Medicine and Health Sciences Commons^™

High Lipoprotein(A): Actionable Strategies For Risk Assessment And Mitigation, Gissette Reyes-Soffer, Calvin Yeang, Erin D Michos, Wess Boatwright, Christie M Ballantyne

Faculty, Staff and Students Publications

High levels of lipoprotein(a) [Lp(a)] are causal for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is the most prevalent inherited dyslipidemia and strongest genetic ASCVD risk factor. This risk persists in the presence of at target, guideline-recommended, LDL-C levels and adherence to lifestyle modifications. Epidemiological and genetic evidence supporting its causal role in ASCVD and calcific aortic stenosis continues to accumulate, although various facets regarding Lp(a) biology (genetics, pathophysiology, and expression across race/ethnic groups) are not yet fully understood. The evolving nature of clinical guidelines and consensus statements recommending universal measurements of Lp(a) and the scientific data supporting its role in multiple …

Racial And Ethnic Disparities In Cardiovascular Disease – Analysis Across Major Us National Databases, Abdul Mannan Khan Minhas, Khawaja M Talha, Dmitry Abramov, Heather M Johnson, Steve Antoine, Fatima Rodriguez, Marat Fudim, Erin D Michos, Arunima Misra, Layla Abushamat, Vijay Nambi, Gregg C Fonarow, Christie M Ballantyne, Salim S Virani

Faculty, Staff and Students Publications

Background: There are several studies that have analyzed disparities in cardiovascular disease (CVD) health using a variety of different administrative databases; however, a unified analysis of major databases does not exist. In this analysis of multiple publicly available datasets, we sought to examine racial and ethnic disparities in different aspects of CVD, CVD-related risk factors, CVD-related morbidity and mortality, and CVD trainee representation in the US.

Methods: We used National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, National Inpatient Sample, Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research, United Network for Organ Sharing, …

Chagasin From Trypanosoma Cruzi As A Molecular Scaffold To Express Epitopes Of Tsa-1 As Soluble Recombinant Chimeras, Rosa Elena Cárdenas-Guerra, Octavio Montes-Flores, Edgar Ezequiel Nava-Pintor, Gerardo Reséndiz-Cardiel, Claudia Ivonne Flores-Pucheta, Yasmín Irene Rodríguez-Gavaldón, Rossana Arroyo, Maria Elena Bottazzi, Peter J Hotez, Jaime Ortega-López

Faculty, Staff and Students Publications

Trypanosoma cruzi is the causative agent of Chagas disease, a global public health problem. New therapeutic drugs and biologics are needed. The TSA-1 recombinant protein of T. cruzi is one such promising antigen for developing a therapeutic vaccine. However, it is overexpressed in E. coli as inclusion bodies, requiring an additional refolding step. As an alternative, in this study, we propose the endogenous cysteine protease inhibitor chagasin as a molecular scaffold to generate chimeric proteins. These proteins will contain combinations of two of the five conserved epitopes (E1 to E5) of TSA-1 in the L4 and L6 chagasin loops. Twenty …

An Indocyanine Green-Based Liquid Biopsy Test For Circulating Tumor Cells For Pediatric Liver Cancer, Andres F Espinoza, Pavan Kureti, Roma H Patel, Susan L Do, Saiabhiroop R Govindu, Bryan W Armbruster, Martin Urbicain, Kalyani R Patel, Dolores Lopez-Terrada, Sanjeev A Vasudevan, Sarah E Woodfield

Faculty, Staff and Students Publications

Background: Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy.

Methods: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery. We assessed ICG accumulation in cell lines using fluorescence microscopy and flow cytometry. For our CTC test, we developed a panel of liver tumor-specific markers, including ICG, Glypican-3, and DAPI, …

Egg-Induced Adult Food Protein-Induced Enterocolitis Syndrome: Clinical Phenotypes, Natural History And Immunological Characteristics, Purificación Gonzalez-Delgado, Sara Anvari, Jordi Barrachina, Ana L Jimenez Portillo, Teodorikez Jimenez, Francisco M Marco De La Calle, Javier Fernandez

Faculty, Staff and Students Publications

No abstract provided.

Rural Veterans With Hiv And Alcohol Use Disorder Receive Less Video Telehealth Than Urban Veterans, Alan Z Sheinfil, Giselle Day, Annette Walder, Julianna Hogan, Thomas P Giordano, Jan Lindsay, Anthony Ecker

Faculty, Staff and Students Publications

Purpose: Alcohol use disorder (AUD) is highly prevalent among Veterans with HIV. Rural Veterans with HIV are at especially high risk for not receiving appropriate treatment. This retrospective cohort cross-sectional study aimed to investigate patterns of mental health treatment utilization across delivery modality among Veterans diagnosed with HIV and AUD. It was hypothesized that rural Veterans with HIV and AUD would receive a lower rate of mental health treatment delivered via video telehealth than urban Veterans with HIV and AUD.

Methods: A national Veterans Health Association administrative database was used to identify a cohort of Veterans diagnosed with HIV and …

Pre-Heart Failure, Heart Stress, And Subclinical Heart Failure: Bridging Heart Health And Heart Failure, Antoni Bayes-Genis, Biykem Bozkurt

Faculty, Staff and Students Publications

No abstract provided.

Development Of Clinical Screening Tool For Exocrine Pancreatic Insufficiency In Patients With Definite Chronic Pancreatitis, Mohamed O Othman, Christopher Forsmark, Dhiraj Yadav, Vikesh K Singh, Luis F Lara, Walter Park, Zuoyi Zhang, Jun Yu, Jens J Kort

Faculty, Staff and Students Publications

Background/objectives: No simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP.

Methods: This was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional …

Cadherin-11 Targeted Cell-Specific Liposomes Enabled Skin Fibrosis Treatment By Inducing Apoptosis, Himanshu N Bhatt, Rimpy Diwan, Igor L Estevao, Rui Dong, Jennifer Smith, Chuan Xiao, Sandeep K Agarwal, Md Nurunnabi

Faculty, Staff and Students Publications

Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we …

Convolutional Neural Networks To Study Contrast-Enhanced Magnetic Resonance Imaging-Based Skeletal Calf Muscle Perfusion In Peripheral Artery Disease, Bijen Khagi, Tatiana Belousova, Christina M Short, Addison A Taylor, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) is associated with impaired blood flow in the lower extremities and histopathologic changes of the skeletal calf muscles, resulting in abnormal microvascular perfusion. We studied the use of convolution neural networks (CNNs) to differentiate patients with PAD from matched controls using perfusion pattern features from contrast-enhanced magnetic resonance imaging (CE-MRI) of the skeletal calf muscles. We acquired CE-MRI based skeletal calf muscle perfusion in 56 patients (36 patients with PAD and 20 matched controls). Microvascular perfusion imaging was performed after reactive hyperemia at the midcalf level, with a temporal resolution of 409 ms. We analyzed perfusion …

Associations Between Social Determinants Of Health And Cardiovascular Health Of Us Adult Cancer Survivors, Danish Iltaf Satti, Jeffrey Shi Kai Chan, Edward Christopher Dee, Yan Hiu Athena Lee, Abraham Ka Chung Wai, Sourbha S Dani, Salim S Virani, Michael D Shapiro, Garima Sharma, Tong Liu, Gary Tse

Faculty, Staff and Students Publications

Background: Relationships between the social determinants of health (SDOH) and cardiovascular health (CVH) of cancer survivors are underexplored.

Objectives: This study sought to investigate associations between the SDOH and CVH of adult cancer survivors.

Methods: Data from the U.S. National Health Interview Survey (2013-2017) were used. Participants reporting a history of cancer were included, excluding those with only nonmelanotic skin cancer, or with missing data for any domain of SDOH or CVH. SDOH was quantified with a 6-domain, 38-item score, consistent with the Centers for Disease Control and Prevention recommendations (higher score indicated worse deprivation). CVH was quantified based on …

Statin Utilization And Cardiovascular Outcomes In A Real-World Primary Prevention Cohort Of Older Adults, Aaron J Walker, Jianhui Zhu, Floyd Thoma, Oscar Marroquin, Amber Makani, Martha Gulati, Eugenia Gianos, Salim S Virani, Fatima Rodriguez, Steven E Reis, Christie Ballantyne, Suresh Mulukutla, Anum Saeed

Faculty, Staff and Students Publications

Background: Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years).

Objective: Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network.

Methods: We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and 'moderate or high' intensity statins with a follow up period of ∼7 years. Cox regression models were used to …

New Approaches To Triglyceride Reduction: Is There Any Hope Left?, Annalisa Filtz, Siddhant Parihar, Garred S Greenberg, Christine M Park, Andrea Scotti, Daniel Lorenzatti, Juan J Badimon, Daniel E Soffer, Peter P Toth, Carl J Lavie, Vera Bittner, Salim S Virani, Leandro Slipczuk

Faculty, Staff and Students Publications

Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor …

Long-Term Sustained Effects Of The Look Ahead Lifestyle Intervention On Body Composition Among Adults With Type 2 Diabetes, Maxine Ashby-Thompson, Stanley Heshka, Andrea Anderson, Henry Pownall, Blandine Laferrère, Ashok Balasubramanyam, Steven B Heymsfield, Thomas A Wadden, Dympna Gallagher

Faculty, Staff and Students Publications

Objective: The objective of the study was to test whether there are sustained effects of the Look AHEAD intensive lifestyle intervention (ILI), versus diabetes support and education (DSE), on weight and body composition 12 to 16 years after randomization.

Methods: Participants were a subset of enrollees in the Look AHEAD dual-energy x-ray absorptiometry substudy who completed the final visit, composed of men (DSE = 99; ILI = 94) and women (DSE = 134; ILI = 135) with type 2 diabetes and mean (SD) age 57.2 (6.4) years and BMI 34.9 (5.1) kg/m2 at randomization. Dual-energy x-ray absorptiometry measured total and …

Efemp1 Haploinsufficiency Causes A Marfan-Like Hereditary Connective Tissue Disorder, Irman Forghani, Steven H Lang, Matthew J Rodier, Stephanie A Bivona, Alejo A Morales, Stephan Zuchner, Guney Bademci, Mustafa Tekin

Faculty, Staff and Students Publications

Phenotypic features of a hereditary connective tissue disorder, including craniofacial characteristics, hyperextensible skin, joint laxity, kyphoscoliosis, arachnodactyly, inguinal hernia, and diverticulosis associated with biallelic pathogenic variants in EFEMP1 have been previously described in four patients. Genome sequencing on a proband and her mother with comparable phenotypic features revealed that both patients were heterozygous for a stop-gain variant c.1084C>T (p.Arg362*). Complementary RNA-seq on fibroblasts revealed significantly reduced levels of mutant EFEMP1 transcript. Considering the absence of other molecular explanations, we extrapolated that EFEMP1 could be the cause of the patient's phenotypes. Furthermore, nonsense-mediated decay was demonstrated for the mutant allele …

Loss-Of-Function Variants In Ubap1l Cause Autosomal Recessive Retinal Degeneration, Ji Hoon Han, Kim Rodenburg, Tamar Hayman, Giacomo Calzetti, Karolina Kaminska, Mathieu Quinodoz, Molly Marra, Sandrine Wallerich, Gilad Allon, Zoltán Z Nagy, Krisztina Knézy, Yumei Li, Rui Chen, Mirella Telles Salgueiro Barboni, Paul Yang, Mark E Pennesi, L Ingeborgh Van Den Born, Balázs Varsányi, Viktória Szabó, Dror Sharon, Eyal Banin, Tamar Ben-Yosef, Susanne Roosing, Robert K Koenekoop, Carlo Rivolta

Faculty, Staff and Students Publications

Purpose: Inherited retinal diseases (IRDs) are a group of monogenic conditions that can lead to progressive blindness. Their missing heritability is still considerable, due in part to the presence of disease genes that await molecular identification. The purpose of this work was to identify novel genetic associations with IRDs.

Methods: Patients underwent a comprehensive ophthalmological evaluation using standard-of-care tests, such as detailed retinal imaging (macular optical coherence tomography and short-wavelength fundus autofluorescence) and electrophysiological testing. Exome and genome sequencing, as well as computer-assisted data analysis were used for genotyping and detection of DNA variants. A minigene-driven splicing assay was performed …

Genetic Evaluation For Monogenic Disorders Of Low Bone Mass And Increased Bone Fragility: What Clinicians Need To Know, Emily Busse, Brendan Lee, Sandesh C S Nagamani

Faculty, Staff and Students Publications

Purpose of review: The purpose of this review is to outline the principles of clinical genetic testing and to provide practical guidance to clinicians in navigating genetic testing for patients with suspected monogenic forms of osteoporosis.

Recent findings: Heritability assessments and genome-wide association studies have clearly shown the significant contributions of genetic variations to the pathogenesis of osteoporosis. Currently, over 50 monogenic disorders that present primarily with low bone mass and increased risk of fractures have been described. The widespread availability of clinical genetic testing offers a valuable opportunity to correctly diagnose individuals with monogenic forms of osteoporosis, thus instituting …

Patient- And System-Level Factors Associated With Racial/Ethnic Disparities In The Delivery Of Guideline-Concordant Therapy Among Us Patients With Gastric Cancer, Wilson L Da Costa, Mimi C Tan, E Ramsay Camp, Aaron P Thrift

Faculty, Staff and Students Publications

Background: Disparities in gastric cancer (GC) outcomes show a higher disease burden among minorities. We aimed to evaluate the associations between sociodemographic and system-level factors and guideline-concordant treatment among GC patients.

Methods: Cohort study with GC patients in the National Cancer Data Base (2006-2018) treated with upfront resection or neoadjuvant therapy (NAT). We used logistic regression to identify associations between deviations from guideline-concordant therapy and patient- and system-level factors, and Cox regression models to assess risk of death.

Results: The cohort included 43 597 GC patients treated with endoscopic resection (8.9%), surgery only (47.1%), surgery and adjuvant therapy (20.6%), or …

Anoctamin 4 Defines Glucose-Inhibited Neurons In The Ventromedial Hypothalamus, Longlong Tu, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

No abstract provided.

Neighborhood-Level Disadvantage And Delayed Adjuvant Therapy In Head And Neck Cancer, Evan M Graboyes, Joshua Lee Cagle, Salma Ramadan, Kavita Prasad, Flora Yan, John Pearce, Angela L Mazul, Jean-Sebastien Anoma, Elizabeth G Hill, Bhisham S Chera, Sidharth V Puram, Ryan Jackson, Vlad C Sandulache, Samantha Tam, Michael C Topf, Russel Kahmke, Nosayaba Osazuwa-Peters, Brian Nussenbaum, Anthony J Alberg, Katherine R Sterba, Chanita Hughes Halbert

Faculty, Staff and Students Publications

Importance: For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined.

Objective: To characterize the association of neighborhood-level disadvantage with delays in receiving PORT.

Design, setting, and participants: This retrospective cohort study included 681 adult patients with HNSCC undergoing curative-intent surgery and PORT from 2018 to 2020 at 4 US academic medical …

Serum Extracellular Vesicle Protein Profiling For Prediction Of Corneal Transplant Rejection, Hyun Ju Lee, Eun-Hye Bae, Jong Min Choi, Hyemee Kim, Hyeon Ji Kim, Heather Barreda, Sung Yun Jung, Joo Youn Oh, Ryang Hwa Lee

Faculty, Staff and Students Publications

Background: Corneal transplantation is the most common transplant procedure worldwide. Despite immune and angiogenic privilege of the cornea, 50% to 70% of corneal transplants fail in high-risk recipients, primarily because of immune rejection. Therefore, it is crucial to identify predictive biomarkers of rejection to improve transplant survival.

Methods: In search for predictive biomarkers, we performed proteomics analysis of serum extracellular vesicles (EVs) in a fully major histocompatibility complex-mismatched (C57BL/6-to-BALB/c) murine corneal transplantation model, wherein 50% of transplants undergo rejection by day 28 following transplantation.

Results: Our time course study revealed a decrease in the number of serum EVs on day …

Generation Of A Humanized Mace2 And A Conditional Hace2 Mouse Models Permissive To Sars-Cov-2 Infection, I-Wen Song, Megan Washington, Carolina Leynes, Jason Hsu, Kempaiah Rayavara, Yangjin Bae, Nele Haelterman, Yuqing Chen, Ming-Ming Jiang, Aleksandra Drelich, Vivian Tat, Denise G Lanza, Isabel Lorenzo, Jason D Heaney, Chien-Te Kent Tseng, Brendan Lee, Ronit Marom

Faculty, Staff and Students Publications

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains a public health concern and a subject of active research effort. Development of pre-clinical animal models is critical to study viral-host interaction, tissue tropism, disease mechanisms, therapeutic approaches, and long-term sequelae of infection. Here, we report two mouse models for studying SARS-CoV-2: A knock-in mAce2F83Y,H353K mouse that expresses a mouse-human hybrid form of the angiotensin-converting enzyme 2 (ACE2) receptor under the endogenous mouse Ace2 promoter, and a Rosa26 conditional knock-in mouse carrying the human ACE2 allele (Rosa26hACE2). Although the mAce2F83Y,H353K mice were susceptible to …

Seeing Beyond Reality: Considering The Impact Of Mainstream Virtual Reality Adoption On Ocular Health And The Evolving Role Of Ophthalmologists, Venkata Soumith Jonnakuti, Benjamin Jay Frankfort

Faculty, Staff and Students Publications

No abstract provided.

Impact Of Spherical Aberration On Visual Quality And Depth Of Focus, Jack T Holladay, Karim Kozhaya, Douglas D Koch, Li Wang

Faculty, Staff and Students Publications

No abstract provided.

Individual Disruption Of 12 Testis-Enriched Genes Via The Crispr/Cas9 System Does Not Affect The Fertility Of Male Mice, Akira Suzuki, Norikazu Yabuta, Keisuke Shimada, Daisuke Mashiko, Keizo Tokuhiro, Yuki Oyama, Haruhiko Miyata, Thomas X Garcia, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

More than 1200 genes have been shown in the database to be expressed predominantly in the mouse testes. Advances in genome editing technologies such as the CRISPR/Cas9 system have made it possible to create genetically engineered mice more rapidly and efficiently than with conventional methods, which can be utilized to screen genes essential for male fertility by knocking out testis-enriched genes. Finding such genes related to male fertility would not only help us understand the etiology of human infertility but also lead to the development of male contraceptives. In this study, we generated knockout mice for 12 genes (Acrv1, Adgrf3, …

Comparison Of Cefiderocol In-Vitro Susceptibility Testing Modalities, Nicholas S Teran, Linh Vuong, Kady Phe, Todd M Lasco, William R Miller, Vincent H Tam

Faculty, Staff and Students Publications

No abstract provided.

Continuous Renal Replacement Therapy: Current State And Future Directions For Worldwide Practice, Katja M Gist, Dana Y Fuhrman, Akash Deep, Taiki Haga, Demet Demirkol, Michael J Bell, Ayse Akcan-Arikan

Faculty, Staff and Students Publications

No abstract provided.

Social Connectedness And Adolescent Suicide Risk, Alejandra Arango, David Brent, Jacqueline Grupp-Phelan, Bradley J Barney, Anthony Spirito, Megan M Mroczkowski, Rohit Shenoi, Melinda Mahabee-Gittens, T Charles Casper, Cheryl King

Faculty, Staff and Students Publications

Background: Despite evidence of the importance of interpersonal connectedness to our understanding of suicide risk, relatively little research has examined the protective and buffering effects of connectedness among adolescents. The aims of this study were to determine: (a) whether overall connectedness (composite of family, peer, and school) and specific domains of connectedness were related to a lower likelihood of suicide attempts, and (b) whether these factors buffer the prospective risk of suicide attempt for high-risk subgroups (i.e., recent suicidal ideation and/or lifetime history of suicide attempt, peer victimization, or sexual and gender minority status).

Methods: Participants were 2,897 adolescents (64.7% …

Expanding The Phenotype Of Ppp1r21-Related Neurodevelopmental Disorder, Mohammed Almannai, Dana Marafi, Maha S Zaki, Reza Maroofian, Stephanie Efthymiou, Nebal Waill Saadi, Bilal Filimban, Hormos Salimi Dafsari, Fatima Rahman, Shazia Maqbool, Eissa Faqeih, Fuad Al Mutairi, Hind Alsharhan, Omar Abdelaty, Saadoun Bin-Hasan, Ruizhi Duan, Mahmoud M Noureldeen, Alaa Alqattan, Henry Houlden, Jill V Hunter, Jennifer E Posey, James R Lupski, Ayman W El-Hattab

Faculty, Staff and Students Publications

PPP1R21 encodes for a conserved protein that is involved in endosomal maturation. Biallelic pathogenic variants in PPP1R21 have been associated with a syndromic neurodevelopmental disorder from studying 13 affected individuals. In this report, we present 11 additional individuals from nine unrelated families and their clinical, radiological, and molecular findings. We identified eight different variants in PPP1R21, of which six were novel variants. Global developmental delay and hypotonia are neurological features that were observed in all individuals. There is also a similar pattern of dysmorphic features with coarse faces as a gestalt observed in several individuals. Common findings in 75% of …

Unveiling Microbial Diversity: Harnessing Long-Read Sequencing Technology, Daniel P Agustinho, Yilei Fu, Vipin K Menon, Ginger A Metcalf, Todd J Treangen, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Long-read sequencing has recently transformed metagenomics, enhancing strain-level pathogen characterization, enabling accurate and complete metagenome-assembled genomes, and improving microbiome taxonomic classification and profiling. These advancements are not only due to improvements in sequencing accuracy, but also happening across rapidly changing analysis methods. In this Review, we explore long-read sequencing's profound impact on metagenomics, focusing on computational pipelines for genome assembly, taxonomic characterization and variant detection, to summarize recent advancements in the field and provide an overview of available analytical methods to fully leverage long reads. We provide insights into the advantages and disadvantages of long reads over short reads and …