Medicine and Health Sciences Commons^™

Endothelial Cell Piezo1 Promotes Vascular Smooth Muscle Cell Differentiation On Large Arteries, Javier Abello, Ying Yin, Yonghui Zhao, Josh Maurer, Jihui Lee, Cherokee Bodell, Jahmiera Richee, Zarek Burton, Megan E Goeckel, Michelle Lin, Carmen M Halabi, Rajan Sah, Amber N Stratman, Et Al.

2020-Current year OA Pubs

Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating klf2a, a blood flow responsive transcription factor, expression levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed klf2a and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased klf2a levels and …

Rationale And Design Of The Defiance Study: A Randomized Controlled Trial Of Mechanical Thrombectomy Versus Anticoagulation Alone For Iliofemoral Deep Vein Thrombosis., Steven D Abramowitz, Xhorlina Marko, Donna D'Souza, Sonya Noor, Keith Pereira, Mitchell J Silver, Stuart P Rosenberg, Craig D Markovitz, Thomas Tu, Ido Weinberg, Stephen Black

Heart and Vascular Articles

BACKGROUND: Deep vein thrombosis (DVT) is a common medical condition that is associated with clinically significant sequelae, including postthrombotic syndrome (PTS). Anticoagulation alone remains the guideline-recommended treatment for many patients with iliofemoral DVT. Recent technological advances have led to an increase in the use of mechanical thrombectomy for DVT, but mechanical thrombectomy-based procedures have not yet been compared with standard-of-care anticoagulation therapy in randomized studies.

METHODS: The DEFIANCE study (ClinicalTrials.gov: NCT05701917) is an international and actively enrolling randomized controlled trial (RCT) in lower extremity DVT assessing an interventional strategy that includes mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, …

New-Onset Atrioventricular Nodal Reentrant Tachycardia After Transaortic Valve Replacement: Is There A Causal Link?, Nagesh Chopra, Auroa Badin, Ankur Shah, Sreedhar Billakanty, Eugene Fu, Anish Amin

Heart and Vascular Articles

No abstract provided.

Bevacizumab Beyond Progression: Impact Of Subsequent Bevacizumab Re-Treatment In Patients With Ovarian, Fallopian Tube, And Peritoneal Cancer After Progression, Amma Asare, Rebecca Ann Previs, Daniel Spinosa, Bryan Fellman, Amelia L Scott, Isabelle Mulder, May Mahmoud, Ahmed Enbaya, Jean Hansen Siedel, Lauren Cobb, Pamela T Soliman, Anil K Sood, Robert L Coleman, Angeles Alvarez Secord, Shannon N Westin

Faculty, Staff and Student Publications

Background: This study evaluated whether patients with epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) who are immediately re-treated with bevacizumab derive benefit after disease progression on a bevacizumab-containing regimen.

Methods: This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier product-limit estimator and modeled via Cox proportional hazards regression.

Results: Among 226 patients with OC …

A Neoantigen Vaccine Generates Antitumour Immunity In Renal Cell Carcinoma, David A Braun, Giorgia Moranzoni, Vipheaviny Chea, Bradley A Mcgregor, Eryn Blass, Chloe R Tu, Allison P Vanasse, Cleo Forman, Juliet Forman, Alexander B Afeyan, Nicholas R Schindler, Yiwen Liu, Shuqiang Li, Jackson Southard, Steven L Chang, Michelle S Hirsch, Nicole R Leboeuf, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Susan Klaeger, Siranush Sarkizova, Christina B Pedersen, Matthew Mossanen, Isabel Carulli, Anna Tarren, Joseph Duke-Cohan, Alexis A Howard, J Bryan Iorgulescu, Bohoon Shim, Jeremy M Simon, Sabina Signoretti, Jon C Aster, Liudmila Elagina, Steven A Carr, Ignaty Leshchiner, Gad Getz, Stacey Gabriel, Nir Hacohen, Lars R Olsen, Giacomo Oliveira, Donna S Neuberg, Kenneth J Livak, Sachet A Shukla, Edward F Fritsch, Catherine J Wu, Derin B Keskin, Patrick A Ott, Toni K Choueiri

Faculty, Staff and Student Publications

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 …

Exome Sequencing Identifies Helb As A Novel Susceptibility Gene For Non-Mucinous, Non-High-Grade-Serous Epithelial Ovarian Cancer, Ed M Dicks, Jonthan P Tyrer, Suzana Ezquina, Michelle Jones, John Baierl, Pei-Chen Peng, Michael Diaz, Ellen Goode, Stacey J Winham, Thilo Dörk, Toon Van Gorp, Anna De Fazio, David D L Bowtell, Dale W Garsed, Kunle Odunsi, Kirsten Moysich, Marina Pavanello, Florentia Fostira, Penelope M Webb, Jana Soukupová, Paul A Cohen, Weiva Sieh, Renée Turzanski Fortner, Charite Ricker, Beth Karlan, Ian Campbell, James D Brenton, Susan J Ramus, Simon A Gayther, Paul D P Pharoah

Faculty, Staff and Student Publications

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which …

Immunelens Characterizes Systemic Immune Dysregulation In Aging And Cancer, Robert Bentham, Thomas P Jones, James R M Black, Carlos Martinez-Ruiz, Michelle Dietzen, Maria Litovchenko, Kerstin Thol, Thomas B K Watkins, Chris Bailey, Oriol Pich, Zhihui Zhang, Peter Van Loo, Genomics England Consortium, Tracerx Consortium, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower …

Scai Expert Consensus Statement On Alternative Access For Transcatheter Aortic Valve Replacement., Matthew Sherwood, Keith B Allen, Thom G Dahle, Chandan M Devireddy, Jeffrey Gaca, Santiago Garcia, Kendra J Grubb, Tsuyoshi Kaneko, Chad A Kliger, Robert J Lederman, John C Messenger, Puja B Parikh, Marie-France Poulin, Carlos Sanchez, Anene Ukaigwe, James J Yun, Paul D Mahoney

Heart and Vascular Articles

Transcatheter aortic valve replacement (TAVR) has become a widely accepted procedure for treating patients with symptomatic aortic stenosis. While transfemoral access remains the primary route due to its lower complication rates and favorable outcomes, a subset of patients have anatomical or clinical factors precluding this approach. For these patients, alternative access routes such as transaxillary, transcarotid, and transcaval provide viable options. This expert consensus statement aims to provide a comprehensive review of case selection, technical considerations, and outcomes associated with these alternative access routes in TAVR. Additionally, this document highlights the advancements in device technology and imaging guidance that have …

Walking Performance Is Worse In Black Than White People With Multiple Sclerosis, Robert W. Motl, Deborah Backus, Jeffrey R. Hebert, Alexander V. Ng, Kevin K. Mccully, Whitney N. Neal, Hollie Schmidt, Robert Mcburney, Prudence Plummer, Francois Bethoux, John Lowman, Gary R. Cutter

Exercise Science Faculty Research and Publications

Background

There is emerging evidence for poor health outcomes among Black people with MS, and Black people with MS may have worse walking performance than White counterparts.

Purpose

The current study examined if Black participants with MS had slower walking speed (timed 25-foot walk, T25FW) and shorter walking distance (six-minute walk, 6MW) than White participants, and if these differences were accounted for by demographic variables, physical activity, disease/clinical characteristics, and Social Determinants of Health (SDOH).

Method

The analysis included samples of Black (N = 105) and White (N = 246) participants with MS who completed the T25FW and 6MW, underwent …

The Vivid Trial 12-Month Outcomes Of The Venous Stent For The Iliofemoral Vein Using The Duo Venous Stent System., Mahmood Razavi, Michael Lichtenberg, Kush Desai, David Dexter, Peter Soukas, Nicolas Shammas, Ankur Lodha, Paul Gagne, Anna Nordell, Raghu Kolluri, Mark Garcia

Heart and Vascular Articles

OBJECTIVE: There are varying anatomical and mechanical demands of stent placement in the iliofemoral venous segment; the Duo Venous Stent System is designed to address these issues. The purpose of the VIVID (Venous stent for the Iliofemoral Vein Investigational clinical trial using the Duo Venous Stent System) study was to investigate the safety and efficacy of the Duo Venous Stent System for the treatment of patients with nonmalignant iliofemoral venous obstructive disease.

METHODS: This was an international, prospective, multicenter, single-arm study that enrolled patients with symptomatic nonthrombotic (NT), post-thrombotic (PTS), or acute deep vein thrombotic (aDVT) iliofemoral venous outflow obstruction. …

Does Social Media Increase Perioperative Anxiety In Patients Undergoing Impacted Third Molar Surgery?, Ufuk Tatli, Tahayasin Kalkan

School of Dentistry Faculty Research and Publications

Background

In anticipation of third molar surgery, patients may experience increased anxiety. Patients frequently access social media platforms and view content about surgical treatments.

Purpose

The study purpose was to measure the level of perioperative anxiety of patients scheduled for third molar surgery exposed to social media and identify factors associated with patient anxiety.

Study Design, Setting, Sample

This is a prospective cohort study of patients undergoing impacted mandibular third molar surgery from September 2021 to August 2022 at the outpatient clinic of Cukurova University School of Dentistry.

Predictor Variable

The predictor variable was level of exposure to viewing third …

Implant Placement-Associated Tissue Swelling: A Digital Three-Dimensional And Patient-Based Assessment, Vrisiis Kofina, Juan Valencia Rincon, Swati Y. Rawal, Andrew R. Dentino, Shengtong Han, Dimitris N. Tatakis

School of Dentistry Faculty Research and Publications

Objectives

There is scarce evidence on immediate soft tissue and patient-reported outcome measures (PROMs) following implant surgery. This prospective study aimed to quantify post-implant placement intraoral swelling and to correlate it with PROMs.

Materials and methods

Twenty-six patients undergoing standardized single implant placement (two-stage protocol) were recruited. Soft tissue swelling was recorded by intraoral scans immediately pre-surgery (PS) and post-operatively (IP), and at 2 (2d), 7 (7d) and 14 days (14d) and 2 months (2 m). Ridge width, height, and volume changes from IP were recorded. PROMs (pain, swelling, difficulty of mouth opening, and OHIP-14) were recorded pre- and post-operatively. …

Bilateral Condylar Hyperplasia: Importance Of Its Diagnosis In The Treatment And Long-Term Stability Of Skeletal Class Iii Correction, Diego Fernando Lopez, Martin Fernando Orozco, Sofia Ochoa Gomez, Santiago Herrera Guardiola, Luis Eduardo Almeida

School of Dentistry Faculty Research and Publications

Background: Condylar hyperplasia (CH) leads to mandibular overgrowth with anatomical, aesthetic, and functional consequences, particularly affecting facial harmony. It is characterized by severe mandibular prognathism (MP) in bilateral cases. This study aims to propose a therapeutic algorithm for diagnosing and treating bilateral condylar hyperplasia (BCH) based on demographic, clinical, craniofacial growth, and clivus ratio uptake conditions. Methods: Ten patients with severe skeletal Class III by MP, whose alteration was clinically associated with BCH, were consecutively evaluated in a specialized dentofacial deformity center between the period of 2019 and 2024. A detailed protocol was followed to gather clinical history, assess anatomical …

Assessing Predictions On Fitness Effects Of Missense Variants In Hmbs In Cagi6, Jing Zhang, Lisa Kinch, Panagiotis Katsonis, Olivier Lichtarge, Milind Jagota, Yun S Song, Yuanfei Sun, Yang Shen, Nurdan Kuru, Onur Dereli, Ogun Adebali, Muttaqi Ahmad Alladin, Debnath Pal, Emidio Capriotti, Maria Paola Turina, Castrense Savojardo, Pier Luigi Martelli, Giulia Babbi, Rita Casadio, Fabrizio Pucci, Marianne Rooman, Gabriel Cia, Matsvei Tsishyn, Alexey Strokach, Zhiqiang Hu, Warren Van Loggerenberg, Frederick P Roth, Predrag Radivojac, Steven E Brenner, Qian Cong, Nick V Grishin

Faculty, Staff and Students Publications

This paper presents an evaluation of predictions submitted for the "HMBS" challenge, a component of the sixth round of the Critical Assessment of Genome Interpretation held in 2021. The challenge required participants to predict the effects of missense variants of the human HMBS gene on yeast growth. The HMBS enzyme, critical for the biosynthesis of heme in eukaryotic cells, is highly conserved among eukaryotes. Despite the application of a variety of algorithms and methods, the performance of predictors was relatively similar, with Kendall's tau correlation coefficients between predictions and experimental scores around 0.3 for a majority of submissions. Notably, the …

The Glu86 Residue In Tbx4 Proves Critical For Human Lung Development, Przemyslaw Szafranski, Tomasz Gambin, Gail Deutsch, Salma A Nassef, Mary Clay Bailey, Debra L Kearney, Paweł Stankiewicz

Faculty, Staff and Students Publications

T-box transcription factors are a group of evolutionarily conserved T-box-containing regulators of mesoderm specification and development. Heterozygous single nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving dosage-sensitive TBX4 have been associated with pulmonary arterial hypertension (PAH), ischiocoxopodopatellar syndrome with or without PAH, and lethal lung developmental disorders (LLDDs), including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD), and other unspecified primary pulmonary hypoplasias. Loss- and gain-of-function variants have been proposed to cause pediatric PAH and LLDDs, and adult forms of PAH, respectively. Of more than 50 missense SNVs scattered across the entire TBX4, only three have been reported in patients …

Anesthetic Considerations For Endovascular Repair Of The Thoracic Aorta, Olivia M Valencia, Thomas Powell, Ali Khalifa, Vicente Orozco-Sevilla, Daniel A Tolpin

Faculty, Staff and Students Publications

Thoracic aorta pathologies, especially those of the ascending aorta and aortic arch, were traditionally approached via open surgical repair. This carries risk of ischemic end-organ damage and other complications. Endovascular repair of ascending aorta and aortic arch pathologies is becoming more successful and widespread, thereby posing numerous challenges to the anesthesiologist. This article reviews the anesthesia-pertinent pathophysiology, repair techniques, preoperative evaluation, intraoperative management, and postoperative care of patients presenting for endovascular repair of thoracic aorta pathologies.

Ethnoracial Disparities In Gray Matter Atrophy Are Mediated By Structural Disconnectivity In Multiple Sclerosis, Ahmed Bayoumi, Joseph A Thomas, Breanna R Alonzo, Juan Jimenez, Christopher M Orlando, Carlos A Pérez, Khader M Hasan, Jerry S Wolinsky, John A Lincoln

Faculty, Staff and Student Publications

Objective: To investigate ethnoracial disparities in gray matter (GM) atrophy, the contribution of white matter lesions and consequent structural disconnectivity among patients with multiple sclerosis (MS).

Methods: This retrospective study included 297 patients with MS (pwMS), 98 Hispanic/Latinx (H-MS), 82 non-Hispanic Black (B-MS), and 117 non-Hispanic White (W-MS). GM atrophy was assessed using univariate, voxel-based morphometry, and multivariate techniques, source-based morphometry. Structural disconnectivity secondary to white matter lesions was evaluated using the network modification tool. Mediation analyses explored relationships between ethnoracial groups, white matter lesions, structural disconnectivity, and gray matter atrophy.

Results: B-MS and H-MS generally exhibited greater gray matter …

Evaluating Dry Air Personnel Decontamination Of Methyl Salicylate As A Chemical Agent Surrogate In Extreme Cold Environments To Reduce Airborne Risks Using A Manikin, Lance E. Campbell

Theses and Dissertations

This research investigated a mobile air shower as an alternative to water washing for personnel chemical decontamination in Arctic environments, where traditional methods like disrobing and rinsing are impractical. Interest in Arctic operations has grown with recent U.S. military focus on strategic advancements by Russia and China, yet research on air shower effectiveness for chemical decontamination remains limited. This study examined whether a commercial off-the-shelf air shower could effectively decontaminate methyl salicylate (MES), a surrogate for chemical warfare blister agents, from a manikin outfitted in military cold-weather gear. Researchers used a ppbRAE 3000 photo-ionization detector to measure MES concentrations following …

Personal Decontamination Of Copper Oxide Powder As A Radiological Surrogate On Ambulatory Patients In Arctic Environments: Assessing Residual Airborne Risks After Air Shower Or Vacuum Decontamination Of A Manikin, Quinn G. Pelichoff

Theses and Dissertations

This study assessed air-based decontamination methods for treating patients exposed to dry radiological contamination while minimizing reaerosolization during disrobing, particularly in extreme cold environments. A full-size manikin,  simulating an able-bodied Airman, was dressed in military-issue extreme cold weather gear and coated with 28 grams of Copper Oxide. The manikin underwent one of three treatments: HEPA vacuuming, a mobile personal air shower, or no treatment (control). After treatment, researchers removed the uniform and used optical particle counters to measure airborne dust concentrations that could pose risks during disrobing. Each method was tested ten times (30 trials total). Statistical analyses (ANOVA, Tukey’s …

Anesthetic Considerations For Repair Of Thoracoabdominal Aortic Aneurysms, David A Lyubashevsky, Thomas Powell, Ali Khalifa, Vicente Orozco-Sevilla, Daniel A Tolpin

Faculty, Staff and Students Publications

Anesthetic management of open thoracoabdominal aneurysm (TAAA) repair poses a number of challenges for even the most experienced of cardiovascular anesthesiologists. This procedure encompasses a large number of unique anesthetic techniques, including one-lung ventilation, invasive hemodynamic monitoring, left-heart bypass, massive transfusion, selective renal and visceral perfusion, and central nervous system monitoring with CSF drainage. In this article, we aim to describe the anesthetic management for thoracoabdominal aortic aneurysm repair, including preoperative workup, intraoperative management, as well as postoperative concerns in the intensive care unit.

Trends In Kidney Allograft Failure Among First-Time Transplant Recipients In The United States, Pascale Khairallah, Elizabeth C Lorenz, Amy Waterman, Nidhi Aggarwal, Akshta Pai, Wolfgang C Winkelmayer, Jingbo Niu

Faculty, Staff and Students Publications

Rationale & objective: The management and outcomes of kidney transplant recipients have evolved over the past 3 decades. This study of US patients whose first kidney allograft failed examined long-term trends in subsequent waitlisting, retransplantation, and all-cause mortality.

Study design: Retrospective cohort study.

Setting & participants: Patients recorded in the US Renal Data System (USRDS) whose first kidney allograft failed between 1990 and 2019.

Exposure: The 5-year period in which the allograft failure occurred: 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, or 2015-2019.

Outcome: (1) Waitlisting for retransplantation, (2) retransplantation, and (3) all-cause mortality following first allograft failure.

Analytical approach: Competing risk …

Paving The Way For Integrated Advanced Heart Failure And Adult Congenital Heart Disease Training, William H Marshall V, Ryan D Byrne, Andrew Civitello, William J Dreyer, Peter R Ermis, Brent C Lampert, Lauren T Lastinger, Deipanjan Nandi, Joseph A Spinner, Curt J Daniels

Faculty, Staff and Students Publications

No abstract provided.

Sodium-Glucose Cotransporter 2 Inhibitors In Patients With Type 2 Diabetes And Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Systematic Review And Meta-Analysis, Huzaifa Ul Haq Ansari, Muhammad Ammar Samad, Eman Mahboob, Eeshal Zulfiqar, Shurjeel Uddin Qazi, Areeba Ahsan, Mushood Ahmed, Faizan Ahmed, Raheel Ahmed, Shafaqat Ali, Mahboob Alam, Jamal S Rana, Gregg C Fonarow

Faculty, Staff and Students Publications

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown benefits in improving cardiovascular (CV) outcomes in patients with heart failure (HF) and may mitigate symptom progression in myocardial infarction (MI). However, their effectiveness in patients with type 2 diabetes and MI undergoing percutaneous coronary intervention (PCI) is unclear.

Methods: To identify eligible studies, a comprehensive search of electronic databases, PubMed, Cochrane Library, Scopus and Embase, was conducted from inception until May 2024. Results were presented as risk ratios (RR) and their corresponding 95 % confidence intervals (CIs).

Results: Our analysis included 8 observational studies comprising 24,229 patients. The results indicated that …

Epidemiology Of Diagnostic Errors In Pediatric Emergency Departments Using Electronic Triggers, Prashant Mahajan, Emily White, Kathy Shaw, Sarah J Parker, James Chamberlain, Richard M Ruddy, Elizabeth R Alpern, Jacqueline Corboy, Andrew Krack, Brandon Ku, Daphne Morrison Ponce, Asha S Payne, Elizabeth Freiheit, Gregor Horvath, Giselle Kolenic, Michele Carney, Nicole Klekowski, Karen J O'Connell, Hardeep Singh

Faculty, Staff and Students Publications

Objectives: We applied three electronic triggers to study frequency and contributory factors of missed opportunities for improving diagnosis (MOIDs) in pediatric emergency departments (EDs): return visits within 10 days resulting in admission (Trigger 1), care escalation within 24 h of ED presentation (Trigger 2), and death within 24 h of ED visit (Trigger 3).

Methods: We created an electronic query and reporting template for the triggers and applied them to electronic health record systems of five pediatric EDs for visits from 2019. Clinician reviewers manually screened identified charts and initially categorized them as "unlikely for MOIDs" or "unable to rule …

Distinct Single-Cell Transcriptional Profile In Cd4+ T-Lymphocytes Among Obese Children With Asthma, Vickram Tejwani, Rulin Wang, Andres Villabona-Rueda, Karthik Suresh, Tianshi David Wu, Ian M Adcock, Nazanin Z Kermani, Joe Zein, Nadia N Hansel, Srinivasan Yegnasubramanian, Meredith C Mccormack, Franco R D'Alessio

Faculty, Staff and Students Publications

Obesity is a risk factor for asthma morbidity, associated with less responsiveness to inhaled corticosteroids. CD4+ T cells are central to the immunology of asthma and may contribute to the unique obese asthma phenotype. We sought to characterize the single-cell CD4+ transcriptional profile differences in obese children with asthma compared with normal-weight children with asthma. Eight normal-weight and obese participants with asthma were clinically phenotyped and matched based on asthma control. Peripheral blood (PB) CD4+ T cells were sorted, and single-cell RNA sequencing was conducted. Cell clusters were identified by canonical gene expression and differential gene expression and reactome pathway …

Irisin-Mediated Muscle-Renal Crosstalk As A Protective Mechanism Against Contrast-Induced Acute Kidney Injury Via Cgas-Sting Signalling Inhibition, Long Peng, Suhua Li, Qiang Huang, Yuxiang Sun, Juan Sun, Ting Luo, Yanlin Wang, Zhaoyong Hu, Weiyan Lai, Hui Peng

Faculty, Staff and Students Publications

Background: Contrast-induced acute kidney injury (CI-AKI) continues to pose a pressing clinical challenge during invasive cardiovascular procedures due to the limited availability of preventative strategies. We aimed to demonstrate that irisin, a myokine induced by exercise, protects against CI-AKI by inhibiting the cGAS-STING inflammatory pathway.

Methods and results: We explored the relationship between serum irisin levels and CI-AKI incidence in patients administered the contrast media iohexol. Notably, lower serum irisin levels were strongly associated with an increased incidence of CI-AKI following contrast media administration. To establish a causal link between serum irisin levels and CI-AKI, we utilised a mouse model …

Cagi6 Id Panel Challenge: Assessment Of Phenotype And Variant Predictions In 415 Children With Neurodevelopmental Disorders (Ndds), Maria Cristina Aspromonte, Alessio Del Conte, Shaowen Zhu, Wuwei Tan, Yang Shen, Yexian Zhang, Qi Li, Maggie Haitian Wang, Giulia Babbi, Samuele Bovo, Pier Luigi Martelli, Rita Casadio, Azza Althagafi, Sumyyah Toonsi, Maxat Kulmanov, Robert Hoehndorf, Panagiotis Katsonis, Amanda Williams, Olivier Lichtarge, Su Xian, Wesley Surento, Vikas Pejaver, Sean D Mooney, Uma Sunderam, Rajgopal Srinivasan, Alessandra Murgia, Damiano Piovesan, Silvio C E Tosatto, Emanuela Leonardi

Faculty, Staff and Students Publications

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age. Here, we assess the ability and accuracy of computational methods to predict comorbid phenotypes based on clinical …

Genomic Balancing Act: Deciphering Dna Rearrangements In The Complex Chromosomal Aberration Involving 5p152, 2q311, And 18q2132, Zain Dardas, Dana Marafi, Ruizhi Duan, Jawid M Fatih, Omnia F El-Rashidy, Christopher M Grochowski, Claudia M B Carvalho, Shalini N Jhangiani, Weimin Bi, Haowei Du, Richard A Gibbs, Jennifer E Posey, Daniel G Calame, Maha S Zaki, James R Lupski

Faculty, Staff and Students Publications

Despite extensive research into the genetic underpinnings of neurodevelopmental disorders (NDD), many clinical cases remain unresolved. We studied a female proband with a NDD, mildly dysmorphic facial features, and brain stem hypoplasia on neuroimaging. Comprehensive genomic analyses revealed a terminal 5p loss and a terminal 18q gain in the proband while a diploid copy number for chromosomes 5 and 18 in both parents. Genomic investigations in the proband identified an unbalanced translocation t(5;18) with additional genetic material from chromosome 2 (2q31.3) inserted at the breakpoint, pointing to a complex chromosomal rearrangement (CCR) involving 5p15.2, 2q31.3, and 18q21.32. Breakpoint junction analyses …

Analysis And Benchmarking Of Small And Large Genomic Variants Across Tandem Repeats, Adam C English, Egor Dolzhenko, Helyaneh Ziaei Jam, Sean K Mckenzie, Nathan D Olson, Wouter De Coster, Jonghun Park, Bida Gu, Justin Wagner, Michael A Eberle, Melissa Gymrek, Mark J P Chaisson, Justin M Zook, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Tandem repeats (TRs) are highly polymorphic in the human genome, have thousands of associated molecular traits and are linked to over 60 disease phenotypes. However, they are often excluded from at-scale studies because of challenges with variant calling and representation, as well as a lack of a genome-wide standard. Here, to promote the development of TR methods, we created a catalog of TR regions and explored TR properties across 86 haplotype-resolved long-read human assemblies. We curated variants from the Genome in a Bottle (GIAB) HG002 individual to create a TR dataset to benchmark existing and future TR analysis methods. We …

Meeting Report: 1st International Conference On Polyploid Giant Cancer Cells-Biology, Clinical Applications, And The Birth Of A New Field In Cancer Research, Tao P Wu, Xiaoran Li, Sujuan Ba, Phil Jones, Donna E Hansel, Jinsong Liu

Faculty, Staff and Students Publications

No abstract provided.