Medicine and Health Sciences Commons^™

Temporal Recording Of Mammalian Development And Precancer, Mirazul Islam, Yilin Yang, Alan J Simmons, Vishal M Shah, Krushna Pavan Musale, Yanwen Xu, Naila Tasneem, Zhengyi Chen, Linh T Trinh, Paola Molina, Marisol A Ramirez-Solano, Iannish D Sadien, Jinzhuang Dou, Andrea Rolong, Ken Chen, Mark A Magnuson, Jeffrey C Rathmell, Ian G Macara, Douglas J Winton, Qi Liu, Hamim Zafar, Reza Kalhor, George M Church, Martha J Shrubsole, Robert J Coffey, Ken S Lau

Faculty, Staff and Student Publications

Temporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations1,2, an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering3–5. Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell …

Neoadjuvant And Adjuvant Treatments For Early Stage Resectable Nsclc: Consensus Recommendations From The International Association For The Study Of Lung Cancer, Jonathan D Spicer, Tina Cascone, Murry W Wynes, Myung-Ju Ahn, Sanja Dacic, Enriqueta Felip, Patrick M Forde, Kristin A Higgins, Mark G Kris, Tetsuya Mitsudomi, Mariano Provencio, Suresh Senan, Benjamin J Solomon, Ming Sound Tsao, Masahiro Tsuboi, Heather A Wakelee, Yi-Long Wu, James Chih-Hsin Yang, Caicun Zhou, David H Harpole, Karen L Kelly

Faculty, Staff and Student Publications

Advances in the multidisciplinary care of early stage resectable NSCLC (rNSCLC) are emerging at an unprecedented pace. Numerous phase 3 trials produced results that have transformed patient outcomes for the better, yet these findings also require important modifications to the patient treatment journey trajectory and reorganization of care pathways. Perhaps, most notably, the need for multispecialty collaboration for this patient population has never been greater. These rapid advances have inevitably left us with important gaps in knowledge for which definitive answers will only become available in several years. To this end, the International Association for the Study of Lung Cancer …

Multi-Modal Segmentation With Missing Image Data For Automatic Delineation Of Gross Tumor Volumes In Head And Neck Cancers, Yao Zhao, Xin Wang, Jack Phan, Xinru Chen, Anna Lee, Cenji Yu, Kai Huang, Laurence E Court, Tinsu Pan, He Wang, Kareem Abdul Wahid, Abdalah S R Mohamed, Mohamed Naser, Clifton D Fuller, Jinzhong Yang

Faculty, Staff and Student Publications

Background: Head and neck (HN) gross tumor volume (GTV) auto-segmentation is challenging due to the morphological complexity and low image contrast of targets. Multi-modality images, including computed tomography (CT) and positron emission tomography (PET), are used in the routine clinic to assist radiation oncologists for accurate GTV delineation. However, the availability of PET imaging may not always be guaranteed.

Purpose: To develop a deep learning segmentation framework for automated GTV delineation of HN cancers using a combination of PET/CT images, while addressing the challenge of missing PET data.

Methods: Two datasets were included for this study: Dataset I: 524 (training) …

Optical Genome Mapping Improves The Accuracy Of Classification, Risk Stratification, And Personalized Treatment Strategies For Patients With Acute Myeloid Leukemia, Sanam Loghavi, Qing Wei, Farhad Ravandi, Andres E Quesada, Mark J Routbort, Shimin Hu, Gokce A Toruner, Sa A Wang, Wei Wang, Roberto N Miranda, Shaoying Li, Jie Xu, Courtney D Dinardo, Naval Daver, Tapan M Kadia, Ghayas C Issa, Hagop M Kantarjian, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four …

Identification Of Molecular Signatures In Epicardial Adipose Tissue In Heart Failure With Preserved Ejection Fraction, Shan He, Lei Zhao, Jianjun Zhang, Xinchun Yang, Huagang Zhu

Faculty, Staff and Student Publications

AIMS: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non-coding RNAs (lncRNAs) in EAT that might modulate HFpEF development.

METHODS: RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real-time PCR (qRT-PCR). Bioinformatics analysis (Gene Ontology and …

Interest In And Willingness To Use Prep: A Cross-Sectional Study Of Individuals With Problematic Substance Use Residing In A High Hiv Prevalence Jurisdiction, Angela M Heads, Constanza De Dios, Kaixuan An, Jin H Yoon, Robert Suchting, Adrienne Gilmore-Thomas, Joy M Schmitz

Faculty, Staff and Student Publications

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting …

Quantifying Placenta Accreta Spectrum Severity And Its Associated Blood Loss: A Novel Transvaginal Ultrasound Scoring System, Neha Agarwal, Edgar Hernandez-Andrade, Baha M Sibai, Farah H Amro, Jennie O Coselli, Michal F Bartal, Dejian Lai, Eleazar E Soto Torres, Sami Backley, Anthony Johnson, Jimmy Espinoza, Eric P Bergh, Sen Zhu, Ashley Salazar, Sean C Blackwell, Ramesha Papanna

Faculty, Staff and Student Publications

Background: Hemorrhage associated with placenta accreta spectrum (PAS) is a leading cause of maternal morbidity and mortality. Estimating blood loss in these individuals is a critical component of comprehensive preoperative planning.

Objective: A semiquantitative score based on transvaginal ultrasound was developed and tested to predict PAS, estimate its severity, and blood loss in individuals with clinical and ultrasound evidence suggesting PAS.

Study design: A secondary analysis was conducted of prospectively collected data from a quaternary center of patients with suspected accreta on 2D ultrasound and clinical suspicion. A predetermined scoring system was applied based on three components: (1) uterine wall …

A Protein Expression Atlas On Tissue Samples And Cell Lines From Cancer Patients Provides Insights Into Tumor Heterogeneity And Dependencies, Jun Li, Wei Liu, Kamalika Mojumdar, Hong Kim, Zhicheng Zhou, Zhenlin Ju, Shwetha V Kumar, Patrick Kwok-Shing Ng, Han Chen, Michael A Davies, Yiling Lu, Rehan Akbani, Gordon B Mills, Han Liang

Faculty, Staff and Student Publications

The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) are foundational resources in cancer research, providing extensive molecular and phenotypic data. However, large-scale proteomic data across various cancer types for these cohorts remain limited. Here, we expand upon our previous work to generate high-quality protein expression data for approximately 8,000 TCGA patient samples and around 900 CCLE cell line samples, covering 447 clinically relevant proteins, using reverse-phase protein arrays. These protein expression profiles offer profound insights into intertumor heterogeneity and cancer dependency and serve as sensitive functional readouts for somatic alterations. We develop a systematic protein-centered strategy …

Development Of An Engineered Extracellular Vesicles-Based Vaccine Platform For Combined Delivery Of Mrna And Protein To Induce Functional Immunity, Xin Luo, Kathleen M Mcandrews, Kent A Arian, Sami J Morse, Viktoria Boeker, Shreyasee V Kumbhar, Yingying Hu, Krishnan K Mahadevan, Kaira A Church, Sriram Chitta, Nicolas T Ryujin, Janine Hensel, Jianli Dai, Dara P Dowlatshahi, Hikaru Sugimoto, Michelle L Kirtley, Valerie S Lebleu, Shabnam Shalapour, Joe H Simmons, Raghu Kalluri

Faculty, Staff and Student Publications

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EVX-M+P vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EVOvaM+P vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors. EVOvaM+P administration to mice …

Oculomics Analysis In Multiple Sclerosis: Current Ophthalmic Clinical And Imaging Biomarkers, Alex Suh, Gilad Hampel, Aditya Vinjamuri, Joshua Ong, Sharif Amit Kamran, Ethan Waisberg, Phani Paladugu, Nasif Zaman, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. Early recognition and treatment are important for preventing or minimizing the long-term effects of the disease. Current gold standard modalities of diagnosis (e.g., CSF and MRI) are invasive and expensive in nature, warranting alternative methods of detection and screening. Oculomics, the interdisciplinary combination of ophthalmology, genetics, and bioinformatics to study the molecular basis of eye diseases, has seen rapid development through various technologies that detect structural, functional, and visual changes in the eye. Ophthalmic biomarkers (e.g., tear composition, …

Social Determinants Of Health And Surgical Desirability Of Outcome Ranking In Older Veterans, Michael A Jacobs, Yubo Gao, Susanne Schmidt, Paula K Shireman, Michael Mader, Carly A Duncan, Leslie R M Hausmann, Karyn B Stitzenberg, Lillian S Kao, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Importance: Evaluating how social determinants of health (SDOH) influence veteran outcomes is crucial, particularly for quality improvement.

Objective: To measure associations between SDOH, care fragmentation, and surgical outcomes using a Desirability of Outcome Ranking (DOOR).

Design, setting, and participants: This was a cohort study of US veterans using data from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP; 2013-2019) limited to patients aged 65 years or older with inpatient stays between 2 and 30 days, merged with multiple data sources, including Medicare. Race and ethnicity data were retrieved from VASQIP, Medicare and Medicaid beneficiary summary files, the Veterans Health …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

The Undiagnosed Diseases Network: Characteristics Of Solvable Applicants And Diagnostic Suggestions For Nonaccepted Ones, John J Mulvihill, Laura Findley, Weihong Ni, Janet S Sinsheimer, F Session Cole, Cecilia Esteves, Jonathan A Bernstein, John H Newman, Matthew T Wheeler, Jill R Mokry, Undiagnosed Diseases Network

Faculty, Staff and Students Publications

Purpose: Can certain characteristics identify as solvable some undiagnosed patients who seek extensive evaluation and thorough record review, such as by the Undiagnosed Diseases Network (UDN)?

Methods: The UDN is a national research resource to solve medical mysteries through team science. Applicants provide informed consent to access to their medical records. After review, expert panels assess if applicants meet inclusion and exclusion criteria to select participants. When not accepting applicants, UDN experts may offer suggestions for diagnostic efforts. Using minimal information from initial applications, we compare features in applicants who are not accepted with those who are accepted and either …

Evaluating Progress And Accountability For Achieving Cop26 Health Programme International Ambitions For Sustainable, Low-Carbon, Resilient Health-Care Systems, Iris Martine Blom, Fawzia N Rasheed, Hardeep Singh, Matthew J Eckelman, Meghnath Dhimal, Martin Hensher, Renzo R Guinto, Alice Mcgushin, Xuejuan Ning, Poornima Prabhakaran, Marina Romanello, Dana Van Alphen, Nick Watts, Jessica C Yu, Carol Zavaleta-Cortijo, Andrea J Macneill, Jodi D Sherman

Faculty, Staff and Students Publications

A global initiative to develop low-carbon, resilient health systems-the COP26 Health Programme-launched at the UN Framework Convention on Climate Change 26th Conference of the Parties (COP26) in 2021. As of May, 2024, 83 nations have committed to participate in this initiative. This analysis evaluates the effectiveness of existing and proposed indicators towards public monitoring and accountability to these commitments. Our findings reveal substantial gaps in data availability and indicator relevance, with many countries reporting process indicators that do not reflect actual progress towards achieving sustainable health-care systems. We found a dearth of suitable indicators and an urgent need to develop …

Long Covid Among Undocumented Latino Immigrant Populations In The Emergency Department, Karen P Reyes, Zubaid Rafique, Brian Chinnock, Vijaya Arun Kumar, Michael Gottlieb, Kristin L Rising, Robert M Rodriguez

Faculty, Staff and Students Publications

This cross-sectional study assesses the understanding of and access to care for long COVID symptoms among undocumented Latino immigrants in US emergency departments (EDs).

Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng

Faculty, Staff and Students Publications

Perineuronal nets (PNNs), specialized extracellular matrix (ECM) structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole body blood glucose is examined. This review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms, and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs …

Metabolic Dependencies Of Acute Myeloid Leukemia Stem Cells, Xiangguo Shi, Mengdie Feng, Daisuke Nakada

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy primarily driven by an immature population of AML cells termed leukemia stem cells (LSCs) that are implicated in AML development, chemoresistance, and relapse. An emerging area of research in AML focuses on identifying and targeting the aberrant metabolism in LSCs. Dysregulated metabolism is involved in sustaining functional properties of LSCs, impeding myeloid differentiation, and evading programmed cell death, both in the process of leukemogenesis and in response to chemotherapy. This review discusses recent discoveries regarding the aberrant metabolic processes of AML LSCs that have begun to change the therapeutic landscape of …

Characterization And Visualization Of Tandem Repeats At Genome Scale, Egor Dolzhenko, Adam English, Harriet Dashnow, Guilherme De Sena Brandine, Tom Mokveld, William J Rowell, Caitlin Karniski, Zev Kronenberg, Matt C Danzi, Warren A Cheung, Chengpeng Bi, Emily Farrow, Aaron Wenger, Khi Pin Chua, Verónica Martínez-Cerdeño, Trevor D Bartley, Peng Jin, David L Nelson, Stephan Zuchner, Tomi Pastinen, Aaron R Quinlan, Fritz J Sedlazeck, Michael A Eberle

Faculty, Staff and Students Publications

Tandem repeat (TR) variation is associated with gene expression changes and numerous rare monogenic diseases. Although long-read sequencing provides accurate full-length sequences and methylation of TRs, there is still a need for computational methods to profile TRs across the genome. Here we introduce the Tandem Repeat Genotyping Tool (TRGT) and an accompanying TR database. TRGT determines the consensus sequences and methylation levels of specified TRs from PacBio HiFi sequencing data. It also reports reads that support each repeat allele. These reads can be subsequently visualized with a companion TR visualization tool. Assessing 937,122 TRs, TRGT showed a Mendelian concordance of …

Polycaprolactone-Based Shape Memory Foams As Self-Fitting Vaginal Stents, Ashley J Hicks, Courteney Roberts, Andrew Robinson, Kailey Wilson, Varsha Kotamreddy, Trace Larue, Arian Veyssi, Felipe Beltran, Julie Hakim, Manuel K Rausch, Melissa Grunlan, Elizabeth Cosgriff-Hernandez

Faculty, Staff and Students Publications

There is an urgent critical need for a patient-forward vaginal stent that can prevent debilitating vaginal stenosis that occurs after pelvic radiation treatments and vaginal reconstruction. To this end, we developed a self-fitting vaginal stent based on a shape-memory polymer (SMP) foam that can assume a secondary, compressed shape for ease of deployment. Upon insertion, the change in temperature and hydration initiates foam expansion to shape fit to the individual patient and restore the lumen of the stent to allow egress of vaginal secretions. To achieve rapid actuation at physiological temperature, we investigated the effect of architecture of two photocurable, …

Circulating Blood Plasma Profiling Reveals Proteomic Signature And A Causal Role For Svep1 In Sudden Cardiac Death, Thuyvy Duong, Thomas R Austin, Jennifer A Brody, Ali Shojaie, Alexis Battle, Joel S Bader, Yun Soo Hong, Christie M Ballantyne, Josef Coresh, Robert E Gerszten, Russell P Tracy, Bruce M Psaty, Nona Sotoodehnia, Dan E Arking

Faculty, Staff and Students Publications

No abstract provided.

The Fallacy Of Electronic Cigarettes For Tobacco Dependence, Harold J Farber, Carlos Rábade Castedo, Carlos A Jimenez-Ruiz, Manuel Conrado Pacheco

Faculty, Staff and Students Publications

No abstract provided.

Dsm-5 Criterion-A-Based Trauma Types In Service Members And Veterans Seeking Treatment For Posttraumatic Stress Disorder, Natasha Benfer, Breanna Grunthal, Katherine A Dondanville, Stacey Young-Mccaughan, Abby Blankenship, Chadi G Abdallah, Sudie E Back, Julianne Flanagan, Edna B Foa, Peter T Fox, John H Krystal, Brian P Marx, Donald D Mcgeary, Carmen P Mclean, Kristi E Pruiksma, Patricia A Resick, John D Roache, Paulo Shiroma, Denise M Sloan, Daniel J Taylor, Jennifer Schuster Wachen, Argelio L López-Roca, Karin L Nicholson, Richard P Schobitz, Christian C Schrader, Allah-Fard M Sharrieff, Jeffrey S Yarvis, Jim Mintz, Terence M Keane, Alan L Peterson, Brett T Litz

Faculty, Staff and Students Publications

Objective: In posttraumatic stress disorder (PTSD), the assumption of the equipotentiality of traumas ignores potentially unique contexts and consequences of different traumas. Accordingly, Stein et al. (2012) developed a reliable typing scheme in which assessors categorized descriptions of traumatic events into six "types": life threat to self (LTS), life threat to other, aftermath of violence (AV), traumatic loss, moral injury by self (MIS), and moral injury by other (MIO). We extended this research by validating the typing scheme using participant endorsements of type, rather than assesor-based types. We examined the concordance of participant and assesor types, frequency, and validity …

Association Of Aortic Valve Calcium With Dementia And Stroke: The Multi-Ethnic Study Of Atherosclerosis, Natalie Marrero, Kunal Jha, Timothy M Hughes, Alexander C Razavi, Jelani K Grant, Ellen Boakye, Khalil Anchouche, Omar Dzaye, Matthew J Budoff, Jerome I Rotter, Xiuqing Guo, Jie Yao, Alexis C Wood, Roger S Blumenthal, Erin D Michos, George Thanassoulis, Wendy S Post, Michael J Blaha, Chinwe Ibeh, Seamus P Whelton

Faculty, Staff and Students Publications

Background and aims: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional …

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy In Patients With Atrial Fibrillation And Stable Coronary Artery Disease, Mushood Ahmed, Areeba Ahsan, Aimen Shafiq, Raheel Ahmed, Mahboob Alam, Pierre Sabouret, Jamal S Rana, Gregg C Fonarow

Faculty, Staff and Students Publications

BACKGROUND: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited.

METHODS: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with …

A Virtual Breakthrough Series Collaborative For Missed Test Results: A Stepped-Wedge Cluster-Randomized Clinical Trial, Lisa Zubkoff, Andrew J Zimolzak, Ashley N D Meyer, Jennifer Sloane, Umber Shahid, Traber Giardina, Sahar A Memon, Taylor M Scott, Daniel R Murphy, Hardeep Singh

Faculty, Staff and Students Publications

IMPORTANCE: Missed test results, defined as test results not followed up within an appropriate time frame, are common and lead to delays in diagnosis and treatment.

OBJECTIVE: To evaluate the effect of a quality improvement collaborative, the Virtual Breakthrough Series (VBTS), on the follow-up rate of 2 types of test results prone to being missed: chest imaging suspicious for lung cancer and laboratory findings suggestive of colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted between February 2020 and March 2022 at 12 Department of Veterans Affairs (VA) medical centers, with a predefined 3-cohort roll-out. Each …

Discordance Between Aptt And Anti-Xa In Monitoring Heparin Anticoagulation In Mechanical Circulatory Support, Song Li, Ang Li, Jennifer A Beckman, Christopher Kim, Marian A Granich, John Mondin, Daniel E Sabath, David A Garcia, Claudius Mahr

Faculty, Staff and Students Publications

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance.

METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning …

Cellular Prion Protein Acts As Mediator Of Amyloid Beta Uptake By Caveolin-1 Causing Cellular Dysfunctions In Vitro And In Vivo, Angela Da Silva Correia, Matthias Schmitz, Anna-Lisa Fischer, Susana Da Silva Correia, Franco L Simonetti, Gesine Saher, Roberto Goya-Maldonado, Amandeep Singh Arora, Andre Fischer, Tiago F Outeiro, Inga Zerr

Faculty, Staff and Student Publications

Introduction: Cellular prion protein (PrPC) was implicated in amyloid beta (Aβ)-induced toxicity in Alzheimer's disease (AD), but the precise molecular mechanisms involved in this process are unclear.

Methods: Double transgenic mice were generated by crossing Prnp knockout (KO) with 5xFAD mice, and light-sheet microscopy was used for whole brain tissue analyses. PrPC-overexpressing cells were developed for in vitro studies, and microscopy was used to assess co-localization of proteins of interest. Surface-plasmon resonance (SPR) was used to investigate protein-binding characteristics.

Results: In vivo, PrPC levels correlated with reduced lifespan and cognitive and motor function, and its ablation disconnected behavior deficits from …

Outcomes In Solid Organ Transplant Recipients Receiving Organs From A Donor With Fusarium Solani Species Complex Meningitis, Isabel S Griffin, Dallas J Smith, Pallavi Annambhotla, Jeremy A W Gold, Luis Ostrosky-Zeichner, Carol A Kauffman, Lalitha Gade, Anastasia Litvintseva, Daniel Zp Friedman, Angie G Nishio Lucar, Tarina C Parpia, Joshua Lieberman, Janet Bujan, Julie Corkrean, Mukul K Divatia, Kevin Grimes, Jiejian Lin, Constance Mobley, Mary R Schwartz, Bashar Hannawi, Anne Malilay, Anne O'Boye, Jeffrey Lysne, Mrinalini Venkata Subramani, Hayley Heckmann, Venice Servellita, Charles Chiu, Sridhar V Basavaraju

Faculty, Staff and Student Publications

Background: Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico.

Methods: After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS.

Results: Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored …

A Single-Cell Atlas Of The Murine Pancreatic Ductal Tree Identifies Novel Cell Populations With Potential Implications In Pancreas Regeneration And Exocrine Pathogenesis, Ángel Fernández, Joan Casamitjana, Adrián Holguín-Horcajo, Katarina Coolens, Loris Mularoni, Li Guo, Olga Hartwig, Tim Düking, Noemi Vidal, Lincoln N Strickland, Lorenzo Pasquali, Jennifer M Bailey-Lundberg, Ilse Rooman, Yue J Wang, Meritxell Rovira

Faculty, Staff and Student Publications

Background & aims: Pancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar cells, terminal, intercalated, intracalated ducts, and the main pancreatic duct. Ductal heterogeneity at the single-cell level has been poorly characterized; therefore, our understanding of the role of ductal cells in pancreas regeneration and exocrine pathogenesis has been hampered by the limited knowledge and unexplained diversity within the ductal network.

Methods: We used single cell RNA sequencing to comprehensively characterize mouse ductal heterogeneity at single-cell resolution of the entire ductal epithelium from centroacinar cells …

Technical Pitfalls For Fenestrated-Branched Endovascular Aortic Repair Following Petticoat, Aidin Baghbani-Oskouei, Emanuel R Tenorio, Marina Dias-Neto, Andrea Vacirca, Aleem K Mirza, Naveed Saqib, Bernardo C Mendes, Laura Ocasio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

Purpose: The Provisional Extension to Induce Complete Attachment Technique (PETTICOAT) uses a bare-metal stent to scaffold the true lumen in patients with acute or subacute aortic dissections. While it is designed to facilitate remodeling, some patients with chronic post-dissection thoracoabdominal aortic aneurysms (TAAAs) require repair. This study describes the technical pitfalls of fenestrated-branched endovascular aortic repair (FB-EVAR) in patients who underwent prior PETTICOAT repair.

Technique: We report 3 patients with extent II TAAAs who had prior bare-metal dissection stents treated by FB-EVAR. Two patients required maneuvers to reroute the aortic guidewire, which was initially placed in-between stent struts. This was …