toxicity from injection of methylene blue into the vitreous cavity resulting in profound vision loss. Standardization, vigilant verification, and safer packaging are critical to preventing these never events.

The Anatomy Of Change: A Scoping Review Of Surgical Curriculum Renewal Processes, Marc A. Seifman, Robyn Woodward-Kron, Roi Y. Kagan, Kirsten Dalrymple, Aimee K. Gardner, Ian Incoll, Lars Konge, John T. Paige, Debra Nestel

School of Medicine Faculty Publications

PURPOSE: Renewal of surgical curricula is critical in maintaining relevance to contemporary healthcare needs. A curriculum document usually describes its purpose, intended outcomes, content, methods, and assessment and evaluation processes. The document may also consider cultural, professional, political, and social contexts. While there are published curriculum development approaches, guidance on renewal processes is limited. This scoping review aims to synthesise literature on surgical curriculum renewal, to understand the key elements of this process, and identify areas for improvement. METHODS: A scoping review was conducted by the core author team, with co-creation involving a Knowledge User Group (KUG). Seven databases were …

Medial Artery Calcification As A Hidden Driver Of Osteomyelitis: The Impact Of Sad-Mac On Microvascular Perfusion And Antibiotic Delivery In The Diabetic Foot, Yasim Zafar, Paul Tran, Ofsman Quintana, Dustin Prins, Hooman Mir

School of Podiatric Medicine - Student Research

Purpose: To evaluate the association between small arterial disease with medial artery calcification (SAD-MAC) and increased risk of osteomyelitis in diabetic foot patients. This study explores how impaired microvascular perfusion contributes to ischemic ulcers, infection progression, and reduced antibiotic efficacy, leading to poor healing and higher amputation rates.

Methods: A retrospective review was conducted on nine diabetic patients with chronic kidney disease, hypertension, and peripheral vascular disease who presented with ischemic or gangrenous toes. Patients lacking radiographs or with non-diabetic ischemic etiologies were excluded. Radiographs were evaluated for small arterial disease with medial artery calcification (SAD-MAC) and graded using the …

A Comprehensive Study Of C-Kit-Expressing Amacrine Cells In The Mammalian Retina, Zheng Jiang, Wen Shen

Faculty, Staff and Students Publications

Amacrine cells assemble complex circuits in the inner retina, where they integrate, modulate, and relay spatial and temporal information to retinal ganglion cells. Nevertheless, their organization and functional diversity are still not fully understood. In this study, we identify a distinct group of amacrine cells that express the stem cell factor receptor-c-Kit. Using combined techniques of anti-CD117 (c-Kit) immunolabeling, confocal imaging, and computational algorithms, we characterize the morphological features and spatial distribution of the c-Kit-expressing amacrine cells. Our results show that c-Kit-expressing amacrine cells are GABA-positive neurons with medium to wide dendritic fields that stratify within the specific strata in …

Dinaciclib Improves Treatment Response In Chemoresistant Hepatoblastoma, Brian T Hickner, Andres F Espinoza, Rohit K Srivastava, Roma H Patel, Priyanka Rao, Nicholas A O'Brien, Kalyani R Patel, Andrew A Badachhape, Abhishek Kona, Dolores H López-Terrada, Sarah E Woodfield, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

Chemoresistant hepatoblastoma (HB) is associated with poor outcomes. Cyclin-dependent kinases (CDKs) are potential therapeutic targets because of their critical role in cell growth and chemoresistance. To evaluate the efficacy of CDK inhibition, HB cell lines were treated with dinaciclib and evaluated with cytotoxic, cell-death reversal, and immunoblotting assays. A HB patient-derived xenograft (PDX) model was treated with placebo, vincristine + irinotecan (VI), dinaciclib, or VI + dinaciclib to evaluate tumor growth and response to therapy. We found that dinaciclib had a marked effect on HB cell viability, induced PARP cleavage, and decreased CDK9 protein expression in vitro. Overexpression of CDK9 …

Pitx2 Dosage-Dependent Changes In Pacemaker Cell State Underlie Sinus Node Dysfunction And Atrial Arrhythmias, Lieve E Van Der Maarel, M Ridwane Mungroo, Otto J Mulleners, Mathilde R Rivaud, Arie O Verkerk, Karel Van Duijvenboden, Freek H T Tiel Groenestege, Jeffrey D Steimle, Lianne Fokkert, Corrie De Gier-De Vries, Mischa Klerk, Arie R Boender, James F Martin, Bjarke Jensen, Gerard J J Boink, Harsha D Devalla, Vincent M Christoffels

Faculty, Staff and Students Publications

Physiologically relevant increases in transcription factor dosage and their role in development and disease remain largely unexplored. Genomic deletions upstream of the Paired-like homeodomain transcription factor gene (PITX2), identified in patients with sinus node dysfunction and atrial fibrillation and modeled in mice (delB), rewire the local epigenetic landscape, increasing PITX2 expression. Here, we demonstrate that pacemaker cardiomyocytes in the embryonic delB sinus node ectopically express PITX2 at physiological dosages in a heterogeneous pattern. The prenatal delB sinus node forms discrete subdomains showing PITX2 dosage-dependent mild or severe loss of pacemaker cardiomyocyte identity. Respective subdomain sizes and severity of sinus node …

Functional Vs Anatomical Cortico-Striatal Connectivity In The Macaque Brain, Wei Tang, Megan E Monko, Zoe Liu, Ana M G Manea, Fernando A Ortega, Damyan Hart, Jason Zhou, Jan Zimmermann, Sarah R Heilbronner

Faculty, Staff and Students Publications

The cerebral cortex provides the main input to the striatum, constituting the first step in cortico-basal ganglia loops. Decades of careful anatomical tract-tracing research have established the exquisite topography of each cortical region's projection to the striatum in nonhuman primates. In parallel, neuroimaging research has demonstrated the relationship between cortico-striatal resting-state functional connectivity and specific cognitive, behavioral, psychiatric, and neurological states in humans. However, still unclear is the extent to which functional connectivity recapitulates the specific topographies of cortico-striatal anatomical connectivity. Here, we combined datasets of cortico-striatal anatomical and functional connectivity in macaques to determine the degree of overlap between …

Radiation-Induced Brachial Plexopathy: Current Understanding, Diagnosis, And Treatment Options, Alex G. Lambi, Tomas Holly, Ryan E. Tomlinson, Mary F. Barbe

Department of Orthopaedic Surgery Faculty Papers

Radiation-induced brachial plexopathy (RIBP) is a gruesome complication of cancers treated with radiation therapy around the lung and chest wall, head and neck, and breast and axilla. It can occur in an early-onset (transient) or a late-onset (chronic) fashion. The diagnosis involves exclusion of a compressive neoplastic process, either new or recurrent, and relies largely on patient symptomatology without well-validated, objective scoring systems. Treatment options remain limited as no major advances have been made to prevent or halt disease progression. This article reviews the background incidence, pathophysiology, and diagnosis of RIBP. In addition to surgical treatment options, nonsurgical modalities, often …