Investigative Techniques Commons^™

Use Of Electrocardiograms To Identify Coronary Artery Disease: Cross-Validation Of An Artificial Intelligence Model, Michael Leasure, Indu Poornima, Adam Butchy, Utkars Jain, Devin Vasoya, Michael Warnick, Brent Williams, John Rehder, Prahlad Menon, Veronica A. Covalesky, Gary S. Mintz

Department of Medicine Faculty Papers

BACKGROUND: The current gold standard for the diagnosis of coronary artery disease (CAD) is invasive angiography; however, it is an invasive procedure. Therefore, we developed an artificial intelligence model designed to predict significant CAD from a resting digital 12-lead electrocardiogram (ECG).

OBJECTIVES: This retrospective study assessed the model's ability to predict clinically significant CAD in a patient population presenting for coronary angiography.

METHODS: From 2019 to 2021, 16,476 patients had a resting 12-lead digital ECG recorded within 90 days prior to coronary angiography. The artificial intelligence model was developed using 10-fold cross-validation methodology. Clinically significant disease was defined as angiographic …

Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation …

Plans4care, A Web Application Providing Caregivers Personalized Solutions To Manage Dementia-Related Care Challenges: Proof Of Concept And Efficacy Trial, Laura N. Gitlin, Eric Jutkowitz, Catherine V. Piersol, Sokha Koeuth, Taylor Sivori, Melinda J. Webster, Rachel N. Barnett, David L. Roth

Department of Occupational Therapy Faculty Papers

OBJECTIVE: Few dementia caregivers have access to evidence-based support programs. Web applications (app) may address this gap. Plans4Care, a web app, provides caregivers with on-demand personalized solutions to address care challenges. We present results of a proof-of-concept study and describe a trial protocol to test efficacy.

METHODS: To use Plans4Care, caregivers respond to brief onboarding questions, assess dementia patients' cognitive function, identify care challenges, and generate "action plans" (personalized strategies). Telehealth sessions with dementia-trained care advisors are available. A proof-of-concept study evaluated a clickable prototype using standardized technology scales to determine if >75 % scored positively on four criteria (acceptability, …

Clinical Performance Of A Novel Point-Of-Care High-Sensitivity Cardiac Troponin I Assay, Alan H. B. Wu, Simon A. Mahler, Stacey L. House, Saeed A. Jortani, Michael H. Creer, Kristin L. Rising, Jason J. Bischof, Chad Crystal, Gary F. Headden, Fred S. Apple, Nicholas E. Harrison, Andrew C. Meltzer, Justin T. Baca, Brian Tiffany, Mark Sochor, Grace U. Pentecostes, Katrina P. Di Tullio, Manish S. Gupta, Adam J. Singer, James L. Januzzi

Department of Emergency Medicine Faculty Papers

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays performed in the central laboratory have long turnaround times. This study evaluates the clinical performance of a novel bedside point-of-care (POC) hs-cTnI assay (i-STAT® hs-TnI) to aid in the diagnosis of myocardial infarction (MI).

METHODS: A prospective multisite cohort study involving emergency department (ED) patients with symptoms suggestive of acute coronary syndrome was conducted at 28 sites across the United States. Serial whole blood samples were collected at 0-1 h and >1-3 h from ED presentation. Primary outcome was MI or non-MI. Sensitivity, specificity, and negative predictive value (NPV) for MI were calculated with …

Micrornas In Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, And Treatment Monitoring, Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang, Behzad Mansoori

Student Papers, Posters & Projects

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are …

Thoracolumbar Fractures: Historical Systems And Advancements With The Ao Spine Classification, Barry Ting Sheen Kweh, Alex R. Vaccaro, Gregory D. Schroeder, Jose A. Canseco, Maximilian Reinhold, Mohamed M. Aly, Sebastian Bigdon, Mohammad El-Skarkawi, Richard J. Bransford, Andrei Fernandes Joaquim, Harvinder Singh Chhabra, Emiliano Vialle, Rishi M. Kanna, Charlotte Dandurand, Cumhur Öner, Jin Wee Tee

Rothman Institute Papers

Study Design: Systematic Review. Objective: To describe the historical classifications of thoracolumbar injuries and their evolution into the AO Spine Thoracolumbar Injury Classification System. Methods: A systematic review of MEDLINE, EMBASE and Cochrane Databases was performed in keeping with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Results: 445 articles were crystallized to 14 included studies. Simple categorization systems offered by Bohler or Watson-Jones merely identify fracture morphology. Holdsworth and Denis conveyed a sense of the stability of injuries by noting columns of stability, but still failed to take into consideration important factors such as neurological status or …

Metastatic Uveal Melanoma Surveillance: A Delphi Panel Consensus, Juan Alban, R. Christopher Bowen, David A. Reichstein, Meredith Mckean, Jose Lutzky, Ezekiel Weis, Richard D. Carvajal, Susan Dulka, Brian G. Morse, Marcus O. Butler, Suthee Rapisuwon, Kevin B. Kim, Sanjay Chandrasekaran, Allison Betof Warner, Jonathan S. Zager, Bartosz Chmielowski, Sapna P. Patel, Leonel Fernando Hernandez-Aya, Zelia M. Correa, Leslie A. Fecher, Yana G. Najjar, Kamaneh Montazeri, Alexander N. Shoushtari, Asad Javed, Dan S. Gombos, April K. S. Salama, Katy Tsai, Frank H. Miller, Nikhil Khushalani, Rino S. Seedor, Evan J. Lipson, Sunil A. Reddy, Elizabeth Buchbinder, Shailender Bhatia, Anna Pavlick, Inderjit Mehmi, Thomas Aaberg, Alexandra P. Ikeguchi, Ivana K. Kim, Scott D. Walter, Arun D. Singh, Ryan J. Sullivan, Jacob S. Choi, Basil K. Williams, Marlana Orloff, Prithvi Mruthyunjaya, Megan D. Schollenberger, Namita Gandhi, J. William Harbour, Sunandana Chandra

Department of Radiology Faculty Papers

BACKGROUND/OBJECTIVES: Uveal melanoma is a rare but aggressive intraocular malignancy that metastasizes in up to half of patients, most commonly to the liver, despite effective local treatment. In the absence of robust evidence, there are no standardized guidelines for post-treatment surveillance, resulting in wide variation in imaging modalities, frequency, and duration across physicians and institutions. This study aimed to develop expert consensus recommendations for surveillance strategies in patients with uveal melanoma.

METHODS: A modified Delphi method was conducted across three iterative survey rounds between September 2024 and February 2025 using an online platform. Panelists included medical oncologists, ocular oncologists, radiologists, …

Concentric Macular Rings And Oct Corrugations In Foveal Hypoplasia: Proof Of Concept For An Optical Interference Mechanism, Ari August, Ralph Eagle, Tatyana Milman, Rebecca Procopio, Bruce Schnall, Jose Pulido

Wills Eye Hospital Papers

BACKGROUND: Concentric macular rings (CMR) and Henle fiber layer (HFL) corrugations, potential clinical biomarkers of foveal hypoplasia, have been observed in laser fundus photographs and optical coherence tomography (OCT) images, respectively. Some believe these findings represent true anatomical structural changes while others hypothesize that they are artifacts of interference; however, to our knowledge, no previous study has provided evidence to support either theory.

METHODS: This retrospective case series analyzed CMR and OCT corrugations in 3 patients (6 eyes) with foveal hypoplasia. Dark fringe diameters of CMR at different wavelengths (λ: red = 635, green = 532, blue = 488 nm) …

A Phase-Ii Randomized Controlled Pilot And Feasibility Study Of Nicotinamide Riboside Supplementation In Older Adults With Amnestic Mild Cognitive Impairment, Christopher R. Martens, Kevin P. Decker, Theodore M. Deconne, Faria Sanjana, Fiona Horvat, Nicholas A. Rizzi, Catherine Awad, Elizabeth Habash, Joshua C. Hobson, Michael L. Armstrong, Nichole Reisdorph, Ryan T. Pohlig, Alyssa M. Lanzi, Curtis L. Johnson, Matthew L. Cohen, James M. Ellison

Department of Psychiatry and Human Behavior Faculty Papers

Abstract

Background

The decline of nicotinamide adenine dinucleotide (NAD+) with aging may elevate risk of Alzheimer’s disease and related neurocognitive disorders (ADRD) by impairing cellular energy metabolism and reducing cerebral blood flow.

Method

We conducted a 12-week double-blind, randomized, placebo-controlled pilot study to evaluate the safety, tolerability, and preliminary efficacy of the NAD+ precursor, nicotinamide riboside (NR; 500 mg b.i.d.), for enhancing cognitive function and cerebral perfusion in older adults with mild cognitive impairment (MCI).

Result

52 participants (33 females, 19 males) were randomized and 42 completed the trial (NR = 22, placebo = 20). Adherence was similar between groups …

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …

Radiogenomic Profiling Of Prostate Tumors Prior To External Beam Radiotherapy Converges On A Transcriptomic Signature Of Tgf-Β Activity Driving Tumor Recurrence, Anson T. Ku, Uma Shankavaram, Shana Y. Trostel, Hong Zhang, Sumeyra Kartal, Houssein A. Sater, Stephanie A. Harmon, Nicole V. Carrabba, Yang Liu, Hyunnam Ryu, James A. Proudfoot, Boon Hao Hong, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Mack Roach, Howard M. Sandler, Stephanie L. Pugh, Kenneth L. Zeitzer, Lucas C. Mendez, Nirav S. Kapadia, William A. Hall, Anand B. Desai, Radka S. Stoyanova, Alan Pollack, Elai Davicioni, Melvin L. K. Chua, Baris Turkbey, Adam G. Sowalsky, Deborah E. Citrin

Einstein Health Papers

PURPOSE: Clinical risk grouping based on PSA, tumor grade, and disease extent guides treatment intensity for localized prostate cancer. However, many patients with intermediate- or high-risk disease treated with external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) still develop biochemical recurrence (BCR). Early identification of patients at high risk for BCR could enable personalized treatment strategies.

EXPERIMENTAL DESIGN: We prospectively enrolled 29 patients with intermediate- or high-risk prostate cancer undergoing EBRT and ADT. Pretreatment biopsies (n = 60) underwent whole-transcriptome microarray and whole-exome sequencing. Patients received multiparametric MRI at baseline and 6 months after treatment, with a median follow-up …

Electrochemical Sensors For In Situ Monitoring Of Reactive Species During Cold Atmospheric Plasma-Based Therapies, Jonathan Thomas, Suneel Kumar, Gagana Karkada, Julia Sutter, Kristina Pattison, Jason Rainone, Dhruv Patel, Shashank Madhavan, Fred Krebs, Francois Berthiaume, Vandana Miller, Katharina Stapelmann

Kimmel Cancer Center Faculty Papers

Cold atmospheric pressure plasma (CAP) is emerging as a clinically relevant therapy for dermatological conditions such as actinic keratosis, warts, and chronic wounds. However, these therapies lack strategies to monitor CAP delivery in situ and to ensure delivery of an effective CAP dose without unwanted toxicity. CAP acts as a therapeutic agent in these biomedical applications primarily (but not solely) through reactive oxygen and nitrogen species (RONS) generated at transiently high local concentrations. Here we demonstrate the use of bio-electrochemical sensors capable of real-time measurements of key CAP RONS: hydrogen peroxide and oxidation-reduction-potential (ORP). In in vitro scratch assays and …

Model For Calculating Impact Force For Individualized Hip Fracture Prediction During A Fall, Alisha Agarwal, Daniel Kargilis, Nishtha Gupta, Michael Chang, Rui Feng, Gregory Chang, Chamith S. Rajapakse

Student Papers, Posters & Projects

Osteoporotic-related weakening of bone is a common cause of hip fractures. The standard of care for the diagnosis and management of osteoporosis is the dual-energy x-ray absorptiometry bone mineral density T-scores. Many individuals considered nonosteoporotic, however, still sustain fractures since these tools do not incorporate vital bone parameters and subject-specific characteristics. The purpose of this work was to (1) develop a simple analytical model for estimating the force exerted on the femur during a fall (i.e., impact force) based on measurable patient metrics and (2) define a quantifiable fracture risk index by comparing finite-element-derived bone strength and impact force, which …

Laboratory Monitoring In Patients With Moderate To Severe Plaque Psoriasis, Jonathan M. Fenkel, John A. Osborne, April W. Armstrong, Bruce Strober, Linda Stein Gold, Michael Cameron, Mark Lebwohl

Department of Medicine Faculty Papers

OBJECTIVES: Plaque psoriasis is a common immune-mediated disease associated with various comorbidities, including cardiovascular disease, diabetes, psoriatic arthritis, liver disease, and mood disorders. Biologic and small-molecule therapies are efficacious and well tolerated in adults with moderate to severe plaque psoriasis. However, dermatologists may be uncertain about appropriate laboratory monitoring in patients treated with these therapies, especially those with comorbidities.

METHODS: This review summarizes prescribing information and provides expert recommendations based on real-world experience in the monitoring of concerning laboratory values in patients with psoriasis.

RESULTS: Individualized monitoring is essential for maximizing the benefits and minimizing the risks associated with biologic …

Per Se Driving Under The Influence Of Cannabis Statutes And Blood Delta-9-Tetrahydrocannabinol Concentrations Following Short-Term Cannabis Abstinence, Robert L. Fitzgerald, Anya Umlauf, Raymond T. Suhandynata, David J. Grelotti, Marilyn A. Huestis, Kyle F. Mastropietro, Igor Grant, Thomas D. Marcotte

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Several US states have per se laws using 2 or 5 ng/mL of delta-9-tetrahydrocannabinol (THC) as cutpoints for driving under the influence of cannabis, while some have zero-tolerance statutes. These cutpoints are considered prima facia evidence of driving impairment.

METHODS: In a cohort of people who regularly use cannabis (N = 190) we measured baseline concentrations of THC after instructing participants to abstain from cannabis for at least 48 hours. Baseline driving performance was evaluated using a driving simulator. We also measured blood THC concentrations serially following a smoking session (placebo or active cannabis).

RESULTS: Forty-three percent of the …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

Liver-Directed Base Editing Of Abcc6 Prevents Ectopic Calcification In A Variant-Humanized Mouse Model Of Pseudoxanthoma Elasticum, Lauren C. Testa, Dora Obiri-Yeboah, Hooda Said, Ping Qu, Michael A. Levine, Mohamad-Gabriel Alameh, Kiran Musunuru, Qiaoli Li, Xiao Wang

Department of Biochemistry and Molecular Biology Faculty Papers

Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder characterized by ectopic calcification of elastic fibers throughout the skin, retina, and arteries. It is caused by pathogenic variants in ABCC6 , which encodes a transmembrane transporter that primarily localizes to hepatocytes. Loss of ABCC6 function in hepatocytes leads to systemic deficiency of inorganic pyrophosphate (PPi), a potent inhibitor of calcification; such depletion of PPi from the circulation is responsible for multisystemic ectopic calcification seen in PXE. Therefore, liver-targeted variant correction by genome editing and subsequent restoration of systemic PPi may offer a one-and-done therapeutic approach for PXE. The ABCC6 …

Promising Effects Of Car T-Cell Therapy In Refractory Stiff Person Syndrome And A Hopeful Future For All Neuroautoimmunities, Marinos Dalakas

Department of Neurology Faculty Papers

Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases. The CD19 CAR T cells-targeting those CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts-are now extensively explored in refractory neuroautoimmunities with promising benefits based on case series in patients with myasthenia gravis (MG), stiff person syndrome (SPS), neuromyelitis, myositis, and multiple sclerosis; some patients …

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

Long-Term Liver-Targeted Aav8 Gene Therapy For Mucopolysaccharidosis Iva, Shaukat A. Khan, Eliana Benincore-Florez, Fnu Nidhi, Jose Victor Álvarez, Dione A. Holder, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme, which leads to the accumulation of chondroitin-6-sulfate and keratan sulfate, primarily in cartilage and its extracellular matrix, resulting in a direct impact on cartilage and bone development, as well as subsequent systemic skeletal dysplasia. ERT and HSCT are current treatment options, but they have a limited effect on bone lesions. In this article, we investigated liver-specific AAV8 vectors with a thyroxine-binding globulin promoter in the MPS IVA murine model to evaluate the long-term (24 weeks in males …

Validation Of A Prognostic Nomogram For Locally Advanced Oropharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy With/Without Systemic Therapy, P. Bossi, R. Gili, S. Calza, L. Licitra, M. Maddalo, A. Bacigalupo, L. Belgioia, J. Cacicedo, N. Facchinetti, A. Garcia Castano, M. Oliva, P. Bonomo, G. Sanguineti, P. Franco, A. Argiris, A. Psyrri, E. Orlandi

Kimmel Cancer Center Faculty Papers

BACKGROUND: Head and neck squamous-cell carcinoma (HNSCC), particularly oropharyngeal cancer (OPC), exhibits diverse prognostic factors influenced by demographic and lifestyle variables. Prognostic nomograms, such as the one developed by Fakhry et al., incorporate clinical and biological markers to predict overall survival (OS) and progression-free survival (PFS) in OPC patients. However, their applicability to European populations remains unverified. This study aimed to externally validate Fakhry's prognostic nomogram in a large European cohort of locally advanced OPC patients treated with definitive intensity-modulated radiotherapy (IMRT) with or without systemic therapy.

METHODS: This is a retrospective external validation study conducted on 805 OPC patients …

Discriminative Accuracy Of Cha2ds2-Vasc Score, And Development Of Predictive Accuracy Model Using Machine Learning For Ischemic Stroke Risk In Cardiac Amyloidosis And Atrial Fibrillation, Waqas Ullah, Abhinav Nair, Eric Warner, Salman Zahid, Mansoor Rahman, Palwasha Khan, Indranee Rajapreyar, Sridhara S. Yaddanapudi, M. Chadi Alraies, Said Ashraf, Jeffery Van Hook, Yegeny Brailovsky

Department of Medicine Faculty Papers

BACKGROUND: CHA2DS2-VASc score in cardiac amyloidosis (CA) with atrial fibrillation (AF) is believed to underestimate ischemic stroke risk, necessitating a better predictive model.

METHODS: Data were obtained from the National Readmission Database (NRD). Outcomes between CA-AF and no-CA-AF were compared using multivariate regression analysis to calculate adjusted odds ratios (aORs). AutoScore, an interpretable machine learning framework, was used to develop a stroke risk prediction model, and its predictive accuracy was evaluated with an area under the curve (AUC) using the receiver operating characteristic analysis.

RESULTS: A total of 11,860,804 (CA-AF 22,687 (0.19%) and no-CA-AF 11,838,117) patients were identified from 2015 …

Evaluating The Potential And Limitations Of Nanopore Adaptive Sampling For Targeted Transcriptome Sequencing, Nicole Debruyne, Feng Wang, Yang Xu, Lan Lin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Long-read RNA sequencing is a powerful technology for transcriptomics, but low throughput and high cost pose challenges. Adaptive sampling, a feature of Oxford Nanopore Technologies, offers real-time enrichment by selectively ejecting non-target molecules. We evaluate adaptive sampling for human transcriptome analysis. Adaptive sampling modestly enriches target transcripts (1.3 × for cDNA sequencing, 1.9 × for direct RNA sequencing) while preserving gene expression and splicing profiles, but is significantly less effective than cDNA hybridization capture. Short read lengths and low sequencing quality limit performance. Adaptive sampling on direct RNA sequencing can boost target yield (~ 20%) within fixed run times, potentially …

Comparison Of Anterior And Posterior Surgical Approaches For Cervical Ossification Of The Posterior Longitudinal Ligament Stratified By Spinal Levels: A Systematic Review And Meta-Analysis, Seyed Danial Alizadeh, Sepehr Khosravi, Farzin Farahbakhsh, Vali Baigi, Moein Khormali, Mohsen Hajiqasemi, Zahra Eskandari, Mahgol Sadat Hassan Zadeh Tabatabaei, Amirmahdi Khayyamfar, Mohammad-Rasoul Jalalifar, Sepehr Armaghan, Masoud Pourghahramani Koltapeh, Zahra Ghodsi, Michael G. Fehlings, Alex R. Vaccaro, Vafa Rahimi-Movaghar

Rothman Institute Papers

OBJECTIVE: To compare the outcomes of anterior and posterior surgical approaches for treating cervical ossification of the posterior longitudinal ligament across multiple spinal levels, including 1-2 spinal levels, ≥ 3 levels, or studies that operated on both spinal levels, called mixed spinal levels.

METHODS: A search strategy using pertinent keywords was employed in the MEDLINE, Embase, Scopus, and Web of Science databases. Data on Modified Japanese Orthopaedic Association (mJOA) scores, radiographic outcomes, and complications were extracted. A random-effects meta-analysis, subgroup meta-analysis, and sensitivity analysis were performed.

RESULTS: Among 13 included studies, the anterior approach was statistically associated with improved C2-C7 …

Apostel-R Recommendations For Reporting Retinal Optical Coherence Tomography Studies In Rodents, Frederike Cosima Oertel, Delia Cabrera Debuc, Peter A. Calabresi, Mei Chen, Christian Cordano, Michael Dietrich, Nicolas Feltgen, Oliver Gramlich, Ari J. Green, Janos Groh, Su-Chun Huang, Benjamin Knier, Thomas Korn, Letizia Leocani, Anat Loewenstein, Christian Van Oterendorp, Tunde Peto, Sven Schippling, Leopold Schmetterer, Steffen Schmitz-Valckenberg, Mathias W. Seeliger, Kenneth S. Shindler, Joel Schuman, Mustafa Sindi, Adnan Tufail, Jui-Kai Wang, Sebastian Wolf, Yuyi You, Martin Zinkernagel, Wolf Lagrèze, Philipp Albrecht

Department of Medicine Faculty Papers

BACKGROUND AND OBJECTIVES: Retinal optical coherence tomography (OCT) in rodent models has been used to longitudinally image retinal changes, to define end points for more costly or time-consuming experiments, and to better understand the pathophysiology underlying OCT findings in human diseases. No standardization of rodent OCT reporting currently exists. Here, we aim to establish consensus recommendation for reporting results from retinal OCT studies in rodents.

METHODS: Initial recommendations were developed based on the APOSTEL criteria for quantitative OCT reporting in humans by a core team. Using a modified Delphi process, an expert panel of rodent OCT researchers (N = 31) …

Performing Dual Glucose Clamp Experiments In Sedated Farm Swine: A Practical Method, Marc Torjman, Winston Hamilton, Katherine Dillon, Channy Loeum, Jeffrey Joseph

Department of Anesthesiology Faculty Papers

The hyperinsulinemic-euglycemic clamp technique is considered the gold standard for measuring insulin sensitivity in large animals. We developed a practical method for conducting concurrent glucose clamp experiments in a pair of sedated farm swine positioned in a sling. Descriptions of customized equipment and central venous access surgical procedures for blood collection are provided. Personnel functions are described for execution of the clamp protocol. A total of 24 hyperinsulinemic-euglycemic clamp studies were performed over 6 weeks. Infusaports remained functional for 1454 blood samples. There were three CSII catheter occlusions during bolus administration, and the swine showed no signs of infection or …

A Comparative Evaluation Of Two Subharmonic-Aided Pressure Estimation (Shape) Analysis Methods, Hailee Mayer, Priscilla Machado, Trang Vu, Annalisa Berzigotti, Jaume Bosch, Elton Dajti, Antonina Antonenko, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

Pressure measurement in clinical practice is a valuable tool for diagnostic evaluation, especially in diseases such as portal hypertension. Currently, portal pressures are measured by invasive hepatic vein catheterization, posing risks to patients, and limiting how often measurements can be obtained. Subharmonic-aided pressure estimation (SHAPE) is an ultrasound-based technique that leverages ultrasound contrast agents (UCAs) to estimate changes in hydrostatic pressure. UCAs act as nonlinear oscillators when exposed to high enough acoustic pressures (typically > 200 kPa) and produce significant energy components ranging from subharmonics to higher harmonics. Tissues do not generate significant subharmonic components, thus making it the optimal component …

Enhancing Methods For Research On Cannabis: A Workshop Report, Jonathan Samet, Jessica Barrington-Trimis, Lisa Bero, Ashley Brooks-Russell, Meghan Buran, Julia Dilley, Darin Erickson, Marilyn Huestis, Kent Hutchison, Thomas Jeanne, Michael Kosnett, David Kroll, Stephen Lankenau, Richard Miech, Rosalie Liccardo Pacula, Paula Riggs, Neeloofar Soleimanpour, Steven Teutsch, Gregory Tung, George Sam Wang

College of Health Professions Faculty Papers

AIMS: Progressive legalization of medical and recreational cannabis markets at the state-level has led to rapid growth of medical and recreational cannabis markets and to product diversification with emerging products having high concentrations of delta-9-tetrahydrocannabinol. Research on these products is still limited and the evidence available for policy formulation is diminished by methodological limitations.

METHODS: As a step towards addressing these limitations, the Colorado School of Public Health convened a multidisciplinary workshop that addressed four areas of cannabis research: epidemiological, clinical, surveillance, and policy. Workshop participants provided recommendations in each area to advance research on cannabis to make it more …

Uncovering The Pml::Rara Fusion In Cytogenetically Cryptic And Fish-Negative Acute Promyelocytic Leukemia-A Case Report And Comprehensive Literature Review, Busra Delikkaya, Jaime Eberle-Singh, Arianna Morton, Jerald Gong, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The PML::RARA fusion resulting from t(15;17) is the genetic hallmark of acute promyelocytic leukemia (APL), typically detected by cytogenetics and/or fluorescence in situ hybridization (FISH) studies. Rarely, APL patients present with normal cytogenetics and FISH findings, complicating diagnosis and delaying life-saving therapy. We report a 23-year-old male with clinical, morphologic and immunophenotypic features consistent with APL but negative for FISH studies. Despite prompt initiation of all-trans retinoic acid (ATRA) based on clinical suspicion, the patient succumbed to intracranial hemorrhage. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed a long isoform PML::RARA fusion. A review of 34 published cytogenetics- and FISH-negative cases since …

Comparison Of Authentic Urine N-Ethylpentedrone Metabolites To Predicted In Silico And In Vitro Human Hepatocyte Metabolism, Gloria Daziani, Omayema Taoussi, Diletta Berardinelli, Giulia Bambagiotti, Marilyn A. Huestis, Francesco P. Busardò, Jeremy Carlier

Institute of Emerging Health Professions Faculty Papers

Synthetic cathinones are the second most common class of substances belonging to the category of new psychoactive substances (NPS). N-ethylpentedrone (NEPD) self-administration was reported, making it important to elucidate its metabolic pathway to improve its detection. NEPD is often taken together with other substances; confidently identifying its intake is important for accurate toxicological analysis and understanding its toxicity. NEPD metabolism was studied following incubation with human hepatocytes and analysis by liquid chromatography-high-resolution mass spectrometry paired with Compound Discoverer software (Thermo Fisher Scientific). Prediction of possible metabolites was performed with the online software GLORYx. In vivo NEPD metabolism was evaluated by …