Medical Specialties Commons^™

Unilateral Acute Iris Transillumination Syndrome With Glaucoma And Iris Pigment Epithelium Dispersion Simulating Iris Melanoma, Orlando Gonzalez Martinez, Carol L. Shields, Jerry Shields, Patricia Chévez-Barrios, Debbie Rigney Walley, Ralph C. Eagle Jr., Tatyana Milman

Wills Eye Hospital Papers

Purpose

To report a patient with a unilateral presentation of glaucoma, pain, and acute iris transillumination syndrome simulating iris melanoma.

Observations

A 53-year-old male presented with blurred vision and pain in his right eye several weeks following a respiratory sinus infection managed by oral azithromycin. Examination of the right eye was notable for elevated intraocular pressure of 46 mm Hg, an irregular mid-dilated pupil, and diffuse iris transillumination with pigmentary seeding on the iris surface, in the anterior chamber angle, and on the sclera, suspicious for diffuse iris melanoma with glaucoma and extrascleral extension. Ultrasound biomicroscopy (UBM) of the right …

Multiomic Investigations Into Lung Health And Disease, Sarah E Blutt, Cristian Coarfa, Josef Neu, Mohan Pammi

Faculty, Staff and Students Publications

Diseases of the lung account for more than 5 million deaths worldwide and are a healthcare burden. Improving clinical outcomes, including mortality and quality of life, involves a holistic understanding of the disease, which can be provided by the integration of lung multi-omics data. An enhanced understanding of comprehensive multiomic datasets provides opportunities to leverage those datasets to inform the treatment and prevention of lung diseases by classifying severity, prognostication, and discovery of biomarkers. The main objective of this review is to summarize the use of multiomics investigations in lung disease, including multiomics integration and the use of machine learning …

Investigating The Complications And Causes Of Failure Of The Angiovac System: A Post-Marketing Surveillance From The Maude Database, Chaitu Dandu, Sardar Muhammad Alamzaib, Dhruvil Patel, Ryan Naughton, Aws Polina, Maria Najam, Rashid Alhusain, Neel Patel, Yasar Sattar, M. Chadi Alraies

School of Medicine Publications

Background Aspiration thrombectomy devices, such as the AngioVac, allow the removal of thrombus, especially in patients with contraindications to anticoagulation use. The AngioVac was approved by the U.S. Food and Drug Administration to remove fresh, soft thrombi or emboli during extracorporeal bypass for up to six hours. Real-world data on the most common modes of failure and complications associated with the AngioVac are unavailable.

Methods The Manufacturer and User Facility Device Experience database was queried for reports of the AngioVac device failure and adverse events from April 2013 to March 2022. Categorical variables were described as numbers, and all statistical …

Systematic Design And Data-Driven Evaluation Of Social Determinants Of Health Ontology (Sdoho), Yifang Dang, Fang Li, Xinyue Hu, Vipina K Keloth, Meng Zhang, Sunyang Fu, Muhammad F Amith, J Wilfred Fan, Jingcheng Du, Evan Yu, Hongfang Liu, Xiaoqian Jiang, Hua Xu, Cui Tao

Faculty, Staff and Student Publications

Objective: Social determinants of health (SDoH) play critical roles in health outcomes and well-being. Understanding the interplay of SDoH and health outcomes is critical to reducing healthcare inequalities and transforming a "sick care" system into a "health-promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way.

Material and methods: Drawing on the content of existing ontologies relevant to certain aspects of SDoH, we used a top-down approach to formally model classes, relationships, and …

Early-Adulthood Spike In Protein Translation Drives Aging Via Juvenile Hormone/Germline Signaling, Harper S Kim, Danitra J Parker, Madison M Hardiman, Erin Munkácsy, Nisi Jiang, Aric N Rogers, Yidong Bai, Colin Brent, James A Mobley, Steven N Austad, Andrew M Pickering

Faculty, Staff and Student Publications

Protein translation (PT) declines with age in invertebrates, rodents, and humans. It has been assumed that elevated PT at young ages is beneficial to health and PT ends up dropping as a passive byproduct of aging. In Drosophila, we show that a transient elevation in PT during early-adulthood exerts long-lasting negative impacts on aging trajectories and proteostasis in later-life. Blocking the early-life PT elevation robustly improves life-/health-span and prevents age-related protein aggregation, whereas transiently inducing an early-life PT surge in long-lived fly strains abolishes their longevity/proteostasis benefits. The early-life PT elevation triggers proteostatic dysfunction, silences stress responses, and drives age-related …

One Size Does Not Fit All: Advanced Practice Provider Considerations For The Antimicrobial Steward., Kyleen E. Swords, Gina Weddle, Joshua C. Herigon, Paula D. Stering, Matthew S L Lee

Manuscripts, Articles, Book Chapters and Other Papers

Advanced practice providers are a diverse and established group of antimicrobial prescribers in both ambulatory and inpatient settings. We outline important considerations for antimicrobial stewardship programs and stewards to consider when engaging this important group of providers.

Cultivated Autologous Limbal Epithelial Cell (Calec) Transplantation: Development Of Manufacturing Process And Clinical Evaluation Of Feasibility And Safety, Ula V Jurkunas, Jia Yin, Lynette K Johns, Sanming Li, Helene Negre, Kit L Shaw, Lassana Samarakoon, Allison R Ayala, Ahmad Kheirkhah, Kishore Katikireddy, Alex Gauthier, Stephan Ong Tone, Aaron R Kaufman, Stacey Ellender, Diego E Hernandez Rodriguez, Heather Daley, Reza Dana, Myriam Armant, Jerome Ritz

Faculty, Staff and Student Publications

To treat unilateral limbal stem cell (LSC) deficiency, we developed cultivated autologous limbal epithelial cells (CALEC) using an innovative xenobiotic-free, serum-free, antibiotic-free, two-step manufacturing process for LSC isolation and expansion onto human amniotic membrane with rigorous quality control in a good manufacturing practices facility. Limbal biopsies were used to generate CALEC constructs, and final grafts were evaluated by noninvasive scanning microscopy and tested for viability and sterility. Cultivated cells maintained epithelial cell phenotype with colony-forming and proliferative capacities. Analysis of LSC biomarkers showed preservation of "stemness." After preclinical development, a phase 1 clinical trial enrolled five patients with unilateral LSC …

Fetal Metabolic Adaptations To Cardiovascular Stress In Twin-Twin Transfusion Syndrome, Jacqueline G Parchem, Huihui Fan, Lovepreet K Mann, Qiuying Chen, Jong H Won, Steven S Gross, Zhongming Zhao, Heinrich Taegtmeyer, Ramesha Papanna

Faculty, Staff and Student Publications

Monochorionic-diamniotic twin pregnancies are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples from severe TTTS cases vs. singleton controls. Amniotic fluid metabolites demonstrated alterations in fatty acid, glucose, and steroid hormone metabolism in TTTS. Among TTTS cases, unsupervised principal component analysis revealed two …

Incidence Of Resting-State Functional Connectivity To Secondary Language Areas And Contralateral Language Areas In Patients With Brain Tumors, Angela L Young, Suprateek Kundu, Karthik K Tappa, Ping Hou, Ho-Ling Liu, Vinodh A Kumar

Faculty, Staff and Student Publications

Purpose: Secondary language areas, including the pre-supplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), and the visual word form area (VWFA) play important roles in speech, but have been under-evaluated in the realm of resting-state (rs)-fMRI. The purpose of this study is to determine the incidence that secondary language areas and contralateral language areas can be localized using seed-based correlation (SBC) rs-fMRI.

Methods: We retrospectively reviewed 40 rs-fMRIs for functional connectivity (FC) to secondary language areas in cases where FC to Broca's or Wernicke's area near tumor in the left hemisphere were successfully generated using SBC analysis. Logistical regression was …

Advances In The Radiological Evaluation Of And Theranostics For Glioblastoma, Grayson W Hooper, Shehbaz Ansari, Jason M Johnson, Daniel T Ginat

Faculty, Staff and Student Publications

Imaging is essential for evaluating patients with glioblastoma. Traditionally a multimodality undertaking, CT, including CT cerebral blood profusion, PET/CT with traditional fluorine-18 fluorodeoxyglucose (18F-FDG), and MRI have been the mainstays for diagnosis and post-therapeutic assessment. However, recent advances in these modalities, in league with the emerging fields of radiomics and theranostics, may prove helpful in improving diagnostic accuracy and treating the disease.

The Interplay Between H3k36 Methylation And Dna Methylation In Cancer, Jiameng Dan, Zeling Du, Jinghong Zhang, Taiping Chen

Faculty, Staff and Student Publications

No abstract provided.

Developing Electronic Clinical Quality Measures To Assess The Cancer Diagnostic Process, Daniel R Murphy, Andrew J Zimolzak, Divvy K Upadhyay, Li Wei, Preeti Jolly, Alexis Offner, Dean F Sittig, Saritha Korukonda, Riyaa Murugaesh Rekha, Hardeep Singh

Faculty, Staff and Student Publications

OBJECTIVE: Measures of diagnostic performance in cancer are underdeveloped. Electronic clinical quality measures (eCQMs) to assess quality of cancer diagnosis could help quantify and improve diagnostic performance.

MATERIALS AND METHODS: We developed 2 eCQMs to assess diagnostic evaluation of red-flag clinical findings for colorectal (CRC; based on abnormal stool-based cancer screening tests or labs suggestive of iron deficiency anemia) and lung (abnormal chest imaging) cancer. The 2 eCQMs quantified rates of red-flag follow-up in CRC and lung cancer using electronic health record data repositories at 2 large healthcare systems. Each measure used clinical data to identify abnormal results, evidence of …

A Defective Mechanosensing Pathway Affects Fibroblast-To-Myofibroblast Transition In The Old Male Mouse Heart, Aude Angelini, Joann Trial, Alexander B Saltzman, Anna Malovannaya, Katarzyna A Cieslik

Faculty, Staff and Students Publications

The cardiac fibroblast interacts with an extracellular matrix (ECM), enabling myofibroblast maturation via a process called mechanosensing. Although in the aging male heart, ECM is stiffer than in the young mouse, myofibroblast development is impaired, as demonstrated in 2-D and 3-D experiments. In old male cardiac fibroblasts, we found a decrease in actin polymerization, α-smooth muscle actin (α-SMA), and Kindlin-2 expressions, the latter an effector of the mechanosensing. When Kindlin-2 levels were manipulated via siRNA interference, young fibroblasts developed an old-like fibroblast phenotype, whereas Kindlin-2 overexpression in old fibroblasts reversed the defective phenotype. Finally, inhibition of overactivated extracellular regulated kinases …

Increased Sirt3 Combined With Parp Inhibition Rescues Motor Function Of Sbma Mice, David R Garcia Castro, Joseph R Mazuk, Erin M Heine, Daniel Simpson, R Seth Pinches, Caroline Lozzi, Kathryn Hoffman, Phillip Morrin, Dylan Mathis, Maria V Lebedev, Elyse Nissley, Kang Hoo Han, Tyler Farmer, Diane E Merry, Qiang Tong, Maria Pennuto, Heather L Montie

Faculty, Staff and Students Publications

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease with substantial mitochondrial and metabolic dysfunctions. SBMA is caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Activating or increasing the NAD+-dependent deacetylase, SIRT3, reduced oxidative stress and death of cells modeling SBMA. However, increasing diminished SIRT3 in AR100Q mice failed to reduce acetylation of the SIRT3 target/antioxidant, SOD2, and had no effect on increased total acetylated peptides in quadriceps. Yet, overexpressing SIRT3 resulted in a trend of motor recovery, and corrected TCA cycle activity by decreasing acetylation of SIRT3 target proteins. We sought to boost blunted SIRT3 activity …

The Safety And Efficacy Of Spironolactone Versus Oral Antibiotics For Moderate-Severe Acne In Post-Adolescent Females, Bhav Patel

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

• Acne is a common skin condition when the pores are clogged by particles like dead skin or oil, affecting approximately 50 million individuals in the U.S.¹
• Over a third of females experience moderate-severe forms that persist into adulthood and that number seems to be on the rise³
• Persistent moderate-severe acne often requires systemic medications and oral antibiotics are the most frequently prescribed therapy²
• Dermatologists prescribe more antibiotics per provider than any other specialty, and often for longer durations than recommended²
• The inappropriate use of oral antibiotics is contributing to bacterial resistance and disruption of the …

The Effectiveness Of Tirzepatide (Gip/Glp-1 Receptor Co-Agonist) Vs Glp-1 Receptor Agonists On Lowering A1c In Adults With Type 2 Diabetes Mellitus, Madison Laplante

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

In the United States, 34.2 million people are currently diagnosed with diabetes mellitus, which accounts for 10.5% of the total population.¹ Type 2 diabetes mellitus (T2DM) holds 94.2% of all diabetes diagnoses. The American Association of Diabetes estimates approximately $327 billion annually and is broken up as follows:¹

The Efficacy Of Fecal Microbiota Transplantation (Fmt) On Symptom Reduction In Patients With Irritable Bowel Syndrome (Ibs), Carly Liberatore

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Background

• IBS is a functional gastrointestinal tract disorder that affects 5-10% of the population.¹
• Symptom severity ranges from mild to severe interference with daily life.¹
• Current treatments are highly ineffective and focus on relieving symptoms rather than solving the root problem, gut dysbiosis.^{5, 6}
• Aim: To determine if FMT significantly reduces symptom severity in IBS patients

Systematic Review Of Needlestick Injuries In The Operating Room: A Case For Surgical Glove Redesigning, Shalmali Mirajkar, Zachary Bauman, Bethany Lowndes

EMET Projects

Background: Sharps or needlestick injuries (NSI) occur in roughly 15% of surgeries and are largely preventable. With such injuries, healthcare workers have a high risk of exposure to blood borne pathogens. Despite the implementation of several prevention measures such as double gloving and using blunt suture needles, there is still a high prevalence of NSIs. The aim of the current study is to conduct a systematic review to identify the most vulnerable parts of the hand for needlestick injuries, the most common tasks during which injuries occurred, and the most common instrument associated with the injury.

Methods: A …

A Novel Virtual-Based Comprehensive Clinical Approach To Headache Care, Thomas Berk, Stephen Silberstein, Peter Mcallister

Department of Jefferson Headache Center Papers and Presentations

One major innovation, a result of the coronavirus pandemic, has been the proliferation of telemedicine. Telehealth can help solve the access problems that plague headache medicine, allowing patients in areas with no headache expertise to consult and work with a headache specialist. This is a retrospective chart review of patients seen by Neura Health, a comprehensive app-based telehealth headache center. Patients are seen by a specialist and, in addition to any medical recommendations, are given care plans individualized to their condition and recommendations at the end of their clinical appointments. The primary outcome of this study is a decrease in …

Defining The Roles Of Pyruvate Oxidation, Tca Cycle, And Mannitol Metabolism In Methicillin-Resistant Staphylococcus Aureus Catheter-Associated Urinary Tract Infection, Santosh Paudel, Sarah Guedry, Chloe L P Obernuefemann, Scott J Hultgren, Jennifer N Walker, Ritwij Kulkarni

Faculty, Staff and Student Publications

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of complicated urinary tract infection (UTI) associated with the use of indwelling urinary catheters. Previous reports have revealed host and pathogen effectors critical for MRSA uropathogenesis. Here, we sought to determine the significance of specific metabolic pathways during MRSA UTI. First, we identified four mutants from the Nebraska transposon mutant library in the MRSA JE2 background that grew normally in rich medium but displayed significantly reduced growth in pooled human urine (HU). This prompted us to transduce the uropathogenic MRSA 1369 strain with the transposon mutants in sucD and fumC (tricarboxylic acid …

Systemic Anticancer Therapy And Thromboembolic Outcomes In Hospitalized Patients With Cancer And Covid-19, Shuchi Gulati, Chih-Yuan Hsu, Surbhi Shah, Pankil K. Shah, Rebecca Zon, Susan Alsamarai, Joy Awosika, Ziad El-Bakouny, Babar Bashir, Alicia Beeghly, Stephanie Berg, Daniel De-La-Rosa-Martinez, Deborah B. Doroshow, Pamela C. Egan, Joshua Fein, Daniel B. Flora, Christopher R. Friese, Ariel Fromowitz, Elizabeth A. Griffiths, Clara Hwang, Chinmay Jani, Monika Joshi, Hina Khan, Elizabeth J. Klein, Natalie Knox Heater, Vadim S. Koshkin, Daniel H. Kwon, Chris Labaki, Tahir Latif, Rana R. Mckay, Gayathri Nagaraj, Elizabeth S. Nakasone, Taylor Nonato, Hyma V. Polimera, Matthew Puc, Pedram Razavi, Erika Ruiz-Garcia, Renee Maria Saliby, Aditi Shastri, Sunny R.K. Singh, Vicky Tagalakis, Diana Vilar-Compte, Lisa B. Weissmann, Cy R. Wilkins, Trisha M. Wise-Draper, Michael T. Wotman, James J. Yoon, Sanjay Mishra, Petros Grivas, Yu Shyr, Jeremy L. Warner, Jean M. Connors, Dimpy P. Shah, Rachel P. Rosovsky

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.

OBJECTIVE: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.

DESIGN, SETTING, AND PARTICIPANTS: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.

EXPOSURE: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune …

Psychometric Results Of A New Patient-Reported Outcome Measure For Uveal Melanoma Post-Brachytherapy Treatment: The Prom-Um, Ezekiel Weis, Jing Jiang, Alison H. Skalet, Carol L. Shields, R. Trafford Crump

Wills Eye Hospital Papers

The objective of this study was to evaluate the psychometric properties of a new patient-reported outcome instrument intended for use with patients who have undergone brachytherapy for uveal melanoma (PROM-UM). Classical test theory and item response theory were used to evaluate the performance of individual items and domains. A convenience sample of 439 participants who had undergone brachytherapy for uveal melanoma from one of three North American ocular oncology treatment centers were included in this cross-sectional study. Exploratory factor analysis identified three domains which were labelled “Symptom Impairment”, “Worry”, and “Discomfort”. The acceptability of the instrument was supported by little …

Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial., Chris A Rees, David C. Brousseau, Daniel M Cohen, Anthony Villella, Carlton Dampier, Kathleen Brown, Andrew Campbell, Corrie E Chumpitazi, Gladstone Airewele, Todd Chang, Christopher Denton, Angela Ellison, Alexis Thompson, Fahd Ahmad, Nitya Bakshi, Keli D Coleman, Sara Leibovich, Deborah Leake, Dunia Hatabah, Hagar Wilkinson, Michelle Robinson, T Charles Casper, Elliott Vichinsky, Claudia R Morris

Department of Pediatrics Faculty Papers

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 …

Pyruvate Anaplerosis Is A Targetable Vulnerability In Persistent Leukaemic Stem Cells, Kevin M Rattigan, Zuzana Brabcova, Daniele Sarnello, Martha M Zarou, Kiron Roy, Ryan Kwan, Lucie De Beauchamp, Amy Dawson, Angela Ianniciello, Ahmed Khalaf, Eric R Kalkman, Mary T Scott, Karen Dunn, David Sumpton, Alison M Michie, Mhairi Copland, Saverio Tardito, Eyal Gottlieb, G Vignir Helgason

Faculty, Staff and Student Publications

Deregulated oxidative metabolism is a hallmark of leukaemia. While tyrosine kinase inhibitors (TKIs) such as imatinib have increased survival of chronic myeloid leukaemia (CML) patients, they fail to eradicate disease-initiating leukemic stem cells (LSCs). Whether TKI-treated CML LSCs remain metabolically deregulated is unknown. Using clinically and physiologically relevant assays, we generate multi-omics datasets that offer unique insight into metabolic adaptation and nutrient fate in patient-derived CML LSCs. We demonstrate that LSCs have increased pyruvate anaplerosis, mediated by increased mitochondrial pyruvate carrier 1/2 (MPC1/2) levels and pyruvate carboxylase (PC) activity, in comparison to normal counterparts. While imatinib reverses BCR::ABL1-mediated LSC metabolic …

The Pyrimidinosome: Orchestrating Pyrimidine Biosynthesis And Ferroptosis Defense, Boyi Gan

Faculty, Staff and Student Publications

A recent study by Yang et al.1 uncovers the pyrimidinosome, a multienzyme complex where enzymes from different subcellular compartments collaborate to enable efficient pyrimidine biosynthesis and ferroptosis defense, highlighting the remarkable adaptability of cellular metabolism and new therapeutic opportunities.

Genetic Dissection Of Crossover Mutants Defines Discrete Intermediates In Mouse Meiosis, Tolkappiyan Premkumar, Lakshmi Paniker, Rhea Kang, Mathilde Biot, Ericka Humphrey, Honorine Destain, Isabella Ferranti, Iyinyeoluwa Okulate, Holly Nguyen, Vindhya Kilaru, Melissa Frasca, Parijat Chakraborty, Francesca Cole

Faculty, Staff and Student Publications

Crossovers (COs), the exchange of homolog arms, are required for accurate chromosome segregation during meiosis. Studies in yeast have described the single-end invasion (SEI) intermediate: a stabilized 3' end annealed with the homolog as the first detectible CO precursor. SEIs are thought to differentiate into double Holliday junctions (dHJs) that are resolved by MutLgamma (MLH1/MLH3) into COs. Currently, we lack knowledge of early steps of mammalian CO recombination or how intermediates are differentiated in any organism. Using comprehensive analysis of recombination in thirteen different genetic conditions with varying levels of compromised CO resolution, we infer CO precursors include asymmetric SEI-like …

Detection Method Has Independent Prognostic Significance In The Plco Lung Screening Trial, James P Long, Yu Shen

Faculty, Staff and Student Publications

Prognostic models in cancer use patient demographic and tumor characteristics to predict survival and dynamic disease prognosis. Past work in breast cancer has shown that cancer detection method, screen-detected or symptom-detected, has prognostic significance. We investigate this phenomenon in the lung component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial. Patients were randomized to intervention, receiving four annual chest x-rays (CXRs), or to control, receiving usual care. Patients were followed for a total of approximately 13 years. In PLCO, lung cancer detection method has independent prognostic value exceeding that of variables commonly used in lung cancer prognostic models, …

Computational Modeling And Minimization Of Unintended Neuronal Excitation In A Lifu Stimulation, Boqiang Fan, Wayne Goodman, Raymond Y Cho, Sameer A Sheth, Richard R Bouchard, Behnaam Aazhang

Faculty, Staff and Student Publications

The neuromodulation effect of low-intensity focused ultrasound (LIFU) is highly target-specific. Unintended off-target neuronal excitation can be elicited when the beam focusing accuracy and resolution are limited, whereas the resulted side effect has not been evaluated quantitatively. There is also a lack of methods addressing the minimization of such side effects. Therefore, this work introduces a computational model of unintended neuronal excitation during LIFU neuromodulation, which evaluates the off-target activation area (OTAA) by integrating an ultrasound field model with the neuronal spiking model. In addition, a phased array beam focusing scheme called constrained optimal resolution beamforming (CORB) is proposed to …

The Rise Of Degrader Drugs, Mingxing Teng, Nathanael S Gray

Faculty, Staff and Students Publications

The cancer genomics revolution has served up a plethora of promising and challenging targets for the drug discovery community. The field of targeted protein degradation (TPD) uses small molecules to reprogram the protein homeostasis system to destroy desired target proteins. In the last decade, remarkable progress has enabled the rational development of degraders for a large number of target proteins, with over 20 molecules targeting more than 12 proteins entering clinical development. While TPD has been fully credentialed by the prior development of immunomodulatory drug (IMiD) class for the treatment of multiple myeloma, the field is poised for a "Gleevec …

Incarcerated Gravid Uterus - A Systematic Review, Sujatha Narayanamoorthy, Allix Hillebrand, Rakshitha Pendam, Rodney Mclaren

Department of Obstetrics and Gynecology Faculty Papers

Incarcerated gravid uterus (IGU) is a serious complication of pregnancy that leads to adverse obstetric outcomes. The aim of this review was to describe this entity in detail. We also aimed to understand if pregnancies with predisposing risk factors that increase the risk of developing IGU had a difference in their clinical manifestations, treatment, and obstetric outcomes. The PubMed, MEDLINE, Embase, Scopus databases and clinicaltrials.gov were searched from inception to July 2023. Case reports and series that provided all the details of the pregnancy and IGU outcome were included. Study quality and risk of bias were assessed using a tool …