Digital Commons Network^™

Determining Predictors Of Actual Living Kidney Donation Based On Potential Donor Characteristics, Andrea M Meinders, Edward A Graviss, Duc T Nguyen, Jonathan Daw, Krista L Lentine, John Devin Peipert, Ahmed Osama Gaber, David A Axelrod, Francis L Weng, Amy D Waterman

Faculty, Staff and Students Publications

Background: Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons.

Methods: At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing.

Results: Among 2184 …

A Novel Deep Learning Model Based On Transformer And Cross Modality Attention For Classification Of Sleep Stages, Sahar Hassanzadeh Mostafaei, Jafar Tanha, Amir Sharafkhaneh

Faculty, Staff and Students Publications

The classification of sleep stages is crucial for gaining insights into an individual's sleep patterns and identifying potential health issues. Employing several important physiological channels in different views, each providing a distinct perspective on sleep patterns, can have a great impact on the efficiency of the classification models. In the context of neural networks and deep learning models, transformers are very effective, especially when dealing with time series data, and have shown remarkable compatibility with sequential data analysis as physiological channels. On the other hand, cross-modality attention by integrating information from multiple views of the data enables to capture relationships …

Molecular Detection Of Intestinal Parasites In A Rural Community Of Colombia: A One Health Approach To Explore Potential Environmental-Zoonotic Transmission, Sergio Castañeda, Claudia Patricia Acosta, Luis Reinel Vasquez-A, Luz H Patiño, Rojelio Mejía, Juan David Ramírez

Faculty, Staff and Students Publications

Aims: Protozoan and helminth parasitic infections pose significant public health challenges, especially in developing countries with rural populations marked by suboptimal hygiene practices and socio-economic constraints. The parasites are the etiological agents of these infections and have a notably elevated global prevalence. Therefore, this study focuses on estimating the frequency and transmission dynamics of several parasitic species, including Blastocystis, Giardia, Cryptosporidium spp., Entamoeba histolytica, Ascaris lumbricoides, Trichuris trichiura, Taenia spp. and hookworms, within a rural community in southwest Colombia with a particular emphasis on the One Health framework, considering environmental and zoonotic transmission potentials.

Methods and results: This study involved …

Potentially Functional Variants Of Chmp4a And Panx1 In The Pyroptosis-Related Pathway Predict Survival Of Patients With Non-Oropharyngeal Head And Neck Squamous Cell Carcinoma, Xiaozhun Tang, Huiling Wang, Hongliang Liu, Guojun Li, Erich M Sturgis, Sanjay Shete, Qingyi Wei

Faculty, Staff and Students Publications

Background: Pyroptosis has been implicated in the advancement of various cancers. Triggering pyroptosis within tumors amplifies the immune response, thereby fostering an antitumor immune environment. Nonetheless, few published studies have evaluated associations between functional variants in the pyroptosis-related genes and clinical outcomes of patients with non-oropharyngeal head and neck squamous cell carcinoma (NON-ORO HNSCC).

Methods: We conducted an association study of 985 NON-ORO HNSCC patients who were randomly divided into two groups: the discovery group of 492 patients and the replication group of 493 patients. We used Cox proportional hazards regression analysis to examine associations between genetic variants of the …

Smeltermen's Day Weekend 2024, Anaconda, Montana, Kika Bradford, Megan Schultz

Institute for Tourism and Recreation Research Publications

This study was conducted for Discover Anaconda to provide insights into the characteristics of attendees of the Smeltermen’s Day Weekend 2024. Surveys were completed by 79 attendees of the event. Results show that 86.1% of respondents were residents of Montana, with 66.2% from Deer Lodge County. Out-of-county respondents spent an average of 4 nights in Deer Lodge County, reporting a total spending of $21,566.00, primarily in accommodations, restaurants, and gasoline. The study provides event organizers and Discover Anaconda with valuable data for future event planning, improving the event experience, refining marketing strategies, and understanding the economic impact of visitor spending …

Itrr Annual Report - 2023, Melissa Weddell

Institute for Tourism and Recreation Research Publications

Within this report, you will discover a comprehensive overview of our past and future research projects, travel and outdoor recreation information, and behind-the-scenes stories of our impact. By transparently sharing our work, we aim to foster stakeholder engagement that supports rigorous and impartial research focused on continuous improvement. Reflecting on 37 years of milestones, ITRR has evolved and flourished through innovation, collaboration, and an unwavering mission to serve Montanans.

Pnpla3, Obesity, And Heavy Alcohol Use In Cirrhosis Patients May Exert A Synergistic Increase Hepatocellular Carcinoma Risk, Aaron P Thrift, Fasiha Kanwal, Hyeyeun Lim, Hao Duong, Yanhong Liu, Amit G Singal, Saira Khaderi, Sumeet K Asrani, Christopher I Amos, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors.

METHODS: We analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint …

Clinical Features Of Chagas Disease Progression And Severity, Maria Carmo P Nunes, Caryn Bern, Eva H Clark, Antonio L Teixeira, Israel Molina

Faculty, Staff and Students Publications

Chagas disease, the most common form of nonischaemic cardiomyopathy globally, is one of the leading causes of morbidity and mortality in Latin America. Chagas cardiomyopathy has a wide clinical spectrum and prognosis, which is primarily determined by the severity of left ventricular dysfunction. Chagas disease also affects the brain, particularly manifesting as cardioembolic strokes and cognitive impairments. Disease progression is influenced by various factors such as anti-parasite treatments, host-parasite interactions, and other determinants. This review explores Chagas disease, covering clinical presentations, the range of severity of Chagas cardiomyopathy, and neurological manifestations. We investigate factors that influence the progression of cardiomyopathy, …

Targeting Nuclear Receptor Coactivator Src-1 Prevents Colorectal Cancer Immune Escape By Reducing Transcription And Protein Stability Of Pd-L1, Yilin Hong, Qiang Chen, Zinan Wang, Yong Zhang, Bei Li, Hanshi Guo, Chuanzhong Huang, Xu Kong, Pingli Mo, Nengming Xiao, Jianming Xu, Yunbin Ye, Chundong Yu

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8

Foreword, David L. Schwartz, Kat M. Albrecht

Northwestern University Law Review

Offering a critique is often easier than proposing a solution. This refrain echoed frequently in the months and years that we spent developing what would become the Systematic Content Analysis of Litigation EventS (SCALES) Open Knowledge Network, a project born from the collaborative efforts of experts across various disciplines.

Collagen: The Superior Material For Full-Thickness Oral Mucosa Tissue Engineering, Alexandra Gelin, Daniela S. Masson-Meyers, Fatemeh Amini, Keyvan Moharamzadeh, Lobat Tayebi

School of Dentistry Faculty Research and Publications

Background

Tissue engineering has significantly progressed in developing full-thickness oral mucosa constructs designed to replicate the natural oral mucosa. These constructs serve as valuable in vitro models for biocompatibility. testing and oral disease modeling and hold clinical potential for replacing damaged or lost oral soft tissue. However, one of the major challenges in tissue engineering of the oral mucosa is the identification of an appropriate scaffold with optimal porosity, interconnected porous networks, biodegradability, and biocompatibility. These characteristics facilitate cell migration, nutrient delivery, and vascularization. Various biomaterials have been investigated for constructing tissue-engineered oral mucosa models; collagen has demonstrated superior outcomes …

Characteristics Of Patients With Spontaneous Coronary Artery Dissection Presenting With Sudden Cardiac Arrest In The United States And The Potential Role Of Implantable Cardioverter Defibrillator Therapy, Chayakrit Krittanawong, Yusuf Kamran Qadeer, Song Peng Ang, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized.

METHODS: This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest.

RESULTS: Our findings showed that the SCAD …

Contributions Of White Adipose Tissue To Energy Requirements For Female Reproduction, Elizabeth S Anaya, Evelyn L De Groot, John P Lydon, Stephanie A Pangas, Sean M Hartig

Faculty, Staff and Students Publications

Body composition impacts female fertility and there are established relationships between adipose tissue and the reproductive system. Maintaining functional adipose tissue is vital for meeting the energetic demands during the reproductive process, from ovulation to delivery and lactation. White adipose tissue (WAT) shows plastic responses to daily physiology and secretes diverse adipokines that affect the hypothalamic-pituitary-ovarian axis, but many other interorgan interactions remain to be determined. This review summarizes the current state of research on the dialogue between WAT and the female reproductive system, focusing on the impact of this crosstalk on ovarian and endometrial factors essential for fecundity.

Leveraging Preclinical Models Of Metastatic Breast Cancer, Diego A Pedroza, Yang Gao, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women that present to the clinic with established breast cancer metastases have limited treatment options. Yet, the majority of preclinical studies are actually not directed at developing treatment regimens for established metastatic disease. In this review we will discuss the current state of preclinical macro-metastatic breast cancer models, including, but not limited to syngeneic GEMM, PDX and xenografts. Challenges within these models which are often overlooked include fluorophore-immunogenic neoantigens, differences in experimental vs spontaneous metastasis and tumor heterogeneity. Furthermore, due to cell plasticity in the tumor immune microenvironment (TIME) of the metastatic landscape, the treatment efficacy of newly approved immune …

Prolonged Cytopenias After Immune Effector Cell Therapy And Lymphodepletion In Patients With Leukemia, Lymphoma And Solid Tumors, Anne Miller, Rachel Daum, Tao Wang, Mengfen Wu, Candise Tat, Thomas Pfeiffer, Shoba Navai, Andras Heczey, Meenakshi Hegde, Nabil Ahmed, Sarah B Whittle, Laquisa Hill, Caridad Martinez, Robert Krance, Carlos A Ramos, Rayne H Rouce, Premal Lulla, Helen E Heslop, Bilal Omer, Meghan Shekar

Faculty, Staff and Students Publications

Background aims: The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited. …

A Prospective Cohort Study Of Pregnancy Outcomes Following Antepartum Infection With Sars-Cov-2, James D Doss, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony B Carter, Indira U Mysorekar, Jeannie C Kelly

Faculty, Staff and Students Publications

Objectives: Our study aimed to explore the impact of COVID-19 infection on pregnancy outcomes, accounting for the progression of variants, vaccines, and treatment modalities.

Study design: We performed a prospective longitudinal cohort study at two urban tertiary centers enrolling patients with a confirmed intrauterine singleton pregnancy from December 23, 2020 to July 18, 2022. Patients were evaluated for SARS-CoV-2 infection at enrollment and every trimester using serum antibody testing. The primary outcome was preterm birth. Symptom and treatment data were collected from pregnant patients with COVID-19 infections. Variant strain infection status was determined from local wastewater analysis.

Results: 448 patients …

Characterization Of High-Risk-Other Human Papillomavirus Genotypes In Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, And Cervical Cancer, Caitlin E. Witt, Elizabeth F. Sutton, Ashley M. Stansbury, Ashley N. Winters, Luke C. Konur, Meng Luo, Jennifer E. Cameron, Beverly Ogden

School of Medicine Faculty Publications

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for …

A Genome-Wide Association Meta-Analysis Of All-Cause And Vascular Dementia, Mega Vascular Cognitive Impairment And Dementia (Megavcid) Consortium

Faculty, Staff and Students Publications

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.

RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability …

Update On The Diagnosis Of Tuberculosis, Irina Kontsevaya, Andrea Maurizio Cabibbe, Daniela Maria Cirillo, Andrew R Dinardo, Nicole Frahm, Stephen H Gillespie, David Holtzman, Lennard Meiwes, Elisa Petruccioli, Maja Reimann, Morten Ruhwald, Wilber Sabiiti, Francesca Saluzzo, Elisa Tagliani, Delia Goletti

Faculty, Staff and Students Publications

Background: Tuberculosis (TB) remains a global public health threat, and the development of rapid and precise diagnostic tools is the key to enabling the early start of treatment, monitoring response to treatment, and preventing the spread of the disease.

Objectives: An overview of recent progress in host- and pathogen-based TB diagnostics.

Sources: We conducted a PubMed search of recent relevant articles and guidelines on TB screening and diagnosis.

Content: An overview of currently used methods and perspectives in the following areas of TB diagnostics is provided: immune-based diagnostics, X-ray, clinical symptoms and scores, cough detection, culture of Mycobacterium tuberculosis and …

Age Modifies The Association Between Severe Sleep Apnea And All-Cause Mortality, Amin Ramezani, Mehrnaz Azarian, Amir Sharafkhaneh, Arash Maghsoudi, Melissa B Jones, Thomas Penzel, Javad Razjouyan

Faculty, Staff and Students Publications

Purpose: While sleep apnea (SA) gets more prevalent with advancing age, the impact of age on the association between SA and health outcomes is not well known. We assessed the association between the severity of SA and all-cause mortality in different age groups using large longitudinal data.

Method: We applied a Natural Language Processing pipeline to extract the apnea-hypopnea index (AHI) from the physicians' interpretation of sleep studies performed at the Veteran Health Administration (FY 1999-2022). We categorized the participants as no SA (n-SA, AHI< 5) and severe SA (s-SA, AHI≥30). We grouped the cohort based on age: Young≤40; Middle-aged:40-65; and Older adults≥65; and calculated the odds ratio (aOR) of mortality adjusted for age, sex, race, ethnicity, BMI, and Charlson-Comorbidity Index (CCI) using n-SA as the reference.

Results: We identified 146,148 participants (age 52.23 ± 15.02; BMI 32.11 ± 6.05; male 86.7 …

Phase Ii Study Of Samotolisib In Children And Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target Of Rapamycin Pathway Alterations: Pediatric Match Apec1621d, Theodore W Laetsch, Kathleen Ludwig, P Mickey Williams, Sinchita Roy-Chowdhuri, David R Patton, Brent Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Joyce Mhlanga, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, Donald Williams Parsons

Faculty, Staff and Students Publications

Purpose: Patients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib.

Methods: Patients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity. A rolling 6 limited dose escalation was performed as, to our knowledge, this was …

Phylogenetically Diverse Bacterial Species Produce Histamine, Kristen A Engevik, Amber Hazzard, Brenton Puckett, Kathleen M Hoch, Sigmund J Haidacher, Anthony M Haag, Jennifer K Spinler, James Versalovic, Melinda A Engevik, Thomas D Horvath

Faculty, Staff and Students Publications

Histamine is an important biogenic amine known to impact a variety of patho-physiological processes ranging from allergic reactions, gut-mediated anti-inflammatory responses, and neurotransmitter activity. Histamine is found both endogenously within specialized host cells and exogenously in microbes. Exogenous histamine is produced through the decarboxylation of the amino acid L-histidine by bacterial-derived histidine decarboxylase enzymes. To investigate how widespread histamine production is across bacterial species, we examined 102,018 annotated genomes in the Integrated Microbial Genomes Database and identified 3,679 bacterial genomes (3.6 %) which possess the enzymatic machinery to generate histamine. These bacteria belonged to 10 phyla: Bacillota, Bacteroidota, Actinomycetota, Pseudomonadota, …

Targeting Calpain-2-Mediated Junctophilin-2 Cleavage Delays Heart Failure Progression Following Myocardial Infarction, Satadru K Lahiri, Jiao Lu, Yuriana Aguilar-Sanchez, Hui Li, Lucia M Moreira, Mohit M Hulsurkar, Arielys Mendoza, Mara R Turkieltaub Paredes, Jose Alberto Navarro-Garcia, Elda Munivez, Brooke Horist, Oliver M Moore, Gunnar Weninger, Sören Brandenburg, Christof Lenz, Stephan E Lehnart, Rana Sayeed, George Krasopoulos, Vivek Srivastava, Lilei Zhang, Jason M Karch, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Coronary heart disease (CHD) is a prevalent cardiac disease that causes over 370,000 deaths annually in the USA. In CHD, occlusion of a coronary artery causes ischemia of the cardiac muscle, which results in myocardial infarction (MI). Junctophilin-2 (JPH2) is a membrane protein that ensures efficient calcium handling and proper excitation-contraction coupling. Studies have identified loss of JPH2 due to calpain-mediated proteolysis as a key pathogenic event in ischemia-induced heart failure (HF). Our findings show that calpain-2-mediated JPH2 cleavage yields increased levels of a C-terminal cleaved peptide (JPH2-CTP) in patients with ischemic cardiomyopathy and mice with experimental MI. We created …

Bempedoic Acid In Secondary Prevention, Idine Mousavi, Vijay Nambi, Layla A Abushamat, Sadeer G Al-Kindi, Michael D Shapiro, Laurence Sperling, Salim S Virani, Abdul Mannan Khan Minhas

Faculty, Staff and Students Publications

•Bempedoic acid has been shown to reduce major adverse cardiovascular outcomes in patients unable to take statins due to statin-associated side effects.•Analysis of CLEAR Outcomes trial data reveals possible differences in baseline characteristics between the primary and secondary prevention subgroups.•Further research is needed to optimize use of bempedoic acid and clarify its impact on cardiovascular outcomes in diverse patient populations.

High-Sensitivity Troponin T, Nt-Probnp, And Cognitive Outcomes In Sprint, Devin Haney, Yuan Ma, Djhenne Dalmacy, Nicholas M Pajewski, Ihab Hajjar, James A De Lemos, Wenxin Zhang, Elsayed Z Soliman, Christie M Ballantyne, Vijay Nambi, Naveed Sattar, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry, Simon B Ascher

Faculty, Staff and Students Publications

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.

Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.

Results: Over a median …

Clinical Outcomes Of Patients With Newly Diagnosed Large B-Cell Lymphoma In A Safety-Net Hospital System, Jun Y Jiang, Chijioke Nze, Danielle Guffey, Rockbum Kim, Abiodun O Oluyomi, Omar Rosales, Raka Bandyo, Courtney N Miller-Chism, Mark M Udden, Martha P Mims, Hilary Ma, Gustavo A Rivero, Akiva Diamond, Purnima S Teegavarapu, Ang Li, Christopher R Flowers

Faculty, Staff and Students Publications

Real-world outcome data for patients with large B-cell lymphomas (LBCLs) who are uninsured or have socioeconomic barriers to care are limited. We performed a retrospective cohort study of patients with newly diagnosed LBCL treated in a large safety-net hospital system. Between January 2011 and June 2022, 496 patients aged >18 years were diagnosed with LBCL at Harris Health System, Houston, Texas. The median age was 53 years, 75% were uninsured, and 81% were in the most disadvantaged Area Deprivation Index national quartiles. Most (69%) had stage III/IV disease, 44% had poor-risk disease by the Revised International Prognostic Index (R-IPI), and …

X-Linked Genetic Associations In Sporadic Thoracic Aortic Dissection, Fadi I Musfee, Goo Jun, Laura E Mitchell, Han Chen, Dongchuan Guo, Siddharth K Prakash, Shaunak Sanjay Adkar, Megan L Grove, Ryan Bohyun Choi, Derek Klarin, Million Veteran Program, Eric Boerwinkle, Dianna M Milewicz

Faculty, Staff and Students Publications

The male predominance in sporadic thoracic aortic aneurysm and dissection (TAD) suggests that the X chromosome contributes to TAD, but this has not been tested. We investigated whether X-linked variation-common (minor allele frequency [MAF] ≥0.01) and rare (MAF < 0.01)-was associated with sporadic TAD in three cohorts of European descent (Discovery: 364 cases, 874 controls; Replication: 516 cases, 440,131 controls, and ARIC [Atherosclerosis Risk in Communities study]: 753 cases, 2247 controls). For analysis of common variants, we applied a sex-stratified logistic regression model followed by a meta-analysis of sex-specific odds ratios. Furthermore, we conducted a meta-analysis of overlapping common variants between the Discovery and Replication cohorts. For analysis of rare variants, we used a sex-stratified optimized sequence kernel association test model. Common variants results showed no statistically significant findings in the Discovery cohort. An intergenic common variant near SPANXN1 was statistically significant in the Replication cohort (p = 1.81 × 10-8). The highest signal from the meta-analysis of the Discovery and Replication cohorts was a ZNF182 intronic common variant (p = 3.5 × 10-6). In rare variants results, RTL9 reached statistical significance (p = 5.15 × 10-5). Although most of our results were statistically insignificant, our analysis is the most comprehensive X-chromosome association analysis of sporadic TAD to date.

Relationship Between Epicardial Adipose Tissue And Coronary Atherosclerosis By Ccta In Young Adults (18–45), Annalisa Filtz, Daniel Lorenzatti, Andrea Scotti, Pamela Piña, Carol Fernandez-Hazim, Dou Huang, Paul Ippolito, John P Skendelas, Toshiki Kuno, Carlos J Rodriguez, Aldo L Schenone, Azeem Latib, Carl J Lavie, Leslee J Shaw, Ron Blankstein, Michael D Shapiro, Mario J Garcia, Daniel S Berman, Damini Dey, Salim S Virani, Leandro Slipczuk

Faculty, Staff and Students Publications

Objective: Epicardial adipose tissue (EAT) is implicated in the pathogenesis and progression of coronary artery disease (CAD). Limited data exists on the interplay between EAT and atherosclerosis in young individuals. Our study aims to explore the relationship between EAT and CAD in a young cohort.

Methods: All young (18-45 years) patients without prior CAD, referred for coronary computed tomography angiography (CCTA) from 2016 to 2022 were included. EAT volume and coronary artery calcium (CAC) were calculated from dedicated non-contrast scans. Coronary plaque presence, extent, and volume were quantified from CCTA. Multivariable logistic regression models for the presence of CAD, defined …

Tuberculosis Prevention: Current Strategies And Future Directions, Anca Vasiliu, Leonardo Martinez, Rishi K Gupta, Yohhei Hamada, Tara Ness, Alexander Kay, Maryline Bonnet, Martina Sester, Stefan H E Kaufmann, Christoph Lange, Anna M Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key …

A Systematic Review And Expert Delphi Consensus Recommendation On The Use Of Vaccines In Patients Receiving Dupilumab: A Position Paper Of The American College Of Allergy, Asthma And Immunology, Jay A Lieberman, Derek K Chu, Tasnuva Ahmed, Timothy E Dribin, Elissa M Abrams, Aikaterini Anagnostou, Kimberly G Blumenthal, Mark Boguniewicz, Nicole M Chase, David B K Golden, Nicholas L Hartog, Jennifer R Heimall, Tina Ho, Monica G Lawrence, David A Khan, Timothy Dean Minniear, S Shahzad Mustafa, John J Oppenheimer, Elizabeth J Phillips, Allison Ramsey, Nicholas L Rider, Lynda Schneider, Marcus S Shaker, Jonathan M Spergel, Cosby A Stone, David R Stukus, Julie Wang, Matthew J Greenhawt

Faculty, Staff and Students Publications

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the …